Monitoring survival and function of transfused platelets in Bernard-Soulier syndrome by flow cytometry and a cone and plate(let) analyzer (Impact-R).

PubMed

Panzer, Simon; Eichelberger, Beate; Koren, Daniela; Kaufmann, Karin; Male, Christoph

2007-01-01

Bernard-Soulier syndrome (BSS) patients may repeatedly require transfusion of platelets (PLTs). The hemostatic competence of transfused PLTs requires monitoring. Flow cytometry and a cone and plate(let) analyzer (Impact-R, DiaMed) were used to monitor survival and function of transfused PLTs in a 7-year-old girl with BSS undergoing surgery. Flow cytometry was applied to differentiate autologous PLTs from transfused PLTs by staining for CD42b. The Impact, which measures PLT adhesion and aggregation in response to high shear stress, was used to evaluate PLT function. Transfused PLTs were detectable by flow cytometry for 1 week after transfusion. While the patient's PLTs did not respond to high shear stress before transfusion, a normal response was documented by the Impact on the day after transfusion and 1 week thereafter. Transfused PLTs were detectable by flow cytometry, and their functional activity was demonstrated by the Impact.

[Septic shock following platelet transfusion contaminated with Citrobacter koseri in a child with postchemotherapy febrile neutropenia].

PubMed

Tichit, R; Saumet, L; Marchandin, H; Haouy, S; Latry, P; Sirvent, N

2016-01-01

The bacterial transfusion risk is currently the greatest infectious risk of blood transfusion. We report the case of a child with postchemotherapy febrile neutropenia who presented septic shock following platelet transfusion contaminated with Citrobacter koseri. The life-threatening development could have been avoided by strict compliance with good clinical practice. The stability of mortality rates due to adverse effects of bacterial proliferation during platelet transfusions in France since 1994 calls for optimization of all preventive measures throughout the transfusion chain and perfect knowledge of transfusion rules by medical staff and care givers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Impact of ABO-Identical vs ABO-Compatible Nonidentical Plasma Transfusion in Trauma Patients

DTIC Science & Technology

2010-09-01

and B patients in turn could receive AB donor plasma. Few studies have examined the im- pact of compatible nonidentical plasma transfusion . In platelet ... transfusion ,19 the administration of compatible nonidenti- cal platelets to patients undergoing coro- nary artery bypass grafting or valve re...significantly different (in boldface) and for the volume of packed red blood cells, plasma, platelets , cryoprecipitate, and factor VIIa transfused . cBecause

Risk factors for platelet transfusion in glioblastoma surgery.

PubMed

Lagman, Carlito; Sheppard, John P; Romiyo, Prasanth; Nguyen, Thien; Prashant, Giyarpuram N; Nagasawa, Daniel T; Liau, Linda M; Yang, Isaac

2018-04-01

The objectives of this study are to identify risk factors for and to evaluate clinical outcomes of platelet transfusion in glioblastoma surgery. The medical records of adult patients who underwent craniotomy for glioblastoma resection at a single academic medical center were retrospectively reviewed. We stratified patients into 2 groups: those who were transfused at least 1 unit of platelets intraoperatively or postoperatively (no more than 7 days after surgery), and those who were not transfused with platelets. Through the use of a 1:3 matched cohort analysis, we compared complications, length of stay, discharge disposition, and mortality, across groups. One hundred and five consecutive adult patients were included in this study. Thirteen patients (12.38%) received platelet transfusions. Prior antiplatelet therapy (odds ratio [OR] 8.21, 95% confidence interval [CI]: 2.36-28.58), preoperative platelet count less than 200,000 cells/µL (OR 8.46, 95% CI: 2.16-33.22), and longer operative times (OR 1.73, 95% CI: 1.10-2.72) were significant risk factors for platelet transfusion. There were no significant differences in the outcomes of interest in the matched cohort analysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Different doses of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Blanco, Patricia; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews; this review compares different platelet transfusion doses. Objectives To determine whether different doses of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect their efficacy and safety in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy with or without haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria Randomised controlled trials involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with malignant haematological disorders or undergoing HSCT that compared different platelet component doses (low dose 1.1 × 1011/m2 ± 25%, standard dose 2.2 × 1011/m2 ± 25%, high dose 4.4 × 1011/m2 ± 25%). Data collection and analysis We used the standard methodological procedures expected by The Cochrane Collaboration. Main results We included seven trials (1814 participants) in this review; six were conducted during one course of treatment (chemotherapy or HSCT). Overall the methodological quality of studies was low to moderate across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Five studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no difference in the number of participants with a clinically significant bleeding episode between the low-dose and standard-dose groups (four studies; 1170 participants; risk ratio (RR) 1.04, 95% confidence interval (CI) 0.95 to 1.13; moderate-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence); or high-dose and standard-dose groups (two studies; 951 participants; RR 1.02, 95% CI 0.93 to 1.11; moderate-quality evidence). Three studies reported the number of days with a clinically significant bleeding event per participant. There was no difference in the number of days of bleeding per participant between the low-dose and standard-dose groups (two studies; 230 participants; mean difference −0.17, 95% CI −0.51 to 0.17; low quality evidence). One study (855 participants) showed no difference in the number of days of bleeding per participant between high-dose and standard-dose groups, or between low-dose and high-dose groups (849 participants). Three studies reported the number of participants with severe or life-threatening bleeding. There was no difference in the number of participants with severe or life-threatening bleeding between a low-dose and a standard-dose platelet transfusion policy (three studies; 1059 participants; RR 1.33, 95% CI 0.91 to 1.92; low-quality evidence); low-dose and high-dose groups (one study; 849 participants; RR 1.20, 95% CI 0.82 to 1.77; low-quality evidence); or high-dose and standard-dose groups (one study; 855 participants; RR 1.11, 95% CI 0.73 to 1.68; low-quality evidence). Two studies reported the time to first bleeding episodes; we were unable to perform a meta-analysis. Both studies (959 participants) individually found that the time to first bleeding episode was either the same, or longer, in the low-dose group compared to the standard-dose group. One study (855 participants) found that the time to the first bleeding episode was the same in the high-dose group compared to the standard-dose group. Three studies reported all-cause mortality within 30 days from the start of the study. There was no difference in all-cause mortality between treatment arms (low-dose versus standard-dose: three studies; 1070 participants; RR 2.04, 95% CI 0.70 to 5.93; low-quality evidence; low-dose versus high-dose: one study; 849 participants; RR 1.33, 95% CI 0.50 to 3.54; low-quality evidence; and high-dose versus standard-dose: one study; 855 participants; RR 1.71, 95% CI 0.51 to 5.81; low-quality evidence). Six studies reported the number of platelet transfusions; we were unable to perform a meta-analysis. Two studies (959 participants) out of three (1070 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a standard-dose. One study (849 participants) found that a low-dose transfusion strategy led to more transfusion episodes than a high-dose strategy. One study (855 participants) out of three (1007 participants) found no difference in the number of platelet transfusions between the high-dose and standard-dose groups. One study reported on transfusion reactions. This study’s authors suggested that a high-dose platelet transfusion strategy may lead to a higher rate of transfusion-related adverse events. None of the studies reported quality-of-life. Authors’ conclusions In haematology patients who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found no evidence to suggest that a low-dose platelet transfusion policy is associated with an increased bleeding risk compared to a standard-dose or high-dose policy, or that a high-dose platelet transfusion policy is associated with a decreased risk of bleeding when compared to a standard-dose policy. A low-dose platelet transfusion strategy leads to an increased number of transfusion episodes compared to a standard-dose strategy. A high-dose platelet transfusion strategy does not decrease the number of transfusion episodes per participant compared to a standard-dose regimen, and it may increase the number of transfusion-related adverse events. Findings from this review would suggest a change from current practice, with low-dose platelet transfusions used for people receiving in-patient treatment for their haematological disorder and high-dose platelet transfusion strategies not being used routinely. PMID:26505729

Prophylactic platelet transfusions prior to surgery for people with a low platelet count

PubMed Central

Estcourt, Lise J; Malouf, Reem; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Birchall, Janet

2017-01-01

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical effectiveness and safety of prophylactic platelet transfusions prior to surgery for people with a low platelet count or platelet dysfunction (inherited or acquired). PMID:29151812

Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies.

PubMed

Martin, Isabelle; Kriaa, Fayçal; Proulle, Valérie; Guillet, Benoît; Kaplan, Cécile; D'Oiron, Roseline; Debré, Marianne; Fressinaud, Edith; Laurian, Yyes; Tchernia, Gil; Charpentier, Bernard; Lambert, Thierry; Dreyfus, Marie

2002-12-01

Type I Glanzmann's thrombasthenia is a rare congenital platelet function disorder, characterized by undetectable platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa). Severe bleeding is controlled by transfusion of normal platelets, leading in some cases to the occurrence of anti-GPIIb-IIIa isoantibodies, which induces a loss of transfused platelet efficacy. We used immunoadsorption on protein A Sepharose (IA-PA), which has been shown to be efficient in decreasing the titre of antibodies in several immune diseases, in three patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies on five different occasions. IA-PA was well tolerated with no deleterious side-effects reported. It induced a dramatic decrease of total immunoglobulin (Ig)G, including anti-GPIIb-IIIa isoantibody levels, as assessed by the monoclonal antibody-specific immobilization of platelet antigens test and the ex vivo inhibition of normal platelet aggregation induced by the patient's platelet-rich or platelet-poor plasma. Elimination of the antibody was associated with a correction of the bleeding time following platelet transfusion. IA-PA combined with platelet transfusion made it possible to control two life-threatening haemorrhages, and allowed two surgical procedures and one bone marrow transplantation to be performed safely. Our experience suggests that IA-PA, which restores the haemostatic efficacy of platelet transfusion, is a valuable therapeutic strategy in patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies.

Progress in bio-manufacture of platelets for transfusion.

PubMed

Heazlewood, Shen Y; Nilsson, Susan K; Cartledge, Kellie; Be, Cheang Ly; Vinson, Andrew; Gel, Murat; Haylock, David N

2017-11-01

Blood transfusion services face an ever-increasing demand for donor platelets to meet clinical needs. Whilst strategies for increasing platelet storage life and improving the efficiency of donor platelet collection are important, in the longer term, platelets generated by bio-manufacturing processes will be required to meet demands. Production of sufficient numbers of in vitro-derived platelets for transfusion represents a significant bioengineering challenge. In this review, we highlight recent progress in this area of research and outline the main technical and biological obstacles that need to be met before this becomes feasible and economic. A critical consideration is assurance of the functional properties of these cells as compared to their fresh, donor collected, counterparts. We contend that platelet-like particles and in vitro-derived platelets that phenotypically resemble fresh platelets must deliver the same functions as these cells upon transfusion. We also note recent progress with immortalized megakaryocyte progenitor cell lines, molecular strategies for reducing expression of HLA Class I to generate universal donor platelets and the move to early clinical studies with in vitro-derived platelets.

Identification of platelet refractoriness in oncohematologic patients

PubMed Central

Ferreira, Aline Aparecida; Zulli, Roberto; Soares, Sheila; de Castro, Vagner; Moraes-Souza, Helio

2011-01-01

OBJECTIVES: To identify the occurrence and the causes of platelet refractoriness in oncohematologic patients. INTRODUCTION: Platelet refractoriness (unsatisfactory post-transfusion platelet increment) is a severe problem that impairs the treatment of oncohematologic patients and is not routinely investigated in most Brazilian services. METHODS: Forty-four episodes of platelet concentrate transfusion were evaluated in 16 patients according to the following parameters: corrected count increment, clinical conditions and detection of anti-platelet antibodies by the platelet immunofluorescence test (PIFT) and panel reactive antibodies against human leukocyte antigen class I (PRA-HLA). RESULTS: Of the 16 patients evaluated (median age: 53 years), nine (56%) were women, seven of them with a history of pregnancy. An unsatisfactory increment was observed in 43% of the transfusion events, being more frequent in transfusions of random platelet concentrates (54%). Platelet refractoriness was confirmed in three patients (19%), who presented immunologic and non-immunologic causes. Alloantibodies were identified in eight patients (50%) by the PIFT and in three (19%) by the PRA-HLA. Among alloimmunized patients, nine (64%) had a history of transfusion, and three as a result of pregnancy (43%). Of the former, two were refractory (29%). No significant differences were observed, probably as a result of the small sample size. CONCLUSION: The high rate of unsatisfactory platelet increment, refractoriness and alloimmunization observed support the need to set up protocols for the investigation of this complication in all chronically transfused patients, a fundamental requirement for the guarantee of adequate management. PMID:21437433

Preoperative platelet transfusions to reverse antiplatelet therapy for urgent non-cardiac surgery: an observational cohort study.

PubMed

Baschin, M; Selleng, S; Hummel, A; Diedrich, S; Schroeder, H W; Kohlmann, T; Westphal, A; Greinacher, A; Thiele, T

2018-04-01

Essentials An increasing number of patients requiring surgery receive antiplatelet therapy (APT). We analyzed 181 patients receiving presurgery platelet transfusions to reverse APT. No coronary thrombosis occurred after platelet transfusion. This justifies a prospective trial to test preoperative platelet transfusions to reverse APT. Background Patients receiving antiplatelet therapy (APT) have an increased risk of perioperative bleeding and cardiac adverse events (CAE). Preoperative platelet transfusions may reduce the bleeding risk but may also increase the risk of CAE, particularly coronary thrombosis in patients after recent stent implantation. Objectives To analyze the incidence of perioperative CAE and bleeding in patients undergoing non-cardiac surgery using a standardized management of transfusing two platelet concentrates preoperatively and restart of APT within 24-72 h after surgery. Methods A cohort of consecutive patients on APT treated with two platelet concentrates before non-cardiac surgery between January 2012 and December 2014 was retrospectively identified. Patients were stratified by the risk of major adverse cardiac and cerebrovascular events (MACCE). The primary objective was the incidence of CAE (myocardial infarction, acute heart failure and cardiac troponine T increase). Secondary objectives were incidences of other thromboembolic events, bleedings, transfusions and mortality. Results Among 181 patients, 88 received aspirin, 21 clopidogrel and 72 dual APT. MACCE risk was high in 63, moderate in 103 and low in 15 patients; 67 had cardiac stents. Ten patients (5.5%; 95% CI, 3.0-9.9%) developed a CAE (three myocardial infarctions, four cardiac failures and three troponin T increases). None was caused by coronary thrombosis. Surgery-related bleeding occurred in 22 patients (12.2%; 95% CI, 8.2-17.7%), making 12 re-interventions necessary (6.6%; 95% CI, 3.8-11.2%). Conclusion Preoperative platelet transfusions and early restart of APT allowed urgent surgery and did not cause coronary thromboses, but non-thrombotic CAEs and re-bleeding occurred. Randomized trials are warranted to test platelet transfusion against other management strategies. © 2018 International Society on Thrombosis and Haemostasis.

The role of point-of-care assessment of platelet function in predicting postoperative bleeding and transfusion requirements after coronary artery bypass grafting.

PubMed

Mishra, Pankaj Kumar; Thekkudan, Joyce; Sahajanandan, Raj; Gravenor, Mike; Lakshmanan, Suresh; Fayaz, Khazi Mohammed; Luckraz, Heyman

2015-01-01

OBJECTIVE platelet function assessment after cardiac surgery can predict postoperative blood loss, guide transfusion requirements and discriminate the need for surgical re-exploration. We conducted this study to assess the predictive value of point-of-care testing platelet function using the Multiplate® device. Patients undergoing isolated coronary artery bypass grafting were prospectively recruited ( n = 84). Group A ( n = 42) patients were on anti-platelet therapy until surgery; patients in Group B ( n = 42) stopped anti-platelet treatment at least 5 days preoperatively. Multiplate® and thromboelastography (TEG) tests were performed in the perioperative period. Primary end-point was excessive bleeding (>2.5 ml/kg/h) within first 3 h postoperative. Secondary end-points included transfusion requirements, re-exploration rates, intensive care unit and in-hospital stays. Patients in Group A had excessive bleeding (59% vs. 33%, P = 0.02), higher re-exploration rates (14% vs. 0%, P < 0.01) and higher rate of blood (41% vs. 14%, P < 0.01) and platelet (14% vs. 2%, P = 0.05) transfusions. On multivariate analysis, preoperative platelet function testing was the most significant predictor of excessive bleeding (odds ratio [OR]: 2.3, P = 0.08), need for blood (OR: 5.5, P < 0.01) and platelet transfusion (OR: 15.1, P < 0.01). Postoperative "ASPI test" best predicted the need for transfusion (sensitivity - 0.86) and excessive blood loss (sensitivity - 0.81). TEG results did not correlate well with any of these outcome measures. Peri-operative platelet functional assessment with Multiplate® was the strongest predictor for bleeding and transfusion requirements in patients on anti-platelet therapy until the time of surgery.

Platelet utilization: a Canadian Blood Services research and development symposium.

PubMed

Webert, Kathryn E; Alam, Asim Q; Chargé, Sophie B; Sheffield, William P

2014-04-01

Considerable progress has been made in recent years in understanding platelet biology and in strengthening the clinical evidence base around platelet transfusion thresholds and appropriate platelet dosing. Platelet alloimmunization rates have also declined. Nevertheless, controversies and uncertainties remain that are relevant to how these products can best be used for the benefit of platelet transfusion recipients. Platelets are unique among the blood products directly derived from whole blood or apheresis donations in requiring storage, with shaking, at ambient temperature. Storage is accordingly constrained between the need to limit the growth of any microbes in the product and the need to minimize losses in platelet function associated with storage. Proteomic and genomic approaches are being applied to the platelet storage lesion. Platelet inventory management is made challenging by these constraints. Although bacterial screening has enhanced the safety of platelet transfusions, pathogen reduction technology may offer further benefits. Continuing clinical investigations are warranted to understand the value of transfusing platelets prophylactically or only in response to bleeding in different patient groups and how best to manage the most grievously injured trauma patients. Patients refractory to platelet transfusions also require expert clinical management. The engineering of platelet substitute products is an active area of research, but considerable hurdles remain before any clinical uses may be contemplated. Roles for platelets in biological areas distinct from hemostasis are also emerging. Platelet utilization is variably affected by all of the above factors, by demographic changes, by new medications, and by new patient care approaches. Copyright © 2014 Elsevier Inc. All rights reserved.

Administration of platelet concentrates suspended in bicarbonated Ringer's solution in children who had platelet transfusion reactions.

PubMed

Kobayashi, J; Yanagisawa, R; Ono, T; Tatsuzawa, Y; Tokutake, Y; Kubota, N; Hidaka, E; Sakashita, K; Kojima, S; Shimodaira, S; Nakamura, T

2018-02-01

Adverse reactions to platelet transfusions are a problem. Children with primary haematological and malignant diseases may experience allergic transfusion reactions (ATRs) to platelet concentrates (PCs), which can be prevented by giving washed PCs. A new platelet additive solution, using bicarbonated Ringer's solution and acid-citrate-dextrose formula A (BRS-A), may be better for platelet washing and storage, but clinical data are scarce. A retrospective cohort study for consecutive cases was performed between 2013 and 2017. For 24 months, we transfused washed PCs containing BRS-A to children with primary haematological and malignant diseases and previous adverse reactions. Patients transfused with conventional PCs (containing residual plasma) were assigned as controls, and results were compared in terms of frequency of ATRs, corrected count increment (CCI) and occurrence of bleeding. We also studied children transfused with PCs washed by a different system as historical controls. Thirty-two patients received 377 conventional PC transfusions. ATRs occurred in 12 (37·5%) patients from transfused with 18 (4·8%) bags. Thirteen patients, who experienced reactions to regular PCs in plasma, then received 119 transfusion bags of washed PCs containing BRS-A, and none had ATRs to washed PCs containing BRS-A. Before study period, six patients transfused 137 classical washed PCs with different platelet additive solution, under same indication, ATRs occurred in one (16·7%) patient from transfused with one (0·7%) bags. CCIs (24 h) in were lower with classical washed PCs (1·26 ± 0·54) compared to regular PCs in plasma (2·07 ± 0·76) (P < 0·001), but there was no difference between washed PCs containing BRS-A (2·14 ± 0·77) and regular PCs (2·21 ± 0·79) (P = 0·769), and we saw no post-transfusion bleeding. Washed PCs containing BRS-A appear to prevent ATRs without loss of transfusion efficacy in children with primary haematological and malignant diseases. Their efficacy should be further evaluated through larger prospective clinical trials. © 2017 International Society of Blood Transfusion.

The clearance mechanism of chilled blood platelets.

PubMed

Hoffmeister, Karin M; Felbinger, Thomas W; Falet, Hervé; Denis, Cécile V; Bergmeier, Wolfgang; Mayadas, Tanya N; von Andrian, Ulrich H; Wagner, Denisa D; Stossel, Thomas P; Hartwig, John H

2003-01-10

Platelet transfusion is a very common lifesaving medical procedure. Not widely known is the fact that platelets, unlike other blood cells, rapidly leave the circulation if refrigerated prior to transfusion. This peculiarity requires blood services to store platelets at room temperature, limiting platelet supplies for clinical needs. Here, we describe the mechanism of this clearance system, a longstanding mystery. Chilling platelets clusters their von Willebrand (vWf) receptors, eliciting recognition of mouse and human platelets by hepatic macrophage complement type 3 (CR3) receptors. CR3-expressing but not CR3-deficient mice exposed to cold rapidly decrease platelet counts. Cooling primes platelets for activation. We propose that platelets are thermosensors, primed at peripheral sites where most injuries occurred throughout evolution. Clearance prevents pathologic thrombosis by primed platelets. Chilled platelets bind vWf and function normally in vitro and ex vivo after transfusion into CR3-deficient mice. Therefore, GPIb modification might permit cold platelet storage.

Pathogen inactivation treatment of plasma and platelet concentrates and their predicted functionality in massive transfusion protocols.

PubMed

Arbaeen, Ahmad F; Schubert, Peter; Serrano, Katherine; Carter, Cedric J; Culibrk, Brankica; Devine, Dana V

2017-05-01

Trauma transfusion packages for hemorrhage control consist of red blood cells, plasma, and platelets at a set ratio. Although pathogen reduction improves the transfusion safety of platelet and plasma units, there is an associated reduction in quality. This study aimed to investigate the impact of riboflavin/ultraviolet light-treated plasma or platelets in transfusion trauma packages composed of red blood cell, plasma, and platelet units in a ratio of 1:1:1 in vitro by modeling transfusion scenarios for trauma patients and assessing function by rotational thromboelastometry. Pathogen-reduced or untreated plasma and buffy coat platelet concentrate units produced in plasma were used in different combinations with red blood cells in trauma transfusion packages. After reconstitution of these packages with hemodiluted blood, the hemostatic functionality was analyzed by rotational thromboelastometry. Hemostatic profiles of pathogen-inactivated buffy coat platelet concentrate and plasma indicated decreased activity compared with their respective controls. Reconstitution of hemodiluted blood (hematocrit = 20%) with packages that contained treated or nontreated components resulted in increased alpha and maximum clot firmness and enhanced clot-formation time. Simulating transfusion scenarios based on 30% blood replacement with a transfusion trauma package resulted in a nonsignificant difference in rotational thromboelastometry parameters between packages containing treated and nontreated blood components (p ≥ 0.05). Effects of pathogen inactivation treatment were evident when the trauma package percentage was 50% or greater and contained both pathogen inactivation-treated plasma and buffy coat platelet concentrate. Rotational thromboelastometry investigations suggest that there is relatively little impact of pathogen inactivation treatment on whole blood clot formation unless large amounts of treated components are used. © 2017 AABB.

Multiwavelength UV/visible spectroscopy for the quantitative investigation of platelet quality

NASA Astrophysics Data System (ADS)

Mattley, Yvette D.; Leparc, German F.; Potter, Robert L.; Garcia-Rubio, Luis H.

1998-04-01

The quality of platelets transfused is vital to the effectiveness of the transfusion. Freshly prepared, discoid platelets are the most effective treatment for preventing spontaneous hemorrhage or for stopping an abnormal bleeding event. Current methodology for the routine testing of platelet quality involves random pH testing of platelet rich plasma and visual inspection of platelet rich plasma for a swirling pattern indicative of the discoid shape of the cells. The drawback to these methods is that they do not provide a quantitative and objective assay for platelet functionality that can be used on each platelet unit prior to transfusion. As part of a larger project aimed at characterizing whole blood and blood components with multiwavelength UV/vis spectroscopy, isolated platelets and platelet in platelet rich plasma have been investigated. Models based on Mie theory have been developed which allow for the extraction of quantitative information on platelet size, number and quality from multi-wavelength UV/vis spectra. These models have been used to quantify changes in platelet rich plasma during storage. The overall goal of this work is to develop a simple, rapid quantitative assay for platelet quality that can be used prior to platelet transfusion to ensure the effectiveness of the treatment. As a result of this work, the optical properties for isolated platelets, platelet rich plasma and leukodepleted platelet rich plasma have been determined.

Bacterial detection of platelets: current problems and possible resolutions.

PubMed

Blajchman, Morris A; Beckers, Erik A M; Dickmeiss, Ebbe; Lin, Lilly; Moore, Gillian; Muylle, Ludo

2005-10-01

The greatest transfusion-transmitted disease risk facing a transfusion recipient is that of bacterial sepsis. The prevalence of bacterial contamination in platelets and red blood cells is approximately 1 in 3,000 units transfused. The available data indicate that transfusion-associated sepsis develops after 1 in 25,000 platelet transfusions and 1 in 250,000 red blood cell transfusions. One of the most widely used strategies for decreasing bacterial sepsis risk is bacterial detection. A roundtable meeting of experts was convened during the XXVIII Annual Congress of the International Society of Blood Transfusion (Edinburgh, UK, July 2004) to provide a forum for experts to share their experiences in the routine bacterial detection of platelet products. This article summarizes the presentations, discussions, and recommendations of the panel. The data presented indicate that some of the current bacterial screening technology is useful for blocking the issuance of platelet units that contain relatively high levels of contaminating bacteria. Platelet units are usually released based on a test-negative status, which often become test-positive only upon longer storage. These data thus suggest that bacterial screening may not prevent all transfusion-transmitted bacterial infections. Two transfusion-transmitted case reports further highlighted the limitation of the routine bacterial screening of platelet products. It was felt that newer technologies, such as pathogen inactivation, may represent a more reliable process, with a higher level of safety. The panel thus recommended that the Transfusion Medicine community may need to change its thinking (paradigm) about bacterial detection, toward the possibility of the pathogen inactivation of blood products, to deal with the bacterial contamination issue. It was suggested, where permitted by regulatory agencies, that blood centers should consider adopting first-generation pathogen inactivation systems as a more effective approach to reducing the risk of transfusion-associated sepsis than some of the approaches currently available.

Evidence-based advances in transfusion practice in neonatal intensive care units.

PubMed

Christensen, Robert D; Carroll, Patrick D; Josephson, Cassandra D

2014-01-01

Transfusions to neonates convey both benefits and risks, and evidence is needed to guide wise use. Such evidence is accumulating, but more information is needed to generate sound evidence-based practices. We sought to analyze published information on nine aspects of transfusion practice in neonatal intensive care units. We assigned 'categories of evidence' and 'recommendations' using the format of the United States Preventive Services Task Force of the Agency for Healthcare Research and Quality. The nine practices studied were: (1) delayed clamping or milking of the umbilical cord at preterm delivery - recommended, high/substantial A; (2) drawing the initial blood tests from cord/placental blood from very low birth weight (VLBW, <1,500 g) infants at delivery - recommended, moderate/moderate B; (3) limiting phlebotomy losses of VLBW infants - recommended, moderate/substantial B; (4) selected use of erythropoiesis-stimulating agents to prevent transfusions - recommended, moderate/moderate-moderate/small B, C; (5) using platelet mass, rather than platelet count, in platelet transfusion decisions - recommended, moderate/small C; (6) permitting the platelet count to fall to <20,000/µl in 'stable' neonates before transfusing platelets - recommended, low/small I; (8) permitting the platelet count to fall to <50,000/µl in 'unstable' neonates before transfusing platelets - recommended, moderate/small C, and (9) not performing routine coagulation test screening on every VLBW infant - recommended, moderate/small C. We view these recommendations as dynamic, to be revised as additional evidence becomes available. We predict this list will expand as new studies provide more information to guide best transfusion practices. © 2014 S. Karger AG, Basel.

Heterogeneity of antibody response to human platelet transfusion.

PubMed Central

Wu, K K; Thompson, J S; Koepke, J A; Hoak, J C; Flink, R

1976-01-01

To study the antibody response to human platelet transfusions, nine thrombocytopenia patients with bone marrow failure were given 6 U (3X10(11)) of random platelet concentrates twice a week. Before transfusion, none of the patients had preexisting antibodies detectable with lymphocytotoxicity, platelet aggregation, or capillary leukoagglutination techniques. After receiving 18-78 U of platelets, they became refractory to further transfusions of random platelets and alloantibodies were detectable. Two patterns of antibody response could be identified. In three patients, the sera were not lymphocytotoxic with a panel of standard cells in which all the known HLA antigens in the first and second series were represented at least once. Yet, they caused platelet aggregation with 30, 24, and 60%, respectively, of a donor population studied. The aggregating activities were inhibited by antihuman IgG but not by antihuman IgA or antihuman IgM antiserum. The aggregating antibodies could be absorbed out with donor platelets but not lymphocytes or granulocytes. Antibodies from two of these patients aggregated platelets of their respective siblings matched for both HLA haplotypes. Transfusion of platelets from these two siblings did not increase the platelet count while platelets obtained from aggregation-negative donors did. The sera from the remaining six patients were lymphocytotoxic with 15-100% of the panel of standard cells. They also had aggregating antibodies, which could be absorbed out by both platelets and lymphocytes, suggesting that they were HLA antibodies. These data suggest that the development of platelet-specific antibodies may play an important role in the immunological rejection of isologous platelets, and should be considered in the selection of donors for patients who are refractory to platelets from random donors. PMID:956376

Epsilon aminocaproic acid prevents bleeding in severely thrombocytopenic patients with hematological malignancies.

PubMed

Antun, Ana G; Gleason, Shannon; Arellano, Martha; Langston, Amelia A; McLemore, Morgan L; Gaddh, Manila; el Rassi, Fuad; Bernal-Mizrachi, Leon; Galipeau, Jacques; Heffner, Leonard T; Winton, Elliott F; Khoury, Hanna J

2013-11-01

Despite prophylactic platelet transfusions, bleeding remains a significant problem in thrombocytopenic patients. The antifibrinolytic agent epsilon aminocaproic acid (EACA) was administered to 44 chronically (median duration, 273 days) and severely (platelet count, 8 × 10(9)/L; range, 1 × 10(9)/L-19 × 10(9)/L) thrombocytopenic patients with hematological malignancies. Prophylactic EACA at a dose of 1 g twice daily was orally administered for a median duration of 47 days (range, 7 days-209 days) until the platelet count recovered to > 30; × 10(9) /L. Platelets were only transfused if bleeding occurred. While receiving EACA, 59% of the patients did not bleed, 25% had 19 episodes of spontaneously resolving minor bleeding that did not require platelet transfusion, and 16% received a median of 4 platelet transfusions (range, 1 transfusion-8 transfusions) for 1 major traumatic and 9 spontaneous grade 2 to grade 3 bleeding (based on the World Health Organization classification of idiopathic thrombocytopenic purpura). No EACA toxicities were noted, and venous thromboses were not observed. EACA is well tolerated and is associated with a low risk of major bleeding in patients with hematological malignancies who are experiencing chronic severe thrombocytopenia. © 2013 American Cancer Society.

Platelet transfusions in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit.

PubMed

Habr, Bassem; Charpentier, Julien; Champigneulle, Benoît; Dechartres, Agnès; Daviaud, Fabrice; Geri, Guillaume; Cariou, Alain; Chiche, Jean-Daniel; Mira, Jean-Paul; Pène, Frédéric

2015-12-01

Thrombocytopenia is a frequent finding in critically ill cancer patients for whom indications of platelet transfusions are unclear. We herein addressed the current practices in platelet transfusion and the risk of bleeding in cancer patients with hypoproliferative thrombocytopenia in the intensive care unit (ICU). A retrospective monocenter study over a 7-year period was conducted in a medical ICU. Adult patients with malignancies and hypoproliferative thrombocytopenia, and who received at least one platelet concentrate during their ICU stay, were included. 296 patients were included and received a total of 904 platelet transfusions, for prophylactic indications in 300 (33.2 %) episodes, for securing an invasive procedure in 257 (28.4 %), and for treatment of minor to major bleeding manifestations in 347 (38.4 %). Most prophylactic transfusions (80 %) were performed at platelet count thresholds below 10-20 × 10(9)/L. Platelet increments were generally low in all three indications, 10 (interquartile range 2-25), 11 (2-25), and 8 (0-21) × 10(9)/L, respectively. A total of 97 major ICU-acquired bleeding events occurred in 40 patients. About half of those bleeding episodes (54.7 %) occurred at platelet counts below 20 × 10(9)/L. However, neither low admission platelet count nor low nadir platelet counts were predictive of ICU-acquired bleeding. The in-ICU mortality rate tended to be higher in patients with severe ICU-acquired bleeding events (50 vs. 36 %). Most prophylactic platelet transfusions were given using thresholds of 10-20 × 10(9)/L in critically ill thrombocytopenic cancer patients. The individual risk of ICU-acquired severe bleeding appears hardly predictable with the depth of thrombocytopenia.

The kinetics of unmatched and HLA-matched 111in-labelled homologous platelets in recipients with chronic marrow hypoplasia and anti-platelet immunity.

PubMed

Peters, A M; Porter, J B; Saverymuttu, S H; Malik, F; Zuiable, A; Lavender, J P; Schwarz, G; Lewis, S M; Gordon-Smith, E C

1985-05-01

The kinetics of homologous platelets, labelled in plasma with 111In-tropolonate, have been studied in five recipients with chronic marrow hypoplasia and severe thrombocytopenia, who were refractory to platelet transfusions as a result of alloimmunization. Mean platelet life span (MPLS), recovery, plasma 111In level and splenic and hepatic uptake kinetics were studied on two occasions, one using HLA-matched platelets and the other unmatched platelets. In each case, recovery of labelled platelets at 1 h post-injection and MPLS improved with HLA matching, although this improvement was highly variable. Only two of the five subjects would have derived any significant benefit from HLA-matched as compared with unmatched platelet transfusions. It was concluded that the need exists for additional cross-matching procedures, possibly related to platelet specific antigens, in patients who remain refractory to platelet transfusion.

Dual roles for hepatic lectin receptors in the clearance of chilled platelets.

PubMed

Rumjantseva, Viktoria; Grewal, Prabhjit K; Wandall, Hans H; Josefsson, Emma C; Sørensen, Anne Louise; Larson, Göran; Marth, Jamey D; Hartwig, John H; Hoffmeister, Karin M

2009-11-01

Rapid chilling causes glycoprotein-Ib (GPIb) receptors to cluster on blood platelets. Hepatic macrophage beta(2) integrin binding to beta-N-acetylglucosamine (beta-GlcNAc) residues in the clusters leads to rapid clearance of acutely chilled platelets after transfusion. Although capping the beta-GlcNAc moieties by galactosylation prevents clearance of short-term-cooled platelets, this strategy is ineffective after prolonged refrigeration. We report here that prolonged refrigeration increased the density and concentration of exposed galactose residues on platelets such that hepatocytes, through Ashwell-Morell receptor binding, become increasingly involved in platelet removal. Macrophages rapidly removed a large fraction of transfused platelets independent of their storage conditions. With prolonged platelet chilling, hepatocyte-dependent clearance further diminishes platelet recovery and survival after transfusion. Inhibition of chilled platelet clearance by both beta(2) integrin and Ashwell-Morell receptors may afford a potentially simple method for storing platelets in the cold.

[Allergic transfusion reactions in a patient with multiple food allergies].

PubMed

Strobel, E; Schöniger, M; Münz, M; Hiefinger-Schindlbeck, R

2012-07-01

A 13-year-old girl with an osteosarcoma was treated by surgery and chemotherapy. During three transfusions of apheresis platelet concentrates allergic reactions occurred, partly in spite of premedication with an antihistamine and a corticoid. As the patient declared to be allergic to some foods, in-vitro tests for allergen-specific IgE antibodies were performed and showed markedly positive results for specific IgE to carrot and celery, less so to hazelnut, peanut and a lot of other food antigens. The donor of one of the unsuitable platelet concentrates remembered when questioned, that he had eaten carrots and chocolate with hazelnuts during the evening before platelet donation. Two washed platelet concentrates were transfused without any problem. Furthermore, transfusions of nine red blood cell concentrates and one unit of virus-inactivated frozen pooled plasma were well tolerated. Patients should be asked for allergies previous to transfusions to be alert to allergic reactions in patients with a positive history of food or drug allergies. If premedication with antihistamines does not prevent severe allergic transfusion reactions, transfusion of washed platelet concentrates and of virus-inactivated frozen pooled plasma can be considered. © Georg Thieme Verlag KG Stuttgart · New York.

Platelet transfusion therapy in sub-Saharan Africa: bacterial contamination, recipient characteristics and acute transfusion reactions

PubMed Central

Hume, Heather A.; Ddungu, Henry; Angom, Racheal; Baluku, Hannington; Kajumbula, Henry; Kyeyune-Byabazaire, Dorothy; Orem, Jackson; Ramirez-Arcos, Sandra; Tobian, Aaron A.R.

2017-01-01

Background Little data are available on bacterial contamination (BC) of platelet units or acute transfusion reactions to platelet transfusions (PT) in sub-Saharan Africa (SSA). Methods This prospective observational study evaluated the rate of BC of whole blood derived platelet units (WB-PU), the utility of performing Gram stains (GS) to prevent septic reactions, characteristics of patients receiving PT and the rate of acute reactions associated with PT at the Uganda Cancer Institute in Kampala, Uganda. An aliquot of each WB-PU studied was taken to perform GS and culture using the Bactec™ 9120 instrument. Study participants were monitored for reactions. Results 337 WB-PU were evaluated for BC, of which 323 units were transfused in 151 transfusion episodes to 50 patients. The frequency of BC ranged from 0.3%–2.1% (according to criteria used to define BC). The GS had high specificity (99.1%), but low sensitivity to detect units with BC. The median platelet count prior to PT was 10,900 (IQR 6,000–18,900) cells/μL. 78% of PT were given to patients with no bleeding. Acute reactions occurred in 11 transfusion episodes, involving 13 WB-PU, for a rate of 7.3% (95%CI=3.7–12.7%) per transfusion episode. All recipients of units with positive bacterial cultures were receiving antibiotics at the time of transfusion; none experienced a reaction. Conclusions The rate of BC observed in this study is lower than previously reported in SSA, but still remains a safety issue. As GS appears to be an ineffective screening tool, alternate methods should be explored to prevent transfusing bacterially-contaminated platelets in SSA. PMID:27079627

HPA antibodies in Algerian multitransfused patients: Prevalence and involvement in platelet refractoriness.

PubMed

Brouk, Hacene; Bertrand, Gérald; Zitouni, Selma; Djenouni, Amel; Martageix, Corinne; Griffi, Fatiha; Kaplan, Cecile; Ouelaa, Hanifa

2015-06-01

Patients receiving cellular blood components may form HLA or HPA antibodies. The frequency and the specificity of HPA antibodies after a series of blood transfusions have never been reported in the Algerian population which is ethnically diverse and runs a higher risk of platelet alloimmunization due to high b allelic frequencies observed for the HPA systems. 117 polytransfused patients were included in this study; the detection of HPA antibodies was performed by the Monoclonal Antibody-specific Immobilization of Platelet Antigens method (MAIPA). Post-transfusion platelet effectiveness was evaluated by the calculation of corrected count increment (CCI). The antibodies against platelets were detected in 10.26% of the patients. In this study, the platelet systems concerned by the alloimmunizations were specifically HPA-1, -3 and -5 with particular predominance of HPA-1. Twenty two patients were refractory to platelet transfusion, as assessed by a CCI; in which 64% have factors associated with increased platelet consumption. Platelet Immunization was found in 14% of platelet refractoriness (PTR) cases. 03 Anti-platelet antibodies were directed against GPIb-IX (n = 1), anti-HPA-1b (n = 1) and anti HPA-5b (n = 1) associated with anti-HLA antibodies in two cases. HLA and HPA alloimmunization is common among chronically transfused patients. PTR detection, identification of the underlying causes, and selection of the appropriate product for transfusion are fundamental to reduce the risk of major bleedings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dual roles for hepatic lectin receptors in the clearance of chilled platelets

PubMed Central

Rumjantseva, Viktoria; Grewal, Prabhjit K.; Wandall, Hans H.; Josefsson, Emma C.; Sørensen, Anne Louise; Larson, Göran; Marth, Jamey D.; Hartwig, John H.; Hoffmeister, Karin M.

2015-01-01

Chilling rapidly (<4 h) clusters Glycoprotein - (GP)Ib receptors on blood platelets, and ß2-integrins of hepatic macrophages bind ßGlcNAc residues in the clusters leading to rapid clearance of acutely chilled platelets following transfusion. Although capping the ßGlcNAc moieties by galactosylation prevents clearance, this strategy is ineffective after prolonged (>24 h) refrigeration. We report here that prolonged refrigeration increases the density/concentration of exposed galactose residues such that hepatocytes become increasingly involved in the removal of platelets using their Ashwell-Morell receptors. Macrophages always rapidly remove a large fraction of transfused platelets (~40%). With platelet cooling, hepatocyte-dependent clearance further diminishes their recoveries following transfusion. PMID:19783995

Role of platelet transfusion in children with bleeding in dengue fever.

PubMed

Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

2015-12-01

The indications for platelet transfusion in dengue fever are clearly defined in World Health Organization (WHO) guidelines (2011) for dengue fever, but physicians face practical difficulty in its implementation in an epidemic setting. On one hand there is an intense social pressure created by the panic-struck parents to transfuse platelets in presence of bleeding and on the other hand there is a need for its judicious use as the requirement is more than its availability. The study was aimed to assess the clinico-hematological parameters, and the requirement and need for platelet transfusion in children with dengue fever. All children (0-12 yr of age) diagnosed and confirmed with dengue fever at a tertiary care hospital in Puducherry between 1 August 2012 and 31 January 2015 were reviewed retrospectively from hospital case records as per the revised WHO guidelines for dengue fever. The diagnosis was confirmed by NS1 antigen- based ELISA test or dengue serology for IgM and IgG antibodies and the data were analyzed using SPSS 16.0 statistical software. Out of 261 cases of dengue fever, hemorrhagic manifestations were observed in 52 children (19.9%), which mainly included petechiae (38.5%), gum bleeding (34.6%) and melena (26.9%). Thrombocytopenia was seen in 211 (80.8%) cases. Bleeding manifestations were present in 20(39.2%), 8(15.7%), 13(25.5%) and 11(21.6%) cases with platelet count <50,000/mm3, 50,000-100,000/mm3, 1-1.50,000/mm3, and >1.50,000/mm3 respectively. Bleeding manifestations did not always correlate with platelet count in non-severe dengue infection in comparison to severe dengue infection. The most common mode of presentation of severe dengue infection was shock with 102(39.1%) cases and among them only 22 children (21.6%) had bleeding. About 17 children (6.5%) with severe dengue infection required platelet transfusion and out of them, 12 children (70.6%) had a platelet count <20,000/ mm3 whereas five children (29.4%) had platelet count in the range of 20,000-50,000/mm3. Platelet transfusion was required in children with severe dengue infection in the form of significant spontaneous bleed, shock and severe thrombocytopenia. Bleeding should not be considered only indicator to transfuse platelets as it occurred in children even with normal platelet counts. The community and treating physicians should be educated regarding the judicious transfusion of platelets. Unnecessary and empirical use of platelets should be completely avoided especially during an epidemic when there is scarcity in its availability.

Agonist-induced platelet reactivity correlates with bleeding in haemato-oncological patients.

PubMed

Batman, B; van Bladel, E R; van Hamersveld, M; Pasker-de Jong, P C M; Korporaal, S J A; Urbanus, R T; Roest, M; Boven, L A; Fijnheer, R

2017-11-01

Prophylactic platelet transfusions are administered to prevent bleeding in haemato-oncological patients. However, bleeding still occurs, despite these transfusions. This practice is costly and not without risk. Better predictors of bleeding are needed, and flow cytometric evaluation of platelet function might aid the clinician in identifying patients at risk of bleeding. This evaluation can be performed within the hour and is not hampered by low platelet count. Our objective was to assess a possible correlation between bleeding and platelet function in thrombocytopenic haemato-oncological patients. Inclusion was possible for admitted haemato-oncology patients aged 18 years and above. Furthermore, an expected need for platelet transfusions was necessary. Bleeding was graded according to the WHO bleeding scale. Platelet reactivity to stimulation by either adenosine diphosphate (ADP), cross-linked collagen-related peptide (CRP-xL), PAR1- or PAR4-activating peptide (AP) was measured using flow cytometry. A total of 114 evaluations were available from 21 consecutive patients. Platelet reactivity in response to stimulation by all four studied agonists was inversely correlated with significant bleeding. Odds ratios (OR) for bleeding were 0·28 for every unit increase in median fluorescence intensity (MFI) [95% confidence interval (CI) 0·11-0·73] for ADP; 0·59 [0·40-0·87] for CRP-xL; 0·59 [0·37-0·94] for PAR1-AP; and 0·43 [0·23-0·79] for PAR4-AP. The platelet count was not correlated with bleeding (OR 0·99 [0·96-1·02]). Agonist-induced platelet reactivity was significantly correlated to bleeding. Platelet function testing could provide a basis for a personalized transfusion regimen, in which platelet transfusions are limited to those at risk of bleeding. © 2017 International Society of Blood Transfusion.

Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

PubMed

Poon, Man-Chiu; d'Oiron, Roseline

2018-06-07

Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

A prospective, active haemovigilance study with combined cohort analysis of 19 175 transfusions of platelet components prepared with amotosalen–UVA photochemical treatment

PubMed Central

Knutson, F; Osselaer, J; Pierelli, L; Lozano, M; Cid, J; Tardivel, R; Garraud, O; Hervig, T; Domanovic, D; Cukjati, M; Gudmundson, S; Hjalmarsdottir, I B; Castrillo, A; Gonzalez, R; Brihante, D; Santos, M; Schlenke, P; Elliott, A; Lin, J-S; Tappe, D; Stassinopoulos, A; Green, J; Corash, L

2015-01-01

Background and Objectives A photochemical treatment process (PCT) utilizing amotosalen and UVA light (INTERCEPT™ Blood System) has been developed for inactivation of viruses, bacteria, parasites and leucocytes that can contaminate blood components intended for transfusion. The objective of this study was to further characterize the safety profile of INTERCEPT-treated platelet components (PCT-PLT) administered across a broad patient population. Materials and Methods This open-label, observational haemovigilance programme of PCT-PLT transfusions was conducted in 21 centres in 11 countries. All transfusions were monitored for adverse events within 24 h post-transfusion and for serious adverse events (SAEs) up to 7 days post-transfusion. All adverse events were assessed for severity (Grade 0–4), and causal relationship to PCT-PLT transfusion. Results Over the course of 7 years in the study centres, 4067 patients received 19 175 PCT-PLT transfusions. Adverse events were infrequent, and most were of Grade 1 severity. On a per-transfusion basis, 123 (0·6%) were classified an acute transfusion reaction (ATR) defined as an adverse event related to the transfusion. Among these ATRs, the most common were chills (77, 0·4%) and urticaria (41, 0·2%). Fourteen SAEs were reported, of which 2 were attributed to platelet transfusion (<0·1%). No case of transfusion-related acute lung injury, transfusion-associated graft-versus-host disease, transfusion-transmitted infection or death was attributed to the transfusion of PCT-PLT. Conclusion This longitudinal haemovigilance safety programme to monitor PCT-PLT transfusions demonstrated a low rate of ATRs, and a safety profile consistent with that previously reported for conventional platelet components. PMID:25981525

Platelet Storage Lesions: What More Do We Know Now?

PubMed

Ng, Monica Suet Ying; Tung, John-Paul; Fraser, John Francis

2018-04-17

Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage. This article will review advancements in clinical and mechanistic PSL research. In brief, exposure to artificial surfaces and high centrifugation forces during PC preparation initiate PSLs by causing platelet activation, fragmentation, and biochemical release. During room temperature storage, enhanced glycolysis and reduced mitochondrial function lead to glucose depletion, lactate accumulation, and product acidification. Impaired adenosine triphosphate generation reduces platelet capacity to perform energetically demanding processes such as hypotonic stress responses and activation/aggregation. Storage-induced alterations in platelet surface proteins such as thrombin receptors and glycoproteins decrease platelet aggregation. During storage, there is an accumulation of immunoactive proteins such as leukocyte-derive cytokines (tumor necrosis factor α, interleukin (IL) 1α, IL-6, IL-8) and soluble CD40 ligand which can participate in transfusion-related acute lung injury and nonhemolytic transfusion reactions. Storage-induced microparticles have been linked to enhanced platelet aggregation and immune system modulation. Clinically, stored PCs have been correlated with reduced corrected count increment, posttransfusion platelet recovery, and survival across multiple meta-analyses. Fresh PC transfusions have been associated with superior platelet function in vivo; however, these differences were abrogated after a period of circulation. There is currently insufficient evidence to discern the effect of PSLs on transfusion safety. Various bag and storage media changes have been proposed to reduce glycolysis and platelet activation during room temperature storage. Moreover, cryopreservation and cold storage have been proposed as potential methods to prolong PC shelf life by reducing platelet metabolism and bacterial proliferation. However, further work is required to elucidate and manage the PSLs specific to these storage protocols before its implementation in blood banks. Copyright © 2018 Elsevier Inc. All rights reserved.

Improving platelet transfusion safety: biomedical and technical considerations

PubMed Central

Garraud, Olivier; Cognasse, Fabrice; Tissot, Jean-Daniel; Chavarin, Patricia; Laperche, Syria; Morel, Pascal; Lefrère, Jean-Jacques; Pozzetto, Bruno; Lozano, Miguel; Blumberg, Neil; Osselaer, Jean-Claude

2016-01-01

Platelet concentrates account for near 10% of all labile blood components but are responsible for more than 25% of the reported adverse events. Besides factors related to patients themselves, who may be particularly at risk of side effects because of their underlying illness, there are aspects of platelet collection and storage that predispose to adverse events. Platelets for transfusion are strongly activated by collection through disposal equipment, which can stress the cells, and by preservation at 22 °C with rotation or rocking, which likewise leads to platelet activation, perhaps more so than storage at 4 °C. Lastly, platelets constitutively possess a very large number of bioactive components that may elicit pro-inflammatory reactions when infused into a patient. This review aims to describe approaches that may be crucial to minimising side effects while optimising safety and quality. We suggest that platelet transfusion is complex, in part because of the complexity of the “material” itself: platelets are highly versatile cells and the transfusion process adds a myriad of variables that present many challenges for preserving basal platelet function and preventing dysfunctional activation of the platelets. The review also presents information showing - after years of exhaustive haemovigilance - that whole blood buffy coat pooled platelet components are extremely safe compared to the gold standard (i.e. apheresis platelet components), both in terms of acquired infections and of immunological/inflammatory hazards. PMID:26674828

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation

PubMed Central

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. Objectives To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. Selection criteria We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 × 109/L); standard trigger (10 × 109/L); higher trigger (20 × 109/L, 30 × 109/L, 50 × 109/L); or alternative platelet trigger (for example platelet mass)). Data collection and analysis We used the standard methodological procedures expected by Cochrane. Main results Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 × 109/L) versus a higher trigger (20 × 109/L or 30 × 109/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations. The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review. Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity. Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence). One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors’ own results; low-quality evidence). Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence). Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence). Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence). Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference −2.09, 95% CI −3.20 to −0.99; low-quality evidence). One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09). None of the studies reported on quality of life. Authors’ conclusions In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 × 109/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 × 109/L or 30 × 109/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 × 109/L or 30 × 109/L). Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 × 109/L) in the absence of other risk factors for bleeding. PMID:26576687

Comparison of different platelet count thresholds to guide administration of prophylactic platelet transfusion for preventing bleeding in people with haematological disorders after myelosuppressive chemotherapy or stem cell transplantation.

PubMed

Estcourt, Lise J; Stanworth, Simon J; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Murphy, Michael F

2015-11-18

Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people who are thrombocytopenic due to bone marrow failure. Although considerable advances have been made in platelet transfusion therapy in the last 40 years, some areas continue to provoke debate, especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding.This is an update of a Cochrane review first published in 2004, and previously updated in 2012 that addressed four separate questions: prophylactic versus therapeutic-only platelet transfusion policy; prophylactic platelet transfusion threshold; prophylactic platelet transfusion dose; and platelet transfusions compared to alternative treatments. This review has now been split into four smaller reviews looking at these questions individually; this review compares prophylactic platelet transfusion thresholds. To determine whether different platelet transfusion thresholds for administration of prophylactic platelet transfusions (platelet transfusions given to prevent bleeding) affect the efficacy and safety of prophylactic platelet transfusions in preventing bleeding in people with haematological disorders undergoing myelosuppressive chemotherapy or haematopoietic stem cell transplantation (HSCT). We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library 2015, Issue 6, 23 July 2015), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950), and ongoing trial databases to 23 July 2015. We included RCTs involving transfusions of platelet concentrates, prepared either from individual units of whole blood or by apheresis, and given to prevent bleeding in people with haematological disorders (receiving myelosuppressive chemotherapy or undergoing HSCT) that compared different thresholds for administration of prophylactic platelet transfusions (low trigger (5 x 10(9)/L); standard trigger (10 x 10(9)/L); higher trigger (20 x 10(9)/L, 30 x 10(9)/L, 50 x 10(9)/L); or alternative platelet trigger (for example platelet mass)). We used the standard methodological procedures expected by Cochrane. Three trials met our predefined inclusion criteria and were included for analysis in the review (499 participants). All three trials compared a standard trigger (10 x 10(9)/L) versus a higher trigger (20 x 10(9)/L or 30 x 10(9)/L). None of the trials compared a low trigger versus a standard trigger or an alternative platelet trigger. The trials were conducted between 1991 and 2001 and enrolled participants from fairly comparable patient populations.The original review contained four trials (658 participants); in the previous update of this review we excluded one trial (159 participants) because fewer than 80% of participants had a haematological disorder. We identified no new trials in this update of the review.Overall, the methodological quality of the studies was low across different outcomes according to GRADE methodology. None of the included studies were at low risk of bias in every domain, and all the included studies had some threats to validity.Three studies reported the number of participants with at least one clinically significant bleeding episode within 30 days from the start of the study. There was no evidence of a difference in the number of participants with a clinically significant bleeding episode between the standard and higher trigger groups (three studies; 499 participants; risk ratio (RR) 1.35, 95% confidence interval (CI) 0.95 to 1.90; low-quality evidence).One study reported the number of days with a clinically significant bleeding event (adjusted for repeated measures). There was no evidence of a difference in the number of days of bleeding per participant between the standard and higher trigger groups (one study; 255 participants; relative proportion of days with World Health Organization Grade 2 or worse bleeding (RR 1.71, 95% CI 0.84 to 3.48, P = 0.162; authors' own results; low-quality evidence).Two studies reported the number of participants with severe or life-threatening bleeding. There was no evidence of any difference in the number of participants with severe or life-threatening bleeding between a standard trigger level and a higher trigger level (two studies; 421 participants; RR 0.99, 95% CI 0.52 to 1.88; low-quality evidence).Only one study reported the time to first bleeding episode. There was no evidence of any difference in the time to the first bleeding episode between a standard trigger level and a higher trigger level (one study; 255 participants; hazard ratio 1.11, 95% CI 0.64 to 1.91; low-quality evidence).Only one study reported on all-cause mortality within 30 days from the start of the study. There was no evidence of any difference in all-cause mortality between standard and higher trigger groups (one study; 255 participants; RR 1.78, 95% CI 0.83 to 3.81; low-quality evidence).Three studies reported on the number of platelet transfusions per participant. Two studies reported on the mean number of platelet transfusions per participant. There was a significant reduction in the number of platelet transfusions per participant in the standard trigger group (two studies, mean difference -2.09, 95% CI -3.20 to -0.99; low-quality evidence).One study reported on the number of transfusion reactions. There was no evidence to demonstrate any difference in transfusion reactions between the standard and higher trigger groups (one study; 79 participants; RR 0.07, 95% CI 0.00 to 1.09).None of the studies reported on quality of life. In people with haematological disorders who are thrombocytopenic due to myelosuppressive chemotherapy or HSCT, we found low-quality evidence that a standard trigger level (10 x 10(9)/L) is associated with no increase in the risk of bleeding when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L). There was low-quality evidence that a standard trigger level is associated with a decreased number of transfusion episodes when compared to a higher trigger level (20 x 10(9)/L or 30 x 10(9)/L).Findings from this review were based on three studies and 499 participants. Without further evidence, it is reasonable to continue with the current practice of administering prophylactic platelet transfusions using the standard trigger level (10 x 10(9)/L) in the absence of other risk factors for bleeding.

The role of lectins and glycans in platelet clearance

PubMed Central

Hoffmeister, Karin M.

2015-01-01

Summary In recent years, it has become increasingly apparent that the life span of transfused platelets in circulation is regulated, at least in part, by glycan-lectin mediated mechanisms. There is clear evidence that refrigerated platelets are cleared by glycan-lectin mediated clearance mechanisms. Acute platelet cooling clusters glycoprotein (GP) Ibα receptors bearing uncovered N-acetylglucosamine (GlcNAc), and αMβ2 integrins on hepatic macrophages recognise clustered GlcNAc to rapidly clear these platelets from circulation. With prolonged refrigeration GPIbα clustering bearing uncovered galactose increases, which mediates the removal of long-term refrigerated platelets via hepatic Ashwell-Morell receptors (AMR), originally named as asialoglycoprotein receptors. In contrast, little is known about the molecular mechanisms of transfused room temperature platelet clearance. This review examines the role of glycan-lectin mediated clearance of exogenous, i.e. transfused chilled platelet clearance and briefly addresses the current knowledge of stored platelet function, degradation and its relation to platelet clearance. PMID:21781240

The Ratio of Blood Products Transfused Affects Mortality in Patients Receiving Massive Transfusions at a Combat Support Hospital

DTIC Science & Technology

2007-10-01

therapy resuscitation, and exacer- bated by hemorrhagic shock, metabolic acidosis, hypother- mia, hyperfibrinolysis, hypocalcemia , and anemia.11,14–19...outcome studies examining the effect of blood product transfusion ratios for trauma patients requiring massive transfusion. Most deaths (80% to 85%) that...calculation of apheresis platelet units transfused, though FWB has previously been shown to be as effective as 10 units of platelet concentrate.33 The

The practice of platelet transfusion prior to central venous catheterization in presence of coagulopathy: a national survey among clinicians.

PubMed

van de Weerdt, E K; Peters, A L; Goudswaard, E J; Binnekade, J M; van Lienden, K P; Biemond, B J; Vlaar, A P J

2017-05-01

Correction of coagulopathy prior to central venous catheter (CVC) placement is advocated by guidelines, while retrospective studies support restrictive use of transfusion products. We conducted a mixed vignette and questionnaire web survey to investigate current practice and preferences for CVC placement. Clinical vignettes were used to quantify the tendency to administer platelet concentrate. A positive ß-coefficient is in favour of administering platelet concentrate. Ninety-seven physicians answered the survey questions (36 critical care physicians, 14 haematologists, 20 radiologists and 27 anaesthesiologist). Eighty-six physicians subsequently completed the clinical vignettes (response rate 71%). Preferences in favour of correcting thrombocytopenia prior CVC placement were platelet counts of 10 × 10 9 /L and 20 × 10 9 /L (ß = 3·9; ß = 3·2, respectively), the subclavian insertion site (ß = 0·8). An elevated INR (INR = 3; ß = 0·6) and an elevated aPTT (aPTT = 60 s; ß = 0·4) showed a positive trend towards platelet transfusion. Platelet transfusion was less likely in an emergency setting (ß = -0·4). Reported transfusion thresholds for CVC placement varied from <10 × 10 9 /L to 80 × 10 9 /L for platelet count, from 1·0 to 10·0 for INR and from 25 s to 150 s for aPTT. Implementation of ultrasound guidance as standard practice was limited. Current transfusion practice prior to CVC placement is highly variable. Physicians adjust the decision to correct coagulopathy prior CVC placement based on clinical parameters, insertion site and technique applied. © 2017 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation.

PubMed

Fayed, Nirmeen; Mourad, Wessam; Yassen, Khaled; Görlinger, Klaus

2015-03-01

The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. Preoperative thromboelastometric analysis is helpful to predict transfusion requirements in adult living donor liver transplant recipients. This may allow for better preparation and less cross-matching prior to surgery. The findings of our study need to be re-validated in a second prospective patient population.

Platelet and not erythrocyte microparticles are procoagulant in transfused thalassaemia major patients.

PubMed

Agouti, Imane; Cointe, Sylvie; Robert, Stéphane; Judicone, Coralie; Loundou, Anderson; Driss, Fathi; Brisson, Alain; Steschenko, Dominique; Rose, Christian; Pondarré, Corinne; Bernit, Emmanuelle; Badens, Catherine; Dignat-George, Françoise; Lacroix, Romaric; Thuret, Isabelle

2015-11-01

The level of circulating platelet-, erythrocyte-, leucocyte- and endothelial-derived microparticles detected by high-sensitivity flow cytometry was investigated in 37 β-thalassaemia major patients receiving a regular transfusion regimen. The phospholipid procoagulant potential of the circulating microparticles and the microparticle-dependent tissue factor activity were evaluated. A high level of circulating erythrocyte- and platelet-microparticles was found. In contrast, the number of endothelial microparticles was within the normal range. Platelet microparticles were significantly higher in splenectomized than in non-splenectomized patients, independent of platelet count (P < 0·001). Multivariate analysis indicated that phospholipid-dependent procoagulant activity was influenced by both splenectomy (P = 0·001) and platelet microparticle level (P < 0·001). Erythrocyte microparticles were not related to splenectomy, appear to be devoid of proper procoagulant activity and no relationship between their production and haemolysis, dyserythropoiesis or oxidative stress markers could be established. Intra-microparticle labelling with anti-HbF antibodies showed that they originate only partially (median of 28%) from thalassaemic erythropoiesis. In conclusion, when β-thalassaemia major patients are intensively transfused, the procoagulant activity associated with thalassaemic erythrocyte microparticles is probably diluted by transfusions. In contrast, platelet microparticles, being both more elevated and more procoagulant, especially after splenectomy, may contribute to the residual thrombotic risk reported in splenectomized multi-transfused β-thalassaemia major patients. © 2015 John Wiley & Sons Ltd.

The role of platelets and ε-aminocaproic acid in arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome associated hemorrhage

PubMed Central

Weyand, Angela C.; Lombel, Rebecca M.; Pipe, Steven W.; Shavit, Jordan A.

2015-01-01

Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling Gray Platelet Syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from post-procedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. PMID:26505894

[Platelet allo-antibodies identification strategies for preventing and managing platelet refractoriness].

PubMed

Basire, A; Picard, C

2014-11-01

Platelet refractoriness is a serious complication for patients receiving recurrent platelet transfusions, which can be explained by non-immune and immune causes. Human Leukocyte Antigens (HLA) allo-immunization, especially against HLA class I, is the major cause for immune platelet refractoriness. To a lesser extent, allo-antibodies against specific Human Platelet Antigen (HPA) are also involved. Pregnancy, transplantation and previous transfusions can lead to allo-immune reaction against platelet antigens. After transfusion, platelet count is decreased by accelerated platelet destruction related to antibodies fixation on incompatible platelet antigens. New laboratory tests for allo-antibodies identification were developed to improve sensibility and specificity, especially with the LUMINEX(®) technology. The good use and interpretation of these antibodies assays can improve strategies for platelet refractoriness prevention and management with a patient adapted response. Compatible platelets units can be selected according to their identity with recipient typing or immune compatibility regarding HLA or HPA antibodies or HLA epitope compatibility. Prospective studies are needed to further confirm the clinical benefit of new allo-antibodies identification methods and consensus strategies for immune platelet refractoriness management. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Fate in humans of the plasticizer, DI (2-ethylhexyl) phthalate, arising from transfusion of platelets stored in vinyl plastic bags. [plasticizer migration into human blood from vinyl plastic bags during transfusion

NASA Technical Reports Server (NTRS)

Rubin, R. J.; Schiffer, C. A.

1975-01-01

Platelet concentrates were shown to contain 18-38 mg/100 ml of a phthalate plasticizer (DEHP) which arose by migration from the vinyl plastic packs in which the plateletes were prepared and stored. Transfusion of these platelets into 6 adult patients with leukemia resulted in peak blood plasma levels of DEHP ranging from 0.34 - 0.83 mg/100 ml. The blood levels fell mono-exponentially with a mean rate of 2.83 percent per minute and a half-life of 28.0 minutes. Urine was assayed by a method that would measure unchanged DEHP as well as all phthalic acid-containing metabolities. In two patients, at most 60 and 90% of the infused dose, respectively, was excreted in the urine collected for 24 hours post-transfusion. These estimates, however, could be high due to the simultaneous excretion of DEHP remaining from previous transfusions or arising from uncontrolled environmental exposures.

Rationale and design of platelet transfusions in haematopoietic stem cell transplantation: the PATH pilot study.

PubMed

Tay, Jason; Allan, David; Beattie, Sara; Bredeson, Christopher; Fergusson, Dean; Maze, Dawn; Sabloff, Mitchell; Thavorn, Kednapa; Tinmouth, Alan

2016-10-24

In patients with transient thrombocytopenia being treated with high-dose chemotherapy followed by stem cell rescue-haematopoietic stem cell transplantation (HSCT), prophylactic transfusions are standard therapy to prevent bleeding. However, a recent multicentre trial suggests that prophylactic platelet transfusions in HSCT may not be necessary. Additionally, the potential overuse of platelet products places a burden on a scarce healthcare resource. Moreover, the benefit of prophylactic platelet transfusions to prevent clinically relevant haemorrhage is debatable. Current randomised data compare different thresholds for administering prophylactic platelets or prophylactic versus therapeutic platelet transfusions. An alternative strategy involves prescribing prophylactic antifibrinolytic agents such as tranexamic acid to prevent bleeding. This report describes the design of an open-labelled randomised pilot study comparing the prophylactic use of oral tranexamic acid with platelet transfusions in the setting of autologous HSCT. In 3-5 centres, 100 patients undergoing autologous HSCT will be randomly assigned to either a prophylactic tranexamic acid or prophylactic platelets bleeding prevention strategy-based daily platelet values up to 30 days post-transplant. The study will be stratified by centre and type of transplant. The primary goal is to demonstrate study feasibility while collecting clinical outcomes on (1) WHO and Bleeding Severity Measurement Scale (BSMS), (2) transplant-related mortality, (3) quality of life, (4) length of hospital stay, (5) intensive care unit admission rates, (6) Bearman toxicity scores, (7) incidence of infections, (8) transfusion requirements, (9) adverse reactions and (10) economic analyses. This study is funded by a peer-reviewed grant from the Canadian Institutes of Health Research (201 503) and is registered on Clinicaltrials.gov NCT02650791. It has been approved by the Ottawa Health Science Network Research Ethics Board. Study results will presented at national and international conferences. Importantly, the results of this trial will inform the feasibility and conduct of a larger study. NCT02650791; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Comparison of Platelet Transfusion as Fresh Whole Blood Versus Apheresis Platelets for Massively Transfused Combat Trauma patients

DTIC Science & Technology

2011-02-01

transfusion (10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation . Admission...characteristics, resuscitation , and survival were compared between groups. Multivari- ate regression analyses were performed comparing sur- vival of patients at...days. CONCLUSIONS: Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT

Prophylactic platelet transfusion plus supportive care versus supportive care alone in adults with dengue and thrombocytopenia: a multicentre, open-label, randomised, superiority trial.

PubMed

Lye, David C; Archuleta, Sophia; Syed-Omar, Sharifah F; Low, Jenny G; Oh, Helen M; Wei, Yuan; Fisher, Dale; Ponnampalavanar, Sasheela S L; Wijaya, Limin; Lee, Linda K; Ooi, Eng-Eong; Kamarulzaman, Adeeba; Lum, Lucy C; Tambyah, Paul A; Leo, Yee-Sin

2017-04-22

Dengue is the commonest vector-borne infection worldwide. It is often associated with thrombocytopenia, and prophylactic platelet transfusion is widely used despite the dearth of robust evidence. We aimed to assess the efficacy and safety of prophylactic platelet transfusion in the prevention of bleeding in adults with dengue and thrombocytopenia. We did an open-label, randomised, superiority trial in five hospitals in Singapore and Malaysia. We recruited patients aged at least 21 years who had laboratory-confirmed dengue (confirmed or probable) and thrombocytopenia (≤20 000 platelets per μL), without persistent mild bleeding or any severe bleeding. Patients were assigned (1:1), with randomly permuted block sizes of four or six and stratified by centre, to receive prophylactic platelet transfusion in addition to supportive care (transfusion group) or supportive care alone (control group). In the transfusion group, 4 units of pooled platelets were given each day when platelet count was 20 000 per μL or lower; supportive care consisted of bed rest, fluid therapy, and fever and pain medications. The primary endpoint was clinical bleeding (excluding petechiae) by study day 7 or hospital discharge (whichever was earlier), analysed by intention to treat. Safety outcomes were analysed according to the actual treatment received. This study was registered with ClinicalTrials.gov, number NCT01030211, and is completed. Between April 29, 2010, and Dec 9, 2014, we randomly assigned 372 patients to the transfusion group (n=188) or the control group (n=184). The intention-to-treat analysis included 187 patients in the transfusion group (one patient was withdrawn immediately) and 182 in the control group (one was withdrawn immediately and one did not have confirmed or probable dengue). Clinical bleeding by day 7 or hospital discharge occurred in 40 (21%) patients in the transfusion group and 48 (26%) patients in the control group (risk difference -4·98% [95% CI -15·08 to 5·34]; relative risk 0·81 [95% CI 0·56 to 1·17]; p=0·16). 13 adverse events occurred in the transfusion group and two occurred in the control group (5·81% [-4·42 to 16·01]; 6·26 [1·43 to 27·34]; p=0·0064). Adverse events that were possibly, probably, or definitely related to transfusion included three cases of urticaria, one maculopapular rash, one pruritus, and one chest pain, as well as one case each of anaphylaxis, transfusion-related acute lung injury, and fluid overload that resulted in serious adverse events. No death was reported. In adult patients with dengue and thrombocytopenia, prophylactic platelet transfusion was not superior to supportive care in preventing bleeding, and might be associated with adverse events. National Medical Research Council, Singapore. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Role of Platelets and ε-Aminocaproic Acid in Arthrogryposis, Renal Dysfunction, and Cholestasis (ARC) Syndrome Associated Hemorrhage.

PubMed

Weyand, Angela C; Lombel, Rebecca M; Pipe, Steven W; Shavit, Jordan A

2016-03-01

Arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome is a rare disorder associated with platelet abnormalities resembling gray platelet syndrome. Affected patients have normal platelet numbers but abnormal morphology and function. Bleeding symptomatology ranges from postprocedural to spontaneous life-threatening hemorrhage. We report a patient with ARC syndrome and compound heterozygous mutations in VPS33B (vacuolar protein sorting 33B) who presented with significant bleeding requiring numerous admissions and transfusions. She was treated with prophylactic platelet transfusions and ε-aminocaproic acid. This was well-tolerated and significantly decreased transfusion requirements and admissions for bleeding. Our experience provides support for consideration of prophylactic measures in these patients as well as the possibility of using prophylaxis in related disorders. © 2015 Wiley Periodicals, Inc.

Review of in vivo studies of dimethyl sulfoxide cryopreserved platelets.

PubMed

Slichter, Sherrill J; Jones, Melinh; Ransom, Janet; Gettinger, Irena; Jones, Mary Kay; Christoffel, Todd; Pellham, Esther; Bailey, S Lawrence; Corson, Jill; Bolgiano, Doug

2014-10-01

A literature review was conducted to assess the efficacy and safety of dimethyl sulfoxide (DMSO) cryopreserved platelets for potential military use. In vivo DMSO cryopreserved platelet studies published between 1972 and June of 2013 were reviewed. Assessed were the methods of cryopreservation, posttransfusion platelet responses, prevention or control of bleeding, and adverse events. Using the Department of Defense's preferred 6% DMSO cryopreservation method with centrifugation to remove the DMSO plasma before freezing at -65°C and no postthaw wash, mean radiolabeled platelet recoveries in 32 normal subjects were 33% ± 10% (52% ± 12% of the same subject's fresh platelet recoveries), and survivals were 7.5 ± 1.2 days (89% ± 15% of fresh platelet survivals). Using a variety of methods to freeze autologous platelets from 178 normal subjects, mean radiolabeled platelet recoveries were consistently 39% ± 9%, and survivals, 7.4 ± 1.4 days. More than 3000 cryopreserved platelet transfusions were given to 1334 patients. There were 19 hematology/oncology patient studies, and, in 9, mean 1-hour corrected count increments were 11 100 ± 3600 (range, 5700-15 800) after cryopreserved autologous platelet transfusions. In 5 studies, bleeding times improved after transfusion; in 3, there was either no improvement or a variable response. In 4 studies, there was immediate cessation of bleeding after transfusion; in 3 studies, patients being supported only with cryopreserved platelets had no bleeding. In 1 cardiopulmonary bypass study, cryopreserved platelets resulted in significantly less bleeding vs standard platelets. In 3 trauma studies, cryopreserved platelets were hemostatically effective. No significant adverse events were reported in any study. In summary, cryopreserved platelets have platelet recoveries that are about half of fresh platelets, but survivals are only minimally reduced. The platelets appear hemostatically effective and have no significant adverse events. Copyright © 2014 Elsevier Inc. All rights reserved.

38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

Code of Federal Regulations, 2014 CFR

2014-07-01

... platelets or red cells at least once every six weeks, or; infections recurring at least once every six weeks 100 Requiring transfusion of platelets or red cells at least once every three months, or; infections recurring at least once every three months 60 Requiring transfusion of platelets or red cells at least once...

38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

Code of Federal Regulations, 2012 CFR

2012-07-01

... platelets or red cells at least once every six weeks, or; infections recurring at least once every six weeks 100 Requiring transfusion of platelets or red cells at least once every three months, or; infections recurring at least once every three months 60 Requiring transfusion of platelets or red cells at least once...

38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

Code of Federal Regulations, 2013 CFR

2013-07-01

... platelets or red cells at least once every six weeks, or; infections recurring at least once every six weeks 100 Requiring transfusion of platelets or red cells at least once every three months, or; infections recurring at least once every three months 60 Requiring transfusion of platelets or red cells at least once...

38 CFR 4.117 - Schedule of ratings-hemic and lymphatic systems.

Code of Federal Regulations, 2011 CFR

2011-07-01

... platelets or red cells at least once every six weeks, or; infections recurring at least once every six weeks 100 Requiring transfusion of platelets or red cells at least once every three months, or; infections recurring at least once every three months 60 Requiring transfusion of platelets or red cells at least once...

The Non-Hemostatic Aspects of Transfused Platelets

PubMed Central

Sut, Caroline; Tariket, Sofiane; Aubron, Cécile; Aloui, Chaker; Hamzeh-Cognasse, Hind; Berthelot, Philippe; Laradi, Sandrine; Greinacher, Andreas; Garraud, Olivier; Cognasse, Fabrice

2018-01-01

Platelets transfusion is a safe process, but during or after the process, the recipient may experience an adverse reaction and occasionally a serious adverse reaction (SAR). In this review, we focus on the inflammatory potential of platelet components (PCs) and their involvement in SARs. Recent evidence has highlighted a central role for platelets in the host inflammatory and immune responses. Blood platelets are involved in inflammation and various other aspects of innate immunity through the release of a plethora of immunomodulatory cytokines, chemokines, and associated molecules, collectively termed biological response modifiers that behave like ligands for endothelial and leukocyte receptors and for platelets themselves. The involvement of PCs in SARs—particularly on a critically ill patient’s context—could be related, at least in part, to the inflammatory functions of platelets, acquired during storage lesions. Moreover, we focus on causal link between platelet activation and immune-mediated disorders (transfusion-associated immunomodulation, platelets, polyanions, and bacterial defense and alloimmunization). This is linked to the platelets’ propensity to be activated even in the absence of deliberate stimuli and to the occurrence of time-dependent storage lesions. PMID:29536007

Effects of platelet and plasma transfusion on outcome in traumatic brain injury patients with moderate bleeding diatheses.

PubMed

Anglin, Catherine O; Spence, Jeffrey S; Warner, Matthew A; Paliotta, Christopher; Harper, Caryn; Moore, Carol; Sarode, Ravi; Madden, Christopher; Diaz-Arrastia, Ramon

2013-03-01

Object Coagulopathy and thrombocytopenia are common after traumatic brain injury (TBI), yet transfusion thresholds for mildly to moderately abnormal ranges of international normalized ratio and platelet count remain controversial. This study evaluates associations between fresh frozen plasma (FFP) and platelet transfusions with long-term functional outcome and survival in TBI patients with moderate hemostatic laboratory abnormalities. Methods This study is a retrospective review of prospectively collected data of patients with mild to severe TBI. Data include patient demographics, several initial injury severity metrics, daily laboratory values, Glasgow Outcome Score- Extended (GOSE) scores, Functional Status Examination (FSE) scores, and survival to 6 months. Correlations were evaluated between these variables and transfusion of FFP, platelets, packed red blood cells (RBCs), cryoprecipitate, recombinant factor VIIa, and albumin. Ordinal regression was performed to account for potential confounding variables to further define relationships between transfusion status and long-term outcome. By analyzing collected data, mild to moderate coagulopathy was defined as an international normalized ratio 1.4-2.0, moderate thrombocytopenia as platelet count 50 × 10(9)/L to 107 × 10(9)/L, and moderate anemia as 21%-30% hematocrit. Results In patients with mild to moderate laboratory hematological abnormalities, univariate analysis shows significant correlations between poor outcome scores and FFP, platelet, or packed RBC transfusion; the volume of FFP or packed RBCs transfused also correlated with poor outcome. Several measures of initial injury and laboratory abnormalities also correlated with poor outcome. Patient age, initial Glasgow Coma Scale score, and highest recorded serum sodium were included in the ordinal regression model using backward variable selection. In the moderate coagulopathy subgroup, patients transfused with FFP were more likely to have a lower GOSE score relative to those who did not receive a transfusion (OR 5.20 [95% CI 1.72-15.73]). Patients with moderate coagulopathy who received FFP and packed RBCs were even more likely to be have a lower GOSE score (OR 7.17 [95% CI 2.12-24.12]). Moderately anemic patients who received packed RBCs alone were more likely to have a worse long-term functional outcome as determined by GOSE and FSE scores (GOSE: OR 2.41 [95% CI 1.51-3.85]; and FSE: OR 3.27 [95% CI 2.00-5.35]). No transfusion types or combinations were noted to significantly correlate with the 6-month mortality in ordinal regression. Conclusions In TBI patients with moderate coagulopathy, FFP transfusions alone or a combination of FFP and packed RBCs were associated with poorer long-term functional outcomes as measured by the GOSE. Red blood cell transfusions were associated with poor long-term functional outcome in TBI patients with moderate anemia. Platelet transfusion in patients with moderate thrombocytopenia was not significantly associated with outcome. Although transfusion is beneficial to many patients with severe hematological abnormalities, it is not without risk, and the indications for transfusion should be carefully considered in patients with moderate hematological abnormalities.

Intranasal desmopressin versus blood transfusion in cirrhotic patients with coagulopathy undergoing dental extraction: a randomized controlled trial.

PubMed

Stanca, Carmen M; Montazem, Andre H; Lawal, Adeyemi; Zhang, Jin X; Schiano, Thomas D

2010-01-01

Cirrhotic patients waiting for liver transplantation who need dental extractions are given fresh frozen plasma and/or platelets to correct coagulopathy. This is costly and may be associated with transfusion reactions and fluid overload. We evaluated the efficacy of intranasal desmopressin as an alternative to transfusion to correct the coagulopathy of cirrhotic patients undergoing dental extraction. Cirrhotic patients with platelet counts of 30,000 to 50,000/microL and/or international normalized ratio (INR) 2.0 to 3.0 were enrolled in a prospective, controlled, randomized clinical trial. Blood transfusion (fresh frozen plasma 10 mL/kg and/or 1 unit of single donor platelets, respectively) or intranasal desmopressin (300 microg) were given before dental extraction. A standard oral and maxillofacial surgical treatment protocol was performed by the same surgeon. Patients were followed for postextraction bleeding and side-effects over the next 24 to 48 hours. No significant differences were noted between the 2 groups in gender, age, INR, platelet count, creatinine, total bilirubin, ALT, albumin, MELD score, or number of teeth removed (median 3 vs 4). The number of teeth removed ranged between 1 and 31 in the desmopressin group and 1 and 22 in the transfusion group. No patients in desmopressin group required rescue blood transfusion after extraction. One patient in the transfusion group had bleeding after the procedure and required an additional transfusion. Another patient experienced an allergic reaction at the end of transfusion, which was effectively treated with diphenhydramine. Treatment associated average costs were lower for desmopressin ($700/patient) compared with transfusion ($1,173/patient). Intranasal desmopressin was as effective as blood transfusion in achieving hemostasis in cirrhotic patients with moderate coagulopathy undergoing dental extraction. Intranasal desmopressin was much more convenient, less expensive, and well tolerated.

[Platelet transfusion role in neonatal immune thrombocytopenia].

PubMed

Petermann, R

2016-11-01

Neonatal immune thrombocytopenia represent less than 5% of cases of early thrombocytopenia (early-onset<72hours post-delivery). As in adults, thrombocytopenia in neonates is defined as a platelet count less than 150G/L. They are either auto- or allo-immune. Thrombocytopenia resulting from transplacental passage of maternal antibodies directed to platelet membrane glycoproteins can be severe. The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial haemorrhage and neurologic sequelea following. However, auto- and allo-immune thrombocytopenia have very different characteristics including the treatment management. In fact, this treatment is based on platelet transfusion associated or not to intravenous immunoglobulin administration. The purpose of this article is to remind platelet transfusion's place in neonatal immune thrombocytopenia in terms of recently published French guidelines and international practices. Copyright © 2016. Published by Elsevier SAS.

[Point-of-Care Testing in Trauma Patients - Methods and Evidence].

PubMed

Dirkmann, Daniel; Britten, Martin W; Frey, Ulrich H

2018-06-01

In severely injured patients, trauma-induced coagulopathy (TIC) present at hospital admission is associated with increased transfusion requirements, morbidity and mortality. Early and effective treatment contributes to improved survival rates. Laboratory coagulation assays have long turn-around times and evidence for their usefulness, especially in the context of TIC, is weak. Due to the lack of appropriate guidance, transfusion of allogeneic blood products frequently follows a ratio-based concept (e.g., transfusion of erythrocytes and plasma in a 1 : 1 ratio). Point-of-care (PoC) tests enable the assessment of prothrombin time (PT) and activated partial thromboplastin time in few minutes. However, although normal PT in these tests allows to rule out relevant effects of several anticoagulants, they are not able to detect patients with TIC and/or requiring subsequent massive transfusion. Viscoelastic tests (VETs) make it possible to assess defects in thrombin generation, hypofibrinogenaemia, thrombocytopenia, and hyperfibrinolysis, and thus enable targeted therapy. Impairment of platelet function is the common blind spot not detectable using both standard laboratory-based tests and VETs. However, PoC platelet function tests enable to detect platelet defects and patients taking anti-platelet. Furthermore, impaired platelet function has been identified as a strong predictor for coagulopathy and massive transfusion in trauma patients. In other clinical settings, coagulation management based on VETs is associated with decreased transfusion requirements, incidence of acute kidney failure, and mortality, respectively. Data of the first small prospective randomised trial indicate superiority of VET guided coagulation management solely using coagulation factor concentrates, when compared to plasma transfusions in severe trauma. Georg Thieme Verlag KG Stuttgart · New York.

Transfusion in critically ill children: indications, risks, and challenges.

PubMed

Parker, Robert I

2014-03-01

To provide a concise review of transfusion-related issues and practices in the pediatric patient population, with a focus on those issues of particular importance to the care of critically ill children. Electronic search of the PubMed database using the search terms "pediatric transfusion," "transfusion practices," "transfusion risks," "packed red blood cell transfusion," "white blood cell transfusion," "platelet transfusion," "plasma transfusion," and "massive transfusion" either singly or in combination. All identified articles published since 2000 were manually reviewed for study design, content, and support for indicated conclusions, and the bibliographies were scrutinized for pertinent references not identified in the PubMed search. Selected studies from this group were then manually reviewed for possible inclusion in this review. Well-designed studies have demonstrated the benefit of "restrictive" transfusion practices across the entire age spectrum of pediatric patients across a wide spectrum of pediatric illness. However, clinician implementation of the more restrictive transfusion practices supported by these studies is variable. Additionally, the utilization of both platelet and plasma transfusions in either a "prophylactic" or "therapeutic" setting appears to be greater than that supported by published data. The preponderance of prospective, randomized trials and retrospective analyses support the use of a restrictive packed RBC transfusion policy in most clinical conditions in children. Neonatal transfusions guidelines rely largely on "expert opinion" rather than experimental data. Current transfusion practices for both platelets and coagulant products (e.g., fresh-frozen plasma and recombinant-activated factor VII) are poorly aligned with recommended transfusion guidelines. As with adults, current transfusion practices in children often do not reflect implementation of our current knowledge on the need for transfusion. Greater efforts to implement current evidence-based transfusion practices are needed.

Fibrinogen concentrate as first-line therapy in aortic surgery reduces transfusion requirements in patients with platelet counts over or under 100×109/L

PubMed Central

Solomon, Cristina; Rahe-Meyer, Niels

2015-01-01

Background Administration of fibrinogen concentrate, targeting improved maximum clot firmness (MCF) of the thromboelastometric fibrin-based clot quality test (FIBTEM) is effective as first-line haemostatic therapy in aortic surgery. We performed a post-hoc analysis of data from a randomised, placebo-controlled trial of fibrinogen concentrate, to investigate whether fibrinogen concentrate reduced transfusion requirements for patients with platelet counts over or under 100×109/L. Material and methods Aortic surgery patients with coagulopathic bleeding after cardiopulmonary bypass were randomised to receive either fibrinogen concentrate (n=29) or placebo (n=32). Platelet count was measured upon removal of the aortic clamp, and coagulation and haematology parameters were measured peri-operatively. Transfusion of allogeneic blood components was recorded and compared between groups. Results After cardiopulmonary bypass, haemostatic and coagulation parameters worsened in all groups; plasma fibrinogen level (determined by the Clauss method) decreased by 43–58%, platelet count by 53–64%, FIBTEM maximum clot firmness (MCF) by 38–49%, FIBTEM maximum clot elasticity (MCE) by 43–54%, extrinsically activated test (EXTEM) MCF by 11–22%, EXTEM MCE by 25–41% and the platelet component of the clot by 23–39%. Treatment with fibrinogen concentrate (mean dose 7–9 g in the 4 groups) significantly reduced post-operative allogeneic blood component transfusion requirements when compared to placebo both for patients with a platelet count ≥100×109/L and for patients with a platelet count <100×109/L. Discussion FIBTEM-guided administration of fibrinogen concentrate reduced transfusion requirements when used as a first-line haemostatic therapy during aortic surgery in patients with platelet counts over or under 100×109/L. PMID:25369608

Relative risk of reducing the lifetime blood donation deferral for men who have had sex with men versus currently tolerated transfusion risks.

PubMed

Vamvakas, Eleftherios C

2011-01-01

The risks of known and emerging transfusion-transmitted infections (TTIs) from reducing the current lifetime blood donation deferral for men who have had sex with men (MSM) to 1 or 5 years were compared to the risk from continuing to transfuse in the United States 12.5% of platelet doses as pooled whole-blood-derived (rather than single-donor) platelets. Assumptions made in mathematical models and blood donor/transfusion studies of the risks of TTIs since 2000 were evaluated. The number of HIV, hepatitis B virus, or hepatitis C virus TTIs from reducing the MSM deferral to 1 year is, respectively, 0.88, 2.94, or 66.9, many more than 10 times smaller than the risk from pooled platelets. If erroneous release of HIV-positive units (a risk independent of a donor's source of infection) is not considered, the MSM risk is 1 HIV-infectious donation per 17 to 56 million MSM donations. Any purportedly increased risk of human herpesvirus-8 transmission from MSM donors is far smaller than the risk of transfusion-associated sepsis from pooled platelets. Single-donor platelets from MSM after 5 years' abstinence are as safe or 5 times safer than our current pooled platelets--if the next TTI to emerge were transmitted, respectively, sexually or by another route. Thus, acceptance of MSM as blood donors after 1 or 5 years' abstinence may result in a postulated increase in risk that is so much smaller than the currently tolerated transfusion risk and so small in absolute terms that the ethical question of fairness to the MSM group justifies the change in policy. Copyright © 2011 Elsevier Inc. All rights reserved.

Low Titer Group O Whole Blood in Emergency Situations

DTIC Science & Technology

2014-01-01

ABO incompatibility is defined as transfusion of donor anti-A and/or anti-B to a patient whose RBCs carry A or B antigens . Clinical consequences are...typically minor and frequently subclinical (12). Platelet transfusions with ABO- incompatible plasma occur routinely in hospitals in the United States...minor ABO incompatibility as nonidentical platelet transfusion . It is therefore a paradox that in some countries the regula- tory authorities have

Reduction in blood transfusion in a cohort of infants having cardiac surgery with cardiopulmonary bypass after instituting a goal-directed transfusion policy.

PubMed

Machovec, Kelly A; Smigla, Gregory; Ames, Warwick A; Schwimer, Courtney; Homi, H Mayumi; Dhakal, Ishwori B; Jaquiss, Robert D B; Lodge, Andrew J; Jooste, Edmund H

2016-10-01

Current trends in pediatric cardiac surgery and anesthesiology include goal-directed allogeneic blood transfusion, but few studies address the transfusion of platelets and cryoprecipitate. We report a quality improvement initiative to reduce the transfusion of platelets and cryoprecipitate in infants having cardiac surgery with cardiopulmonary bypass (CPB). Data from 50 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB were prospectively collected after the institution of a policy to obtain each patient's platelet and fibrinogen levels during the rewarming phase of CPB. Data from 48 consecutive patients weighing four to ten kilograms having cardiac surgery with CPB prior to the implementation of the policy change were retrospectively collected. Demographics, laboratory values and blood product transfusion data were compared between the groups, using the Chi-square/Fisher's exact test or the T-Test/Wilcoxon Rank-Sum test, as appropriate. The results showed more total blood product exposures in the control group during the time from bypass through the first twenty-four post-operative hours (median of 2 units versus 1 unit in study group, p=0.012). During the time period from CPB separation through the first post-operative day, 67% of patients in the control group received cryoprecipitate compared to 32% in the study group (p=0.0006). There was no difference in platelet exposures between the groups. Checking laboratory results during the rewarming phase of CPB reduced cryoprecipitate transfusion by 50%. This reproducible strategy avoids empiric and potentially unnecessary transfusion in this vulnerable population. © The Author(s) 2016.

Pathogen reduction by ultraviolet C light effectively inactivates human white blood cells in platelet products.

PubMed

Pohler, Petra; Müller, Meike; Winkler, Carla; Schaudien, Dirk; Sewald, Katherina; Müller, Thomas H; Seltsam, Axel

2015-02-01

Residual white blood cells (WBCs) in cellular blood components induce a variety of adverse immune events, including nonhemolytic febrile transfusion reactions, alloimmunization to HLA antigens, and transfusion-associated graft-versus-host disease (TA-GVHD). Pathogen reduction (PR) methods such as the ultraviolet C (UVC) light-based THERAFLEX UV-Platelets system were developed to reduce the risk of transfusion-transmitted infection. As UVC light targets nucleic acids, it interferes with the replication of both pathogens and WBCs. This preclinical study aimed to evaluate the ability of UVC light to inactivate contaminating WBCs in platelet concentrates (PCs). The in vitro and in vivo function of WBCs from UVC-treated PCs was compared to that of WBCs from gamma-irradiated and untreated PCs by measuring cell viability, proliferation, cytokine secretion, antigen presentation in vitro, and xenogeneic GVHD responses in a humanized mouse model. UVC light was at least as effective as gamma irradiation in preventing GVHD in the mouse model. It was more effective in suppressing T-cell proliferation (>5-log reduction in the limiting dilution assay), cytokine secretion, and antigen presentation than gamma irradiation. The THERAFLEX UV-Platelets (MacoPharma) PR system can substitute gamma irradiation for TA-GVHD prophylaxis in platelet (PLT) transfusion. Moreover, UVC treatment achieves suppression of antigen presentation and inhibition of cytokine accumulation during storage of PCs, which has potential benefits for transfusion recipients. © 2014 AABB.

Proteomics meets blood banking: identification of protein targets for the improvement of platelet quality.

PubMed

Schubert, Peter; Devine, Dana V

2010-01-03

Proteomics has brought new perspectives to the fields of hematology and transfusion medicine in the last decade. The steady improvement of proteomic technology is propelling novel discoveries of molecular mechanisms by studying protein expression, post-translational modifications and protein interactions. This review article focuses on the application of proteomics to the identification of molecular mechanisms leading to the deterioration of blood platelets during storage - a critical aspect in the provision of platelet transfusion products. Several proteomic approaches have been employed to analyse changes in the platelet protein profile during storage and the obtained data now need to be translated into platelet biochemistry in order to connect the results to platelet function. Targeted biochemical applications then allow the identification of points for intervention in signal transduction pathways. Once validated and placed in a transfusion context, these data will provide further understanding of the underlying molecular mechanisms leading to platelet storage lesion. Future aspects of proteomics in blood banking will aim to make use of protein markers identified for platelet storage lesion development to monitor proteome changes when alterations such as the use of additive solutions or pathogen reduction strategies are put in place in order to improve platelet quality for patients. (c) 2009 Elsevier B.V. All rights reserved.

Apheresis platelet concentrates contain platelet-derived and endothelial cell-derived microparticles.

PubMed

Rank, A; Nieuwland, R; Liebhardt, S; Iberer, M; Grützner, S; Toth, B; Pihusch, R

2011-02-01

Microparticles (MP) are membrane vesicles with thrombogenic and immunomodulatory properties. We determined MP subgroups from resting platelets, activated platelets and endothelial cells in donors and apheresis platelet concentrates (PC). MP were double stained with annexin V and CD61 (platelet-derived MP; PMP), P-selectin or CD63 (MP from activated platelets) and CD144 plus E-selectin (endothelial cell-derived MP; EMP) and detected by flow cytometry in platelet donors (n=36) and apheresis PC (n=11; Trima™). PC contained MP, mainly from resting platelets [93% (90-95)], and minor fractions of PMP from activated platelets [P-selectin(+) or CD63(+); 4·8% (3·2-7·7) and 2·6% (2·0-4·0)]. Compared to donors, levels of annexin V+ MP, PMP, P-selectin(+) and CD63(+) MP were 1·7-, 2·3-, 8·6- and 3·1-fold higher in PC (all P<0·05). During storage (1-5 days), levels of annexin V+ MP and PMP did not increase, although small increases in the fraction of P-selectin(+) or CD63(+) MP occurred (both P<0·05). PC also contained EMP, which were 2·6- to 3·7-fold enriched in PC compared to donors (P<0·05). Transfusion of apheresis PC also results in transfusion of HLA-carrying PMP and EMP. This might counteract the aim of reducing transfused HLA load by leucodepletion. The increases in PMP exposing P-selectin or CD63 reflect mild platelet activation during storage. We conclude that in leucodepleted platelet apheresis using fluidized particle bed technology, MP are harvested mainly from the donor by apheresis. Improvement in apheresis technology might reduce MP load. © 2010 The Author(s). Vox Sanguinis © 2010 International Society of Blood Transfusion.

Scalable Generation of Universal Platelets from Human Induced Pluripotent Stem Cells

PubMed Central

Feng, Qiang; Shabrani, Namrata; Thon, Jonathan N.; Huo, Hongguang; Thiel, Austin; Machlus, Kellie R.; Kim, Kyungho; Brooks, Julie; Li, Feng; Luo, Chenmei; Kimbrel, Erin A.; Wang, Jiwu; Kim, Kwang-Soo; Italiano, Joseph; Cho, Jaehyung; Lu, Shi-Jiang; Lanza, Robert

2014-01-01

Summary Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid “surge” capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness. PMID:25418726

Scalable generation of universal platelets from human induced pluripotent stem cells.

PubMed

Feng, Qiang; Shabrani, Namrata; Thon, Jonathan N; Huo, Hongguang; Thiel, Austin; Machlus, Kellie R; Kim, Kyungho; Brooks, Julie; Li, Feng; Luo, Chenmei; Kimbrel, Erin A; Wang, Jiwu; Kim, Kwang-Soo; Italiano, Joseph; Cho, Jaehyung; Lu, Shi-Jiang; Lanza, Robert

2014-11-11

Human induced pluripotent stem cells (iPSCs) provide a potentially replenishable source for the production of transfusable platelets. Here, we describe a method to generate megakaryocytes (MKs) and functional platelets from iPSCs in a scalable manner under serum/feeder-free conditions. The method also permits the cryopreservation of MK progenitors, enabling a rapid "surge" capacity when large numbers of platelets are needed. Ultrastructural/morphological analyses show no major differences between iPSC platelets and human blood platelets. iPSC platelets form aggregates, lamellipodia, and filopodia after activation and circulate in macrophage-depleted animals and incorporate into developing mouse thrombi in a manner identical to human platelets. By knocking out the β2-microglobulin gene, we have generated platelets that are negative for the major histocompatibility antigens. The scalable generation of HLA-ABC-negative platelets from a renewable cell source represents an important step toward generating universal platelets for transfusion as well as a potential strategy for the management of platelet refractoriness.

Romiplostim for Immune Thrombocytopenia in Neuroblastoma Patients Receiving Chemotherapy.

PubMed

Fassel, Hannah; Bussel, James B; Roberts, Stephen S; Modak, Shakeel

2018-04-20

Thrombocytopenia, a serious complication of myelosuppressive chemotherapy in cancer patients, is managed with platelet transfusions until recovery of platelet counts. However, children receiving chemotherapy can rarely develop immune thrombocytopenia (ITP) that is refractory to transfused platelets. This limits the ability to achieve adequate platelet counts and administer further myelosuppressive chemotherapy safely, especially if first-line ITP therapy is ineffective. We report 2 cases of intravenous immunoglobulin refractory ITP in children receiving chemotherapy for high-risk neuroblastoma. ITP was successfully treated with the thrombopoietin-receptor-agonist romiplostim, allowing safe and timely continuation of antineuroblastoma therapies in these high-risk patients.

Postoperative acute kidney injury following intraoperative blood product transfusions during cardiac surgery.

PubMed

Kindzelski, Bogdan A; Corcoran, Philip; Siegenthaler, Michael P; Horvath, Keith A

2018-01-01

This study explored the nature of the association between intraoperative usage of red blood cell, fresh frozen plasma, cryoprecipitate or platelet transfusions and acute kidney injury. A total of 1175 patients who underwent cardiac surgery between 2008 and 2013 were retrospectively analyzed. We assessed the association between: (1) preoperative patient characteristics and acute kidney injury, (2) intraoperative blood product usage and acute kidney injury, (3) acute kidney injury and 30-day mortality or re-hospitalization. In our cohort of 1175 patients, 288 patients (24.5%) developed acute kidney injury. This included 162 (13.8%), 69 (5.9%) and 57 (4.9%) developing stage 1, stage 2 or stage 3 acute kidney injury, respectively. Increased red blood cell, fresh frozen plasma or platelet transfusions increased the odds of developing acute kidney injury. Specifically, every unit of red blood cells, fresh frozen plasma or platelets transfused was associated with an increase in the covariate-adjusted odds ratio of developing ⩾ stage 2 kidney injury of 1.18, 1.19 and 1.04, respectively. Intraoperative blood product transfusions were independently associated with an increased odds of developing acute kidney injury following cardiac surgery. Further randomized studies are needed to better define intraoperative transfusion criteria.

Recent advances in transfusions in neonates/infants

PubMed Central

Goel, Ruchika; Josephson, Cassandra D.

2018-01-01

Transfusions of red blood cells (RBCs), platelets, and plasma are critical therapies for infants and neonates (particularly preterm neonates) in the neonatal intensive care unit, who are the most frequently transfused subpopulation across all ages. Although traditionally a significant gap has existed between the blood utilization and the evidence base essential to adequately guide transfusion practices in infants and neonates, pediatric transfusion medicine is evolving from infancy and gradually coming of age. It is entering an exciting era with recognition as an independent discipline, a new and evolving high-quality evidence base for transfusion practices, novel technologies and therapeutics, and national/international collaborative research, educational, and clinical efforts. Triggers and thresholds for red cell transfusion are accumulating evidence with current phase III clinical trials. Ongoing trials and studies of platelet and plasma transfusions in neonates are anticipated to provide high-quality evidence in years to come. This article aims to summarize the most current evidence-based practices regarding blood component therapy in neonates. Data on the use of specific components (RBCs, plasma, and platelets) are provided. We attempt to define thresholds for anemia, thrombocytopenia, and abnormal coagulation profile in neonates to highlight the difficulties in having a specific cutoff value in neonates and preterm infants. Indications for transfusion of specific products, transfusion thresholds, and current practices and guidelines are provided, and possible adverse outcomes and complications are discussed. Finally, the critical research knowledge gaps in these practices as well as ongoing and future research areas are discussed. In an era of personalized medicine, neonatal transfusion decisions guided by a strong evidence base must be the overarching goal, and this underlies all of the strategic initiatives in pediatric and neonatal transfusion research highlighted in this article. PMID:29904575

Implementation of secondary bacterial culture testing of platelets to mitigate residual risk of septic transfusion reactions.

PubMed

Bloch, Evan M; Marshall, Christi E; Boyd, Joan S; Shifflett, Lisa; Tobian, Aaron A R; Gehrie, Eric A; Ness, Paul M

2018-04-01

Bacterial contamination of platelets remains a major transfusion-associated risk despite long-standing safety measures in the United States. We evaluated an approach using secondary bacterial culture (SBC) to contend with residual risk of bacterial contamination. Phased implementation of SBC was initiated in October 2016 for platelets (all apheresis collected) received at our institution from the blood donor center (Day 3 post collection). Platelet products were sampled aseptically (5 mL inoculated into an aerobic bottle [BacT/ALERT BPA, BioMerieux, Inc.]) by the blood bank staff upon receipt, using a sterile connection device and sampling kit. The platelet sample was inoculated into an aerobic blood culture bottle and incubated at 35°C for 3 days. The cost of SBC was calculated on the basis of consumables and labor costs at time of implementation. In the 13 months following implementation (October 6, 2016, to November 30, 2017), 23,044/24,653 (93.47%) platelet products underwent SBC. A total of eight positive cultures were detected (incidence 1 in 2881 platelet products), seven of which were positive within 24 hours of SBC. Coagulase negative Staphyloccus spp. were identified in four cases. Five of the eight cases were probable true positive (repeat reactive) and interdicted (cost per averted case was US$77,935). The remaining three cases were indeterminate. No septic transfusion reactions were reported during the observation period. We demonstrate the feasibility of SBC of apheresis platelets to mitigate bacterial risk. SBC is lower cost than alternative measures (e.g., pathogen reduction and point-of-release testing) and can be integrated into workflow at hospital transfusion services. © 2018 AABB.

Platelet bioreactor-on-a-chip

PubMed Central

Mazutis, Linas; Wu, Stephen; Sylman, Joanna L.; Ehrlicher, Allen; Machlus, Kellie R.; Feng, Qiang; Lu, Shijiang; Lanza, Robert; Neeves, Keith B.; Weitz, David A.; Italiano, Joseph E.

2014-01-01

Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs. PMID:25606631

Comparison of a therapeutic-only versus prophylactic platelet transfusion policy for people with congenital or acquired bone marrow failure disorders

PubMed Central

Ashraf, Asma; Hadjinicolaou, Andreas V; Doree, Carolyn; Hopewell, Sally; Trivella, Marialena; Estcourt, Lise J

2016-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: To compare a therapeutic-only versus prophylactic platelet transfusion policy for people with myelodysplasia, inherited or acquired aplastic anaemia, and other congenital bone marrow failure disorders. PMID:27660553

Ethical Questions about Platelet Transfusions at the End of Life.

PubMed

Sherbeck, John P; Boss, Renee D

2016-08-01

This case of platelet transfusion in palliative care illustrates a common dilemma in transfusion medicine: approval of the use of a scarce, yet potentially life-saving, resource. As in this case, these decisions often involve seriously ill patients with acute needs and evolving goals of care. The use of resources to treat the patient at hand must be balanced against maintaining adequate resources to treat future patients. In this setting, the ethical principles of beneficence and social justice are in conflict. © 2016 American Medical Association. All Rights Reserved.

Recurrent life-threatening reactions to platelet transfusion in an aplastic anaemia patient with a paroxysmal nocturnal haemoglobinuria clone.

PubMed

Mohamed, M; Bates, G; Richardson, D; Burrows, L

2014-09-01

A 60-year-old woman was diagnosed with non-severe aplastic anaemia when she presented with anaemia and thrombocytopenia. She developed recurrent life-threatening hypotensive reactions during transfusion of leukodepleted platelet concentrates, and washed platelet concentrates prevented the development of such reactions subsequently. A paroxysmal nocturnal haemoglobinuria clone was detected on investigating for aplastic anaemia, which has been speculated to play a role in the recurrent hypotensive reactions. © 2014 The Authors; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.

Propionibacterium acnes lacks the capability to proliferate in platelet concentrates.

PubMed

Störmer, M; Kleesiek, K; Dreier, J

2008-04-01

Propionibacterium acnes is considered to be one of the most frequent contaminants of platelet concentrates (PCs) when anaerobic culture-based detection methods are used. But Propionibacteria are often detected too late when blood products have already been transfused. Therefore, its transfusion relevance is still demanding clarification because studies of the outcome of patients transfused with P. acnes-contaminated PCs are still uncommon. In this study, we monitored clinical effects in patients after transfusion of PCs, which were detected too late in sterility testing. Furthermore, we assessed the bacterial proliferation of Propionibacterium species seeded into PCs to clarify their significance for platelet bacteria screening. In the look-back process, we followed the route of the putative contaminated PC units from storage to transfusion. In the in vitro study, PCs were inoculated with 1-100 colony-forming unit (CFU)/ml of clinical isolates of Propionibacteria (n = 10). Sampling was performed during 10-day aerobic storage at 22 degrees C. The presence of bacteria was assessed by plating culture and automated BacT/Alert culture system. Propionibacterium acnes shows slow or no growth under PC storage conditions. Clinical signs of adverse events after transfusion of potentially contaminated PC units were not reported. Propionibacteria do not proliferate under PC storage conditions and therefore may be missed or detected too late when blood products have already been transfused.

[Fever-shivers reaction and standard platelet concentrates transfusion: a prospective study].

PubMed

Houissa, B; Abdelkefi, S; Bouslama, M; Zaeir, M; Chakroun, T; Ghachem, L; Yacoub, S

2003-09-01

Fever-shivers reaction (FSR) is the most frequent transfusion immediate incident related to platelet transfusions. The aim of our prospective study was to assess the frequency of the different immediate incidents, especially the frequency and the causes of the FSR, observed during the transfusion of standard platelet concentrates (SPC). For each FSR, analysis of causes included: a bacterial culture of the implicated SPC, a blood culture and HLA antibody screening (lymphocytotoxicity assay) among the patients. In the study period, 34 patients were followed during 74 transfusions. Ten immediate incidents were noted; FSR: N = 8, erythema-urticaria: N = 1 and nausea-vomit: N = 1. The FSR was observed in 6 patients who received 56 SPC. Analysis of causes of this reaction revealed that: HLA antibodies were present in one patient; bacterial contamination was not found neither among the patients nor in the implicated SPC, and the risk of the FSR occurrence rose with increased storage time of the SPC transfused. Indeed, a significant difference was noted between the mean age of the SPC implicated in the FSR and the mean age of those not implicated (P = 0,0028). In conclusion, the FSR is a frequent incident observed during SPC transfusions. In the majority of cases, the cause of this reaction was not identified. Further studies will be necessary to better understand the physiological mechanisms of the FSR.

Quality indicators for the hospital transfusion chain: a national survey conducted in 100 dutch hospitals.

PubMed

Zijlker-Jansen, P Y; Janssen, M P; van Tilborgh-de Jong, A J W; Schipperus, M R; Wiersum-Osselton, J C

2015-10-01

The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of hospitals measured the pretransfusion platelet count in over 80% of platelet transfusions and 87% of hospitals complied with the legally mandatory traceability of blood components in over 95% of transfusions. With the current blood transfusion indicators, it is feasible to monitor aspects of the quality of the hospital transfusion chain and blood transfusion practice and to assess guideline compliance. The results from this study suggest that there are opportunities for significant improvement in blood transfusion practice in the Netherlands. These indicators could potentially be used for national and international benchmarking of blood transfusion practice. © 2015 International Society of Blood Transfusion.

Oral surgery in a patient with cirrhosis and thrombocytopenia: a case report.

PubMed

Patel, Seena; Perry, Maureen Munnelly; Spolarich, Ann Eshenaur

2016-01-01

While most oral surgical procedures can be safely performed in an outpatient setting, certain medical conditions may present a higher chance of postoperative complications. In particular, those predisposing the patient to bleeding abnormalities pose a potential risk when performing such treatments. The authors report a case involving full-mouth extractions in a patient with cirrhosis and thrombocytopenia after obtaining a platelet transfusion. A 62-year-old Caucasian female presented to a university special care dental clinic requiring extractions. Her pertinent medical history was remarkable for cirrhosis and thrombocytopenia, with a platelet count of 32,000/uL. Upon medical consultation, the patient was appointed for a prophylactic platelet transfusion. The surgery was rendered uneventfully, and the patient achieved adequate hemostasis without hospitalization. Patients with cirrhosis pose a potential bleeding risk with dental surgical procedures. Pre-operative medical consultation, review of pertinent laboratory values, and prophylactic platelet transfusion allow these patients to be managed safely in an outpatient setting. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.

PubMed

Moreau, Thomas; Evans, Amanda L; Vasquez, Louella; Tijssen, Marloes R; Yan, Ying; Trotter, Matthew W; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M; Pask, Dean C; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H; Pedersen, Roger A; Ghevaert, Cedric

2016-04-07

The production of megakaryocytes (MKs)--the precursors of blood platelets--from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 10(5) mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology.

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review.

PubMed

Desborough, Michael; Hadjinicolaou, Andreas V; Chaimani, Anna; Trivella, Marialena; Vyas, Paresh; Doree, Carolyn; Hopewell, Sally; Stanworth, Simon J; Estcourt, Lise J

2016-10-31

People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions. We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016. We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion. Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI).We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions.We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I 2 statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane 'Risk of bias' tool. The quality of the evidence was assessed using GRADE methods. We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified.We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies.The GRADE quality of the evidence was very low to moderate across the different outcomes.There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence).There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence).There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence).There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence).There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence).There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence).No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness.In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance). There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting.

Alternative agents to prophylactic platelet transfusion for preventing bleeding in people with thrombocytopenia due to chronic bone marrow failure: a meta-analysis and systematic review

PubMed Central

Desborough, Michael; Hadjinicolaou, Andreas V; Chaimani, Anna; Trivella, Marialena; Vyas, Paresh; Doree, Carolyn; Hopewell, Sally; Stanworth, Simon J; Estcourt, Lise J

2017-01-01

Background People with thrombocytopenia due to bone marrow failure are vulnerable to bleeding. Platelet transfusions have limited efficacy in this setting and alternative agents that could replace, or reduce platelet transfusion, and are effective at reducing bleeding are needed. Objectives To compare the relative efficacy of different interventions for patients with thrombocytopenia due to chronic bone marrow failure and to derive a hierarchy of potential alternative treatments to platelet transfusions. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (the Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1980) and ongoing trial databases to 27 April 2016. Selection criteria We included randomised controlled trials in people with thrombocytopenia due to chronic bone marrow failure who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII (rFVIIa), desmopressin (DDAVP), recombinant factor XIII (rFXIII), recombinant interleukin (rIL)6 or rIL11, or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard of care or platelet transfusion). We excluded people undergoing intensive chemotherapy or stem cell transfusion. Data collection and analysis Two review authors independently screened search results, extracted data and assessed trial quality. We estimated summary risk ratios (RR) for dichotomous outcomes. We planned to use summary mean differences (MD) for continuous outcomes. All summary measures are presented with 95% confidence intervals (CI). We could not perform a network meta-analysis because the included studies had important differences in the baseline severity of disease for the participants and in the number of participants undergoing chemotherapy. This raised important concerns about the plausibility of the transitivity assumption in the final dataset and we could not evaluate transitivity statistically because of the small number of trials per comparison. Therefore, we could only perform direct pairwise meta-analyses of included interventions. We employed a random-effects model for all analyses. We assessed statistical heterogeneity using the I2 statistic and its 95% CI. The risk of bias of each study included was assessed using the Cochrane ’Risk of bias’ tool. The quality of the evidence was assessed using GRADE methods. Main results We identified seven completed trials (472 participants), and four ongoing trials (recruiting 837 participants) which are due to be completed by December 2020. Of the seven completed trials, five trials (456 participants) compared a TPO mimetic versus placebo (four romiplostim trials, and one eltrombopag trial), one trial (eight participants) compared DDAVP with placebo and one trial (eight participants) compared tranexamic acid with placebo. In the DDAVP trial, the only outcome reported was the bleeding time. In the tranexamic acid trial there were methodological flaws and bleeding definitions were subject to significant bias. Consequently, these trials could not be incorporated into the quantitative synthesis. No randomised trial of artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII, rIL6 or rIL11 was identified. We assessed all five trials of TPO mimetics included in this review to be at high risk of bias because the trials were funded by the manufacturers of the TPO mimetics and the authors had financial stakes in the sponsoring companies. The GRADE quality of the evidence was very low to moderate across the different outcomes. There was insufficient evidence to detect a difference in the number of participants with at least one bleeding episode between TPO mimetics and placebo (RR 0.86, 95% CI 0.56 to 1.31, four trials, 206 participants, low-quality evidence). There was insufficient evidence to detect a difference in the risk of a life-threatening bleed between those treated with a TPO mimetic and placebo (RR 0.31, 95% CI 0.04 to 2.26, one trial, 39 participants, low-quality evidence). There was insufficient evidence to detect a difference in the risk of all-cause mortality between those treated with a TPO mimetic and placebo (RR 0.74, 95%CI 0.52 to 1.05, five trials, 456 participants, very low-quality evidence). There was a significant reduction in the number of participants receiving any platelet transfusion between those treated with TPO mimetics and placebo (RR 0.76, 95% CI 0.61 to 0.95, four trials, 206 participants, moderate-quality evidence). There was no evidence for a difference in the incidence of transfusion reactions between those treated with TPO mimetics and placebo (pOR 0.06, 95% CI 0.00 to 3.44, one trial, 98 participants, very low-quality evidence). There was no evidence for a difference in thromboembolic events between TPO mimetics and placebo (RR 1.41, 95%CI 0.39 to 5.01, five trials, 456 participants, very-low quality evidence). There was no evidence for a difference in drug reactions between TPO mimetics and placebo (RR 1.12, 95% CI 0.83 to 1.51, five trials, 455 participants, low-quality evidence). No trial reported the number of days of bleeding per participant, platelet transfusion episodes, mean red cell transfusions per participant, red cell transfusion episodes, transfusion-transmitted infections, formation of antiplatelet antibodies or platelet refractoriness. In order to demonstrate a reduction in bleeding events from 26 in 100 to 16 in 100 participants, a study would need to recruit 514 participants (80% power, 5% significance). Authors’ conclusions There is insufficient evidence at present for thrombopoietin (TPO) mimetics for the prevention of bleeding for people with thrombocytopenia due to chronic bone marrow failure. There is no randomised controlled trial evidence for artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, rFVIIa, rFXIII or rIL6 or rIL11, antifibrinolytics or DDAVP in this setting. PMID:27797129

Platelet concentrates for transfusion-metabolic and storage aspects.

PubMed

Farrugia, A

1994-01-01

Transfusion of platelets concentrated from donated blood is an established therapeutic modality in clinical medicine. Over the past 25 years much effort has gone into optimising the conditions for the collection, preparation and storage of platelets for transfusion. Despite significant advances, platelet production is still a costly process requiring a dedicated environment and the use of specially formulated plastic storage containers. A progressive lesion over storage limits the shelf life and the availability of donated platelets, while the need to store platelets in the donor's autologous plasma also results in a loss of valuable fresh plasma for fractionation. Recent studies have addressed the issues of platelet quality and plasma economy by examining the possibility of storing platelets in a synthetic medium. Platelets stored in a variety of crystalloid solutions have been shown to retain in vitro and in vivo properties equivalent or superior to platelets stored in autologous donor plasma. Some additional insight has been gained on the metabolic patterns of stored platelets. In particular, studies have shown that, under these conditions, platelets are unable to oxidise dextrose to any significant extent, and that dextrose is invariably broken down to lactate, irrespective of the oxygen tensions in the platelet's environment. This in turn leads to the metabolic lesion of platelet storage, whereby low pH results in loss of platelet viability. Platelets stored in synthetic dextrose-free media are capable of maintaining aerobic ATP generation, and acetate-a component of many media studied-has been shown to be metabolised by platelets. Similarly, platelets prepared from blood collected into a dextrose-free anticoagulant have satisfactory properties both when suspended in autologous plasma or in a dextrose-free synthetic medium. The requirements for storage in special, high gas-permeable, containers, and for constant agitation during storage, were both found to be unnecessary when dextrose was excluded from the platelet's environment. These developments suggest that manipulation of the platelet's metabolic pattern during blood bank storage may allow significant benefits in plasma economy as well as in decreasing the cost of platelet delivery to patients.

Scott Murphy, MD: platelet storage pioneer.

PubMed

Vassallo, Ralph

2011-04-01

Dr Scott Murphy was a leading authority in the science of platelet storage for transfusion. Among the first to advocate room-temperature storage, his work enabled the extension of platelet shelf life, which facilitated the development of aggressive medical and surgical therapies requiring intensive platelet support. During a 38-year career, he characterized the metabolism of stored platelets, worked to optimize storage conditions, and developed a landmark standard for the assessment of platelet quality. As a clinical hematologist, he was devoted to his patients, providing compassionate, comforting care. He was also a cherished mentor, a sage advisor, a fast friend, and a dedicated family man. Dr Murphy was one of those rare, great, humble men who inspire and enrich everyone around him. Truly one of transfusion medicine's leaders, Scott is remembered by those whose lives he touched for his warmth, wit, and wisdom. Copyright © 2011 Elsevier Inc. All rights reserved.

Blood product transfusion in emergency department patients: a case-control study of practice patterns and impact on outcome.

PubMed

Beyer, Alexander; Rees, Ryan; Palmer, Christopher; Wessman, Brian T; Fuller, Brian M

2017-12-01

Blood product transfusion occurs in a significant percentage of intensive care unit (ICU) patients. Pulmonary complications, such as acute respiratory distress syndrome (ARDS), occurring in the setting of transfusion, are associated with increased morbidity and mortality. Contrary to the ICU setting, there is little evidence describing the epidemiology of transfusion in the emergency department (ED) or its potential impact on outcome. The objectives of this study were to: (1) characterize transfusion practices in the ED with respect to patient characteristics and pre-transfusion laboratory values; and (2) investigate the effect of ED blood product transfusion on the incidence of pulmonary complications after admission. We hypothesized that blood product transfusion would increase the event rate for pulmonary complications, and have a negative impact on other clinically significant outcomes. This was a retrospective case-control study with one-one matching of 204 transfused ED patients to 204 non-transfused controls. The primary outcome was a composite pulmonary outcome that included: acute respiratory failure, new need for ICU admission, and ARDS. Multivariable logistic regression was used to evaluate the primary outcome as a function of transfusion. One-hundred twenty four (60.8%) patients were transfused packed red blood cells (PRBC) in the ED. The mean pre-transfusion hemoglobin level was 8.5 g/dl. There were 73 patients with a hemoglobin value ≥10 g/dl; 19 (26.0%) received a PRBC transfusion. A total of 54 (26.5%) patients were transfused platelets. The main indications were thrombocytopenia (27.8%) and neurologic injury (24.1%). Ten patients had a platelet level <10,000 (guideline recommended threshold for transfusion to prevent spontaneous hemorrhage). The mean platelet count for neurologic injury patients was 197,000 prior to transfusion. The primary outcome occurred in 26 control patients (12.7%), as compared with 28 cases (13.7%). In multivariable logistic regression analysis, ED transfusion was not associated with an increased odds of primary outcome [adjusted OR 0.91 (0.48-1.72), P = 0.77]. The mortality rate was 10.8% in the cases and 8.8% in the controls, P = 0.51. A significant percentage of ED blood product transfusions are discordant with guideline recommendations. However, there was no association with ED transfusion and worse clinical outcome.

Revisiting acute normovolemic hemodilution and blood transfusion during pediatric cardiac surgery: a prospective observational study.

PubMed

Sebastian, Roby; Ratliff, Todd; Winch, Peter D; Tumin, Dmitry; Gomez, Daniel; Tobias, Joseph; Galantowicz, Mark; Naguib, Aymen N

2017-01-01

The majority of allogeneic transfusions occur in the perioperative setting, especially during cardiac surgery. In addition to the economic implications, there is emerging evidence that blood transfusion may increase both morbidity and mortality. Acute normovolemic hemodilution (ANH) may limit the need for blood products. The primary objective of this study was to determine if the method of blood collection (syringe or bag) during the ANH process impacted the platelet count and function. The secondary objectives included the need for perioperative blood transfusions during the procedure and in the intensive care unit. In addition, we assessed these outcomes' associations with ANH parameters including the method of collection, time of storage, and volume removed. Data were collected prospectively from 50 patients undergoing cardiac surgery on cardiopulmonary bypass over a 6-month period. Platelet count and function were measured for the ANH blood immediately after collection and again prior to transfusing to the patient at the end of cardiopulmonary bypass. Other data collected included ANH volume, length of storage, and the quantity of all blood products given throughout the perioperative period. No change in platelet count or function was noted regardless of the length of time or collection method for the ANH blood. Twenty-three patients received blood or blood products in the operating room or the intensive care unit, while 27 patients received no blood transfusion during their entire hospitalization. Higher ANH volume (ml·kg -1 ) and longer storage time were associated with a greater need for intraoperative transfusions. Acute normovolemic hemodilution protects the platelets from the untoward effects of cardiopulmonary bypass and offers an important autologous blood product that improves hemostasis at the conclusion of surgery. Platelet count and function are preserved regardless of the method of collection or the length of storage. The volume of ANH removed appears to be an important determinant of blood product use and further understanding of the impact of this variable is a future direction of upcoming prospective research. © 2016 John Wiley & Sons Ltd.

Platelets are dispensable for antibody-mediated transfusion-related acute lung injury in the mouse.

PubMed

Hechler, B; Maître, B; Magnenat, S; Heim, V; El Mdawar, M-B; Gachet, C; de la Salle, H

2016-06-01

Essentials Role of platelets in immunological transfusion-related acute lung injury (TRALI) is debated. Immunological TRALI was tested in mice exhibiting severe thrombocytopenia or platelet dysfunction. Platelets are required to prevent lung hemorrhage but not edema formation and respiratory distress. Platelets are dispensable for the initiation and development of TRALI. Background Transfusion-related acute lung injury (TRALI) is a serious transfusion-related complication. Previous conflicting studies have indicated that platelets are either crucial or dispensable for TRALI. Objectives To evaluate the role of platelets in major histocompatibility complex (MHC) I-induced-TRALI. Methods Antibody-mediated TRALI was experimentally induced in mice by lipopolysaccharide priming followed by the administration of an anti-MHC I mAb. Results TRALI was tested in the context of severe thrombocytopenia provoked by the administration of diphtheria toxin (DT) in transgenic iDTR mice selectively expressing DT receptor in megakaryocytes. The pathologic responses occurring within the first 10 min following the injection of the anti-MHC I mAb, i.e. the severity of lung edema and the drop in aortic blood oxygenation, were similar in severely thrombocytopenic DT-iDTR and control mice. At later times, mortality was nevertheless increased in DT-iDTR mice, owing to lung hemorrhages. When less severe thrombocytopenia was induced with an antiplatelet mAb, TRALI started and developed similarly as in control mice, but hemorrhages were absent. Furthermore, when platelet functions were defective because of administration of aspirin or clopidogrel, or because of glycoprotein (GP)IIbIIIa deficiency, TRALI still developed but no lung hemorrhages were observed. In contrast, when GPVI was immunodepleted, TRALI still occurred, but was occasionally accompanied by hemorrhages. Conclusions Platelets are dispensable for the initiation and development of MHC I-induced TRALI. Although they do not protect against the disruption of the vascular endothelial cell barrier and the subsequent plasma leakage and edema formation, platelets are essential to prevent more serious damage resulting in hemorrhages in alveoli. © 2016 International Society on Thrombosis and Haemostasis.

Alternatives, and adjuncts, to prophylactic platelet transfusion for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation

PubMed Central

Desborough, Michael; Estcourt, Lise J; Doree, Carolyn; Trivella, Marialena; Hopewell, Sally; Stanworth, Simon J; Murphy, Michael F

2016-01-01

Background Platelet transfusions are used in modern clinical practice to prevent and treat bleeding in people with thrombocytopenia. Although considerable advances have been made in platelet transfusion therapy since the mid-1970s, some areas continue to provoke debate especially concerning the use of prophylactic platelet transfusions for the prevention of thrombocytopenic bleeding. Objectives To determine whether agents that can be used as alternatives, or adjuncts, to platelet transfusions for people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation are safe and effective at preventing bleeding. Search methods We searched 11 bibliographic databases and four ongoing trials databases including the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 4), MEDLINE (OvidSP, 1946 to 19 May 2016), Embase (OvidSP, 1974 to 19 May 2016), PubMed (e-publications only: searched 19 May 2016), ClinicalTrials.gov, World Health Organization (WHO) ICTRP and the ISRCTN Register (searched 19 May 2016). Selection criteria We included randomised controlled trials in people with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation who were allocated to either an alternative to platelet transfusion (artificial platelet substitutes, platelet-poor plasma, fibrinogen concentrate, recombinant activated factor VII, desmopressin (DDAVP), or thrombopoietin (TPO) mimetics) or a comparator (placebo, standard care or platelet transfusion). We excluded studies of antifibrinolytic drugs, as they were the focus of another review. Data collection and analysis Two review authors screened all electronically derived citations and abstracts of papers identified by the review search strategy. Two review authors assessed risk of bias in the included studies and extracted data independently. Main results We identified 16 eligible trials. Four trials are ongoing and two have been completed but the results have not yet been published (trial completion dates: April 2012 to February 2017). Therefore, the review included 10 trials in eight references with 554 participants. Six trials (336 participants) only included participants with acute myeloid leukaemia undergoing intensive chemotherapy, two trials (38 participants) included participants with lymphoma undergoing intensive chemotherapy and two trials (180 participants) reported participants undergoing allogeneic stem cell transplantation. Men and women were equally well represented in the trials. The age range of participants included in the trials was from 16 years to 81 years. All trials took place in high-income countries. The manufacturers of the agent sponsored eight trials that were under investigation, and two trials did not report their source of funding. No trials assessed artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin. Nine trials compared a TPO mimetic to placebo or standard care; seven of these used pegylated recombinant human megakaryocyte growth and differentiation factor (PEG-rHuMGDF) and two used recombinant human thrombopoietin (rhTPO). One trial compared platelet-poor plasma to platelet transfusion. We considered that all the trials included in this review were at high risk of bias and meta-analysis was not possible in seven trials due to problems with the way data were reported. We are very uncertain whether TPO mimetics reduce the number of participants with any bleeding episode (odds ratio (OR) 0.40, 95% confidence interval (CI) 0.10 to 1.62, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce the risk of a life-threatening bleed after 30 days (OR 1.46, 95% CI 0.06 to 33.14, three trials, 209 participants, very low quality evidence); or after 90 days (OR 1.00, 95% CI 0.06 to 16.37, one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce platelet transfusion requirements after 30 days (mean difference -3.00 units, 95% CI -5.39 to -0.61, one trial, 120 participants, very low quality evidence). No deaths occurred in either group after 30 days (one trial, 120 participants, very low quality evidence). We are very uncertain whether TPO mimetics reduce all-cause mortality at 90 days (OR 1.00, 95% CI 0.24 to 4.20, one trial, 120 participants, very low quality evidence). No thromboembolic events occurred for participants treated with TPO mimetics or control at 30 days (two trials, 209 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed or quality of life. One trial with 18 participants compared platelet-poor plasma transfusion with platelet transfusion. We are very uncertain whether platelet-poor plasma reduces the number of participants with any bleeding episode (OR 16.00, 95% CI 1.32 to 194.62, one trial, 18 participants, very low quality evidence). We are very uncertain whether platelet-poor plasma reduces the number of participants with severe or life-threatening bleeding (OR 4.00, 95% CI 0.56 to 28.40, one trial, 18 participants, very low quality evidence). We found no trials that looked at: number of days on which bleeding occurred, time from randomisation to first bleed, number of platelet transfusions, all-cause mortality, thromboembolic events or quality of life. Authors’ conclusions There is insufficient evidence to determine if platelet-poor plasma or TPO mimetics reduce bleeding for participants with haematological malignancies undergoing intensive chemotherapy or stem cell transplantation. To detect a decrease in the proportion of participants with clinically significant bleeding from 12 in 100 to 6 in 100 would require a trial containing at least 708 participants (80% power, 5% significance). The six ongoing trials will provide additional information about the TPO mimetic comparison (424 participants) but this will still be underpowered to demonstrate this level of reduction in bleeding. None of the included or ongoing trials include children. There are no completed or ongoing trials assessing artificial platelet substitutes, fibrinogen concentrate, recombinant activated factor VII or desmopressin in people undergoing intensive chemotherapy or stem cell transplantation for haematological malignancies. PMID:27548292

Reversal of anemia with allogenic RBC transfusion prevents post-cardiopulmonary bypass acute kidney injury in swine

PubMed Central

Patel, Nishith N.; Lin, Hua; Toth, Tibor; Welsh, Gavin I.; Jones, Ceri; Ray, Paramita; Satchell, Simon C.; Sleeman, Philippa; Angelini, Gianni D.

2011-01-01

Anemia during cardiopulmonary bypass (CPB) is strongly associated with acute kidney injury in clinical studies; however, reversal of anemia with red blood cell (RBC) transfusions is associated with further renal injury. To understand this paradox, we evaluated the effects of reversal of anemia during CPB with allogenic RBC transfusion in a novel large-animal model of post-cardiac surgery acute kidney injury with significant homology to that observed in cardiac surgery patients. Adult pigs undergoing general anesthesia were allocated to a Sham procedure, CPB alone, Sham+RBC transfusion, or CPB+RBC transfusion, with recovery and reassessment at 24 h. CPB was associated with dilutional anemia and caused acute kidney injury in swine characterized by renal endothelial dysfunction, loss of nitric oxide (NO) bioavailability, vasoconstriction, medullary hypoxia, cortical ATP depletion, glomerular sequestration of activated platelets and inflammatory cells, and proximal tubule epithelial cell stress. RBC transfusion in the absence of CPB also resulted in renal injury. This was characterized by endothelial injury, microvascular endothelial dysfunction, platelet activation, and equivalent cortical tubular epithelial phenotypic changes to those observed in CPB pigs, but occurred in the absence of severe intrarenal vasoconstriction, ATP depletion, or reductions in creatinine clearance. In contrast, reversal of anemia during CPB with RBC transfusion prevented the reductions in creatinine clearance, loss of NO bioavailability, platelet activation, inflammation, and epithelial cell injury attributable to CPB although it did not prevent the development of significant intrarenal vasoconstriction and endothelial dysfunction. In conclusion, contrary to the findings of observational studies in cardiac surgery, RBC transfusion during CPB protects pigs against acute kidney injury. Our study underlines the need for translational research into indications for transfusion and prevention strategies for acute kidney injury. PMID:21653630

Importance of fibrinogen in dilutional coagulopathy after neurosurgical procedures: A descriptive study.

PubMed

Nair, Shalini; Nair, Bijesh Ravindran; Vidyasagar, Ajay; Joseph, Mathew

2016-08-01

The routine management of coagulopathy during surgery involves assessing haemoglobin, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelets. Correction of these parameters involves administration of blood, fresh frozen plasma and platelet concentrates. The study was aimed at identifying the most common coagulation abnormality during neurosurgical procedures and the treatment of dilutional coagulopathy with blood components. During 2 years period, all adult patients undergoing neurosurgical procedures who were transfused two or more units of red cells were prospectively evaluated for the presence of a coagulopathy. PT, aPTT, platelet count and fibrinogen levels were estimated before starting a component therapy. After assessing PT, aPTT, platelet count and fibrinogen levels following two or more blood transfusions, thirty patients were found to have at least one abnormal parameter that required administration of a blood product. The most common abnormality was a low fibrinogen level, seen in 26 patients; this was the only abnormality in three patients. No patient was found to have an abnormal PT or aPTT without either the fibrinogen concentration or platelet count or both being low. Low fibrinogen concentration was the most common coagulation abnormality found after blood transfusions for neurosurgical procedures.

Evaluation of real-time clinical decision support systems for platelet and cryoprecipitate orders.

PubMed

Collins, Ryan A; Triulzi, Darrell J; Waters, Jonathan H; Reddy, Vivek; Yazer, Mark H

2014-01-01

To evaluate cryoprecipitate and platelet ordering practices after the implementation of real-time clinical decision support systems (CDSSs) in a computerized physician order entry (CPOE) system. Uniform platelet and cryoprecipitate transfusion thresholds were implemented at 11 hospitals in a regional health care system with a common CPOE system. Over 6 months, a variety of information was collected on the ordering physicians and the number of alerts generated by the CDSSs when these products were ordered outside of the institutional guidelines. There were 1,889 orders for platelets and 152 orders for cryoprecipitate placed in 6 months. Of these, 1,102 (58.3%) platelet and 74 (48.7%) cryoprecipitate orders triggered an alert. The proportion of orders canceled after an alert was generated ranged from 13.5% to 17.9% for platelets and 0% to 50.0% for cryoprecipitate orders. CDSS alerts reduce, but do not eliminate, platelet and cryoprecipitate transfusions that do not meet institutional guidelines.

Extension of platelet shelf life from 4 to 5 days by implementation of a new screening strategy in Germany.

PubMed

Sireis, W; Rüster, B; Daiss, C; Hourfar, M K; Capalbo, G; Pfeiffer, H-U; Janetzko, K; Goebel, M; Kempf, V A J; Seifried, E; Schmidt, M

2011-10-01

The Paul-Ehrlich-Institute analysed all fatalities due to bacterial infections between 1997 and 2007. Thereafter, the platelet shelf life was reduced to a maximum of 4 days after blood donation because the majority of all cases of severe transfusion-transmitted bacterial infections occurred with day 5 platelets. The current study compares the analytical sensitivity and the diagnostic specificity of four rapid bacterial detection procedures. Nine transfusion-relevant bacterial strains were spiked in pooled platelets or apheresis platelets at a low concentration (10 CFU/bag). Samples were collected after day 3, day 4 and day 5 and investigated by four rapid bacterial detection methods (modified BacT/ALERT, Bactiflow, FACS method and 16s DNA PCR methods). Seven out of nine bacterial strains were adequately detected by BacT/ALERT, Bactiflow and PCR in apheresis platelets and pooled platelets after sample collection at day 3, day 4 and day 5. For three bacterial strains, analytical sensitivity was reduced for the FACS method. Two bacterial strains did not grow under the storage conditions in either pooled or apheresis platelets. A late sample collection on day 3, day 4 or day 5 after blood donation in combination with a rapid bacterial detection method offers a new opportunity to improve blood safety and reduce errors due to sampling., BacT/ALERT, Bactiflow or 16s ID-NAT are feasible for late bacterial screening in platelets may provide data which support the extension of platelet shelf life in Germany to 5 days. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Overview on platelet preservation: better controls over storage lesion.

PubMed

Ohto, Hitoshi; Nollet, Kenneth E

2011-06-01

Platelet storage lesion (PSL), correlating with reduced in vivo recovery/survival and hemostatic capacity after transfusion, is characterized essentially by morphological and molecular evidence of platelet activation and energy consumption in the medium. Processes that limit shelf-life are multifactorial, and include both necrosis and apoptosis. PSL is greatly influenced by factors including duration of storage, temperature, ratio of platelet number to media volume, solution composition with respect to energy content and buffering capacity, and gas permeability of the container. Recent progress for slowing PSL has been made with storage media that more effectively fuel ATP production and buffer the inevitable effects of metabolism. Improved oxygen-permeability of containers also helps to maintain aerobic-dominant glycolysis. Patients stand to benefit from platelet products of higher intrinsic quality that store well until the moment of transfusion. Copyright © 2011. Published by Elsevier Ltd.

[Whole-blood transfusion for hemorrhagic shock resuscitation: two cases in Djibouti].

PubMed

Cordier, P Y; Eve, O; Dehan, C; Topin, F; Menguy, P; Bertani, A; Massoure, P L; Kaiser, E

2012-01-01

Hemorrhagic shock requires early aggressive treatment, including transfusion of packed red blood cells and hemostatic resuscitation. In austere environments, when component therapy is not available, warm fresh whole-blood transfusion is a convenient treatment. It provides red blood cells, clotting factors, and functional platelets. Therefore it is commonly used in military practice to treat hemorrhagic shock in combat casualties. At Bouffard Hospital Center in Djibouti, the supply of packed red blood cells is limited, and apheresis platelets are unavailable. We used whole blood transfusion in two civilian patients with life-threatening non-traumatic hemorrhages. One had massive bleeding caused by disseminated intravascular coagulation due to septic shock; the second was a 39 year-old pregnant woman with uterine rupture. In both cases, whole blood transfusion (twelve and ten 500 mL bags respectively), combined with etiological treatment, enabled coagulopathy correction, hemorrhage control, and satisfactory recovery.

Severe thrombocytopenia in a child with typhoid fever: a case report.

PubMed

Al Reesi, Mohammed; Stephens, Glenn; McMullan, Brendan

2016-11-30

Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 10 9 /L). Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

Transfusion: -80°C Frozen Blood Products Are Safe and Effective in Military Casualty Care.

PubMed

Noorman, Femke; van Dongen, Thijs T C F; Plat, Marie-Christine J; Badloe, John F; Hess, John R; Hoencamp, Rigo

2016-01-01

The Netherlands Armed Forces use -80°C frozen red blood cells (RBCs), plasma and platelets combined with regular liquid stored RBCs, for the treatment of (military) casualties in Medical Treatment Facilities abroad. Our objective was to assess and compare the use of -80°C frozen blood products in combination with the different transfusion protocols and their effect on the outcome of trauma casualties. Hemovigilance and combat casualties data from Afghanistan 2006-2010 for 272 (military) trauma casualties with or without massive transfusions (MT: ≥6 RBC/24hr, N = 82 and non-MT: 1-5 RBC/24hr, N = 190) were analyzed retrospectively. In November 2007, a massive transfusion protocol (MTP; 4:3:1 RBC:Plasma:Platelets) for ATLS® class III/IV hemorrhage was introduced in military theatre. Blood product use, injury severity and mortality were assessed pre- and post-introduction of the MTP. Data were compared to civilian and military trauma studies to assess effectiveness of the frozen blood products and MTP. No ABO incompatible blood products were transfused and only 1 mild transfusion reaction was observed with 3,060 transfused products. In hospital mortality decreased post-MTP for MT patients from 44% to 14% (P = 0.005) and for non-MT patients from 12.7% to 5.9% (P = 0.139). Average 24-hour RBC, plasma and platelet ratios were comparable and accompanying 24-hour mortality rates were low compared to studies that used similar numbers of liquid stored (and on site donated) blood products. This report describes for the first time that the combination of -80°C frozen platelets, plasma and red cells is safe and at least as effective as standard blood products in the treatment of (military) trauma casualties. Frozen blood can save the lives of casualties of armed conflict without the need for in-theatre blood collection. These results may also contribute to solutions for logistic problems in civilian blood supply in remote areas.

Reflections on multiple strategies to reduce transfusion in cancer patients: A joint narrative.

PubMed

Goubran, Hadi; Seghatchian, Jerard; Prokopchuk-Gauk, Oksana; Radosevic, Julia; Sabry, Waleed; Iqbal, Nayyer; Burnouf, Thierry

2017-06-01

Transfusion of red blood cells, platelets and plasma is widely used in the management of anemia and coagulopathy in cancer patients undergoing surgery, chemotherapy, and radiation. The decision to transfuse should not be made lightly as exposure to transfused blood, whether from an allogeneic or even autologous source, is not without risk and the long-term effect of blood transfusion on cancer outcomes remains questionable. Recognition of anemia associated with nutritional deficiency should be promptly corrected while avoiding the use of erythropoiesis stimulating agents. Minimizing blood loss and the prompt control of bleeding, coupled with a restrictive transfusion strategy, seem to be a reasonable approach that does not appear to be associated with long-term sequelae. Limiting platelet transfusion to patients with severe hypo-proliferative thrombocytopenia, and implementation of local hemostatic measures, together with the use of fractionated coagulation factor concentrates, as an alternative to frozen plasma transfusion, may reduce the exposure of cancer patients to potentially harmful thrombogenic and pro-inflammatory cellular microparticles. This joint narrative highlights current opinions for minimizing blood usage in patients with cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Platelet Vascular Endothelial Growth Factor is a Potential Mediator of Transfusion-Related Acute Lung Injury.

PubMed

Maloney, James P; Ambruso, Daniel R; Voelkel, Norbert F; Silliman, Christopher C

The occurrence of non-hemolytic transfusion reactions is highest with platelet and plasma administration. Some of these reactions are characterized by endothelial leak, especially transfusion related acute lung injury (TRALI). Elevated concentrations of inflammatory mediators secreted by contaminating leukocytes during blood product storage may contribute to such reactions, but platelet-secreted mediators may also contribute. We hypothesized that platelet storage leads to accumulation of the endothelial permeability mediator vascular endothelial growth factor (VEGF), and that intravascular administration of exogenous VEGF leads to extensive binding to its lung receptors. Single donor, leukocyte-reduced apheresis platelet units were sampled over 5 days of storage. VEGF protein content of the centrifuged supernatant was determined by ELISA, and the potential contribution of VEGF from contaminating leukocytes was quantified. Isolated-perfused rat lungs were used to study the uptake of radiolabeled VEGF administered intravascularly, and the effect of unlabeled VEGF on lung leak. There was a time-dependent release of VEGF into the plasma fraction of the platelet concentrates (62 ± 9 pg/ml on day one, 149 ± 23 pg/ml on day 5; mean ± SEM, p<0.01, n=8) and a contribution by contaminating leukocytes was excluded. Exogenous 125I-VEGF bound avidly and specifically to the lung vasculature, and unlabeled VEGF in the lung perfusate caused vascular leak. Rising concentrations of VEGF occur during storage of single donor platelet concentrates due to platelet secretion or disintegration, but not due to leukocyte contamination. Exogenous VEGF at these concentrations rapidly binds to its receptors in the lung vessels. At higher VEGF concentrations, VEGF causes vascular leak in uninjured lungs. These data provide further evidence that VEGF may contribute to the increased lung permeability seen in TRALI associated with platelet products.

Regulating billions of blood platelets: glycans and beyond

PubMed Central

Grozovsky, Renata; Giannini, Silvia; Falet, Hervé

2015-01-01

The human body produces and removes 1011 platelets daily to maintain a normal steady state platelet count. Platelet production must be regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. This review will focus on different mechanisms of platelet senescence and clearance with specific emphasis on the role of posttranslational modifications. It will also briefly address platelet transfusion and the role of glycans in the clearance of stored platelets. PMID:26330242

Blood transfusion in trauma patients: unresolved questions.

PubMed

Cushing, M; Shaz, B H

2011-03-01

Massive transfusion is an essential part of resuscitation efforts in acute trauma patients. The goal is to quickly correct trauma-induced coagulopathy and replace red blood cell (RBC) mass with the minimal number as well as the appropriate choice of blood components to minimize the possible adverse effects of transfusions. Early trauma induced coagulopathy (ETIC) is present in about 20% of patients upon hospital admission and predicts for decreased survival. The mechanism of ETIC is still being elucidated; however, most theories of ETIC's pathophysiology justify the early use of plasma. Most massive transfusion protocol (MTP) ratios deliver blood products in a ratio of 1:1:1 for RBCs:plasma:platelets, which is supported by the majority of the literature demonstrating improved patient survival with higher ratios (>1 plasma and platelet for every 2 RBCs transfused). Indeed, formula-driven MTPs allow trauma services to react quickly to ETIC and provide coagulation factors and platelets in these ratios without having to wait for the results of coagulation assays while the patient's coagulopathy worsens. New MTPs are being created which are adjusted according to an individual's coagulation laboratory values based on point-of-care laboratory tests, such as thromboelastography. When creating an MTP, product wastage due to inappropriate activation and improper product storage should be considered and closely monitored. Another area of discussion regarding transfusion in trauma includes the potential association of prolonged storage of RBCs and adverse outcomes, which has yet to be confirmed. Significant progress has been made in the transfusion management of trauma patients, but further studies are required to optimize patient care and outcomes.

Platelet Immunology in China: Research and Clinical Applications.

PubMed

Wu, Guoguang; Zhou, Yan; Li, Lilan; Zhong, Zhoulin; Li, Hengchong; Li, Haiyan; Yu, Mei; Shen, Weidong; Ni, Heyu

2017-04-01

Immunization against human platelet alloantigens (HPAs) is associated with a number of clinical complications. The detection and identification of clinically relevant platelet antibodies are important for the diagnosis and management of patients affected with immune-mediated thrombocytopenias. Human platelet alloantigen frequencies and the characteristics of antiplatelet antibodies vary widely between ethnic groups. Since 2008, the importance of platelet immunology in the field of transfusion medicine has gained greater recognition by clinical laboratories in China. Laboratories in China have established and improved methods for platelet antibody detection and HPA genotyping techniques, which are used for the diagnosis of alloimmune platelet disorders in clinic and research environments. Research has revealed the frequencies of HPA alleles in different Chinese ethnic groups and compared the differences in HPA gene frequencies between the Chinese Han and other ethnic groups of the world. Production of anti-CD36 isoantibodies is an important risk factor for immune-mediated thrombocytopenia in the Chinese population. Advances in research and clinical application of platelet immunology have significantly improved the clinical diagnosis, treatment including transfusion support, and prevention of alloimmune platelet disorders in the Chinese population. Copyright © 2017. Published by Elsevier Inc.

How do we approach thrombocytopenia in critically ill patients?

PubMed

Thachil, Jecko; Warkentin, Theodore E

2017-04-01

A low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count <20 × 10 9 /l) can be associated with bleeding, even moderate-degree thrombocytopenia is associated with organ failure and adverse prognosis. The aetiology for thrombocytopenia in ITU is often multifactorial and correcting one aetiology may not normalise the low platelet count. The classical view for thrombocytopenia in this setting is consumption associated with thrombin-mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk-benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia. © 2016 John Wiley & Sons Ltd.

Evaluation of Dried Storage of Platelets for Transfusion: Physiologic Integrity and Hemostatic Functionality

DTIC Science & Technology

1994-10-27

paraformaidehyde in 500 mM Trehalose stored desiccated at RT, 4* C, or at -70,° C. Neither prep maintained good morphology at any temperature, and there...platelets, or para-platelets dried in Trehalose are as susceptible to loss of integrity over time as other preps. Our platelet handling techniques have

Disorders of Platelet Function

PubMed Central

Huebsch, Lothar B.; Harker, Laurence A.

1981-01-01

Platelets play an important role in hemostasis, and alterations in platelet function may be the cause of abnormal bleeding in a wide variety of congenital and acquired clinical disorders. Platelet dysfunction may be classified as disorders of (1) substrate connective tissue, (2) adhesion, (3) aggregation and (4) platelet-release reaction. The congenital defects of platelet function, although uncommon, have provided important insights into platelet physiology and pathophysiology and, as a group, are less common, better characterized and more readily classified than the acquired defects. The severity of bleeding resulting from platelet dysfunction varies greatly and is substantially increased when another defect of hemostasis coexists. A disorder of platelet function is suspected on the basis of the history and physical examination and is confirmed by the finding of a prolonged bleeding time in the presence of an adequate number of platelets. A specific diagnosis often requires measurements of the factor VIII and von Willebrand factor complex and other tests of platelet function. Some of these tests may be available only in specialized laboratories. Therapy for bleeding episodes resulting from platelet dysfunction is directed at (1) removing or treating the underlying cause of the platelet disorder; (2) replacing the missing plasma cofactors needed to support normal platelet function (such as by the transfusion of cryoprecipitate in patients with von Willebrand disease, and (3) transfusing functional platelets in the form of platelet concentrates in patients with disorders of intrinsic platelet dysfunction. ImagesFigure 1.Figure 2.Figure 3. PMID:7013276

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia.

PubMed

Titano, J J; Biederman, D M; Marinelli, B S; Patel, R S; Kim, E; Tabori, N E; Nowakowski, F S; Lookstein, R A; Fischman, A M

2016-05-01

Transradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions. Patients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications. From July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6% with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9%) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1%) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups. Transradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

Allogeneic blood transfusion in bilateral lung transplantation: impact on early function and mortality.

PubMed

Ong, Lay Ping; Thompson, Emily; Sachdeva, Ashwin; Ramesh, B C; Muse, Hazel; Wallace, Kirstie; Parry, Gareth; Clark, Stephen Charles

2016-02-01

Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. Three hundred and eleven adult patients who underwent bilateral lung transplant between 2003 and 2013 were retrospectively reviewed. Patients were stratified according to pretransplant diagnoses and amount of blood products transfused within 24 h of transplant. All-cause mortality at the 1-year follow-up was analysed using a Cox proportional hazards regression model. One hundred and seventy-four male patients and 137 female patients (mean age = 41.4 ± 14.0 years) underwent bilateral lung transplant using cardiopulmonary bypass for cystic fibrosis (48.9%), fibrotic lung disease (12.2%), emphysema (27.0%), bronchiectasis (5.8%), pulmonary hypertension (1.3%) and others (4.5%). The median number of red blood cells in the first 24 h was 3 (0-40) units, fresh frozen plasma (FFP) = 2 (0-26) units and platelets = 1 (0-7) units. The unadjusted all-cause mortality at the 1-year follow-up did not appear to be different between patient subgroups stratified by the median number of units of red blood cells (P = 0.827) or FFP transfused (P = 0.456). However, 1-year mortality was adversely affected when more than the median number of units of platelets was transfused (P = 0.010). Upon adjustment for confounding variables, 1-year mortality was noted to be greater among patients transfused more than the median unit of platelets (adjusted hazard ratios: 2.3, 95% confidence interval: 1.15-4.61, P = 0.019) and those with longer bypass times (P = 0.046). No significant difference in the number of units transfused was noted when patients were stratified by pretransplant diagnosis. Predicted lung function at 3 and 6 months was not significantly affected by greater blood product use. Unlike general cardiothoracic surgery, blood transfusion had no effect on all-cause mortality, whereas a greater administration of platelets was observed to be associated with higher adjusted 1-year mortality. Transfusion rates were not significantly influenced by pretransplant diagnoses. Interestingly, lung function at 3 and 6 months was similar for patients who received more blood product transfusion. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Responsiveness of platelets during storage studied with flow cytometry--formation of platelet subpopulations and LAMP-1 as new markers for the platelet storage lesion.

PubMed

Södergren, A L; Tynngård, N; Berlin, G; Ramström, S

2016-02-01

Storage lesions may prevent transfused platelets to respond to agonists and arrest bleeding. The aim of this study was to evaluate and quantify the capacity of platelet activation during storage using flow cytometry and new markers of platelet activation. Activation responses of platelets prepared by apheresis were measured on days 1, 5, 7 and 12. In addition, comparisons were made for platelet concentrates stored until swirling was affected. Lysosome-associated membrane protein-1 (LAMP-1), P-selectin and phosphatidylserine (PS) exposure were assessed by flow cytometry on platelets in different subpopulations in resting state or following stimulation with platelet agonists (cross-linked collagen-related peptide (CRP-XL), PAR1- and PAR4-activating peptides). The ability to form subpopulations upon activation was significantly decreased already at day 5 for some agonist combinations. The agonist-induced exposure of PS and LAMP-1 also gradually decreased with time. Spontaneous exposure of P-selectin and PS increased with time, while spontaneous LAMP-1 exposure was unchanged. In addition, agonist-induced LAMP-1 expression clearly discriminated platelet concentrates with reduced swirling from those with retained swirling. This suggests that LAMP-1 could be a good marker to capture changes in activation capacity in stored platelets. The platelet activation potential seen as LAMP-1 exposure and fragmentation into platelet subpopulations is potential sensitive markers for the platelet storage lesion. © 2015 International Society of Blood Transfusion.

Ultraviolet-Based Pathogen Inactivation Systems: Untangling the Molecular Targets Activated in Platelets

PubMed Central

Schubert, Peter; Johnson, Lacey; Marks, Denese C.; Devine, Dana V.

2018-01-01

Transfusions of platelets are an important cornerstone of medicine; however, recipients may be subject to risk of adverse events associated with the potential transmission of pathogens, especially bacteria. Pathogen inactivation (PI) technologies based on ultraviolet illumination have been developed in the last decades to mitigate this risk. This review discusses studies of platelet concentrates treated with the current generation of PI technologies to assess their impact on quality, PI capacity, safety, and clinical efficacy. Improved safety seems to come with the cost of reduced platelet functionality, and hence transfusion efficacy. In order to understand these negative impacts in more detail, several molecular analyses have identified signaling pathways linked to platelet function that are altered by PI. Because some of these biochemical alterations are similar to those seen arising in the context of routine platelet storage lesion development occurring during blood bank storage, we lack a complete picture of the contribution of PI treatment to impaired platelet functionality. A model generated using data from currently available publications places the signaling protein kinase p38 as a central player regulating a variety of mechanisms triggered in platelets by PI systems. PMID:29868586

Flow Cytometric Panel-Reactive Antibody Results and the Ability to Find Transfusion-Compatible Platelets after Antibody-Desensitization for Allogeneic Bone Marrow Transplant.

PubMed

Rosenbaum, Eric R; Pandey, Soumya; Harville, Terry O; Drobena, Gina A; Cottler-Fox, Michele

2016-12-01

Panel reactive antibody (PRA) reduction protocols are used to decrease anti-HLA antibodies with concomitant PRA monitoring as a measure of successful treatment prior to organ and haploidentical blood and marrow transplant (BMT). We hypothesized that the more sensitive flow cytometry (FC) based assays for PRA [FlowPRA ® and Luminex ® based Single Antigen Bead (SAB)] would also correlate with the ability to find compatible platelets for allosensitized recipients. A female patient with myelodysplastic syndrome and a high HLA class I PRA [>90% PRA and cPRA by complement-dependent cytotoxicity (CDC) assay and Flow PRA] required allogeneic BMT. Baseline HLA Class I and class II antigen typing was performed and a matched sibling donor was identified. Although baseline anti-HLA class I and class II antibodies measured by FC and CDC revealed no donor specific antibodies (DSA), the decision was made to attempt antibody desensitization to facilitate platelet transfusion during BMT. FC and CDC assays were performed to determine anti-HLA class I antibodies and cPRA/%PRA prior to starting desensitization and at the end of desensitization. Over the course of desensitization and BMT, a total of 194 apheresis platelet units underwent cross-match (XM) using Capture-P ® . We compared temporally-related PRA results with platelet XM results. High PRA by FC or CDC assays correlates with a high % of XM-positive (incompatible) platelet units. When the CDC PRA fell to 2% after desensitization, platelet XM incompatibility fell from 100% to 63% positive (incompatible). When the FC PRA fell to 5% the positive platelet XM fell to 5%. Antibody desensitization facilitated platelet transfusion. PRA determination by FC appeared better correlated than determination by CDC with the ability to find XM-compatible platelets. © 2016 by the Association of Clinical Scientists, Inc.

Age of platelet concentrates and time to the next transfusion.

PubMed

Caram-Deelder, Camila; van der Bom, Johanna G; Putter, Hein; Leyte, Anja; Kerkhof, Daan van de; Evers, Dorothea; Beckers, Erik A; Weerkamp, Floor; Hudig, Francisca; Zwaginga, Jaap Jan; Rondeel, Jan M M; de Vooght, Karen M K; Péquériaux, Nathalie C V; Visser, Otto; Wallis, Jonathan P; Middelburg, Rutger A

2018-01-01

Storage time of platelet (PLT) concentrates has been negatively associated with clinical efficacy outcomes. The aim of this study was to quantify the association between storage time of PLT concentrates and interval to the next PLT transfusion for different types of PLT components, stored for up to 7 days and transfused to transfusion-dependent hematooncology patients with thrombocytopenia. From a cohort of patients from 10 major Dutch hospitals, patients were selected whose transfusion patterns were compatible with PLT transfusion dependency due to hematooncologic disease. Mean time to the next transfusion and mean differences in time to the next transfusion for different storage time categories (i.e., fresh, <4 days; intermediate, 4-5 days; and old, >5 days) were estimated, per component type, using multilevel mixed-effects linear models. Among a cohort of 29,761 patients who received 140,896 PLT transfusions we selected 4441 hematooncology patients who had received 12,724 PLT transfusions during periods of PLT transfusion dependency. Transfusion of fresh, compared to old, buffy coat-derived PLTs in plasma was associated with a delay to the next transfusion of 6.2 hours (95% confidence interval [CI], 4.5-8.0 hr). For buffy coat-derived PLTs in PAS-B and -C this difference was 7.7 hours (95% CI, 2.2-13.3 hr) and 3.9 hours (95% CI, -2.1 to 9.9 hr) while for apheresis PLTs in plasma it was only 1.8 hours (95% CI, -3.5 to 7.1 hr). Our results indicate that the time to the next transfusion shortens with increasing age of transfused buffy coat-derived PLT concentrates. This association was not observed for apheresis PLTs. © 2017 AABB.

Demographic and epidemiologic characterization of transfusion recipients from four US regions: evidence from the REDS-III recipient database.

PubMed

Karafin, Matthew S; Bruhn, Roberta; Westlake, Matt; Sullivan, Marian T; Bialkowski, Walter; Edgren, Gustaf; Roubinian, Nareg H; Hauser, Ronald G; Kor, Daryl J; Fleischmann, Debra; Gottschall, Jerome L; Murphy, Edward L; Triulzi, Darrell J

2017-12-01

Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers. © 2017 AABB.

Leukocyte-reduced blood components: patient benefits and practical applications.

PubMed

Higgins, V L

1996-05-01

To review the various types of filters used for red blood cell and platelet transfusions and to explain the trend in the use of leukocyte removal filters, practical information about their use, considerations in the selection of a filtration method, and cost-effectiveness issues. Published articles, books, and the author's experience. Leukocyte removal filters are used to reduce complications associated with transfused white blood cells that are contained in units of red blood cells and platelets. These complications include nonhemolytic febrile transfusion reactions (NHFTRs), alloimmunization and refractoriness to platelet transfusion, transfusion-transmitted cytomegalovirus (CMV), and immunomodulation. Leukocyte removal filters may be used at the bedside, in a hospital blood bank, or in a blood collection center. Factors that affect the flow rate of these filters include the variations in the blood component, the equipment used, and filter priming. Studies on the cost-effectiveness of using leukocyte-reduced blood components demonstrate savings based on the reduction of NHFTRs, reduction in the number of blood components used, and the use of filtered blood components as the equivalent of CMV seronegative-screened products. The use of leukocyte-reduced blood components significantly diminishes or prevents many of the adverse transfusion reactions associated with donor white blood cells. Leukocyte removal filters are cost-effective, and filters should be selected based on their ability to consistently achieve low leukocyte residual levels as well as their ease of use. Physicians may order leukocyte-reduced blood components for specific patients, or the components may be used because of an established institutional transfusion policy. Nurses often participate in deciding on a filtration method, primarily based on ease of use. Understanding the considerations in selecting a filtration method will help nurses make appropriate decisions to ensure quality patient care.

A national common massive transfusion protocol (MTP) is a feasible and advantageous option for centralized blood services and hospitals.

PubMed

Chay, J; Koh, M; Tan, H H; Ng, J; Ng, H J; Chia, N; Kuperan, P; Tan, J; Lew, E; Tan, L K; Koh, P L; Desouza, K A; Bin Mohd Fathil, S; Kyaw, P M; Ang, A L

2016-01-01

A common national MTP was jointly implemented in 2011 by the national blood service (Blood Services Group) and seven participating acute hospitals to provide rapid access to transfusion support for massively haemorrhaging patients treated in all acute care hospitals. Through a systematic clinical workflow, blood components are transfused in a ratio of 1:1:1 (pRBC: whole blood-derived platelets: FFP), together with cryoprecipitate for fibrinogen replacement. The composition of components for the MTP is fixed, although operational aspects of the MTP can be adapted by individual hospitals to suit local hospital workflow. The MTP could be activated in support of any patient with critical bleeding and at risk of massive transfusion, including trauma and non-trauma general medical, surgical and obstetric patients. There were 434 activations of the MTP from October 2011 to October 2013. Thirty-nine per cent were for trauma patients, and 30% were for surgical patients with heavy intra-operative bleeding, with 25% and 6% for patients with gastrointestinal bleeding and peri-partum haemorrhage, respectively. Several hospitals reported reduction in mean time between request and arrival of blood. Mean transfusion ratio achieved was one red cell unit: 0·8 FFP units: 0·8 whole blood-derived platelet units: 0·4 units of cryoprecipitate. Although cryoprecipitate usage more than doubled after introduction of MTP, there was no significant rise in overall red cells, platelet and FFP usage following implementation. This successful collaboration shows that shared transfusion protocols are feasible and potentially advantageous for hospitals sharing a central blood provider. © 2015 International Society of Blood Transfusion.

The effects of platelet lysate patches on the activity of tendon-derived cells.

PubMed

Costa-Almeida, Raquel; Franco, Albina R; Pesqueira, Tamagno; Oliveira, Mariana B; Babo, Pedro S; Leonor, Isabel B; Mano, João F; Reis, Rui L; Gomes, Manuela E

2018-03-01

Platelet-derived biomaterials are widely explored as cost-effective sources of therapeutic factors, holding a strong potential for endogenous regenerative medicine. Particularly for tendon repair, treatment approaches that shift the injury environment are explored to accelerate tendon regeneration. Herein, genipin-crosslinked platelet lysate (PL) patches are proposed for the delivery of human-derived therapeutic factors in patch augmentation strategies aiming at tendon repair. Developed PL patches exhibited a controlled release profile of PL proteins, including bFGF and PDGF-BB. Additionally, PL patches exhibited an antibacterial effect by preventing the adhesion, proliferation and biofilm formation by S. aureus, a common pathogen in orthopaedic surgical site infections. Furthermore, these patches supported the activity of human tendon-derived cells (hTDCs). Cells were able to proliferate over time and an up-regulation of tenogenic genes (SCX, COL1A1 and TNC) was observed, suggesting that PL patches may modify the behavior of hTDCs. Accordingly, hTDCs deposited tendon-related extracellular matrix proteins, namely collagen type I and tenascin C. In summary, PL patches can act as a reservoir of biomolecules derived from PL and support the activity of native tendon cells, being proposed as bioinstructive patches for tendon regeneration. Platelet-derived biomaterials hold great interest for the delivery of therapeutic factors for applications in endogenous regenerative medicine. In the particular case of tendon repair, patch augmentation strategies aiming at shifting the injury environment are explored to improve tendon regeneration. In this study, PL patches were developed with remarkable features, including the controlled release of growth factors and antibacterial efficacy. Remarkably, PL patches supported the activity of native tendon cells by up-regulating tenogenic genes and enabling the deposition of ECM proteins. This patch holds great potential towards simultaneously reducing post-implantation surgical site infections and promoting tendon regeneration for prospective in vivo applications. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

In vitro properties of concentrated canine platelets stored in two additive solutions: a comparative study.

PubMed

Hlavac, N; Lasta, C S; Dalmolin, M L; Lacerda, L A; de Korte, D; Marcondes, N A; Terra, S R; Fernandes, F B; González, F H D

2017-11-15

Platelet transfusion therapy poses many challenges in veterinary clinical practice. Lack of readily available blood donors, short shelf-life, and inability to administer a sufficient number of platelets to meet a dog's transfusion need are the major difficulties encountered. Platelet additive solutions are already in use at American and European human blood banks, showing to be a realistic alternative. This study compares the in vitro platelet function in plasma, Composol, or SSP+ during storage for 13 days. Platelet rich plasma-platelet concentrate with 35% plasma and 65% platelet additive solutions (Composol or SSP+) and a control group (100% plasma) were prepared. Swirling, platelet count, blood gases, metabolic variables, platelet activation markers, and apoptosis markers were analyzed on days 1, 5, 9 and 13. Swirling was well preserved and pH was acceptable (> 6.2) during storage for all platelet additive solutions units until day 9. SSP + units showed more stable pH and metabolic variables until day 13. Platelets in plasma showed higher glucose consumption than in Composol or in SSP+. The platelet additive solutions units showed better platelet metabolism maintenance, reduced glucose consumption and lactate production. The apoptotic markers were still low for 9 days in platelet concentrates with platelet additive solutions, suggesting the possibility to extend the shelf life with the use of SSP+ or Composol. Our findings suggest that the uses of Composol and SSP+ in canine platelet concentrates are potential alternatives in veterinary blood banks.

Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming

PubMed Central

Moreau, Thomas; Evans, Amanda L.; Vasquez, Louella; Tijssen, Marloes R.; Yan, Ying; Trotter, Matthew W.; Howard, Daniel; Colzani, Maria; Arumugam, Meera; Wu, Wing Han; Dalby, Amanda; Lampela, Riina; Bouet, Guenaelle; Hobbs, Catherine M.; Pask, Dean C.; Payne, Holly; Ponomaryov, Tatyana; Brill, Alexander; Soranzo, Nicole; Ouwehand, Willem H.; Pedersen, Roger A.; Ghevaert, Cedric

2016-01-01

The production of megakaryocytes (MKs)—the precursors of blood platelets—from human pluripotent stem cells (hPSCs) offers exciting clinical opportunities for transfusion medicine. Here we describe an original approach for the large-scale generation of MKs in chemically defined conditions using a forward programming strategy relying on the concurrent exogenous expression of three transcription factors: GATA1, FLI1 and TAL1. The forward programmed MKs proliferate and differentiate in culture for several months with MK purity over 90% reaching up to 2 × 105 mature MKs per input hPSC. Functional platelets are generated throughout the culture allowing the prospective collection of several transfusion units from as few as 1 million starting hPSCs. The high cell purity and yield achieved by MK forward programming, combined with efficient cryopreservation and good manufacturing practice (GMP)-compatible culture, make this approach eminently suitable to both in vitro production of platelets for transfusion and basic research in MK and platelet biology. PMID:27052461

Detection of microbial contamination in platelets

NASA Astrophysics Data System (ADS)

Berg, Tracy L.; Leparc, German; Huffman, Debra E.; Gennaccaro, Angela L.; Garcia-Lopez, Alicia; Klungness, Greta; Stephans, Christie; Garcia-Rubio, Luis H.

2005-03-01

In the United States, approximately 100 patients develop fatal sepsis associated with platelet transfusions every year. Current culture methods take 24-48 hours to acquire results, which in turn decrease the shelf life of platelets. Many of the microorganisms that contaminate platelets can replicate easily at room temperature, which is the necessary storage temperature to keep platelets functional. Therefore, there is a need for in-situ quality control assessment of the platelet quality. For this purpose, a real time spectrophotometric technique has been developed. The Spectral Acquisition Processing Detection (SAPD) method, comprised of a UV-vis spectrophotometer and modeling algorithms, is a rapid method that can be performed prior to platelet transfusion to decrease the risk of bacterial infection to patients. The SAPD method has been used to determine changes in cell suspensions, based on size, shape, chemical composition and internal structure. Changes in these cell characteristics can in turn be used to determine microbial contamination, platelet aging and other physiologic changes. Detection limits of this method for platelet suspensions seeded with bacterial contaminants were identified to be less than 100 cfu/ml of sample. Bacterial counts below 1000 cfu/ml are not considered clinically significant. The SAPD method can provide real-time identification of bacterial contamination of platelets affording patients an increased level of safety without causing undue strain on laboratory budgets or personnel while increasing the time frame that platelets can be used by dramatically shortening contaminant detection time.

Platelet-Rich Plasma and Platelet Gel: A Review

PubMed Central

Everts, Peter A.M.; Knape, Johannes T.A.; Weibrich, Gernot; Schönberger, Jacques P.A.M.; Hoffmann, Johannes; Overdevest, Eddy P.; Box, Henk A.M.; van Zundert, André

2006-01-01

Abstract: Strategies to reduce blood loss and transfusion of allogeneic blood products during surgical procedures are important in modern times. The most important and well-known autologous techniques are preoperative autologous predonation, hemodilution, perioperative red cell salvage, postoperative wound blood autotransfusion, and pharmacologic modulation of the hemostatic process. At present, new developments in the preparation of preoperative autologous blood component therapy by whole blood platelet-rich plasma (PRP) and platelet-poor plasma (PPP) sequestration have evolved. This technique has been proven to reduce the number of allogeneic blood transfusions during open heart surgery and orthopedic operations. Moreover, platelet gel and fibrin sealant derived from PRP and PPP mixed with thrombin, respectively, can be exogenously applied to tissues to promote wound healing, bone growth, and tissue sealing. However, to our disappointment, not many well-designed scientific studies are available, and many anecdotic stories exist, whereas questions remain to be answered. We therefore decided to study perioperative blood management in more detail with emphasis on the application and production of autologous platelet gel and the use of fibrin sealant. This review addresses a large variety of aspects relevant to platelets, platelet-rich plasma, and the application of platelet gel. In addition, an overview of recent animal and human studies is presented. PMID:16921694

Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Titano, J. J., E-mail: joseph.titano@mountsinai.org; Biederman, D. M., E-mail: derek.biederman@mountsinai.org; Marinelli, B. S., E-mail: brett.marinelli@exchange.mssm.edu

PurposeTransradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions.Methods and MaterialsPatients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications.ResultsFrom July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µLmore » (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6 % with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9 %) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1 %) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups.ConclusionsTransradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.« less

Blood transfusion during pregnancy, birth, and the postnatal period.

PubMed

Patterson, Jillian A; Roberts, Christine L; Bowen, Jennifer R; Irving, David O; Isbister, James P; Morris, Jonathan M; Ford, Jane B

2014-01-01

To identify risk factors for transfusion and trends in transfusion rates across pregnancy and the postnatal period. Linked hospital and birth data on all births in hospitals in New South Wales, Australia, between 2001 and 2010 were used to identify blood transfusions for women during pregnancy, at birth, and in the 6 weeks postpartum. Poisson regression was used to identify risk factors for red cell transfusion in the birth admission. Separate models were fitted for cesarean and vaginal births. Between 2001 and 2010, there were 12,147 transfusions across 891,914 pregnancies, with a transfusion rate of 1.4%. The transfusion rate increased steadily from 1.2% in 2001 to 1.6% in 2010. The majority of transfusions (91%) occurred during the birth admission, and 81% of these transfusions were associated with a diagnosis of hemorrhage. Women with bleeding or platelet disorders (vaginal: number transfused 529, relative risk [RR] 7.8, 99% confidence interval [CI] 6.9-8.7, cesarean: n=592, RR 8.7, CI 7.7-9.7) and placenta previa: (vaginal n=73, RR 4.6, CI 3.4-6.3, cesarean: n=875, RR 5.7, CI 5.1-6.4) were at highest risk of transfusion. Among vaginal births, increased risk was evident for forceps (n=1,036, RR 2.8, CI 2.5-3.0) or vacuum births (n=1,073, RR 1.9, CI 1.7-2.0) compared with nonoperative births. Rates of obstetric blood product transfusion have increased by 33% since 2001, with the majority of this associated with hemorrhage. Women with bleeding or platelet disorders and placenta previa are at increased risk of transfusion and should be treated accordingly. II.

Factors associated with excessive bleeding after cardiac surgery: A prospective cohort study.

PubMed

Lopes, Camila Takao; Brunori, Evelise Fadini Reis; Cavalcante, Agueda Maria Ruiz Zimmer; Moorhead, Sue Ann; Swanson, Elizabeth; Lopes, Juliana de Lima; de Barros, Alba Lucia Bottura Leite

2016-01-01

To identify factors associated with excessive bleeding (ExB) after cardiac surgery in adults. Excessive bleeding after cardiac surgery must be anticipated for implementation of timely interventions. A prospective cohort study with 323 adults requiring open-chest cardiac surgery. Potential factors associated with ExB were investigated through univariate analysis and logistic regression. The accuracy of the relationship between the independent variables and the outcome was depicted through the receiver-operating characteristic (ROC) curve. The factors associated with ExB included gender, body mass index (BMI), preoperative platelet count, intraoperative heparin doses and intraoperative platelet transfusion. The ROC curve cut-off points were 26.35 for the BMI; 214,000 for the preoperative platelet count, and 6.25 for intraoperative heparin dose. This model had an accuracy = 77.3%, a sensitivity = 81%, and a specificity = 62%. Male gender, BMI, preoperative platelet count, dose of intraoperative heparin >312.5 mg without subsequent platelet transfusion, are factors associated with ExB. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of platelet transfusion as fresh whole blood versus apheresis platelets for massively transfused combat trauma patients (CME).

PubMed

Perkins, Jeremy G; Cap, Andrew P; Spinella, Philip C; Shorr, Andrew F; Beekley, Alec C; Grathwohl, Kurt W; Rentas, Francisco J; Wade, Charles E; Holcomb, John B

2011-02-01

At major combat hospitals, the military is able to provide blood products to include apheresis platelets (aPLT), but also has extensive experience using fresh whole blood (FWB). In massively transfused trauma patients, we compared outcomes of patients receiving FWB to those receiving aPLT. This study was a retrospective review of casualties at the military hospital in Baghdad, Iraq, between January 2004 and December 2006. Patients requiring massive transfusion (≥10 units in 24 hr) were divided into two groups: those receiving FWB (n = 85) or aPLT (n = 284) during their resuscitation. Admission characteristics, resuscitation, and survival were compared between groups. Multivariate regression analyses were performed comparing survival of patients at 24 hours and at 30 days. Secondary outcomes including adverse events and causes of death were analyzed. Unadjusted survival between groups receiving aPLT and FWB was similar at 24 hours (84% vs. 81%, respectively; p = 0.52) and at 30 days (60% versus 57%, respectively; p = 0.72). Multivariate regression failed to identify differences in survival between patients receiving PLT transfusions either as FWB or as aPLT at 24 hours or at 30 days. Survival for massively transfused trauma patients receiving FWB appears to be similar to patients resuscitated with aPLT. Prospective trials will be necessary before consideration of FWB in the routine management of civilian trauma. However, in austere environments where standard blood products are unavailable, FWB is a feasible alternative. © 2010 American Association of Blood Banks.

Current concepts in platelet transfusion

PubMed Central

Mohanty, Dipika

2009-01-01

This is the era of component therapy. Therefore there is a need for rational use of platelet concentrate. Lot of knowledge has been added recently in the field of platelet specially about the platelet rich plasma and its application in clinical practice. The current review focuses on improvement in preparation of platelet rich plasma, the procedure to make the same more safe and its rational use. Furthermore newer aspects of platelet concentrate use in surgical practice and for regenerative medicine has also been discussed. It also covers some progress and hurdles in preparation of platelet substitutes. PMID:20041092

Blood Product Utilization Among Trauma and Nontrauma Massive Transfusion Protocols at an Urban Academic Medical Center.

PubMed

Patel, Eshan U; Ness, Paul M; Marshall, Christi E; Gniadek, Thomas; Efron, David T; Miller, Peter M; Zeitouni, Joseph A; King, Karen E; Bloch, Evan M; Tobian, Aaron A R

2017-09-01

Hospital-wide massive transfusion protocols (MTPs) primarily designed for trauma patients may lead to excess blood products being prepared for nontrauma patients. This study characterized blood product utilization among distinct trauma and nontrauma MTPs at a large, urban academic medical center. A retrospective study of blood product utilization was conducted in patients who required an MTP activation between January 2011 and December 2015 at an urban academic medical center. Trauma MTP containers included 6 red blood cell (RBC) units, 5 plasma units, and 1 unit of apheresis platelets. Nontrauma MTP containers included 6 RBC and 3 plasma units. There were 334 trauma MTP activations, 233 nontrauma MTP activations, and 77 nontrauma MTP activations that subsequently switched to a trauma MTP ("switched activations"). All nontrauma MTP activations were among bleeding patients who did not have a traumatic injury (100% [233/233]). Few patients with a nontrauma activation required ad hoc transfusion of RBC units (1.3% [95% confidence interval {CI}, 0.3%-3.7%]) or plasma (3.4% [95% CI, 1.5%-6.7%]), and only 45.5% (95% CI, 39.0%-52.1%) required ad hoc transfusion of apheresis platelets. Compared to trauma and switched activations, nontrauma activations transfused a lower median number of RBC, plasma, and apheresis platelet units (P < .001 for all comparisons). There was also a lower median number of prepared but unused plasma units for nontrauma activations (3; [interquartile range {IQR}, 3-5]) compared to trauma (7; [IQR, 5-10]; P < .001) and switched activations (8; [IQR, 5-11]; P < .001). The median number of unused apheresis platelet units was 1 (IQR, 1-2) for trauma activations and 0 (IQR, 0-1) for switched activations. There was a high proportion of trauma and switched activations in which all of the prepared apheresis platelet units were unused (28.1% [95% CI, 23.4%-33.3%] and 9.1% [95% CI, 3.7%-17.8%], respectively). The majority of initial nontrauma MTP activations did not require a switch to a trauma MTP. Patients remaining under a nontrauma MTP activation were associated with a lower number of transfused and unused plasma and apheresis platelet units. Future studies evaluating the use of hospital-wide nontrauma MTPs are warranted since an MTP designed for nontrauma patient populations may yield a key strategy to optimize blood product utilization in comparison to a universal MTP for both trauma and nontrauma patients.

Maximising platelet availability by delaying cold storage.

PubMed

Wood, B; Johnson, L; Hyland, R A; Marks, D C

2018-04-06

Cold-stored platelets may be an alternative to conventional room temperature (RT) storage. However, cold-stored platelets are cleared more rapidly from circulation, reducing their suitability for prophylactic transfusion. To minimise wastage, it may be beneficial to store platelets conventionally until near expiry (4 days) for prophylactic use, transferring them to refrigerated storage to facilitate an extended shelf life, reserving the platelets for the treatment of acute bleeding. Two ABO-matched buffy-coat-derived platelets (30% plasma/70% SSP+) were pooled and split to produce matched pairs (n = 8 pairs). One unit was stored at 2-6°C without agitation (day 1 postcollection; cold); the second unit was stored at 20-24°C with constant agitation until day 4 then stored at 2-6°C thereafter (delayed-cold). All units were tested for in vitro quality periodically over 21 days. During storage, cold and delayed-cold platelets maintained a similar platelet count. While pH and HSR were significantly higher in delayed-cold platelets, other metabolic markers, including lactate production and glucose consumption, did not differ significantly. Furthermore, surface expression of phosphatidylserine and CD62P, release of soluble CD62P and microparticles were not significantly different, suggesting similar activation profiles. Aggregation responses of delayed-cold platelets followed the same trend as cold platelets once transferred to cold storage, gradually declining over the storage period. The metabolic and activation profile of delayed-cold platelets was similar to cold-stored platelets. These data suggest that transferring platelets to refrigerated storage when near expiry may be a viable option for maximising platelet inventories. © 2018 International Society of Blood Transfusion.

Blood-Banking Techniques for Plateletpheresis in Swine

PubMed Central

Sondeen, Jill L; Prince, Malcolm D; Polykratis, Irene A; Hernandez, Orlando; Torres-Mendoza, Jaime; Guzman, Rodolfo De; Aden, James K; Dubick, Michael A

2014-01-01

During the past several years, trauma resuscitation in human patients has evolved from decreased use of crystalloids to increased use of blood products. Of high interest is the role of platelets in trauma resuscitation. Because conducting prehospital resuscitation in human trauma patients is very difficult, swine are often the animal model of choice for such studies because their coagulation and hemodynamic systems are similar to those in humans. However, consistent production of sufficient swine platelets for such studies has not previously been achieved. We developed a method for producing swine platelets by using standard human techniques and equipment. We assessed pH, pO2, pCO2, lactate, thromboelastography, and platelet aggregation over 5 d of storage to determine whether the swine platelet product met the American Association of Blood Banks (AABB) standards for transfusion. Swine platelets met AABB standards at 24 h but not at later time points. In addition, we fluorescently labeled nonautologous platelets and then measured their percentage recovery over 5 h (the time used in subsequent experimental studies) when transfused into a recipient pig. We showed that 80% of the platelets stored for 24 h remained in the circulation and increased the recipient pigs’ thromboelastographic responses, indicating that the platelets were viable and active. Therefore, swine platelets stored for 24 h by using standard human products met the AABB criteria and were functional. PMID:24827574

Blood Mixing Upregulates Platelet Membrane-Bound CD40 Ligand Expression in vitro Independent of Abo Compatibility.

PubMed

Huang, Go-Shine; Hu, Mei-Hua; Lin, Tso-Chou; Lin, Yi-Chang; Tsai, Yi-Ting; Lin, Chih-Yuan; Ke, Hung-Yen; Zheng, Xu-Zhi; Tsai, Chien-Sung

2017-11-30

Platelets play a central role in the inflammation response via CD40 ligand (CD40L) expression, which may lead to transfusion reactions. The precise role of platelet CD40L-mediated inflammation in transfusion reactions is unclear. Therefore, we assessed the effects of in vitro blood mixing on platelet CD40L expression. In addition, we examined the effect of ABO compatibility on CD40L expression. Donor packed red blood cells were acquired from a blood bank, and recipient blood was obtained from patients undergoing cardiac surgery and prepared as washed platelets. Donor blood was mixed with suspended, washed recipient platelets to obtain a final mixing ratio of 1%, 5%, or 10% (vol/vol). The blood mixtures were divided into three groups: Group M, cross-matched blood-type mixing (n = 20); Group S, ABO type-specific uncross-matched blood (n = 20); and Group I, ABO incompatibility (not ABO type-specific blood and not process cross-matched) mixing (n = 20). The blood mixtures were used to detect platelet membrane-bound CD40L expression by flow cytometry. Blood mixing resulted in an increase in CD40L expression in Group M (P < 0.001), Group S (P < 0.001), and Group I (P < 0.001). CD40L expression following blood mixing potentially led to a transfusion reaction in each of the groups. There were no differences in CD40L expression among the three groups (P = 0.988) correlated with ABO compatibility or incompatibility. This indicates that the reactions between red blood cell surface antigens and plasma antibodies do not play a role in the induction of CD40L expression.

Platelet Transfusion – the Art and Science of Compromise

PubMed Central

Cid, Joan; Harm, Sarah K.; Yazer, Mark H.

2013-01-01

Summary Many modern therapies depend on platelet (PLT) transfusion support. PLTs have a 4- to 7-day shelf life and are frequently in short supply. In order to optimize the inventory PLTs are often transfused to adults without regard for ABO compatibility. Hemolytic reactions are infrequent despite the presence of ‘high titer’ anti-A and anti-B antibodies in some of the units. Despite the low risk for hemolysis, some centers provide only ABO identical PLTs to their recipients; this practice might have other beneficial outcomes that remain to be proven. Strategies to mitigate the risk of hemolysis and the clinical and laboratory outcomes following ABO-matched and mismatched transfusions will be discussed. Although the PLTs themselves do not carry the D antigen, a small number of RBCs are also transfused with every PLT dose. The quantity of RBCs varies by the type of PLT preparation, and even a small quantity of D+ RBCs can alloimmunize a susceptible D− host. Thus PLT units are labeled as D+/–, and most transfusion services try to prevent the transfusion of D+ PLTs to D– females of childbearing age. A similar policy for patients with hematological diseases is controversial, and the elements and mechanisms of anti-D alloimmunization will be discussed. PMID:23922541

Estimating the ratio of multivariate recurrent event rates with application to a blood transfusion study.

PubMed

Ning, Jing; Rahbar, Mohammad H; Choi, Sangbum; Piao, Jin; Hong, Chuan; Del Junco, Deborah J; Rahbar, Elaheh; Fox, Erin E; Holcomb, John B; Wang, Mei-Cheng

2017-08-01

In comparative effectiveness studies of multicomponent, sequential interventions like blood product transfusion (plasma, platelets, red blood cells) for trauma and critical care patients, the timing and dynamics of treatment relative to the fragility of a patient's condition is often overlooked and underappreciated. While many hospitals have established massive transfusion protocols to ensure that physiologically optimal combinations of blood products are rapidly available, the period of time required to achieve a specified massive transfusion standard (e.g. a 1:1 or 1:2 ratio of plasma or platelets:red blood cells) has been ignored. To account for the time-varying characteristics of transfusions, we use semiparametric rate models for multivariate recurrent events to estimate blood product ratios. We use latent variables to account for multiple sources of informative censoring (early surgical or endovascular hemorrhage control procedures or death). The major advantage is that the distributions of latent variables and the dependence structure between the multivariate recurrent events and informative censoring need not be specified. Thus, our approach is robust to complex model assumptions. We establish asymptotic properties and evaluate finite sample performance through simulations, and apply the method to data from the PRospective Observational Multicenter Major Trauma Transfusion study.

Rotational Thromboelastometry or Conventional Coagulation Tests in Liver Transplantation: Comparing Blood Loss, Transfusions, and Cost.

PubMed

Smart, Laura; Mumtaz, Khalid; Scharpf, Danielle; Gray, Nicole O'Bleness; Traetow, Daniel; Black, Sylvester; Michaels, Anthony J; Elkhammas, Elmahdi; Kirkpatrick, Robert; Hanje, A James

Orthotopic liver transplantation (OLT) can be associated with significant bleeding requiring multiple blood product transfusions. Rotational thromboelastometry (ROTEM) is a point-of-care device that has been used to monitor coagulation during OLT. Whether it reduces blood loss/transfusions during OLT remains controversial. We aim to compare ROTEM with conventional coagulation tests (aPTT, PT, INR, platelet count, fibrinogen) to guide transfusion of platelets, cryoprecipitate, and fresh frozen plasma (FFP) during OLT over 3 years. Thirty-four patients who had transfusions guided by ROTEM were compared to 34 controls who received transfusions guided by conventional coagulation tests (CCT). Intraoperative blood loss, type/ amount of blood products transfused, and direct costs were compared between the two groups. The ROTEM group had significantly less intra-operative blood loss (2.0 vs. 3.0 L, p = 0.04) and fresh frozen plasma (FFP) transfusion (4 units vs. 6.5 units, p = 0.015) compared to the CCT group (2.0L vs. 3.0L, p = 0.04). However, total number of patients transfused cryoprecipitate was increased in ROTEM (n = 25;73%) as compared to CCT (n = 19; 56%), p = 0.033. The direct cost of blood products plus testing was reduced in the ROTEM group ($113,142.89 vs. $127,814.77). In conclusion implementation of a ROTEM-guided transfusion algorithm resulted in a reduction in intra-operative blood loss, FFP transfusion and a decrease in direct cost during OLT. ROTEM is a useful and safe point of care device in OLT setting.

Bacterial contamination of platelet components not detected by BacT/ALERT®.

PubMed

Abela, M A; Fenning, S; Maguire, K A; Morris, K G

2018-02-01

To investigate the possible causes for false negative results in BacT/ALERT ® 3D Signature System despite bacterial contamination of platelet units. The Northern Ireland Blood Transfusion Service (NIBTS) routinely extends platelet component shelf life to 7 days. Components are sampled and screened for bacterial contamination using an automated microbial detection system, the BacT/ALERT ® 3D Signature System. We report on three platelet components with confirmed bacterial contamination, which represent false negative BacT/ALERT ® results and near-miss serious adverse events. NIBTS protocols for risk reduction of bacterial contamination of platelet components are described. The methodology for bacterial detection using BacT/ALERT ® is outlined. Laboratory tests, relevant patient details and relevant follow-up information are analysed. In all three cases, Staphylococcus aureus was isolated from the platelet residue and confirmed on terminal sub-culture using BacT/ALERT ® . In two cases, S. aureus with similar genetic makeup was isolated from the donors. Risk reduction measures for bacterial contamination of platelet components are not always effective. Automated bacterial culture detection does not eliminate the risk of bacterial contamination. Visual inspection of platelet components prior to release, issue and administration remains an important last line of defence. © 2017 British Blood Transfusion Society.

Auditoría transfusional en un Hospital de Alta Especialidad. Análisis retrospectivo de 12 meses.

PubMed

Cano-Palmeros, Miguel Ángel; Castañón-González, Jorge; Cano-Quevedo, Miguel Ángel; Morales-Uchino, Dora Stephanie; Benavides-González, Araceli; Espinosa-Kuri, Alejandro; Ruiz-Moreno, Diana Elvia

2017-01-01

Human blood is the only source of red blood cells, platelets and plasma, and includes the clotting factors. Transfusion of concentrated erythrocyte and blood products is a simple form of organ transplant, the benefits of blood transfusion are real, and the life of the patients depends on how is used. to know the transfusion adherence to the recommendations in the Hospital of High Specialty of Veracruz. For a period of 12 months an audit took place in the Transfusion Service of the Hospital of High Specialty of Veracruz, México, on a basis of 3 168 requests for transfusion from which 2314 corresponded to erythrocyte concentrate, 220 to platelet concentrate, 493 to fresh frozen plasma and 41 to cryoprecipitate. An analysis of concordance was made with the different established regulations for a right indication and the results showed that 2171 (67.26%) were appropriate and 1037 were inadequate, which means that the lack of academic training in medicine transfusional affects the risk for patients and cost for Health Institutions. Copyright: © 2017 SecretarÍa de Salud

Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial.

PubMed

Holcomb, John B; Tilley, Barbara C; Baraniuk, Sarah; Fox, Erin E; Wade, Charles E; Podbielski, Jeanette M; del Junco, Deborah J; Brasel, Karen J; Bulger, Eileen M; Callcut, Rachael A; Cohen, Mitchell Jay; Cotton, Bryan A; Fabian, Timothy C; Inaba, Kenji; Kerby, Jeffrey D; Muskat, Peter; O'Keeffe, Terence; Rizoli, Sandro; Robinson, Bryce R H; Scalea, Thomas M; Schreiber, Martin A; Stein, Deborah M; Weinberg, Jordan A; Callum, Jeannie L; Hess, John R; Matijevic, Nena; Miller, Christopher N; Pittet, Jean-Francois; Hoyt, David B; Pearson, Gail D; Leroux, Brian; van Belle, Gerald

2015-02-03

Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2% [95% CI, -9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7% [95% CI, -10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4% [95% CI, -10.4% to -0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. clinicaltrials.gov Identifier: NCT01545232.

Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a 1:1:2 Ratio and Mortality in Patients With Severe Trauma

PubMed Central

Holcomb, John B.; Tilley, Barbara C.; Baraniuk, Sarah; Fox, Erin E.; Wade, Charles E.; Podbielski, Jeanette M.; del Junco, Deborah J.; Brasel, Karen J.; Bulger, Eileen M.; Callcut, Rachael A.; Cohen, Mitchell Jay; Cotton, Bryan A.; Fabian, Timothy C.; Inaba, Kenji; Kerby, Jeffrey D.; Muskat, Peter; O’Keeffe, Terence; Rizoli, Sandro; Robinson, Bryce R. H.; Scalea, Thomas M.; Schreiber, Martin A.; Stein, Deborah M.; Weinberg, Jordan A.; Callum, Jeannie L.; Hess, John R.; Matijevic, Nena; Miller, Christopher N.; Pittet, Jean-Francois; Hoyt, David B.; Pearson, Gail D.; Leroux, Brian; van Belle, Gerald

2015-01-01

IMPORTANCE Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials. OBJECTIVE To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013. INTERVENTIONS Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled). MAIN OUTCOMES AND MEASURES Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status. RESULTS No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, −4.2% [95% CI, −9.6% to 1.1%]; P = .12) or at 30 days (22.4% vs 26.1%, respectively; difference, −3.7% [95% CI, −10.2% to 2.7%]; P = .26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, −5.4% [95% CI, −10.4% to −0.5%]; P = .03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P = .006). Despite the 1:1:1 group receiving more plasma (median of 7 U vs 5 U, P < .001) and platelets (12 U vs 6 U, P < .001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications. CONCLUSIONS AND RELEVANCE Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01545232 PMID:25647203

The impact of a massive transfusion protocol (1:1:1) on major hepatic injuries: does it increase abdominal wall closure rates?

PubMed

Ball, Chad G; Dente, Christopher J; Shaz, Beth; Wyrzykowski, Amy D; Nicholas, Jeffrey M; Kirkpatrick, Andrew W; Feliciano, David V

2013-10-01

Massive transfusion protocols (MTPs) using high plasma and platelet ratios for exsanguinating trauma patients are increasingly popular. Major liver injuries often require massive resuscitations and immediate hemorrhage control. Current published literature describes outcomes among patients with mixed patterns of injury. We sought to identify the effects of an MTP on patients with major liver trauma. Patients with grade 3, 4 or 5 liver injuries who required a massive blood component transfusion were analyzed. We compared patients with high plasma:red blood cell:platelet ratio (1:1:1) transfusions (2007-2009) with patients injured before the creation of an institutional MTP (2005-2007). Among 60 patients with major hepatic injuries, 35 (58%) underwent resuscitation after the implementation of an MTP. Patient and injury characteristics were similar between cohorts. Implementation of the MTP significantly improved plasma: red blood cell:platelet ratios and decreased crystalloid fluid resuscitation (p = 0.026). Rapid improvement in early acidosis and coagulopathy was superior with an MTP (p = 0.009). More patients in the MTP group also underwent primary abdominal fascial closure during their hospital stay (p = 0.021). This was most evident with grade 4 injuries (89% vs. 14%). The mean time to fascial closure was 4.2 days. The overall survival rate for all major liver injuries was not affected by an MTP (p = 0.61). The implementation of a formal MTP using high plasma and platelet ratios resulted in a substantial increase in abdominal wall approximation. This occurred concurrently to a decrease in the delivered volume of crystalloid fluid.

Bacterial screening of apheresis platelets with a rapid test: a 113-month single center experience.

PubMed

Ruby, Kristen N; Thomasson, Reggie R; Szczepiorkowski, Zbigniew M; Dunbar, Nancy M

2018-04-17

The 2016 Food and Drug Administration draft guidance describes the use of a rapid test (RT) to enhance platelet transfusion safety and availability. This study reports a 113-month experience of screening of apheresis platelets (APs) by RT. From July 2008 to October 2015, all APs underwent an RT on Day 4. Day 6 and 7 units were transfused with transfusion medicine physician approval. Any units remaining on Day 8 had a second RT performed. From November 2015 to November 2017, APs underwent an RT on Day 5 with a repeat RT on Days 6 and 7. During both periods, positive RTs underwent confirmatory testing with culture when repeat testing was positive. A total of 9009 APs underwent an RT on Day 4 or 5. Of these, 45 (0.5%) were RT positive, with no true positives. A total of 754 underwent a second RT on Day 8, with no positives. Since November 2015, 1152 platelets have undergone a second RT on Day 6; 391 have undergone a third RT on Day 7. Of these, five (0.4%) were RT positive on Day 6, with no true positives. There were no septic transfusion reactions identified by passive surveillance at our institution during either study period. To date, we have not detected any true positives after performing 11,306 tests on 9009 APs. A total of 1906 underwent testing twice, and 391 underwent testing three times. We did not identify any conversions from negative to positive on repeat testing. © 2018 AABB.

The effects of platelet apheresis on blood saving and coagulation in bilateral total hip replacement: A prospective study on 60 patients.

PubMed

Qu, Zhijun; Wang, Geng; Xu, Chengshi; Zhang, Dazhi; Qu, Xiangdong; Zhou, Haibin; Ma, Jun

2016-10-01

Preoperative platelet rich plasma (PRP) harvest has been used in cardiopulmonary surgery for more than 10 years. There is no previous study dealing with PRP in bilateral total hip replacement. This study was to investigate the effects of PRP on blood saving and blood coagulation function in patients with bilateral total hip replacement. A prospective, randomized, clinical trial was conducted. Sixty patients were enrolled, including 30 patients undergoing PRP in the PRP group and 30 controls. The surgery time, total transfusion volume, blood loss, allogenic blood transfusion, autologous blood transfusion, urine volume, drainage volume, some blood parameters (including Fibrinogen, D-dimer, Prothrombin time, international normalizedratio, activated partial thromboplastin time, Platelet, Haemoglobin B), thrombelastogram (TEG) and blood-gas parameters were studied in the perioperative stage. The measurement data were analyzed statistically. There was no statistical difference between the two groups in baseline characteristics, surgery time, total transfusion volume, blood loss, autologous blood transfusion, etc. Allogenic blood transfusion in the PRP group was less than the control group with statistical difference (p = 0.024). Fibrinogen in the PRP group was higher than the control group (p = 0.008). Among the TEG indicators, activated clotting time and coagulation time K in the PRP group were less than the control group. Clotting rate and maximum amplitude in the PRP group were higher. The blood-gas parameters presented no statistical difference. The results suggested that PRP probably played a positive role in blood coagulation function as well as blood saving in patients with bilateral total hip replacement. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Clinical and Laboratory Associations with Persistent Hyperferritinemia in 373 Black Hemochromatosis and Iron Overload Screening Study Participants.

PubMed

Barton, James C; Barton, J Clayborn; Adams, Paul C

2017-01-01

373 black participants had elevated screening and post-screening serum ferritin (SF) (> 300 μg/L men; > 200 μg/L women). We retrospectively studied SF and post-screening age; sex; body mass index; transferrin saturation (TS); ALT; AST; GGT; elevated C-reactive protein; ß-thalassemia; neutrophils; lymphocytes; monocytes; platelets; metacarpophalangeal joint hypertrophy; hepatomegaly; splenomegaly; diabetes; HFE H63D positivity; iron/alcohol intakes; and blood/erythrocyte transfusion units. Liver disease was defined as elevated ALT or AST. We computed correlations of SF and TS with: age; body mass index; ALT; AST; GGT; C-reactive protein; blood cell counts; and iron/alcohol. We compared participants with SF > 1,000 and ≤ 1,000 μg/L and performed regressions on SF. There were 237 men (63.5%). Mean age was 55 ± 13 (SD) y. 143 participants had liver disease (62 hepatitis B or C). There were significant correlations of SF: TS, ALT, AST, GGT, and monocytes (positive); and SF and TS with platelets (negative). 22 participants with SF > 1,000 μg/L had significantly higher median TS, ALT, and AST, and prevalences of anemia and transfusion > 10 units; and lower median platelets. Regression on SF revealed significant associations: TS; male sex; age; GGT; transfusion units (positive); and splenomegaly (negative) (p < 0.0001, 0.0016, 0.0281, 0.0025, 0.0001, and 0.0096, respectively). Five men with SF > 1,000 μg/L and elevated TS had presumed primary iron overload (hemochromatosis). Four participants had transfusion iron overload. Persistent hyperferritinemia in 373 black adults was associated with male sex, age, TS, GGT, and transfusion. 2.4% had primary iron overload (hemochromatosis) or transfusion iron overload.

Manual exchange transfusion for severe imported falciparum malaria: a retrospective study.

PubMed

Lin, Jinfeng; Huang, Xiaoying; Qin, Gang; Zhang, Suyan; Sun, Weiwei; Wang, Yadong; Ren, Ke; Xu, Junxian; Han, Xudong

2018-01-16

This study was designed to evaluate the efficacy of exchange transfusion in patients with severe imported falciparum malaria. Twelve patients who met the diagnostic criteria for severe malaria were treated with exchange transfusion 14 times according to a conventional anti-malarial treatment. This study evaluated the efficacy of exchange transfusion for severe imported falciparum malaria. Clinical data of severe imported falciparum malaria patients admitted to the intensive care unit (ICU) of Nantong Third People's Hospital from January 2007 to December 2016 were investigated in this retrospective study. Patients were divided into the intervention group, which received exchange transfusion, and the control group. This study assessed parasite clearance and outcomes of the two groups, and levels of erythrocytes, haemoglobin, platelets, coagulation, liver function, lactate, C-reactive protein, and procalcitonin, before and after exchange transfusion in the intervention group. There was no significant difference in the severity of admitted patients. Exchange transfusion was successfully applied 14 times in the intervention group. Differences in the levels of erythrocytes, haemoglobin and platelets did not reach statistical significance. Exchange transfusion improved coagulation, liver function, lactic acid, C-reactive protein, and procalcitonin. No differences were observed in parasite clearance, ICU and hospital length of stay, in-hospital mortality, and costs of hospitalization between the two groups. Exchange transfusion as adjunctive therapy for severe malaria was observed to be safe in this setting. Exchange transfusion can improve liver function and coagulation and reduce inflammation, but it failed to improve parasite clearance and the outcomes of severe imported falciparum malaria in this case series.

Novel and unexpected clearance mechanisms for cold platelets

PubMed Central

Rumjantseva, Viktoria; Hoffmeister, Karin M.

2015-01-01

Storage at room temperature is limited to 5 days because of the risk of bacterial growth and loss of platelet functionality. Platelet refrigeration remains impossible, because once chilled, platelets are rapidly removed from circulation. Chilling platelets (<4 h) clusters glycoprotein (GP) Ibα receptors, and β2 integrins on hepatic macrophages recognize clustered βGlcNAc residues leading to rapid clearance of acutely chilled platelets. Prolonged refrigeration increases the exposure of galactose residues such that, unexpectedly, hepatocytes remove platelets using their asialoglycoprotein receptors. Here we review current knowledge of the mechanisms of platelet removal, the existing knowledge of refrigerated platelet function, and methods to preserve platelet concentrates long-term for transfusion. PMID:19932055

Quality Assessment of Established and Emerging Blood Components for Transfusion

PubMed Central

Marks, Denese C.

2016-01-01

Blood is donated either as whole blood, with subsequent component processing, or through the use of apheresis devices that extract one or more components and return the rest of the donation to the donor. Blood component therapy supplanted whole blood transfusion in industrialized countries in the middle of the twentieth century and remains the standard of care for the majority of patients receiving a transfusion. Traditionally, blood has been processed into three main blood products: red blood cell concentrates; platelet concentrates; and transfusable plasma. Ensuring that these products are of high quality and that they deliver their intended benefits to patients throughout their shelf-life is a complex task. Further complexity has been added with the development of products stored under nonstandard conditions or subjected to additional manufacturing steps (e.g., cryopreserved platelets, irradiated red cells, and lyophilized plasma). Here we review established and emerging methodologies for assessing blood product quality and address controversies and uncertainties in this thriving and active field of investigation. PMID:28070448

Additive solutions differentially affect metabolic and functional parameters of platelet concentrates.

PubMed

Leitner, G C; List, J; Horvath, M; Eichelberger, B; Panzer, S; Jilma-Stohlawetz, P

2016-01-01

Pathogen inactivation (PI) of platelet concentrates with extension of shelf life to 7 days requires the use of platelet additive solutions (PAS). We examined the quality of platelets resuspended in three different PAS stored for up to 7 days. Twelve triple adult dose platelet concentrates (PC) were collected using the TrimaAccel® collection system. Each highly concentrated product was divided into three equal parts, and the additive solutions (Composol® or SSP+® or Intersol™) were added to a final concentration of 56% PAS and 44% plasma. Samples were drawn on days 1, 5 and 7 to measure pH, glucose, lactate dehydrogenase (LDH), lactate, mean platelet volume (MPV) and the aggregation response to collagen and the thrombin receptor agonist peptide-6. Further, p-selectin expression on platelets was assessed. No statistically significant changes were observed for pH and MPV during 7 days of storage in all PAS containing PCs, whereas glucose decreased and LDH and lactate increased over time (P < 0·05). These changes were particularly evident in Intersol PCs on days 5 and 7 compared with Composol® PCs or SSP+® PCs (P < 0·05). Platelets from Intersol PCs exhibited the highest baseline activation of p-selectin and showed reduced collagen- and TRAP-6-induced aggregation. Resuspension of platelets in Intersol for 7 days results in increased platelet activation and platelet metabolism compared with SSP+® or Composol®. Further clinical studies are needed to evaluate whether the observed differences in PAS-PCs affect the recovery rate or the life span of transfused platelets. © 2015 International Society of Blood Transfusion.

Prospective change control analysis of transfer of platelet concentrate production from a specialized stem cell transplantation unit to a blood transfusion center.

PubMed

Sigle, Joerg-Peter; Medinger, Michael; Stern, Martin; Infanti, Laura; Heim, Dominik; Halter, Joerg; Gratwohl, Alois; Buser, Andreas

2012-01-01

Specialized centers claim a need for blood component production independent from the general blood transfusion services. We performed a prospective change control analysis of the transfer of platelet (PLT) production for hematological patients at the University Hospital Basel from the Department of Hematology to the Blood Transfusion Centre, Swiss Red Cross, Basel in February 2006. We wanted to demonstrate that neither quality nor transfusion outcome was affected. Production quantity and efficiency, product quality and transfusion outcome were systematically recorded. A 2-year pretransfer period was compared to a 2 year post-transfer period. After transfer production quantity at the Blood Transfusion Centre increased from 4,483 to 6,190 PLT concentrates. Production efficiency increased with a significant decrease in the rate of expired products (18% vs. 8%; P < 0.001). Product quality showed a slight decrease in median PLT count per unit (2.84 vs. 2.75 × 10(11); P < 0.001) and a slight increase in mean storage time prior to transfusion (3.18 vs. 3.30 days; P < 0.001). Transfusion outcome measured as median corrected count increment one hour post-transfusion (10.5 vs. 10.7; P = 0.3) and the rate of patients with inadequate post-transfusion increment (31.5% vs. 32.1%; P = 0.6) did not differ. Supply and quality of PLT products was maintained after the transfer of PLT production to the Blood Transfusion Centre. An optimization of the supply chain process with markedly decreased expiration rates was achieved. These results argue against the need of specialized PLT production sites for selected patient groups. Copyright © 2012 Wiley Periodicals, Inc.

The Blood Group A Genotype Determines the Level of Expression of the Blood Group A on Platelets But Not the Anti-B Isotiter

PubMed Central

Lehner, Barbara; Eichelberger, Beate; Jungbauer, Christof; Panzer, Simon

2015-01-01

Summary Background The extent of expression of the blood group A on platelets is controversial. Further, the relation between platelets' blood group A expression and the titers of isoagglutinins has not been thoroughly investigated, so far. Methods We evaluated the relation between the genotype with platelets' blood group A and H expression estimated by flow cytometry and the titers of isoagglutinins. Results The A expression varied between genotypes and within genotypes. However, the expression in A1 was stronger than in all other genotypes (p < 0.0001). An overlap of expression levels was apparent between homozygous A1A1 and heterozygous A1 individuals. Still, The A1A1 genotype is associated with a particularly high antigen expression (p = 0.009). Platelets' A expression in A2 versus blood group O donors was also significant (p = 0.007), but there was again an overlap of expression. The secretor status had only little influence on the expression (p = 0.18). Also, isoagglutinin titers were not associated with genotypes. Conclusion: To distinguish between A1 and A2 donors may reduce incompatible platelet transfusions and therefore be favorable on platelet transfusion increment. Clinical data are needed to support this notion. PMID:26733767

Extending The Shelf Life Of Blood Platelets

NASA Technical Reports Server (NTRS)

Surgenor, Douglas M.

1988-01-01

New method of storing human blood platelets extends vitality for transfusions. Packaged as suspension in sterile liquid in plastic blood bags. Each bag placed between pair of plastic grids, and rubberbands placed around sandwich thus formed to hold together. Stored upright in open air or in container through which air pumped at rate of at least 45 L/min. Ensures that platelets receive ample oxygen and expiratory carbon dioxide form platelets removed before pH drops to harmful levels.

Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and Other Dehydration Techniques

DTIC Science & Technology

1991-01-31

that a short incubation of platelets with 0.1% (final conc.) KMnO4 seems optimal, but a protective agent such as trehalose , sucrose, or albumin must...yields were improved also by inclusion of albumin during platelet washing and trehalose during the lyophilization step (74% recovery under best... trehalose is advantageous in this protocol has yet to be decided. Vesiculation of platelet membranes is still evident by flow cytometry in the

Differences in levels of platelet-derived microparticles in platelet components prepared using the platelet rich plasma, buffy coat, and apheresis procedures.

PubMed

Noulsri, Egarit; Udomwinijsilp, Prapaporn; Lerdwana, Surada; Chongkolwatana, Viroje; Permpikul, Parichart

2017-04-01

There has been an increased interest in platelet-derived microparticles (PMPs) in transfusion medicine. Little is known about PMP status during the preparation of platelet concentrates for transfusion. The aim of this study is to compare the PMP levels in platelet components prepared using the buffy coat (BC), platelet-rich plasma platelet concentrate (PRP-PC), and apheresis (AP) processes. Platelet components were prepared using the PRP-PC and BC processes. Apheresis platelets were prepared using the Trima Accel and Amicus instruments. The samples were incubated with annexin A5-FITC, CD41-PE, and CD62P-APC. At day 1 after processing, the PMPs and activated platelets were determined using flow cytometry. Both the percentage and number of PMPs were higher in platelet components prepared using the Amicus instrument (2.6±1.8, 32802±19036 particles/μL) than in platelet components prepared using the Trima Accel instrument (0.5±0.4, 7568±5298 particles/μL), BC (1.2±0.6, 12,920±6426 particles/μL), and PRP-PC (0.9±0.6, 10731±5514 particles/μL). Both the percentage and number of activated platelets were higher in platelet components prepared using the Amicus instrument (33.2±13.9, 427553±196965 cells/μL) than in platelet components prepared using the Trima Accel instrument (16.2±6.1, 211209±87706 cells/μL), BC (12.9±3.2, 140624±41003 cells/μL), and PRP-PC (21.1±6.3, 265210±86257 cells/μL). The study suggests high variability of PMPs and activated platelets in platelet components prepared using different processes. This result may be important in validating the instruments involved in platelet blood collection and processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relative effects of plasma, fibrinogen concentrate, and factor XIII on ROTEM coagulation profiles in an in vitro model of massive transfusion in trauma.

PubMed

Schmidt, David E; Halmin, Märit; Wikman, Agneta; Östlund, Anders; Ågren, Anna

2017-10-01

Massive traumatic haemorrhage is aggravated through the development of trauma-induced coagulopathy, which is managed by plasma transfusion and/or fibrinogen concentrate administration. It is yet unclear whether these treatments are equally potent in ensuring adequate haemostasis, and whether additional factor XIII (FXIII) administration provides further benefits. In this study, we compared ROTEM whole blood coagulation profiles after experimental massive transfusion with different transfusion regimens in an in vitro model of dilution- and transfusion-related coagulopathy. Healthy donor blood was mixed 1 + 1 with six different transfusion regimens. Each regimen contained RBC, platelet concentrate, and either fresh frozen plasma (FFP) or Ringer's acetate (RA). The regimens were further augmented through addition of a low- or medium-dose fibrinogen concentrate and FXIII. Transfusion with FFP alone was insufficient to maintain tissue-factor activated clot strength, coincidental with a deficiency in fibrin-based clot strength. Fibrinogen concentrate conserved, but did not improve coagulation kinetics and overall clot strength. Only combination therapy with FFP and low-dose fibrinogen concentrate improved both coagulation kinetics and fibrin-based clot strength. Administration of FXIII did not result in an improvement of clot strength. In conclusion, combination therapy with both FFP and low-dose fibrinogen concentrate improved clotting time and produced firm clots, representing a possible preferred first-line regimen to manage trauma-induced coagulopathy when RBC and platelets are also transfused. Further research is required to identify optimal first-line transfusion fluids for massive traumatic haemorrhage.

Induced Pluripotent Stem Cell-Derived Red Blood Cells and Platelet Concentrates: From Bench to Bedside.

PubMed

Focosi, Daniele; Amabile, Giovanni

2017-12-27

Red blood cells and platelets are anucleate blood components indispensable for oxygen delivery and hemostasis, respectively. Derivation of these blood elements from induced pluripotent stem (iPS) cells has the potential to develop blood donor-independent and genetic manipulation-prone products to complement or replace current transfusion banking, also minimizing the risk of alloimmunization. While the production of erythrocytes from iPS cells has challenges to overcome, such as differentiation into adult-type phenotype that functions properly after transfusion, platelet products are qualitatively and quantitatively approaching a clinically-applicable level owing to advances in expandable megakaryocyte (MK) lines, platelet-producing bioreactors, and novel reagents. Guidelines that assure the quality of iPS cells-derived blood products for clinical application represent a novel challenge for regulatory agencies. Considering the minimal risk of tumorigenicity and the expected significant demand of such products, ex vivo production of iPS-derived blood components can pave the way for iPS translation into the clinic.

Hematopoietic recovery after administration of deferasirox for transfusional iron overload in a case of myelodysplastic syndrome.

PubMed

OKABE, Hiroshi; SUZUKI, Takahiro; OMORI, Tsukasa; MORI, Masaki; UEHARA, Eisuke; HATANO, Kaoru; UEDA, Masuzu; MATSUYAMA, Tomohiro; TOSHIMA, Masaki; QZAKI, Katsutoshi; NAGAI, Tadashi; MUROI, Kazuo; OZAWA, Keiya

2009-11-01

Deferasirox (DFX) is a newly developed oral iron chelator that enables effective chelation with once daily administration. We describe here a case of transfusional-iron overloaded patient who experienced hematopoietic recovery after DFX administration. A 75-year-old woman with iron overload, who had been diagnosed with MDS (RCMD) and had received a transfusion of red blood cells and platelets regularly for 3 years, enrolled in the phase I clinical trial of ICL670 (DFX) in Japan. DFX administration steadily decreased her serum ferritin levels and chelated overloaded iron effectively. Interestingly, a year after initiation of the trial, she needed fewer blood transfusions, and no more transfusions after the 17th month of the trial. Even after suspending transfusions, her hemoglobin level and platelet count increased continuously, and she now has stable disease without blood transfusions. She has not received any specific treatment for MDS during this period. Examination of the bone marrow aspirates in the 35th month revealed dysplastic cells, indicating no remarkable change in the state of MDS. This case suggests that excess iron hampers hematopoiesis and that adequate iron chelation may improve hematological data in some iron-overloaded patients.

A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions.

PubMed

Cotton, Bryan A; Podbielski, Jeanette; Camp, Elizabeth; Welch, Timothy; del Junco, Deborah; Bai, Yu; Hobbs, Rhonda; Scroggins, Jamie; Hartwell, Beth; Kozar, Rosemary A; Wade, Charles E; Holcomb, John B

2013-10-01

To determine whether resuscitation of severely injured patients with modified whole blood (mWB) resulted in fewer overall transfusions compared with component (COMP) therapy. For decades, whole blood (WB) was the primary product for resuscitating patients in hemorrhagic shock. After dramatic advances in blood banking in the 1970s, blood donor centers began supplying hospitals with individual components [red blood cell (RBC), plasma, platelets] and removed WB as an available product. However, no studies of efficacy or hemostatic potential in trauma patients were performed before doing so. Single-center, randomized trial of severely injured patients predicted to large transfusion volume. Pregnant patients, prisoners, those younger than 18 years or with more than 20% total body surface area burns (TBSA) burns were excluded. Patients were randomized to mWB (1 U mWB) or COMP therapy (1 U RBC+ 1 U plasma) immediately on arrival. Each group also received 1 U platelets (apheresis or prepooled random donor) for every 6 U of mWB or 6 U of RBC + 6 U plasma. The study was performed under the Exception From Informed Consent (Food and Drug Administration 21 code of federal regulations [CFR] 50.24). Primary outcome was 24-hour transfusion volumes. A total of 107 patients were randomized (55 mWB, 52 COMP therapy) over 14 months. There were no differences in demographics, arrival vitals or laboratory values, injury severity, or mechanism. Transfusions were similar between groups (intent-to-treat analysis). However, when excluding patients with severe brain injury (sensitivity analysis), WB group received less 24-hour RBC (median 3 vs 6, P = 0.02), plasma (4 vs 6, P = 0.02), platelets (0 vs 3, P = 0.09), and total products (11 vs 16, P = 0.02). Compared with COMP therapy, WB did not reduce transfusion volumes in severely injured patients predicted to receive massive transfusion. However, in the sensitivity analysis (patients without severe brain injuries), use of mWB significantly reduced transfusion volumes, achieving the prespecified endpoint of this initial pilot study.

Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders

PubMed Central

Estcourt, Lise J; Desborough, Michael; Brunskill, Susan J; Doree, Carolyn; Hopewell, Sally; Murphy, Michael F; Stanworth, Simon J

2016-01-01

Background People with haematological disorders are frequently at risk of severe or life-threatening bleeding as a result of thrombocytopenia (reduced platelet count). This is despite the routine use of prophylactic platelet transfusions to prevent bleeding once the platelet count falls below a certain threshold. Platelet transfusions are not without risk and adverse events may be life-threatening. A possible adjunct to prophylactic platelet transfusions is the use of antifibrinolytics, specifically the lysine analogues tranexamic acid (TXA) and epsilon aminocaproic acid (EACA). This is an update of a Cochrane review first published in 2013. Objectives To determine the efficacy and safety of antifibrinolytics (lysine analogues) in preventing bleeding in people with haematological disorders. Search methods We searched for randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (The Cochrane Library 2016, Issue 3), MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1937), the Transfusion Evidence Library (from 1950) and ongoing trial databases to 07 March 2016. Selection criteria We included RCTs involving participants with haematological disorders, who would routinely require prophylactic platelet transfusions to prevent bleeding. We only included trials involving the use of the lysine analogues TXA and EACA. Data collection and analysis Two review authors independently screened all electronically-derived citations and abstracts of papers, identified by the review search strategy, for relevancy. Two review authors independently assessed the full text of all potentially relevant trials for eligibility, completed the data extraction and assessed the studies for risk of bias using The Cochrane Collaboration’s ‘Risk of bias’ tool. We requested missing data from one author but the data were no longer available. The outcomes are reported narratively: we performed no meta-analyses because of the heterogeneity of the available data. Main results We identified three new studies in this update of the review. In total seven studies were eligible for inclusion, three were ongoing RCTs and four were completed studies. The four completed studies were included in the original review and the three ongoing studies were included in this update. We did not identify any RCTs that compared TXA with EACA. Of the four completed studies, one cross-over TXA study (eight participants) was excluded from the outcome analysis because it had very flawed study methodology. Data from the other three studies were all at unclear risk of bias due to lack of reporting of study methodology. Three studies (two TXA (12 to 56 participants), one EACA (18 participants) reported in four articles (published 1983 to 1995) were included in the narrative review. All three studies compared the drug with placebo. All three studies included adults with acute leukaemia receiving chemotherapy. One study (12 participants) only included participants with acute promyelocytic leukaemia. None of the studies included children. One of the three studies reported funding sources and this study was funded by a charity. We are uncertain whether antifibrinolytics reduce the risk of bleeding (three studies; 86 participants; very low-quality evidence). Only one study reported the number of bleeding events per participant and there was no difference in the number of bleeding events seen during induction or consolidation chemotherapy between TXA and placebo (induction; 38 participants; mean difference (MD) 1.70 bleeding events, 95% confidence interval (CI) −0.37 to 3.77: consolidation; 18 participants; MD −1.50 bleeding events, 95% CI −3.25 to 0.25; very low-quality evidence). The two other studies suggested bleeding was reduced in the antifibrinolytic study arm, but this was statistically significant in only one of these two studies. Two studies reported thromboembolism and no events occurred (68 participants, very low-quality evidence). All three studies reported a reduction in platelet transfusion usage (three studies, 86 participants; very low-quality evidence), but this was reported in different ways and no meta-analysis could be performed. No trials reported the number of platelet transfusions per participant. Only one study reported the number of platelet components per participant and there was a reduction in the number of platelet components per participant during consolidation chemotherapy but not during induction chemotherapy (consolidation; 18 participants; MD −5.60 platelet units, 95% CI −9.02 to −2.18: induction; 38 participants, MD −1.00 platelet units, 95% CI −9.11 to 7.11; very low-quality evidence). Only one study reported adverse events of TXA as an outcome measure and none occurred. One study stated side effects of EACA were minimal but no further information was provided (two studies, 74 participants, very low-quality evidence). None of the studies reported on the following pre-specified outcomes: overall mortality, adverse events of transfusion, disseminated intravascular coagulation (DIC) or quality of life (QoL). Authors’ conclusions Our results indicate that the evidence available for the use of antifibrinolytics in haematology patients is very limited. The trials were too small to assess whether or not antifibrinolytics decrease bleeding. No trials reported the number of platelet transfusions per participant. The trials were too small to assess whether or not antifibrinolytics increased the risk of thromboembolic events or other adverse events. There are three ongoing RCTs (1276 participants) due to be completed in 2017 and 2020. PMID:26978005

Poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit can reduce transfusion of platelet products compared to heparin-coated circuit during aortic arch surgery.

PubMed

Hosoyama, Katsuhiro; Ito, Koki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Akiyama, Masatoshi; Adachi, Osamu; Kawatsu, Satoshi; Sasaki, Konosuke; Suzuki, Marina; Sugawara, Yumi; Shimizu, Yuya; Saiki, Yoshikatsu

2016-09-01

Several coating techniques for extracorporeal circulation have been developed to reduce the systemic inflammatory response during cardiopulmonary bypass (CPB). We compared the clinical effectiveness and biocompatibility of poly-2-methoxyethylacrylate (PMEA)- and heparin-coated CPB circuits in total aortic arch replacement (TAR) with the prolonged use of the bypass technique. Twenty patients who underwent elective TAR were divided randomly into two equal groups: group P (n = 10) to use PMEA-coated circuits and group H (n = 10) to use heparin-coated circuits. Clinical outcomes, hematological variables, and acute phase inflammatory response were analyzed perioperatively. Demographic, CPB, and clinical outcome data were similar for both groups. Hemoglobin and platelet count showed similar time-course curves. However, the amount of platelet products transfused intraoperatively was significantly larger in group H (group P 26.0 ± 7.0 units; group H 33.0 ± 6.7 units, p = 0.04). Total protein, and albumin levels were significantly higher in group P during and after the operation (total protein, p = 0.04; albumin, p = 0.02). The use of PMEA-coated circuit is associated with retainment of perioperative plasma proteins levels and may help to reduce transfusion of platelet products in TAR in comparison with the heparin-coated circuit.

Evaluation of Dried Storage of Platelets and RBC for Transfusion: Lyophilization and other Dehydration Techniques.

DTIC Science & Technology

1992-11-02

linking agents. Water replacement molecules, such as trehalose or sucrose at concentrations up to 1 M, did not suffice to stabilize platelets for...concentration of albumin (5% w/v) or trehalose (250 mM - I M) is required in the final suspension prior to freeze-drying to ensure platelet yield and...structurally or functionally intact platelets post- rehydration; the presence of albumin or trehalose raises this yield to 90-100%. Lvophilization and Storage

21 CFR 640.27 - Emergency provisions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Platelets § 640.27 Emergency provisions. The use of... must be transfused with the platelets from a specific donor, and (b) the plateletpheresis procedure is... donor and the physician has certified in writing that the donor's health permits plateletpheresis. [40...

Failure of bacterial screening to detect Staphylococcus aureus: the English experience of donor follow-up.

PubMed

Brailsford, S R; Tossell, J; Morrison, R; McDonald, C P; Pitt, T L

2018-05-24

Between February 2011 and December 2016, over 1·6 million platelet units, 36% pooled platelets, underwent bacterial screening prior to issue. Contamination rates for apheresis and pooled platelets were 0·02% and 0·07%, respectively. Staphylococcus aureus accounted for 21 contaminations, including four pooled platelets, one confirmed transfusion-transmitted infection (TTI) and three 'near-miss' incidents detected on visual inspection which were negative on screening. We describe follow-up investigations of 16 donors for skin carriage of S. aureus and molecular characterisation of donor and pack isolates. Units were screened by the BacT/ALERT 3D detection system. Contributing donors were interviewed and consent requested for skin and nasal swabbing. S. aureus isolates were referred for spa gene type and DNA macrorestriction profile to determine identity between carriage strains and packs. Donors of 10 apheresis and two pooled packs screen positive for S. aureus were confirmed as the source of contamination; seven had a history of skin conditions, predominantly eczema; 11 were nasal carriers. The 'near-miss' incidents were associated with apheresis donors, two donors harboured strains indistinguishable from the pack strain. The TTI was due to a screen-negative pooled unit, and a nasal isolate of one donor was indistinguishable from that in the unit. Staphylococcus aureus contamination is rare but potentially harmful in platelet units. Donor isolates showed almost universal correspondence in molecular type with pack isolates, thus confirming the source of contamination. The importance of visual inspection of packs prior to transfusion is underlined by the 'near-miss' incidents. © 2018 International Society of Blood Transfusion.

Selective Inhibition of ADAM17 Efficiently Mediates Glycoprotein Ibα Retention During Ex Vivo Generation of Human Induced Pluripotent Stem Cell‐Derived Platelets

PubMed Central

Hirata, Shinji; Murata, Takahiko; Suzuki, Daisuke; Nakamura, Sou; Jono‐Ohnishi, Ryoko; Hirose, Hidenori; Sawaguchi, Akira; Nishimura, Satoshi; Sugimoto, Naoshi

2016-01-01

Abstract Donor‐independent platelet concentrates for transfusion can be produced in vitro from induced pluripotent stem cells (iPSCs). However, culture at 37°C induces ectodomain shedding on platelets of glycoprotein Ibα (GPIbα), the von Willebrand factor receptor critical for adhesive function and platelet lifetime in vivo, through temperature‐dependent activation of a disintegrin and metalloproteinase 17 (ADAM17). The shedding can be suppressed by using inhibitors of panmetalloproteinases and possibly of the upstream regulator p38 mitogen‐activated protein kinase (p38 MAPK), but residues of these inhibitors in the final platelet products may be accompanied by harmful risks that prevent clinical application. Here, we optimized the culture conditions for generating human iPSC‐derived GPIbα+ platelets, focusing on culture temperature and additives, by comparing a new and safe selective ADAM17 inhibitor, KP‐457, with previous inhibitors. Because cultivation at 24°C (at which conventional platelet concentrates are stored) markedly diminished the yield of platelets with high expression of platelet receptors, 37°C was requisite for normal platelet production from iPSCs. KP‐457 blocked GPIbα shedding from iPSC platelets at a lower half‐maximal inhibitory concentration than panmetalloproteinase inhibitor GM‐6001, whereas p38 MAPK inhibitors did not. iPSC platelets generated in the presence of KP‐457 exhibited improved GPIbα‐dependent aggregation not inferior to human fresh platelets. A thrombus formation model using immunodeficient mice after platelet transfusion revealed that iPSC platelets generated with KP‐457 exerted better hemostatic function in vivo. Our findings suggest that KP‐457, unlike GM‐6001 or p38 MAPK inhibitors, effectively enhances the production of functional human iPSC‐derived platelets at 37°C, which is an important step toward their clinical application. Stem Cells Translational Medicine 2017;6:720–730 PMID:28297575

Photodynamic decontamination of blood for transfusion

NASA Astrophysics Data System (ADS)

Ben-Hur, Ehud; Margolis-Nunno, H.; Gottlieb, P.; Lustigman, S.; Horowitz, Bernard

1995-01-01

Currently transfused cellular components of blood are not available in a sterile form and carry a small risk of transmitting viral and parasite diseases. Using phthalocyanines and red light, lipid enveloped viruses, e.g., HIV-1, can be inactivated in red blood cell concentrates (RBCC). Under conditions leading to virus sterilization the blood borne parasites Trypanosoma cruzi (Chagas disease) and Plasmodium falciparum (malaria) could be eliminated to undetectable levels (> 4 log10 kill). RBC damage during treatment could be avoided by increasing the light fluence rate to 80 mW/cm2, and by including the free radical scavenger glutathione and the vitamin E derivative Trolox during light exposure. Similar sterilization of platelet concentrates was achieved with the psoralen derivative AMT and UVA light. Platelet damage due to PUVA treatment was avoided by including the plant flavonoid rutin during irradiation. It is concluded that elimination of the risk of transmitting pathogens during blood transfusion is feasible with photochemical treatments.

Refined methods to evaluate the in vivo hemostatic function and viability of transfused human platelets in rabbit models.

PubMed

Watanabe, Naohide; Nogawa, Masayuki; Ishiguro, Mariko; Maruyama, Hitomi; Shiba, Masayuki; Satake, Masahiro; Eto, Koji; Handa, Makoto

2017-08-01

To bridge the gap between in vitro function and clinical efficacy of platelet (PLT) transfusion products, reliable in vivo PLT functional assays for hemostasis and survival in animal models are required. However, there are no standardized methods for assessing the in vivo quality of transfused human PLTs. Plasma-depleted human PLT concentrates (PCs; Day 3, Day 5, Day 7, Day 10, and damaged) were transfused into busulfan-induced rabbits with thrombocytopenia with prolonged bleeding times 1 day after treatment with ethyl palmitate (EP) to block their reticuloendothelial systems. The hemostatic effect of PC transfusion was evaluated by the ear fine vein bleeding time. For the in vivo survival assay, splenectomized EP-treated rabbits were transfused with human PCs, and viability of the human PLTs in the rabbits was determined by flow cytometry using human PLT-specific antibodies and Trucount tubes. The hemostatic effect of PCs was slightly reduced with increasing storage periods for early time points, but more dramatically reduced for later time points. PLT survival was similar after 3 and 7 days of storage, but PLTs stored for 10 days showed significantly poorer survival than those stored only 3 days. Our new and improved protocol for in vivo assessment of transfused PLTs is sufficiently sensitive to detect subtle changes in hemostatic function and viability of human PLTs transfused into rabbit models. This protocol could contribute to preclinical in vivo functional assessment and clinical quality assurance of emerging novel PLT products such as cultured cell-derived human PLTs. © 2017 AABB.

[Single-donor (apheresis) platelets and pooled whole-blood-derived platelets--significance and assessment of both blood products].

PubMed

Hitzler, Walter E

2014-01-01

The transfusion efficacy of ATK, which contain fully functional platelets, is beyond all doubt. The equivalence of ATK and PTK has been subject of many studies. Some of those studies show the superiority of ATK's, while others do not, but there have been no studies that demonstrated a superiority of PTK's. The superiority of platelets stored in plasma and in third generation additive solution was demonstrated in clinical studies; therefore, it cannot be said that all the platelet concentrates on the German market are equivalent in efficacy. Of decisive importance, above all, is the risk of transfusion-transmitted infections with known pathogens, or those not yet discovered. This risk is different for ATK compared to PTK. Taking this difference in risk and the difference in donor exposure of transfused patients into account, it can definitely be said that ATK and PTK are not equivalent. In 2012, the Robert-Koch-Institute (RKI) published a mathematical risk model for different platelet concentrates and assessed the risk of transmitting known pathogens such as HIV, HCV, and HBV. The risk was higher for PTK compared to ATK. The relative risks for PTK derived from 4BCs were 2.2 (95%--CI: 2.1-2.4) for HIV, 2.7 (95%--CI: 2.5-3.0) for HCV, and 2.2 (95%--CI: 2.8-3.7) for HBV. At the present time, these are the relative risks of transfusion-transmitted infections with the traditional pathogens for PTK compared to ATK. In addition to the RKI assessed risks, there is the theoretical risk of a new, unknown agent, transmitted through blood exposure. The magnitude of this risk is hardly predictable for PTK. The experience gathered so far, especially in the last three decades, with the emergence of HIV, prions, and West Nil virus, shows that the biological nature of a next transfusion-transmissible infectious agent cannot be predictable. This agent, if we think at a conventional sexually transmissible agent with nucleic acid and long latent period, would spread first in areas with high population density and thereby reduce the theoretical advantage of ATK (but definitely would not nullify it!). It is equally plausible, however, that this agent would behave like a prion, non-sexual transmission, or like a West-Nil virus, a non-contagious vector-transmitted agent. For PTK this would mean a relative risk up to 4 times (PTK from 4 BCs) or 5 times (PTK from 5 BCs) higher than the risk estimated by the Robert-Koch-Institute. If, taking the passive surveillance data and the changing variables (donor frequency, donor population, and donor location) into account, the risk of transmission of an infection via ATK (exposure to 1 donor) with HIV, HCV, and HBV moves closer to the higher risk of PTK (exposure to 4 or 8 donors, in case of double ATK per patient), this result of the risk model calculation by no means indicates any equivalency between PTK and ATK with respect to the risk of transmission of infection. The modifiable variables of donor frequency, donor population, and donor location need to be modified, as scientific deductions, in such a way that the avoidable risk of ATK which is influenced by these variables can be corrected to the minimum risk of a transmission of infection of HIV, HBV, and HCV via ATK in comparison to PTK. The minimum risk of a possible transmission of infection via ATK (exposure to 1 donor) is the basic intrinsic risk of each individual blood donation. The basic intrinsic risk increases relative to the number of blood donations or exposure to donors (PtK has an unalterable, production-dependent exposure to 4 or 8 donors). Let us consider a 1:1.000 prevalence for a new pathogen, which is spread equally in each donor population (apheresis and whole blood) and the present case of approximately 500,000 transfused platelet concentrates in Germany. This means that for the production of 4 PTK about 2 million donations are processed, 2,000 infectious Buffy-Coats are obtained and, thereby, 2,000 infectious PTK. In the case of ATK, considering five (5) donations per year, theoretically, it would mean 100 donors infected and 500 infectious ATK. Considering 15 apheresis donations per donor per year, this would mean that 33 donors are infected, but still 500 infectious ATK would be produced. The prion is an example of a pathogen that, although its existence is well known, cannot be proven or pathogen-reduced. In addition, it has a very long incubation period compared to the donation intervals. Due to the manufacturing process, PTK has a 4-fold higher donor exposure and therefore a 4-fold higher risk for transfusion-transmitted infections compared to ATK. If a patient needs the transfusion of two platelet concentrates, by transfusing a double-ATK from the same donor the risk of transfusion-transmitted infections will remain the same. On the other hand, the risk will increase by 8-fold by transfusing two PTK. The only current possibility to prevent or to minimize the risk of infection with prions is to minimize the donor exposure by transfusing ATK instead of PTK. Hypothetical risk scenarios carry significant weight in law. This can be seen in the constant rulings of the German Federal Supreme Court (Bundesgerichtshofs (BGH)) on the so-called hypothetical risk explanations (BGH, NJW 1996, 776, 777; 2000, 1784, 1787; 2005, 2614, 2616). Therefore, a risk does not need to be confirmed to be subject to compulsory explanation. It is sufficient that serious voices in the medical scientific community point to specific risks, which cannot be set aside as insignificant outside opinions, but must be viewed as serious warnings. According to the rulings, patients must even be informed of rare and often extremely rare risks, which could, should they come true, significantly impact daily life and, despite their rarity, are specific to the treatment and are startling for the ordinary person (BGH, 15.02.2000- VI ZR 48199 -; BGH, 30.11.2004 - VI ZR 209104 -; OLG Hamm, 29.09.2010 - 1-3 V 169109). These conditions have been fulfilled for PTK according to current knowledge, especially since, in the meantime in several rulings, the federal supreme court has required the reference to as yet unknown risks (refer to BGH, 13.06.2006 - VI ZR 323104 - for the use of new medical treatment methods, BGH, 27.06.2007 - VI ZR 55105 for experimental therapy using new, unapproved medication BGH, 06.07.2010 - VI ZR 198109 - for unknown risks cannot be excluded, for example based on anatomical conditions). ATK and PTK are therapeutic alternatives with the same range of indications for treatment using thrombocytes, however, with differing risks of infection, with different exposures to donors, and with different efficacy. ATK and PTK. ATK and PTK are therapeutic alternatives in terms of pharmaceutical law based on the different risks and the different quality. Patients must be informed of therapeutic alternatives such as ATK and PTK according to the patient rights law. Denial of reimbursement for additional fees for ATK by individual insurance companies (or paying authorities) deviates blatantly, as seen in the ruling of the Social Court of of the Saarland in this matter, from the basic requirement of the Transfusion Law (Transfusionsgesetz (TFG)) and is legally incorrect. The legality of the question whether the transfusion of ATK is indicated or if PTK had sufficed, is not allowable within the context of an MDK-Test according to subsection 275 ff. SGB V. The denial is a direct infringment on the treatment authority of the attending hospital physician and is illegal according to subsection 275 Abs. 5 SGBV. It is certainly possible to establish a full ATK supply and can be immediately realized by increasing donation rates from 5 to 8.3 apheresis donations per year in the current scenario of apheresis structure and donor population. The donation interval between two apheresis donations would be 49 days. A complete supply with ATK can also be immediately implemented by enlarging the donor population, keeping the current apheresis donation frequency. The donor pool must be increased by 24,576 donors, which means a 67% increase of the existing donor population. A transition to an ATK supply that can cover the entire demand can certainly be realized in a short period of time, while assuring a complete supply with PTK is not a realistic option. All existing studies advise taking extreme caution with any alternative to the current German gold standard for the treatment of hyporegenerative thrombocytopenia. A prophylactic transfusion of a non-pathogen-inactivated platelet concentrate with on average 3 x 10(11) platelets is recommended when the platelet count drops below the threshold of 10,000/microL. All other alternatives to this strategy show an increase in intracranial bleeding events. The existing studies on platelet dose (PLADO-Trial and StoP-Trial) do not recommend deviating from 3 x 10(11) platelets per unit. On the contrary, these studies demonstrate that the only practicable way is to individually correlate every platelet transfusion to the patient body surface. Considering the current knowledge, it is not justified to lower the standard dose and, for certain patient groups, to switch from prophylaxis to therapeutic platelet transfusion. Applying ATK or PTK with a lower platelet content and only for therapeutic purposes, could considerably increase the bleeding risk, especially for WHO grades III and IV. This will also affect all the patients who receive an induction treatment. Through pathogen reduction, in parallel with platelet loss (Apoptosis), the function of the treated platelets is impaired. Alternatively, the cell destruction caused during this process could result in a release of platelet microRNA directly into the supernatant or in microvesicles. This reduction of microRNA will affect the storage of the platelets. (ABSTRACT TRUNCATED)

Non-polar lipids accumulate during storage of transfusion products and do not contribute to the onset of transfusion-related acute lung injury.

PubMed

Peters, A L; Vervaart, M A T; van Bruggen, R; de Korte, D; Nieuwland, R; Kulik, W; Vlaar, A P J

2017-01-01

The accumulation of non-polar lipids arachidonic acid, 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE and 15-HETE during storage of transfusion products may play a role in the onset of transfusion-related acute lung injury (TRALI), a syndrome of respiratory distress after transfusion. We investigated non-polar lipid accumulation in red blood cells (RBCs) stored for 42 days, plasma stored for 7 days at either 4 or 20°C and platelet (PLT) transfusion products stored for 7 days. Furthermore, we investigated whether transfusion of RBCs with increased levels of non-polar lipids induces TRALI in a 'two-hit' human volunteer model. All products were produced following Dutch Blood Bank protocols and are according to European standards. Non-polar lipids were measured with high-performance liquid chromotography followed by mass spectrometry. All non-polar lipids increased in RBCs after 21 days of storage compared to baseline. The non-polar lipid concentration in plasma increased significantly, and the increase was even more pronounced in products stored at 20°C. In platelets, baseline levels of 5-HETE and 15-HETE were higher than in RBCs or plasma. However, the non-polar lipids did not change significantly during storage of PLT products. Infusion of RBCs with increased levels of non-polar lipids did not induce TRALI in LPS-primed human volunteers. We conclude that non-polar lipids accumulate in RBC and plasma transfusion products and that accumulation is temperature dependent. Accumulation of non-polar lipids does not appear to explain the onset of TRALI (Dutch Trial Register - NTR4455). © 2016 International Society of Blood Transfusion.

Low hemorrhage-related mortality in trauma patients in a Level I trauma center employing transfusion packages and early thromboelastography-directed hemostatic resuscitation with plasma and platelets.

PubMed

Johansson, Pär I; Sørensen, Anne Marie; Larsen, Claus F; Windeløv, Nis A; Stensballe, Jakob; Perner, Anders; Rasmussen, Lars S; Ostrowski, Sisse R

2013-12-01

Hemorrhage accounts for most preventable trauma deaths, but still the optimal strategy for hemostatic resuscitation remains debated. This was a prospective study of adult trauma patients admitted to a Level I trauma center. Demography, Injury Severity Score (ISS), transfusion therapy, and mortality were registered. Hemostatic resuscitation was based on a massive transfusion protocol encompassing transfusion packages and thromboelastography (TEG)-guided therapy. A total of 182 patients were included (75% males, median age 43 years, ISS of 17, 92% with blunt trauma). Overall 28-day mortality was 12% with causes of death being exsanguinations (14%), traumatic brain injury (72%, two-thirds expiring within 24 hr), and other (14%). One-fourth, 16 and 15% of the patients, received red blood cells (RBCs), plasma, or platelets (PLTs) within 2 hours from admission and 68, 71, and 75%, respectively, of patients transfused within 24 hours received the respective blood products within the first 2 hours. In patients transfused within 24 hours, the median number of blood products at 2 hours was 5 units of RBCs, 5 units of plasma, and 2 units of PLT concentrates. Nonsurvivors had lower clot strength by kaolin-activated TEG and TEG functional fibrinogen and lower kaolin-tissue factor-activated TEG α-angle and lysis after 30 minutes compared to survivors. None of the TEG variables were independent predictors of massive transfusion or mortality. Three-fourths of the patients transfused with plasma or PLTs within 24 hours received these in the first 2 hours. Hemorrhage caused 14% of the deaths. We introduced transfusion packages and early TEG-directed hemostatic resuscitation at our hospital 10 years ago and this may have contributed to reducing hemorrhagic trauma deaths. © 2013 American Association of Blood Banks.

Concise review: stem cell-based approaches to red blood cell production for transfusion.

PubMed

Shah, Siddharth; Huang, Xiaosong; Cheng, Linzhao

2014-03-01

Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.

Fetal and neonatal alloimmune thrombocytopenia: evidence based antenatal and postnatal management strategies.

PubMed

Winkelhorst, Dian; Oepkes, Dick; Lopriore, Enrico

2017-08-01

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare but potentially lethal disease, leading to severe bleeding complications in 1 in 11.000 newborns. It is the leading cause of thrombocytopenia in healthy term-born neonates. Areas covered: This review summarizes the antenatal as well as postnatal treatment, thus creating a complete overview of all possible management strategies for FNAIT. Expert commentary: The optimal antenatal therapy in order to prevent bleeding complications in pregnancies complicated by FNAIT is non-invasive treatment with weekly intravenous immunoglobulin (IVIG). Based on risk stratification, weekly doses of IVIG of 0.5 or 1.0g/kg should be administered started early in the second in high risk cases or at the end of the second trimester in low risk cases. The optimal postnatal treatment depends on the platelet count and the clinical condition of the newborn. Prompt administration of compatible platelet transfusion is the first treatment of choice in case of severe thrombocytopenia or active bleeding. In case matched platelets are not directly available, random platelets can also be administered initially to gain time until matched platelets are available. In case of persistent thrombocytopenia despite transfusions, IVIG 1.0-2.0g/kg can be administered.

Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion.

PubMed

Carless, Paul A; Rubens, Fraser D; Anthony, Danielle M; O'Connell, Dianne; Henry, David A

2011-03-16

Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p < 0.00001; I² = 79%). When the four trials by Boldt are excluded, the RR is 0.76 (95% CI 0.62 to 0.93). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. Trials were generally small and of poor methodological quality. Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity of treatment effects and the trials were of poor methodological quality. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.

Providing ABO-identical platelets and cryoprecipitate to (almost) all patients: approach, logistics, and associated decreases in transfusion reaction and red blood cell alloimmunization incidence.

PubMed

Henrichs, Kelly F; Howk, Nedda; Masel, Debra S; Thayer, Mark; Refaai, Majed A; Kirkley, Scott A; Heal, Joanna M; Blumberg, Neil

2012-03-01

There are multiple benefits to transfusing only ABO-identical blood components. Historically our institution routinely transfused ABO-nonidentical platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we implemented a policy of transfusing only ABO-identical components whenever feasible, regardless of outdating or logistic considerations. Technical staff closely monitored product usage and adjusted blood center orders based on recent utilization and planned transfusions. When unable to provide ABO-identical PLTs, ABO-compatible PLTs were washed to remove incompatible plasma. Data on outdating were collected for 18 months before and after implementation. We compared transfusion reaction and red blood cell (RBC) alloimmunization incidence for 4 years preceding (2001-2004) and subsequent (2006-2009) to implementation. In the year after implementation, only 11 of 410 surgical patients received ABO-nonidentical PLTs (2.7%). There was a 5.6% increase in outdating of PLTs. Transfusing ABO-identical components was associated with significant reductions in febrile (-46%; 8.0 to 4.3 per 10,000 components; p < 0.0001) and allergic transfusion reactions (-23%; from 7.0 to 5.4 per 10,000 components; p = 0.025). A progressive reduction in de novo RBC alloimmunization incidence also occurred (-50% by 2009; p = 0.03). Providing ABO-identical PLTs to almost all patients was feasible in our setting by changing ordering and inventorying procedures and making the ABO-identical policy a staff priority. Unexpected and striking reductions in febrile and allergic reactions and RBC alloimmunization were observed, of uncertain causal relationship to this ABO policy change, which will require further study. © 2011 American Association of Blood Banks.

Safety and efficacy of cryopreserved autologous platelet concentrates in HLA-alloimmunized patients with hematologic malignancies.

PubMed

Gerber, Bernhard; Alberio, Lorenzo; Rochat, Sophie; Stenner, Frank; Manz, Markus G; Buser, Andy; Schanz, Urs; Stussi, Georg

2016-10-01

Curative chemotherapy approaches in patients with malignancies and platelet (PLT) transfusion refractoriness due to alloimmunization may be hampered by the lack of suitable PLT donors. For these patients, transfusion of cryopreserved autologous PLTs is an option, but is time- and resource-consuming. We aimed at further simplifying this process. A retrospective single-center analysis was conducted on the transfusion of cryopreserved autologous PLTs in nine female alloimmunized, PLT transfusion-refractory patients treated for acute leukemia (n = 8) and non-Hodgkin's lymphoma (n = 1). No additional processing was used before transfusion, and most notably, washing and centrifugation steps were omitted. Clinical efficacy and safety, as well as a flow cytometric assessment of structural and functional PLT changes, were analyzed. A total of 40 autologous PLT concentrates were thawed at bedside and transfused a median of 32 (range, 9 to 994) days after cryopreservation. No major bleeds and no severe dimethyl sulfoxide toxicity were observed. The median PLT count increments did not differ 1 and 18 to 24 hours after transfusion and reached 6 × 10 9 /L (interquartile range [IQR], 3 × 10 9 -7.5 × 10 9 /L) and 6 × 10 9 /L (IQR, 2.5 × 10 9 -9.5 × 10 9 /L), respectively. Cryopreservation resulted in partial activation of one-third of the PLTs. In vitro stimulation with strong agonists induced additional full activation of cryopreserved PLTs: median, 55% (IQR, 42%-60%) after thrombin and 39% (IQR, 36%-39%) after convulxin. The transfusion of cryopreserved autologous PLTs is feasible and safe. Despite the cryopreservation process, PLT functionality is partially maintained. © 2016 AABB.

Replaced platelet concentrates containing a new additive solution, M-sol: safety and efficacy for pediatric patients.

PubMed

Yanagisawa, Ryu; Shimodaira, Shigetaka; Kojima, Shunsuke; Nakasone, Nobuhiko; Ishikawa, Shinsuke; Momose, Kayo; Honda, Takayuki; Yoshikawa, Kentaro; Saito, Shoji; Tanaka, Miyuki; Nakazawa, Yozo; Sakashita, Kazuo; Shiohara, Masaaki; Akino, Mitsuaki; Hirayama, Junichi; Azuma, Hiroshi; Koike, Kenichi

2013-09-01

Allergic transfusion reactions (ATRs), particularly those caused by plasma-rich platelet concentrates (P-PCs), are an important concern in transfusion medicine. Replacing P-PCs with PCs containing M-sol (M-sol-R-PCs) is expected to prevent ATRs. However, this has not yet been verified by sufficient clinical evidence. A retrospective cohort study was performed between 2008 and 2011. Pediatric patients with hematologic disorders, solid tumors, primary immunodeficiency disorders, or inherited metabolic disorders were transfused with M-sol-R-PCs between 2010 and 2011; the transfusions of P-PCs administered between 2008 and 2011 were compared in terms of frequency and severity of ATRs, corrected count increment (CCI), and occurrence of bleeding. Data were collected for 6 consecutive months on a per-patient basis. Data obtained during 2008 to 2011 showed that of the 78 patients receiving 515 P-PC transfusions, 14 (17.9%) had 17 ATRs (3.3%); 14 and three ATRs were of Grades 1 and 2, respectively. In 2010 to 2011, 49 patients received 620 transfusions of M-sol-R-PCs, and two patients (4.1%) had Grade 1 ATRs (0.3%). Thus, the frequency of ATRs per bag and per patient differed significantly between the two transfusions. No steroid agents were used for the prevention or treatment of ATRs in the M-sol-R-PC group. The CCI (24 hr) for M-sol-R-PCs did not differ from that for P-PCs. M-sol-R-PCs were found to be effective in preventing ATRs without loss of transfusion efficiency in children; however, its efficacy should be further evaluated in prospective clinical trials. © 2012 American Association of Blood Banks.

Improved platelet survival after cold storage by prevention of glycoprotein Ibα clustering in lipid rafts

PubMed Central

Gitz, Eelo; Koekman, Cornelis A; van den Heuvel, Dave J.; Deckmyn, Hans; Akkerman, Jan W.; Gerritsen, Hans C.; Urbanus, Rolf T.

2012-01-01

Background Storing platelets for transfusion at room temperature increases the risk of microbial infection and decreases platelet functionality, leading to out-date discard rates of up to 20%. Cold storage may be a better alternative, but this treatment leads to rapid platelet clearance after transfusion, initiated by changes in glycoprotein Ibα, the receptor for von Willebrand factor. Design and Methods: We examined the change in glycoprotein Ibα distribution using Förster resonance energy transfer by time-gated fluorescence lifetime imaging microscopy. Results Cold storage induced deglycosylation of glycoprotein Ibα ectodomain, exposing N-acetyl-Dglucosamine residues, which sequestered with GM1 gangliosides in lipid rafts. Raft-associated glycoprotein Ibα formed clusters upon binding of 14-3-3ζ adaptor proteins to its cytoplasmic tail, a process accompanied by mitochondrial injury and phosphatidyl serine exposure. Cold storage left glycoprotein Ibα surface expression unchanged and although glycoprotein V decreased, the fall did not affect glycoprotein Ibα clustering. Prevention of glycoprotein Ibα clustering by blockade of deglycosylation and 14-3-3ζ translocation increased the survival of cold-stored platelets to above the levels of platelets stored at room temperature without compromising hemostatic functions. Conclusions We conclude that glycoprotein Ibα translocates to lipid rafts upon cold-induced deglycosylation and forms clusters by associating with 14-3-3ζ. Interference with these steps provides a means to enable cold storage of platelet concentrates in the near future. PMID:22733027

Glucose ameliorates the metabolic profile and mitochondrial function of platelet concentrates during storage in autologous plasma

PubMed Central

Amorini, Angela M.; Tuttobene, Michele; Tomasello, Flora M.; Biazzo, Filomena; Gullotta, Stefano; De Pinto, Vito; Lazzarino, Giuseppe; Tavazzi, Barbara

2013-01-01

Background It is essential that the quality of platelet metabolism and function remains high during storage in order to ensure the clinical effectiveness of a platelet transfusion. New storage conditions and additives are constantly evaluated in order to achieve this. Using glucose as a substrate is controversial because of its potential connection with increased lactate production and decreased pH, both parameters triggering the platelet lesion during storage. Materials and methods In this study, we analysed the morphological status and metabolic profile of platelets stored for various periods in autologous plasma enriched with increasing glucose concentrations (13.75, 27.5 and 55 mM). After 0, 2, 4, 6 and 8 days, high energy phosphates (ATP, GTP, ADP, AMP), oxypurines (hypoxanthine, xanthine, uric acid), lactate, pH, mitochondrial function, cell lysis and morphology, were evaluated. Results The data showed a significant dose-dependent improvement of the different parameters in platelets stored with increasing glucose, compared to what detected in controls. Interestingly, this phenomenon was more marked at the highest level of glucose tested and in the period of time generally used for platelet transfusion (0–6 days). Conclusion These results indicate that the addition of glucose during platelet storage ameliorates, in a dose-dependent manner, the biochemical parameters related to energy metabolism and mitochondrial function. Since there was no correspondence between glucose addition, lactate increase and pH decrease in our experiments, it is conceivable that platelet derangement during storage is not directly caused by glucose through an increase of anaerobic glycolysis, but rather to a loss of mitochondrial functions caused by reduced substrate availability. PMID:22682337

The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas' disease by reducing the platelet sialic acid contents.

PubMed

Tribulatti, María Virginia; Mucci, Juan; Van Rooijen, Nico; Leguizamón, María Susana; Campetella, Oscar

2005-01-01

Strong thrombocytopenia is observed during acute infection with Trypanosoma cruzi, the parasitic protozoan agent of American trypanosomiasis or Chagas' disease. The parasite sheds trans-sialidase, an enzyme able to mobilize the sialyl residues on cell surfaces, which is distributed in blood and is a virulence factor. Since the sialic acid content on the platelet surface is crucial for determining the half-life of platelets in blood, we examined the possible involvement of the parasite-derived enzyme in thrombocytopenia induction. We found that a single intravenous injection of trans-sialidase into naive mice reduced the platelet count by 50%, a transient effect that lasted as long as the enzyme remained in the blood. CD43(-/-) mice were affected to a similar extent. When green fluorescent protein-expressing platelets were treated in vitro with trans-sialidase, their sialic acid content was reduced together with their life span, as determined after transfusion into naive animals. No apparent deleterious effect on the bone marrow was observed. A central role for Kupffer cells in the clearance of trans-sialidase-altered platelets was revealed after phagocyte depletion by administration of clodronate-containing liposomes and splenectomy. Consistent with this, parasite strains known to exhibit more trans-sialidase activity induced heavier thrombocytopenia. Finally, the passive transfer of a trans-sialidase-neutralizing monoclonal antibody to infected animals prevented the clearance of transfused platelets. Results reported here strongly support the hypothesis that the trans-sialidase is the virulence factor that, after depleting the sialic acid content of platelets, induces the accelerated clearance of the platelets that leads to the thrombocytopenia observed during acute Chagas' disease.

Clinical Decision Support Reduces Overuse of Red Blood Cell Transfusions: Interrupted Time Series Analysis.

PubMed

Kassakian, Steven Z; Yackel, Thomas R; Deloughery, Thomas; Dorr, David A

2016-06-01

Red blood cell transfusion is the most common procedure in hospitalized patients in the US. Growing evidence suggests that a sizeable percentage of these transfusions are inappropriate, putting patients at significant risk and increasing costs to the health care system. We performed a retrospective quasi-experimental study from November 2008 until November 2014 in a 576-bed tertiary care hospital. The intervention consisted of an interruptive clinical decision support alert shown to a provider when a red blood cell transfusion was ordered in a patient whose most recent hematocrit was ≥21%. We used interrupted time series analysis to determine whether our primary outcome of interest, rate of red blood cell transfusion in patients with hematocrit ≥21% per 100 patient (pt) days, was reduced by the implementation of the clinical decision support tool. The rate of platelet transfusions was used as a nonequivalent dependent control variable. A total of 143,000 hospital admissions were included in our analysis. Red blood cell transfusions decreased from 9.4 to 7.8 per 100 pt days after the clinical decision support intervention was implemented. Interrupted time series analysis showed that significant decline of 0.05 (95% confidence interval [CI], 0.03-0.07; P < .001) units of red blood cells transfused per 100 pt days per month was already underway in the preintervention period. This trend accelerated to 0.1 (95% CI, 0.09-0.12; P < .001) units of red blood cells transfused per 100 pt days per month following the implementation of the clinical decision support tool. There was no statistical change in the rate of platelet transfusion resulting from the intervention. The implementation of an evidence-based clinical decision support tool was associated with a significant decline in the overuse of red blood cell transfusion. We believe this intervention could be easily replicated in other hospitals using commercial electronic health records and a similar reduction in overuse of red blood cell transfusions achieved. Copyright © 2016 Elsevier Inc. All rights reserved.

Automated typing of red blood cell and platelet antigens: a whole-genome sequencing study.

PubMed

Lane, William J; Westhoff, Connie M; Gleadall, Nicholas S; Aguad, Maria; Smeland-Wagman, Robin; Vege, Sunitha; Simmons, Daimon P; Mah, Helen H; Lebo, Matthew S; Walter, Klaudia; Soranzo, Nicole; Di Angelantonio, Emanuele; Danesh, John; Roberts, David J; Watkins, Nick A; Ouwehand, Willem H; Butterworth, Adam S; Kaufman, Richard M; Rehm, Heidi L; Silberstein, Leslie E; Green, Robert C

2018-06-01

There are more than 300 known red blood cell (RBC) antigens and 33 platelet antigens that differ between individuals. Sensitisation to antigens is a serious complication that can occur in prenatal medicine and after blood transfusion, particularly for patients who require multiple transfusions. Although pre-transfusion compatibility testing largely relies on serological methods, reagents are not available for many antigens. Methods based on single-nucleotide polymorphism (SNP) arrays have been used, but typing for ABO and Rh-the most important blood groups-cannot be done with SNP typing alone. We aimed to develop a novel method based on whole-genome sequencing to identify RBC and platelet antigens. This whole-genome sequencing study is a subanalysis of data from patients in the whole-genome sequencing arm of the MedSeq Project randomised controlled trial (NCT01736566) with no measured patient outcomes. We created a database of molecular changes in RBC and platelet antigens and developed an automated antigen-typing algorithm based on whole-genome sequencing (bloodTyper). This algorithm was iteratively improved to address cis-trans haplotype ambiguities and homologous gene alignments. Whole-genome sequencing data from 110 MedSeq participants (30 × depth) were used to initially validate bloodTyper through comparison with conventional serology and SNP methods for typing of 38 RBC antigens in 12 blood-group systems and 22 human platelet antigens. bloodTyper was further validated with whole-genome sequencing data from 200 INTERVAL trial participants (15 × depth) with serological comparisons. We iteratively improved bloodTyper by comparing its typing results with conventional serological and SNP typing in three rounds of testing. The initial whole-genome sequencing typing algorithm was 99·5% concordant across the first 20 MedSeq genomes. Addressing discordances led to development of an improved algorithm that was 99·8% concordant for the remaining 90 MedSeq genomes. Additional modifications led to the final algorithm, which was 99·2% concordant across 200 INTERVAL genomes (or 99·9% after adjustment for the lower depth of coverage). By enabling more precise antigen-matching of patients with blood donors, antigen typing based on whole-genome sequencing provides a novel approach to improve transfusion outcomes with the potential to transform the practice of transfusion medicine. National Human Genome Research Institute, Doris Duke Charitable Foundation, National Health Service Blood and Transplant, National Institute for Health Research, and Wellcome Trust. Copyright © 2018 Elsevier Ltd. All rights reserved.

Coagulation monitoring during extracorporeal membrane oxygenation: the role of thrombelastography.

PubMed

Stammers, A H; Willett, L; Fristoe, L; Merrill, J; Stover, T; Hunt, A; Morrow, J; Newberry, J

1995-09-01

Patients undergoing extracorporeal membrane oxygenation (ECMO) are at an increased risk for developing coagulopathies due to the adverse effects of extracorporeal circulation on the hemostatic mechanism. Methods of determining causative factors of bleeding diathesis are often inconsistent and non-specific. ECMO patients require aggressive transfusion therapy with autogenic blood products to stabilize and maintain hemostasis. The present study evaluated the coagulation status of newborn patients undergoing ECMO therapy, using a viscoelastic monitor (Thrombelastograph -TEG) that measures functional aspects of clot development and stabilization. Seventeen neonatal patients undergoing ECMO for severe respiratory dysfunction were entered into this study. Serial blood samples were obtained and routine coagulation assessment including fibrinogen concentration, platelet count and ionized calcium was performed. In addition, fibrin(ogen) degradation products (FDP), d-Dimers, antithrombin III and plasma free hemoglobin were measured. Transfusion indicators were established and total transfusion requirements recorded. TEG profiles were determined with the use of heparinase, an enzyme that degrades heparin but has little effect on other coagulation factors. The most commonly encountered complication was hemorrhaging which was diagnosed by laboratory and clinical assessment in 11 of 17 patients. Transfusion requirements (measured in ml/kg/ECMO hour) were the following: packed red blood cells--1.34 +/- 0.5; platelets--0.71 +/- 0.57; fresh frozen plasma--0.09 +/- 0.12; cryoprecipitate 0.05 +/- 0.05. Thrombelastograph profiles reflected hemostatic conditions that ranged from severe coagulopathies (DIC) to hypercoagulability. Interpretation of TEG profiles identified hemostatic abnormalities in 57 of 101 profiles (46.5%), with the most common etiology related to platelet dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Transfusion Patterns in All Patients Admitted to the Intensive Care Unit and in Those Who Die in Hospital: A Descriptive Analysis.

PubMed

Shehata, Nadine; Forster, Alan J; Lawrence, Nadine; Ducharme, Robin; Fergusson, Dean A; Chassé, Michaël; Rothwell, Deanna M; Hébert, Paul C; Tinmouth, Alan T; Wilson, Kumanan

2015-01-01

While it is known that the use of health care resources increases at the end of life in patients admitted to the Intensive Care Unit (ICU), the allocation of blood products at the end of life has not been described. The objective of this study was to describe overall transfusion patterns in the ICU, and specifically in patients who die in hospital. We conducted a retrospective cohort study of adult patients admitted to the ICU of a university-affiliated hospital, who were discharged or died between November 1, 2006 and June 30, 2012. During the study period, 10,642 patients were admitted at least once to the ICU. Of these patients, 4079 (38.3%) received red blood cells (RBCs), plasma or platelets in the ICU. The ICU mortality rate was 28.1% and in-hospital mortality rate was 32.3%. Among 39,591 blood product units transfused over the course of the study in the ICU (18,144 RBC units, 16,920 plasma units and 4527 platelet units), 46.2% were administered to patients who later died within the same hospitalization (41.2% of RBCs, 50.4% of plasma and 50.8% of platelets). Of all blood product units (RBCs, plasma and platelets) administered in the ICU over the study period, 11% were given within the last 24 hours before death. A large proportion of blood products used in the ICU are administered to patients who ultimately succumb to their illness in hospital, and many of these blood units are given in close proximity to death.

A structured blood conservation programme reduces transfusions and costs in cardiac surgery.

PubMed

Ternström, Lisa; Hyllner, Monica; Backlund, Erika; Schersten, Henrik; Jeppsson, Anders

2014-11-01

Transfusions of blood products can be lifesaving, but they are also associated with considerable risks and adverse effects, including immune response and infections. In cardiac surgery, transfusions have also been associated with increased mortality. We prospectively studied the effects of a structured programme to reduce transfusions and transfusion-associated costs in cardiac surgery. The programme included: (i) education of all staff about the risks and benefits of blood transfusions; (ii) revised guidelines for transfusions; and (iii) a transfusion log where indication for transfusion, status of the patient and prescribing physician were registered. Transfusion prevalence, complications and costs for blood products were registered for all acute and elective cardiac operations during a 12-month period before (n = 1128) and after (n = 1034) the programme was started. The two time periods were compared. In addition, the prevalence of transfusions was registered for 2 more years after the programme was initiated. The first year after the programme was initiated the proportion of patients transfused with red blood cell concentrate decreased by 21.8% (from 58.2 to 45.5%, P <0.001), plasma by 37.4% (from 30.8 to 19.3%, P <0.001) and platelets by 21.0% (from 20.5 to 16.2%, P = 0.010). Reoperations for bleeding (5.8 vs 5.0%), early complication rate and 30-day mortality (2.5 vs 2.6%) were not significantly different before and after the start date. Based on the 2009 institutional prices for red blood cell concentrate (102 €/unit), plasma (35 €/unit) and platelets (290 €/unit), the savings on blood products were €161,623 during the first 12 months after the programme was launched. The proportion of patients transfused with any blood product was 60.9% before the programme was started and 48.3, 54.0 and 50.7% 1-3 years after its start (all P <0.001), respectively. A structured blood conservation programme reduces transfusions and costs for blood products in cardiac surgery, without any signs of compromised medical safety. The effects of introducing such a programme are maintained over at least 3 years. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

[Newborn with phocomelia and thrombocytopenia. Case report].

PubMed

Maas, C; Arand, J; Orlikowsky, Th; Goelz, R

2002-01-01

Associated malformations and symptoms may be decisive in the differential diagnosis of neonatal phocomelia. We report on a neonate with phocomelia, petechiae and thrombocytopenia. This constellation is typical for the phocomelia-thrombocytopenia-syndrome, a variant of the thrombocytopenia-absent radius-(TAR) syndrome. During the neonatal period platelet transfusions were necessary. Relevant bleeding and development delays were not evident until the age of seven months. Cardinal symptoms of the TAR syndrome are bilaterally absent radius and neonatal thrombocytopenia. The patient presented with phocomelia of the upper extremities which occurs in only 5 - 10 % of the patients with TAR syndrome. Further abnormalities include additional bone and joint disorders and haematopoietic problems, such as thrombocytopenia. Bleeding episodes mainly occur in the first year of life, hence platelet transfusions may be necessary during this period. A new experimental approach is the Interleukin-6-mediated stimulation of thrombopoiesis. Usually platelet counts reach normal values in adults. The main problem remains a satisfactory management of various limb defects.

Probable transfusion-transmitted Zika virus in Brazil.

PubMed

Barjas-Castro, Maria L; Angerami, Rodrigo N; Cunha, Mariana S; Suzuki, Akemi; Nogueira, Juliana S; Rocco, Iray M; Maeda, Adriana Y; Vasami, Fernanda G S; Katz, Gizelda; Boin, Ilka F S F; Stucchi, Raquel S B; Resende, Mariângela R; Esposito, Danillo L A; de Souza, Renato P; da Fonseca, Benedito A; Addas-Carvalho, Marcelo

2016-07-01

Zika virus (ZIKV) is an emerging arthropod-borne flavivirus transmitted by Aedes mosquitoes. Recent commentaries regarding ZIKV routes of transmission describe a potential transmission by transfusion. Herein, we report a probable case of transfusion-transmitted ZIKV infection through a platelet transfusion that was detected from postdonation information. A blood donor made a voluntary telephone report to the blood donor facility 3 days after donation and informed the facility of a febrile illness (fever, malaise, and headaches). Due to the ongoing dengue epidemic, the initial clinical investigation included dengue among other possible diagnoses. The serology and molecular laboratory results excluded dengue infection. However, stored samples from the donation were positive for ZIKV on reverse transcription-polymerase chain reaction (RT-PCR) analysis. A retrospective investigation demonstrated that the platelet concentrate, which was part of a pool, had been transfused after a liver transplantation. A physician had evaluated the patient 4 days after surgery. Laboratory investigation showed enzyme-linked immunosorbent assay results that were negative for dengue immunoglobulin M antibodies; however, the results were positive for hemagglutination inhibition antibodies against flavivirus. ZIKV RT-PCR and virus isolation analyses in cell cultures from recipient serum were both positive. The sequencing confirmed ZIKV in the donor and patient samples. Ten partial nucleotide sequences from the ZIKV strain that were detected in the donor were aligned and compared with the ZIKV genome detected in the recipient, revealing a 99.8% homology between the two strains. This is a case of probable transmission of ZIKV through blood transfusion. The patient had been transfused with the blood product from an infected donor, most likely in the incubation period after ZIKV infection but prior to clinical disease onset. This report emphasizes the importance of postdonation information and recipient investigations during outbreaks of potentially blood-borne infections. © 2016 AABB.

Transfusion rate as a quality metric: is blood conservation a learnable skill?

PubMed

Paone, Gaetano; Brewer, Robert; Likosky, Donald S; Theurer, Patricia F; Bell, Gail F; Cogan, Chad M; Prager, Richard L

2013-10-01

Between January 2008 and December 2012, a multicenter quality collaborative initiated a focus on blood conservation as a quality metric, with educational presentations and quarterly reporting of institutional-level perioperative transfusion rates and outcomes. This prospective cohort study was undertaken to determine the effect of that initiative on transfusion rates after isolated coronary artery bypass grafting (CABG). Between January 1, 2008, and December 31, 2012, 30,271 patients underwent isolated CABG in Michigan. Evaluated were annual crude and adjusted trends in overall transfusion rates for red blood cells (RBCs), fresh frozen plasma (FFP), and platelets, and in operative death. Transfusion rates continuously decreased for all blood products. RBC use decreased from 56.4% in 2008 (baseline) to 38.3% in 2012, FFP use decreased from 14.8% to 9.1%, and platelet use decreased from 20.5% to 13.4% (ptrend < 0.001 for all). A significant reduction occurred in deep sternal wound infection, reoperation for bleeding, renal failure, prolonged ventilation, initial ventilator time, and intensive care unit duration. The percentage of patients discharged home significantly increased (ptrend < 0.001). Mortality rates did not differ significantly (ptrend = 0.11). In a multicenter quality collaborative, increased attention to transfusion-related outcomes and blood conservation techniques, coincident with regular reporting and review of perioperative transfusion rates as a quality metric, was associated with a significant decrease in blood product utilization. These reductions were concurrent with significant improvement in most perioperative outcomes. This intervention was also safe, as it was not associated with any increases in mortality. Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Optimization of the management of platelet concentrate stocks in the Basque Country using mathematical simulation.

PubMed

Pérez Vaquero, M Á; Gorria, C; Lezaun, M; López, F J; Monge, J; Eguizabal, C; Vesga, M A

2016-05-01

The management of platelet concentrate (PC) stocks is not simple given their short shelf life and variable demand. In general, managers decide on PC production based on personal experience. The objective of this study was to provide a tool to help decide how many PC units to produce each day in a more rational and objective way. From the historical data on PCs produced, transfused and discarded in the Basque Country in 2012, a mathematical model was built, based on the normality of the time series of the transfusions performed on each day of the week throughout the year. This model was implemented in an easy-to-use Excel spreadsheet and validated using real production data from 2013. Comparing with real 2013 data, in the best scenario, the number of PC units that expired was 87·7% lower, PC production, 14·3% lower and the age of the PCs transfused nearly 1-day younger in the simulation. If we want to ensure a minimum stock at the end of each day, the outdating rate and average age of the transfused PCs progressively increase. The practical application of the designed tool can facilitate decision-making about how many PC units to produce each day, resulting in very significant reductions in PC production and wastage and corresponding cost savings, together with an almost 1 day decrease in the mean age of PCs transfused. © 2016 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.

A comprehensive program to minimize platelet outdating.

PubMed

Fuller, Alice K; Uglik, Kristin M; Braine, Hayden G; King, Karen E

2011-07-01

Platelet (PLT) transfusions are essential for patients who are bleeding or have an increased risk of bleeding due to a decreased number or abnormal function of circulating PLTs. A shelf life of 5 days for PLT products presents an inventory management challenge. In 2006, greater than 10% of apheresis PLTs made in the United States outdated. It is imperative to have a sufficient number of products for patients requiring transfusion, but outdating PLTs is a financial burden and a waste of a resource. We present the approach used in our institution to anticipate inventory needs based on current patient census and usage. Strategies to predict usage and to identify changes in anticipated usage are examined. Annual outdating is reviewed for a 10-year period from 2000 through 2009. From January 1, 2000, through December 2009, there were 128,207 PLT transfusions given to 15,265 patients. The methods used to anticipate usage and adjust inventory resulted in an annual outdate rate of approximately 1% for the 10-year period reviewed. In addition we have not faced situations where inventory was inadequate to meet the needs of the patients requiring transfusions. We have identified three elements of our transfusion service that can minimize outdate: a knowledgeable proactive staff dedicated to PLT management, a comprehensive computer-based transfusion history for each patient, and a strong two-way relationship with the primary product supplier. Through our comprehensive program, based on the principles of providing optimal patient care, we have minimized PLT outdating for more than 10 years. © 2011 American Association of Blood Banks.

Identification of anti-Lea by platelet complement fixation.

PubMed

Ando, B; Ibayashi, H

1986-01-01

Two anti-Lea sera which were able to detect Lea antigen on platelets were identified in a screening for anti-platelet antibodies by means of a platelet complement fixation test. These two antisera hemolyzed erythrocytes without enzyme treatment. The anti-Lea activity could be completely absorbed by red cells, platelets and lymphocytes of Le(a+b-) donors but not by cells from Le(a-b+) or Le(a-b-) donors. The antibody activity against red cells was eliminated by treatment of the antisera with dithiothreitol, thereby suggesting that the activity resided in the IgM class of immunoglobulins. As the anti-Lea was more reactive at 37 degrees C than at room temperature against both red cells and platelets, we suggest that transfusion of platelets of Lea-negative donors should be considered for patients with this type of anti-Lea.

Bacterial screening by flow cytometry offers potential for extension of platelet storage: results of 14 months of active surveillance.

PubMed

Vollmer, T; Engemann, J; Kleesiek, K; Dreier, J

2011-06-01

Bacterial contamination is currently the major infectious hazard of platelet transfusion in developed countries. It has been demonstrated that a significant transfusion risk remains, in particular with older platelet concentrates (PCs). In 2009, the shelf life of PCs was therefore reduced in Germany to 4 days after the day of production according to Vote 38. The aim of the present study was the application and implementation of a recently developed flow cytometry-based rapid screening method (BactiFlow) for bacterial contamination at the end of PC shelf life as a routine in-process control. A total of 472 apheresis-derived PCs were tested using the BactiFlow flow cytometric assay to detect and count bacteria based on esterase activity in viable bacterial cells, while the BacT/Alert automated culture system served as the reference method. The automation potential of the flow cytometric assay was analysed by applying the semi-automated BactiFlow ALS system. An algorithm was developed for use in routine blood bank operations to extend the storage period of PCs. Two of the 472 apheresis PCs tested were positive in culture and identified as Propionibacterium species. One PC was positive for Staphylococcus aureus by both methods. All remaining specimens were tested negative by both methods. Our study demonstrates that routine bacterial testing of PCs was successfully implemented and the established algorithm proved efficient. The BactiFlow flow cytometric assay is the first rapid screening method which is suitable for a routine application combined with a high sensitivity. © 2011 The Authors. Transfusion Medicine © 2011 British Blood Transfusion Society.

Human platelet antigens in Burmese, Karen and north-eastern Thais.

PubMed

Phuangtham, R; Romphruk, A; Puapairoj, C; Leelayuwat, C; Romphruk, A V

2017-02-01

A comparative study of allele frequencies at HPA-1 to -6 and HPA-15 in Burmese and Karen populations as well as at HPA-15 in north-eastern Thais (NET) is presented. Human platelet antigens (HPAs) are clinically important in several immune platelet disorders, including foetal and neonatal alloimmune thrombocytopenia (FNAIT), post-transfusion purpura (PTP) and platelet transfusion refractoriness (PTR). The knowledge of antigen frequencies in a population is essential for the evaluation of patients suffering from immune-mediated platelet disorders. A total of 285 unrelated, healthy Burmese, 242 Karen and 300 NET were recruited to this study. Genotype and allele frequencies of HPA-1 to -6 and HPA-15 were defined using polymerase chain reaction sequence-specific primers (PCR-SSP) RESULTS: No individuals homozygous for HPA-1bb, -2bb, -4bb, -5bb and -6bb were detected. HPA-1a, -2a, -4a, -5a and -6a were present in all samples of Burmese and Karen origin. HPA-1b, -2b, -4b, -5b and -6b were rare in these populations. The frequencies of HPA-3a/-3b were 60·4/39·6% in Burmese and 55·8/44·2% in Karen, respectively. Frequencies of HPA-15a/-15b were 57·2/42·8% in Burmese, 52·5/47·5% in Karen and 49·8/50·2% in NET. The frequencies of HPA genotypes in our study indicates that HPA-1a, -2a, -4a, -5a and -6a are unlikely involved in FNAIT, PTP and PTR in Burmese and Karen populations. However, HPA-1b, -2b, -3a, -3b, -4b, -5b, -6b, -15a and -15b may likely stimulate alloantibodies in these populations. © 2016 British Blood Transfusion Society.

Adverse Effects of Hemorrhagic Shock Resuscitation with Stored Blood are Ameliorated by Inhaled Nitric Oxide in Lambs

PubMed Central

Baron, David M.; Beloiartsev, Arkadi; Nakagawa, Akito; Martyn, Trejeeve; Stowell, Christopher P.; Malhotra, Rajeev; Mayeur, Claire; Bloch, Kenneth D.; Zapol, Warren M.

2013-01-01

Objectives Transfusion of stored red blood cells (RBCs) is associated with increased morbidity and mortality in trauma patients. Plasma hemoglobin scavenges nitric oxide (NO), which can cause vasoconstriction, induce inflammation and activate platelets. We hypothesized that transfusion of RBCs stored for prolonged periods would induce adverse effects (pulmonary vasoconstriction, tissue injury, inflammation, and platelet activation) in lambs subjected to severe hemorrhagic shock, and that concurrent inhalation of NO would prevent these adverse effects. Design Animal study. Setting Research laboratory at the Massachusetts General Hospital, Boston, MA. Subjects Seventeen awake Polypay-breed lambs. Interventions Lambs were subjected to 2 h of hemorrhagic shock by acutely withdrawing 50% of their blood volume. Lambs were resuscitated with autologous RBCs stored for 2 h or less (fresh) or 39±2 (mean±SD) days (stored). Stored RBCs were administered with or without breathing NO (80 ppm) during resuscitation and for 21 h thereafter. Measurements and Main Results We measured hemodynamic and oxygenation parameters, markers of tissue injury and inflammation, plasma hemoglobin concentrations, and platelet activation. Peak pulmonary arterial pressure was higher after resuscitation with stored than with fresh RBCs (24±4 vs. 14±2 mmHg, p<0.001) and correlated with peak plasma hemoglobin concentrations (R2=0.56, p=0.003). At 21 h after resuscitation, pulmonary myeloperoxidase activity was higher in lambs resuscitated with stored than with fresh RBCs (11±2 vs. 4±1 U/g, p=0.007). Furthermore, transfusion of stored RBCs increased plasma markers of tissue injury and sensitized platelets to adenosine diphosphate activation. Breathing NO prevented the pulmonary hypertension, and attenuated the pulmonary myeloperoxidase activity, as well as tissue injury and sensitization of platelets to adenosine diphosphate. Conclusions Our data suggest that resuscitation of lambs from hemorrhagic shock with autologous stored RBCs induces pulmonary hypertension and inflammation, which can be ameliorated by breathing NO. PMID:23887236

[To inadequate indication of blood transfusion in a reference hospital in Lima, Peru].

PubMed

Flores-Paredes, Wilfredo

2011-12-01

To determine frequency and clinical criteria associated to the inadequate indication of blood products. A cross-sectional study was performed between June and October 2002. Clinical charts and the laboratory tests from patients receiving blood transfusions were examined. A blood transfusion guideline was elaborated based on published consensus, and used to determine whether the indications for blood products transfusion was adequate or inadequate. A total of 311 blood transfusions were evaluated. The global prevalence of inappropriate indication was of 33.8 %. Red blood cells (RBC) were used inappropriately in 25 %, fresh frozen plasma (FFP) in 59 %, platelets in 13 % and cryoprecipitate in 88 %. From surgery related transfusions half of the indications were inadequate. In internal medicine, ICU and emergency related transfusions, approximately one third of the indications were inadequate. The FFP is the worst used blood product. We found a high frequency of inadequate blood transfusion. The identification of the specific clinical criteria used in inadequate indications transfusions will help in designing a better educational strategy towards a more rational use of the blood products.

A Civilian/Military Trauma Institute: National Trauma Coordinating Center

DTIC Science & Technology

2016-12-01

temperature , higher inci- dence of both early (G6 hours) red blood cell transfusion and massive transfusion, higher mechanical ventilation require- ments, and... temperature on maintenance of platelet viabilityVdeleterious effect of refrigerated storage. N Engl J Med. 1969;280(20):1094Y1098. 9. Murphy DL, Colburn...Cohen, MD, University of California, San Francisco. b) Comparative Effectiveness of Clinical Care Processes in Resuscitation and Management of

Development of blood transfusion product pathogen reduction treatments: a review of methods, current applications and demands.

PubMed

Salunkhe, Vishal; van der Meer, Pieter F; de Korte, Dirk; Seghatchian, Jerard; Gutiérrez, Laura

2015-02-01

Transfusion-transmitted infections (TTI) have been greatly reduced in numbers due to the strict donor selection and screening procedures, i.e. the availability of technologies to test donors for endemic infections, and routine vigilance of regulatory authorities in every step of the blood supply chain (collection, processing and storage). However, safety improvement is still a matter of concern because infection zero-risk in transfusion medicine is non-existent. Alternatives are required to assure the safety of the transfusion product and to provide a substitution to systematic blood screening tests, especially in less-developed countries or at the war-field. Furthermore, the increasing mobility of the population due to traveling poses a new challenge in the endemic screening tests routinely used, because non-endemic pathogens might emerge in a specific population. Pathogen reduction treatments sum a plethora of active approaches to eliminate or reduce potential threatening pathogen load from blood transfusion products. Despite the success of pathogen reduction treatments applied to plasma products, there is still a long way to develop and deploy pathogen reduction treatments to cellular transfusion products (such as platelets, RBCs or even to whole blood) and there is divergence on its acceptance worldwide. While the use of pathogen reduction treatments in platelets is performed routinely in a fair number of European blood banks, most of these treatments are not (or just) licensed in the USA or elsewhere in the world. The development of pathogen reduction treatments for RBC and whole blood is still in its infancy and under clinical trials. In this review, we discuss the available and emerging pathogen reduction treatments and their advantages and disadvantages. Furthermore, we highlight the importance of characterizing standard transfusion products with current and emerging approaches (OMICS) and clinical outcome, and integrating this information on a database, thinking on the benefits it might bring in the future toward personalized transfusion therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

Changes in blood transfusion practices in the UK role 3 medical treatment facility in Afghanistan, 2008-2011.

PubMed

Jansen, J O; Morrison, J J; Midwinter, M J; Doughty, H

2014-06-01

To document blood component usage in the UK medical treatment facility, Afghanistan, over a period of 4 years; and to examine the relationship with transfusion capability, injury pattern and survival. Haemostatic resuscitation is now firmly established in military medical practice, despite the challenges of providing such therapy in austere settings. Retrospective study of blood component use in service personnel admitted for trauma. Data were extracted from the UK Joint Theatre Trauma Registry. A total of 2618 patients were identified. Survival increased from 76 to 84% despite no change in injury severity. The proportion of patients receiving blood components increased from 13 to 32% per annum; 417 casualties received massive transfusion (≥10 units of RCC), the proportion increasing from 40 to 62%. Use of all blood components increased significantly in severely injured casualties, to a median (IQR) of 16 (9-25) units of red cell concentrate (P = 0·006), 15 (8-24) of plasma (P = 0·002), 2 (0-5) of platelets (P < 0·001) and 1 (0-3) of cryoprecipitate (P < 0·001). Cryoprecipitate (P = 0·009) and platelet use (P = 0·005) also increased in moderately injured casualties. The number of blood components transfused to individual combat casualties increased during the 4-year period, despite no change in injury severity or injury pattern. Survival also increased. Combat casualties requiring massive transfusion have a significantly higher chance of survival than civilian patients. Survival is the product of the entire system of care. However, we propose that the changes in military transfusion practice and capability have contributed to increased combat trauma survival. © 2013 Crown copyright. Transfusion Medicine © 2013 British Blood Transfusion Society. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.

Immunological complications of blood transfusions.

PubMed

Brand, Anneke

2016-01-01

Most adverse blood transfusion (BT) events are immune-mediated and in the majority of severe reactions antibodies can be identified as causal factors. Alloimmunization not only causes symptomatic reactions, transfused cells can also be (silently) destroyed. Immunization by BT can contribute to hemolytic disease of the newborn as well as to allograft rejection after transplantation. Reversely, pregnancy and transplantation may evoke immunity hampering transfusion therapy. Besides causing mortality and morbidity, alloimmunization has a huge economic impact. Transfusion reactions prolong hospital stay, require diagnostic tests and complex donor selection procedures and create the need for typed donor registries. In the 1970s, Opeltz and colleagues described that pre-transplantation BT impaired rejection of renal transplants. Leukocytes were essential for this immunosuppressive BT effect that raised concern about negative effects on cancer growth and resistance against infections. Studies on the mechanism were however preliminary abandoned when calcineurin inhibitors for prevention of graft rejection became available and since all blood products underwent leukoreduction in most countries as precautionary measure against transmission of variant Creutzfeldt-Jacob disease. Whether current leukoreduced BT are immunosuppressive and for which patients or circumstances this may contribute to worse outcome, is unknown. The last decades of the previous century, leukoreduction of cellular blood products for leukemia patients significantly reduced the incidence of immunological platelet transfusion refractoriness. The first decade of this century the avoidance of plasma- and platelet-products from females, that may contain donor-derived leukocyte antibodies, decreased transfusion related acute lung injury (TRALI) by more than 30%. These were major achievements. Challenge for the near future is to further reduce alloimmunization in particular against red blood cells (RBC) as a cause of severe hemolytic transfusion reactions and problems to find compatible donors. This can be achieved by extended matching. Inventory limitations prevent to match all BT for clinically relevant RBC antigens. A (European-wide) registration of clinical and genetic risk factors associated with alloimmunization could support effective use of matched blood products. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Recent developments in the supportive therapy of acute myelogenous leukemia.

PubMed

Levine, A S; Deisseroth, A B

1978-08-01

The prognosis for patients with AML is improving, but mortality due to bleeding and infection remains significant. HLA compatibility has been the cornerstone of matching for prophylactic platelet transfusion; while HLA matched platelets are often of benefit, we have observed that HLA matching does not reliably predict transfusion responses. The platelet migration inhibition assay is, however, consistently predictive. The matching problem may be circumvented by the use of frozen autologous platelets, which circulate and function hemostatically. In the granulocytopenic patient with de novo fever (frequently due to bacterial sepsis), the immediate empiric use of broad spectrum antibiotics is mandatory. If the marrow begins to recover from chemotherapy shortly after the onset of infection, such that the peripheral granulocyte count will approach normal within 10 days, the likelihood of survival from an episode of septicemia after antibiosis now approaches 80%. If the marrow does not recover shortly, however, the likelihood of survival with antibiosis alone is poor. In this setting, survival is improved if patients are given granulocyte transfusions in addition to antibiotics. Patients who receive chemotherapy in a laminar air-flow room (LAFR) experience fewer severe infections than do patients in a conventional ward. However, most patients who are unresponsive to initial chemotherapy remain so in spite of protection from infection. Thus, the available results do not suggest that the LAFR is likely to improve appreciably the rate or duration of remission. Using malignant lymphoma as a model, we have found that cryopreserved autologous marrow infusions can hasten hematopoietic recovery in man after high-dose chemotherapy, and earlier reconstitution may be of clinical benefit to the patient; techniques are at hand that might permit the application of this concept to AML.

Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis

PubMed Central

Koupenova, Milka; Vitseva, Olga; MacKay, Christopher R.; Beaulieu, Lea M.; Benjamin, Emelia J.; Mick, Eric; Kurt-Jones, Evelyn A.; Ravid, Katya

2014-01-01

Viral infections have been associated with reduced platelet counts, the biological significance of which has remained elusive. Here, we show that infection with encephalomyocarditis virus (EMCV) rapidly reduces platelet count, and this response is attributed to platelet Toll-like receptor 7 (TLR7). Platelet-TLR7 stimulation mediates formation of large platelet-neutrophil aggregates, both in mouse and human blood. Intriguingly, this process results in internalization of platelet CD41-fragments by neutrophils, as assessed biochemically and visualized by microscopy, with no influence on platelet prothrombotic properties. The mechanism includes TLR7-mediated platelet granule release, translocation of P-selectin to the cell surface, and a consequent increase in platelet-neutrophil adhesion. Viral infection of platelet-depleted mice also led to increased mortality. Transfusion of wild-type, TLR7-expressing platelets into TLR7-deficient mice caused a drop in platelet count and increased survival post EMCV infection. Thus, this study identifies a new link between platelets and their response to single-stranded RNA viruses that involves activation of TLR7. Finally, platelet-TLR7 stimulation is independent of thrombosis and has implications to the host immune response and survival. PMID:24755410

Transfusions of blood products and cancer outcomes.

PubMed

Velásquez, J F; Cata, J P

2015-10-01

Approximately half of cancer patients scheduled for major surgery are anemic. Also, a significant number of patients will present to the operating room with low platelet counts and coagulopathic disorders. Unfortunately, administration of red blood cells, platelets concentrates and fresh-frozen plasma is associated with unwanted adverse effects including fever, hemolytic reactions and transfusion-related immunomodulation (TRIM). TRIM is a multifactorial immunologic phenomenon in the recipient mediated by donor leukocytes, microparticles such as ectosomes, and growth factors. As some of these molecules are secreted in a time-dependent manner, blood storage time may play an important in TRIM, although the evidence is limited. Perioperative administration of red blood cells and associated TRIM has also been associated with increased recurrence of certain solid tumors, such as colorectal, lung, and hepatobiliary tumors. In this continuing education article, we review the available evidence on how perioperative blood product transfusions can affect oncological outcomes, such as cancer recurrence. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Impact of Blood Mixing and ABO Compatibility on Platelet-Leukocyte Aggregations and Platelet P-Selectin Expression: An in Vitro Study.

PubMed

Huang, Go-Shine; Hu, Mei-Hua; Lin, Tso-Chou; Tsai, Yi-Ting; Lin, Chih-Yuan; Ke, Hung-Yen; Zheng, Xu-Zhi; Lin, Yi-Chang; Tsai, Chien-Sung

2018-05-01

Effects of blood transfusions on platelet- and leukocyte-related inflammation are unclear. We simulated transfusion using in vitro blood mixing to evaluate platelet-leukocyte aggregations (PLA) and platelet P-selectin expression, and the mechanism of PLA. Donor packed red blood cells (pRBCs) were obtained from a blood bank. Recipient whole blood samples were obtained from patients undergoing cardiac surgery. Blood sample mixtures were divided into four groups: group M, cross-matched blood type mixing; group O, donor type O with other blood type mixing (A, B, or AB); group S, ABO type-specific uncross-matched blood mixing; and group I, ABO incompatibility mixing. Donor pRBCs were added to recipient blood to reach 1%, 5%, and 10% (vol/vol) concentrations. Blood sample mixtures were analyzed to determine the PLA; P-selectin expression; and leukocyte CD11a, CD11b, and CD18 subunits of integrin expression. Analysis of variance tests were used to analyze differences. PLA significantly increased only in groups O and I (P = 0.003 and P < 0.001). Subpopulations of leukocytes significantly increased in all groups. There were no significant differences among the four groups (P = 0.578) in PLA increase. Although there was no significant effect on P-selectin expression (P = 1.000) and leukocyte CD11a and CD18 expression (P = 0.999, P = 0.422) within and between the groups, there was an increase in CD11b expression (P = 0.018). Blood mixing can increase PLA, especially in platelet-neutrophil and platelet-monocyte aggregations, possibly through nonhemolytic reactions. The CD11b integrin with CD18 may play a role in the formation of PLA.

Refrigeration, cryopreservation and pathogen inactivation: an updated perspective on platelet storage conditions.

PubMed

Waters, L; Cameron, M; Padula, M P; Marks, D C; Johnson, L

2018-05-01

Conventional storage of platelet concentrates limits their shelf life to between 5 and 7 days due to the risk of bacterial proliferation and the development of the platelet storage lesion. Cold storage and cryopreservation of platelets may facilitate extension of the shelf life to weeks and years, and may also provide the benefit of being more haemostatically effective than conventionally stored platelets. Further, treatment of platelet concentrates with pathogen inactivation systems reduces bacterial contamination and provides a safeguard against the risk of emerging and re-emerging pathogens. While each of these alternative storage techniques is gaining traction individually, little work has been done to examine the effect of combining treatments in an effort to further improve product safety and minimize wastage. This review aims to discuss the benefits of alternative storage techniques and how they may be combined to alleviate the problems associated with conventional platelet storage. © 2018 International Society of Blood Transfusion.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications

PubMed Central

Koltai, Katalin; Kesmarky, Gabor; Feher, Gergely; Tibold, Antal

2017-01-01

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing. PMID:28820484

Operative delay for orthopedic patients on clopidogrel (plavix): a complete lack of consensus.

PubMed

Lavelle, William F; Demers Lavelle, Elizabeth A; Uhl, Richard

2008-04-01

: Because of its irreversible nature, Plavix (clopidogrel) has become a double edged sword in the care of some of our sickest patients, particularly when surgical intervention is required. Platelets exposed to a single dose of clopidogrel are affected for the remainder of their lifespan and recover normal platelet function at a rate consistent with platelet turnover, which is within 5 days to 7 days (1-3) with the generation of new platelets not influenced by the drug; however, delay of surgical fixation for orthopedic patients, particularly patients with hip fractures may lead to increased morbidity and mortality. : A Web-based survey was created and administered to the program directors of academic orthopedic surgery programs. : Seventy-three percent of orthopedic residency programs responded that waiting 3 days or less for urgent but nonemergent operative interventions on patients on clopidogrel is acceptable with 23% feeling that no delay at all is necessary. For emergent surgery, the vast majority of programs 66 (89%) reported no delay to the operating room for patients on clopidogrel. : The majority of orthopedic surgery residency programs who responded to the survey wait less than 3 days for urgent surgery and do not delay surgery for emergency cases for patients on clopidogrel. At this point we feel that an early intervention that occurs within approximately 2 days, with the acceptance of the possibility of increased blood loss is in the patient's best interest. Based on the reviewed physiology, a perioperative platelet transfusion may be of some benefit as the transfused platelets would be effective in forming a viable plug.

Serious hazards of transfusion (SHOT) initiative: analysis of the first two annual reports.

PubMed

Williamson, L M; Lowe, S; Love, E M; Cohen, H; Soldan, K; McClelland, D B; Skacel, P; Barbara, J A

1999-07-03

To receive and collate reports of death or major complications of transfusion of blood or components. Haematologists were invited confidentially to report deaths and major complications after blood transfusion during October 1996 to September 1998. Hospitals in United Kingdom and Ireland. Patients who died or experienced serious complications, as defined below, associated with transfusion of red cells, platelets, fresh frozen plasma, or cryoprecipitate. Death, "wrong" blood transfused to patient, acute and delayed transfusion reactions, transfusion related acute lung injury, transfusion associated graft versus host disease, post-transfusion purpura, and infection transmitted by transfusion. Circumstances relating to these cases and relative frequency of complications. Over 24 months, 366 cases were reported, of which 191 (52%) were "wrong blood to patient" episodes. Analysis of these revealed multiple errors of identification, often beginning when blood was collected from the blood bank. There were 22 deaths from all causes, including three from ABO incompatibility. There were 12 infections: four bacterial (one fatal), seven viral, and one fatal case of malaria. During the second 12 months, 164/424 hospitals (39%) submitted a "nil to report" return. Transfusion is now extremely safe, but vigilance is needed to ensure correct identification of blood and patient. Staff education should include awareness of ABO incompatibility and bacterial contamination as causes of life threatening reactions to blood.

Successful management of a hydropic fetus with severe anemia and thrombocytopenia caused by anti-CD36 antibody.

PubMed

Xu, Xiuzhang; Li, Lin; Xia, Wenjie; Ding, Haoqiang; Chen, Dawei; Liu, Jing; Deng, Jing; Chen, Yangkai; He, Zhiming; Wang, Jiali; Shao, Yuan; Santoso, Sentot; Ye, Xin; Fang, Qun

2018-02-01

Cases of CD36 deficiency are not rare in Asian populations, foetal and neonatal alloimmune thrombocytopenia (FNAIT) caused by anti-CD36 isoantibodies appears more frequent than other HPA alloantibodies. However, little is known about the treatment of anti-CD36 mediated FNAIT in this region. A Chinese male foetus, whose mother had a history of multiple intrauterine foetal demise and/or hydrops, was diagnosed with severe FNAIT at 27 weeks of gestational age. Immunological analysis revealed total absence of CD36 on platelets and monocytes from mother, caused by a 329-330delAC mutation of the CD36 gene. Anti-CD36 and anti-HLA class I antibodies were detected in the maternal serum, whereas only anti-CD36 isoantibodies were detectable in the foetal blood sample. Serial intrauterine transfusions with red blood cells (RBC) and platelets from a CD36null donor were performed to improve the severe anaemia and thrombocytopenia. The baby (2250 g; Apgar scores 10) was delivered vaginally at 32 weeks of gestation with normal haemoglobin (186 g/L) but low platelet count (48 × 10 9 /L). After 2 days the platelet count rose to 121 × 10 9 /L. This report suggests that intrauterine transfusions with compatible RBC and CD36null platelets are useful in preventing the deleterious clinical effects of anti-CD36-mediated severe FNAIT.

Increased blood product use among coronary artery bypass patients prescribed preoperative aspirin and clopidogrel

PubMed Central

Ray, Joel G; Deniz, Stacy; Olivieri, Anthony; Pollex, Erika; Vermeulen, Marian J; Alexander, Kurian S; Cain, David J; Cybulsky, Irene; Hamielec, Cindy M

2003-01-01

Background The administration of antiplatelet drugs before coronary artery bypass graft surgery (CABG) is associated with an increased risk of major hemorrhage and related surgical reexploration. Little is known about the relative effect of combined clopidogrel and aspirin on blood product use around the time of CABG. We evaluated the associated risk between the combined use of aspirin and clopidogrel and the transfusion of blood products perioperatively. Methods We retrospectively studied a cohort of 659 individuals who underwent a first CABG, without concomitant valvular or aortic surgery, at a single large Canadian cardiac surgical centre between January 2000 and April 2002. The four study exposure groups were those prescribed aspirin (n = 105), clopidogrel (n = 11), the combination of both (n = 46), or neither drug (n = 497), within 7 days prior to CABG. The primary study outcome was the excessive transfusion of blood products during CABG and up to the second post-operative day, defined as ≥ 2 units of packed red blood cells (PRBC), ≥ 2 units of fresh frozen plasma, ≥ 5 units of cryoprecipitate or ≥ 5 units of platelets. Secondary outcomes included the mean number of transfused units of each type of blood product. Results A greater mean number of units of PRBC were transfused among those who received clopidogrel alone (2.9) or in combination with aspirin (2.4), compared to those on aspirin alone (1.9) or neither antiplatelet drug (1.4) (P = 0.001). A similar trend was seen for the respective mean number of transfused units of platelets (3.6, 3.7, 1.3 and 1.0; P < 0.001) and fresh frozen plasma (2.5, 3.1, 2.3, 1.6; P = 0.01). Compared to non-users, the associated risk of excessive blood product transfusion was highest among recipients of aspirin and clopidogrel together (adjusted OR 2.2, 95% CI 1.1–4.3). No significant association was seen among lone users of aspirin (adjusted OR 1.0, 95% CI 0.6–1.6) or clopidogrel (adjusted OR 0.7, 95% CI 0.2–2.5), compared to non-users. Conclusions While combined use of aspirin and clopidogrel shortly before CABG surgery may increase the associated risk of excess transfusion of blood products perioperatively, several study limitations prevent any confident conclusions from being drawn. Beyond challenging these findings, future research might focus on the value of both intraoperative monitoring of platelet function, and the effectiveness of antifibrinolytic agents, at reducing the risk of postoperative bleeding. PMID:12769833

Monitoring and reporting transfusion reactions as a quality indicator - a clinical audit.

PubMed

Hussain, Shabneez; Moiz, Bushra; Ausat, Fatima Azra; Khurshid, Mohammad

2015-02-01

This audit was conducted as a part of a quality assurance activity to assess the frequency of receiving completely filled out blood transfusion reaction forms which were accompanied by the required samples. Once this information is known, we will elevate the bar each year to achieve 100% compliance. The sub-aim was to evaluate the frequency of the reported transfusion reactions. The study was conducted from 1st April 2010 to 30th April 2011. The information was evaluated and the frequency of receiving completely filled blood transfusion reaction forms was assessed. The variables identified were the type of transfusion reaction, the blood component transfused, the health care personnel filling the form, and whether there was legible handwriting and a completely filled form. Transfusion reactions were reported as a percentage of the total number of units transfused. During the study period, 17,880 packed red cells, 13,200 platelets, 13,620 fresh frozen plasma and 2256 cryoprecipitate were transfused and 106 transfusion reactions (0.23%) were reported. Of these, febrile non hemolytic transfusion reaction was the most common (47%), the majority caused by packed red cells. Eighty-four percent of the transfusion reaction forms were completely filled as per our criteria. Febrile non hemolytic transfusion reactions were the most common reactions reported. Copyright © 2014 Elsevier Ltd. All rights reserved.

Continued decline in blood collection and transfusion in the United States–2015

PubMed Central

Ellingson, Katherine D.; Sapiano, Mathew R. P.; Haass, Kathryn A.; Savinkina, Alexandra A.; Baker, Misha L.; Chung, Koo-Whang; Henry, Richard A.; Berger, James J.; Kuehnert, Matthew J.; Basavaraju, Sridhar V.

2017-01-01

BACKGROUND In 2011 and 2013, the National Blood Collection and Utilization Survey (NBCUS) revealed declines in blood collection and transfusion in the United States. The objective of this study was to describe blood services in 2015. STUDY DESIGN AND METHODS The 2015 NBCUS was distributed to all US blood collection centers, all hospitals performing at least 1000 surgeries annually, and a 40% random sample of hospitals performing 100 to 999 surgeries annually. Weighting and imputation were used to generate national estimates for units of blood and components collected, deferred, distributed, transfused, and outdated. RESULTS Response rates for the 2015 NBCUS were 78.4% for blood collection centers and 73.9% for transfusing hospitals. In 2015, 12,591,000 units of red blood cells (RBCs) (95% confidence interval [CI], 11,985,000–13,197,000 units of RBCs) were collected, and 11,349,000 (95% CI, 10,592,000–11,747,000) were transfused, representing declines since 2013 of 11.6% and 13.9%, respectively. Total platelet units distributed (2,436,000; 95% CI, 2,230,000–2,642,000) and transfused (1,983,000; 95% CI, 1,816,000=2,151,000) declined by 0.5% and 13.1%, respectively, since 2013. Plasma distributions (3,714,000; 95% CI, 3,306,000–4,121,000) and transfusions (2,727,000; 95% CI, 2,594,000–2,859,000) in 2015 declined since 2013. The median price paid per unit in 2015—$211 for leukocyte-reduced RBCs, $524 for apheresis platelets, and $54 for fresh frozen plasma—was less for all components than in 2013. CONCLUSIONS The 2015 NBCUS findings suggest that continued declines in demand for blood products resulted in fewer units collected and distributed Maintaining a blood inventory sufficient to meet routine and emergent demands will require further monitoring and understanding of these trends. PMID:28591469

Analyses of Blood Bank Efficiency, Cost-Effectiveness and Quality

NASA Astrophysics Data System (ADS)

Lam, Hwai-Tai Chen

In view of the increasing costs of hospital care, it is essential to investigate methods to improve the labor efficiency and the cost-effectiveness of the hospital technical core in order to control costs while maintaining the quality of care. This study was conducted to develop indices to measure efficiency, cost-effectiveness, and the quality of blood banks; to identify factors associated with efficiency, cost-effectiveness, and quality; and to generate strategies to improve blood bank labor efficiency and cost-effectiveness. Indices developed in this study for labor efficiency and cost-effectiveness were not affected by patient case mix and illness severity. Factors that were associated with labor efficiency were identified as managerial styles, and organizational designs that balance workload and labor resources. Medical directors' managerial involvement was not associated with labor efficiency, but their continuing education and specialty in blood bank were found to reduce the performance of unnecessary tests. Surprisingly, performing unnecessary tests had no association with labor efficiency. This suggested the existence of labor slack in blood banks. Cost -effectiveness was associated with workers' benefits, wages, and the production of high-end transfusion products by hospital-based donor rooms. Quality indices used in this study included autologous transfusion rates, platelet transfusion rates, and the check points available in an error-control system. Because the autologous transfusion rate was related to patient case mix, severity of illness, and possible inappropriate transfusion, it was not recommended to be used for quality index. Platelet-pheresis transfusion rates were associated with the transfusion preferences of the blood bank medical directors. The total number of check points in an error -control system was negatively associated with government ownership and workers' experience. Recommendations for improving labor efficiency and cost-effectiveness were focused on an incentive system that encourages team effort, and the use of appropriate measurements for laboratory efficiency and operational system designs.

A comprehensive proteomics study on platelet concentrates: Platelet proteome, storage time and Mirasol pathogen reduction technology.

PubMed

Salunkhe, Vishal; De Cuyper, Iris M; Papadopoulos, Petros; van der Meer, Pieter F; Daal, Brunette B; Villa-Fajardo, María; de Korte, Dirk; van den Berg, Timo K; Gutiérrez, Laura

2018-03-19

Platelet concentrates (PCs) represent a blood transfusion product with a major concern for safety as their storage temperature (20-24°C) allows bacterial growth, and their maximum storage time period (less than a week) precludes complete microbiological testing. Pathogen inactivation technologies (PITs) provide an additional layer of safety to the blood transfusion products from known and unknown pathogens such as bacteria, viruses, and parasites. In this context, PITs, such as Mirasol Pathogen Reduction Technology (PRT), have been developed and are implemented in many countries. However, several studies have shown in vitro that Mirasol PRT induces a certain level of platelet shape change, hyperactivation, basal degranulation, and increased oxidative damage during storage. It has been suggested that Mirasol PRT might accelerate what has been described as the platelet storage lesion (PSL), but supportive molecular signatures have not been obtained. We aimed at dissecting the influence of both variables, that is, Mirasol PRT and storage time, at the proteome level. We present comprehensive proteomics data analysis of Control PCs and PCs treated with Mirasol PRT at storage days 1, 2, 6, and 8. Our workflow was set to perform proteomics analysis using a gel-free and label-free quantification (LFQ) approach. Semi-quantification was based on LFQ signal intensities of identified proteins using MaxQuant/Perseus software platform. Data are available via ProteomeXchange with identifier PXD008119. We identified marginal differences between Mirasol PRT and Control PCs during storage. However, those significant changes at the proteome level were specifically related to the functional aspects previously described to affect platelets upon Mirasol PRT. In addition, the effect of Mirasol PRT on the platelet proteome appeared not to be exclusively due to an accelerated or enhanced PSL. In summary, semi-quantitative proteomics allows to discern between proteome changes due to Mirasol PRT or PSL, and proves to be a methodology suitable to phenotype platelets in an unbiased manner, in various physiological contexts.

MHC class I–specific antibody binding to nonhematopoietic cells drives complement activation to induce transfusion-related acute lung injury in mice

PubMed Central

Strait, Richard T.; Hicks, Wyenona; Barasa, Nathaniel; Mahler, Ashley; Khodoun, Marat; Köhl, Jörg; Stringer, Keith; Witte, David; Van Rooijen, Nico; Susskind, Brian M.

2011-01-01

Transfusion-related acute lung injury (TRALI), a form of noncardiogenic pulmonary edema that develops during or within 6 h after a blood transfusion, is the most frequent cause of transfusion-associated death in the United States. Because development of TRALI is associated with donor antibodies (Abs) reactive with recipient major histocompatibility complex (MHC), a mouse model has been studied in which TRALI-like disease is caused by injecting mice with anti–MHC class I monoclonal Ab (mAb). Previous publications with this model have concluded that disease is caused by FcR-dependent activation of neutrophils and platelets, with production of reactive oxygen species that damage pulmonary vascular endothelium. In this study, we confirm the role of reactive oxygen species in the pathogenesis of this mouse model of TRALI and show ultrastructural evidence of pulmonary vascular injury within 5 min of anti–MHC class I mAb injection. However, we demonstrate that disease induction in this model involves macrophages rather than neutrophils or platelets, activation of complement and production of C5a rather than activation of FcγRI, FcγRIII, or FcγRIV, and binding of anti–MHC class I mAb to non-BM–derived cells such as pulmonary vascular endothelium. These observations have important implications for the prevention and treatment of TRALI. PMID:22025304

Blood and bombs: the demand and use of blood following the London Bombings of 7 July 2005--a retrospective review.

PubMed

Glasgow, S M; Allard, S; Doughty, H; Spreadborough, P; Watkins, E

2012-08-01

Mass casualty events (MCE) present health systems with a sudden demand on key services. The overall objective of this study was to describe the experience of the National Blood Service (NBS) following the largest UK MCE in recent times. Data was collated from the NBS database and directly from the hospitals involved. All data was collected immediately following the event and included: all blood components requested, issued and transfused in relation to the bombings, blood stock levels at the time and the injury profiles of the casualties transfused. The total NBS order from hospitals for the event was 1455 units of blood components. All requests were fulfilled, this included: 978 units of red cells (RC), 36 doses of platelets, 141 units of fresh frozen plasma (FFP) and 300 doses of cryoprecipitate. The amount of blood ordered was three times that initially used and the total number of RC transfused in treating all victims from admission to discharge was approximately 440 units. The greatest use of blood components was for those casualties who had sustained traumatic amputations amongst their injury profile. Published data with which to compare these results is lacking, although the RC use was similar to the initial mean individual usage described in previous military and civilian bombings. The overall implication for any blood service remains, there is now likely to be a far greater demand for plasma, platelets and cryoprecipitate in any future incidents involving victims suffering major haemorrhage. © 2012 The Authors. Transfusion Medicine © 2012 British Blood Transfusion Society.

Apheresis technology correlates with bacterial contamination of platelets and reported septic transfusion reactions.

PubMed

Eder, Anne F; Dy, Beth A; DeMerse, Barbara; Wagner, Stephen J; Stramer, Susan L; O'Neill, E Mary; Herron, Ross M

2017-12-01

Apheresis technology to collect platelet (PLT) components differs among devices. We evaluated the relationship of the plateletpheresis device with bacterial contamination and reported septic transfusion reactions. Plateletpheresis was performed using Amicus (Fenwal, a Fresenius Kabi Company) or Trima (Trima Accel, TerumoBCT) from 2010 to 2014. All donations used inlet-line sample diversion and were tested by quality control (QC; Day 1) aerobic culture. Rates of bacterial contamination and septic reactions to PLTs were calculated for both devices. During the 5-year study period, plateletpheresis collections using Amicus and Trima devices totaled 1,486,888 and 671,955 donations, respectively. The rate of confirmed-positive bacterial cultures of apheresis PLT donations was significantly higher with Amicus than with Trima (252 vs. 112 per 10 6 donations [odds ratio {OR}, 2.3; 95% confidence interval {CI}, 1.8-2.9]). Septic transfusion reactions were caused by 30 apheresis PLT units from 25 contaminated Amicus procedures and three apheresis PLT units from three contaminated Trima procedures. The overall rate of septic reactions was significantly higher with apheresis PLT components collected with Amicus than with Trima (16.8 vs. 4.5 per 10 6 donations [OR, 3.8; 95% CI, 1.1-12.5]). All apheresis PLT components implicated in septic transfusion reactions had negative QC culture results incubated through Day 5 (i.e., false negatives). Apheresis technology affects bacterial contamination of plateletpheresis collections. The device-specific, higher rate of confirmed-positive bacterial culture results also correlated with a significantly higher rate of reported septic transfusion reactions to apheresis PLTs. © 2017 AABB.

The role of microRNAs in platelet biology during storage.

PubMed

Yan, Yuzhong; Zhang, Jingjun; Zhang, Qi; Chen, Yanping; Zhu, Xinfang; Xia, Rong

2017-04-01

Platelet storage lesions seriously affect the quality of stored platelets, even causing them to be ineffective in vivo after transfusion. Past research have been focused on what mechanism(s) cause the formation of storage lesions. One proposed mechanism is microRNAs (miRNAs)-based molecular regulation of the platelet mRNAs that are relevant to the storage lesion. Platelets continue to translate proteins from mRNA while in a storage environment. A strong correlation exists between the platelet transcriptome and its subsequent proteomic profile, which supports de novo platelet translational capabilities. Thus, miRNA may play a crucial role in platelet biology during storage conditions. Importantly, this suggests the exciting possibility of post-transcriptional regulation of gene expression in platelets that are in storage. Given this, the differential profiling of miRNAs could be a useful tool in identifying changes to ex vivo stored platelets. Any identified miRNAs could then be considered as potential markers to assess the viability of platelet concentrates. The present review summarizes the current experimental and clinical evidence that clarifies the role miRNAs play during platelet ex vivo storage. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of Acute Transfusion Reactions and Their Occurrence Times

PubMed Central

Hatayama, Yuki; Matsumoto, Satoko; Hamada, Eiko; Kojima, Nao; Hara, Ayako; Hino, Norihiko; Motokura, Toru

2018-01-01

Acute transfusion reactions (ATRs) are significantly relevant to the morbidity and mortality of patients. ATRs are mostly not severe and rarely cause severe conditions, including anaphylactic shock. The aim of this study was to clarify the frequency of ATRs and the time of event occurrence. A total of 18,745 transfusions were administered to 11,718 patients during a 3-year period. Adverse reactions including at least one sign or symptom were collected through a report system in 143 of 2,478 (5.7%) platelet concentrate transfusions, 105 of 6,629 (1.6%) red blood cell component transfusions and 51 of 2,307 (2.2%) fresh frozen plasma transfusions. Allergic signs and symptoms accounted for 70% of all adverse events. Severe signs and symptoms were observed in 7.1% of patients. These events appeared significantly earlier than those of non-severe signs and symptoms (median time 20 min vs 100 min, P < 0.05). For patients who have had repetitive transfusion-associated adverse events, preventive treatments for adverse events should be proactively promoted. PMID:29599628

Pathogen reduction of blood components.

PubMed

Solheim, Bjarte G

2008-08-01

Thanks to many blood safety interventions introduced in developed countries the risk of transfusion transmitted infections has become exceedingly small in these countries. However, emerging pathogens still represent a serious challenge, as demonstrated by West Nile virus in the US and more recently by Chikungunya virus in the Indian Ocean. In addition bacterial contamination, particularly in platelets, and protozoa transmitted by blood components still represent sizeable risks in developed countries. In developing countries the risk of all transfusion transmitted infections is still high due to insufficient funding and organisation of the health service. Pathogen reduction of pooled plasma products has virtually eliminated the risk of transfusion transmitted infections, without compromising the quality of the products significantly. Pathogen reduction of blood components has been much more challenging. Solvent detergent treatment which has been so successfully applied for plasma products dissolves cell membranes, and can, therefore, only be applied for plasma and not for cellular blood components. Targeting of nucleic acids has been another method for pathogen inactivation of plasma and the only approach possible for cellular blood products. As documented in more than 15 year's track record, solvent detergent treatment of pooled plasma can yield high quality plasma. The increased risk for contamination by unknown viruses due to pooling is out weighed by elimination of TRALI, significant reduction in allergic reactions and standardisation of the product. Recently, a promising method for solvent detergent treatment of single donor plasma units has been published. Methylene blue light treatment of single donor plasma units has a similar long track record as pooled solvent detergent treated plasma; but the method is less well documented and affects coagulation factor activity more. Psoralen light treated plasma has only recently been introduced (CE marked in Europe, but not licensed by the FDA), while the method of Riboflavin light treatment of plasma still is under development. In addition to pathogen reduction the methods, however, result in some reduction of coagulation factor activity. For platelets only Psoralen and Riboflavin light treatment have been implemented. Both are CE marked products in Europe but only approved for clinical trials in the USA. The methods affect platelet activity, but result in clinically acceptable platelets with only slightly reduced CCI and increased demand for platelet transfusions. Pathogen reduction of red blood cells with FRALE (S-303) or INACTINE (PEN110) has so far resulted in the formation of antibodies against neo-epitopes on red blood cells. A promising method for Riboflavin treatment of red blood cells is under development. This manuscript reviews the current experience and discusses future trends.

[Trauma-induced coagulopathy--mechanisms and state of the art treatment].

PubMed

Misgav, Mudi; Martinowitz, Uri

2011-02-01

Uncontrolled bleeding is a major cause for early death in both military and civilian trauma. The process of massive bleeding which begins as "surgical bleed" from injured vessels may rapidly evolve into a complex coagulopathy that can be detected early, sometimes within minutes of injury. The magnitude of coagulopathy is directly related to the severity of the injury and its presence is also an independent predictor of early mortality. Therefore, an early "hemostatic resuscitation" is now the "state of the art" in trauma management. Combined mechanisms contribute to the complex coagulopathy as described herein: excessive consumption of coagulation factors and platelets, dilutional coagulopathy due to administration of large volumes of fluids, especially high molecular solutions such as Hydroxyethyl starch (HES); the use of multiple red blood cells (RBC) transfusion without sufficient fresh frozen plasma (FFP) and platelets; acidosis that markedly attenuates thrombin generation and platelets function; hypothermia that slows down enzymatic reactions and platelets function and hyperfibrinolysis which accelerates the degradation of fibrin and might cause platelet dysfunction. An important breakthrough was the understanding that abnormal coagulation tests early in the process of trauma are not the consequences of disseminated intravascular coagulation (DIC). Supported by these new data, an aggressive approach to hemostatic resuscitation was developed which is based on the following principles: permissive hypotension to avoid "dilutional" coagulopathy, awareness of the prevention of hypothermia and acidosis and the use of hemostatic agents such as rFVIIa, fibrinogen concentrate and tranexamic acid early in the course of trauma. Importantly, the common practice of blood component therapy was revised and it is recommended that RBC, FFP and platelets will be transfused early and preferably in 1:1:1 ratio.

Reduction of Zika virus infectivity in platelet concentrates after treatment with ultraviolet C light and in plasma after treatment with methylene blue and visible light.

PubMed

Fryk, Jesse J; Marks, Denese C; Hobson-Peters, Jody; Watterson, Daniel; Hall, Roy A; Young, Paul R; Reichenberg, Stefan; Tolksdorf, Frank; Sumian, Chryslain; Gravemann, Ute; Seltsam, Axel; Faddy, Helen M

2017-11-01

Zika virus (ZIKV) has emerged as a potential threat to transfusion safety worldwide. Pathogen inactivation is one approach to manage this risk. In this study, the efficacy of the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system to inactivate ZIKV in platelet concentrates (PCs) and plasma was investigated. PCs spiked with ZIKV were treated with the THERAFLEX UV-Platelets system at 0.05, 0.10, 0.15, and 0.20 J/cm 2 UVC. Plasma spiked with ZIKV was treated with the THERAFLEX MB-Plasma system at 20, 40, 60, and 120 J/cm 2 light at 630 nm with at least 0.8 µmol/L methylene blue (MB). Samples were taken before the first and after each illumination dose and tested for residual virus. For each system the level of viral reduction was determined. Treatment of PCs with THERAFLEX UV-Platelets system resulted in a mean of 5 log reduction in ZIKV infectivity at the standard UVC dose (0.20 J/cm 2 ), with dose dependency observed with increasing UVC dose. For plasma treated with MB and visible light, ZIKV infectivity was reduced by a mean of at least 5.68 log, with residual viral infectivity reaching the detection limit of the assay at 40 J/cm 2 (one-third the standard dose). Our study demonstrates that the THERAFLEX UV-Platelets system and THERAFLEX MB-Plasma system can reduce ZIKV infectivity in PCs and pooled plasma to the detection limit of the assays used. These findings suggest both systems have the capacity to be an effective option to manage potential ZIKV transfusion transmission risk. © 2017 AABB.

The influence of four different anticoagulants on dynamic light scattering of platelets.

PubMed

Raczat, T; Kraemer, L; Gall, C; Weiss, D R; Eckstein, R; Ringwald, J

2014-08-01

For testing of dynamic light scattering of platelets with ThromboLUX (TLX) in platelet-rich plasma (PRP) derived from venous whole blood (vWB), anticoagulation is needed. We compared TLX score in PRPs containing citrate, ethylene-diamine-tetraacetic-acid (EDTA), citrate-phosphate-dextrose-adenine (CPDA) or citrate-theophylline-adenosine-dipyridamole. Initial and late TLX scores were measured after 30-120 min or four to six hours, respectively. Compared with citrate, mean differences in initial TLX score were only significant for CPDA. Also, mean differences between initial and late TLX scores were only significant for CPDA. TLX failed to detect EDTA-induced platelet alterations. The clinical relevance of TLX needs further studies. © 2014 International Society of Blood Transfusion.

Blood transfusions in children: a multi-institutional analysis of practices and complications.

PubMed

Slonim, Anthony D; Joseph, Jill G; Turenne, Wendy M; Sharangpani, Aditi; Luban, Naomi L C

2008-01-01

Blood product transfusions are a valuable health-care resource. Guidelines for transfusion exist, but variability in their application, particularly in children, remains. The risk factors that threaten transfusion safety are well established, but because their occurrence in children is rare, single-institution studies have limited utility in determining the rates of occurrence. An epidemiologic approach that investigates blood transfusions in hospitalized children may help improve our understanding of transfused blood products in this vulnerable population. This was a nonconcurrent cohort study of pediatric patients not more than 18 years of age hospitalized from 2001 to 2003 at 35 academic children's hospitals that are members of the Pediatric Health Information System (PHIS). A total of 51,720 (4.8%) pediatric patients received blood product transfusions during the study period. Red blood cells (n = 44,632) and platelets (n = 14,274) were the two most frequently transfused products. The rate of transfusions was highest among children with neutropenia, agranulocytosis, and sickle cell crisis. Asian and American Indian patients had important differences in the rate of blood transfusions and their complications. Resource use in terms of length of stay and costs were higher in patients who received transfusion. Of those patients who received transfusions, 492 (0.95%) experienced a complication from the administered blood product. This accounted for a rate of complications of 10.7 per 1,000 units transfused. The administration of blood products to children is a common practice in academic children's hospitals. Complications associated with these transfused products are rare.

Canine and feline blood transfusions: controversies and recent advances in administration practices.

PubMed

Kisielewicz, Caroline; Self, Ian A

2014-05-01

To discuss and review blood transfusion practices in dogs and cats including collection and storage of blood and administration of products. To report new developments, controversial practices, less conventional blood product administration techniques and where applicable, describe the relevance to anaesthetists and anaesthesia. PubMed and Google Scholar using dog, cat, blood transfusion, packed red blood cells and whole blood as keywords. Blood transfusions improve oxygen carrying capacity and the clinical signs of anaemia. However there are numerous potential risks and complications possible with transfusions, which may outweigh their benefits. Storage of blood products has improved considerably over time but whilst extended storage times may improve their availability, a phenomenon known as the storage lesion has been identified which affects erythrocyte viability and survival. Leukoreduction involves removing leukocytes and platelets thereby preventing their release of cytokines and bioactive compounds which also contribute to storage lesions and certain transfusion reactions. Newer transfusion techniques are being explored such as cell salvage in surgical patients and subsequent autologous transfusion. Xenotransfusions, using blood and blood products between different species, provide an alternative to conventional blood products. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Platelet Disorders: MedlinePlus Health Topic

MedlinePlus

... von Willebrand Factor Test (American Association for Clinical Chemistry) What Are Bone Marrow Tests? (National Heart, Lung, and Blood Institute) Treatments and Therapies Splenectomy (Mayo Foundation for Medical Education and Research) Also in Spanish What Is a Blood Transfusion? ( ...

The use of antifibrinolytics in pediatric patients with hypoproliferative thrombocytopenia.

PubMed

Delaney, Meghan; Matthews, Dana C; Gernsheimer, Terry B

2017-12-01

Despite the use of evidence-based platelet transfusion therapy during periods of hypoproliferative thrombocytopenia, a large proportion of pediatric hematology/oncology patients continue to suffer from clinically significant bleeding. Antifibrinolytic (AF) drugs have been shown in certain surgical and trauma settings to decrease bleeding, blood transfusion, and improve survival. We conducted a retrospective assessment of the safety of using AF drugs in pediatric patients with hypoproliferative thrombocytopenia at our center as well as the impact on bleeding occurrence and severity. © 2017 Wiley Periodicals, Inc.

The Red Blood Cell Transfusion Trigger: Has the Sin of Commission Now Become a Sin of Omission?.

DTIC Science & Technology

1997-05-01

disease. N . Engl. J. Med. 1995;333:251-253. 85. Ignarro LJ, Buga GM, Wood KS, et al. Endothelium -derived relaxing factor produced and released from...George D, Loscalzo J. Inhibition of fibrinogen binding to human platelets by S-nitroso- N - acetylcysteine . J. Biol. Chem. 1990;265:19028-19034. 28 92...attributable primarily to shear stress-induced nitric oxide release from the endothelium , it would seem logical that transfusing red blood cells to the 30

Dose Response of Sodium Nitrite on Vasoactivity Associated with HBOC-201 in a Swine Model of Controlled Hemorrhage

DTIC Science & Technology

2011-01-01

collected in blood bags containing stan- dard anticoagulant (CPD-A) (Fenwal, Deerfield, IL) and later used for autologous transfusion, when...as 8.1 J.lmollkg first injection, 16.2 J.lmoVkg second injection, 24.3 J.lmol/kg third injection. HEX is 6% hydroxy-ethyl starch (MW = 670 Kd...effect of starch on platelets. Aggregation increased in the HEX groups in hospital phase due to blood transfusion. NaN02 did not have any remarkable

Human platelet antigen genotypes in Turkish and Caucasian blood donors in Germany.

PubMed

Hauck-Dlimi, B; Hammon, K; Eckstein, R; Ott, S; Zimmermann, R; Dengler, T; Ringwald, J

2012-09-01

Exposition to allogenic human platelet antigens (HPAs) can lead to antibody formation causing neonatal alloimmune thrombocytopenia (NAIT), post-transfusion purpura or platelet (PLT) transfusion refractoriness. The frequencies of HPA differ between ethnical groups which could be associated with different potential alloimmunization risk. The Turkish population is the largest ethnic minority group living in Germany. However, no data are available about the HPA frequency among Turkish population. We compared the frequency of HPA between Caucasian and Turkish blood donors. DNA from blood samples of 119 Caucasian and 117 Turkish blood donors was isolated. The genotype of HPA-1, -2, -3 -4, -5 and -15 was determined using a commercialized polymerase chain reaction kit with sequence-specific primers. In Turkish blood donors, the gene frequencies of HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b were 0.863/0.137, 0.868/0.133, 0.607/0.393, 0.996/0.004, 0.893/0.107 and 0.474/0.256, respectively. In Caucasians, we observed 0.798/0.202, 0.908/0.092, 0.567/0.432, 1.000/0.000, 0.916/0.084 and 0.517/0.483 for HPA-1a/1b, -2a/2b, -3a/3b, -4a/4b, -5a/5b and -15a/15b, respectively. No statistically significant difference between genotypes in these populations could be observed. Due to the similar distribution of HPA genotypes in both ethnical groups, no increased risk of NAIT for children of mixed couples or of post-transfusion purpura or PLT transfusion refractoriness secondary to antibodies to HPAs for recipients of PLT concentrates from blood donors of the other ethnicity is given. © 2012 John Wiley & Sons A/S.

The Effects of Platelet-Rich Plasma on Bone Marrow Stromal Cell Transplants for Tendon Healing In Vitro

PubMed Central

Morizaki, Yutaka; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C.

2010-01-01

Purpose In this study we investigated the effect of platelet-rich plasma (PRP) and bone-marrow derived stromal cell (BMSC)-seeded interposition in an in vitro canine tendon repair model. Methods Bone marrow, peripheral blood, and tendons were harvested from mixed breed dogs. BMSC were cultured and passaged from adherent cells of bone marrow suspension. PRP was purified from peripheral blood using a commercial kit. 192 flexor digitorum profundus tendons were used for the study. Tendons repaired with a simple suture were used as a control group. In treatment groups, a collagen gel patch was interposed at the tendon repair site prior to suture. There were three treatment groups according to the type of collagen patch; a patch with PRP, a patch with BMSC, and a patch with PRP and BMSC. The repaired tendons were evaluated by biomechanical testing and by histological survey after 2 and 4 weeks in tissue culture. To evaluate viability, cells were labeled with PKH26 and surveyed under confocal microscopy after culture. Results The maximum breaking strength and stiffness of the healing tendons with the BMSC-seeded PRP patch was significantly higher than the healing tendons without a patch or with a cell-seeded patch (p<0.02). Viable BMSC were present at both 2 and 4 weeks. Conclusions PRP enhanced the effect of BMSC-seeded collagen gel interposition in this in vitro model. Based on these results we now plan to investigate this effect in vivo. PMID:20951509

Wide variations in blood product transfusion practices among providers who care for patients with acute leukemia in the United States.

PubMed

Pine, Alexander B; Lee, Eun-Ju; Sekeres, Mikkael; Steensma, David P; Zelterman, Daniel; Prebet, Thomas; DeZern, Amy; Komrokji, Rami; Litzow, Mark; Luger, Selina; Stone, Richard; Erba, Harry P; Garcia-Manero, Guillermo; Lee, Alfred I; Podoltsev, Nikolai A; Barbarotta, Lisa; Kasberg, Stephanie; Hendrickson, Jeanne E; Gore, Steven D; Zeidan, Amer M

2017-02-01

Transfusion of blood products is a key component of the supportive management in patients with acute leukemia (AL). However high-quality trial evidence and clinical outcome data to support specific transfusion goals for blood products for patients with AL remain limited leading to diverse transfusion practices. The primary objective of this study was to determine the spectrum of transfusion patterns in a variety of care settings among providers who treat AL patients. A 31-question survey queried providers caring for AL patients about the existence of institutional guidelines for transfusion of blood products, transfusion triggers for hemoglobin (Hb), platelets (PLTs), and fibrinogen in various settings including inpatient and outpatient and before procedures. We analyzed 130 responses and identified divergent transfusion Hb goals in hospitalized and ambulatory patients, fibrinogen goals for cryoprecipitate transfusions, and variation in practice for use of certain PLTs and red blood cell products. The least variable transfusion patterns were reported for PLT goals in thrombocytopenia and in the setting of invasive procedures such as bone marrow biopsy and lumbar punctures. This survey confirmed wide variations in blood product transfusion practices across several clinical scenarios in patients with AL. The findings emphasized the need for large prospective randomized trials to develop standardized evidence-based guidelines for blood product transfusions in patients with AL with the goal of limiting unnecessary transfusions without compromising outcomes. © 2016 AABB.

Eltrombopag Use in Thrombocytopenia for Endoscopic Submucosal Dissection of a Gastric Carcinoid

PubMed Central

Kaltenbach, Tonya; Martin, Beth; Rouse, Robert V.; Soetikno, Roy

2014-01-01

Severe thrombocytopenia is a contraindication for therapeutic endoscopy due to the risk of bleeding. Platelet transfusions can temporarily increase platelet count, but are difficult to administer in the 2 weeks following endoscopic resection, during which the patient is at high risk for delayed bleeding. We present the use of a novel thrombopoietin receptor agonist, eltrombopag, to sustain platelet levels for the safe and complete endoscopic submucosal dissection of a gastric carcinoid in a patient with severe thrombocytopenia due to cirrhosis and idiopathic thrombocytopenic purpura. We performed complete and safe endoscopic removal of a gastric carcinoid after correcting the thrombocytopenia. PMID:26157896

Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion

PubMed Central

Kim, Minjeong; Park, Jisun

2018-01-01

Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/µL to 2000/µL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described. PMID:29214792

Collection, storage, inspection and quality control of platelet concentrates obtained by apheresis: The situation in Spain.

PubMed

Castrillo, Azucena; Jimenez-Marco, Teresa; Arroyo, José L; Jurado, María L; Larrea, Luis; Maymo, Rosa M; Monge, Jorge; Muñoz, Carmen; Pajares, Ángel; Yáñez, Marta

2017-06-01

Diverse variables are involved in apheresis platelet collection, processing and storage. This survey shows how these are realized in Spain. An analysis of collected data was performed in a questionnaire completed by ten Transfusion Centers (TC) which perform between 50 and 520 apheresis procedures per month. This information comprises the procedures used to collect, inspect and store apheresis platelet concentrates (PC), and quality control data. Macroscopic inspection of PC is performed in all TC, especially during the first few hours post-collection and before distribution. The type of processor, duration of post-collection resting periods and temperature from the time of collection until distribution are similar in all TC. In 80% of TC, PC with small and scarce aggregates are distributed to transfusion services. The presence of clumps is influenced by type of processor, female donor, cold ambient temperature and collection of hyperconcentrated platelets, and is often recurrent in the same donor, although some TC have not found any influential variables. Overall, no objective inspection methods are followed, although there are exceptions. The degree of compliance with quality control parameters, such as the number of units studied, mean platelet yield, residual leukocyte counts and pH at expiry date, is acceptable in all TC. Compliance in terms of number of microbiological culture samples is variable. The usual practice in Spanish TC with respect to the collection, post-collection handling and storage of apheresis PC can be considered uniform, although some specific aspects of analyses should follow more objective methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Massive transfusion: an overview of the main characteristics and potential risks associated with substances used for correction of a coagulopathy.

PubMed

Seghatchian, Jerard; Samama, Meyer Michel

2012-10-01

Massive transfusion (MT) is an empiric mode of treatment advocated for uncontrolled bleeding and massive haemorrhage, aiming at optimal resuscitation and aggressive correction of coagulopathy. Conventional guidelines recommend early administration of crystalloids and colloids in conjunction with red cells, where the red cell also plays a critical haemostatic function. Plasma and platelets are only used in patients with microvascular bleeding with PT/APTT values >1.5 times the normal values and if PLT counts are below 50×10(9)/L. Massive transfusion carries a significant mortality rate (40%), which increases with the number of volume expanders and blood components transfused. Controversies still exist over the optimal ratio of blood components with respect to overall clinical outcomes and collateral damage. While inadequate transfusion is believed to be associated with poor outcomes but empirical over transfusion results in unnecessary donor exposure with an increased rate of sepsis, transfusion overload and infusion of variable amounts of some biological response modifiers (BRMs), which have the potential to cause additional harm. Alternative strategies, such as early use of tranexamic acid are helpful. However in trauma settings the use of warm fresh whole blood (WFWB) instead of reconstituted components with a different ratio of stored components might be the most cost effective and safer option to improve the patient's survival rate and minimise collateral damage. This manuscript, after a brief summary of standard medical intervention in massive transfusion focuses on the main characteristics of various substances currently available to overcome massive transfusion coagulopathy. The relative levels of some BRMs in fresh and aged blood components of the same origin are highlighted and some myths and unresolved issues related to massive transfusion practice are discussed. In brief, the coagulopathy in MT is a complex phenomenon, often complicated by chronic activation of coagulation, platelets, complement and vascular endothelial cells, where haemolysis, microvesiculation, exposure of phosphatidyl serine positive cells, altered red cells with reduced adhesive proteins and the presence of some BRM, could play a pivotal role in the coagulopathy and untoward effects. The challenges of improving the safety of massive transfusion remain as numerous and as varied as ever. The answer may reside in appropriate studies on designer whole blood, combined with new innovative tools to diagnosis a coagulopathy and an evidence based mode of therapy to establish the optimal survival benefit of patients, always taking into account the concept of harm reduction and reduction of collateral damage. Copyright © 2012 Elsevier Ltd. All rights reserved.

Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function

PubMed Central

Osman, Abdimajid; Hitzler, Walter E.; Meyer, Claudius U.; Landry, Patricia; Corduan, Aurélie; Laffont, Benoit; Boilard, Eric; Hellstern, Peter; Vamvakas, Eleftherios C.

2015-01-01

Pathogen reduction (PR) systems for platelets, based on chemically induced cross-linking and inactivation of nucleic acids, potentially prevent transfusion transmission of infectious agents, but can increase clinically significant bleeding in some clinical studies. Here, we documented the effects of PR systems on microRNA and mRNA levels of platelets stored in the blood bank, and assessed their impact on platelet activation and function. Unlike platelets subjected to gamma irradiation or stored in additive solution, platelets treated with Intercept (amotosalen + ultraviolet-A [UVA] light) exhibited significantly reduced levels of 6 of the 11 microRNAs, and 2 of the 3 anti-apoptotic mRNAs (Bcl-xl and Clusterin) that we monitored, compared with platelets stored in plasma. Mirasol (riboflavin + UVB light) treatment of platelets did not produce these effects. PR neither affected platelet microRNA synthesis or function nor induced cross-linking of microRNA-sized endogenous platelet RNA species. However, the reduction in the platelet microRNA levels induced by Intercept correlated with the platelet activation (p < 0.05) and an impaired platelet aggregation response to ADP (p < 0.05). These results suggest that Intercept treatment may induce platelet activation, resulting in the release of microRNAs and mRNAs from platelets. The clinical implications of this reduction in platelet nucleic acids secondary to Intercept remain to be established. PMID:24749844

Relative safety of pooled whole blood-derived versus single-donor (apheresis) platelets in the United States: a systematic review of disparate risks.

PubMed

Vamvakas, Eleftherios C

2009-12-01

Risks of transfusion-transmitted infections (TTIs), transfusion-associated sepsis (TAS), and transfusion-related acute lung injury (TRALI) were compared between pooled whole blood-derived (PWBD) and single-donor platelets (PLTs) transfused in the United States. The literature was searched for estimates of the risk of TTIs and TAS and of the effect on bacterial contamination of PLTs of process improvements, bacterial culture, and surrogate methods to detect bacteria. Seven studies published between January 2005 and December 2008 and comparing bacterial contamination frequency between PWBD and single-donor PLTs after implementing bacterial culture testing of both components were subjected to meta-analysis. The three retrieved studies diagnosing TRALI based on the 2004 consensus definition in settings transfusing both PWBD and single-donor PLTs were not amenable to meta-analysis and were assessed qualitatively. Under a best-case scenario, if 100% (from the current 12.5%) of PLT doses were provided as PWBD PLTs, the number of additional transmissions of human immunodeficiency virus, hepatitis C virus, hepatitis B virus, bacteria, or a novel pathogen annually could be 1.2, 1.3, 9.0, 105.3, or 69.2 to 252.6, respectively. Compared with single-donor PLTs, US PLT pools of five concentrates have a 5.6-fold higher risk of bacterial contamination (summary odds ratio, 5.58; 95% confidence interval, 2.60-11.98; p < 0.05). The three studies that diagnosed TRALI based on the consensus definition did not demonstrate a difference in risk between PWBD and single-donor PLTs. TTIs and TAS determine the relative safety of PWBD versus single-donor PLTs. The available limited data do not support a higher risk of TRALI from single-donor (compared with PWBD) PLTs.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

PubMed

Pagano, M B; Metcalf, R A; Hess, J R; Reyes, J; Perkins, J D; Montenovo, M I

2018-04-01

During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P < 0·0001) and 1178 ml (747-1178) (P < 0·0001) of RBC were used in excess compared to the high ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P < 0·0001) of RBC in excess when compared to high ratio in the univariable and multivariable analysis, respectively. In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions. © 2018 International Society of Blood Transfusion.

A major haemorrhage protocol improves the delivery of blood component therapy and reduces waste in trauma massive transfusion.

PubMed

Khan, Sirat; Allard, Shubha; Weaver, Anne; Barber, Colin; Davenport, Ross; Brohi, Karim

2013-05-01

Major haemorrhage protocols (MHP) are required as part of damage control resuscitation regimens in modern trauma care. The primary objectives of this study were to ascertain whether a MHP improved blood product administration and reduced waste compared to traditional massive transfusion protocols (MTP). Datasets on adult trauma admissions 1 year prior and 1 year post implementation of a MHP at a Level 1 trauma centre were obtained from the trauma registry. Demographic and clinical data were collected prospectively including mechanism of injury, physiological observations, ICU admission and length of stay. The volume of blood components (packed red blood cells, platelets, cryoprecipitate and fresh frozen plasma) issued, transfused, returned to stock and wasted within the first 24h was gathered retrospectively. Over the 2-year study period 2986 patient records were available for analysis. 40 patients required a 10+ Units of packed red blood ells transfusion in the MTP group vs. 56 patients post MHP implementation. The administration of blood component therapy improved significantly post MHP implementation. FFP:PRBC transfusion improved from 1:3 to 1:2 (p<0.01) and CRYO:PRBC improved from 1:10 to 1:7 (p<0.05). We reported a significant reduction in the waste of platelets from 14% to 2% (p<0.01). Outcomes had improved: Median hospital length of stay was reduced from 54 days to 26 days (p<0.05). Implementation of a MHP results in improved delivery of blood components and a reduction in the waste of blood products compared to the older model of MTP. In combination with educational programmes MHP can significantly improve blood product administration and patient outcomes in trauma haemorrhage. Level III diagnostic test study. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Impact of blood products on platelet function in patients with traumatic injuries: a translational study.

PubMed

Henriksen, Hanne Hee; Grand, Alexandra G; Viggers, Sandra; Baer, Lisa A; Solbeck, Sacha; Cotton, Bryan A; Matijevic, Nena; Ostrowski, Sisse R; Stensballe, Jakob; Fox, Erin E; Chen, Tzu-An; Holcomb, John B; Johansson, Pär I; Cardenas, Jessica C; Wade, Charles E

2017-06-15

Reductions in platelet (PLT) count and function are associated with poor outcomes in trauma patients. We proposed to determine if patients expected to receive blood products have a decrease in PLT function higher than expected based on the reduction in PLT count, and if the reduction in function could be associated with the donor plasma/supernatant received. PLT count and function were measured on admission to the emergency department and intensive care unit in severely injured patients expected to receive a transfusion. PLT function was measured by Multiplate aggregometry in response to five agonists. Function was corrected for alterations in count. In vitro studies were conducted in the blood of normal subjects to assess the effect of dilutions with AB donor plasma on PLT function. Forty-six patients were enrolled, with 87% requiring a transfusion. Median Injury Severity Score was 23 (13, 29) and mortality 15%. PLT count and function were decreased from emergency department to intensive care unit admission by 25% and 58%, respectively. Decreases in function persisted after adjustment for count. Patients requiring large volumes of blood products had reductions in function that were disproportionately greater. Reductions in PLT function were greatest after transfusion of PLTs. In in vitro studies with a 30% dilution by autologous plasma caused a relational reduction in function, whereas allogenic plasma resulted in greater decreases that were highly variable between donors. Within hours of injury a decrease in both PLT count and function occurs, that is aggravated with the administration of blood products, with transfusion of PLTs showing the greatest effect. The effect on PLT function of allogenic transfused plasma appears to be highly donor related. Copyright © 2017 Elsevier Inc. All rights reserved.

Preoperative Recipient Parameters Allow Early Estimation of Postoperative Outcome and Intraoperative Transfusion Requirements in Liver Transplantation.

PubMed

Schumacher, Carsten; Eismann, Hendrik; Sieg, Lion; Friedrich, Lars; Scheinichen, Dirk; Vondran, Florian W R; Johanning, Kai

2018-01-01

Liver transplantation is a complex intervention, and early anticipation of personnel and logistic requirements is of great importance. Early identification of high-risk patients could prove useful. We therefore evaluated prognostic values of recipient parameters commonly available in the early preoperative stage regarding postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. All adult patients undergoing first liver transplantation at Hannover Medical School between January 2005 and December 2010 were included in this retrospective study. Demographic, clinical, and laboratory data as well as clinical courses were recorded. Prognostic values regarding 30- and 90-day outcomes were evaluated by uni- and multivariate statistical tests. Identified risk parameters were used to calculate risk scores. There were 426 patients (40.4% female) included with a mean age of 48.6 (11.9) years. Absolute 30-day mortality rate was 9.9%, and absolute 90-day mortality rate was 13.4%. Preoperative leukocyte count >5200/μL, platelet count <91 000/μL, and creatinine values ≥77 μmol/L were relevant risk factors for both observation periods ( P < .05, respectively). A score based on these factors significantly differentiated between groups of varying postoperative outcomes and intraoperative transfusion requirements ( P < .05, respectively). A score based on preoperative creatinine, leukocyte, and platelet values allowed early estimation of postoperative 30- and 90-day outcomes and intraoperative transfusion requirements in liver transplantation. Results might help to improve timely logistic and personal strategies.

How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity

PubMed Central

Strauss, Ronald G.

2010-01-01

Many aspects of hematopoiesis are either incompletely developed in preterm infants or still functioning to serve the fetus (i.e., the intrauterine counterpart to a liveborn preterm neonate). This delayed development and/or slow adaptation to extrauterine life diminishes the capacity of the neonate to produce red blood cells (RBCs), platelets (PLTs), and neutrophils—particularly during the stress of life-threatening illnesses encountered after preterm birth such as sepsis, severe pulmonary dysfunction, necrotizing enterocolitis, and immune cytopenias. The serious medical and/or surgical problems of preterm birth can be further complicated by phlebotomy blood losses, bleeding, hemolysis, and consumptive coagulopathy. To illustrate, some preterm infants, especially those with birth weight less than 1.0 kg and respiratory distress, are given numerous RBC transfusions early in life owing to several interacting factors. Neonates delivered before 28 weeks of gestation (birth weight, <1.0 kg) are born before the bulk of iron transport has occurred from mother to fetus via the placenta and before the onset of marked erythropoietic activity of fetal marrow during the third trimester. Soon after preterm birth, severe respiratory disease can lead to repeated blood sampling for laboratory studies and, consequently, to replacement RBC transfusions. Additionally, preterm infants are unable to mount an effective erythropoietin (EPO) response to decreasing numbers of RBCs, and this factor contributes to the diminished ability to compensate for anemia—thus enhancing need for RBC transfusions. PMID:18194380

Development and evaluation of an automatic method for the study of platelet osmotic response.

PubMed

Gigout, T; Blondel, W; Didelon, J; Latger, V; Dumas, D; Schooneman, F; Stoltz, J F

1999-01-01

Study of the osmotic resistance to hypotonic medium of platelets has often been suggested as a global test to assess the viability of these cells in transfusion or to study modification during haematological pathologies. A number of authors have analysed the behaviour of platelets in hypotonic media by a variety of methods (cell count, determinations of substances released, morphology, etc.), but most studies are currently based on the so-called "Hypotonic Shock Response" test (HSR). In this study, the authors describe a new automated and reproducible apparatus, called fragilimeter, using slow dialysis to assess platelet osmotic resistance. The variations in light transmission through a platelet suspension according to ionic strength are linked to the change in cellular volume and lysis and characterise the osmotic behaviour of the cells. The results revealed the good reproducibility and sensibility of the technique. This apparatus allows also the realisation of the "HSR" test.

Microparticle and mitochondrial release during extended storage of different types of platelet concentrates.

PubMed

Marcoux, Geneviève; Duchez, Anne-Claire; Rousseau, Matthieu; Lévesque, Tania; Boudreau, Luc H; Thibault, Louis; Boilard, Eric

2017-05-01

On activation, platelets release vesicles called microparticles (MPs). MPs are heterogeneous with regard to the presence or absence of mitochondria. We quantified MPs in platelet concentrates (PCs) taking their mitochondrial content into account. Platelet-rich plasma (PRP), buffy coat (BC) and apheresis (AP) PCs were tested through 7 days of storage. A combination of flow cytometry and spanning-tree progression analysis of density-normalized events (SPADE) was used to determine MP and mitochondrial release during storage. All the PC biochemical parameters complied with transfusion standards at all times. Platelet activation markers increased during storage and were higher for PRP than other types of PCs. Concentrations of MPs and extracellular mitochondria interpreted by SPADE algorithm were significantly higher in PRP than other in PCs and were stable throughout storage. The mode of preparation, rather than storage duration, impacts the release of MPs and mitochondria in PCs.

[Anaesthetic implications in a pregnant patient with an extreme thrombocytopenia due to a May-Hegglin anomaly: general o regional anaesthesia?].

PubMed

García Vallejo, G; Cabellos, M; Kabiri, M; Fraile, J R; Cuesta, J

2014-10-01

The May-Hegglin anomaly is an inherited disorder, so uncommon that the incidence is still unknown. It is characterized by macro-thrombocytopenia with normal platelet function and cytoplasmic inclusion bodies in granulocytes. The case is reported of a 28-year-old primiparous patient who had an urgent caesarean section due to failed induction of labour. The patient had no history of abnormal bleeding. Other causes of thrombocytopenia or platelet dysfunction, such as preeclampsia, HELLP syndrome, or placental abruption, were ruled out. The platelet count prior to surgery was 20,900/mm(3) with normal platelet function. General anaesthesia was performed. No excessive bleeding occurred and a platelet transfusion was not needed. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia.

PubMed

Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho; Seo, Kyoung-Won

2015-01-01

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly with improved clinical signs while the third dog with recurrent IMT was euthanized due to its deteriorating condition. This case report describes the efficacy of VLP therapy in refractory IMT patients.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia

PubMed Central

Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho

2015-01-01

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly withimproved clinical signs while the third dogwith recurrent IMT was euthanized due to its deteriorating condition. This case report describesthe efficacy of VLP therapy in refractory IMT patients. PMID:25269722

Transfusion Medicine and Molecular Genetic Methods

PubMed Central

Saleh, Rozieyati Mohamed; Zefarina, Zulkafli; Che Mat, Nor Fazila; Chambers, Geoffrey Keith; Edinur, Hisham Atan

2018-01-01

Transfusion procedures are always complicated by potential genetic mismatching between donor and recipient. Compatibility is determined by several major antigens, such as the ABO and Rhesus blood groups. Matching for other blood groups (Kell, Kidd, Duffy, and MNS), human platelet antigens, and human leukocyte antigens (HLAs) also contributes toward the successful transfusion outcomes, especially in multitransfused or highly immunized patients. All these antigens of tissue identity are highly polymorphic and thus present great challenges for finding suitable donors for transfusion patients. The ABO blood group and HLA markers are also the determinants of transplant compatibility, and mismatched antigens will cause graft rejection or graft-versus-host disease. Thus, a single and comprehensive registry covering all of the significant transfusion and transplantation antigens is expected to become an important tool in providing an efficient service capable of delivering safe blood and quickly locating matching organs/stem cells. This review article is intended as an accessible guide for physicians who care for transfusion-dependent patients. In particular, it serves to introduce the new molecular screening methods together with the biology of these systems, which underlies the tests. PMID:29899883

Functional Comparison of Induced Pluripotent Stem Cell- and Blood-Derived GPIIbIIIa Deficient Platelets

PubMed Central

Haas, Jessica; Sandrock-Lang, Kirstin; Gärtner, Florian; Jung, Christian Billy; Zieger, Barbara; Parrotta, Elvira; Kurnik, Karin; Sinnecker, Daniel; Wanner, Gerhard; Laugwitz, Karl-Ludwig; Massberg, Steffen; Moretti, Alessandra

2015-01-01

Human induced pluripotent stem cells (hiPSCs) represent a versatile tool to model genetic diseases and are a potential source for cell transfusion therapies. However, it remains elusive to which extent patient-specific hiPSC-derived cells functionally resemble their native counterparts. Here, we generated a hiPSC model of the primary platelet disease Glanzmann thrombasthenia (GT), characterized by dysfunction of the integrin receptor GPIIbIIIa, and compared side-by-side healthy and diseased hiPSC-derived platelets with peripheral blood platelets. Both GT-hiPSC-derived platelets and their peripheral blood equivalents showed absence of membrane expression of GPIIbIIIa, a reduction of PAC-1 binding, surface spreading and adherence to fibrinogen. We demonstrated that GT-hiPSC-derived platelets recapitulate molecular and functional aspects of the disease and show comparable behavior to their native counterparts encouraging the further use of hiPSC-based disease models as well as the transition towards a clinical application. PMID:25607928

Time-based analysis of the apheresis platelet supply chain in England.

PubMed

Wilding, R; Cotton, S; Dobbin, J; Chapman, J; Yates, N

2011-10-01

During 2009/2010 loss of platelets within NHS Blood and Transplant (NHSBT) due to time expiry was 9.3%. Hospitals remain reluctant to hold stocks of platelets due to the poor shelf life at issue. The purpose of this study was to identify areas for time compression in the apheresis platelet supply chain to extend the shelf life available for hospitals and reduce wastage in NHSBT. This was done within the context of NHSBT reconfiguring their supply chain and moving towards a consolidated and centralised approach. Time based process mapping was applied to identify value and non-value adding time in two manufacturing models. A large amount of the non-value adding time in the apheresis platelet supply chain is due to transportation and waiting for the next process in the manufacturing process to take place. Time based process mapping provides an effective 'lens' for supply chain professionals to identify opportunities for improvement in the platelet supply chain. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Thrombocytopenia after liver transplantation: Should we care?

PubMed Central

Takahashi, Kazuhiro; Nagai, Shunji; Safwan, Mohamed; Liang, Chen; Ohkohchi, Nobuhiro

2018-01-01

Transient thrombocytopenia is a common phenomenon after liver transplantation. After liver transplantation (LT), platelet count decreases and reaches a nadir on postoperative days 3-5, with an average reduction in platelet counts of 60%; platelet count recovers to preoperative levels approximately two weeks after LT. The putative mechanisms include haemodilution, decreased platelet production, increased sequestration, medications, infections, thrombosis, or combination of these processes. However, the precise mechanisms remain unclear. The role of platelets in liver transplantation has been highlighted in recent years, and particular attention has been given to their effects beyond hemostasis and thrombosis. Previous studies have demonstrated that perioperative thrombocytopenia causes poor graft regeneration, increases the incidence of postoperative morbidity, and deteriorates the graft and decreases patient survival in both the short and long term after liver transplantation. Platelet therapies to increase perioperative platelet counts, such as thrombopoietin, thrombopoietin receptor agonist, platelet transfusion, splenectomy, and intravenous immunoglobulin treatment might have a potential for improving graft survival, however clinical trials are lacking. Further studies are warranted to detect direct evidence on whether thrombocytopenia is the cause or result of poor-graft function and postoperative complications, and to determine who needs platelet therapies in order to prevent postoperative complications and thus improve post-transplant outcomes. PMID:29632420

Determinants of ABH expression on human blood platelets.

PubMed

Cooling, Laura L W; Kelly, Kathleen; Barton, James; Hwang, Debbie; Koerner, Theodore A W; Olson, John D

2005-04-15

Platelets express ABH antigens, which can adversely effect platelet transfusion recovery and survival in ABH-incompatible recipients. To date, there has been no large, comprehensive study comparing specific donor factors with ABH expression on platelet membranes and glycoconjugates. We studied ABH expression in 166 group A apheresis platelet donors by flow cytometry, Western blotting, and thin layer chromatography relative to donor age, sex, A1/A2 subgroup, and Lewis phenotype. Overall, A antigen on platelet membranes, glycoproteins, and glycosphingolipids was linked to an A1 red blood cell (RBC) phenotype. Among A1 donors, platelet ABH varied significantly between donors (0%-87%). Intradonor variability, however, was minimal, suggesting that platelet ABH expression is a stable, donor-specific characteristic, with 5% of A1 donors typing as either ABH high- or low-expressers. Group A2 donors, in contrast, possessed a Bombay-like phenotype, lacking both A and H antigens. Unlike RBCs, ABH expression on platelets may be determined primarily by H-glycosyltransferase (FUT1) activity. Identification of A2 and A1 low expressers may increase the availability and selection of crossmatched and HLA-matched platelets. Platelets from group A2 may also be a superior product for patients undergoing A/O major mismatch allogeneic progenitor cell transplantation.

Platelets generated from human embryonic stem cells are functional in vitro and in the microcirculation of living mice

PubMed Central

Lu, Shi-Jiang; Li, Feng; Yin, Hong; Feng, Qiang; Kimbrel, Erin A; Hahm, Eunsil; Thon, Jonathan N; Wang, Wei; Italiano, Joseph E; Cho, Jaehyung; Lanza, Robert

2011-01-01

Platelets play an essential role in hemostasis and atherothrombosis. Owing to their short storage time, there is constant demand for this life-saving blood component. In this study, we report that it is feasible to generate functional megakaryocytes and platelets from human embryonic stem cells (hESCs) on a large scale. Differential-interference contrast and electron microscopy analyses showed that ultrastructural and morphological features of hESC-derived platelets were indistinguishable from those of normal blood platelets. In functional assays, hESC-derived platelets responded to thrombin stimulation, formed microaggregates, and facilitated clot formation/retraction in vitro. Live cell microscopy demonstrated that hESC-platelets formed lamellipodia and filopodia in response to thrombin activation, and tethered to each other as observed in normal blood. Using real-time intravital imaging with high-speed video microscopy, we have also shown that hESC-derived platelets contribute to developing thrombi at sites of laser-induced vascular injury in mice, providing the first evidence for in vivo functionality of hESC-derived platelets. These results represent an important step toward generating an unlimited supply of platelets for transfusion. Since platelets contain no genetic material, they are ideal candidates for early clinical translation involving human pluripotent stem cells. PMID:21221130

Improved outcomes and reduced costs associated with a health-system-wide patient blood management program: a retrospective observational study in four major adult tertiary-care hospitals.

PubMed

Leahy, Michael F; Hofmann, Axel; Towler, Simon; Trentino, Kevin M; Burrows, Sally A; Swain, Stuart G; Hamdorf, Jeffrey; Gallagher, Trudi; Koay, Audrey; Geelhoed, Gary C; Farmer, Shannon L

2017-06-01

Patient blood management (PBM) programs are associated with improved patient outcomes, reduced transfusions and costs. In 2008, the Western Australia Department of Health initiated a comprehensive health-system-wide PBM program. This study assesses program outcomes. This was a retrospective study of 605,046 patients admitted to four major adult tertiary-care hospitals between July 2008 and June 2014. Outcome measures were red blood cell (RBC), fresh-frozen plasma (FFP), and platelet units transfused; single-unit RBC transfusions; pretransfusion hemoglobin levels; elective surgery patients anemic at admission; product and activity-based costs of transfusion; in-hospital mortality; length of stay; 28-day all-cause emergency readmissions; and hospital-acquired complications. Comparing final year with baseline, units of RBCs, FFP, and platelets transfused per admission decreased 41% (p < 0.001), representing a saving of AU$18,507,092 (US$18,078,258) and between AU$80 million and AU$100 million (US$78 million and US$97 million) estimated activity-based savings. Mean pretransfusion hemoglobin levels decreased 7.9 g/dL to 7.3 g/dL (p < 0.001), and anemic elective surgery admissions decreased 20.8% to 14.4% (p = 0.001). Single-unit RBC transfusions increased from 33.3% to 63.7% (p < 0.001). There were risk-adjusted reductions in hospital mortality (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.67-0.77; p < 0.001), length of stay (incidence rate ratio, 0.85; 95% CI, 0.84-0.87; p < 0.001), hospital-acquired infections (OR, 0.79; 95% CI, 0.73-0.86; p < 0.001), and acute myocardial infarction-stroke (OR, 0.69; 95% CI, 0.58-0.82; p < 0.001). All-cause emergency readmissions increased (OR, 1.06; 95% CI, 1.02-1.10; p = 0.001). Implementation of a unique, jurisdiction-wide PBM program was associated with improved patient outcomes, reduced blood product utilization, and product-related cost savings. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Military walking blood bank and the civilian blood service.

PubMed

Berséus, Olle; Hervig, Tor; Seghatchian, Jerard

2012-06-01

In most countries whole blood transfusions have been replaced by component therapy. This has allowed for both better usage of the blood donations and better quality during storage. While this strategy was initially motivated by the commercial need for plasma the plasma reduction also reduced the levels of low grade proteases and sialidase, hence minimizing the cellular storage lesion/microvesiculation during prolonged storage. Plasma reduction also reduces transfusion reactions associated with plasma. During special military conditions, however, blood transfusion is urgently needed without corresponding access to blood components, in particular platelets. Accordingly, new focus on whole blood has aroused and added a new challenge to the blood transfusion services. This special issue of "what is happening" highlights the planed efforts by Swedish and Norwegian groups in the developments of military walking blood bank, which is applicable to civil blood services. Copyright © 2012 Elsevier Ltd. All rights reserved.

Evolution de la reanimation transfusionnelle du blesse hemorragique grave au sein des forces militaires americaines (Evolution of US Military Transfusion Support for Resuscitation of Trauma and Hemorrhagic Shock)

DTIC Science & Technology

2013-04-15

Trauma Registry; Fresh whole blood; 1:1:1 component therapy; Platelet:RBC; FFP:RBC; Freeze-dried plasma; Tranexamic acid ∗ Auteur correspondant. Adresse e...Effects of tranexamic acid on death, vascular occlu- sive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a...randomised, placebo-controlled trial. Lancet 2010;376:23–32. [74] Morrison JJ, et al. Military application of tranexamic acid in trauma emer- gency

Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion.

PubMed

Park, Mihwa; Kim, Minjeong; Park, Jisun; Cho, Jinhyun

2018-01-01

Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/μL to 2000/μL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described. © Copyright: Yonsei University College of Medicine 2018.

Development of a Strategy Based on the Surface Plasmon Resonance Technology for Platelet Compatibility Testing.

PubMed

Wu, Chang-Lin; He, Jian-An; Gu, Da-Yong; Shao, Chao-Peng; Zhu, Yi; Dang, Xin-Tang

2018-01-01

This study was aimed to establish a novel strategy based on the surface plasmon resonance (SPR) technology for platelet compatibility testing. A novel surface matrix was prepared based on poly (OEGMA-co-HEMA) via surface-initiated polymerization as a biosensor surface platform. Type O universal platelets and donor platelets were immobilized on these novel matrices via amine-coupling reaction and worked as a capturing ligand for binding the platelet antibody. Antibodies binding to platelets were monitored in real time by injecting the samples into a microfluidic channel. Clinical serum samples (n = 186) with multiple platelet transfusions were assayed for platelet antibodies using the SPR technology and monoclonal antibody-immobilized platelet antigen (MAIPA) assay. The novel biosensor surface achieved nonfouling background and high immobilization capacity and showed good repeatability and stability after regeneration. The limit of detection of the SPR biosensor for platelet antibody was estimated to be 50 ng/mL. The sensitivity and specificity were 92% and 98.7%. It could detect the platelet antibody directly in serum samples, and the results were similar to MAIPA assay. A novel strategy to facilitate the sensitive and reliable detection of platelet compatibility for developing an SPR-based biosensor was established in this study. The SPR-based biosensor combined with novel surface chemistry is a promising method for platelet compatibility testing.

Prevalence of bacterial contamination in platelet concentrates at the National Center of Blood Transfusion (Mexico).

PubMed

Ibáñez-Cervantes, G; Bello-López, J M; Fernández-Sánchez, V; Domínguez-Mendoza, C A; Acevedo-Alfaro, L I

2017-06-01

Most common bacterial sepsis associated with transfusion is caused by contaminated Platelet Concentrates (PC). The screening of PC to detect bacterial contamination is obligatory in Mexico, and it is carried out in quality control programs. In Mexico, the identification and molecular characterization of bacterial contaminants to detect contamination sources have not been implemented due to high costs; however, it is an actual current need. One hundred PC were randomly selected and microbiologically analyzed. This sample size corresponds to 1% of the PC obtained by the National Center of Blood Transfusion (NCBT) in Mexico City according to the Official Mexican Standard NOM-253-SSA1-2012. Additionally, molecular biology tests were implemented in order to identify the possible contamination sources. Nine of the 100 PC analyzed (9%) showed bacterial contamination; analysis of the nucleotide sequences revealed the presence of characteristic microbiota from donor skin and soil. Diverse clonal relationship between the strains was identified in Staphylococcus epidermidis. Detection of contaminants associated with environmental and skin flora, shows the need to implement measures in the process of disinfecting skin at the site of phlebotomy and cleaning each of the areas involved in blood collection. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The HAT Score-A Simple Risk Stratification Score for Coagulopathic Bleeding During Adult Extracorporeal Membrane Oxygenation.

PubMed

Lonergan, Terence; Herr, Daniel; Kon, Zachary; Menaker, Jay; Rector, Raymond; Tanaka, Kenichi; Mazzeffi, Michael

2017-06-01

The study objective was to create an adult extracorporeal membrane oxygenation (ECMO) coagulopathic bleeding risk score. Secondary analysis was performed on an existing retrospective cohort. Pre-ECMO variables were tested for association with coagulopathic bleeding, and those with the strongest association were included in a multivariable model. Using this model, a risk stratification score was created. The score's utility was validated by comparing bleeding and transfusion rates between score levels. Bleeding also was examined after stratifying by nadir platelet count and overanticoagulation. Predictive power of the score was compared against the risk score for major bleeding during anti-coagulation for atrial fibrillation (HAS-BLED). Tertiary care academic medical center. The study comprised patients who received venoarterial or venovenous ECMO over a 3-year period, excluding those with an identified source of surgical bleeding during exploration. None. Fifty-three (47.3%) of 112 patients experienced coagulopathic bleeding. A 3-variable score-hypertension, age greater than 65, and ECMO type (HAT)-had fair predictive value (area under the receiver operating characteristic curve [AUC] = 0.66) and was superior to HAS-BLED (AUC = 0.64). As the HAT score increased from 0 to 3, bleeding rates also increased as follows: 30.8%, 48.7%, 63.0%, and 71.4%, respectively. Platelet and fresh frozen plasma transfusion tended to increase with the HAT score, but red blood cell transfusion did not. Nadir platelet count less than 50×10 3 /µL and overanticoagulation during ECMO increased the AUC for the model to 0.73, suggesting additive risk. The HAT score may allow for bleeding risk stratification in adult ECMO patients. Future studies in larger cohorts are necessary to confirm these findings. Copyright © 2017 Elsevier Inc. All rights reserved.

Establishment of the first international repository for transfusion-relevant bacteria reference strains: ISBT working party transfusion-transmitted infectious diseases (WP-TTID), subgroup on bacteria.

PubMed

Störmer, M; Arroyo, A; Brachert, J; Carrero, H; Devine, D; Epstein, J S; Gabriel, C; Gelber, C; Goodrich, R; Hanschmann, K-M; Heath, D G; Jacobs, M R; Keil, S; de Korte, D; Lambrecht, B; Lee, C-K; Marcelis, J; Marschner, S; McDonald, C; McGuane, S; McKee, M; Müller, T H; Muthivhi, T; Pettersson, A; Radziwon, P; Ramirez-Arcos, S; Reesink, H W; Rojo, J; Rood, I; Schmidt, M; Schneider, C K; Seifried, E; Sicker, U; Wendel, S; Wood, E M; Yomtovian, R A; Montag, T

2012-01-01

Bacterial contamination of platelet concentrates (PCs) still remains a significant problem in transfusion with potential important clinical consequences, including death. The International Society of Blood Transfusion Working Party on Transfusion-Transmitted Infectious Diseases, Subgroup on Bacteria, organised an international study on Transfusion-Relevant Bacteria References to be used as a tool for development, validation and comparison of both bacterial screening and pathogen reduction methods. Four Bacteria References (Staphylococcus epidermidis PEI-B-06, Streptococcus pyogenes PEI-B-20, Klebsiella pneumoniae PEI-B-08 and Escherichia coli PEI-B-19) were selected regarding their ability to proliferate to high counts in PCs and distributed anonymised to 14 laboratories in 10 countries for identification, enumeration and bacterial proliferation in PCs after low spiking (0·3 and 0·03 CFU/ml), to simulate contamination occurring during blood donation. Bacteria References were correctly identified in 98% of all 52 identifications. S. pyogenes and E. coli grew in PCs in 11 out of 12 laboratories, and K. pneumoniae and S. epidermidis replicated in all participating laboratories. The results of bacterial counts were very consistent between laboratories: the 95% confidence intervals were for S. epidermidis: 1·19-1·32 × 10(7) CFU/ml, S. pyogenes: 0·58-0·69 × 10(7) CFU/ml, K. pneumoniae: 18·71-20·26 × 10(7) CFU/ml and E. coli: 1·78-2·10 × 10(7) CFU/ml. The study was undertaken as a proof of principle with the aim to demonstrate (i) the quality, stability and suitability of the bacterial strains for low-titre spiking of blood components, (ii) the property of donor-independent proliferation in PCs, and (iii) their suitability for worldwide shipping of deep frozen, blinded pathogenic bacteria. These aims were successfully fulfilled. The WHO Expert Committee Biological Standardisation has approved the adoption of these four bacteria strains as the first Repository for Transfusion-Relevant Bacteria Reference Strains and, additionally, endorsed as a project the addition of six further bacteria strain preparations suitable for control of platelet contamination as the next step of enlargement of the repository. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Management of tooth extraction in a patient with a rare bleeding disorder associated with Hermansky-Pudlak syndrome: a case report.

PubMed

Minkin, Patton; Bertetti, Richard; Lindsey, Sean; Bovino, Brian

2015-02-01

This report describes the case of a 27-year-old man who had been diagnosed with Hermansky-Pudlak syndrome shortly after birth. Because the patient had a major bleeding disorder associated with his syndrome, local and systemic hemostatic protection recommendations had to be considered before tooth extraction. Synthetic vasopressin (1-deamino-8-d-arginine vasopressin [DDAVP]) was transfused intravenously before surgery. During surgery the patient was transfused with 1 U of human leukocyte antigen (HLA)-matched apheresis platelets. A hemostatic packing of Avitene and Gelfoam was adapted to the extraction site. Treatment with DDAVP, HLA-matched platelets, and local application of a packing with Avitene and Gelfoam resulted in sustained hemostasis and an excellent healing response. Surgical and routine extractions appear to be safe procedures in patients with Hermansky-Pudlak syndrome when appropriate local and systemic hemostatic measures are used. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Biochemistry of storage lesions of red cell and platelet concentrates: A continuous fight implying oxidative/nitrosative/phosphorylative stress and signaling.

PubMed

Rinalducci, Sara; Zolla, Lello

2015-06-01

The mechanisms responsible for the reduced lifespan of transfused red blood cells (RBCs) and platelets (PLTs) are still under investigation, however one explanation refers to the detrimental biochemical changes occurring during ex vivo storage of these blood products. A myriad of historical and more recent studies has contributed to advance our understanding of storage lesion. Without any doubts, proteomics had great impact on transfusion medicine by profiling the storage-dependent changes in the total detectable protein pool of both RBCs and PLTs. This review article focuses on the role of oxidative/nitrosative stress in developing RBC and PLT storage lesions, with a special glance at its biochemistry and cross-talk with phosphorylative signal transduction. In this sense, we enlighten the potential contribution of new branches of proteomics in identifying novel points of intervention for the improvement of blood product quality. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transformation of human mesenchymal cells and skin fibroblasts into hematopoietic cells.

PubMed

Harris, David M; Hazan-Haley, Inbal; Coombes, Kevin; Bueso-Ramos, Carlos; Liu, Jie; Liu, Zhiming; Li, Ping; Ravoori, Murali; Abruzzo, Lynne; Han, Lin; Singh, Sheela; Sun, Michael; Kundra, Vikas; Kurzrock, Razelle; Estrov, Zeev

2011-01-01

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy.

Transformation of Human Mesenchymal Cells and Skin Fibroblasts into Hematopoietic Cells

PubMed Central

Harris, David M.; Hazan-Haley, Inbal; Coombes, Kevin; Bueso-Ramos, Carlos; Liu, Jie; Liu, Zhiming; Li, Ping; Ravoori, Murali; Abruzzo, Lynne; Han, Lin; Singh, Sheela; Sun, Michael; Kundra, Vikas; Kurzrock, Razelle; Estrov, Zeev

2011-01-01

Patients with prolonged myelosuppression require frequent platelet and occasional granulocyte transfusions. Multi-donor transfusions induce alloimmunization, thereby increasing morbidity and mortality. Therefore, an autologous or HLA-matched allogeneic source of platelets and granulocytes is needed. To determine whether nonhematopoietic cells can be reprogrammed into hematopoietic cells, human mesenchymal stromal cells (MSCs) and skin fibroblasts were incubated with the demethylating agent 5-azacytidine (Aza) and the growth factors (GF) granulocyte-macrophage colony-stimulating factor and stem cell factor. This treatment transformed MSCs to round, non-adherent cells expressing T-, B-, myeloid-, or stem/progenitor-cell markers. The transformed cells engrafted as hematopoietic cells in bone marrow of immunodeficient mice. DNA methylation and mRNA array analysis suggested that Aza and GF treatment demethylated and activated HOXB genes. Indeed, transfection of MSCs or skin fibroblasts with HOXB4, HOXB5, and HOXB2 genes transformed them into hematopoietic cells. Further studies are needed to determine whether transformed MSCs or skin fibroblasts are suitable for therapy. PMID:21731684

Hemoperitoneum from corpus luteum rupture in patients with aplastic anemia.

PubMed

Wang, Huaquan; Guo, Lifang; Shao, Zonghong

2015-01-01

Aplastic anemia is a rare hematopoietic stem-cell disorder that results in pancytopenia and hypocellular bone marrow. Women with aplastic anemia usually are at increased risk of corpus luteum rupture due to thrombocytopenia and infection. Here we report two cases had hemoperitoneum from corpus luteum rupture in patients with aplastic anemia in our center. Case 1 involved two episodes of hemoperitoneum resulting from rupture of the corpus luteum in a 23-year-old unmarried female with severe aplastic anemia. This patient was managed conservatively with platelet and packed red cell transfusion. Case 2 involved two episodes of hemoperitoneum resulting from rupture of the corpus luteum in a 33-year-old married patient with aplastic anemia. Emergency laparoscopy revealed massive hemoperitoneum. Bilateral salpingo-oophorectomy were performed successively with platelet and packed red cell transfusion. Hemoperitoneum resulting from a ruptured corpus luteum is a life-threatening condition in patients with aplastic anemia. Prompt and appropriate evaluation of corpus luteum rupture and emergent therapy are needed.

Platelet function measurement-based strategy to reduce bleeding and waiting time in clopidogrel-treated patients undergoing coronary artery bypass graft surgery: the timing based on platelet function strategy to reduce clopidogrel-associated bleeding related to CABG (TARGET-CABG) study.

PubMed

Mahla, Elisabeth; Suarez, Thomas A; Bliden, Kevin P; Rehak, Peter; Metzler, Helfried; Sequeira, Alejandro J; Cho, Peter; Sell, Jeffery; Fan, John; Antonino, Mark J; Tantry, Udaya S; Gurbel, Paul A

2012-04-01

Aspirin and clopidogrel therapy is associated with a variable bleeding risk in patients undergoing coronary artery bypass graft surgery (CABG). We evaluated the role of platelet function testing in clopidogrel-treated patients undergoing CABG. One hundred eighty patients on background aspirin with/without clopidogrel therapy undergoing elective first time isolated on-pump CABG were enrolled in a prospective single-center, nonrandomized, unblinded investigation (Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG [TARGET-CABG] study) between September 2008 and January 2011. Clopidogrel responsiveness (ADP-induced platelet-fibrin clot strength [MA(ADP)]) was determined by thrombelastography; CABG was done within 1 day, 3-5 days, and >5 days in patients with an MA(ADP) >50 mm, 35-50 mm, and <35 mm, respectively. The primary end point was 24-hour chest tube drainage and key secondary end point was total number of transfused red blood cells. Equivalence was defined as ≤25% difference between groups. ANCOVA was used to adjust for confounders. Mean 24-hour chest tube drainage in clopidogrel-treated patients was 93% (95% confidence interval, 81-107%) of the amount observed in clopidogrel-naive patients, and the total amount of red blood cells transfused did not differ between groups (1.80 U versus 2.08 U, respectively, P=0.540). The total waiting period in clopidogrel-treated patients was 233 days (mean, 2.7 days per patient). A strategy based on preoperative platelet function testing to determine the timing of CABG in clopidogrel-treated patients was associated with the same amount of bleeding observed in clopidogrel-naive patients and ≈50% shorter waiting time than recommended in the current guidelines. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00857155.

Parvovirus B19 Passive Transmission by Transfusion of Intercept® Blood System-Treated Platelet Concentrate

PubMed Central

Gowland, Peter; Fontana, Stefano; Stolz, Martin; Andina, Nicola; Niederhauser, Christoph

2016-01-01

Summary Background Pathogen reduction methods for blood components are effective for a large number of viruses though less against small, non-enveloped viruses such as Parvovirus B19 (B19V). This article describes the passive transmission by transfusion of two B19V-contaminated pooled platelet concentrates (PCs) which were treated with the Intercept® blood pathogen reduction system. Case Reports Two transfusion cases of B19V-contaminated Intercept-treated pooled PCs were described. Due to the analysis delay, the PCs were already transfused. The viral content of each donation was 4.87 × 1010 IU/ml in case 1and 1.46 × 108 IU/ml in case 2. B19V (52 IU/ml) was detected in the recipient of the case 1 PC, whereas no virus could be detected in the case 2 PC recipient. A B19V IgM response and a transient boost of the underlying B19V IgG immune status and was observed in recipient 1. Recipient of the case 2 PC remained B19V IgG- and IgM-negative. B19V DNA sequence and phylogenetic analysis revealed a 100% homology between donor and recipient. Conclusion This report describes passive B19V transmission by a PC with very high B19 viral load which elicited a transient boost of the B19V immunity, but not by a PC with a lower B19V content, suggesting that there is a B19 viral load threshold value at which B19V inactivation is exceeded. PMID:27403092

An epidemiologic cohort study reviewing the practice of blood product transfusions among a population of pediatric oncology patients.

PubMed

Lieberman, Lani; Liu, Yang; Portwine, Carol; Barty, Rebecca L; Heddle, Nancy M

2014-10-01

Despite the high utilization of blood products by pediatric oncology patients, literature in this population remains scarce. The primary objective of this study was to assess red blood cell (RBC) and platelet (PLT) utilization rates and transfusion thresholds in pediatric oncology patients. The secondary objective was to describe transfusion-related complications including RBC alloantibody development and transfusion reactions. This epidemiologic cohort study involved pediatric oncology patients at a Canadian academic children's hospital between April 2002 and December 2011. Demographic, clinical, laboratory, and transfusion variables were collected from the Transfusion Registry for Utilization Statistics and Tracking database, a large database that captures more than 50 demographic and clinical variables as well as comprehensive transfusion information and laboratory test results. Of 647 pediatric oncology patients, 430 (66%) received a RBC or PLT transfusion or both during this time period. The median transfusion threshold before a RBC and PLT transfusion was a hemoglobin (Hb) value of 72 g/L (interquartile range [IQR], 68-76 g/L) and a PLT count of 16 × 10(9) /L (IQR, 10 × 10(9) -23 × 10(9) /L), respectively. Ninety-two percent of the issued RBC and PLT products (7507/8154) were cytomegalovirus negative and 90% were irradiated (7299/8154). RBC alloantibody development and transfusion reactions were reported infrequently in 0.5% (2/423) and 4.5% (8/179) of the patients, respectively. This study assessed utilization rates, transfusion thresholds, alloantibody development, and transfusion reactions in pediatric oncology patients. The descriptive results from this epidemiologic study provide baseline information to generate hypotheses to be tested in future interventional studies. © 2014 AABB.

Prognostic Significance of Blood Transfusion in Elderly Patients with Primary Diffuse Large B-Cell Lymphoma

PubMed Central

Fan, Liping; Fu, Danhui; Hong, Jinquan; He, Wenqian; Zeng, Feng; Lin, Qiuyan; Xie, Qianling

2018-01-01

The current study sought to evaluate whether blood transfusions affect survival of elderly patients with primary diffuse large B-cell lymphoma (DLBCL). A total of 104 patients aged 60 years and over were enrolled and divided into two groups: 24 patients who received transfusions and 80 patients who did not. Statistical analyses showed significant differences in LDH levels, platelet (Plt) counts, and hemoglobin (Hb) and albumin (Alb) levels between the two groups. Univariate analyses showed that LDH level ≥ 245 IU/L, cell of origin (germinal center/nongerminal center), and blood transfusion were associated with both overall survival (OS) and progression-free survival (PFS). Higher IPI (3–5), Alb level < 35 g/L, and rituximab usage were associated with OS. Appearance of B symptoms was associated with PFS. Multivariate analyses showed that cell of origin and rituximab usage were independent factors for OS and LDH level was an independent factor for PFS. Blood transfusion was an independent factor for PFS, but not for OS. Our preliminary results suggested that elderly patients with primary DLBCL may benefit from a restrictive blood transfusion strategy. PMID:29750167

Observational study of haemostatic dysfunction and bleeding in neonates with hypoxic-ischaemic encephalopathy.

PubMed

Pakvasa, Mitali A; Winkler, Anne M; Hamrick, Shannon E; Josephson, Cassandra D; Patel, Ravi M

2017-02-09

Evaluate the relationship between initial haemostatic parameters and the frequency and severity of bleeding in neonates with hypoxic-ischaemic encephalopathy (HIE). Retrospective observational cohort study. 2 academically affiliated level III neonatal intensive care units in Atlanta, Georgia. 98 neonates with moderate-to-severe HIE who underwent haemostatic testing within 12 hours of birth and were born from 1 January 2008 to 31 December 2013. Initial haemostatic dysfunction was defined as one or more of the following: prothrombin time (PT) ≥18 s, platelet count <100×10 3 /μL or fibrinogen <150 mg/dL. Bleeding assessed using the Neonatal Bleeding Assessment Tool and graded according to the WHO bleeding scale. The robust Poisson regression was used to evaluate the independent association between components of initial haemostatic dysfunction and bleeding. Among the 98 neonates evaluated, the prevalence of initial haemostatic dysfunction was 69% (95% CI 59% to 78%). 27 neonates (28%; 95% CI 19% to 38%) had abnormal bleeding events and 56 (57%) received at least 1 blood product transfusion. 3 neonates died from bleeding complications. The most common products transfused were fresh-frozen plasma (71%), followed by packed red blood cells (24%) and platelets (21%). In multivariable analysis, fibrinogen <150 mg/dL (adjusted relative risk 2.41, 95% CI 1.09 to 5.36) and platelet count <100×10 3 /μL (adjusted relative risk 2.59, 95% CI 1.30 to 5.16), but not initial PT, were associated with an increased risk of bleeding. The most severe bleeding occurred in neonates with a fibrinogen <150 mg/dL. Among neonates with moderate-to-severe HIE, haemostatic dysfunction is prevalent and associated with an increased risk of bleeding and high transfusion burden. Further studies are needed to determine the appropriate transfusion approaches in this population to prevent bleeding. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Use of 8-methoxypsoralen and long-wavelength ultraviolet radiation for decontamination of platelet concentrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, L.; Wiesehahn, G.P.; Morel, P.A.

1989-07-01

Transmission of viral diseases through blood products remains an unsolved problem in transfusion medicine. We have developed a psoralen photochemical system for decontamination of platelet concentrates in which platelets are treated with long wavelength ultraviolet radiation (UVA, 320-400 nm) in the presence of 8-methoxypsoralen (8-MOP). Bacteria, RNA viruses, and DNA viruses ranging in genome size from 1.2 x 10(6) daltons, encompassing the size range of human pathogens, were inoculated into platelet concentrates and subjected to treatment. This system inactivated 25 to 30 logs/h of bacteria Escherichia coli or Staphylococcus aureus, 6 logs/h of bacteriophage fd, 0.9 log/h of bacteriophage R17more » and 1.1 logs/h of feline leukemia virus (FeLV) in platelet concentrates maintained in standard storage bags. Platelet integrity and in vitro function before, immediately following photochemical treatment, and during prolonged storage after treatment, were evaluated by measuring: (1) extracellular pH; (2) platelet yields; (3) extracellular lactate dehydrogenase (LDH) levels; (4) platelet morphology; (5) platelet aggregation responsiveness; (6) thromboxane beta-2 (TXB-2) production; (7) dense body secretion; and (8) alpha granule secretion. These assays demonstrated that this photochemical inactivation system inactivated bacteria and viruses in platelet concentrates with minimal adverse effects on the in vitro function of platelets in comparison to untreated control concentrates maintained under current, standard blood bank conditions.« less

Clopidogrel (Plavix) and cardiac surgical patients: implications for platelet function monitoring and postoperative bleeding.

PubMed

Tanaka, Kenichi A; Szlam, Fania; Kelly, Andrew B; Vega, J David; Levy, Jerrold H

2004-08-01

The use of clopidogrel (Plavix), an inhibitor of adenosine diphosphate (ADP)-induced platelet aggregation, has been proven to reduce ischemic events in cardiovascular patients, but little information is available for optimal monitoring of platelet function in patients receiving the drug preoperatively. In the first part of the study we compared different testing modalities (thrombelastography (TEG), platelet aggregometry, and whole blood aggregation) to assess platelet ADP receptor inhibition. Because clopidogrel is a pro-drug, we used an in vitro model of ADP inhibition with 5'-p-fluorosulfonylbenzoyladenosine (FSBA). FSBA at final concentration of 80 microM completely inhibited platelet aggregation but had no effect on TEG maximum amplitude (MA). In the second part of the study, antiplatelet effects of clopidogrel were clinically assessed and correlated to postoperative bleeding in 18 coronary bypass surgery patients. Preoperative TEG results were normal or hypercoagulable in clopidogrel-treated patients, although platelet aggregation responses to ADP were inhibited. Clopidogrel-treated patients who underwent cardiopulmonary bypass had a high incidence (84.6%) of platelet transfusion therapy due to increased chest tube drainage. In conclusion, we have demonstrated that normal preoperative TEG-MA does not preclude clopidogrel-induced ADP receptor blockade; however, TEG can be a reliable monitor for CPB-induced platelet dysfunction related to GPIIb/IIIa. For monitoring clopidogrel, it is necessary to perform more specific platelet function tests (aggregometry or platelet count ratio) using ADP as an activator.

All Clinically-Relevant Blood Components Transmit Prion Disease following a Single Blood Transfusion: A Sheep Model of vCJD

PubMed Central

de Wolf, Christopher; Tan, Boon Chin; Smith, Antony; Groschup, Martin H.; Hunter, Nora; Hornsey, Valerie S.; MacGregor, Ian R.; Prowse, Christopher V.; Turner, Marc; Manson, Jean C.

2011-01-01

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion. PMID:21858015

NOD2 Receptor is Expressed in Platelets and Enhances Platelet Activation and Thrombosis

PubMed Central

Zhang, Si; Zhang, Shenghui; Hu, Liang; Zhai, Lili; Xue, Ruyi; Ye, Jianqin; Chen, Leilei; Cheng, Guanjun; Mruk, Jozef; Kunapuli, Satya P.; Ding, Zhongren

2015-01-01

Background Pattern recognition receptor NOD2 (nucleotide binding oligomerization domain 2) is well investigated in immunity, its expression and function in platelets has never been explored. Method and Results Using RT-PCR and Western blot we show that both human and mouse platelets express NOD2, and its agonist MDP induced NOD2 activation as evidenced by receptor dimerization. NOD2 activation potentiates platelet aggregation and secretion induced by low concentration of thrombin or collagen, as well as clot retraction. These potentiating effects of MDP were not seen in platelets from NOD2-deficient mice. Plasma from septic patients also potentiates platelet aggregation induced by thrombin or collagen NOD2-dependently. Using intravital microscopy, we found that MDP administration accelerated in vivo thrombosis in FeCl3-injured mesenteric arteriole thrombosis mouse model. Platelet depletion and transfusion experiments confirmed that NOD2 from platelets contributes to the in vivo thrombosis in mice. NOD2 activation also accelerates platelet-dependent hemostasis. We further found that platelets express RIP2 (receptor-interacting protein 2), and provided evidences suggesting that MAPK and NO/sGC/cGMP/PGK pathways downstream of RIP2 mediate the role of NOD2 in platelets. Finally, MDP stimulates proinflammatory cytokine IL-1β maturation and accumulation in human and mouse platelets NOD2-dependently. Conclusions NOD2 is expressed in platelets and functions in platelet activation and arterial thrombosis, possibly during infection. To our knowledge, this is the first study on NOD-like receptors in platelets which links thrombotic events to inflammation. PMID:25825396

The influence of platelets, plasma and red blood cells on functional haemostatic assays.

PubMed

Bochsen, Louise; Johansson, Pär I; Kristensen, Annemarie T; Daugaard, Gedske; Ostrowski, Sisse R

2011-04-01

Functional whole blood haemostatic assays are used increasingly to guide transfusion therapy and monitor medical treatment and are also applied for in-vitro evaluations of the haemostatic potential of stored platelets. We investigated how the cellular and plasmatic elements, both isolated and combined, influenced the two methodologically different assays, thrombelastography (TEG) and impedance aggregometry (Multiplate). Platelet-rich plasma (200 × 10/l) or pure plasma (0 platelets), with and without added red blood cells (RBCs), hematocrit 0, 0.15 or 0.29, were produced in vitro from platelet concentrates, fresh frozen plasma and stored RBC. Pure platelets were investigated by removing plasma components from platelet concentrates by diafiltration against the platelet storage solution Intersol. Plasma was readded by diafiltration against plasma in Intersol. Haemostatic function was evaluated by TEG and Multiplate. In the TEG, increasing amounts of RBC reduced clot strength and clot kinetics (α-angle), most markedly in plasma/RBC without platelets. In contrast, RBC in a platelet concentrate matrix enhanced Multiplate aggregation in response to weak agonists (ADP and arachidonic acid). Furthermore, removing plasma from platelet concentrates eliminated the TEG response and diminished the Multiplate aggregation response, but readding plasma to the pure platelet concentrates restored the response. Each of the elements in whole blood, plasma, platelets and RBC, affected the Multiplate and TEG results differently. The results emphasize that the concentrations of all cellular and plasmatic components in whole blood should be taken into account when interpreting results obtained by TEG and multiplate.

Lea blood group antigen on human platelets.

PubMed

Dunstan, R A; Simpson, M B; Rosse, W F

1985-01-01

One- and two-stage radioligand assays were used to determine if human platelets possess the Lea antigen. Goat IgG anti-Lea antibody was purified by multiple adsorptions with Le(a-b-) human red blood cells, followed by affinity chromatography with synthetic Lea substance and labeling with 125I. Human IgG anti-Lea antibody was used either in a two stage radioassay with 125I-labeled mouse monoclonal IgG anti-human IgG as the second antibody or, alternatively, purified by Staph protein A chromatography, labeled with 125I, and used in a one-stage radioassay. Platelets from donors of appropriate red blood cell phenotypes were incubated with the antisera, centrifuged through phthalate esters, and assayed in a gamma scintillation counter. Dose response and saturation curve analysis demonstrate the presence of Lewis a antigen on platelets from Lea+ donors. Furthermore, platelets from an Le(a-b-) donor incubated in Le (a+b-) plasma adsorb Lea antigen in a similar manner to red blood cells. The clinical significance of these antigens in platelet transfusion remains undefined.

Changes in blood product utilization in a seven-hospital system after the implementation of a patient blood management program: A 9-year follow-up.

PubMed

Verdecchia, Nicole M; Wisniewski, Mary Kay; Waters, Jonathan H; Triulzi, Darrell J; Alarcon, Louis H; Yazer, Mark H

2016-09-01

To analyze changes in red blood cell (RBC), platelet (PLT), and plasma transfusion volumes 9 years after the implementation of a multifaceted patient blood management (PBM) program across multiple hospitals. Between fiscal years 2007 and 2015, the annual transfusion volumes for seven hospitals in a regional healthcare system were analyzed by hospital, and between 2014 and 2015, by four service lines including emergency department, intensive care unit (ICU), medical/surgical ward, and operating room at each hospital. The number of units of RBCs administered to transfused recipients on the wards and in ICUs was also enumerated. For these seven hospitals combined, there was a 29.9% reduction in the number of RBCs transfused between 2007 and 2015, a 24.8% reduction in plasma units, and a 25.7% reduction in PLT units. The two largest hospitals saw some of the largest reductions in RBC transfusions (40.1, 25.1%), and plasma transfusions (26.1, 33.8%), and one of those hospitals had a 49.5% reduction in PLT transfusions. Smaller-sized hospitals also had reductions in transfusion volumes, while some volumes increased at hospitals when new or expanded clinical services were introduced. The number of RBC units per transfused recipient was generally between 1.5 and 2 units on the wards and slightly higher in the ICUs. Although the overall volume of transfusions has generally decreased at each hospital site over time, the appropriateness of the administered transfusions cannot be evaluated by these data. The system-wide implementation of a PBM program has reduced transfusion volumes.

Neonatal alloimmune thrombocytopenia due to anti-human leukocyte antigen antibody: a case report.

PubMed

Sasaki, M; Yagihashi, A; Kobayashi, D; Watanabe, N; Fujikawa, T; Chiba, S; Sato, S; Morishita, K; Sekimoto, T; Ikeda, H

2001-12-01

Anti-HLA antibodies reportedly exist in 31% of pregnant women. However, few ocurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibody have been reported. In this study, maternal anti-HLA B60 and B61 antibodies were identified in patient serum at birth, but no anti-platelet antibodies were present. No maternal anti-HLA A2, A24, B51, or B52 antibodies were detected in patient serum. Platelet transfusion from the third donor was effective because these platelets expressed HLA A24 and B52 but not B60 or B61. Cross-matching tests between patient leukocytes or platelets and maternal serum were strongly positive, indicating that maternal anti-HLA antibodies were responsible for NAIT. This report is the first to demonstrate NAIT probably caused by maternal anti-HLA A24 and B52.

The impact of oral arsenic and all-trans-retinoic acid on coagulopathy in acute promyelocytic leukemia.

PubMed

Zhu, Hong-Hu; Guo, Zhi-Ping; Jia, Jin-Song; Jiang, Qian; Jiang, Hao; Huang, Xiao-Jun

2018-02-01

The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4mg/m 2 per day for 5-7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n=45) or with ATO (n=38). Since induction therapy with RIF and ATRA, the median levels of Fbg, PT and platelets were recovered to the normal range within 4days, 10days and 28days, respectively. The last day of platelet and plasma transfusion was day 12 (range: 0-24 days) and day 3 (range: 0-27 days), respectively. Among the 42 patients with a disseminated intravascular coagulation (DIC) score=4, the consumption of transfused platelets was less in the RIF group than that in the ATO group (P=0.037). In the 17 patients with a DIC score <4, prompt recovery of Fbg levels (P=0.028) was observed in the RIF group compared with that in the ATO group (P=0.401). RIF and ATO showed similar effects on the recovery of coagulopathy in APL patients. RIF had a potential beneficial effect in accelerating the recovery of thrombocytopenia and hypofibrinogenemia for subclinical DIC patients. Copyright © 2017. Published by Elsevier Ltd.

Platelet granule release is associated with reactive oxygen species generation during platelet storage: A direct link between platelet pro-inflammatory and oxidation states.

PubMed

Ghasemzadeh, Mehran; Hosseini, Ehteramolsadat

2017-08-01

Upon platelet stimulation with agonists, reactive oxygen species (ROS) generation enhances platelet activation and granule release. Whether ROS generation during platelet storage could be directly correlated with the expression of proinflammatory molecules and granule release has been investigated in this study. PRP-platelet concentrates were subjected to flowcytometry analysis to assess the expression of platelet activation marker, P-selectin and CD40L during storage. Intracellular ROS generation was also detected in platelet by flowcytometry using dihydrorhodamine (DHR) 123. Through the dual staining, ROS production was analyzed in either P-selectin positive or negative populations. ROS formation in platelet population was significantly increased by either TRAP (a potent agonist that induces granule release) or PMA (a classic inducer of ROS generation), while the effects of each agonists on P-selectin expression and ROS generation in platelets were comparable. Platelet storage was also associated with the increasing levels of ROS (day 0 vs. day 5; p<0.001) while this increasing pattern was directly correlated with the either expressed P-selectin or CD40L. In addition, in 5 day-stored platelets, samples with ROS levels above 40% showed significantly higher levels of P-selectin and CD40L expression. P-selectin negative population of platelet did not show significant amount of ROS. Our data demonstrated decreased levels of important platelet pro-inflammatory molecules in stored platelets with lower levels of intraplatelet ROS. However, whether quenching of ROS generation during platelet storage can attenuate adverse transfusion reactions raised by platelet pro-inflammatory status is required to be further studied. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development and validation of a predictive score for perioperative transfusion in patients with hepatocellular carcinoma undergoing liver resection.

PubMed

Wang, Hai-Qing; Yang, Jian; Yang, Jia-Yin; Wang, Wen-Tao; Yan, Lu-Nan

2015-08-01

Liver resection is a major surgery requiring perioperative blood transfusion. Predicting the need for blood transfusion for patients undergoing liver resection is of great importance. The present study aimed to develop and validate a model for predicting transfusion requirement in HBV-related hepatocellular carcinoma patients undergoing liver resection. A total of 1543 consecutive liver resections were included in the study. Randomly selected sample set of 1080 cases (70% of the study cohort) were used to develop a predictive score for transfusion requirement and the remaining 30% (n=463) was used to validate the score. Based on the preoperative and predictable intraoperative parameters, logistic regression was used to identify risk factors and to create an integer score for the prediction of transfusion requirement. Extrahepatic procedure, major liver resection, hemoglobin level and platelets count were identified as independent predictors for transfusion requirement by logistic regression analysis. A score system integrating these 4 factors was stratified into three groups which could predict the risk of transfusion, with a rate of 11.4%, 24.7% and 57.4% for low, moderate and high risk, respectively. The prediction model appeared accurate with good discriminatory abilities, generating an area under the receiver operating characteristic curve of 0.736 in the development set and 0.709 in the validation set. We have developed and validated an integer-based risk score to predict perioperative transfusion for patients undergoing liver resection in a high-volume surgical center. This score allows identifying patients at a high risk and may alter transfusion practices.

Transfusion-related alloimmune neutropenia with no pulmonary complications: one donor-five cases.

PubMed

Hauck-Dlimi, Barbara; Ruppel, Renate; Zimmermann, Robert; Strobel, Julian; Reil, Angelika; Eckstein, Reinhold; Zingsem, Juergen

2016-01-01

Neutrophil alloantibodies are well-known triggers of transfusion-related acute lung injury (TRALI) and also cause immune neutropenia. Alloimmune neutropenia due to transfusion is an isolated phenomenon that is only rarely identified. Its incidence is specified in the literature as being less than one in 10,000 transfused plasma-containing units. We expect that this phenomenon is underreported. We observed five cases of alloimmune neutropenia with no respiratory complications with only one case initially reported as a suspected transfusion reaction. The other four cases were detected in the course of the subsequent lookback investigation. The first case was reported as a potential transfusion reaction when a female patient showed a decrease in the white blood cell count after a platelet (PLT) transfusion. Examinations of the donor blood revealed an antibody against the human neutrophil antigen HNA-1b; the recipient was typed HNA-1b positive and HNA-1a negative. After examining the blood counts of other patients who previously received PLT concentrates from the same donor, we identified four other patients with an unreported decrease in the leukocyte and/or granulocyte count of more than approximately 50% after transfusion. HNA antibodies are generally regarded as potential triggers of TRALI. Here we describe an HNA antibody that reproducibly caused transfusion-related neutropenia only without pulmonary complications. Factors predisposing patients to TRALI development are widely discussed. Our case suggests that antibody characteristics are also relevant in the development of TRALI. Current measures to prevent TRALI should also prevent transfusion-related alloimmune neutropenia. © 2015 AABB.

Prophylactic platelet transfusions in patients with blood malignancies: cost analysis of a randomized trial.

PubMed

Campbell, Helen E; Estcourt, Lise J; Stokes, Elizabeth A; Llewelyn, Charlotte A; Murphy, Michael F; Wood, Erica M; Stanworth, Simon J

2014-10-01

This cost analysis uses data from a randomized trial comparing a no prophylaxis versus prophylactic platelet (PLT) transfusion policy (counts <10 × 10(9) /L) in adult patients with hematologic malignancies. Results are presented for all patients and separately for autologous hematopoietic stem cell transplantation (HSCT) (autoHSCT) and chemotherapy/allogeneic HSCT (chemo/alloHSCT) patients. Data were collected to 30 days on PLT and red blood cell (RBC) transfusions, major bleeds, serious adverse events, critical care, and hematology ward stay. Data were costed using 2011 to 2012 UK unit costs and converted into US$. Sensitivity analyses were performed on uncertain cost variables. Across the whole trial no prophylaxis saved costs compared to prophylaxis: -$1760 per patient (95% confidence interval [CI], -$3250 to -$249; p < 0.05). For autoHSCT patients there was no cost difference between arms: -$110 per patient (95% CI, -$1648 to $1565; p = 0.89). For chemo/alloHSCT patients no prophylaxis cost significantly less than prophylaxis: -$5686 per patient (95% CI, -$8580 to -$2853; p < 0.01). The cost impact of no prophylaxis differed significantly between subgroups. Sensitivity analyses varying daily treatment costs and ward stay for chemo/alloHSCT patients reduced cost differences to -$941 per patient (p = 0.21) across the whole trial and -$2927 per patient (p < 0.05) in chemo/alloHSCT subgroup. It is unclear whether a no-prophylaxis policy saves costs overall. In chemo/alloHSCT patients cost savings are apparent but their magnitude is sensitive to a number of variables and must be considered alongside clinical data showing increased bleeding rates. In autoHSCT patients savings generated through lower PLT use in no-prophylaxis arm were offset by cost increases elsewhere, for example, additional RBC transfusions. Cost-effectiveness analyses of alternative PLT transfusion policies simultaneously considering costs and patient-reported outcomes are warranted. © 2014 AABB.

Noninvasive pH monitoring of platelet concentrates: a large field test.

PubMed

Gkoumassi, Effimia; Klein-Bosgoed, Christa; Dijkstra-Tiekstra, Margriet J; de Korte, Dirk; de Wildt-Eggen, Janny

2013-10-01

Developing new quality control methods for platelet concentrates (PCs) can contribute to increasing transfusion safety and efficiency. The aim of this study was to investigate in a large field test the quality of expired PCs and whether 100% noninvasive pH monitoring can be used to predict PC quality. The pH of 13,693 PCs produced for transfusion was monitored daily using Blood Storage, Inc.'s pH sterile, automated fluoroscopic evaluation technology. Upon indication of compromised quality or expiration, PCs were returned and in vitro tests were performed. A total of 998 PCs were returned, of which 962 outdated, 26 had a positive BacT/ALERT reaction, seven had aggregates, one was without swirl, one had low pH, and one had high pH. BacT/ALERT was faster in identifying bacterial contamination than pH measurements. The pH at the end of the storage period was significantly lower than at the beginning. In vitro tests indicated that while the PC quality was acceptable upon expiration, it rapidly declined after expiration. In this setting where the vast majority of PCs were of good quality and within acceptable pH limits, daily, noninvasive routine pH measurement has limited added value in identifying quality-compromised PCs. © 2013 Sanquin Research. Transfusion © 2013 American Association of Blood Banks.

Point-of-Care Coagulation Monitoring in Trauma Patients.

PubMed

Stein, Philipp; Kaserer, Alexander; Spahn, Gabriela H; Spahn, Donat R

2017-06-01

Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-directed way based on point-of-care (POC) and routine laboratory measurements. Viscoelastic POC measurement of the developing clot in whole blood and POC platelet function testing allow rapid and tailored coagulation and transfusion treatment based on goal-directed, factor concentrate-based algorithms. The first studies have been published showing that this concept reduces the need for allogeneic blood transfusion and improves outcome. This review highlights the concept of goal-directed POC coagulation management in trauma patients, introduces a selection of POC devices, and presents algorithms which allow a reduction in allogeneic blood product transfusion and an improvement of trauma patient outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Deletion of Crry and DAF on murine platelets stimulates thrombopoiesis and increases factor H-dependent resistance of peripheral platelets to complement attack.

PubMed

Barata, Lidia; Miwa, Takashi; Sato, Sayaka; Kim, David; Mohammed, Imran; Song, Wen-Chao

2013-03-15

Complement receptor 1-related gene/protein y (Crry) and decay-accelerating factor (DAF) are two murine membrane C3 complement regulators with overlapping functions. Crry deletion is embryonically lethal whereas DAF-deficient mice are generally healthy. Crry(-/-)DAF(-/-) mice were viable on a C3(-/-) background, but platelets from such mice were rapidly destroyed when transfused into C3-sufficient mice. In this study, we used the cre-lox system to delete platelet Crry in DAF(-/-) mice and studied Crry/DAF-deficient platelet development in vivo. Rather than displaying thrombocytopenia, Pf4-Cre(+)-Crry(flox/flox) mice had normal platelet counts and their peripheral platelets were resistant to complement attack. However, chimera mice generated with Pf4-Cre(+)-Crry(flox/flox) bone marrows showed platelets from C3(-/-) but not C3(+/+) recipients to be sensitive to complement activation, suggesting that circulating platelets in Pf4-Cre(+)-Crry(flox/flox) mice were naturally selected in a complement-sufficient environment. Notably, Pf4-Cre(+)-Crry(flox/flox) mouse platelets became complement susceptible when factor H function was blocked. Examination of Pf4-Cre(+)-Crry(flox/flox) mouse bone marrows revealed exceedingly active thrombopoiesis. Thus, under in vivo conditions, Crry/DAF deficiency on platelets led to abnormal platelet turnover, but peripheral platelet count was compensated for by increased thrombopoiesis. Selective survival of Crry/DAF-deficient platelets aided by factor H protection and compensatory thrombopoiesis demonstrates the cooperation between membrane and fluid phase complement inhibitors and the body's ability to adaptively respond to complement regulator deficiencies.

The effect of blood transfusion on pulmonary permeability in cardiac surgery patients: a prospective multicenter cohort study.

PubMed

Vlaar, Alexander P J; Cornet, Alexander D; Hofstra, Jorrit J; Porcelijn, Leendert; Beishuizen, Albertus; Kulik, Willem; Vroom, Margreeth B; Schultz, Marcus J; Groeneveld, A B Johan; Juffermans, Nicole P

2012-01-01

There is an association between blood transfusion and pulmonary complications in cardiac surgery. Mediators of increased pulmonary vascular leakage after transfusion are unknown. We hypothesized that factors may include antibodies or bioactive lipids, which have been implicated in transfusion-related acute lung injury. We performed a prospective cohort study in two university hospital intensive care units in the Netherlands. Pulmonary vascular permeability was measured in cardiac surgery patients after receiving no, restrictive (one or two transfusions), or multiple (five or more transfusions) transfusions (n=20 per group). The pulmonary leak index (PLI), using (67) Ga-labeled transferrin, was determined within 3 hours postoperatively. Blood products were screened for bioactive lipid accumulation and the presence of antibodies. The PLI was elevated in all groups after cardiac surgery. Transfused patients had a higher PLI compared to nontransfused patients (33×10(-3) ± 20×10(-3) vs. 23×10(-3) ± 11×10(-3)/min, p<0.01). The amount of red blood cell (RBC) products, but not of fresh-frozen plasma or platelets, was associated with an increase in PLI (β, 1.6 [0.2-3.0]). Concerning causative factors in the blood product, neither the level of bioactive lipids nor the presence of antibodies was associated with an increase in PLI. Patient factors such as surgery risk and time on cardiopulmonary bypass did not influence the risk of pulmonary leakage after blood transfusion. Transfusion in cardiothoracic surgery patients is associated with an increase in pulmonary capillary permeability, an effect that was dose dependent for RBC products. The level of bioactive lipids or the presence of HLA or HNA antibodies in the transfused products were not associated with increased pulmonary capillary permeability. © 2011 American Association of Blood Banks.

Blood products use in France: a nationwide cross-sectional survey.

PubMed

Fillet, Anne-Marie; Desmarets, Maxime; Assari, Suzanne; Quaranta, Jean-François; François, Anne; Pugin, Aurore; Schuhmacher, Anne; Lassale, Bernard; Monnet, Elisabeth; Cabre, Philippe; Legrand, Dominique; Binda, Delphine; Djoudi, Rachid

2016-12-01

Blood products use has increased in France between 2000 and 2011. To understand the reasons for this increase, data about transfused patients and transfusion practices needed to be updated. A nationwide cross-sectional survey was performed with health care establishments. Diagnoses and indication for the transfusion, pretransfusion laboratory results, and blood products used were collected during a randomly selected 24-hour period in 2011. All patients who received at least one blood product delivered on the survey day were included. A total of 10,794 blood products were requested for 4720 patients: 8688 red blood cell (RBC) units, 842 platelet (PLT) concentrates, and 1264 fresh-frozen plasma (FFP) units. Hematologic and cancer pathologies included 46% of transfused patients, 34% of the patients had transfusions in a surgical context, and 32.4% of transfused patients were receiving medication with an impact on transfusion. Nearly half of RBC transfusions were performed with hemoglobin levels of less than 8 g/dL. PLT transfusions for prophylactic indication were prescribed with PLT counts of less than 20 × 10 9 and 50 × 10 9 /L in 56.9 and 86.6% of patients, respectively. RBCs and PLTs transfusion practices were in agreement with national guidelines. FFP units were involved in 8.0% of all prescriptions. Among these, 57.4% were requested in the context of an acute hemorrhage and 8.4% for plasma exchange. The median of FFP use (n = 2) in a nonsurgical context, excluding plasma exchange, suggests an insufficient dosing of FFP. Except for insufficient FFP dosing per patient and limitations on assessment of indications for prescribing, transfusion practices were in agreement with national guidelines. © 2016 AABB.

Addressing the risk of bacterial contamination in platelets: a hospital economic perspective.

PubMed

Li, Justin W; Brecher, Mark E; Jacobson, Jessica L; Harm, Sarah K; Chen, Dorothy; El-Gamil, Audrey; Dobson, Al; Mintz, Paul D

2017-10-01

Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood. We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical). Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03). The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

Initial blood storage experiment

NASA Technical Reports Server (NTRS)

Surgenor, Douglas MACN.

1988-01-01

The possibility of conducting experiments with the formed elements of the blood under conditions of microgravity opens up important opportunities to improve the understanding of basic formed element physiology, as well as, contribution to improved preservation of the formed elements for use in transfusion. The physiological, biochemical, and physical changes of the membrane of the erythrocyte, platelet, and leukocyte was studied during storage under two specific conditions: standard blood bank conditions and microgravity, utilizing three FDA approved plastic bags. Storage lesions; red cell storage on Earth; platelet storage on Earth; and leukocyte storage Earth were examined. The interaction of biomaterials and blood cells was studied during storage.

A Case Report of Drug-Induced Thrombocytopenia after Living Donor Liver Transplantation

PubMed Central

ARAI, KEISUKE; KURAMITSU, KAORI; FUKUMOTO, TAKUMI; KIDO, MASAHIRO; TAKEBE, ATSUSHI; TANAKA, MOTOFUMI; KINOSHITA, HISOKA; AJIKI, TETSUO; TOYAMA, HIROCHIKA; ASARI, SADAKI; GOTO, TADAHIRO; KU, YONSON

2016-01-01

There are few descriptions of severe thrombocytopenia during the early postoperative period after liver transplantation, and these have not been fully documented in the literature. Here, we report a case of drug-induced thrombocytopenia requiring transfusion of blood products after living donor liver transplantation. We determined that this was not caused by the interferon-free anti-viral therapy but by tacrolimus A 61-year-old woman with hepatitis C-related cirrhosis and hepatorenal syndrome underwent living donor liver transplantation using a left lobe graft from her son. After transplantation, immunosuppression consisted of tacrolimus and steroid. Seven weeks after transplantation, interferon-free therapy with daclatasvir and asunaprevir was started. Thirteen days thereafter, hepatitis C virus tested negative. However, the platelet count had begun to gradually decrease just before starting anti-viral therapy. Daclatasvir and asunaprevir were stopped because this was suspected to be a side-effect of these drugs, but the patient nonetheless went on to develop severe thrombocytopenia (platelet count 17,000/μL), which needed transfusions. Now suspecting tacrolimus as the inducer of this side effect, we changed to cyclosporin, after which the platelet count gradually recovered. Viral markers were still not detectable up to 2 months after discontinuation of the antiviral drugs. We conclude that when severe thrombocytopenia occurs, possible drug-induced thrombocytopenia as well as other disorders must be investigated. PMID:27492209

Blood donation and blood transfusion in Spain (1997 - 2007): the effects of demographic changes and universal leucoreduction.

PubMed

García-Erce, José Antonio; Campos, Arturo; Muñoz, Manuel

2010-04-01

As epidemiological information is useful in planning the provision and assessing the efficiency of product use, we reviewed Spanish data on population, blood donation and blood component transfusion from 1997 to 2007, and the possible effect of universal leucoreduction. Data on the Spanish population were obtained from the National Institute of Statistics, whereas data on blood donation and blood component transfusion were acquired from the Spanish Ministry of Health. During the study period, the Spanish population increased by 5.6 million persons (14.4%), and blood donation by 28.1%, although the amount of red blood cells (RBC) obtained increased by only 21.5% whereas RBC transfusions increased by 28.3%. The RBC transfusion rate was significantly higher after the implementation of universal leucoreduction (2002 - 2006) than during the pre-leucoreduction period (1997 - 2001) (difference = 2.54 units/1,000 population/year; 95%CI 1.81 - 3.27; P<0.001). We also observed statistical ly, but not clinically, significant differences for platelet and plasma transfusions. The increase observed in the RBC transfusion index after implementation of universal leucoreduction may have been due to a reduction of the haemoglobin content in the RBC units. Our data on blood use do, therefore, seem to add to the case against universal leucoreduction, which has led to an incremental cost for unknown, but probably slight, benefits for patients.

Prognostic Significance of Blood Transfusion in Newly Diagnosed Multiple Myeloma Patients without Autologous Hematopoietic Stem Cell Transplantation

PubMed Central

Fan, Liping; Fu, Danhui; Zhang, Jinping; Wang, Qingqing; Ye, Yamei; Xie, Qianling

2017-01-01

The aim of this study was to evaluate whether blood transfusions affect overall survival (OS) and progression-free survival (PFS) in newly diagnosed multiple myeloma (MM) patients without hematopoietic stem cell transplantation. A total of 181 patients were enrolled and divided into two groups: 68 patients in the transfused group and 113 patients in the nontransfused group. Statistical analyses showed that there were significant differences in ECOG scoring, Ig isotype, platelet (Plt) counts, hemoglobin (Hb) level, serum creatinine (Scr) level, and β2-microglobulin (β2-MG) level between the two groups. Univariate analyses showed that higher International Staging System staging, Plt counts < 100 × 109/L, Scr level ≥ 177 μmol/L, serum β2-MG ≥ 5.5 μmol/L, serum calcium (Ca) ≥ 2.75 mmol/L, and thalidomide use were associated with both OS and PFS in MM patients. Age ≥ 60 was associated with OS and Ig isotype was associated with PFS in MM patients. Moreover, blood transfusion was associated with PFS but not OS in MM patients. Multivariate analyses showed that blood transfusion was not an independent factor for PFS in MM patients. Our preliminary results suggested that newly diagnosed MM patients may benefit from a liberal blood transfusion strategy, since blood transfusion is not an independent impact factor for survival. PMID:28567420

Coagulation management in trauma-associated coagulopathy: allogenic blood products versus coagulation factor concentrates in trauma care.

PubMed

Klages, Matthias; Zacharowski, Kai; Weber, Christian Friedrich

2016-04-01

Coagulation management by transfusion of allogenic blood products and coagulation factors are competing concepts in current trauma care. Rapid and adequate therapy of trauma-associated coagulopathy is crucial to survival of severely injured patients. Standard coagulation tests such as prothrombin time and activated partial thromboplastin time are commonly used, but these tests are inappropriate for monitoring and guiding therapy in trauma patients. Coagulation factor-based treatment showed promising results, but randomized trials have not yet been performed. In addition, viscoelastic tests are needed to guide therapy, although there is in fact limited evidence for these in tests in trauma care. Regarding transfusion therapy with allogenic blood products, plasma transfusion has been associated with improved survival in trauma patients following massive transfusion. In contrast, patients not requiring massive transfusion seem to be at risk for suffering complications with increasing volumes of plasma transfused. The collective of trauma patients is heterogeneous. Despite the lack of evidence, there are strong arguments for individualized patient treatment with coagulation factors for some indications and to abstain from the use of fresh frozen plasma. In patients with severe trauma and major bleeding, plasma, platelets, and red blood cells should be considered to be administered at a ratio of 1 : 1 : 1.

Massive transfusion and nonsurgical hemostatic agents.

PubMed

Perkins, Jeremy G; Cap, Andrew P; Weiss, Brendan M; Reid, Thomas J; Bolan, Charles D; Bolan, Charles E

2008-07-01

Hemorrhage in trauma is a significant challenge, accounting for 30% to 40% of all fatalities, second only to central nervous system injury as a cause of death. However, hemorrhagic death is the leading preventable cause of mortality in combat casualties and typically occurs within 6 to 24 hrs of injury. In cases of severe hemorrhage, massive transfusion may be required to replace more than the entire blood volume. Early prediction of massive transfusion requirements, using clinical and laboratory parameters, combined with aggressive management of hemorrhage by surgical and nonsurgical means, has significant potential to reduce early mortality. Although the classification of massive transfusion varies, the most frequently used definition is ten or more units of blood in 24 hrs. Transfusion of red blood cells is intended to restore blood volume, tissue perfusion, and oxygen-carrying capacity; platelets, plasma, and cryoprecipitate are intended to facilitate hemostasis through prevention or treatment of coagulopathy. Massive transfusion is uncommon in civilian trauma, occurring in only 1% to 3% of trauma admissions. As a result of a higher proportion of penetrating injury in combat casualties, it has occurred in approximately 8% of Operation Iraqi Freedom admissions and in as many as 16% during the Vietnam conflict. Despite its potential to reduce early mortality, massive transfusion is not without risk. It requires extensive blood-banking resources and is associated with high mortality. This review describes the clinical problems associated with massive transfusion and surveys the nonsurgical management of hemorrhage, including transfusion of blood products, use of hemostatic bandages/agents, and treatment with hemostatic medications.

Accurate costs of blood transfusion: a microcosting of administering blood products in the United Kingdom National Health Service.

PubMed

Stokes, Elizabeth A; Wordsworth, Sarah; Staves, Julie; Mundy, Nicola; Skelly, Jane; Radford, Kelly; Stanworth, Simon J

2018-04-01

In an environment of limited health care resources, it is crucial for health care systems which provide blood transfusion to have accurate and comprehensive information on the costs of transfusion, incorporating not only the costs of blood products, but also their administration. Unfortunately, in many countries accurate costs for administering blood are not available. Our study aimed to generate comprehensive estimates of the costs of administering transfusions for the UK National Health Service. A detailed microcosting study was used to cost two key inputs into transfusion: transfusion laboratory and nursing inputs. For each input, data collection forms were developed to capture staff time, equipment, and consumables associated with each step in the transfusion process. Costing results were combined with costs of blood product wastage to calculate the cost per unit transfused, separately for different blood products. Data were collected in 2014/15 British pounds and converted to US dollars. A total of 438 data collection forms were completed by 74 staff. The cost of administering blood was $71 (£49) per unit for red blood cells, $84 (£58) for platelets, $55 (£38) for fresh-frozen plasma, and $72 (£49) for cryoprecipitate. Blood administration costs add substantially to the costs of the blood products themselves. These are frequently incurred costs; applying estimates to the blood components supplied to UK hospitals in 2015, the annual cost of blood administration, excluding blood products, exceeds $175 (£120) million. These results provide more accurate estimates of the total costs of transfusion than those previously available. © 2018 AABB.

Management of Platelet Transfusion Therapy in Patients With Blood Cancer or Treatment-Induced Thrombocytopenia

ClinicalTrials.gov

2018-02-15

Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; B-Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematologic and Lymphocytic Disorder; Hematopoietic Cell Transplantation Recipient; Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Myelofibrosis; T-Cell Non-Hodgkin Lymphoma; Thrombocytopenia; Venous Thromboembolism

Spore-forming organisms in platelet concentrates: a challenge in transfusion bacterial safety.

PubMed

Störmer, M; Vollmer, T; Kleesiek, K; Dreier, J

2008-12-01

Bacterial detection and pathogen reduction are widely used methods of minimizing the risk of transfusion-transmitted bacterial infection. But, bacterial spores are highly resistant to chemical and physical agents. In this study, we assessed the bacterial proliferation of spore-forming organisms seeded into platelet concentrates (PCs) to demonstrate that spores can enter the vegetative state in PCs during storage. In the in vitro study, PCs were inoculated with 1-10 spores mL(-1)of Bacillus cereus (n = 1), Bacillus subtilis (n = 2) and Clostridium sporogenes (n = 2). Sampling was performed during 6-day aerobic storage at 22 degrees C. The presence of bacteria was assessed by plating culture, automated culture and real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Spores of the C. sporogenes do not enter the vegetative phase under PC storage conditions, whereas B. subtilis and B. cereus showed growth in the PC and could be detected using RT-PCR and automated culture. Depending on the species and inoculums, bacterial spores may enter the vegetative phase during PC storage and can be detected by bacterial detection methods.

Individualized strategy for clopidogrel suspension in patients undergoing off-pump coronary surgery for acute coronary syndrome: a case-control study.

PubMed

Mannacio, Vito; Meier, Pascal; Antignano, Anita; Di Tommaso, Luigi; De Amicis, Vincenzo; Vosa, Carlo

2014-10-01

An increasing number of patients presenting for urgent coronary surgery have been exposed to clopidogrel, which constitutes a risk of bleeding and related events. Based on the wide variability in clopidogrel response and platelet function recovery after cessation, we evaluated the role of point-of-care platelet function testing to define the optimal time for off-pump coronary artery bypass graft (CABG) surgery in a case-control study. Three equally matched groups (300 patients in total) undergoing isolated off-pump CABG for acute coronary syndrome were compared. Group A were treated with clopidogrel and prospectively underwent a strategy guided by platelet function testing. Outcomes were compared with 2 propensity score matched groups: group B underwent CABG after the currently recommended 5 days without clopidogrel; group C were never exposed to clopidogrel. Patients in group A had reduced postoperative bleeding compared with those in group B (523±202 mL vs 851±605 mL; P<.001) and a lower number of units packed red blood cells (PRBCs) transfused during the postoperative hospital stay (1.2±1.6 units vs 1.9±1.8 units; P=.004). Postoperative bleeding and the number of units of PRBCs transfused were similar in group A and group C. There was no difference in blood-derived products and platelet consumption, mortality, or the need for reoperation among the groups. Patients in group A waited 3.6±1.7 days for surgery. The strategy used for group A saved 280 days of hospital stay in total. The strategy guided by platelet function testing for off-pump CABG offers improved guidance for optimal timing of CABG in patients treated with clopidogrel. This strategy significantly reduces postoperative bleeding and blood consumption, and has a shorter waiting time for surgery than current clinical practice. Copyright © 2014 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Effect of leukapheresis on blood coagulation in patients with hyperleukocytic acute myeloid leukemia.

PubMed

Van de Louw, Andry

2017-04-01

Leukapheresis has been proposed to reduce white blood cell (WBC) count in hyperleukocytic acute myeloid leukemia (AML). However, no survival benefit has been proven and leukapheresis can potentially affect coagulation and worsen bleeding and disseminated intravascular coagulation (DIC). We analyzed the effect of leukapheresis on coagulation tests in a cohort of hyperleukocytic AML patients. Retrospective chart review of hyperleukocytic AML patients who underwent leukapheresis between 2003 and 2014. Blood coagulation tests (platelets, PT, INR, aPTT, fibrinogen, D-Dimers and fibrin degradation products (FDP)) were collected before and after each procedure and DIC score was computed. Transfusions of platelets and coagulation factors were collected. Ninety patients and 129 leukapheresis sessions were screened. After exclusion of the sessions associated with transfusions, we observed in 44 patients a significant decrease in platelets (from 75.69±89.48 to 44.59±47.71.10 9 /L, p=0.001) and fibrinogen (from 4.05±1.29 to 3.35±1.37g/L, p<0.0005) along with an increase in PT (from 14.62±2.73 to 15.62±3.63s, p=0.001), aPTT (from 33.70±6.32 to 39.24±13.53s, p=0.009) and INR (from 1.33±0.2 to 1.45±0.34, p=0.002) after the first procedure. Bleeding complications, all intracerebral hemorrhages, were documented in 3 patients within 24h of leukapheresis. After combining 73 repeat procedures, we observed similar significant results except for the aPTT prolongation. The platelets and PT components of the DIC score, but not the fibrinogen component, were significantly increased after leukapheresis. In hyperleukocytic AML patients, leukapheresis is associated with clinically significant decreases in platelets and fibrinogen and prolonged clotting times. Copyright © 2016 Elsevier Ltd. All rights reserved.

Implementation of a patient blood management monitoring and feedback program significantly reduces transfusions and costs.

PubMed

Mehra, Tarun; Seifert, Burkhardt; Bravo-Reiter, Silvina; Wanner, Guido; Dutkowski, Philipp; Holubec, Tomas; Moos, Rudolf M; Volbracht, Jörk; Manz, Markus G; Spahn, Donat R

2015-12-01

Patient blood management (PBM) measures have been shown to be effective in reducing transfusions while maintaining patient outcome. The issuance of transfusion guidelines is seen as being key to the success of PBM programs. As the introduction of guidelines alone did not visibly reduce transfusions in our center, a monitoring and feedback program was established. The aim of our study was to show the effectiveness of such measures in reducing transfusions and cost. We designed a prospective, interventional cohort study with a 3-year time frame (January 1, 2012 to December 31, 2014). In total, 101,794 patients aged 18 years or older were included. The PBM monitoring and feedback program was introduced on January 1, 2014, with the subsequent issuance of quarterly reporting. Within the first year of introduction, transfusion of all allogeneic blood products per 1000 patients was reduced by 27% (red blood cell units, -24%; platelet units, -25%; and fresh-frozen plasma units, -37%; all p < 0.001) leading to direct allogeneic blood product related savings of more than 2 million USD. The number of blood products transfused per case was significantly reduced from 9 ± 19 to 7 ± 14 (p < 0.001). With an odds ratio of 0.86 (95% confidence interval, 0.82-0.91), the introduction of our PBM monitoring and feedback program was a significant independent factor in the reduction of transfusion probability (p < 0.001). Our PBM monitoring and feedback program was highly efficacious in reducing the transfusion of allogeneic blood products and transfusion-related costs. © 2015 AABB.

[Transfusion supply optimization in multiple-discipline surgical hospital].

PubMed

Solov'eva, I N; Trekova, N A; Krapivkin, I A

2016-01-01

To define optimal variant of transfusion supply of hospital by blood components and to decrease donor blood expense via application of blood preserving technologies. Donor blood components expense, volume of hemotransfusions and their proportion for the period 2012-2014 were analyzed. Number of recipients of packed red cells, fresh-frozen plasma and packed platelets reduced 18.5%, 25% and 80% respectively. Need for donor plasma decreased 35%. Expense of autologous plasma in cardiac surgery was 76% of overall volume. Preoperative plasma sampling is introduced in patients with aortic aneurysm. Number of cardiac interventions performed without donor blood is increased 7-31% depending on its complexity.

Clinical-grade quality platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelet concentrates promoted expansion of mesenchymal stromal cells.

PubMed

Borghese, C; Agostini, F; Durante, C; Colombatti, A; Mazzucato, M; Aldinucci, D

2016-08-01

The aim of our study was to test a platelet-rich plasma releasate (PRP-R/SRGF) from CaCl2 -activated platelets as a source of growth factors for the expansion of mesenchymal stromal cells (MSCs). PRP-R/SRGF, obtained with a low-cost procedure, is characterized by a reduced variability of growth factor release. PRP-R/SRGF is a clinical-grade quality solution obtained from CaCl2 -activated platelets. Its activity was evaluated by measuring the proliferation, the phenotype, the differentiation potential and the immunosuppressive properties of MSCs derived from bone marrow (BM) and adipose tissue (AT). PRP-R/SRGF was more active than FBS to expand BM- and AT-derived MSCs. PRP-R/SRGF treatment did not affect the expression of typical MSCs surface markers, neither MSCs differentiation potential nor their capability to inhibit activated T-cell proliferation. The clinical-grade PRP-R/SRGF may be used in the clinical setting for the expansion of MSCs. © 2016 International Society of Blood Transfusion.

Ultrasonography-guided central venous catheterisation in haematological patients with severe thrombocytopenia

PubMed Central

Napolitano, Mariasanta; Malato, Alessandra; Raffaele, Francesco; Palazzolo, Manuela; Iacono, Giorgio Lo; Pinna, Roberto; Geraci, Girolamo; Modica, Giuseppe; Saccullo, Giorgia; Siragusa, Sergio; Cajozzo, Massimo

2013-01-01

Background Cannulation of the internal jugular vein (CVC) is a blind surface landmark-guided technique that could be potentially dangerous in patients with very low platelet counts. In such patients, ultrasonography (US)-guided CVC may be a valid approach. There is a lack of published data on the efficacy and safety of urgent US-guided CVC performed in haematological patients with severe thrombocytopenia. Materials and methods We retrospectively studied the safety of urgent CVC procedures in haematological patients including those with severe thrombocytopenia (platelet count <30×109/L). From January 1999 to June 2009, 431 CVC insertional procedures in 431 consecutive patients were evaluated. Patients were included in the study if they had a haematological disorder and required urgent CVC insertion. Patients were placed in Trendelenburg's position, an 18-gauge needle and guide-wire were advanced under real-time US guidance into the last part of the internal jugular vein; central venous cannulation of the internal jugular vein was performed using the Seldinger technique in all the procedures. Major and minor procedure-related complications were recorded. Results All 431 patients studied had haematological disorders: 39 had severe thrombocytopenia, refractory to platelet transfusion (group 1), while 392 did not have severe thrombocytopenia (group 2). The general characteristics of the patients in the two groups differed only for platelet count. The average time taken to perform the procedure was 4 minutes. Success rates were 97.4% and 97.9% in group 1 and group 2, respectively. No major complications occurred in either group. Discussion US-guided CVC is a safe and effective approach in haematological patients with severe thrombocytopenia requiring urgent cannulation for life support, plasma-exchange, chemotherapy and transfusion. PMID:23399356

Automated processing of whole blood units: operational value and in vitro quality of final blood components

PubMed Central

Jurado, Marisa; Algora, Manuel; Garcia-Sanchez, Félix; Vico, Santiago; Rodriguez, Eva; Perez, Sonia; Barbolla, Luz

2012-01-01

Background The Community Transfusion Centre in Madrid currently processes whole blood using a conventional procedure (Compomat, Fresenius) followed by automated processing of buffy coats with the OrbiSac system (CaridianBCT). The Atreus 3C system (CaridianBCT) automates the production of red blood cells, plasma and an interim platelet unit from a whole blood unit. Interim platelet unit are pooled to produce a transfusable platelet unit. In this study the Atreus 3C system was evaluated and compared to the routine method with regards to product quality and operational value. Materials and methods Over a 5-week period 810 whole blood units were processed using the Atreus 3C system. The attributes of the automated process were compared to those of the routine method by assessing productivity, space, equipment and staffing requirements. The data obtained were evaluated in order to estimate the impact of implementing the Atreus 3C system in the routine setting of the blood centre. Yield and in vitro quality of the final blood components processed with the two systems were evaluated and compared. Results The Atreus 3C system enabled higher throughput while requiring less space and employee time by decreasing the amount of equipment and processing time per unit of whole blood processed. Whole blood units processed on the Atreus 3C system gave a higher platelet yield, a similar amount of red blood cells and a smaller volume of plasma. Discussion These results support the conclusion that the Atreus 3C system produces blood components meeting quality requirements while providing a high operational efficiency. Implementation of the Atreus 3C system could result in a large organisational improvement. PMID:22044958

Automated processing of whole blood units: operational value and in vitro quality of final blood components.

PubMed

Jurado, Marisa; Algora, Manuel; Garcia-Sanchez, Félix; Vico, Santiago; Rodriguez, Eva; Perez, Sonia; Barbolla, Luz

2012-01-01

The Community Transfusion Centre in Madrid currently processes whole blood using a conventional procedure (Compomat, Fresenius) followed by automated processing of buffy coats with the OrbiSac system (CaridianBCT). The Atreus 3C system (CaridianBCT) automates the production of red blood cells, plasma and an interim platelet unit from a whole blood unit. Interim platelet unit are pooled to produce a transfusable platelet unit. In this study the Atreus 3C system was evaluated and compared to the routine method with regards to product quality and operational value. Over a 5-week period 810 whole blood units were processed using the Atreus 3C system. The attributes of the automated process were compared to those of the routine method by assessing productivity, space, equipment and staffing requirements. The data obtained were evaluated in order to estimate the impact of implementing the Atreus 3C system in the routine setting of the blood centre. Yield and in vitro quality of the final blood components processed with the two systems were evaluated and compared. The Atreus 3C system enabled higher throughput while requiring less space and employee time by decreasing the amount of equipment and processing time per unit of whole blood processed. Whole blood units processed on the Atreus 3C system gave a higher platelet yield, a similar amount of red blood cells and a smaller volume of plasma. These results support the conclusion that the Atreus 3C system produces blood components meeting quality requirements while providing a high operational efficiency. Implementation of the Atreus 3C system could result in a large organisational improvement.

Assessment of Platelet Function in Traumatic Brain Injury-A Retrospective Observational Study in the Neuro-Critical Care Setting.

PubMed

Lindblad, Caroline; Thelin, Eric Peter; Nekludov, Michael; Frostell, Arvid; Nelson, David W; Svensson, Mikael; Bellander, Bo-Michael

2018-01-01

Despite seemingly functional coagulation, hemorrhagic lesion progression is a common and devastating condition following traumatic brain injury (TBI), stressing the need for new diagnostic techniques. Multiple electrode aggregometry (MEA) measures platelet function and could aid in coagulopathy assessment following TBI. The aims of this study were to evaluate MEA temporal dynamics, influence of concomitant therapy, and its capabilities to predict lesion progression and clinical outcome in a TBI cohort. Adult TBI patients in a neurointensive care unit that underwent MEA sampling were retrospectively included. MEA was sampled if the patient was treated with antiplatelet therapy, bled heavily during surgery, or had abnormal baseline coagulation values. We assessed platelet activation pathways involving the arachidonic acid receptor (ASPI), P2Y 12 receptor, and thrombin receptor (TRAP). ASPI was the primary focus of analysis. If several samples were obtained, they were included. Retrospective data were extracted from hospital charts. Outcome variables were radiologic hemorrhagic progression and Glasgow Outcome Scale assessed prospectively at 12 months posttrauma. MEA levels were compared between patients on antiplatelet therapy. Linear mixed effect models and uni-/multivariable regression models were used to study longitudinal dynamics, hemorrhagic progression and outcome, respectively. In total, 178 patients were included (48% unfavorable outcome). ASPI levels increased from initially low values in a time-dependent fashion ( p  < 0.001). Patients on cyclooxygenase inhibitors demonstrated low ASPI levels ( p  < 0.001), while platelet transfusion increased them ( p  < 0.001). The first ASPI ( p  = 0.039) and TRAP ( p  = 0.009) were significant predictors of outcome, but not lesion progression, in univariate analyses. In multivariable analysis, MEA values were not independently correlated with outcome. A general longitudinal trend of MEA is identified in this TBI cohort, even in patients without known antiplatelet therapies. Values appear also affected by platelet inhibitory treatment and by platelet transfusions. While significant in univariate models to predict outcome, MEA values did not independently correlate to outcome or lesion progression in multivariable analyses. Further prospective studies to monitor coagulation in TBI patients are warranted, in particular the interpretation of pathological MEA values in patients without antiplatelet therapies.

Evaluation of a BED-SIDE platelet function assay: performance and clinical utility.

PubMed

Lau, Wei C; Walker, C Ty; Obilby, David; Wash, Mark M; Carville, David G M; Guyer, Kirk E; Bates, Eric R

2002-01-01

Platelets have a pivotal role in the initial defense against insult to the vasculature and are also recognized of critical importance in the acute care settings of percutaneous coronary intervention and cardiopulmonary bypass. In these environments both platelet count and function may be markedly compromised. Unfortunately, current assays to evaluate the parameters of platelet count and function are of limited utility for bed-side testing. Moreover, it is suggested that there may be significant inter patient variation in response to antiplatelet therapy that may be exacerbated by other agents (e.g. heparin) that are routinely administered during cardiac intervention. Here we describe a practical, rapid and user-friendly whole blood platelet function assay that has been developed for use in bed-side settings. Platelet agonists were formulated with an anticoagulant and lyophilized in blood collection tubes standardised to receive a l mL fresh whole blood sample. In the presence of an agonist, platelets are activated and interact (aggregate). Using traditional cell counting principles, non-aggregated platelets are counted whereas aggregated platelets are not. The percentage (%) of functional platelets in reference to a baseline tube may then be determined. Results are available within four minutes. Platelet aggregation in whole blood demonstrated good correlation with turbidometric aggregometry for both ADP (r=0.91) and collagen (r=0.88). Moreover, in clinical settings where antiplatelet agents were administered, this rapid, bed-side, platelet function assay demonstrated utility in monitoring patient response to these therapies. This novel bed-side assay of platelet function is extremely suitable for the clinical environment with a rapid turn-around time. In addition, it provides a full haematology profile, including platelet count, and should permit enhancement of transfusion and interventional decisions.

Synthetic Strategies for Engineering Intravenous Hemostats

PubMed Central

Chan, Leslie W.-G.; White, Nathan J.; Pun, Suzie H.

2015-01-01

While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods of restoring hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf-life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin crosslinking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This review explores intravenous hemostats under development and strategies to optimize their clotting activity. PMID:25803791

A low birth weight infant with no malformations delivered by a primary immune thrombocytopenia patient treated with eltrombopag.

PubMed

Suzuki, Naruko; Hiraga, Junji; Hariyama, Yumi; Takagi, Yusuke; Ohashi, Haruhiko; Kishigami, Yasuyuki; Oguchi, Hidenori; Kagami, Yoshitoyo

2018-07-01

Primary immune thrombocytopenia (ITP) is defined by a low platelet count secondary to antibody-mediated platelet destruction or reductions in platelet production. Although eltrombopag is a thrombopoietin receptor agonist that increases platelet production in refractory or relapsed ITP, the influence on pregnancy is limited. We present the case of a pregnant 25-year-old ITP patient referred to our hospital with a history of two induced abortions. After eradication of Helicobacter pylori and with oral prednisolone at 8 mg/day, platelet count remained below 10,000/µl. Because she declined splenectomy, eltrombopag was initiated at 12.5 mg/day. Afterward, platelet count was maintained at over 50,000/µl. Twenty-one months later, pregnancy became apparent. She continued treatment, and cesarean section was performed at 37 weeks of gestation after administration of intravenous immunoglobulin, platelet transfusions, and steroids. The baby weighed only 1670 g but showed no malformations, and platelet count at birth was 416,000/µl. Studies of eltrombopag in pregnancy have not been reported. A case with administration of eltrombopag from the last trimester of pregnancy that resulted in low birth weight has been reported. Embryo lethality and reduced fetal weights have been reported from animal experiments. Further investigation about the relationship between low birth weight deliveries and eltrombopag is necessary.

Trends in United States blood collection and transfusion: results from the 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey.

PubMed

Whitaker, Barbee; Rajbhandary, Srijana; Kleinman, Steven; Harris, Andrea; Kamani, Naynesh

2016-09-01

AABB surveyed AABB institutional members about their 2013 blood collection, transfusion, and patient blood management (PBM) programs. Results were compared with previous US national surveys. The 2013 AABB Blood Collection, Utilization, and Patient Blood Management Survey was distributed to AABB blood centers (79) and hospitals (1068). Statistical procedures were used to estimate blood collection and transfusion. Estimated whole blood (WB) and red blood cell (RBC) collections in 2013 totaled 13.6 million units, a 12.1% decrease from 15.5 million units in 2011 (p < 0.0001). Transfusions of WB and RBC units by AABB hospitals totaled 6.1 million units, 7.3% fewer compared to 2011 (p = 0.036). There was no change in overall platelet (PLT) distributions by blood collectors but WB-derived (WBD) PLT distributions increased significantly (27.1%, p < 0.0001). Transfusion of PLTs increased 15.4% totaling 1.3 million units (p = 0.0423), including increases in apheresis PLT (12.2%) and WBD PLT transfusions (30.7%). Distribution of plasma for transfusion declined 22.4% (p < 0.0001), while transfused plasma decreased only 9.9% (p = 0.036). Hospitals reduced outdated WB, RBC, and PLT components by 14.9% to 26.1% and wasted plasma components by 19.0%. PBM programs were reported by 37.8% of AABB hospitals. Compared to 2011, WB and RBC collections declined significantly in 2013 and disproportionately to the significant reductions in WB and RBC transfusions. Distributions of PLTs and plasma for transfusion declined in 2013, as did transfusions of plasma, while transfusion of PLTs increased significantly. Decreases in outdated and wasted components by hospitals suggest improvements in product and inventory management. Ongoing national surveys allow for trend analysis and are important for future planning. © 2016 AABB.

Survey of Blood Collection Centers and Implementation of Guidance for Prevention of Transfusion-Transmitted Zika Virus Infection--Puerto Rico, 2016.

PubMed

Vasquez, Amber M; Sapiano, Mathew R P; Basavaraju, Sridhar V; Kuehnert, Matthew J; Rivera-Garcia, Brenda

2016-04-15

Since November 2015, Puerto Rico has reported active mosquito-borne transmission of Zika virus. Because of the potential for Zika virus to be transmitted through transfusion of blood components, and because a high percentage of persons infected with Zika virus are asymptomatic, the Food and Drug Administration (FDA) recommended that blood collections cease in areas of the United States affected by active vector-borne transmission of Zika virus until laboratory screening of blood donations or pathogen reduction technology (PRT) for treatment of blood components can be implemented. To inform efforts to maintain the safety and availability of the blood supply in Puerto Rico, CDC, in collaboration with the Puerto Rico Department of Health, conducted a rapid assessment of blood collection and use on the island. A total of 139,369 allogeneic red blood cell (RBC) units, 45,243 platelet units, and 56,466 plasma units were collected in or imported to Puerto Rico during 2015, and 135,966 allogeneic RBC units, 13,526 therapeutic platelet units, and 25,775 plasma units were transfused. Because of the potential for local Zika virus transmission in areas with a competent mosquito vector, other areas of the United States should develop plans to ensure local blood safety and adequacy. Blood collection organizations and public health agencies should collaborate to maintain the safety and availability of local blood supplies in accordance with FDA guidance.

The initial experience of antithrombin III in the management of neonates with necrotizing enterocolitis.

PubMed

St Peter, Shawn D; Little, Danny C; Calkins, Casey M; Holcomb, George W; Snyder, Charles L; Ostlie, Daniel J

2007-04-01

Necrotizing enterocolitis (NEC), the devastating enteric process of premature neonates, is marked by severe intravascular abnormalities and disseminated intravascular coagulation. Treatment to date remains historical and continues to be merely supportive without attempts to ameliorate progress within the inflammatory or coagulation cascades. Antithrombin III (ATIII) supplementation has been shown to favorably alter the process of disseminated intravascular coagulation and sepsis in adults. However, no reported use of this treatment exists in neonates. Therefore, we analyze the efficacy of our recent experience with ATIII replacement therapy in neonates with NEC. Age and diseased-matched controls with NEC were identified before the introduction of ATIII in our institution and compared against neonates with NEC undergoing ATIII replacement for diminished ATIII levels. Data collected included demographics, course of treatment parameters, and outcomes. Course of treatment parameters included hemoglobin, platelet count, prothrombin time, and partial thromboplastin time over the first 10 consecutive days of treatment. Outcome variables included packed red blood cell, platelet, fresh frozen plasma, and cryoprecipitate transfusions, as well as transfusion cost, length of stay, and survival. Over a 5-year period, 19 neonates with NEC received ATIII and were compared to 17 historical controls. Treatment hematologic profiles were not worsened in the ATIII-treated patients. The control patients received less overall transfusions and had a shorter length of stay. Antithrombin III appears to be safe in neonates with NEC, and its impact on reversing intravascular pathology in these patients warrants more thorough investigation.

[Thirty years of platelet immunology in fetal and neonatal alloimmune thrombocytopenia management, current situation].

PubMed

Petermann, R

2017-09-01

Fetal and neonatal allo-immune thrombocytopenia (FNAIT) is considered as a rare disease due to the incidence (1/1000-1/2000 births). The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial hemorrhage and neurologic sequelae following. Serology and molecular biology developments have reconfigured the platelet immunology diagnosis. Anti-HPA-1a allo-immunisation is responsible for more than 80% FNAIT cases with a high recurrence rate of severe bleeding complications. Therapeutic management has changed over the coming years from an invasive concept associating fetal blood sampling and in utero platelet transfusion to a non invasive treatment by intravenous immunoglobulins injection (IVIg). The purpose of this article is to provide an update on FNAIT management in the light of current developments over the past 30years. Copyright © 2017. Published by Elsevier SAS.

The epidemiology of blood component transfusion in Catalonia, Northeastern Spain.

PubMed

Bosch, M Alba; Contreras, Enric; Madoz, Pedro; Ortiz, Pilar; Pereira, Arturo; Pujol, M Mar

2011-01-01

Epidemiologic information on blood component usage can help improve the utilization of transfusion resources. Crosssectional survey in 2007 that included every hospital in Catalonia. Clinical data of blood recipients, including the four-digit International Classification of Diseases, 9th Revision, Clinical Modification codes and the indication for transfusion, were prospectively collected according to an established protocol. In total, 19,148 red blood cell (RBC) units, 1812 platelet (PLT) doses, and 3070 plasma units, transfused into 8019 patients (median age, 71 years; 52% males), were surveyed. Half the RBC units were used by patients older than 70 years. Specific diagnosis and procedures with the highest RBC use were lower limb orthopedic surgery (10.6% of all units) and gastrointestinal hemorrhage (6%). Therapeutic plasmapheresis (8.1%) and heart valve surgery (7.2%) were the procedures with the highest plasma use. Oncohematology patients accounted for 73% of transfused PLTs, more that two-thirds being administered for hemorrhage prophylaxis. Acute hemorrhage was the most common indication for RBC and plasma transfusion. Among all blood recipients, 80% received only RBCs and 6.9% received only plasma and/or PLTs, without concomitant RBCs. The population transfusion incidence rates were 35 RBC units, three PLT doses, and 6 plasma units per 1000 population-year. Demographic changes anticipate a 30% increase in RBC transfusion by year 2030. These results allow for identification of blood uses that are susceptible to improvement, help appraise the expected yield of blood safety measures, and will assist in planning the future blood supply. © 2010 American Association of Blood Banks.

Acute lung injury complicating blood transfusion in post-partum hemorrhage: incidence and risk factors.

PubMed

Teofili, Luciana; Bianchi, Maria; Zanfini, Bruno A; Catarci, Stefano; Sicuranza, Rossella; Spartano, Serena; Zini, Gina; Draisci, Gaetano

2014-01-01

We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH). We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed. Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27-604.3, p=0.034). Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended.

Life-threatening haematuria caused by vancomycin-induced thrombocytopenia

PubMed Central

Lobo, Niyati; Ejiofor, Kandi; Thurairaja, Ramesh; Khan, Muhammad Shamim

2015-01-01

Thrombocytopenia is a rare side effect of vancomycin, an antibiotic that is often used to treat Gram-positive bacterial infections. A 67-year-old man developed bilateral pulmonary emboli and hospital-acquired pneumonia following left ureteric reimplantation. He was anticoagulated with rivaroxaban and started on intravenous vancomycin and gentamicin for treatment of pneumonia. After five doses of vancomycin, his platelet count dropped to a nadir of 0×109/L (baseline: 314×109/L) manifesting as visible heavy haematuria and haemodynamic instability due to excessive blood loss. Reversal of the thrombocytopenia was achieved with intravenous immunoglobulin, methylprednisolone and continuous platelet transfusions. PMID:25716041

Comparison of early period results of blood use in open heart surgery.

PubMed

Huseyin, Serhat; Yuksel, Volkan; Guclu, Orkut; Turan, Fatma Nesrin; Canbaz, Suat; Ege, Turan; Sunar, Hasan

2016-01-01

Various adverse effects of homologous blood transfusion detected particularly in open heart surgery, in which it is frequently used, lead researchers to study on autologous blood use and to evaluate the patient's blood better. Due to the complications of homologous blood transfusion, development of techniques that utilize less transfusion has become inevitable. We aimed to evaluate the effects of acute normovolemic hemodilution (ANH) in patients undergoing open heart surgery. In this study, 120 patients who underwent open heart surgery were included. Patients were grouped into three: Autologous transfusion group (Group 1), homologous transfusion group (Group 2), and those received autologous blood and homologous blood products (Group 3). Patient data regarding preoperative characteristics, biochemical parameters, drainage, extubation time, duration of stay at intensive care, atrial fibrillation (AF) development, and hospital stay were recorded. A statistically significant difference ( P < 0.005) was found in favor of autologous group (Group 1) with respect to gender, body surface area, European System for Cardiac Operative Risk Evaluation, smoking, hematocrit levels, platelet counts, urea, C-reactive protein levels, protamine use, postoperative drainage, frequency of AF development, intubation period, stay at intensive care and hospital stay, and amount of used blood products. The use of autologous blood rather than homologous transfusion is not only attenuates side effects and complications of transfusion but also positively affects postoperative recovery process. Therefore, ANH can be considered as an easy, effective, and cheap technique during open heart surgery.

Presurgical levels of circulating cell-derived microparticles discriminate between patients with and without transfusion in coronary artery bypass graft surgery.

PubMed

Jy, Wenche; Gómez-Marín, Orlando; Salerno, Tomas A; Panos, Anthony L; Williams, Donald; Horstman, Lawrence L; Ahn, Yeon S

2015-01-01

Improved understanding of presurgical risk factors for transfusions will lead to reduction in their number and related complications. The goal of this study is to identify these factors in coronary artery bypass graft (CABG) surgery. Presented herein are results of analyses of data from an ongoing study of transfusion in CABG surgery. Of 122 patients, 81 received transfusion (Tx) and 41 did not (NoTx). In addition to routine tests, presurgical levels of microparticles from platelets (PMPs), red cells (RMPs), and other lineages were assayed. The Tx and NoTx groups were similar with respect to most presurgical variables but differed in distribution of gender, blood type, diabetes prevalence, activated partial thromboplastin time (aPTT), hemoglobin (HGB), and microparticle levels. Stepwise multiple logistic regression was used to evaluate presurgical variables and to develop a model to assess risk factors for transfusion. CD41(+) PMP and CD235(+) RMP levels were found to be the main risk factors for transfusion. The Model's discriminating ability was assessed using receiver operating characteristic curve analysis, which showed that the area under the model curve (± standard error) was 0.86 ± 0.04 (95% confidence interval, 0.77-0.94). According to the model, patients with higher presurgical levels of circulating CD41(+) PMP, CD235a(+) RMP, and HGB, as well as a shorter aPTT, are less likely to receive transfusion(s). Presurgical levels of CD41(+) PMPs and CD235a(+) RMPs are the main risk factors for transfusion in CABG, followed by HGB and aPTT. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Human Mesenchymal Stem Cell Transfusion Is Safe and Improves Liver Function in Acute-on-Chronic Liver Failure Patients

PubMed Central

Shi, Ming; Zhang, Zheng; Xu, Ruonan; Lin, Hu; Fu, Junliang; Zou, Zhengsheng; Zhang, Aimin; Shi, Jianfei; Chen, Liming; Lv, Sa; He, Weiping; Geng, Hua; Jin, Lei; Liu, Zhenwen

2012-01-01

Acute-on-chronic liver failure (ACLF) is a severe, life-threatening complication, and new and efficient therapeutic strategies for liver failure are urgently needed. Mesenchymal stem cell (MSC) transfusions have been shown to reverse fulminant hepatic failure in mice and to improve liver function in patients with end-stage liver diseases. We assessed the safety and initial efficacy of umbilical cord-derived MSC (UC-MSC) transfusions for ACLF patients associated with hepatitis B virus (HBV) infection. A total of 43 ACLF patients were enrolled for this open-labeled and controlled study; 24 patients were treated with UC-MSCs, and 19 patients were treated with saline as controls. UC-MSC therapy was given three times at 4-week intervals. The liver function, adverse events, and survival rates were evaluated during the 48-week or 72-week follow-up period. No significant side effects were observed during the trial. The UC-MSC transfusions significantly increased the survival rates in ACLF patients; reduced the model for end-stage liver disease scores; increased serum albumin, cholinesterase, and prothrombin activity; and increased platelet counts. Serum total bilirubin and alanine aminotransferase levels were significantly decreased after the UC-MSC transfusions. UC-MSC transfusions are safe in the clinic and may serve as a novel therapeutic approach for HBV-associated ACLF patients. PMID:23197664

Quality assurance of clinical transfusion practice by implementation of the privilege of blood prescription and computerized prospective audit of blood requests.

PubMed

Marconi, M; Almini, D; Pizzi, M N; Riccardi, D; Bergamaschi, W; Giovanetti, A M; Rebulla, P; Sirchia, G

1996-03-01

Guidelines, algorithms and recommendations have been issued in the attempt to ensure appropriateness of transfusion practice, but the results are less than satisfactory, mainly due to the difficulty to turn paper procedures into actual practice. In our hospital we have tried to overcome this difficulty through the implementation of a quality assurance programme which includes giving the privilege of nonurgent blood prescription to a limited number of physicians and a computerized prospective audit of blood requests. The latter is performed through verification of the compliance of blood requests, which are designed to include a patient's laboratory and clinical data, with hospital guidelines for the proper use of blood. In the 12 months since implementation of the computerized prospective audit the transfusion service has evaluated 7884 requests. Of these, 63.4% (n = 4998) were for red blood cells, 21.1% (n = 1664) for platelets and 15.5% (n = 1222) for fresh frozen plasma. The prospective audit showed that 96.8% and 98.1% of requests for red units and platelets were appropriate, respectively. Conversely, approximately 27% of plasma requests did not comply with guidelines, mainly because the evidence of coagulopathy was missing. However, inappropriateness of plasma requests for elective general surgery decreased from 39% at the onset of the programme to 14% in the last trimester considered. Moreover, the evaluation by retrospective audit of the proportion of patients transfused with both red blood cells and plasma in the perioperative period out of those transfused with red blood cells only, as an indicator of unwanted reconstitution of whole blood, showed that this proportion decreased from 47.6% (320/672) in the 12 months before implementation of computerized audit to 37.8% (244/646) in the following 12 months (difference = -9.8%, 95% confidence interval of the difference from -4.5% to -15.1%; P < 0.005 by chi 2 test). Our initial experience, together with the present system, shows that (1) the restriction of nonurgent blood prescription to a group of clinicians more educated in transfusion medicine than average clinicians practicing in a large multispecialty hospital is feasible; (2) prospective audit is a useful tool for assuring the quality of blood requesting.

Pre-hospital transfusion of plasma in hemorrhaging trauma patients independently improves hemostatic competence and acidosis.

PubMed

Henriksen, Hanne H; Rahbar, Elaheh; Baer, Lisa A; Holcomb, John B; Cotton, Bryan A; Steinmetz, Jacob; Ostrowski, Sisse R; Stensballe, Jakob; Johansson, Pär I; Wade, Charles E

2016-12-09

The early use of blood products has been associated with improved patient outcomes following severe hemorrhage or traumatic injury. We aimed to investigate the influence of pre-hospital blood products (i.e. plasma and/or RBCs) on admission hemostatic properties and patient outcomes. We hypothesized that pre-hospital plasma would improve hemostatic function as evaluated by rapid thrombelastography (rTEG). We conducted a prospective observational study recruiting 257 trauma patients admitted to a Level I trauma center having received either blood products pre-hospital or in-hospital within 6 hours of admission. Clinical data on patient demographics, blood biochemistry, injury severity score and mortality were collected. Admission rTEG was conducted to characterize the coagulation profile and hemostatic function. 75 patients received pre-hospital plasma and/or RBCs (PH group; nearly half received both RBCs and plasma) whereas 182 patients only received in-hospital blood products (RBCs, Plasma and Platelets) within 6 hours of admission (IH group). PH patients had lower Glasgow coma scale (GCS) scores, more penetrating injuries, lower systolic blood pressures, lower hemoglobin levels, lower platelet counts and greater acidosis upon ED admission than the IH group (all p < 0.05). Despite differences in type of injury and admission vitals indicating that the PH group had more signs of bleeding than the IH group, there were no significant differences in in-hospital mortality (PH 26.7% vs. IH 20.9% p = 0.31). When comparing rTEG variables between PH patients transfused with 0, 1 or 2 units of plasma, more pre-hospital plasma transfusion was tendency towards improved rTEG variables. When adjusting for pre-hospital RBC, pre-hospital plasma was associated with significantly higher rTEG MA (p = 0.012) at hospital admission. After adjusting for pre-hospital RBCs, pre-hospital plasma transfusion was independently associated with increased rTEG MA, as well as arrival indices of shock and hemodynamic instability. Besides more severe injury and worse clinical presentation, the group that received pre-hospital transfusion had early and late mortality similar to patients not transfused pre-hospital. These data suggest that early administration of plasma can provide significant hemostatic and potential survival benefit to severely hemorrhaging trauma patients.

Thromboelastometry versus standard coagulation tests versus restrictive protocol to guide blood transfusion prior to central venous catheterization in cirrhosis: study protocol for a randomized controlled trial.

PubMed

Rocha, Leonardo Lima; Pessoa, Camila Menezes Souza; Neto, Ary Serpa; do Prado, Rogerio Ruscitto; Silva, Eliezer; de Almeida, Marcio Dias; Correa, Thiago Domingos

2017-02-27

Liver failure patients have traditionally been empirically transfused prior to invasive procedures. Blood transfusion is associated with immunologic and nonimmunologic reactions, increased risk of adverse outcomes and high costs. Scientific evidence supporting empirical transfusion is lacking, and the best approach for blood transfusion prior to invasive procedures in cirrhotic patients has not been established so far. The aim of this study is to compare three transfusion strategies (routine coagulation test-guided - ordinary or restrictive, or thromboelastometry-guided) prior to central venous catheterization in critically ill patients with cirrhosis. Design and setting: a double-blinded, parallel-group, single-center, randomized controlled clinical trial in a tertiary private hospital in São Paulo, Brazil. adults (aged 18 years or older) admitted to the intensive care unit with cirrhosis and an indication for central venous line insertion. Patients will be randomly assigned to three groups for blood transfusion strategy prior to central venous catheterization: standard coagulation tests-based, thromboelastometry-based, or restrictive. The primary efficacy endpoint will be the proportion of patients transfused with any blood product prior to central venous catheterization. The primary safety endpoint will be the incidence of major bleeding. Secondary endpoints will be the proportion of transfusion of fresh frozen plasma, platelets and cryoprecipitate; infused volume of blood products; hemoglobin and hematocrit before and after the procedure; intensive care unit and hospital length of stay; 28-day and hospital mortality; incidence of minor bleeding; transfusion-related adverse reactions; and cost analysis. This study will evaluate three strategies to guide blood transfusion prior to central venous line placement in severely ill patients with cirrhosis. We hypothesized that thromboelastometry-based and/or restrictive protocols are safe and would significantly reduce transfusion of blood products in this population, leading to a reduction in costs and transfusion-related adverse reactions. In this manner, this trial will add evidence in favor of reducing empirical transfusion in severely ill patients with coagulopathy. ClinicalTrials.gov, identifier: NCT02311985 . Retrospectively registered on 3 December 2014.

Role of blood transfusion product type and amount in deep vein thrombosis after cardiac surgery.

PubMed

Ghazi, Lama; Schwann, Thomas A; Engoren, Milo C; Habib, Robert H

2015-12-01

Postoperative deep vein thrombosis (DVT) is associated with significant morbidity. Even with maximal thromboprophylaxis, postoperative DVT is present in 10% of cardiac surgery patients, and is linked to receiving transfusion. We hypothesized that the incidence of DVT varies with the transfused blood product type, and increases with transfusion dose. 139/1070 cardiac surgery patients have DVT despite maximal chemo and mechanical prophylaxis. DVTs were detected via serial perioperative duplex venous scans (DVS). Red blood cells (RBC), platelets (PLT), plasma (FFP) and cryoprecipitate transfusion data were collected. Transfusion was used in 506(47%) patients: RBC [468(44%); 4.0 ± 4.2u]; FFP [155(14.5%); 3.5 ± 2.3 u]; PLT [185(17.3%); 2.2 ± 1.3 u] and Cryoprecipitate [51(4.8%); 1.3 ± 0.6 u]. Isolated RBC transfusion accounted for 92.6% patients receiving one product, and their DVT rate was increased considerably compared to no transfusion (16.7% versus 7.3%; P<0.001). Incidence of DVT increased substantially for multiple product transfusions; particularly when both RBC and FFP are used (25%-40%). Relative to no RBC (n=602), multivariate logistic regression analysis identified a significant RBC-DVT dose dependent relation (P<0.001) with: 1-3 RBC units [n=285, AOR=1.95(1.23-3.07), adjusted odds ratio (95% confidence interval)]; 4-6 units [n=117; AOR=1.65(0.86-3.20)]; and ≥ 7 RBC units [n=66; 3.19(1.52-6.70)]. This relation also increased according to an RBC∗FFP interaction term [AOR=1.87(1.11-3.22); P=0.022]. RBC transfusion is associated with increased risk of DVT after cardiac surgery in a dose-dependent fashion that is exacerbated when accompanied with FFP. Postoperative screening diagnostic DVS are warranted in this transfused, high risk for DVT population to facilitate timely therapeutic intervention. Copyright © 2015 Elsevier Ltd. All rights reserved.

Current issues with blood transfusions in sickle cell disease.

PubMed

Vichinsky, E P

2001-01-01

With increased recognition of the profound morbidity of sickle cell disease and with growing evidence of the efficacy of transfusion therapy in prevention and treatment of sickle cell complications, most patients now receive intermittent transfusion therapy. The purpose of this report is to review blood component therapy and Its risks for sickle cell patients. Packed red cells are the preferred blood component. Leukocyte-reduced units should be standard because of their beneficial effects in reducing alloimmunization, transfusion reactions, platelet refractoriness, and infection transmission. The use of washed, frozen, or Irradiated units is limited to specific problems. Sickle trait-positive units function normally, but because of difficulties with calculating hemoglobin S percentages and leukocyte filters, they are not routinely used. Transfusion-acquired infections have shown a marked decrease but still present a major risk. Viral hepatitis transmission is currently low, but at least 10% of adult sickle cell patients are hepatitis C positive, and they often have liver damage. Although bacterial infections are rare, they account for 16% of transfusion-related fatalities. Patients who are iron overloaded are particularly vulnerable to Yersina enterocolitica. Red cell alloimmunization is a serious problem that could potentially affect 50% of transfused patients. However, preventive phenotypic matching for common antigens can minimize alloimmunization; limited matching for at least E, C, and K has become the standard of care. Recently, more patients are being identified who have developed red cell autoantibodies, which can mask alloantibodies and occasionally are hemolytic. Careful laboratory evaluation of all cases is essential. Transfusions also may trigger sickle cell events, including pain crises, stroke, and acute pulmonary deterioration. In part, these are induced by blood viscosity and increased blood pressure. Diuretic therapy and close monitoring of transfusion volume and vital signs can minimize these events. In summary, transfusion therapy carries risks, but the routine use of leukocyte-reduced, phenotypically matched units in conjunction with close monitoring of patients can make transfusion therapy safer.

Hospital blood bank information systems accurately reflect patient transfusion: results of a validation study.

PubMed

McQuilten, Zoe K; Schembri, Nikita; Polizzotto, Mark N; Akers, Christine; Wills, Melissa; Cole-Sinclair, Merrole F; Whitehead, Susan; Wood, Erica M; Phillips, Louise E

2011-05-01

Hospital transfusion laboratories collect information regarding blood transfusion and some registries gather clinical outcomes data without transfusion information, providing an opportunity to integrate these two sources to explore effects of transfusion on clinical outcomes. However, the use of laboratory information system (LIS) data for this purpose has not been validated previously. Validation of LIS data against individual patient records was undertaken at two major centers. Data regarding all transfusion episodes were analyzed over seven 24-hour periods. Data regarding 596 units were captured including 399 red blood cell (RBC), 95 platelet (PLT), 72 plasma, and 30 cryoprecipitate units. They were issued to: inpatient 221 (37.1%), intensive care 109 (18.3%), outpatient 95 (15.9%), operating theater 45 (7.6%), emergency department 27 (4.5%), and unrecorded 99 (16.6%). All products recorded by LIS as issued were documented as transfused to intended patients. Median time from issue to transfusion initiation could be calculated for 535 (89.8%) components: RBCs 16 minutes (95% confidence interval [CI], 15-18 min; interquartile range [IQR], 7-30 min), PLTs 20 minutes (95% CI, 15-22 min; IQR, 10-37 min), fresh-frozen plasma 33 minutes (95% CI, 14-83 min; IQR, 11-134 min), and cryoprecipitate 3 minutes (95% CI, -10 to 42 min; IQR, -15 to 116 min). Across a range of blood component types and destinations comparison of LIS data with clinical records demonstrated concordance. The difference between LIS timing data and patient clinical records reflects expected time to transport, check, and prepare transfusion but does not affect the validity of linkage for most research purposes. Linkage of clinical registries with LIS data can therefore provide robust information regarding individual patient transfusion. This enables analysis of joint data sets to determine the impact of transfusion on clinical outcomes. © 2010 American Association of Blood Banks.

Platelets in liver disease, cancer and regeneration.

PubMed

Kurokawa, Tomohiro; Ohkohchi, Nobuhiro

2017-05-14

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

[Coagulation Monitoring and Bleeding Management in Cardiac Surgery].

PubMed

Bein, Berthold; Schiewe, Robert

2018-05-01

The transfusion of allogeneic blood products is associated with increased morbidity and mortality. An impaired hemostasis is frequently found in patients undergoing cardiac surgery and may in turn cause bleeding and transfusions. A goal directed coagulation management addressing the often complex coagulation disorders needs sophisticated diagnostics. This may improve both patients' outcome and costs. Recent data suggest that coagulation management based on a rational algorithm is more effective than traditional therapy based on conventional laboratory variables such as PT and INR. Platelet inhibitors, cumarins, direct oral anticoagulants and heparin need different diagnostic and therapeutic approaches. An algorithm specifically developed for use during cardiac surgery is presented. Georg Thieme Verlag KG Stuttgart · New York.

Whole blood and component use in resource poor settings.

PubMed

Marwaha, Neelam

2010-01-01

Data on blood collection, testing and component preparation has improved worldwide; however, there is limited information on blood utilization from the developing countries. Blood requirement in the Southeast Asia region is 15 million units against a collection of 9.3 million. There is huge diversity in the management of blood transfusion services, the voluntary blood collection (range 40-100%) and proportion of blood separated into components (10-95%). The major indications for transfusion are for emergency obstetric care, surgery, pediatric and trauma patients. The prevalence of thalassemia in this region is high and in India alone 2 million units of packed red cells are required for transfusion to these patients. The Blood Safety Program in India has developed as a component of the National Aids Control Program and has lead to infrastructure development, blood component separation facilities and formulation of a National Blood Policy. In order to facilitate emergency obstetric care nearer home, blood storage centers are being established at primary health care centers. Emerging infectious threats like dengue hemorrhagic fever necessitate platelet transfusion therapy. A few centers in India issue NAT screened blood. It is envisaged to establish a nationally co-ordinated transfusion service for cost-effective quality blood/components for appropriate clinical use. Copyright 2009 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Long wavelength undulations dominate dynamics in large surfactant membrane patches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipfert, Frederik; Holderer, Olaf; Frielinghaus, Henrich

2014-12-03

In this study, by exposing microemulsions to small (80 nm diameter) and large (500 nm) disk shaped clay particles we were able to show the presence of long wavelength undulations that only occur for large membrane patches. A combination of small angle neutron scattering (SANS) and neutron spin echo (NSE) experiments have been applied to study microemulsions. These, consisting of D 2O, d-decane and the surfactant C 10E 4, were used in connection with Laponite (small) and Nanofil (large) clay. To our knowledge our experiments show for the first time that the clay platelets induce lamellar ordering adjacent to themore » clay discs in the otherwise bicontinuous microemulsion. This is due to the fact that in purely structural investigations, radial averaging smears out the signature of the lamellar phase. For thermodynamically fluctuating membranes near interfaces the theory of Seifert predicts a cross-over of the dispersion relationship from k 2 to a k 3-dependence. Lastly, with the correlation length of the membrane patches being confined by the dimension of the clay platelets we were able to show that this in fact takes place but is only present for the larger Nanofil particles.« less

Analysis of early thrombus dynamics in a humanized mouse laser injury model.

PubMed

Wang, Weiwei; Lindsey, John P; Chen, Jianchun; Diacovo, Thomas G; King, Michael R

2014-01-01

Platelet aggregation and thrombus formation at the site of injury is a dynamic process that involves the continuous addition of new platelets as well as thrombus rupture. In the early stages of hemostasis (within minutes after vessel injury) this process can be visualized by transfusing fluorescently labeled human platelets and observing their deposition and detachment. These two counterbalancing events help the developing thrombus reach a steady-state morphology, where it is large enough to cover the injured vessel surface but not too large to form a severe thrombotic occlusion. In this study, the spatial and temporal aspects of early stage thrombus dynamics which result from laser-induced injury on arterioles of cremaster muscle in the humanized mouse were visualized using fluorescent microscopy. It was found that rolling platelets show preference for the upstream region while tethering/detaching platelets were primarily found downstream. It was also determined that the platelet deposition rate is relatively steady, whereas the effective thrombus coverage area does not increase at a constant rate. By introducing a new method to graphically represent the real time in vivo physiological shear stress environment, we conclude that the thrombus continuously changes shape by regional growth and decay, and neither dominates in the high shear stress region.

Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.

PubMed

Lorenz, Viola; Ramsey, Haley; Liu, Zhi-Jian; Italiano, Joseph; Hoffmeister, Karin; Bihorel, Sihem; Mager, Donald; Hu, Zhongbo; Slayton, William B; Kile, Benjamin T; Sola-Visner, Martha; Ferrer-Marin, Francisca

2017-12-01

Congenital amegakaryocytic thrombocytopaenia (CAMT) is a disorder caused by c-MPL mutations that impair thrombopoietin (TPO) signalling, resulting in a near absence of megakaryocytes (MKs). While this phenotype is consistent in adults, neonates with CAMT can present with severe thrombocytopaenia despite normal MK numbers. To investigate this, we characterized MKs and platelets in newborn c-MPL –/– mice. Liver MKs in c-MPL –/– neonates were reduced in number and size compared with wild-type (WT) age-matched MKs, and exhibited ultrastructural abnormalities not found in adult c-MPL –/– MKs. Platelet counts were lower in c-MPL –/– compared with WT mice at birth and did not increase over the first 2 weeks of life. In vivo biotinylation revealed a significant reduction in the platelet half-life of c-MPL –/– newborn mice (P2) compared with age-matched WT pups, which was not associated with ultrastructural abnormalities. Genetic deletion of the pro-apoptotic Bak did not rescue the severely reduced platelet half-life of c-MPL –/– newborn mice, suggesting that it was due to factors other than platelets entering apoptosis early. Indeed, adult GFP+ (green fluorescent protein transgenic) platelets transfused into thrombocytopenic c-MPL –/– P2 pups also had a shortened lifespan, indicating the importance of cell-extrinsic factors. In addition, neonatal platelets from WT and c-MPL –/– mice exhibited reduced P-selectin surface expression following stimulation compared with adult platelets of either genotype, and platelets from c-MPL –/– neonates exhibited reduced glycoprotein IIb/IIIa (GPIIb/IIIa) activation in response to thrombin compared with age-matched WT platelets. Taken together, our findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal MKs and developmental stage-specific defects in platelet function.

Platelet gene therapy improves hemostatic function for integrin αIIbβ3-deficient dogs

PubMed Central

Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

2011-01-01

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects. PMID:21606353

GPIbα is required for platelet-mediated hepatic thrombopoietin generation.

PubMed

Xu, Miao; Li, June; Neves, Miguel Antonio Dias; Zhu, Guangheng; Carrim, Naadiya; Yu, Ruoying; Gupta, Sahil; Marshall, John; Rotstein, Ori; Peng, Jun; Hou, Ming; Kunishima, Shinji; Ware, Jerry; Branch, Donald R; Lazarus, Alan; Ruggeri, Zaverio M; Freedman, John; Ni, Heyu

2018-05-24

Thrombopoietin (TPO), a hematopoietic growth factor produced predominately by the liver is essential for thrombopoiesis. Prevailing theory posits circulating TPO levels are maintained through its clearance by platelets and megakaryocytes via surface c-Mpl receptor internalization. Interestingly, we found in GPIbα-/- mice, a 2-3-fold decrease in circulating TPO compared to wild-type (WT) controls, which was consistent in GPIbα-deficient human Bernard-Soulier Syndrome (BSS) patients. We showed that lower TPO levels in GPIbα-deficient conditions was not due to increased TPO clearance by GPIbα-/- platelets, but rather through decreased hepatic TPO mRNA transcription and production. We found WT, but not GPIbα-/- platelet transfusions rescued both hepatic TPO mRNA and circulating TPO levels in GPIbα-/- mice. In vitro hepatocyte co-cultures with platelets or GPIbα coupled beads further confirm the disruption of platelet-mediated hepatic TPO generation in absence of GPIbα. Treatment of GPIbα-/- platelets with neuraminidase caused significant desialylation, however, strikingly, desialylated GPIbα-/- platelets could not rescue impaired hepatic TPO production both in vivo and in vitro, suggesting GPIbα, independent of platelet desialylation, is a pre-requisite for hepatic TPO generation. Additionally, impaired hepatic TPO production was recapitulated in IL-4/GPIbα transgenic mice as well as with antibodies targeting extracellular portion of GPIbα, demonstrating that the N-terminus of GPIbα is required for platelet-mediated hepatic TPO-generation. These findings reveal a novel non-redundant regulatory role of platelets in hepatic TPO homeostasis, which not only improves our understanding of constitutive TPO regulation but also has important implications in diseases related to GPIbα such as BSS and auto- and alloimmune-mediated thrombocytopenias. Copyright © 2018 American Society of Hematology.

Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.

PubMed

Fang, Juan; Jensen, Eric S; Boudreaux, Mary K; Du, Lily M; Hawkins, Troy B; Koukouritaki, Sevasti B; Cornetta, Kenneth; Wilcox, David A

2011-06-07

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

WITHDRAWN: The platelet storage lesion: A comparative analysis of six leukoreduction processes in terms of biocompatability, microvesiculation, retention of prions, and generation/removal of biological response modifiers.

PubMed

Seghatchian, Jerard

2005-06-16

The Publisher regrets that this article was an accidental duplication of an article that has already been published in Transfus Apher Sci, 34 (1) 125 - 130, doi:10.1016/j.transci.2005.09.002. The duplicate article has therefore been withdrawn.

In vitro platelet quality in storage containers used for pediatric transfusions.

PubMed

Weiss, Sandra; Scammell, Kenneth; Levin, Elena; Culibrk, Brankica; Zolfaghari, Sima; Gyöngyössy-Issa, Maria I C; Acker, Jason P

2012-08-01

The in vitro quality of small-volume platelet (PLT) aliquots for pediatric transfusions was assessed to determine the best practice approach. Small volumes (50 mL) of single apheresis PLT components (APCs), collected on either CaridianBCT Trima or Haemonetics MCS+ instruments, were aliquoted on Days 2, 3, 4, and 5 postcollection into Fenwal PL1240 or 4R2014 bags or 60-mL polypropylene syringes. Samples were tested for in vitro quality at their recommended expiry times (4 hr for 4R2014 bags and syringes or Day 5 for PL1240 bags). Assays included pH, CD62P expression, and metabolic measures. CD62P expression increased throughout storage in all containers. Among the small-volume containers, pH, pCO(2) , lactate, and bicarbonate varied considerably. Regardless of the day of aliquoting, pCO(2) was significantly higher and pO(2) was significantly lower in gas-impermeable syringes than other containers. No bacterial growth was detected in any sample. The quality of APCs aliquoted into small-volume containers meets regulatory requirements and is generally equivalent to that of full-volume APCs at expiry. © 2012 American Association of Blood Banks.

At-Home Application of Autologous Platelet Rich Plasma as Treatment for Pressure Sore and Related Anemia.

PubMed

Tendas, Andrea; Niscola, Pasquale; Giovannini, Marco; Costa, Adriana; Venditti, Daniela; Volta, Laura; Malandruccolo, Luigi; Sabbadini, Stefania; Lasorella, Rosa; Fabritiis, Paolo de; Cassetta, Rita; Perrotti, Alessio P

2017-01-01

Pressure sores are a major complication in the bed-ridden older patient. In this report, we present the case of platelet rich plasma (PRP) application for the treatment of a pressure sore in an 88-year-old female affected by transfusion-dependent chronic inflammatory disease anemia associated with the congenital and inherited condition of thalassemic trait carrier. A weekly application schedule was planned athome, given the patient's debilitation and her decreased performance status as well as personal and family difficulties to go as outpatients at our treatment center. After 9 PRP applications, a remarkable sore improvement was achieved so that PRP was discontinued; nevertheless, sore rapidly improved until the full resolution and the complete closing after 4 months from the start of PRP treatment. Noteworthy, transfusion support was interrupted and a significant recovery and a sustained stabilization of hemoglobin (Hb) level at 1 year after ulcer healing were observed. The present case suggests that PRP application, performed athome in our case, is a feasible and effective treatment for pressure sores and related complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A high-throughput microfluidic approach for 1000-fold leukocyte reduction of platelet-rich plasma

NASA Astrophysics Data System (ADS)

Xia, Hui; Strachan, Briony C.; Gifford, Sean C.; Shevkoplyas, Sergey S.

2016-10-01

Leukocyte reduction of donated blood products substantially reduces the risk of a number of transfusion-related complications. Current ‘leukoreduction’ filters operate by trapping leukocytes within specialized filtration material, while allowing desired blood components to pass through. However, the continuous release of inflammatory cytokines from the retained leukocytes, as well as the potential for platelet activation and clogging, are significant drawbacks of conventional ‘dead end’ filtration. To address these limitations, here we demonstrate our newly-developed ‘controlled incremental filtration’ (CIF) approach to perform high-throughput microfluidic removal of leukocytes from platelet-rich plasma (PRP) in a continuous flow regime. Leukocytes are separated from platelets within the PRP by progressively syphoning clarified PRP away from the concentrated leukocyte flowstream. Filtrate PRP collected from an optimally-designed CIF device typically showed a ~1000-fold (i.e. 99.9%) reduction in leukocyte concentration, while recovering >80% of the original platelets, at volumetric throughputs of ~1 mL/min. These results suggest that the CIF approach will enable users in many fields to now apply the advantages of microfluidic devices to particle separation, even for applications requiring macroscale flowrates.

Automated platelet collection using the latest apheresis devices in an Indian setting.

PubMed

Agarwal, Prashant; Verma, Anupam

2009-10-01

In a developing nation like India where there is a scarcity of resources and voluntary donors, provision of safe and good quality blood and its components is a huge challenge. The demand for platelets is increasing constantly due to better management of various patient categories, specifically hemato-oncological cases, where there is an increased demand of platelet transfusion. The use of apheresis single donor platelets (SDPs) has been attributed to increased gap between demand and supply of whole blood derived random donor platelets (RDPs). Moreover, the other benefits of SDPs such as decreased donor exposure and simplification of inventory management cannot be overlooked. However, the increased costs and logistic problems, compounded by the lack of awareness, limit the donor recruitment and procedures for SDPs. In Indian scenario, there are no specific guidelines or standards available which can be followed, while simultaneously addressing the associated problems. In this review, we have tried to analyze the various problems of donor selection, donor safety and the quality issues regarding plateletpheresis. Based on this we have tried to give certain recommendations which might help the centers in resolving the problems related to plateletpheresis.

Blood transfusion in pediatric cardiac surgery.

PubMed

Durandy, Yves

2010-11-01

The aim of the study is to measure the volume of homologous blood needed for one pediatric patient during his hospital stay. Over a 4-month period, all the patients operated upon with a blood prime or requiring blood transfusion during their hospital stay were included in this study.The cardiopulmonary bypass protocol associates a miniaturized bypass circuit, vacuum-assisted venous drainage, and microplegia. The volume of each blood product opened is known and the volume of blood product remaining, following the last transfusion, is measured. Data collected areas follows: patient weight; hemoglobin level before surgery,during bypass, and in intensive care after the last transfusion;time to extubation; and degree of inotropic support.Forty-six patients weighing 5.1 1.5 kg were included in this study. Cardiopulmonary bypass priming volume was 100 mL for patients up to 3.5 kg, 120 mL for patients between 3.6 and 7.5 kg, and 160 mL for patients between 7.6 and 8.6 kg. The volume of blood transfusion was 271 112 mL, hemoglobin level before surgery was 10.3 1.7 g/dL, hemoglobin level during surgery was 11.0 1.5 g/dL, and hemoglobin level after the last transfusion was 12.3 2.4 g/dL. Time to extubation was 12 3.3 h, and inotropic support was enoximone in 37 patients,whereas 6 patients needed enoximone and epinephrine.No patient needed reexploration for bleeding and one patient received a platelet transfusion.The mean blood transfusion volume was equivalent to 60% of the patient’s total blood volume (estimated to be 80 mL/kg).

Concentration-dependent effect of hypocalcaemia on mortality of patients with critical bleeding requiring massive transfusion: a cohort study.

PubMed

Ho, K M; Leonard, A D

2011-01-01

Mortality of patients with critical bleeding requiring massive transfusion is high. Although hypothermia, acidosis and coagulopathy have been well described as important determinants of mortality in patients with critical bleeding requiring massive transfusion, the risk factors and outcome associated with hypocalcaemia in these patients remain uncertain. This cohort study assessed the relationship between the lowest ionised calcium concentration during the 24-hour period of critical bleeding and the hospital mortality of 352 consecutive patients, while adjusting for diagnosis, acidosis, coagulation results, transfusion requirements and use of recombinant factor VIIa. Hypocalcaemia was common (mean concentrations 0.77 mmol/l, SD 0.19) and had a linear; concentration-dependent relationship with mortality (odds ratio [OR] 1.25 per 0.1 mmol/l decrement, 95% confidence interval [CI]: 1.04 to 1.52; P = 0.02). Hypocalcaemia accounted for 12.5% of the variability and was more important than the lowest fibrinogen concentrations (10.8%), acidosis (7.9%) and lowest platelet counts (7.7%) in predicting hospital mortality. The amount of fresh frozen plasma transfused (OR 1.09 per unit, 95% CI: 1.02 to 1.17; P = 0.02) and acidosis (OR 1.45 per 0.1 decrement, 95% CI: 1.19 to 1.72; P = 0.01) were associated with the occurrence of severe hypocalcaemia (< 0.8 mmol/l). In conclusion, ionised calcium concentrations had an inverse concentration-dependent relationship with mortality of patients with critical bleeding requiring massive transfusion. Both acidosis and the amount of fresh frozen plasma transfused were the main risk factors for severe hypocalcaemia. Further research is needed to determine whether preventing ionised hypocalcaemia can reduce mortality of patients with critical bleeding requiring massive transfusion.

Red blood cell transfusion triggers in acute leukemia: a randomized pilot study.

PubMed

DeZern, Amy E; Williams, Katherine; Zahurak, Marianna; Hand, Wesley; Stephens, R Scott; King, Karen E; Frank, Steven M; Ness, Paul M

2016-07-01

Red blood cell (RBC) transfusion thresholds have yet to be examined in large randomized trials in hematologic malignancies. This pilot study in acute leukemia uses a restrictive compared to a liberal transfusion strategy. A randomized (2:1) study was conducted of restrictive (LOW) hemoglobin (Hb) trigger (7 g/dL) compared to higher (HIGH) Hb trigger (8 g/dL). The primary outcome was feasibility of conducting a larger trial. The four requirements for success required that more than 50% of the eligible patients could be consented, more than 75% of the patients randomized to the LOW arm tolerated the transfusion trigger, fewer than 15% of patients crossed over from the LOW arm to the HIGH arm, and no indication for the need to pause the study for safety concerns. Secondary outcomes included fatigue, bleeding, and RBCs and platelets transfused. Ninety patients were consented and randomly assigned to LOW to HIGH. The four criteria for the primary objective of feasibility were met. When the number of units transfused was compared, adjusting for baseline Hb, the LOW arm was transfused on average 8.0 (95% confidence interval [CI], 6.9-9.1) units/patient while the HIGH arm received 11.7 (95% CI, 10.1-13.2) units (p = 0.0003). There was no significant difference in bleeding events or neutropenic fevers between study arms. This study establishes feasibility for trial of Hb thresholds in leukemia through demonstration of success in all primary outcome metrics and a favorable safety profile. This population requires further study to evaluate the equivalence of liberal and restrictive transfusion thresholds in this unique clinical setting. © 2016 AABB.

Acute Lung Injury Complicating Blood Transfusion in Post-Partum Hemorrhage: Incidence and Risk Factors

PubMed Central

Teofili, Luciana; Bianchi, Maria; Zanfini, Bruno A.; Catarci, Stefano; Sicuranza, Rossella; Spartano, Serena; Zini, Gina; Draisci, Gaetano

2014-01-01

Background We retrospectively investigated the incidence and risk factors for transfusion-related acute lung injury (TRALI) among patients transfused for post-partum hemorrhage (PPH). Methods We identified a series of 71 consecutive patients with PPH requiring the urgent transfusion of three or more red blood cell (RBC) units, with or without transfusion of fresh frozen plasma (FFP) and/or platelets (PLT). Clinical records were then retrieved and examined for respiratory distress events. According to the 2004 consensus definition, cases of new-onset hypoxemia, within 6 hours after transfusion, with bilateral pulmonary changes, in the absence of cardiogenic pulmonary edema were identified as TRALI. If an alternative risk factor for acute lung injury was present, possible TRALI was diagnosed. Results Thirteen cases of TRALI and 1 case of possible TRALI were identified (overall incidence 19.7%). At univariate analysis, patients with TRALI received higher number of RBC, PLT and FFP units and had a longer postpartum hospitalization. Among the diseases occurring in pregnancy- and various pre-existing comorbidities, only gestational hypertension and pre-eclampsia, significantly increased the risk to develop TRALI (p = 0.006). At multivariate analysis including both transfusion- and patient-related risk factors, pregnancy-related, hypertensive disorders were confirmed to be the only predictors for TRALI, with an odds ratio of 27.7 ( 95% CI 1.27–604.3, p=0.034). Conclusions Patients suffering from PPH represent a high-risk population for TRALI. The patients with gestational hypertension and pre-eclampsia, not receiving anti-hypertensive therapy, have the highest risk. Therefore, a careful monitoring of these patients after transfusions is recommended. PMID:25408855

Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.

PubMed

Agra, Isabela Karine Rodrigues; Amorim Filho, Antonio Gomes; Lin, Lawrence Hsu; Biancolin, Sckarlet Ernandes; Francisco, Rossana Pulcineli Vieira; Brizot, Maria de Lourdes

2017-11-01

Objective  To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods  This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results  The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion  We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study. Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.

Nationwide survey on the use of eltrombopag in patients with severe aplastic anemia: a report on behalf of the French Reference Center for Aplastic Anemia.

PubMed

Lengline, Etienne; Drenou, Bernard; Peterlin, Pierre; Tournilhac, Olivier; Abraham, Julie; Berceanu, Ana; Dupriez, Brigitte; Guillerm, Gaelle; Raffoux, Emmanuel; de Fontbrune, Flore Sicre; Ades, Lionel; Balsat, Marie; Chaoui, Driss; Coppo, Paul; Corm, Selim; Leblanc, Thierry; Maillard, Natacha; Terriou, Louis; Socié, Gerard; de Latour, Regis Peffault

2018-02-01

Few therapeutic options are available for patients with aplastic anemia who are ineligible for transplantation or refractory to immunosuppressive therapy. Eltrombopag was recently shown to produce trilineage responses in refractory patients. However, the effects of real-life use of this drug remain unknown. This retrospective study (2012-2016) was conducted by the French Reference Center for Aplastic Anemia on patients with relapsed/refractory aplastic anemia, and patients ineligible for antithymocyte globulin or transplantation, who received eltrombopag for at least 2 months. Forty-six patients with aplastic anemia were given eltrombopag without prior antithymocyte globulin treatment (n=11) or after antithymocyte globulin administration (n=35) in a relapsed/refractory setting. Eltrombopag (median daily dose 150 mg) was introduced 17 months (range, 8-50) after the diagnosis of aplastic anemia. At last followup, 49% were still receiving treatment, 9% had stopped due to a robust response, 2% due to toxicity and 40% due to eltrombopag failure. Before eltrombopag treatment, all patients received regular transfusions. The overall rates of red blood cell and platelet transfusion independence were 7%, 33%, 46% and 46% at 1, 3, 6 months and last follow-up. Responses were slower to develop in antithymocyte treatment-naïve patients. In patients achieving transfusion independence, hemoglobin concentration and platelet counts improved by 3 g/dL (interquartile range, 1.4-4.5) and 42×10 9 /L (interquartile range, 11-100), respectively. Response in at least one lineage (according to National Institutes of Health criteria) was observed in 64% of antithymocyte treatment-naïve and 74% of relapsed/refractory patients, while trilineage improvement was observed in 27% and 34%, respectively. We found high rates of hematologic improvement and transfusion independence in refractory aplastic anemia patients but also in patients ineligible for antithymocyte globulin receiving first-line treatment. In conclusion, elderly patients unfit for antithymocyte globulin therapy may benefit from eltrombopag. Copyright© 2018 Ferrata Storti Foundation.

Multicenter study of crystalloid boluses and transfusion in pediatric trauma-When to go to blood?

PubMed

Polites, Stephanie F; Nygaard, Rachel M; Reddy, Pooja N; Zielinski, Martin D; Richardson, Chad J; Elsbernd, Terri A; Petrun, Branden M; Weinberg, Sean L; Murphy, Sherrie; Potter, Donald D; Klinkner, Denise B; Moir, Christopher R

2018-07-01

The 9th edition of Advanced Trauma Life Support recommends up to three crystalloid boluses in pediatric trauma patients with consideration of transfusion after the second bolus; however, this approach is debated. We aimed to determine if requirement of more than one fluid bolus predicts the need for transfusion. The 2010 to 2016 highest tier activation patients younger than 15 years from two ACS Level I pediatric trauma centers were identified from prospectively maintained trauma databases. Those with a shock index (heart rate/systolic blood pressure) greater than 0.9 were included. Crystalloid boluses (20 ± 10 mL/kg) and transfusions administered prehospital and within 12 hours of hospital arrival were determined. Univariate and multivariable analyses were conducted to determine association between crystalloid volume and transfusion. Among 208 patients, the mean age was 5 ± 4 years (60% male), 91% sustained blunt injuries, and median (interquartile range) Injury Severity Score was 11 (6,25). Twenty-nine percent received one bolus, 17% received two, and 10% received at least three. Transfusion of any blood product occurred in 50 (24%) patients; mean (range) red blood cells was 23 (0-89) mL/kg, plasma 8 (0-69), and platelets 1 (0-18). The likelihood of transfusion increased logarithmically from 11% to 43% for those requiring 2 or more boluses (Fig. 1). This relationship persisted on multivariable analysis that adjusted for institution, age, and shock index with good discrimination (Area under the Receiver Operating Characteristic, 0.84). Shock index was also strongly associated with transfusion. Almost half of pediatric trauma patients with elevated shock index require transfusion following two crystalloid boluses and the odds of requiring a transfusion plateau at this point in resuscitation. This supports consideration of blood with the second bolus in conjunction with shock index though prospective studies are needed to confirm this and its impact on outcomes. Therapeutic study, level IV.

Reduced MHC Alloimmunization and Partial Tolerance Protection With Pathogen Reduction Of Whole Blood

PubMed Central

Jackman, Rachael P.; Muench, Marcus O.; Inglis, Heather; Heitman, John W.; Marschner, Susanne; Goodrich, Raymond P.; Norris, Philip J.

2017-01-01

BACKGROUND Allogeneic blood transfusion can result in an immune response against major histocompatibility complex (MHC) antigens, potentially complicating future transfusions or transplants. We have previously shown that pathogen reduction of platelet-rich plasma (PRP) with riboflavin and UV light (UV+R) can prevent alloimmunization in mice. A similar pathogen reduction treatment is currently under development for the treatment of whole blood using riboflavin and a higher dose of UV light. We sought to determine the effectiveness of this treatment in prevention of alloimmunization. STUDY DESIGN AND METHODS BALB/c mice were transfused with untreated or UV+R treated allogeneic C57Bl/6 whole blood with or without leukoreduction. Mice were evaluated for donor specific antibodies and ex vivo splenocyte cytokine responses, as well as for changes in the frequency of regulatory T (Treg) cells. RESULTS UV+R treatment blocked cytokine priming and reduced anti-MHC alloantibody responses to transfused whole blood. Leukoreduction reduced alloantibody levels in both the untreated and UV+R groups. Mice transfused with UV+R treated whole blood had reduced alloantibody and cytokine responses when subsequently transfused with untreated blood from the same donor type. This reduction in responses was not associated with increased Treg cells. CONCLUSIONS Pathogen reduction of whole blood with UV+R significantly reduces, but does not eliminate the alloimmune response. Exposure to UV+R treated whole blood transfusion does appear to induce tolerance to alloantigens resulting in reduced anti-MHC alloantibody and cytokine responses to subsequent exposures to the same alloantigens. This tolerance does not appear to be driven by an increase in Treg cells. PMID:27859333

Is undertransfusion a problem in modern clinical practice?

PubMed

Hibbs, Stephen; Miles, David; Staves, Julie; Murphy, Michael F

2015-04-01

Significant progress has been made in reducing inappropriate transfusion of blood products. However, there is also a need to monitor for their underutilization in patients who would benefit from transfusion. This study aimed to develop a method to monitor for undertransfusion and conduct a preliminary examination of whether it is a problem in modern clinical practice. All patients with a hemoglobin (Hb) concentration below 6 g/dL or platelet (PLT) count of fewer than 10 × 10(9) /L were identified during a 1-month period in an academic medical center in the United Kingdom. Patients who were transfused within 72 hours of the low reading were excluded from further analysis. For all other patients, records were examined against predefined criteria to ascertain whether the reason for nonadministration of transfusion was justified. During the study period there were 63 eligible Hb readings and 130 eligible PLT counts in 93 patients. Of these, 36 patients were not transfused within 72 hours of the low reading. The majority of nonadministration (n = 28) was justified by either an additional Hb or an additional PLT count on repeat sampling being above the transfusion threshold or the transfusion being medically inappropriate. No documentation was found to indicate that any cases of nonadministration of blood were unjustified. This study did not find that patients with low Hb readings or PLT counts were inappropriately undertransfused. However, systems similar to those described in this study should be developed to monitor for inappropriate undertransfusion as well as continuing efforts to monitor for and reduce inappropriate overtransfusion. © 2014 AABB.

Metabolomics in transfusion medicine.

PubMed

Nemkov, Travis; Hansen, Kirk C; Dumont, Larry J; D'Alessandro, Angelo

2016-04-01

Biochemical investigations on the regulatory mechanisms of red blood cell (RBC) and platelet (PLT) metabolism have fostered a century of advances in the field of transfusion medicine. Owing to these advances, storage of RBCs and PLT concentrates has become a lifesaving practice in clinical and military settings. There, however, remains room for improvement, especially with regard to the introduction of novel storage and/or rejuvenation solutions, alternative cell processing strategies (e.g., pathogen inactivation technologies), and quality testing (e.g., evaluation of novel containers with alternative plasticizers). Recent advancements in mass spectrometry-based metabolomics and systems biology, the bioinformatics integration of omics data, promise to speed up the design and testing of innovative storage strategies developed to improve the quality, safety, and effectiveness of blood products. Here we review the currently available metabolomics technologies and briefly describe the routine workflow for transfusion medicine-relevant studies. The goal is to provide transfusion medicine experts with adequate tools to navigate through the otherwise overwhelming amount of metabolomics data burgeoning in the field during the past few years. Descriptive metabolomics data have represented the first step omics researchers have taken into the field of transfusion medicine. However, to up the ante, clinical and omics experts will need to merge their expertise to investigate correlative and mechanistic relationships among metabolic variables and transfusion-relevant variables, such as 24-hour in vivo recovery for transfused RBCs. Integration with systems biology models will potentially allow for in silico prediction of metabolic phenotypes, thus streamlining the design and testing of alternative storage strategies and/or solutions. © 2015 AABB.

Preoperative Aspirin Does Not Increase Transfusion or Reoperation in Isolated Valve Surgery.

PubMed

Goldhammer, Jordan E; Herman, Corey R; Berguson, Mark W; Torjman, Marc C; Epstein, Richard H; Sun, Jian-Zhong

2017-10-01

Preoperative aspirin has been studied in patients undergoing isolated coronary artery bypass graft surgery. However, there is a paucity of clinical data available evaluating perioperative aspirin in other cardiac surgical procedures. This study was designed to investigate the effects of aspirin on bleeding and transfusion in patients undergoing non-emergent, isolated, heart valve repair or replacement. Retrospective, cohort study. Academic medical center. A total of 694 consecutive patients having non-emergent, isolated, valve repair or replacement surgery at an academic medical center were identified. Of the 488 patients who met inclusion criteria, 2 groups were defined based on their preoperative use of aspirin: those taking (n = 282), and those not taking (n = 206) aspirin within 5 days of surgery. Binary logistic regression was used to examine relationships among demographic and clinical variables. No significant difference was found between the aspirin and non-aspirin groups with respect to the percentage receiving red blood cell (RBC) transfusion, mean RBC units transfused in those who required transfusion, massive transfusion of RBC, or amounts of fresh frozen plasma, cryoprecipitate, or platelets. Aspirin was not associated with an increase in the rate of re-exploration for bleeding (5.3% v 6.3%, p = 0.478). Major adverse cardiocerebral events (MACE), 30-day mortality, and 30-day readmission rates were not statistically different between the aspirin-and non-aspirin-treated groups. Preoperative aspirin therapy in elective, isolated, valve surgery did not result in an increase in transfusion or reoperation for bleeding and was not associated with reduced readmission rate, MACE, or 30-day mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

Big data modeling to predict platelet usage and minimize wastage in a tertiary care system.

PubMed

Guan, Leying; Tian, Xiaoying; Gombar, Saurabh; Zemek, Allison J; Krishnan, Gomathi; Scott, Robert; Narasimhan, Balasubramanian; Tibshirani, Robert J; Pham, Tho D

2017-10-24

Maintaining a robust blood product supply is an essential requirement to guarantee optimal patient care in modern health care systems. However, daily blood product use is difficult to anticipate. Platelet products are the most variable in daily usage, have short shelf lives, and are also the most expensive to produce, test, and store. Due to the combination of absolute need, uncertain daily demand, and short shelf life, platelet products are frequently wasted due to expiration. Our aim is to build and validate a statistical model to forecast future platelet demand and thereby reduce wastage. We have investigated platelet usage patterns at our institution, and specifically interrogated the relationship between platelet usage and aggregated hospital-wide patient data over a recent consecutive 29-mo period. Using a convex statistical formulation, we have found that platelet usage is highly dependent on weekday/weekend pattern, number of patients with various abnormal complete blood count measurements, and location-specific hospital census data. We incorporated these relationships in a mathematical model to guide collection and ordering strategy. This model minimizes waste due to expiration while avoiding shortages; the number of remaining platelet units at the end of any day stays above 10 in our model during the same period. Compared with historical expiration rates during the same period, our model reduces the expiration rate from 10.5 to 3.2%. Extrapolating our results to the ∼2 million units of platelets transfused annually within the United States, if implemented successfully, our model can potentially save ∼80 million dollars in health care costs.

Routine bacterial screening of apheresis platelets on Day 4 using a rapid test: a 4-year single-center experience.

PubMed

Dunbar, Nancy M; Kreuter, Justin D; Marx-Wood, Cynthia R; Dumont, Larry J; Szczepiorkowski, Zbigniew M

2013-10-01

The platelet (PLT) Pan Genera Detection test (PGD) is a rapid bacterial detection system used to screen PLTs for bacterial contamination. We report a single center 46-month experience with secondary screening of apheresis PLTs by PGD testing. Existing testing records of apheresis PLTs screened by PGD from July 2008 to April 2012 were reviewed. All PLT units were initially screened by routine postcollection culture methods. Secondary screening using PGD was performed for indated PLTs on PLT storage Day 4 and for outdated PLTs on Day 8. A total of 8535 apheresis PLTs were available in inventory during the study period. Of these, 5030 (58.9%) were dispensed and transfused before PGD testing and 3505 (41.1%) underwent PGD testing on Day 4. Twenty-five units tested on Day 4 were PGD initial reactive (0.71%). All were confirmed to be false positive by repeat PGD testing in triplicate (n=20) or by confirmatory culture (n=5). An additional 364 units that were PGD nonreactive on Day 4 were approved for transfusion on Day 6 or Day 7 due to urgent clinical need. A total of 371 outdated units underwent repeat PGD testing before discard on Day 8; all were nonreactive. Secondary PGD testing of culture-screened apheresis PLTs results in low yield in a medium-sized transfusion service. Use of PGD testing on Day 4 may allow for extension of the apheresis PLT shelf life to Day 7 for hospitals that face supply constraints. © 2013 American Association of Blood Banks.

Detection of bacterial contamination in platelet concentrates by a sensitive flow cytometric assay (BactiFlow): a multicentre validation study.

PubMed

Vollmer, T; Dreier, J; Schottstedt, V; Bux, J; Tapernon, K; Sibrowski, W; Kleesiek, K; Knabbe, C

2012-08-01

Bacterial contamination of platelet concentrates (PCs) still represents an ongoing risk. As a result of septic complications, particularly observed with older PCs, the shelf life of PCs has been reduced in Germany to 4 days. In this study, bacterial screening of PCs by BactiFlow (BF) flow cytometry was introduced in three German blood services to evaluate the robustness and applicability of the assay. Results were used to discuss the potential for the extension of PC shelf life to 5 days. A total of 1956 PCs were tested on days 4 or 5+ after PC production using the BF, whereas the BacT/Alert culture system served as reference method. Two PCs were confirmed positive by culture only and were identified as Propionibacterium acnes and Staphylococcus species. Two PCs were confirmed positive for Streptococcus mitis by BF and culture. Additionally, two PCs were culture-positive only in one culture bottle (aerobic: S. mitis and anaerobic: S. hominis). Retrospective analysis of bacterial growth kinetics provide the indication that corresponding bacterial titres were most likely below the BF analytical detection limit (<150 CFU mL(-1) ) and had probably no transfusion relevance. All remaining specimens were tested negative. Testing of PCs by BF was successfully implemented. The BF proved sufficient as a rapid screening method to improve PC safety. This study further provides data supporting the extension of PC shelf life to 5 days after negative BF testing on day 4. © 2012 The Authors. Transfusion Medicine © 2012 British Blood Transfusion Society.

[Demography and donation frequencies of blood and plasma donor populations in Germany].

PubMed

Ritter, Sabine; Willand, L; Reinhard, B; Offergeld, R; Hamouda, O

2008-08-01

According to Article 22 of the Transfusion Act, the Robert Koch Institute collects and evaluates nationwide data on the prevalence and incidence of transfusion-relevant infections among blood and plasma donors in Germany. Due to revision of the Transfusion Act in 2005 not only the number of donations but also the number of donors has become available for analysis. Here we give a detailed account on the demographic profile and donation frequencies of German whole blood, plasma and platelet donors in 2006. Overall, 4 % of the German population eligible to donate were active as repeat whole blood donors in 2006; 0.3 % repeatedly donated plasma or platelets. Irrespective of the type of donation, the percentage of donors among the general population was highest among the youngest age group (18 to 24 years). While the age distribution of whole blood repeat donors roughly resembled that of the general population, with the greatest number among those aged 35 to 44, younger age groups were overrepresented among repeat plasma donors. Donation frequency varied depending on donor age and sex, with an average of 1.9 per year for whole blood donations, 11.9 for plasmapheresis and 4.0 for plateletpheresis. With the exception of the latter, men donated more frequently than women. For both sexes, donation frequency increased with age. Detailed knowledge of the demographic profile and changes in the composition of donor populations are essential for planning adequate blood supply. The data presented may serve as reference for assessing the consequences of measures that affect the number of donors and/or donations (for example changing deferral criteria) in Germany.

Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.

PubMed

Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta

2012-01-01

Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

Automated processing of leucocyte-poor platelet concentrates.

PubMed

Tandy, N P; Seghatchian, M J; Bessos, H

1992-10-01

In view of transfusion reactions and alloimmunization associated with leucocyte contamination of platelet concentrates (PC), there is a general move towards the production of leuco-poor PC. This goal is currently pursued by the production of various PC using buffy coat and apheresis techniques. Although there is no overall consensus on the meaning of 'leuco-poor', by assuming that this refers to a level of 5-50 x 10(7) leucocytes per PC, we were able to make comparisons with available systems used in Europe. In addition to platelet and white cell counts, other markers of PC quality were assessed in some cases. These included traditional markers (such as hypotonic stress response, pH, and lactate and beta-thromboglobulin levels) and newer markers (such as glycocalicin and plasma von Willebrand factor levels). Our preliminary results showed appreciable differences in platelet and white cell content of PC prepared by various types of apheresis equipment. Appreciable differences in the quality of stored PC were also observed between routine PC (non-leuco-poor and buffy coat and apheresed PC (leuco-poor).

Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes

PubMed Central

Desmond, Ronan; Dunbar, Cynthia E.; Young, Neal S.

2014-01-01

Aplastic anemia is a bone marrow failure syndrome that causes pancytopenia and can lead to life-threatening complications. Bone marrow transplantation remains the standard of care for younger patients and those with a good performance status but many patients may not have a suitable donor. Immunosuppressive therapy is able to resolve cytopenias in a majority of patients with aplastic anemia but relapses are not uncommon and some patients remain refractory to this approach. Patients may require frequent blood and platelet transfusion support which is expensive and inconvenient. Life-threatening bleeding complications still occur despite prophylactic platelet transfusion. Thrombopoietin (TPO) mimetics, such as romiplostim and eltrombopag, were developed to treat patients with refractory immune thrombocytopenia but are now being investigated for the treatment of bone marrow failure syndromes. TPO is the main regulator for platelet production and its receptor (c-Mpl) is present on megakaryocytes and hematopoietic stem cells. Trilineage hematopoietic responses were observed in a recent clinical trial using eltrombopag in patients with severe aplastic anemia refractory to immunosuppression suggesting that these agents can provide a new therapeutic option for enhancing blood production. In this review, we discuss these recent results and ongoing investigation of TPO mimetics for aplastic anemia and other bone marrow failure states like myelodysplastic syndromes. Clonal evolution or progression to acute myeloid leukemia remains a concern when using these drugs in bone marrow failure and patients should only be treated in the setting of a clinical trial. PMID:23690288

A Rare Case of Transfusion Transmission of Hepatitis A Virus to Two Patients with Haematological Disease

PubMed Central

da Silva, Suely Gonçalves Cordeiro; Leon, Luciane Almeida Amado; Alves, Gilda; Brito, Selma Magalhães; Sandes, Valcieny de Souza; Lima, Magda Maria Adorno Ferreira; Nogueira, Marta Colares; Tavares, Rita de Cássia Barbosa da Silva; Dobbin, Jane; Apa, Alexandre; de Paula, Vanessa Salete; Oliveira, Jaqueline Mendes de Oliveira; Pinto, Marcelo Alves; Ferreira Jr, Orlando da Costa; Motta, Iara de Jesus Ferreira

2016-01-01

Summary Background This paper describes the transmission of hepatitis A virus (HAV) to two blood recipients from a healthy donor that later presented to the blood bank with jaundice. Methods The RNA of HAV was detected by qualitative nested reverse transcription polymerase chain reaction (nested RT-PCR) and quantified by real-time RT-PCR. HAV RNA samples were genotyped by direct sequencing of PCR products. A sequence from a fragment of 168 bp from the VP1/2A HAV region was used to construct a phylogenetic tree. Case Report A 31-year-old male donor accepted for donation of a whole blood unit returned to the blood bank with clinical jaundice 20 days after donation. His serological and NAT tests were negative for HBV and HCV. Serological tests for HAV IgM and IgG were negative on donation sample but positive on follow-up sample, confirming donor's HAV acute infection. Both recipients of red blood cells (R1) and platelet concentrate (R2) from the same implicated donation were HAV IgM-negative and IgG-positive. Qualitative PCR was positive on samples from all three individuals and phylogenetic analysis of viruses proved HAV transmission to the two recipients of blood products. HAV viral load on donor follow-up sample and the platelet recipient was 1.3 and 1.5 × 103 IU/ml, respectively. The RBC recipient, also infected by HCV, was undergoing bone marrow transplantation and died from fulminant hepatitis, 26 days after the implicated HAV transfusion. Conclusion The blood donor, a garbage collector, spontaneously returned to the blood bank when developing jaundice. This highlights the importance of donor education to immediately report to blood banks of any signs and symptoms related to infectious disease developed after blood donation. The fact that one immunocompromised patient with HCV infection died from fulminant hepatitis after receiving a HAV-contaminated platelet transfusion underpins the importance of a HAV vaccination program for these group of patients. PMID:27226795

Two Novel Real-Time Reverse Transcriptase PCR Assays for Rapid Detection of Bacterial Contamination in Platelet Concentrates

PubMed Central

Dreier, Jens; Störmer, Melanie; Kleesiek, Knut

2004-01-01

The incidence of platelet bacterial contamination is approximately 1 per 2,000 units and has been acknowledged as the most frequent infectious risk from transfusion. In preliminary studies, the sterility of platelet concentrates (PCs) was tested with an automated bacterial blood culturing system and molecular genetic assays. Two real-time reverse transcriptase PCR (RT-PCR) assays performed in a LightCycler instrument were developed and compared regarding specificity and sensitivity by the use of different templates to detect the majority of the clinically important bacterial species in platelets. Primers and probes specific for the conserved regions of the eubacterial 23S rRNA gene or the groEL gene (encoding the 60-kDa heat shock protein Hsp60) were designed. During the development of the 23S rRNA RT-PCR, problems caused by the contamination of reagents with bacterial DNA were noted. Treatment with 8-methoxypsoralen and UV irradiation reduced the level of contaminating DNA. The sensitivity of the assays was greatly influenced by the enzyme system which was used. With rTth DNA polymerase in a one-enzyme system, we detected 500 CFU of Escherichia coli or Staphylococcus epidermidis/ml. With a two-enzyme system consisting of Moloney murine leukemia virus RT and Taq DNA polymerase, we detected 16 CFU/ml. With groEL mRNA as the target of RT-PCR under optimized conditions, we detected 125 CFU of E. coli/ml, and no problems with false-positive results caused by reagent contamination or a cross-reaction with human nucleic acids were found. Furthermore, the use of mRNA as an indicator of viability was demonstrated. Here we report the application of novel real-time RT-PCR assays for the detection of bacterial contamination of PCs that are appropriate for transfusion services. PMID:15472337

Blood component use in a sub-Saharan African country: results of a 4-year evaluation of diagnoses associated with transfusion orders in Namibia.

PubMed

Pitman, John P; Wilkinson, Robert; Liu, Yang; von Finckenstein, Bjorn; Smit Sibinga, Cees Th; Lowrance, David W; Marfin, Anthony A; Postma, Maarten J; Mataranyika, Mary; Basavaraju, Sridhar V

2015-01-01

National blood use patterns in sub-Saharan Africa are poorly described. Although malaria and maternal hemorrhage remain important drivers of blood demand across Africa, economic growth and changes in malaria, HIV/AIDS, and noncommunicable disease epidemiology may contribute to changes in blood demand. We evaluated indications for blood use in Namibia, a country in southern Africa, using a nationally representative sample and discuss implications for the region. Clinical and demographic data related to the issuance of blood component units in Namibia were reviewed for a 4-year period (August 1, 2007-July 31, 2011). Variables included blood component type, recipient age and sex, and diagnosis. Diagnoses reported by clinicians were reclassified into International Statistical Classification of Diseases, 10th Revision categories. Multiple imputation methods were used to complete a data set missing age, sex or diagnosis data. Descriptive analyses were conducted to describe indications for transfusions and use of red blood cells (RBCs), platelets, and plasma. A total of 39,313 records accounting for 91,207 blood component units were analyzed. The median age of Namibian transfusion recipients was 45 years (SD, ±19). A total of 78,660 RBC units were issued in Namibia during the study period. Red blood cells transfused for "unspecified anemia" accounted for the single largest category of blood issued (24,798 units). Of the overall total, 38.9% were for diseases of the blood and blood-forming organs (D50-D89). Infectious disease (A00-B99), pregnancy (O00-O99), and gastrointestinal (K20-K93) accounted for 14.8%, 11.1%, and 6.1% of RBC units issued, respectively. Although a specific diagnosis of malaria accounted for only 2.7% of pediatric transfusions, an unknown number of additional transfusions for malaria may have been categorized by requesting physicians as unspecified anemia and counted under diseases of blood forming organs. During the study period, 9751 units of fresh-frozen plasma were issued. Nearly one-quarter of these units (23.1%) were issued for gastrointestinal (K20-K93) diagnoses. Malignant neoplasms (C00-C97) accounted for 38.1% of 2978 platelet units issued. Blood use in Namibia reflects changes in the health care system due to economic development, improvement in HIV/AIDS and malaria epidemiology, high rates of health care facility-based childbirth, and access to noncommunicable disease treatment. However, better documentation of the indications for transfusion is needed to confirm these observations. Changing patterns of health care will result in changing demands for blood components. Improved methods to evaluate blood use patterns in sub-Saharan Africa may help set realistic national blood collection goals. Published by Elsevier Inc.

Blood use in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation: the impact of a health system-wide patient blood management program.

PubMed

Leahy, Michael F; Trentino, Kevin M; May, Colleen; Swain, Stuart G; Chuah, Hun; Farmer, Shannon L

2017-09-01

Little is published on patient blood management (PBM) programs in hematology. In 2008 Western Australia announced a health system-wide PBM program with PBM staff appointments commencing in November 2009. Our aim was to assess the impact this program had on blood utilization and patient outcomes in intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. A retrospective study of 695 admissions at two tertiary hospitals receiving intensive chemotherapy for acute leukemia or undergoing hematopoietic stem cell transplantation between July 2010 and December 2014 was conducted. Main outcomes included pre-red blood cell (RBC) transfusion hemoglobin (Hb) levels, single-unit RBC transfusions, number of RBC and platelet (PLT) units transfused per admission, subsequent day case transfusions, length of stay, serious bleeding, and in-hospital mortality. Over the study period, the mean RBC units transfused per admission decreased 39% from 6.1 to 3.7 (p < 0.001), and the mean PLT units transfused decreased 35% from 6.3 to 4.1 (p < 0.001), with mean RBC and PLT units transfused for follow-up day cases decreasing from 0.6 to 0.4 units (p < 0.001). Mean pre-RBC transfusion Hb level decreased from 8.0 to 6.8 g/dL (p < 0.001), and single-unit RBC transfusions increased 39% to 67% (p < 0.001). This reduction represents blood product cost savings of AU$694,886 (US$654,007). There were no significant changes in unadjusted or adjusted length of stay, serious bleeding events, or in-hospital mortality over the study. The health system-wide PBM program had a significant impact, reducing blood product use and costs without increased morbidity or mortality in patients receiving intensive chemotherapy for acute leukemia or hematopoietic stem cell transplantation. © 2017 AABB.

The effect of ambient exposure to PM2.5 on the transfusion usage of blood components and adverse transfusion reactions in the haze weather.

PubMed

Chang, Chih-Chun; Lin, Hui-Jung; Sun, Jen-Tang; Li, Pei-Yu; Lee, Tai-Chen; Su, Ming-Jang; Yen, Tzung-Hai; Chu, Fang-Yeh

2016-10-01

Accumulating evidence has shown that ambient exposure to PM 2.5 , especially in the haze weather, increased the risk of various diseases. However, the association of air pollution status with blood transfusion utilization and the prevalence and severity of adverse transfusion reactions remain to be clarified. The data of monthly transfusion usage of blood components, adverse transfusion reactions, as well as PM 2.5 and PM 10 levels from 2013 to 2015 were obtained. During the study interval, both PM 2.5 and PM 10 levels were significantly increased in the haze weather when compared with the non-haze weather. The utilization of total blood components per patient-month in the haze weather was prone to be increased when compared with that in the non-haze weather (13.28 ± 1.66 vs. 12.33 ± 1.30, p = 0.068). The usage of RBC products per patient-month in the haze weather was significantly increased when compared with that in the non-haze weather (4.39 ± 0.39 vs. 4.07 ± 0.30, p = 0.009). There was no obvious difference between the haze and non-haze weathers for the usage of platelet and plasma products per patient-month. Besides, no definite differences of the prevalence and severity of transfusion-associated adverse reaction were observed between the haze and non-haze weathers. Our study first indicated that transfusion utilization, particularly the RBC products, was significantly increased in the haze weather when compared with that in the non-haze weather. There was no obvious association of air pollution with the prevalence and severity of adverse transfusion reactions and further research is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

A preliminary report of 123 units of placental umbilical cord whole blood transfusion in HIV-positive patients with anemia and emaciation.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our team's experience (from 1st April 1999 to 1st July 2005) with 123 units of placental umbilical cord whole blood (62 ml-154 ml mean 85 ml +/- 8.4 ml SD, median 82 ml, mean packed cell volume 48.8 +/- 4.2 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.6 g/dl SD; after collection the blood was immediately preserved in a refrigerator and transfused within 72 hours of collection) collected after lower uterine cesarean section (LUCS), and the transfusion to 16 consenting HIV-positive patients (12 cases had full blown AIDS) with anemia and emaciation is presented here. On the basis of our preliminary experience of cord blood transfusion, we are of the opinion that umbilical cord whole blood transfusion is safe in HIV-positive patients. This blood has the potential to carry more oxygen than adult blood and it does not trigger any clinical, immunological or non-immunological reaction after its transfusion to an adult host with a HIV-positive status. Apart from the correction of anemia, there was also definite improvement in the energy and fatigue levels in individuals with HIV, i.e., physical functioning, a sense of well-being and weight gain from two to five pounds, within three to ten months of the commencement of transfusion. There was also an immediate rise in CD34 levels of peripheral blood in the HLA-randomized host after transfusion, without any clinical graft vs host reaction.

A successful experience of the Iranian blood transfusion organization in improving accessibility and affordability of plasma derived medicine.

PubMed

Chegini, Azita; Torab, Seyed Ardeshir; Pourfatollah, Ali Akbar

2017-02-01

Plasma is the liquid part of blood. It is estimated 21.6 million liters of plasma collect from Whole blood annually. From these plasma, 4.2 million liters transfuse, 8.1 million liters fractionate, 9.3 million liters waste. Nowadays, blood products and PDM (plasma derived medicine) consider as essential medicine in modern health care and transfusion medicine. Iranian blood transfusion organization as a non-profit organization was established in 1974 in order to centralize all blood transfusion activities from donor recruitment to distribution of blood components to hospitals. Iran is the only country in EMR region with the rate of 20-29.9 blood donations per 1000 population and reached 100% voluntary non-remunerated blood donation in 2007. RBCs and platelets demand are much more than FFPs so the IBTO was faced the surplus plasma that could cause surplus plasma wastage. Simultaneously, hospitals need more plasma derived medicine especially albumin, IVIG, factor VIII, factor IX. IBTO was faced the challenges such as Fractionators selection, Plasma volume shipment, Contract duration, Product profile, Multiple External audits, Cold chain maintenance, Transporting plasma across international borders, NAT test. To overcome plasma wastage and storage of PDM. IBTO involved toll manufacturing in 2005 and not only prevents plasma wastage but also save MOH (ministry of health) budget. Copyright © 2016. Published by Elsevier Ltd.

Recombinant human erythropoietin in the prevention of late anemia in intrauterine transfused neonates with Rh-isoimmunization.

PubMed

Zuppa, Antonio Alberto; Alighieri, Giovanni; Calabrese, Valentina; Visintini, Federica; Cota, Francesco; Carducci, Chiara; Antichi, Eleonora; Noia, Giuseppe Antonio; Fortunato, Giuseppe; Romagnoli, Costantino

2010-04-01

The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.

Heterogeneous distribution of antigens on human platelets demonstrated by fluorescence flow cytometry.

PubMed

Dunstan, R A; Simpson, M B

1985-12-01

We have used fluorescence flow cytometry to analyse cell-to-cell variability in the density of platelet ABH, Ii, Lewis, P, P1A1, Bak,a and HLA class I antigens. Human IgG and IgM antibodies were used in a two-stage assay with goat FITC-conjugated antihuman IgG (H&L) antibody as the label, followed by single cell analysis of 10 000 platelets per sample using a 256-channel fluorescence flow cytometer (Becton-Dickinson FACS Analyser). Computer analysis of fluorescence intensity histograms for mean and peak channel and coefficient of variation shows that the degree of heterogeneity in platelet antigen density varies with each particular blood group. The broad fluorescence distribution curves with oligosaccharide antigens (CVs: A = 53, B = 40, I = 44, Lea = 40, P = 40) indicate that these antigens possess a greater variability in the number of sites per cell compared to the more homogeneous distribution of P1,A1 BaK,a and HLA (CVs: P1A1 = 24, HLA = 30). These findings may partly account for the mechanism by which transfusion of ABO-incompatible platelets results in a biphasic survival curve, with a period of early rapid removal of those platelets with a high density of antigen sites, followed by a relatively normal survival curve for those platelets that possess only a few or no antigen sites. In contrast, P1A1 and HLA sites are less variable in number from one platelet to another in a given donor, and immune-mediated removal would be more likely to approximate a single exponential curve.

A Systematic Review and Meta-Analysis of the Clinical Appropriateness of Blood Transfusion in China

PubMed Central

Zhu, Changtai; Gao, Yulu; Li, Zhiqiang; Li, Qinyun; Gao, Zongshuai; Liao, Yanqiu; Deng, Zhifeng

2015-01-01

Abstract The issue of the clinical appropriateness of blood transfusion has become a focus of transfusion medicine worldwide. In China, irrational uses of blood have often been reported in recent years. However, to date there lacks a systematic review of the rational uses of blood. This study aimed to determine the clinical appropriateness of blood transfusion in China. We searched PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and Chinese BioMedical Literature Database, and the retrieval cut-off date was June 31, 2015. SPSS 17.0 and MetaAnalyst 3.13 were employed as the statistics tools in this review. A pooled rate of clinical inappropriateness of transfusion was analyzed by DerSimonian–Laird method. In this study, a total of 39 observational studies were included, which related to 75,132 cases of blood transfusion. According to the meta-analysis results, the overall incidence of clinical inappropriateness of transfusion in China was estimated to be 37.3% (95% confidence interval [CI] [32.1, 42.8]). The subgroup analyses revealed that the pooled rates of clinical inappropriateness of transfusion of plasma, red blood cells (RBCs), cryoprecipitate, and platelets were 56.3% (95% CI [45.8, 66.2]), 30.9% (95% CI [27.1, 35.0]), 25.2% (95% CI [13.2, 42.7]), and 14.1% (95% CI [8.8, 21.9]), respectively. However, the pooled incidence of inappropriateness of transfusion in operative departments was 47.5% (95% CI [36.8, 58.3]), which was significantly higher than that in nonoperative departments, 25.8% (95% CI [18.7, 34.4], P < 0.05). The overall rates of inappropriate use were 36.7% (95% CI [30.2, 43.6]) in major cities and 37.5% (95% CI [31.2, 44.3]) in other cities, respectively; there was no statistically significant difference (P > 0.05). In conclusion, China has suffered from a disadvantage in the clinical appropriateness of blood transfusion, especially in plasma and RBC use. In future, comprehensive measures should be implemented in order to improve the clinical appropriateness of blood transfusion. PMID:26683925

A Systematic Review and Meta-Analysis of the Clinical Appropriateness of Blood Transfusion in China.

PubMed

Zhu, Changtai; Gao, Yulu; Li, Zhiqiang; Li, Qinyun; Gao, Zongshuai; Liao, Yanqiu; Deng, Zhifeng

2015-12-01

The issue of the clinical appropriateness of blood transfusion has become a focus of transfusion medicine worldwide. In China, irrational uses of blood have often been reported in recent years. However, to date there lacks a systematic review of the rational uses of blood. This study aimed to determine the clinical appropriateness of blood transfusion in China. We searched PubMed, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database, WanFang Database, and Chinese BioMedical Literature Database, and the retrieval cut-off date was June 31, 2015. SPSS 17.0 and MetaAnalyst 3.13 were employed as the statistics tools in this review. A pooled rate of clinical inappropriateness of transfusion was analyzed by DerSimonian-Laird method. In this study, a total of 39 observational studies were included, which related to 75,132 cases of blood transfusion. According to the meta-analysis results, the overall incidence of clinical inappropriateness of transfusion in China was estimated to be 37.3% (95% confidence interval [CI] [32.1, 42.8]). The subgroup analyses revealed that the pooled rates of clinical inappropriateness of transfusion of plasma, red blood cells (RBCs), cryoprecipitate, and platelets were 56.3% (95% CI [45.8, 66.2]), 30.9% (95% CI [27.1, 35.0]), 25.2% (95% CI [13.2, 42.7]), and 14.1% (95% CI [8.8, 21.9]), respectively. However, the pooled incidence of inappropriateness of transfusion in operative departments was 47.5% (95% CI [36.8, 58.3]), which was significantly higher than that in nonoperative departments, 25.8% (95% CI [18.7, 34.4], P < 0.05). The overall rates of inappropriate use were 36.7% (95% CI [30.2, 43.6]) in major cities and 37.5% (95% CI [31.2, 44.3]) in other cities, respectively; there was no statistically significant difference (P > 0.05). In conclusion, China has suffered from a disadvantage in the clinical appropriateness of blood transfusion, especially in plasma and RBC use. In future, comprehensive measures should be implemented in order to improve the clinical appropriateness of blood transfusion.

Use of a platelet-rich fibrin membrane to repair traumatic tympanic membrane perforations: a comparative study.

PubMed

Gür, Özer Erdem; Ensari, Nuray; Öztürk, Mehmet Türker; Boztepe, Osman Fatih; Gün, Taylan; Selçuk, Ömer Tarık; Renda, Levent

2016-10-01

(1) To evaluate the effects of a platelet-rich fibrin (PRF) membrane in the repair of traumatic tympanic membrane (TM) perforations; and (2) to compare the use of a PRF membrane with the paper patch technique with regard to recovery rates, healing time, and correction of the mean air-bone gap. A randomized, prospective analysis was performed for 60 patients who were treated for traumatic TM perforations using one of the two methods. Closure rate, speed of healing, and hearing gain were compared between the PRF (Group 1) and paper patch (Group 2) groups. Closure was obtained in 28 (93%) perforations in Group 1 and 25 (83%) perforations in Group 2 (p > 0.05). On day 10, full closure of the TM was observed in 24 (80%) patients in Group 1 and 16 (53%) patients in Group 2 (p < 0.05). The improvement in the mean air-bone gap was 14.1 dB in Group 1 and 12.4 dB in Group 2 on post-operative day 45 (p < 0.05). In comparison with the paper patch method, PRF, a new method, provided more rapid healing with more successful audiological results, and with no requirement for a second procedure.

Amelioration of lesions associated with 24-hour suboptimal platelet storage at 16 °C by a p38MAPK inhibitor, VX-702.

PubMed

Wagner, S J; Skripchenko, A; Seetharaman, S; Kurtz, J

2015-04-01

Previous studies with p38MAPK inhibitors at room temperature demonstrated that they improve a large number of platelet storage parameters, but cannot substantially inhibit p38MAPK activation nor protect against widespread decrements in platelet quality parameters during 4 °C storage. In this study, platelet quality parameters and inhibition of p38MAPK by VX-702 were studied after incubation of platelets at 16 °C without agitation, suboptimal storage conditions which produce moderate platelet decrements. Trima apheresis units were collected and aliquoted into three 60-ml CLX storage bags: (i) a control aliquot which was held at 20-24 °C with constant agitation; (ii) a test aliquot which was held at 20-24 °C with agitation until Day 2, when it was reincubated at 16 ± 1 °C for 24 ± 0·5 h without agitation and then returned 20-24 °C with agitation; (iii) a test aliquot containing 1 μm VX-702 stored in an identical fashion as aliquot 2. Aliquots were tested for an array of platelet storage parameters and p38MAPK activation on Days 1, 4 and 7. Many platelet storage parameters and p38MAPK activation were adversely affected by 24-h incubation at 16 °C without agitation. With the exception of ESC, addition of VX-702 prevented p38MAPK activation and the decrements in most observed parameters. Unlike 4 °C storage, VX-702 prevents activation of p38MAPK and decrements in many platelet storage parameters after exposure to 16 °C without agitation for 24 h. © 2014 International Society of Blood Transfusion.

Growth factor and proteinase profile of Vivostat® platelet-rich fibrin linked to tissue repair.

PubMed

Agren, M S; Rasmussen, K; Pakkenberg, B; Jørgensen, B

2014-07-01

Autologous platelet-rich fibrin (PRF(®)) is prepared by the automatic Vivostat(®) system. Conflicting results with Vivostat PRF in acute wound healing prompted us to examine its cellular and biomolecular composition. Specifically, platelets, selected growth factors and matrix metalloproteinase (MMP)-9 were quantified using novel analytical methods. Ten healthy non-thrombocytopenic volunteers donated blood for generation of intermediate fibrin-I and final PRF. Anticoagulated whole blood and serum procured in parallel served as baseline controls. Leucocyte, erythrocyte and platelet counts in whole blood and fibrin-I were determined by automated haematology analyser. Platelet concentration in PRF was quantified manually by stereologic analysis of Giemsa-stained tissue sections, and the total content of five growth factors and MMP-9 by enzyme-linked immunosorbent assays. The number of leucocytes and erythrocytes was reduced (P < 0·001), whereas platelets increased (P < 0·001) in fibrin-I versus whole blood. PRF contained 982 ± 206 × 10(9) platelets/l representing 3·9-fold (P < 0·001) enrichment relative to whole blood. Growth factor abundance in Vivostat PRF and serum was in descending order: transforming growth factor-β1 [5·1-fold higher in PRF than serum, P < 0·001] > platelet-derived growth factor (PDGF)-AB [2·5-fold, P < 0·01] > PDGF-BB [1·6-fold, P < 0·05] > vascular endothelial growth factor > basic fibroblast growth factor [75-fold, P < 0·001]. MMP-9 was reduced 139-fold (P < 0·001) compared with serum, reflecting leucocyte depletion in PRF. The gained knowledge on platelet enrichment and biomolecular constituents may guide clinicians in their optimal use of Vivostat PRF for tissue regenerative applications. © 2013 International Society of Blood Transfusion.

Identification of potential platelet alloantigens in the Equidae family by comparison of gene sequences encoding major platelet membrane glycoproteins.

PubMed

Boudreaux, Mary K; Humphries, Drew M

2013-12-01

Platelet alloantigens in horses may play an important role in the development of neonatal alloimmune thrombocytopenia (NAIT). The objective of this study was to evaluate genes encoding major platelet glycoproteins within the Equidae family in an effort to identify potential alloantigens. DNA was isolated from blood samples obtained from Equidae family members, including a Holsteiner-Oldenburg cross, a Quarter horse, a donkey, and a Plains zebra (Equus burchelli). Gene sequences encoding equine platelet membrane glycoproteins IIb, IIIa (integrin subunits αIIb and β3), Ia (integrin subunit α2), and Ibα were determined using PCR. Gene sequences were compared to the equine genome available on GenBank. Polymorphisms that would be predicted to result in amino acid changes on platelet surfaces were documented and compared with known alloantigenic sites documented on human platelets. Amino acid differences were predicted based on nucleotide sequences for all 4 genes. Nine differences were documented for αIIb, 5 differences were documented for β3, 7 differences were documented for α2, and 16 differences were documented for Ibα outside the macroglycopeptide region. This study represents the first effort at identifying potential platelet alloantigens in members of the Equidae Family based on evaluation of gene sequences. The data obtained form the groundwork for identifying potential platelet alloantigens involved in transfusion reactions and neonatal alloimmune thrombocytopenia (NAIT). More work is required to determine whether the predicted amino acid differences documented in this study play a role in alloimmunity, and whether other polymorphisms not detected in this study are present that may result in alloimmunity. © 2013 American Society for Veterinary Clinical Pathology.

A new clopidogrel (Plavix) point-of-care assay: rapid determination of antiplatelet activity in trauma patients.

PubMed

Bansal, Vishal; Fortlage, Dale; Lee, Jeanne; Doucet, Jay; Potenza, Bruce; Coimbra, Raul

2011-01-01

An increasing proportion of trauma patients are on anticoagulation or antiplatelet therapy. Unlike warfarin, where measuring international normalized ratio can help direct management, measuring platelet inhibition from clopidogrel (Plavix) is not standardized. We report the use of a new P2Y12 point-of-care assay (VerifyNow; Accumetrics, San Diego, CA) to determine the magnitude of platelet inhibition in trauma patients using clopidogrel. Trauma patients in 2009 were queried for clopidogrel use by prehospital personnel and the trauma team. Blood was obtained on admission for patients reportedly taking clopidogrel and was assayed for platelet inhibition using the VerfiyNow-P2Y12 device that measures P2Y12 reaction units and photometrically determines platelet inhibition percentage within 30 minutes. Patient demographics including age, Injury Severity Score, mechanism of injury, and complications from hemorrhage were also analyzed. In the time studied, 46 patients taking clopidogrel were assayed for platelet inhibition. The mean age was 75.9 years±11.8 years, and the most common mechanism of injury was fall (86.9%). Platelet inhibition ranged from 0% to 89%. There were no deaths, and only two patients, from the 0% and>30% inhibition group, had hemorrhagic complications (increased intracranial hemorrhage). The P2Y12 point-of-care assay determined that a large percentage of patients had undetectable or low platelet inhibition despite reportedly being on clopidogrel therapy. These patients may be clopidogrel nonresponders or noncompliant. It is unlikely that clopidogrel reversal therapies, such as platelet transfusions or Desmopressin, would be beneficial in this group. Further studies stratifying the percent platelet inhibition needed to increase bleeding complications is warranted to optimize management strategies.

An assessment of thromboelastometry to monitor blood coagulation and guide transfusion support in liver transplantation.

PubMed

Blasi, Annabel; Beltran, Joan; Pereira, Arturo; Martinez-Palli, Graciela; Torrents, Abiguei; Balust, Jaume; Zavala, Elizabeth; Taura, Pilar; Garcia-Valdecasas, Juan-Carlos

2012-09-01

Rotation thromboelastometry (TEM) has been proposed as a convenient alternative to standard coagulation tests in guiding the treatment of coagulopathy during orthotopic liver transplantation (OLT). This study was aimed at assessing the value of TEM in monitoring blood coagulation and guide transfusion support in OLT. Standard coagulation and TEM (EXTEM and FIBTEM) tests were performed at four preestablished intraoperative time points in 236 OLTs and prospectively recorded in a dedicated database together with the main operative and transfusion data. Transfusion thresholds were based on standard coagulation tests. Spearman's rank correlation (ρ), linear regression, and receiver operating characteristic curves were used when appropriate. EXTEM maximum clot firmness (MCF(EXTEM)) was the TEM variable that best correlated with the platelet (PLT) and fibrinogen levels (ρ = 0.62 and ρ = 0.69, respectively). MCF(FIBTEM) correlated with fibrinogen level (ρ = 0.70). EXTEM clot amplitude at 10 minutes (A10(EXTEM)) was a good linear predictor of MCF(EXTEM) (R(2) =0.93). The cutoff values that best predicted the transfusion threshold for PLTs and fibrinogen were A10(EXTEM) = 35 mm and A10(FIBTEM) = 8 mm. At these values, the negative and positive predictive accuracies of TEM to predict the transfusion thresholds were 95 and 27%, respectively. A10(EXTEM) is an adequate TEM variable to guide therapeutic decisions during OLT. Patients with A10(EXTEM) of greater than 35 mm are unlikely to bleed because of coagulation deficiencies, but using A10(EXTEM) of not more than 35 mm as the sole transfusion criterion can lead to unnecessary utilization of PLTs and fibrinogen-rich products. © 2012 American Association of Blood Banks.

A novel method for automated assessment of megakaryocyte differentiation and proplatelet formation.

PubMed

Salzmann, M; Hoesel, B; Haase, M; Mussbacher, M; Schrottmaier, W C; Kral-Pointner, J B; Finsterbusch, M; Mazharian, A; Assinger, A; Schmid, J A

2018-06-01

Transfusion of platelet concentrates represents an important treatment for various bleeding complications. However, the short half-life and frequent contaminations with bacteria restrict the availability of platelet concentrates and raise a clear demand for platelets generated ex vivo. Therefore, in vitro platelet generation from megakaryocytes represents an important research topic. A vital step for this process represents accurate analysis of thrombopoiesis and proplatelet formation, which is usually conducted manually. We aimed to develop a novel method for automated classification and analysis of proplatelet-forming megakaryocytes in vitro. After fluorescent labelling of surface and nucleus, MKs were automatically categorized and analysed with a novel pipeline of the open source software CellProfiler. Our new workflow is able to detect and quantify four subtypes of megakaryocytes undergoing thrombopoiesis: proplatelet-forming, spreading, pseudopodia-forming and terminally differentiated, anucleated megakaryocytes. Furthermore, we were able to characterize the inhibitory effect of dasatinib on thrombopoiesis in more detail. Our new workflow enabled rapid, unbiased, quantitative and qualitative in-depth analysis of proplatelet formation based on morphological characteristics. Clinicians and basic researchers alike will benefit from this novel technique that allows reliable and unbiased quantification of proplatelet formation. It thereby provides a valuable tool for the development of methods to generate platelets ex vivo and to detect effects of drugs on megakaryocyte differentiation.

Fluorescence quencher improves SCANSYSTEM for rapid bacterial detection.

PubMed

Schmidt, M; Hourfar, M K; Wahl, A; Nicol, S-B; Montag, T; Roth, W K; Seifried, E

2006-05-01

The optimized scansystem could detect contaminated platelet products within 24 h. However, the system's sensitivity was reduced by a high fluorescence background even in sterile samples, which led to the necessity of a well-trained staff for confirmation of microscope results. A new protocol of the optimized scansystem with the addition of a fluorescence quencher was evaluated. Pool platelet concentrates contaminated with five transfusion-relevant bacterial strains were tested in a blind study. In conjunction with new analysis software, the new quenching dye was able to reduce significantly unspecific background fluorescence. Sensitivity was best for Bacillus cereus and Escherichia coli (3 CFU/ml). The application of a fluorescence quencher enables automated discrimination of positive and negative test results in 60% of all analysed samples.

Limiting and detecting bacterial contamination of apheresis platelets: inlet-line diversion and increased culture volume improve component safety.

PubMed

Eder, Anne F; Kennedy, Jean M; Dy, Beth A; Notari, Edward P; Skeate, Robert; Bachowski, Gary; Mair, David C; Webb, Jonathan S; Wagner, Stephen J; Dodd, Roger Y; Benjamin, Richard J

2009-08-01

Septic transfusion reactions to apheresis platelets (PLTs) continue to occur despite preventive measures. This study evaluated the effect of two operational changes designed to reduce bacterial risk: 1) introducing inlet-line sample diversion on two-arm procedures and 2) increasing the sample volume cultured from 4 to 8 mL from all donations. Aerobic culture results and septic transfusion reactions reported between December 1, 2006, and July 31, 2008 (Period 2), were compared to March 1, 2004, to May 31, 2006 (Period 1). During Period 2, a total of 781,936 apheresis PLT collections were cultured, of which 130 donations (1:6015) were confirmed positive and 9 (1:86,882) had negative culture results but were associated with 11 septic reactions. Confirmed-positive cultures from two-arm procedures decreased (27.2 to 14.7 per 105 collections; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.41-0.70) in Period 2, owing to a lower rate of skin flora contamination. Detection of contamination of one-arm collections significantly increased by 54% in Period 2 (13.7 vs. 21.1 per 105 collections; OR, 1.54; 95% CI, 1.05-2.27). Fewer septic transfusion reactions occurred in Period 2, but the difference did not reach significance (1.7 vs. 1.2 per 105 donations; OR, 0.68; 95% CI, 0.30-1.53). Inlet-line diversion decreased bacterial contamination during two-arm collections by more than 46%. Concurrently, doubling the sample volume was associated with a 54% relative increase in culture sensitivity. These interventions act cooperatively to decrease bacterial risk.

Direct costs of dengue hospitalization in Brazil: public and private health care systems and use of WHO guidelines.

PubMed

Vieira Machado, Alessandra A; Estevan, Anderson Oliveira; Sales, Antonio; Brabes, Kelly Cristina da Silva; Croda, Júlio; Negrão, Fábio Juliano

2014-09-01

Dengue, an arboviral disease, is a public health problem in tropical and subtropical regions worldwide. In Brazil, epidemics have become increasingly important, with increases in the number of hospitalizations and the costs associated with the disease. This study aimed to describe the direct costs of hospitalized dengue cases, the financial impact of admissions and the use of blood products where current protocols for disease management were not followed. To analyze the direct costs of dengue illness and platelet transfusion in Brazil based on the World Health Organization (WHO) guidelines, we conducted a retrospective cross-sectional census study on hospitalized dengue patients in the public and private Brazilian health systems in Dourados City, Mato Grosso do Sul State, Brazil. The analysis involved cases that occurred from January through December during the 2010 outbreak. In total, we examined 8,226 mandatorily reported suspected dengue cases involving 507 hospitalized patients. The final sample comprised 288 laboratory-confirmed dengue patients, who accounted for 56.8% of all hospitalized cases. The overall cost of the hospitalized dengue cases was US $210,084.30, in 2010, which corresponded to 2.5% of the gross domestic product per capita in Dourados that year. In 35.2% of cases, blood products were used in patients who did not meet the blood transfusion criteria. The overall median hospitalization cost was higher (p = 0.002) in the group that received blood products (US $1,622.40) compared with the group that did not receive blood products (US $550.20). The comparative costs between the public and the private health systems show that both the hospitalization of and platelet transfusion in patients who do not meet the WHO and Brazilian dengue guidelines increase the direct costs, but not the quality, of health care.

Clinical feature and management of immune thrombocytopenic purpura in a tertiary hospital in Northwest Nigeria

PubMed Central

Hassan, Abdulaziz; Adebayo, Adeshola; Musa, Abubakar Umar; Suleiman, Aishatu Maude; Ibrahim, Ismaila Nda; Kusfa, Ibrahim Usman; Aminu, Mohammed Sirajo

2017-01-01

Background: Immune thrombocytopenic purpura (ITP) is a rare bleeding disorder that may remit spontaneously. Life-threatening bleeding may require transfusion support, steroids, and other immunosuppressive therapy or splenectomy. Objective: To review the clinical presentation and laboratory features of ITP at Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria. Subjects and Methods: A retrospective analytic study of case notes and bone marrow (BM) records of patients diagnosed with ITP at Haematology Department, ABUTH, Zaria, from January 1, 2004, to December 31, 2012. Results: There were nine cases (six females, three males), aged 6–20 (mean 11.11) years. The presentations were epistaxis 8 (88.9%), purpura 4 (44.4%), gum bleeding 4 (44.4%), menorrhagia 2 (22.2%), and intracranial hemorrhage (ICH) 1 (11.1%). Only 1 (11.1%) had clinical splenomegaly. Platelet count of <20 × 109/L was found in 4 (44.4%) while 6 (66.7%) had packed cell volume of <25%. All the nine cases had BM megakaryocytic hyperplasia. Six patients had blood transfusion support while 7 (77.8%) patients received oral prednisolone therapy with time to cessation of bleeding of 12–16 (mean of 8) weeks. One case had spontaneous remission while another had anti-D due to relapse after steroid therapy; this resulted in transient rise in platelet counts. None had other immunosuppressive therapy or splenectomy. Six (66.7%) cases were lost to follow-up after achieving remission and one died of ICH. Conclusion: ITP is not common in our center though its clinical presentations are varied. However, prednisolone and blood transfusion therapy are central to the management of these patients with favorable outcome. PMID:29269984

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation

PubMed Central

El-Chemaly, Souheil; O’Brien, Kevin J.; Nathan, Steven D.; Weinhouse, Gerald L.; Goldberg, Hilary J.; Connors, Jean M.; Cui, Ye; Astor, Todd L.; Camp, Philip C.; Rosas, Ivan O.; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A.; Gahl, William A.

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants. PMID:29547626

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

PubMed

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Ten-Year Analysis of Transfusion in Operation Iraqi Freedom and Operation Enduring Freedom: Increased Plasma and Platelet Use Correlates with Improved Survival

DTIC Science & Technology

2012-01-01

included the publication of the CRASH-2 trial in 2010, followed by the institution of a CPG regarding tranexamic acid (TXA) use in August 2011. 7,11 This...critically ill patients? Trans- fusion. 2011;51:1644 1650. 11. Shakur H, Roberts I, Bautista R, et al. Effects of tranexamic acid on death, vascular occlusive

Diagnostic methods for platelet bacteria screening: current status and developments.

PubMed

Störmer, Melanie; Vollmer, Tanja

2014-02-01

Bacterial contamination of blood components and the prevention of transfusion-associated bacterial infection still remains a major challenge in transfusion medicine. Over the past few decades, a significant reduction in the transmission of viral infections has been achieved due to the introduction of mandatory virus screening. Platelet concentrates (PCs) represent one of the highest risks for bacterial infection. This is due to the required storage conditions for PCs in gas-permeable containers at room temperature with constant agitation, which support bacterial proliferation from low contamination levels to high titers. In contrast to virus screening, since 1997 in Germany bacterial testing of PCs is only performed as a routine quality control or, since 2008, to prolong the shelf life to 5 days. In general, bacterial screening of PCs by cultivation methods is implemented by the various blood services. Although these culturing systems will remain the gold standard, the significance of rapid methods for screening for bacterial contamination has increased over the last few years. These new methods provide powerful tools for increasing the bacterial safety of blood components. This article summarizes the course of policies and provisions introduced to increase bacterial safety of blood components in Germany. Furthermore, we give an overview of the different diagnostic methods for bacterial screening of PCs and their current applicability in routine screening processes.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

PubMed

Hickman, DaShawn A; Pawlowski, Christa L; Sekhon, Ujjal D S; Marks, Joyann; Gupta, Anirban Sen

2018-01-01

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chronic intravascular coagulation associated with chronic myelocytic leukemia. Use of heparin in connection with a surgical procedure.

PubMed

German, H J; Smith, J A; Lindenbaum, J

1976-10-01

A women with Philadelphia chromosome-positive chronic myelocytic leukemia lived nearly 12 years from the time of diagnosis. During most of this period she received no therapy, and marked cyclic oscillations in the white blood cell count were documented. The last two years of her illness were marked by a hemorrhagic disorder associated with hypofibrinogenemia, thrombocytopenia, increased plasma fibrinopeptide A concentration and markedly elevated serum levels of fibrin degradation products. The coagulation disorder was rapidly reversible on several occasions with heparin therapy. After treatment with heparin and platelet transfusions, the patient underwent successful resection of a large ovarian cyst with excellent hemostasis during the procedure. Postoperatively, the administration of heparin and platelets was discontinued and a large wound hematoma developed. After resumption of therapy with heparin and platelets, the remainder of her postoperative course was uneventful. The literature on the subject is reviewed and tentative guidelines are offered concerning the management of patients with intravascular coagulation who require diagnostic or therapeutic surgical procedures.

Use of an autologous leucocyte and platelet-rich fibrin patch on hard-to-heal DFUs: a pilot study.

PubMed

Löndahl, M; Tarnow, L; Karlsmark, T; Lundquist, R; Nielsen, A M; Michelsen, M; Nilsson, A; Zakrzewski, M; Jörgensen, B

2015-04-01

Leucopatch is a leukocyte and platelet-rich fibrin patch that provides concentrated blood cells and signal substances to the surface of an ulcer. It is produced by centrifugation of the patient's own venous blood. The aim of this pilot multicentre cohort study was to evaluate effects of the leucocyte patch in patients with hard-to-heal diabetic foot ulcers (DFUs). Non-ischaemic Wagner grade 1 or 2 DFUs with a duration of more than 6 weeks and a maximal area of 10cm² were included. Patients with >40% ulcer area change during a two-week run-in period were excluded. The treatment was applied once a week for up to 19 treatments or until the foot ulcer was completely epithelialised. The primary endpoint was healing within 20 weeks. Of the 60 patients who gave consent 16 were excluded during run-in period, 44 patients initiated study treatment and 39 were included in the per-protocol analysis. Complete epithelisation was achieved in 34% (per-protocol analysis 36%) at 12 weeks and 52% (59%) at 20 weeks. In patients with ulcer duration less than 6 months, 73% of ulcers healed within 20 weeks. Patients with healed ulcers had larger ulcer area reduction during the first two treatment weeks compared to non-healers. Adverse events were mild and rare. The leucocyte patch is well-tolerated, easy to use and has potential in the armamentarium of the DFU treatment, provided this outcome is confirmed in an appropriately powered randomised clinical trial.

Apheresis platelets are more frequently associated with adverse reactions than pooled platelets both in recipients and in donors: a study from French hemovigilance data.

PubMed

Daurat, Aurélien; Roger, Claire; Gris, JeanChristophe; Daurat, Gérald; Feissel, Michel; Le Manach, Yannick; Lefrant, JeanYves; Muller, Laurent

2016-06-01

Controversy exists regarding the safety of the different types of platelet (PLT) concentrates. This study was aimed at comparing the rate of adverse reactions associated with apheresis PLT concentrates (APCs) and pooled PLT concentrates (PPCs) both in donors and in recipients. From the French national hemovigilance system, types and numbers of recipient adverse reactions were compared over a period from 2009 to 2011. Donor adverse reactions were available for 2010 and 2011. This study involved 23 of 26 French regions. Main outcomes were the rates of adverse reaction in recipients and serious adverse reaction in donors. There were 790,854 PLT transfusions during the study period (477,747 [60%] with APCs, 313,107 [40%] with PPCs). APCs were associated with more adverse reactions (6244 vs. 2469 per 1,000,000, p < 0.001) and more severe and life-threatening reactions (respectively, 241 vs. 131 per 1,000,000, p < 0.001; and 182 vs. 121 per 1,000,000, p = 0.04). Mortality rates due to an adverse transfusion reaction were similar (15 vs. 6 per 1,000,000, p = 0.5). In donors, the number of whole blood (WB) donations was 4,722,685 whereas 266,095 apheresis procedures were performed. Serious adverse reactions were more frequent for apheresis procedures than for WB donations (5445 vs. 803 per 1,000,000, p < 0.001). Our findings suggest that apheresis PLTs may be more hazardous than pooled PLTs both in recipients and in donors. This study calls for randomized trials to confirm or refute these results. © 2016 AABB.

Blood group genotyping: from patient to high-throughput donor screening.

PubMed

Veldhuisen, B; van der Schoot, C E; de Haas, M

2009-10-01

Blood group antigens, present on the cell membrane of red blood cells and platelets, can be defined either serologically or predicted based on the genotypes of genes encoding for blood group antigens. At present, the molecular basis of many antigens of the 30 blood group systems and 17 human platelet antigens is known. In many laboratories, blood group genotyping assays are routinely used for diagnostics in cases where patient red cells cannot be used for serological typing due to the presence of auto-antibodies or after recent transfusions. In addition, DNA genotyping is used to support (un)-expected serological findings. Fetal genotyping is routinely performed when there is a risk of alloimmune-mediated red cell or platelet destruction. In case of patient blood group antigen typing, it is important that a genotyping result is quickly available to support the selection of donor blood, and high-throughput of the genotyping method is not a prerequisite. In addition, genotyping of blood donors will be extremely useful to obtain donor blood with rare phenotypes, for example lacking a high-frequency antigen, and to obtain a fully typed donor database to be used for a better matching between recipient and donor to prevent adverse transfusion reactions. Serological typing of large cohorts of donors is a labour-intensive and expensive exercise and hampered by the lack of sufficient amounts of approved typing reagents for all blood group systems of interest. Currently, high-throughput genotyping based on DNA micro-arrays is a very feasible method to obtain a large pool of well-typed blood donors. Several systems for high-throughput blood group genotyping are developed and will be discussed in this review.

Endoscopy in neutropenic and/or thrombocytopenic patients

PubMed Central

Tong, Michelle C; Tadros, Micheal; Vaziri, Haleh

2015-01-01

AIM: To evaluate the safety of endoscopic procedures in neutropenic and/or thrombocytopenic cancer patients. METHODS: We performed a literature search for English language studies in which patients with neutropenia and/or thrombocytopenia underwent endoscopy. Studies were included if endoscopic procedures were used as part of the evaluation of neutropenic and/or thrombocytopenic patients, yielding 13 studies. Two studies in which endoscopy was not a primary evaluation tool were excluded. Eleven relevant studies were identified by two independent reviewers on PubMed, Scopus, and Ovid databases. RESULTS: Most of the studies had high diagnostic yield with relatively low complication rates. Therapeutic endoscopic interventions were performed in more than half the studies, including high-risk procedures, such as sclerotherapy. Platelet transfusion was given if counts were less than 50000/mm3 in four studies and less than 10000/mm3 in one study. Other thrombocytopenic precautions included withholding of biopsy if platelet count was less than 30000/mm3 in one study and less than 20000/mm3 in another study. Two of the ten studies which examined thrombocytopenic patient populations reported bleeding complications related to endoscopy, none of which caused major morbidity or mortality. All febrile neutropenic patients received prophylactic broad-spectrum antibiotics in the studies reviewed. Regarding afebrile neutropenic patients, prophylactic antibiotics were given if absolute neutrophil count was less than 1000/mm3 in one study, if the patient was undergoing colonoscopy and had a high inflammatory condition without clear definition of significance in another study, and if the patient was in an aplastic phase in a third study. Endoscopy was also withheld in one study for severe pancytopenia. CONCLUSION: Endoscopy can be safely performed in patients with thrombocytopenia/neutropenia. Prophylactic platelet transfusion and/or antibiotic administration prior to endoscopy may be considered in some cases and should be individualized. PMID:26674926

Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy

PubMed Central

Gonzalez, Eduardo; Moore, Ernest E.; Moore, Hunter B.; Chapman, Michael P.; Chin, Theresa L.; Ghasabyan, Arsen; Wohlauer, Max V.; Barnett, Carlton C.; Bensard, Denis D.; Biffl, Walter L.; Burlew, Clay C.; Johnson, Jeffrey L.; Pieracci, Fredric M.; Jurkovich, Gregory J.; Banerjee, Anirban; Silliman, Christopher C.; Sauaia, Angela

2017-01-01

Background Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). Methods This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. Results One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2–11), TEG: 4.5 (2–8)] (P = 0.317), but more plasma units [CCA: 2.0 (0–4), TEG: 0.0 (0–3)] (P = 0.022), and more platelets units [CCA: 0.0 (0–1), TEG: 0.0 (0–0)] (P = 0.041) in the first 2 hours of resuscitation. Conclusions Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation. PMID:26720428

Namibia’s transition from whole blood–derived pooled platelets to single-donor apheresis platelet collections

PubMed Central

Pitman, John P.; Basavaraju, Sridhar V.; Shiraishi, Ray W.; Wilkinson, Robert; von Finckenstein, Bjorn; Lowrance, David W.; Marfin, Anthony A.; Postma, Maarten; Mataranyika, Mary; Sibinga, Cees Th. Smit

2015-01-01

BACKGROUND Few African countries separate blood donations into components; however, demand for platelets (PLTs) is increasing as regional capacity to treat causes of thrombocytopenia, including chemotherapy, increases. Namibia introduced single-donor apheresis PLT collections in 2007 to increase PLT availability while reducing exposure to multiple donors via pooling. This study describes the impact this transition had on PLT availability and safety in Namibia. STUDY DESIGN AND METHODS Annual national blood collections and PLT units issued data were extracted from a database maintained by the Blood Transfusion Service of Namibia (NAMBTS). Production costs and unit prices were analyzed. RESULTS In 2006, NAMBTS issued 771 single and pooled PLT doses from 3054 whole blood (WB) donations (drawn from 18,422 WB donations). In 2007, NAMBTS issued 486 single and pooled PLT doses from 1477 WB donations (drawn from 18,309 WB donations) and 131 single-donor PLT doses. By 2011, NAMBTS issued 837 single-donor PLT doses per year, 99.1% of all PLT units. Of 5761 WB donations from which PLTs were made in 2006 to 2011, a total of 20 (0.35%) were from donors with confirmed test results for human immunodeficiency virus or other transfusion-transmissible infections (TTIs). Of 2315 single-donor apheresis donations between 2007 and 2011, none of the 663 donors had a confirmed positive result for any pathogen. As apheresis replaced WB-derived PLTs, apheresis production costs dropped by a mean of 8.2% per year, while pooled PLT costs increased by an annual mean of 21.5%. Unit prices paid for apheresis- and WB-derived PLTs increased by 9 and 7.4% per year on average, respectively. CONCLUSION Namibia’s PLT transition shows that collections from repeat apheresis donors can reduce TTI risk and production costs. PMID:25727921

Measurement of haemolysis markers following transfusion of uncrossmatched, low-titre, group O+ whole blood in civilian trauma patients: initial experience at a level 1 trauma centre.

PubMed

Seheult, J N; Triulzi, D J; Alarcon, L H; Sperry, J L; Murdock, A; Yazer, M H

2017-02-01

The safety of administering uncrossmatched, group O, cold-stored, whole blood (cWB) during civilian trauma resuscitation was evaluated. Male trauma patients with haemorrhage-induced hypotension who received leuko-reduced uncrossmatched group O+, low titre (<50) anti-A and -B, platelet-replete cWB during initial resuscitation were included. The biochemical markers of haemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, creatinine, serum potassium) were measured on the day of cWB receipt (day 0), and over the next 2 days, reports of transfusion reactions and total blood product administration in first 24 h of admission were recorded. There were 27 non-group O and 17 group O cWB recipients. The median number of cWB units transfused was 1 [interquartile range (IQR): 1-2] in both groups. The median day 0 post-transfusion serum total bilirubin concentration, although still in the normal range, was higher in the non-group O versus group O recipients (1·4 versus 0·5 mg/dL, P < 0·01). There were no significant differences in any of the other biochemical parameters at any other time point. Non-group O recipients received a median of 3 times more red blood cell (RBC) units compared with group O recipients (P = 0·01 RBCs), likely explaining the bilirubin difference on day 0. The median volume of ABO-incompatible plasma transfused to non-group O recipients was 600 mL (IQR: 300-1140 mL). There were no reports of adverse events related to the cWB transfusion in either group. Administration of ≤2 units of cWB in civilian trauma resuscitation was not associated with clinically significant changes in laboratory haemolysis markers. Efficacy will be determined when larger quantities are transfused. © 2016 British Blood Transfusion Society.

Platelet-rich plasma and other cellular strategies in orthopedic surgery.

PubMed

Williams, Phillip N; Moran, George; Bradley, James P; S ElAttrache, Neal; Dines, Joshua S

2015-03-01

The use of biologics in the treatment of musculoskeletal disease has become increasingly more common as research studies continue to provide further elucidation of their mechanisms in healing. Platelet-rich plasma, patches, growth factors, and stem cells are among the many biologics under active investigation and have varying levels of success in augmenting surgical or nonoperative interventions. However, the limitations of these treatments exist, and clear guidelines for their indications and application have yet to be established. Well-designed clinical trials will help determine the appropriate future use of biologics to ensure consistent outcomes.

Normalized levels of red blood cells expressing phosphatidylserine, their microparticles, and activated platelets in young patients with β-thalassemia following bone marrow transplantation.

PubMed

Klaihmon, Phatchanat; Vimonpatranon, Sinmanus; Noulsri, Egarit; Lertthammakiat, Surapong; Anurathapan, Usanarat; Sirachainan, Nongnuch; Hongeng, Suradej; Pattanapanyasat, Kovit

2017-10-01

Bone marrow transplantation (BMT) serves as the only curative treatment for patients with β-thalassemia major; however, hemostatic changes have been observed in these BMT patients. Aggregability of thalassemic red blood cells (RBCs) and increased red blood cell-derived microparticles (RMPs) expressing phosphatidylserine (PS) are thought to participate in thromboembolic events by initially triggering platelet activation. To our knowledge, there has been no report providing quantitation of these circulating PS-expressing RBCs and RMPs in young β-thalassemia patients after BMT. Whole blood from each subject was fluorescently labeled to detect RBC markers (CD235a) and annexin-V together with the known number TruCount™ beads. PS-expressing RBCs, RMPs, and activated platelets were identified by flow cytometry. In our randomized study, we found the decreased levels of three aforementioned factors compared to levels in patients receiving regular blood transfusion (RT). This study showed that BMT in β-thalassemia patients decreases the levels of circulating PS-expressing RBCs, their MPs, and procoagulant platelets when compared to patients who received RT. Normalized levels of these coagulation markers may provide the supportive evidence of the effectiveness of BMT for curing thalassemia.

Pluripotent stem cells reveal the developmental biology of human megakaryocytes and provide a source of platelets for clinical application.

PubMed

Takayama, Naoya; Eto, Koji

2012-10-01

Human pluripotent stem cells [PSCs; including human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs)] can infinitely proliferate in vitro and are easily accessible for gene manipulation. Megakaryocytes (MKs) and platelets can be created from human ESCs and iPSCs in vitro and represent a potential source of blood cells for transfusion and a promising tool for studying the human thrombopoiesis. Moreover, disease-specific iPSCs are a powerful tool for elucidating the pathogenesis of hematological diseases and for drug screening. In that context, we and other groups have developed in vitro MK and platelet differentiation systems from human pluripotent stem cells (PSCs). Combining this co-culture system with a drug-inducible gene expression system enabled us to clarify the novel role played by c-MYC during human thrombopoiesis. In the next decade, technical advances (e.g., high-throughput genomic sequencing) will likely enable the identification of numerous gene mutations associated with abnormal thrombopoiesis. Combined with such technology, an in vitro system for differentiating human PSCs into MKs and platelets could provide a novel platform for studying human gene function associated with thrombopoiesis.

Cost-Effectiveness of POC Coagulation Testing Using Multiple Electrode Aggregometry.

PubMed

Straub, Niels; Bauer, Ekaterina; Agarwal, Seema; Meybohm, Patrick; Zacharowski, Kai; Hanke, Alexander A; Weber, Christian F

2016-01-01

The economic effects of Point-of-Care (POC) coagulation testing including Multiple Electrode Aggregometry (MEA) with the Multiplate device have not been examined. A health economic model with associated clinical endpoints was developed to calculate the effectiveness and estimated costs of coagulation analyses based on standard laboratory testing (SLT) or POC testing offering the possibility to assess platelet dysfunction using aggregometric measures. Cost estimates included pre- and perioperative costs of hemotherapy, intra- and post-operative coagulation testing costs, and hospitalization costs, including the costs of transfusion-related complications. Our model calculation using a simulated true-to-life cohort of 10,000 cardiac surgery patients assigned to each testing alternative demonstrated that there were 950 fewer patients in the POC branch who required any transfusion of red blood cells. The subsequent numbers of massive transfusions and patients with transfusion-related complications were reduced with the POC testing by 284 and 126, respectively. The average expected total cost in the POC branch was 288 Euro lower for every treated patient than that in the SLT branch. Incorporating aggregometric analyses using MEA into hemotherapy algorithms improved medical outcomes in cardiac surgery patients in the presented health economic model. There was an overall better economic outcome associated with POC testing compared with SLT testing despite the higher costs of testing.

Impact of prestorage leucoreduction of autologous whole blood on length of hospital stay with a subgroup analysis in bilateral hip arthroplasty.

PubMed

Sawamura, Y; Ohto, H; Ikeda, K; Kanno, T; Suzuki, Y; Gonda, K; Tasaki, T; Nollet, K E; Takahashi, H; Aota, S

2018-06-20

Although prestorage leucoreduction (LR) of blood components for transfusion has gained favour around the world, evidence of its beneficial clinical effects is ambiguous. To reveal whether leucocytes and/or platelets in transfused blood are related to transfusion-related adverse effects, a prospective randomized crossover study was performed on patients who donated autologous blood prior to elective surgery. Among 1487 primary enrolees, a total of 192 patients undergoing two-stage, bilateral total hip arthroplasty were randomized to receive autologous blood that was either prestorage leucoreduced, or not, for the first procedure. For the second procedure, each patient was crossed over to receive alternatively processed autologous blood. Length of hospital stay served as a primary end-point, with perioperative infectious/thrombotic complications, pre- and postoperative laboratory values, and body temperature serving as secondary endpoints. No significant differences emerged between prestorage LR and non-LR cohorts in length of hospital stay, as well as perioperative infectious/thrombotic complications, postoperative body temperature and duration of fever. Postoperative laboratory values including white blood cell counts and C-reactive protein levels had no significant differences. This study could not prove any superiority of prestorage LR over non-LR for autologous whole blood among patients who underwent total hip arthroplasty. © 2018 International Society of Blood Transfusion.

Blood Type 0 is not associated with increased blood loss in extensive spine surgery✩

PubMed Central

Komatsu, Ryu; Dalton, Jarrod E.; Ghobrial, Michael; Fu, Alexander Y.; Lee, Jae H.; Egan, Cameron; Sessler, Daniel I.; Kasuya, Yusuke; Turan, Alparslan

2016-01-01

Study Objective To investigate whether Type O blood group status is associated with increased intraoperative blood loss and requirement of blood transfusion in extensive spine surgery. Design Retrospective comparative study. Setting University-affiliated, non-profit teaching hospital. Measurements Data from 1,050 ASA physical status 1, 2, 3, 4, and 5 patients who underwent spine surgeries involving 4 or more vertebral levels were analyzed. Patients with Type O blood were matched to similar patients with other blood types using propensity scores, which were estimated via demographic and morphometric data, medical history variables, and extent of surgery. Intraoperative estimated blood loss (EBL) was compared among matched patients using a linear regression model; intraoperative transfusion requirement in volume of red blood cells, fresh frozen plasma, platelet, cryoprecipitate, cell salvaged blood, volume of intraoperative infusion of hetastarch, 5% albumin, crystalloids, and hospital length of hospital (LOS) were compared using Wilcoxon rank-sum tests. Main Results Intraoperative EBL and requirement of blood product transfusion were similar in patients with Type O blood group and those with other blood groups. Conclusion There was no association between Type O blood and increased intraoperative blood loss or blood transfusion requirement during extensive spine surgery, with similar hospital LOS in Type O and non-O patients. PMID:25172503

In vitro storage characteristics of platelet concentrates suspended in 70% SSP+(TM) additive solution versus plasma over a 14-day storage period.

PubMed

Saunders, C; Rowe, G; Wilkins, K; Holme, S; Collins, P

2011-08-01

The non-paired two-arm study compared the in vitro storage characteristics of platelets suspended as concentrates in either 100% plasma or a mixture of additive solution (SSP+™, MacoPharma, Mouveaux, France) and autologous plasma in a 70:30 ratio over a 14-day storage period. The buffy coat-derived pooled platelet concentrates were sampled on days 1, 2, 3, 6, 8, 10 and 14 and tests performed to determine platelet morphology, function, metabolism, activation and apoptosis-like activity. Swirling remained strong (score=3) in SSP+™, whilst scores of 1 and 0 were noted for plasma units by end of storage. In contrast to units in plasma, pH levels remained above seven in SSP+™ units, increasing after day 10. Percent positive expression of CD62P was similar in both groups on day 1 (median of 54% and 56% for plasma (n=13) and SSP+™ (n=12), respectively), with SSP+™ units showing a more moderate increase in activation after day 10. A progressive decrease in mitochondrial membrane potential was evident in both groups from day 1, whilst annexin V binding was relatively stable from days 1 to 3, with median values remaining below 6%. Subsequent to this, the percentage of platelets binding annexin V increased to approximately 30% by day 14. Platelets suspended in a medium of 70:30 SSP+™ to plasma ratio performed at least as well as platelets in 100% autologous plasma for up to 10 days of storage. Further, results are suggestive of an apoptosis-like process being involved in the platelet storage lesion. © 2011 The Author(s). Vox Sanguinis © 2011 International Society of Blood Transfusion.

Effects of preoperative aspirin on perioperative platelet activation and dysfunction in patients undergoing off-pump coronary artery bypass graft surgery: A prospective randomized study.

PubMed

Lee, Jiwon; Jung, Chul-Woo; Jeon, Yunseok; Kim, Tae Kyong; Cho, Youn Joung; Koo, Chang-Hoon; Choi, Yoon Hyeong; Kim, Ki-Bong; Hwang, Ho Young; Kim, Hang-Rae; Park, Ji-Young

2017-01-01

The benefit of aspirin use after coronary artery bypass graft surgery has been well proven. However, the effect of preoperative aspirin use in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB) has not been evaluated sufficiently. To evaluate platelet function changes during OPCAB due to preoperative aspirin use, we conducted a randomized controlled trial using flow cytometry and the Multiplate® analyzer. Forty-eight patients scheduled for elective OPCAB were randomized to the aspirin continuation (100 mg/day until operative day) and discontinuation (4 days before the operative day) groups. Platelet function was measured using the platelet activation markers CD62P, CD63, and PAC-1 by flow cytometry, and platelet aggregation was measured using the Multiplate® analyzer, after the induction of anesthesia (baseline), at the end of the operation, and 24 and 48 h postoperatively. Findings of conventional coagulation assays, thromboelastography by ROTEM® assays, and postoperative bleeding-related clinical outcomes were compared between groups. No significant change in CD62P, CD63, or PAC-1 was observed at the end of the operation or 24 or 48 h postoperatively compared with baseline in either group. The area under the curve for arachidonic acid-stimulated platelet aggregation, measured by the Multiplate® analyzer, was significantly smaller in the aspirin continuation group (P < 0.01). However, chest tube drainage and intraoperative and postoperative transfusion requirements did not differ between groups. Our study showed that preoperative use of aspirin for OPCAB did not affect perioperative platelet activation, but it impaired platelet aggregation, which did not affect postoperative bleeding, by arachidonic acid.

A preliminary study of placental umbilical cord whole blood transfusion in under resourced patients with malaria in the background of anaemia.

PubMed

Bhattacharya, Niranjan

2006-03-23

Malaria is an annual killer of over one million people globally and its essential co-morbidity is anaemia. Cord blood, because of its rich mix of foetal and adult haemoglobin, high platelet and WBC counts, hypo-antigenic nature, altered metabolic profile and high affinity for oxygen as well as its anti-malarial effect, is an ideal choice in malaria with anaemia, necessitating blood transfusion. This paper presents an alternative protocol for fresh whole blood/packed cell transfusion from the hospital's biological waste resources, i.e., the placenta, after the birth of a healthy baby from a healthy mother. This collected blood was routinely transfused to patients admitted in our hospital with severe anaemia in the background of confirmed malaria. 94 units of placental umbilical cord whole blood were collected after lower uterine caesarean section (LUCS) from consenting mothers (from 1st April 1999 to April 2005), and safely transfused to 39 informed, consenting patients (age varying from 8 to 72 years). The collected volume of cord blood from each placenta (Unit) varied from 52 ml to 143 ml, with a mean packed cell volume of 48.9 +/- 4.1 SD and a mean haemoglobin concentration of 16.4 Gm percent +/- 1.6 Gm percent SD. The blood was immediately transfused after following the standard adult blood transfusion protocol of screening and cross-matching between the donor and the recipient. On occasion, the collected cord blood was preserved in the refrigerator, if no volunteer was readily available, and transfused within 72 hours of collection. Cord blood transfusion was tested on twenty two patients infected with Plasmodium falciparum and 17 patients with Plasmodium vivax. For inclusion in this study, the patient's plasma haemoglobin had to be 8 gm percent or less (the pre-transfusion haemoglobin in the malaria-infected patients in this series varied from 5.4 gm/dl to 7.9 gm/dl). The rise of haemoglobin within 72 hours of two units of freshly collected cord blood transfusion was 0.5 gm/dl to 1.6 gm/dl. Each patient received two to six units of freshly collected cord blood transfusion (two units at a time), depending on availability and compatibility. No clinical immunological or non-immunological reaction has been encountered in this series. Properly screened cord blood is safe for transfusion, in victims of severe malarial anaemia who need transfusion support.

Dose Responses of Ibuprofen In Vitro on Platelet Aggregation and Coagulation in Human and Pig Blood Samples.

PubMed

Martini, Wenjun Z; Rodriguez, Cassandra M; Deguzman, Rodolfo; Guerra, Jessica B; Martin, Angela K; Pusateri, Anthony E; Cap, Andrew P; Dubick, Michael A

2016-05-01

Ibuprofen is commonly used by warfighters in the deployed environment. This study investigated its dose effects on in vitro coagulation in human and pig blood. Blood samples were collected from 6 normal volunteers and 6 healthy pigs and processed to make platelet-adjusted samples (100 × 10(3)/μL, common transfusion trigger in trauma). Ibuprofen was added to the samples at concentrations of 0 μg/mL (control), the concentration from the highest recommended oral dose (163 μg/mL, 1×), and 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Platelet aggregation by Chrono-Log aggregometer and coagulation by rotational thrombelastogram (Rotem) were assessed at 15 minutes after the addition of ibuprofen. A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested in human or pig blood. Collagen-stimulated platelet aggregation was inhibited starting at 1× in human blood and 4× in pig blood. Rotem measurements were similarly compromised in pig and human blood starting at 16×, except clot formation time was prolonged at 1× in human blood (all p < 0.05). Ibuprofen inhibited platelet aggregation at recommended doses, and compromised coagulation at higher doses. Human blood was more sensitive to ibuprofen inhibition. Further effort is needed to investigate ibuprofen dose responses on coagulation in vivo. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes.

PubMed

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L; Newman, Peter J

2016-02-11

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the Pl(A1)/Pl(A2) polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33 (+) megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41(+) megakaryocyte progenitors derived from these cells expressed the HPA-1b (Pl(A2)) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b-specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. © 2016 by The American Society of Hematology.

CRISPR/Cas9-mediated conversion of human platelet alloantigen allotypes

PubMed Central

Zhang, Nanyan; Zhi, Huiying; Curtis, Brian R.; Rao, Sridhar; Jobaliya, Chintan; Poncz, Mortimer; French, Deborah L.

2016-01-01

Human platelet alloantigens (HPAs) reside on functionally important platelet membrane glycoproteins and are caused by single nucleotide polymorphisms in the genes that encode them. Antibodies that form against HPAs are responsible for several clinically important alloimmune bleeding disorders, including fetal and neonatal alloimmune thrombocytopenia and posttransfusion purpura. The HPA-1a/HPA-1b alloantigen system, also known as the PlA1/PlA2 polymorphism, is the most frequently implicated HPA among whites, and a single Leu33Pro amino acid polymorphism within the integrin β3 subunit is responsible for generating the HPA-1a/HPA-1b alloantigenic epitopes. HPA-1b/b platelets, like those bearing other low-frequency platelet-specific alloantigens, are relatively rare in the population and difficult to obtain for purposes of transfusion therapy and diagnostic testing. We used CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR associated protein 9) gene-editing technology to transform Leu33+ megakaryocytelike DAMI cells and induced pluripotent stem cells (iPSCs) to the Pro33 allotype. CD41+ megakaryocyte progenitors derived from these cells expressed the HPA-1b (PlA2) alloantigenic epitope, as reported by diagnostic NciI restriction enzyme digestion, DNA sequencing, and western blot analysis using HPA-1b–specific human maternal alloantisera. Application of CRISPR/Cas9 technology to genetically edit this and other clinically-important HPAs holds great potential for production of designer platelets for diagnostic, investigative, and, ultimately, therapeutic use. PMID:26634302

[Factor XIII-guided treatment algorithm reduces blood transfusion in burn surgery].

PubMed

Carneiro, João Miguel Gonçalves Valadares de Morais; Alves, Joana; Conde, Patrícia; Xambre, Fátima; Almeida, Emanuel; Marques, Céline; Luís, Mariana; Godinho, Ana Maria Mano Garção; Fernandez-Llimos, Fernando

Major burn surgery causes large hemorrhage and coagulation dysfunction. Treatment algorithms guided by ROTEM ® and factor VIIa reduce the need for blood products, but there is no evidence regarding factor XIII. Factor XIII deficiency changes clot stability and decreases wound healing. This study evaluates the efficacy and safety of factor XIII correction and its repercussion on transfusion requirements in burn surgery. Randomized retrospective study with 40 patients undergoing surgery at the Burn Unit, allocated into Group A those with factor XIII assessment (n = 20), and Group B, those without assessment (n = 20). Erythrocyte transfusion was guided by a hemoglobin trigger of 10g.dL -1 and the other blood products by routine coagulation and ROTEM ® tests. Analysis of blood product consumption included units of erythrocytes, fresh frozen plasma, platelets, and fibrinogen. The coagulation biomarker analysis compared the pre- and post-operative values. Group A (with factor XIII study) and Group B had identical total body surface area burned. All patients in Group A had a preoperative factor XIII deficiency, whose correction significantly reduced units of erythrocyte concentrate transfusion (1.95 vs. 4.05, p = 0.001). Pre- and post-operative coagulation biomarkers were similar between groups, revealing that routine coagulation tests did not identify factor XIII deficiency. There were no recorded thromboembolic events. Correction of factor XIII deficiency in burn surgery proved to be safe and effective for reducing perioperative transfusion of erythrocyte units. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

2015 Proceedings of the National Heart, Lung, and Blood Institute's State of the Science in Transfusion Medicine Symposium

PubMed Central

Spitalnik, Steven L.; Triulzi, Darrell; Devine, Dana V.; Dzik, Walter H.; Eder, Anne F.; Gernsheimer, Terry; Josephson, Cassandra D.; Kor, Daryl J.; Luban, Naomi L. C.; Roubinian, Nareg H.; Mondoro, Traci; Welniak, Lisbeth A.; Zou, Shimian; Glynn, Simone

2015-01-01

On March 25-26, 2015, the National Heart, Lung, and Blood Institute sponsored a meeting on the State of the Science in Transfusion Medicine on the NIH campus in Bethesda, MD, which was attended by a diverse group of 330 registrants. The meeting's goal was to identify important research questions that could be answered in the next 5-10 years, and which would have the potential to transform the clinical practice of transfusion medicine. These questions could be addressed by basic, translational, and/or clinical research studies and were focused on four areas: the three “classical” transfusion products (i.e., red blood cells, platelets, and plasma) and blood donor issues. Prior to the meeting, four Working Groups, one for each area, prepared five major questions for discussion along with a list of 5-10 additional questions for consideration. At the meeting itself, all of these questions, and others, were discussed in Keynote lectures, small group breakout sessions, and large group sessions with open discourse involving all meeting attendees. In addition to the final lists of questions, provided herein, the meeting attendees identified multiple overarching, cross-cutting themes that addressed issues common to all four areas; the latter are also provided. It is anticipated that addressing these scientific priorities, with careful attention to the overarching themes, will inform funding priorities developed by the NIH and provide a solid research platform for transforming the future practice of transfusion medicine. PMID:26260861

Update on massive transfusion.

PubMed

Pham, H P; Shaz, B H

2013-12-01

Massive haemorrhage requires massive transfusion (MT) to maintain adequate circulation and haemostasis. For optimal management of massively bleeding patients, regardless of aetiology (trauma, obstetrical, surgical), effective preparation and communication between transfusion and other laboratory services and clinical teams are essential. A well-defined MT protocol is a valuable tool to delineate how blood products are ordered, prepared, and delivered; determine laboratory algorithms to use as transfusion guidelines; and outline duties and facilitate communication between involved personnel. In MT patients, it is crucial to practice damage control resuscitation and to administer blood products early in the resuscitation. Trauma patients are often admitted with early trauma-induced coagulopathy (ETIC), which is associated with mortality; the aetiology of ETIC is likely multifactorial. Current data support that trauma patients treated with higher ratios of plasma and platelet to red blood cell transfusions have improved outcomes, but further clinical investigation is needed. Additionally, tranexamic acid has been shown to decrease the mortality in trauma patients requiring MT. Greater use of cryoprecipitate or fibrinogen concentrate might be beneficial in MT patients from obstetrical causes. The risks and benefits for other therapies (prothrombin complex concentrate, recombinant activated factor VII, or whole blood) are not clearly defined in MT patients. Throughout the resuscitation, the patient should be closely monitored and both metabolic and coagulation abnormalities corrected. Further studies are needed to clarify the optimal ratios of blood products, treatment based on underlying clinical disorder, use of alternative therapies, and integration of laboratory testing results in the management of massively bleeding patients.

Is group A thawed plasma suitable as the first option for emergency release transfusion? (CME).

PubMed

Chhibber, Vishesh; Greene, Mindy; Vauthrin, Michelle; Bailey, Jeff; Weinstein, Robert

2014-07-01

Group AB plasma, which lacks anti-A and anti-B isohemagglutinins, is issued for emergency transfusion when a patient's ABO group is unknown, but the relative scarcity of group AB blood donors limits its availability. We sought to establish a thawed plasma inventory to improve the rapid availability of plasma in the emergency release setting but were concerned about potential wastage of group AB plasma. Recognizing that plasma-incompatible apheresis platelets are routinely transfused and only rarely result in hemolytic reactions if the donor is blood group O, and considering that group A plasma would be compatible with approximately 85% of our patient population, we instituted an emergency release policy whereby thawed group A plasma is issued to all patients of unknown blood group or if compatible plasma is not available. ABO-compatible plasma is then issued, if needed, once the patient's blood group is determined. We prospectively assessed the outcomes of all patients who received incompatible plasma under our policy. During the first 5 years under this policy, 385 emergency release requests for plasma were received by our blood bank. Among them, 23 group B or AB patients met criteria for receiving a median of 2 units of incompatible group A plasma. No hemolytic transfusion reactions or other adverse events related to transfusion were seen in any of these 23 patients. We propose that group A plasma may be an acceptable alternative to AB plasma as the first option in the emergency release setting. © 2014 AABB.

Hemovigilance monitoring of platelet septic reactions with effective bacterial protection systems.

PubMed

Benjamin, Richard J; Braschler, Thomas; Weingand, Tina; Corash, Laurence M

2017-12-01

Delayed, large-volume bacterial culture and amotosalen/ultraviolet-A light pathogen reduction are effective at reducing the risk of bacterial proliferation in platelet concentrates (PCs). Hemovigilance programs continue to receive reports of suspected septic transfusion reactions, most with low imputability. Here, we compile national hemovigilance data to determine the relative efficacy of these interventions. Annual reports from the United Kingdom, France, Switzerland, and Belgium were reviewed between 2005 and 2016 to assess the risk of bacterial contamination and septic reactions. Approximately 1.65 million delayed, large-volume bacterial culture-screened PCs in the United Kingdom and 2.3 million amotosalen/ultraviolet-A-treated PCs worldwide were issued with no reported septic fatalities. One definite, one possible, and 12 undetermined/indeterminate septic reactions and eight contaminated "near misses" were reported with delayed, large-volume bacterial cultures between 2011 and 2016, for a lower false-negative culture rate than that in the previous 5 years (5.4 vs. 16.3 per million: odds ratio, 3.0; 95% confidence interval, 1.4-6.5). Together, the Belgian, Swiss, and French hemovigilance programs documented zero probable or definite/certain septic reactions with 609,290 amotosalen/ultraviolet-A-treated PCs (<1.6 per million). The rates were significantly lower than those reported with concurrently transfused, nonpathogen-reduced PCs in Belgium (<4.4 vs. 35.6 per million: odds ratio, 8.1; 95% confidence interval,1.1-353.3) and with historic septic reaction rates in Switzerland (<6.0 vs. 82.9 per million: odds ratio, 13.9; 95% confidence interval, 2.1-589.2), and the rates tended to be lower than those from concurrently transfused, nonpathogen-reduced PCs in France (<4.7 vs. 19.0 per million: odds ratio, 4.1; 95% confidence interval, 0.7-164.3). Pathogen reduction and bacterial culture both reduced the incidence of septic reactions, although under-reporting and strict imputability criteria resulted in an underestimation of risk. © 2017 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

What we have learned about minimized extracorporeal circulation versus conventional extracorporeal circulation: an updated meta-analysis.

PubMed

Sun, Yanhua; Gong, Bing; Yuan, Xin; Zheng, Zhe; Wang, Guyan; Chen, Guo; Zhou, Chenghui; Wang, Wei; Ji, Bingyang

2015-08-01

The benefits of minimized extracorporeal circulation (MECC) compared with conventional extracorporeal circulation (CECC) are still in debate. PubMed, EMBASE and the Cochrane Library were searched until November 10, 2014. After quality assessment, we chose a fixed-effects model when the trials showed low heterogeneity, otherwise a random-effects model was used. We performed univariate meta-regression and sensitivity analysis to search for the potential sources of heterogeneity. Cumulative meta-analysis was performed to access the evolution of outcome over time. 41 RCTs enrolling 3744 patients were included after independent article review by 2 authors. MECC significantly reduced atrial fibrillation (RR, 0.76; 95% CI, 0.66 to 0.89; P < 0.001; I2 = 0%), and myocardial infarction (RR, 0.43; 95% CI, 0.26 to 0.71; P = 0.001; I2 = 0%). In addition, the results regarding chest tube drainage, transfusion rate, blood loss, red blood cell transfusion volume, and platelet count favored MECC as well. MECC diminished morbidity of cardiovascular complications postoperatively, conserved blood cells, and reduced allogeneic blood transfusion.

[Report on notifications pursuant to Section 21 German Transfusion Act for 2007].

PubMed

Henseler, O; Heiden, M; Haschberger, B; Hesse, J; Seitz, R

2009-07-01

The present report contains the data collected in 2007, pursuant to Section 21 Transfusionsgesetz (German Transfusion Act), and an analysis of the supply situation over the past eight years. The recording of the data by online reporting is in the meantime well established and generally accepted. As in previous years, all blood donation centers located in Germany transmitted data on the collection, manufacture, import and export of blood components for transfusion, so that meaningful data are available. According to these data, a total of 6.7 million blood collections were performed in 2007. The number of whole blood donations was at the level of previous years, with 4.7 million, whereas the number of apheresis donations rose again, to 1.9 million. The portion of autologous blood collections accounts for only 1.1% and thus continues to decline. Since 2003, the number of red blood cell concentrates prepared has been a constant 4.5 million transfusion units. The decrease in the portion of decay of red blood cell concentrates on the user side is particularly good news. In 2000, it accounted for 5% and in 2007, it was just above 3%, referred to the total quantity of data reported as transfused and decayed. The manufacture of platelet concentrates rose from 366,000 to 480,000 transfusion units between 2003 and 2007. The production of therapeutic single plasmas also markedly increased in 2007 compared with previous years, accounting for 1.2 million transfusion units. In 2007, 2.2 million liters of plasma for fractionation were collected in Germany. This trend went hand in hand with the increasing number of apheresis donations that year. In addition, 1.0 million liters were imported, and, at the same time, 1.8 million liters were exported. The quantity available in Germany from a pure arithmetic point of view of 1.4 million liters was almost entirely allocated to basic fractionation, so that a sufficient plasma supply can be assumed. The assessment of the degree of self-sufficiency is made difficult because of the influence of imports and exports; however, the results show no deficit for plasma derivatives. Due to the fact that manufacturing capacities are still lacking in Germany, recombinant factors need to be imported in their entirety. Since 2003, Germany has by far been the leader in Europe with more than 20 liters of fractionation plasma collected per 1,000 inhabitants. Furthermore, regarding the manufacturing figures of red blood cell concentrates, platelet concentrates, and therapeutic single plasma, Germany is in the top third for all these products compared with other European countries. The manufacture of allogeneic stem cell products for hematopoietic reconstitution, obtained by apheresis, has continuously risen to 4,700 in the reporting year. A large portion of this, 1,810 transplants could be exported while only a small number, 179 preparations, had to be imported. The manufacture of autologous stem cell preparations from cord blood also rose drastically compared with 2006, to more than 10,000 in 2007. It must be emphasized that these products were entirely placed into stock; none were transplanted in the reporting year. The interest in the figures collected in compliance with Section 21, Transfusion Act remains high both in Germany and at the international level. Reliable data are available thanks to the evaluations of trends over years, above all on the availability of blood components for transfusion. In addition, the Paul Ehrlich Institute will continue to strive to meet the demands for high-quality information on the supply situation in the future.

Bilateral large subconjunctival haemorrhages unmasking immune thrombocytopenic purpura during retinopathy of prematurity screening.

PubMed

Chandra, Parijat; Kumawat, Devesh; Kumar, Vinod; Tewari, Ruchir

2017-10-04

Although thrombocytopenia is known to be associated with pathogenesis of retinopathy of prematurity (ROP), immune thrombocytopenic purpura (ITP) is rare in infancy and not reported to occur with ROP. A preterm infant with aggressive posterior ROP developed bilateral massive subconjunctival haemorrhage after scleral indentation during screening. On evaluation, the infant was found to have severe ITP. Following intravenous transfusion of platelets and immunoglobulin, platelet counts improved and subconjunctival haemorrhage resolved over time. This case highlights the unusual presentation of ITP and also discusses the association of thrombocytopenia with ROP. Ophthalmologists should get prompt haematological work-up of such occurrences. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Red blood cell transfusion and increased length of storage are not associated with deep vein thrombosis in medical and surgical critically ill patients: a prospective observational cohort study

PubMed Central

2011-01-01

Introduction With prolonged storage times, cell membranes of red blood cells (RBCs) undergo morphologic and biochemical changes, termed 'RBC storage lesions'. Storage lesions may promote inflammation and thrombophilia when transfused. In trauma patients, RBC transfusion was an independent risk factor for deep vein thrombosis (DVT), specifically when RBC units were stored > 21 days or when 5 or more units were transfused. The objective of this study was to determine if RBC transfusions or RBC storage age predicts incident DVT in medical or surgical intensive care unit (ICU) patients. Methods Using a database which prospectively enrolled 261 patients over the course of 1 year with an ICU stay of at least 3 days, we analyzed DVT and RBC transfusions using Cox proportional hazards regression. Transfusions were analyzed with 4 thresholds, and storage age using 3 thresholds. DVTs were identified by twice-weekly proximal leg ultrasounds. Multivariable analyses were adjusted for 4 significant DVT predictors in this population (venous thrombosis history, chronic dialysis, platelet transfusion and inotropes). Results Of 261 patients, 126 (48.3%) had at least 1 RBC transfusion; 46.8% of those transfused had ≥ 5 units in ICU. Patients receiving RBCs were older (68.8 vs 64.1 years), more likely to be female (47.0 vs 30.7), sicker (APACHEII 26.8 vs 24.4), and more likely to be surgical (21.4 vs 8.9) (P < 0.05). The total number of RBCs per patient was 1-64, mean was 6.3 (SD 7.5), median was 4 (IQR 2,8). In univariate analyses, there was no association between DVT and RBC exposure (1 day earlier, 3 days earlier, 7 days earlier, or ever) or RBC storage (≤ 7 or > 7 days, ≤ 14 or > 14 days, ≤ 21 or > 21 days). Among patients transfused, no multivariable analyses showed that RBC transfusion or storage age predicted DVT. Trends were counter to the hypothesis (e.g., RBC storage for ≤ 7 days suggested a higher DVT risk compared to > 7 days (HR 5.3; 95% CI 1.3-22.1). Conclusions We were unable to detect any association between RBC transfusions or prolonged red cell storage and increased risk of DVT in medical or surgical ICU patients. Alternate explanations include a lack of sufficient events or patients' interaction, between patient groups, a mixing of red cell storage times creating differential effects on DVT risk, and unmeasured confounders. PMID:22044745

Utilisation of Blood Components in Trauma Surgery: A Single-Centre, Retrospective Analysis before and after the Implementation of an Educative PBM Initiative.

PubMed

Geissler, Raoul Georg; Kösters, Clemens; Franz, Dominik; Buddendick, Hubert; Borowski, Matthias; Juhra, Christian; Lange, Matthias; Bunzemeier, Holger; Roeder, Norbert; Sibrowski, Walter; Raschke, Michael J; Schlenke, Peter

2015-03-01

The aim of our single-centre retrospective study presented here is to further analyse the utilisation of allogeneic blood components within a 5-year observation period (2009-2013) in trauma surgery (15,457 patients) under the measures of an educational patient blood management (PBM) initiative. After the implementation of the PBM initiative in January 2012, the Institute of Transfusion Medicine und Transplantation Immunology educates surgeons and nurses at the Department of Trauma Surgery to avoid unnecessary blood transfusions. A standardised reporting system was used to document the utilisation of blood components carefully for the most frequent diagnoses and surgical interventions in trauma surgery. These measures served as basis for the implementation of an interdisciplinary systematic exchange of information to foster decision-making processes in favour of patient blood management. Since January 2012, the proportion of patients who received a transfusion as well as the number of transfused red blood cell (RBC) (7.3%/6.4%; p = 0.02), fresh frozen plasma (FFP) (1.7%/1.3%; p < 0.05) and platelet (PLT) (1.0%/0.5%; p < 0.001) units were reduced as a result of our PBM initiative. However, among the transfused patients, the number of administered RBC, FFP and PLT units did not decrease significantly. Overall, patients who did not receive transfusions were younger than transfused patients (p = 0.001). The subgroup with the highest probability of blood transfusion administered included patients with intensive care and long-term ventilation (before/after implementation of PBM: RBC 81.5%/75.9%; FFP 33.3%/20.4%; PLT 24.1%/13.0%). Only a total of 60 patients of 531 patients suffering multiple traumas were massively transfused (before/after implementation of PBM: RBC 55.6%/49.8%; FFP 28.4%/20.4%; PLT 17.6%/8.9%). According to our educational PBM initiative, at least the proportion of trauma patients who received allogeneic blood transfusions could be reduced significantly. However, in case of blood transfusions, the total consumption of RBC, FFP and PLT units remained stable in both time periods. This phenomenon might indicate that the actual need of blood transfusions rather depends on the severity of trauma-related blood loss, the coagulopathy rates or the complexity of the surgical intervention which mainly determines the intra-operative blood loss. Taken together, educational training sessions and systematic reporting systems are suitable measures to avoid unnecessary allogeneic blood transfusions and to continuously improve their restrictive application.

Use of freeze-dried plasma in French intensive care unit in Afghanistan.

PubMed

Martinaud, Christophe; Ausset, Sylvain; Deshayes, Anne Virginie; Cauet, Amandine; Demazeau, Nicolas; Sailliol, Anne

2011-12-01

Modern warfare causes severe injuries, and despite rapid transportation to theater regional trauma centers, casualties frequently arrive coagulopathic and in shock. Massive hemorrhage management includes transfusion of red blood cells and plasma in a 1:1 ratio. Fresh frozen plasma requires thawing and badly fits the emergency criteria. Since 1994, the French Military Blood Bank has been producing freeze-dried plasma (FDP) and providing it for overseas operation. The aim of our study was to evaluate the use of FDP in war settings and to assess its clinical efficiency and safety. We performed a prospective study of the FDP delivered at the International Security Assistance Force Role 3 Military Medical Treatment Facility in the Kabul Afghanistan International Airport between February 2010 and February 2011. We included every patient who received at least one unit of FDP. Basic clinical data were recorded at admission. Transfusion requirements were monitored. Biological testing were performed before and after administration of FDP including hemoglobin concentration, platelets count, fibrinogen level, prothrombin time (PT), and thromboelastography. Eighty-seven casualties received FDP during 93 episodes of transfusion. On average, 3.5 FDP units were transfused per episodes of transfusion. Of the 87 patients studied, 7 died because of nonsurvivable injuries and outcomes were unavailable for 11. The other 59 patients survived. PT significantly declined by an average of 3.3 seconds after FDP transfusion. This moderate decrease in PT reflects continued bleeding and resuscitation. It nevertheless suggests improvement in hemostasis before surgical control of bleeding. All FDP users reported ease of use, clinically observed efficacy equivalent to fresh frozen plasma and the absence of adverse effects associated with FDP. Our results provide evidence of the effectiveness of FDP for the prevention or correction of coagulopathy and hemorrhage in combat casualties.

Placental umbilical cord whole blood transfusion to combat anemia in the background of tuberculosis and emaciation and its potential role as an immuno-adjuvant therapy for the under-resourced people of the world.

PubMed

Bhattacharya, N

2006-01-01

Tuberculosis causes approximately 1.5 billion latent infections, 8 million new clinical cases, and 3 million deaths annually, making it the most prevalent infectious disease in the world. Anemia and malnutrition are essential comorbidities with tuberculosis. Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and WBC counts, and a plasma filled with cytokine and growth factors, as well as its hypo-antigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. We transfused 106 units (48 ml-148 ml mean 81 ml +/- 6.6 ml SD, median 82 ml, mean packed cell volume 49.4 +/- 3.1 SD, mean percent hemoglobin concentration 16.3 g/dl +/- 1.7 g/dl SD) of placental umbilical cord whole blood (from 1 April 1999 to 1st 2005) after lower uterine cesarean section from consenting mothers to 21 informed consenting patients with tuberculosis who had percent plasma hemoglobin of 8 g/dl or less. After collection, the blood was immediately transfused following the standard adult blood transfusion protocol. Each case was passed through the institutional ethical committee. The patients received 2-21 units of freshly collected placental umbilical cord blood without encountering any clinical, immunological or non-immunological reactions. Three days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 2.99% to 33%, which returned to base level in 66.66% at the three-month CD34 re-estimation, without provoking any clinical graft vs host reaction in any of the patients.

False-positive pregnancy test after transfusion of solvent/detergent-treated plasma.

PubMed

Jilma-Stohlawetz, Petra; Wreford-Bush, Tim; Mills, Francesca; Davidson, Fiona; Kursten, Friedrich W; Jilma, Bernd; Birchall, Janet

2017-12-01

The transmission of pathogens, antibodies, and proteins is a possible consequence of blood product transfusion. A female patient had an unexpected positive serum β-human chorionic gonadotropin result, indicative of pregnancy, after she had received a transfusion with 1 unit of platelet concentrate, 4 units of red blood cells, and 4 units of pooled solvent/detergent-treated plasma (Octaplas). To investigate the possibility of passive transfusion of β-human chorionic gonadotropin from the plasma transfusion, one additional unit from the same batch was thawed and analyzed. To validate the β-human chorionic gonadotropin assay for use in solvent/detergent-treated plasma and to investigate any interference in the assay, dilution experiments were performed using the implicated plasma batch diluted with male and non-pregnant female sera. Also, plasma from a known pregnant woman was diluted with Octaplas (tested negative for β-human chorionic gonadotropin) and with a male serum to validate the assay for use in solvent/detergent-treated plasma. The implicated solvent/detergent-treated plasma had a mean β-human chorionic gonadotropin level of 91.5 mIU/mL. Results from the dilution experiments revealed an excellent correlation (r > 0.99) between β-human chorionic gonadotropin measurement in solvent/detergent-treated plasma and male serum and no over or under recovery of the expected results. Further measurements of β-human chorionic gonadotropin levels in the female recipient revealed an estimated half-life of 6 hours. This case demonstrates the importance of considering the possibility of passive transmission of analytes to a patient from the transfusion of blood products. Furthermore, the measurement of β-human chorionic gonadotropin is valid in solvent/detergent-treated plasma using a Roche Cobas analyzer. © 2017 AABB.

The LeucoPatch® system in the management of hard-to-heal diabetic foot ulcers: study protocol for a randomised controlled trial.

PubMed

Game, Frances; Jeffcoate, William; Tarnow, Lise; Day, Florence; Fitzsimmons, Deborah; Jacobsen, Judith

2017-10-10

Diabetic foot ulcers are a common and severe complication of diabetes mellitus. Standard treatment includes debridement, offloading, management of infection and revascularisation where appropriate, although healing times may be long. The LeucoPatch® device is used to generate an autologous platelet-rich fibrin and leucocyte wound dressing produced from the patient's own venous blood by centrifugation, but without the addition of any reagents. The final product comprises a thin, circular patch composed predominantly of fibrin together with living platelets and leucocytes. Promising results have been obtained in non-controlled studies this system, but this now needs to be tested in a randomised controlled trial (RCT). If confirmed, the LeucoPatch® may become an important new tool in the armamentarium in the management of diabetic foot ulcers which are hard-to-heal. People with diabetes and hard-to-heal ulcers of the foot will receive either pre-specified good standard care or good standard care supplemented by the application of the LeucoPatch® device. The primary outcome will be the percentage of ulcers healed within 20 weeks. Healing will be defined as complete epithelialisation without discharge that is maintained for 4 weeks and is confirmed by an observer blind to randomisation group. Ulcers of the foot are a major source of morbidity to patients with diabetes and costs to health care economies. The study population is designed to be as inclusive as possible with the aim of maximising the external validity of any findings. The primary outcome measure is healing within 20 weeks of randomisation and the trial also includes a number of secondary outcome measures. Among these are rate of change in ulcer area as a predictor of the likelihood of eventual healing, minor and major amputation of the target limb, the incidence of infection and quality of life. International Standard Randomised Controlled Trial, ISRCTN27665670 . Registered on 5 July 2013.

Diagnostic Methods for Platelet Bacteria Screening: Current Status and Developments

PubMed Central

Störmer, Melanie; Vollmer, Tanja

2014-01-01

Summary Bacterial contamination of blood components and the prevention of transfusion-associated bacterial infection still remains a major challenge in transfusion medicine. Over the past few decades, a significant reduction in the transmission of viral infections has been achieved due to the introduction of mandatory virus screening. Platelet concentrates (PCs) represent one of the highest risks for bacterial infection. This is due to the required storage conditions for PCs in gas-permeable containers at room temperature with constant agitation, which support bacterial proliferation from low contamination levels to high titers. In contrast to virus screening, since 1997 in Germany bacterial testing of PCs is only performed as a routine quality control or, since 2008, to prolong the shelf life to 5 days. In general, bacterial screening of PCs by cultivation methods is implemented by the various blood services. Although these culturing systems will remain the gold standard, the significance of rapid methods for screening for bacterial contamination has increased over the last few years. These new methods provide powerful tools for increasing the bacterial safety of blood components. This article summarizes the course of policies and provisions introduced to increase bacterial safety of blood components in Germany. Furthermore, we give an overview of the different diagnostic methods for bacterial screening of PCs and their current applicability in routine screening processes. PMID:24659944

Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs.

PubMed

Rozanski, Elizabeth A; Callan, Mary Beth; Hughes, Dez; Sanders, Nancy; Giger, Urs

2002-02-15

To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). Prospective case study. 24 dogs with severe primary IMT PROCEDURE: All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to > or = 40,000/microl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to > or = 40,000 platelets/microl than dogs that received prednisone alone (mean +/- SD, 4.9 +/- 1.1 vs 6.8 +/- 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 +/- 0.3 vs 7.3 +/- 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT.

Platelet microparticles: detection and assessment of their paradoxical functional roles in disease and regenerative medicine.

PubMed

Burnouf, Thierry; Goubran, Hadi Alphonse; Chou, Ming-Li; Devos, David; Radosevic, Mirjana

2014-07-01

There is increasing research on and clinical interest in the physiological role played by platelet microparticles (PMPs). PMPs are 0.1-1-μm fragments shed from plasma membranes of platelets that are undergoing activation, stress, or apoptosis. They have a phospholipid-based structure and express functional receptors from platelet membranes. As they are the most abundant microparticles in the blood and they express the procoagulant phosphatidylserine, PMPs likely complement, if not amplify, the functions of platelets in hemostasis, thrombosis, cancer, and inflammation, but also act as promoters of tissue regeneration. Their size and structure make them instrumental in platelet-cell communications as a delivery tool of platelet-borne bioactive molecules including growth factors, other signaling molecules and micro (mi)RNA. PMPs can therefore be a pathophysiological threat or benefit to the cellular environment when interacting with the blood vasculature. There is also increasing evidence that PMP generation is triggered during blood collection, separation into components, and storage, a phenomenon potentially leading to thrombotic and inflammatory side effects in transfused patients. Evaluating PMPs requires strict pre-analytical and analytical procedures to avoid artifactual generation and ensure accurate assessment of the number, size repartitioning, and functional properties. This review describes the physical and functional methods developed for analyzing and quantifying PMPs. It then presents the functional roles of PMPs as markers or triggers of diseases like thrombosis, atherosclerosis, and cancer, and discusses the possible detrimental immunological impact of their generation in blood components. Finally we review the potential function of PMPs in tissue regeneration and the prospects for their use in therapeutic strategies for human health. Copyright © 2014 Elsevier Ltd. All rights reserved.

Plateletworks platelet function test compared to the thromboelastograph for prediction of postoperative outcomes.

PubMed

Ostrowsky, Jacob; Foes, Jennifer; Warchol, Mark; Tsarovsky, Gary; Blay, Jessica

2004-06-01

Approximately 3.5 million units of platelets are transfused in the United States each year to patients undergoing open-heart surgery with cardiopulmonary bypass (CPB). CPB is a known contributor to platelet loss and platelet dysfunction leading to disruption of hemostasis. Impaired hemostasis results in excess bleeding in 5-25% of all patients undergoing CPB. For this reason, it may be beneficial to measure platelet number and function in these patients. The purpose of this study was to compare the Plateletworks platelet function analyzer to the thromboelastograph (TEG) in predicting postoperatiave hemostatic outcomes as measured by blood product use and chest tube (CT) drainage. This study consisted of 35 adult patients undergoing cardiac surgery with cardiopulmonary bypass at Rush-Presbyterian-Saint Luke's Medical Center (RPSLMC). The Plateletworks and TEG tests were performed preoperatively, after protamine was given, and 24 hours postoperatively on all patients. Plateletworks demonstrated a statistically significant change in platelet function as shown by the adenosine diphosphate (ADP) reagent tube from the preoperative period to the removal of the aortic cross clamp (p = .011). The TEG did not demonstrate a significant change in the k-time and maximum amplitude (MA), but did show a significant change in the alpha-angle from the pre-operative to postoperatiave sample (p = .035). A correlation was found between Plateletworks collagen reagent tubes preoperatively and CT drainage (p = .048, r -0.324). No statistical correlation was established between TEG parameters and CT drainage at any time interval. TEG preoperative MA showed a correlation to receipt of blood products (p = .016). When comparing the Plateletworks to the TEG in this study, the Plateletworks system was a more useful predictor of blood product use and chest tube drainage.

Comparison of bacterial attachment to platelet bags with and without preconditioning with plasma.

PubMed

Loza-Correa, M; Kalab, M; Yi, Q-L; Eltringham-Smith, L J; Sheffield, W P; Ramirez-Arcos, S

2017-07-01

Canadian Blood Services produces apheresis and buffy coat pooled platelet concentrates (PCs) stored in bags produced by two different manufacturers (A and B, respectively), both made of polyvinyl chloride-butyryl trihexyl citrate. This study was aimed at comparing Staphylococcus epidermidis adhesion to the inner surface of both bag types in the presence or absence of plasma factors. Sets (N = 2-6) of bags type A and B were left non-coated (control) or preconditioned with platelet-rich, platelet-poor or defibrinated plasma (PRP, PPP and DefibPPP, respectively). Each bag was inoculated with a 200-ml S. epidermidis culture adjusted to 0·5 colony-forming units/ml. Bags were incubated under platelet storage conditions for 7 days. After culture removal, bacteria attached to the plastic surface were either dislodged by sonication for bacterial quantification or examined in situ by scanning electron microscopy (SEM). Higher bacterial adhesion was observed to preconditioned PC bags than control containers for both bag types (P < 0·0001). Bacterial attachment to preconditioned bags was confirmed by SEM. Bacteria adhered equally to both types of containers in the presence of PRP, PPP and DefibPPP residues (P > 0·05). By contrast, a significant increase in bacterial adherence was observed to type A bags compared with type B bags in the absence of plasma (P < 0·05) [Correction added on 16 June 2017, after first online publication: this sentence has been corrected]. The ability of S. epidermidis to adhere to preconditioned platelet collection bags depends on the presence of plasma factors. Future efforts should be focused on reducing plasma proteins' attachment to platelet storage containers to decrease subsequent bacterial adhesion. © 2017 International Society of Blood Transfusion.

TEG-Directed Transfusion in Complex Cardiac Surgery: Impact on Blood Product Usage.

PubMed

Fleming, Kevin; Redfern, Roberta E; March, Rebekah L; Bobulski, Nathan; Kuehne, Michael; Chen, John T; Moront, Michael

2017-12-01

Complex cardiac procedures often require blood transfusion because of surgical bleeding or coagulopathy. Thrombelastography (TEG) was introduced in our institution to direct transfusion management in cardiothoracic surgery. The goal of this study was to quantify the effect of TEG on transfusion rates peri- and postoperatively. All patients who underwent complex cardiac surgery, defined as open multiple valve repair/replacement, coronary artery bypass grafting with open valve repair/replacement, or aortic root/arch repair before and after implementation of TEG were identified and retrospectively analyzed. Minimally invasive cases were excluded. Patient characteristics and blood use were compared with t test and chi-square test. A generalized linear model including patient characteristics, preoperative and postoperative lab values, and autotransfusion volume was used to determine the impact of TEG on perioperative, postoperative, and total blood use. In total, 681 patients were identified, 370 in the pre-TEG period and 311 patients post-TEG. Patient demographics were not significantly different between periods. Mean units of red blood cells, plasma, and cryoprecipitate were significantly reduced after TEG was implemented (all, p < .0001); use of platelets was reduced but did not reach significance. Mean units of all blood products in the perioperative period and over the entire stay were reduced by approximately 40% (both, p < .0001). Total proportion of patients exposed to transfusion was significantly lower after introduction of TEG ( p < .01). Controlling for related factors on multivariate analysis, such as preoperative laboratory values and autotransfusion volume, use of TEG was associated with significant reduction in perioperative and overall blood product transfusion. TEG-directed management of blood product administration during complex cardiac surgeries significantly reduced the units of blood products received perioperatively but not blood usage more than 24 hours after surgery. Overall, fewer patients were exposed to allogenic blood. The use of TEG to guide blood product administration significantly impacted transfusion therapy and associated costs.

Cost-effectiveness of using recombinant activated factor VII as an off-label rescue treatment for critical bleeding requiring massive transfusion.

PubMed

Ho, Kwok M; Litton, Edward

2012-08-01

Recombinant activated factor VII (rFVIIa) is widely used as an off-label rescue treatment for patients with nonhemophilic critical bleeding. Using data from the intensive care unit, transfusion service, and death registry, the long-term survival after using rFVIIa and the associated cost per life-year gained in a consecutive cohort of patients with critical bleeding requiring massive transfusion (≥ 10 red blood cell [RBC] units in 24 hr) were assessed. rFVIIa was only used as a lifesaving treatment when conventional measures had failed. Of the 353 patients with critical bleeding requiring massive transfusion, 81 (23%) required rFVIIa as a lifesaving rescue treatment. The patients requiring rFVIIa received a greater number of transfusions (number of units: RBCs, 18 vs. 12; fresh-frozen plasma, 16 vs. 10; platelets, 4 vs. 2; p < 0.001) and had a shorter survival time (24 months vs. 33 months; p = 0.002) than those who did not require rFVIIa. The total cost per life-year gained of massive transfusion and incremental cost of rFVIIa as a lifesaving treatment were US$1,148,000 (£711,760; 95% confidence interval [CI], US$825,000-US$1,471,000) and US$736,000 (£456,320; 95% CI, US$527,000-US$945,000), respectively. The incremental costs of rFVIIa increased with severity of illness and transfusion requirement and were greater than the usual acceptable cost-effective limit (

The IgE-dependent pathway in allergic transfusion reactions: involvement of donor blood allergens other than plasma proteins.

PubMed

Matsuyama, Nobuki; Yasui, Kazuta; Amakishi, Etsuko; Hayashi, Tomoya; Kuroishi, Ayumu; Ishii, Hiroyuki; Matsukura, Harumichi; Tani, Yoshihiko; Furuta, Rika A; Hirayama, Fumiya

2015-07-01

On transfusion, several plasma proteins can cause anaphylaxis in patients deficient in the corresponding plasma proteins. However, little is known about other allergens, which are encountered much more infrequently. Although it has been speculated that an allergen-independent pathway underlying allergic transfusion reactions (ATRs) is elicited by biological response modifiers accumulated in blood components during storage, the exact mechanisms remain unresolved. Furthermore, it is difficult even to determine whether ATRs are induced via allergen-dependent or allergen-independent pathways. To distinguish these two pathways in ATR cases, we established a basophil activation test, in which the basophil-activating ability of supernatants of residual transfused blood of ATR cases to whole blood basophils was assessed in the presence or absence of dasatinib, an inhibitor of IgE-mediated basophil activation. Three of 37 supernatants from the platelet concentrates with ATRs activated panel blood basophils in the absence, but not in the presence, of dasatinib. The basophil activation was inhibited by treatment of anti-fish collagen I MoAb in one case, suggesting that the involvement of fish allergens may have been present in donor plasma. We concluded that unknown non-plasma proteins, some of which had epitopes similar to fish antigens, in blood component may be involved in ATRs via an allergen/IgE-dependent pathway.

Interim analysis of post-marketing surveillance of eculizumab for paroxysmal nocturnal hemoglobinuria in Japan.

PubMed

Ninomiya, Haruhiko; Obara, Naoshi; Chiba, Shigeru; Usuki, Kensuke; Nishiwaki, Kaichi; Matsumura, Itaru; Shichishima, Tsutomu; Okamoto, Shinichiro; Nishimura, Jun-Ichi; Ohyashiki, Kazuma; Nakao, Shinji; Ando, Kiyoshi; Kanda, Yoshinobu; Kawaguchi, Tatsuya; Nakakuma, Hideki; Harada, Daisuke; Akiyama, Hirozumi; Kinoshita, Taroh; Ozawa, Keiya; Omine, Mitsuhiro; Kanakura, Yuzuru

2016-11-01

Data characterizing the safety and effectiveness of eculizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) are limited. We describe the safety and effectiveness of eculizumab in PNH patients enrolled in a post-marketing surveillance study. Types and frequencies of observed adverse events were similar to those reported in previous clinical trials and no meningococcal infection was reported. Effectiveness outcomes included the reduction of intravascular hemolysis, the change in hemoglobin (Hb) level, the withdrawal of transfusion and corticosteroids, the change of renal function, and overall survival. The effect of eculizumab on intravascular hemolysis was demonstrated by a reduction in lactate dehydrogenase levels at all measurements after baseline. Significant increases in Hb levels from baseline were also observed after 1 month's treatment with eculizumab (p < 0.01). Of those who were transfusion-dependent at baseline, the median number of transfusions decreased significantly from 18 to 0 unit/year after 1 year of treatment with eculizumab (p < 0.001). An increase in Hb and a high rate of transfusion independence were observed, especially in patients with platelet count ≥150 × 10 9 /L. Approximately 97 % of patients showed maintenance or improvement of renal function. Overall survival rate was about 90 % (median follow-up 1.9 years). These results suggest an acceptable safety profile and favorable prognosis after eculizumab intervention.

Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience.

PubMed

Fasano, Ross M; Sullivan, Harold Cliff; Bray, Robert A; Gebel, Howard M; Meyer, Erin K; Winkler, Annie M; Josephson, Cassandra D; Stowell, Sean R; Sandy Duncan, Alexander; Roback, John D

2017-03-01

Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for simultaneous detection of multiple HLA antigens, human platelet antigens, and red blood cell (RBC) antigens. The development of high-resolution, molecular HLA typing has led to improved outcomes in unrelated hematopoietic stem cell transplants by better identifying compatible alleles of the HLA-A, B, C, DRB1, and DQB1 antigens. In solid organ transplantation, the combination of high-resolution HLA typing with solid-phase antibody identification has proven of value for highly sensitized patients and has significantly reduced incompatible crossmatches at the time of organ allocation. This database-driven, combined HLA antigen/antibody testing has enabled routine implementation of "virtual crossmatching" and may even obviate the need for physical crossmatching. In addition, DNA-based testing for RBC antigens provides an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although RBC genotyping has utility in various transfusion settings, it has arguably been most useful for minimizing alloimmunization in the management of transfusion-dependent patients with sickle cell disease or thalassemia. The availability of high-throughput RBC genotyping for both individuals and large populations of donors, along with coordinated informatics systems to compare patients' antigen profiles with available antigen-negative and/or rare blood-typed donors, holds promise for improving the efficiency, reliability, and extent of RBC matching for this population.

Blood product transfusion and wastage rates in obstetric hemorrhage.

PubMed

Yazer, Mark H; Dunbar, Nancy M; Cohn, Claudia; Dillon, Jessica; Eldib, Howida; Jackson, Bryon; Kaufman, Richard; Murphy, Michael F; O'Brien, Kerry; Raval, Jay S; Seheult, Jansen; Staves, Julie; Waters, Jonathan H

2018-03-07

Bleeding emergencies can complicate pregnancies. Understanding the disposition of the products that are issued in this clinical setting can help inform inventory levels at hospitals where obstetric patients are seen. Patients who had an obstetric hemorrhage of any etiology between January 2013 and June 2017, and whose resuscitation began with uncrossmatched red blood cells (RBCs) or emergency-issued plasma or platelets (PLT), were included. The disposition of all blood products issued within 6 hours of the first uncrossmatched or emergency-issued product was documented, as was basic patient demographic information. In total, 301 women with an obstetric hemorrhage from seven academic institutions were identified. Their mean ± standard deviation age was 30.9 ± 6.1 years, 45.2% delivered by Cesarean section, and 40.5% delivered vaginally, while 12% did not deliver. The largest single etiology of hemorrhage was related to abnormal placentation. Of the 2280 issued RBC units, 55% were transfused, 43% were returned, and 2% were wasted. The rates of transfusion of the other blood products ranged from 58% for plasma units to 82% for cryoprecipitate. Seventeen percent of the issued cryoprecipitate units were wasted, the highest of any blood product. The rate of a patient receiving a transfusion when at least one blood product had been ordered ranged from 74% for PLTs to 91% for cryoprecipitate. Although the rates of receiving a transfusion of at least one blood product when one is ordered was high, many of the issued units were returned, especially for RBCs. © 2018 AABB.

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

PubMed

Rios, Jorge A; Schlumpf, Karen S; Kakaiya, Ram M; Triulzi, Darrell J; Roback, John D; Kleinman, Steve H; Murphy, Edward L; Gottschall, Jerome L; Carey, Patricia M

2011-06-01

Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI. © 2010 American Association of Blood Banks.

Reduced Transfusion During OLT by POC Coagulation Management and TEG Functional Fibrinogen: A Retrospective Observational Study.

PubMed

De Pietri, Lesley; Ragusa, Francesca; Deleuterio, Annalisa; Begliomini, Bruno; Serra, Valentina

2016-01-01

Patients undergoing orthotopic liver transplantation are at high risk of bleeding complications. Several Authors have shown that thromboelastography (TEG)-based coagulation management and the administration of fibrinogen concentrate reduce the need for blood transfusion. We conducted a single-center, retrospective cohort observational study (Modena Polyclinic, Italy) on 386 consecutive patients undergoing liver transplantation. We assessed the impact on resource consumption and patient survival after the introduction of a new TEG-based transfusion algorithm, requiring also the introduction of the fibrinogen functional thromboelastography test and a maximum amplitude of functional fibrinogen thromboelastography transfusion cutoff (7 mm) to direct in administering fibrinogen (2012-2014, n = 118) compared with a purely TEG-based algorithm previously used (2005-2011, n = 268). After 2012, there was a significant decrease in the use of homologous blood (1502 ± 1376 vs 794 ± 717 mL, P < 0.001), fresh frozen plasma (537 ± 798 vs 98 ± 375 mL, P < 0.001), and platelets (158 ± 280 vs 75 ± 148 mL, P < 0.005), whereas the use of fibrinogen increased (0.1 ± 0.5 vs 1.4 ± 1.8 g, P < 0.001). There were no significant differences in 30-day and 6-month survival between the 2 groups. The implementation of a new coagulation management method featuring the addition of the fibrinogen functional thromboelastography test to the TEG test according to an algorithm which provides for the administration of fibrinogen has helped in reducing the need for transfusion in patients undergoing liver transplantation with no impact on their survival.

Effects of preoperative aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in patients undergoing off-pump coronary artery bypass graft surgery.

PubMed

Shim, Jae Kwang; Choi, Yong Seon; Oh, Young Jun; Bang, Sou Ouk; Yoo, Kyung Jong; Kwak, Young Lan

2007-07-01

Preoperative exposure to clopidogrel and aspirin significantly increases postoperative bleeding in patients undergoing on-pump coronary artery bypass graft surgery. Off-pump coronary bypass grafting has been proposed as an alternative technique to attenuate postoperative bleeding associated with clopidogrel. This study aimed to determine the effects of aspirin and clopidogrel therapy on perioperative blood loss and blood transfusion requirements in off-pump coronary artery bypass grafting. One hundred six patients scheduled for off-pump coronary artery bypass grafting were divided into three groups: aspirin and clopidogrel discontinued more than 6 days before surgery (group 1, n = 35), aspirin and clopidogrel continued until 3 to 5 days before surgery (group 2, n = 51), and both medications continued within 2 days of surgery (group 3, n = 20). Thromboelastographic tracings were analyzed before induction of anesthesia. Routine coagulation profiles were measured before and after surgery. A cell salvage device was used during surgery and salvaged blood was reinfused. Chest tube drainage and blood transfusion requirement were recorded postoperatively. Patient characteristics, operative data, and thromboelastographic tracings were similar among the groups. There were significant decreases in hematocrit level and platelet count and prolongation in prothrombin time postoperatively in all groups without any intergroup differences. The amounts of perioperative blood loss and blood transfusion required were all similar among the groups. Preoperative clopidogrel and aspirin exposure even within 2 days of surgery does not increase perioperative blood loss and blood transfusion requirements in patients undergoing elective off-pump coronary artery bypass grafting.

Viscoelastic testing inside and beyond the operating room

PubMed Central

Tabaie, Sheida; Ivascu, Natalia

2017-01-01

Hemorrhage is a major contributor to morbidity and mortality during the perioperative period. Current methods of diagnosing coagulopathy have various limitations including long laboratory runtimes, lack of information on specific abnormalities of the coagulation cascade, lack of in vivo applicability, and lack of ability to guide the transfusion of blood products. Viscoelastic testing offers a promising solution to many of these problems. The two most-studied systems, thromboelastography (TEG) and rotational thromboelastometry (ROTEM), offer similar graphical and numerical representations of the initiation, formation, and lysis of clot. In systematic reviews on the clinical efficacy of viscoelastic tests, the majority of trials analyzed were in cardiac surgery patients. Reviews of the literature suggest that transfusions of packed red blood cells (pRBC), plasma, and platelets are all decreased in patients whose transfusions were guided by viscoelastic tests rather than by clinical judgement or conventional laboratory tests. Mortality appears to be lower in the viscoelastic testing groups, despite no difference in surgical re-intervention rates and massive transfusion rates. Cost-effectiveness studies also seem to favor viscoelastic testing. Viscoelastic testing has also been investigated in small studies in other clinical contexts, such as sepsis, obstetric hemorrhage, inherited bleeding disorders, perioperative thromboembolism risk assessment, and management of anticoagulation for patients on mechanical circulatory support systems or direct oral anticoagulants (DOACs). While the results are intriguing, no systematic, larger trials have taken place to date. Viscoelastic testing remains a relatively novel method to assess coagulation status, and evidence for its use appears favorable in reducing blood product transfusions, especially in cardiac surgery patients. PMID:28540073

Viscoelastic testing inside and beyond the operating room.

PubMed

Shen, Liang; Tabaie, Sheida; Ivascu, Natalia

2017-04-01

Hemorrhage is a major contributor to morbidity and mortality during the perioperative period. Current methods of diagnosing coagulopathy have various limitations including long laboratory runtimes, lack of information on specific abnormalities of the coagulation cascade, lack of in vivo applicability, and lack of ability to guide the transfusion of blood products. Viscoelastic testing offers a promising solution to many of these problems. The two most-studied systems, thromboelastography (TEG) and rotational thromboelastometry (ROTEM), offer similar graphical and numerical representations of the initiation, formation, and lysis of clot. In systematic reviews on the clinical efficacy of viscoelastic tests, the majority of trials analyzed were in cardiac surgery patients. Reviews of the literature suggest that transfusions of packed red blood cells (pRBC), plasma, and platelets are all decreased in patients whose transfusions were guided by viscoelastic tests rather than by clinical judgement or conventional laboratory tests. Mortality appears to be lower in the viscoelastic testing groups, despite no difference in surgical re-intervention rates and massive transfusion rates. Cost-effectiveness studies also seem to favor viscoelastic testing. Viscoelastic testing has also been investigated in small studies in other clinical contexts, such as sepsis, obstetric hemorrhage, inherited bleeding disorders, perioperative thromboembolism risk assessment, and management of anticoagulation for patients on mechanical circulatory support systems or direct oral anticoagulants (DOACs). While the results are intriguing, no systematic, larger trials have taken place to date. Viscoelastic testing remains a relatively novel method to assess coagulation status, and evidence for its use appears favorable in reducing blood product transfusions, especially in cardiac surgery patients.

[Heparin-induced thrombocytopenia developed during the acute phase after left upper lobectomy for lung cancer].

PubMed

Mitomo, Hideki; Miyamoto, Akira; Tabata, Toshiharu; Sugawara, Takafumi; Yabuki, Hiroshi; Fujimura, Shigefumi

2014-12-01

Heparin-induced thrombocytopenia (HIT) is a serious adverse effect of heparin administration. This must not be rarely encountered but is not often reported in Japan compared to Western countries. A 68-year-old woman underwent left upper lobectomy for lung cancer. Low-dose unfractionated heparin was administrated to prevent thromboembolism after the operation. Two days later, sudden dyspnea appeared and ultracardiosonography showing an extensive thromboembolus from the main trunk to both main branches of pulmonary artery indicated pulmonary embolization. After the establishment of percutaneous cardiopulmonary support (PCPS) support, the embolus was removed by emergent open heart surgery. However, despite further unfractionated heparin administration following embolization surgery, other thrombus was identified in both the bi-lateral internal jagular veins and inferior vena cava by ultrasonography and contrast computed tomography( CT). Her platelet count was decreased gradually despite platelet transfusion. Plate factor 4( PF4) antibody against heparin in her blood examination was found, and HIT II was diagnosed. Discontinuation of unfractionated heparin and administration of antithrombin agent improved platelet count, and no additional embolization was identified.

In-Silico Analysis of Amotosalen Hydrochloride Binding to CD-61 of Platelets.

PubMed

Chaudhary, Hammad Tufail

2016-11-01

To determine the docking of Amotosalen hydrochloride (AH) at CD-61 of platelets, and to suggest the cause of bleeding in AH treated platelets transfusion. Descriptive study. Medical College, Taif University, Taif, Saudi Arabia, from October 2014 to May 2015. The study was carried out in-silico. PDB (protein data bank) code of Tirofiban bound to CD-61 was 2vdm. CD-61 was docked with Tirofiban using online docking tools, i.e. Patchdock and Firedock. Then, Amotosalen hydrochloride and CD-61 were also docked. Best docking poses to active sites of 2vdm were found. Ligplot of interactions of ligands and CD-61 were obtained. Then comparison of hydrogen bonds, hydrogen bond lengths, and hydrophobic bonds of 2vdm molecule and best poses of docking results were done. Patchdock and Firedock results of best poses were also analysed using SPSS version 16. More amino acids were involved in hydrogen and hydrophobic bonds in Patchdock and Firedock docking of Amotosalen hydrochloride with CD-61 than Patchdock and Firedock docking of CD-61 with Tirofiban. The binding energy was more in latter than former. Amotosalen hydrochloride binds to the active site of CD-61 with weaker binding force. Haemorrhage seen in Amotosalen hydrochloride-treated platelets might be due to binding of Amotosalen hydrochloride to CD-61.

Photochemical Inactivation of Chikungunya Virus in Human Apheresis Platelet Components by Amotosalen and UVA Light

PubMed Central

Tsetsarkin, Konstantin A.; Sampson-Johannes, Adam; Sawyer, Lynette; Kinsey, John; Higgs, Stephen; Vanlandingham, Dana L.

2013-01-01

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in Africa and rapidly spread into countries of the Indian Ocean basin and South-East Asia. The mean viremic blood donation risk for CHIKV on La Réunion reached 1.5% at the height of the 2005–2006 outbreaks, highlighting the need for development of safety measures to prevent transfusion-transmitted infections. We describe successful inactivation of CHIKV in human platelets and plasma using photochemical treatment with amotosalen and long wavelength UVA illumination. Platelet components in additive solution and plasma units were inoculated with two different strains of high titer CHIKV stock (6.0–8.0 logs/mL), and then treated with amotosalen and exposure to 1.0–3.0 J/cm2 UVA. Based on in vitro assays of infectious virus pre- and post-treatment to identify endpoint dilutions where virus was not detectable, mean viral titers could effectively be reduced by > 6.4 ± 0.6 log10 TCID50/mL in platelets and ≥ 7.6 ± 1.4 logs in plasma, indicating this treatment has the capacity to prevent CHIKV transmission in human blood components collected from infected donors in or traveling from areas of CHIKV transmission. PMID:23530077

[Innovative technology and blood safety].

PubMed

Begue, S; Morel, P; Djoudi, R

2016-11-01

If technological innovations are not enough alone to improve blood safety, their contributions for several decades in blood transfusion are major. The improvement of blood donation (new apheresis devices, RFID) or blood components (additive solutions, pathogen reduction technology, automated processing of platelets concentrates) or manufacturing process of these products (by automated processing of whole blood), all these steps where technological innovations were implemented, lead us to better traceability, more efficient processes, quality improvement of blood products and therefore increased blood safety for blood donors and patients. If we are on the threshold of a great change with the progress of pathogen reduction technology (for whole blood and red blood cells), we hope to see production of ex vivo red blood cells or platelets who are real and who open new conceptual paths on blood safety. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Biologic response of human anterior cruciate ligamentocytes on collagen-patches to platelet-rich plasma formulations with and without leucocytes.

PubMed

Krismer, Anna M; Cabra, Romina S; May, Rahel D; Frauchiger, Daniela A; Kohl, Sandro; Ahmad, Sufian S; Gantenbein, Benjamin

2017-12-01

Due to the poor self-healing capacities of the anterior cruciate ligament, previous primary repair attempts have failed. To enhance biologic healing, platelet rich plasma and collagen scaffold have shown promise in animal models. Platelet rich plasma (PRP) is already used in several clinical applications although outcomes are quite debated. The purpose of this study was to examine the effects of different PRP formulations during 21 days: With leucocytes and pure PRP on human anterior cruciate ligament-derived ligamentocytes grown on collagen patches in 3D cell cultures in vitro. Three experimental groups were formed: 2.5% leucocyte rich PRP, 2.5% pure PRP, 20% leucocyte rich PRP, a negative control, and a positive control. Cell proliferation, cell phenotype on mRNA transcript level, and extracellular matrix production (total collagen and glycosaminoglycan content) were evaluated. DNA content and metabolic cell activity increased significantly in all groups on day 21 compared to day 7, except in the negative control. No changes in extracellular matrix production were detected. Different catabolic genes were induced depending on the concentration of leucocyte rich PRP. PRP with and without leucocytes treated anterior cruciate ligamentocytes significantly increased cell proliferation but not extracellular matrix production. However, the specific activation of different catabolic genes was dependent on the relative content of leucocytes. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2733-2739, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Massive blood loss in elective spinal and orthopedic surgery: Retrospective review of intraoperative transfusion strategy.

PubMed

Rankin, Demicha; Zuleta-Alarcon, Alix; Soghomonyan, Suren; Abdel-Rasoul, Mahmoud; Castellon-Larios, Karina; Bergese, Sergio D

2017-02-01

To evaluate the perioperative dynamics of hematologic changes and transfusion ratio in patients undergoing a major spinal surgery accompanied with massive bleeding defined as blood loss >5 liters. Retrospective cohort study. Operating room of a university-affiliated hospital. Adult patients who underwent elective neurosurgical, orthopedic, or combined spinal surgical procedure between 2008 and 2012. Patients who underwent a major spinal or orthopedic surgery and who experienced major bleeding (>5 L) during surgery were identified and selected for final analysis. The following information was analyzed: demographics, clinical diagnoses, hematologic parameters, estimated intraoperative blood loss, blood product transfusions, and survival 1 year after surgery. During the study period, 25 patients, who underwent 28 spinal procedures, experienced intraoperative blood loss >5 L. Mean patient age was 50.5 years and 56.4% were males. The majority of patients underwent procedures to manage spinal metastases. Median estimated intraoperative blood loss was 11.25 L (IQR 6.35-22 L) and median number of units (U) transfused was 24.5 U (IQR 14.0-32.5 U) of packed red blood cells (RBCs), 24.5 U (IQR 14.0-34.0 U) of fresh frozen plasma (FFP), and 4.5 U (IQR 3.0-11.5 U) of platelets (PLTs). The blood product transfusion ratio was 1 and 4 for RBC:FFP, and RBC:PLT, respectively. Hematocrit, hemoglobin, PLTs, partial thromboplastin, prothrombin time, INR, and, fibrinogen varied significantly throughout the procedures. However, acid-base status did not change significantly during surgery. Patients' survival at 1 year was 79.17%. Our results indicate that a 1:1 RBC:FFP and 4:1 RBC:PLT transfusion ratio was associated with significant intraoperative variations in coagulation variables but stable intraoperative acid-base parameters. This transfusion ratio helped clinicians to achieve postoperative coagulation parameters not significantly different to those at baseline. Future studies should assess if more liberal transfusion strategies or point of care monitoring might be warranted in patients undergoing spinal surgery at risk of major blood loss. Copyright © 2016 Elsevier Inc. All rights reserved.

Nandrolone decanoate for the treatment of erythropoietin refractory anemia: a case series.

PubMed

Chawla, Bobby; Iqbal, Fahad M; Chawla, Manjeet S

2009-01-01

Erythropoietin refractory anemias represent a continuing and increasing burden on the healthcare system. The current practice of providing these patients with rHuEPO does not seem to be working. Fewer than 50% of patients respond in some studies. We demonstrate that androgens have multiple benefits in this population. They control anemia and stop transfusion dependence and improve nutritional parameters. In some patients, they also have a salutary effect on both white blood cell and platelet counts.

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

DTIC Science & Technology

2008-10-01

for > 3 platelet transfusion in 30 days • Gr 4 neutropenia • Febrile neutropenia • Attributable Gr > 3 non-hematologic toxicity (excluding infusion...0% No febrile neutropenia (no growth factor use) • Transaminitis (n=12 evaluable) Transient Gr 1 17% (no Gr > 1) Figure-1...therapies and 36% progressed on 1-4 lines of chemotherapy including docetaxel. No DLT’s have been seen. 2 pts experienced reversible Gr 3 neutropenia

Unresolved clinical aspects and safety hazards of blood derived- EV/MV in stored blood components: From personal memory lanes to newer perspectives on the roles of EV/MV in various biological phenomena.

PubMed

Seghatchian, Jerard; Amiral, Jean

2016-08-01

Blood cells generate heterogeneous populations of vesicles that are delivered, as small-specialized packages of highly active cell fragments in blood circulation, having almost similar functional activities, as the mother cells. These so called extracellular vesicles are the essential part of an energy-dependent natural apoptotic process; hence their beneficial and harmful biological functions cannot be ignored. Evidence is accumulating, that cellular derived vesicles, originate from all viable cells including: megakaryocytes, platelets, red blood cells, white blood cells and endothelial cells, the highest in proportions from platelets. Shedding can also be triggered by pathological activation of inflammatory processes and activation of coagulation or complement pathways, or even by shear stress in the circulation. Structurally, so called MV/EV appear to be, sometimes inside-out and sometimes outside-in cell fragments having a bilayered phospholipid structure exposing coagulant-active phosphatidylserine, expressing various membrane receptors, and they serve as cell-to-cell shuttles for bioactive molecules such as lipids, growth factors, microRNAs, and mitochondria. Ex vivo processing of blood into its components, embodying centrifugation, processing by various apheresis procedures, leukoreduction, pathogen reduction, and finally storage in different media and different types of blood bags, also have major impacts on the generation and retention of MV content. These artificially generated small, but highly liable packages, together with the original pool of MVs collected from the donor, do exhibit differing biological activities, and are not inert elements and should be considered as a parameter of blood safety in haemovigilance programmes. Harmonization and consensus in sampling protocols, sample handling, processing, and assessment methods, in particular converting to full automation, are needed to achieve consensual interpretations. This review focuses on some of our past personal studies on the role of MV/EV focusing on characterization of platelet storage lesion and platelet therapy that shows the highest transfusion hazards [up to 25%], and loss of 25% platelet efficacy after various leukoreduction and validated platelet pathogen reduction treatments. The planned paths for the future of EV/MV involvement in immunological and viral/ non-viral transfusion hazards are also discussed. Whilst considerable advances made on the characterization of EV/MV, but disparity still exists between various surrogate markers, showing some subtle differences in the levels of MV/ EV & BRMs in platelet preparations, and the clinical outcome showing platelets derived by all current technologies are equivalents in vivo. One possible reason for such a disparity may be relatedto the fact that MVs, being the end products of apoptotic cells, have little specificity and clear rapidly from circulation [<6 h in thrombocytopoenia]. This makes their clinical usefulness rather short lived. The recent findings that pegylating smaller subsets of EV increases its circulatory life from <15 minutes to approximately about one hour is highly promising, in particular, for drug delivery on specific sides. Hence a promising clinical utility of EV/MV continues, as a journey without end, indeed. This manuscript is based mainly on the selected key readings listed below. Copyright © 2016. Published by Elsevier Ltd.

Direct Costs of Dengue Hospitalization in Brazil: Public and Private Health Care Systems and Use of WHO Guidelines

PubMed Central

Vieira Machado, Alessandra A.; Estevan, Anderson Oliveira; Sales, Antonio; Brabes, Kelly Cristina da Silva; Croda, Júlio; Negrão, Fábio Juliano

2014-01-01

Background Dengue, an arboviral disease, is a public health problem in tropical and subtropical regions worldwide. In Brazil, epidemics have become increasingly important, with increases in the number of hospitalizations and the costs associated with the disease. This study aimed to describe the direct costs of hospitalized dengue cases, the financial impact of admissions and the use of blood products where current protocols for disease management were not followed. Methods and Results To analyze the direct costs of dengue illness and platelet transfusion in Brazil based on the World Health Organization (WHO) guidelines, we conducted a retrospective cross-sectional census study on hospitalized dengue patients in the public and private Brazilian health systems in Dourados City, Mato Grosso do Sul State, Brazil. The analysis involved cases that occurred from January through December during the 2010 outbreak. In total, we examined 8,226 mandatorily reported suspected dengue cases involving 507 hospitalized patients. The final sample comprised 288 laboratory-confirmed dengue patients, who accounted for 56.8% of all hospitalized cases. The overall cost of the hospitalized dengue cases was US $210,084.30, in 2010, which corresponded to 2.5% of the gross domestic product per capita in Dourados that year. In 35.2% of cases, blood products were used in patients who did not meet the blood transfusion criteria. The overall median hospitalization cost was higher (p = 0.002) in the group that received blood products (US $1,622.40) compared with the group that did not receive blood products (US $550.20). Conclusion The comparative costs between the public and the private health systems show that both the hospitalization of and platelet transfusion in patients who do not meet the WHO and Brazilian dengue guidelines increase the direct costs, but not the quality, of health care. PMID:25188295

Real-time polymerase chain reaction in transfusion medicine: applications for detection of bacterial contamination in blood products.

PubMed

Dreier, Jens; Störmer, Melanie; Kleesiek, Knut

2007-07-01

Bacterial contamination of blood components, particularly of platelet concentrates (PCs), represents the greatest infectious risk in blood transfusion. Although the incidence of platelet bacterial contamination is approximately 1 per 2,000 U, the urgent need for a method for the routine screening of PCs to improve safety for patients had not been considered for a long time. Besides the culturing systems, which will remain the criterion standard, rapid methods for sterility screening will play a more important role in transfusion medicine in the future. In particular, nucleic acid amplification techniques (NATs) are powerful potential tools for bacterial screening assays. The combination of excellent sensitivity and specificity, reduced contamination risk, ease of performance, and speed has made real-time polymerase chain reaction (PCR) technology an appealing alternative to conventional culture-based testing methods. When using real-time PCR for the detection of bacterial contamination, several points have to be considered. The main focus is the choice of the target gene; the assay format; the nucleic acid extraction method, depending on the sample type; and the evaluation of an ideal sampling strategy. However, several factors such as the availability of bacterial-derived nucleic acid amplification reagents, the impracticability, and the cost have limited the use of NATs until now. Attempts to reduce the presence of contaminating nucleic acids from reagents in real-time PCR have been described, but none of these approaches have proven to be very effective or to lower the sensitivity of the assay. Recently, a number of broad-range NAT assays targeting the 16S ribosomal DNA or 23S ribosomal RNA for the detection of bacteria based on real-time technology have been reported. This review will give a short survey of current approaches to and the limitations of the application of real-time PCR for bacterial detection in blood components, with emphasis on the bacterial contamination of PCs.

Autotransfusion in cardiac surgery.

PubMed

Cross, M H

2001-09-01

There are a number of problems with allogeneic blood transfusion. Some of these problems are defined and can be quantified, such as the problem of rising cost or the risk of viral infection, but some of the problems are not well defined and it is only outcome data that point to allogeneic blood transfusion contributing to patient mortality and morbidity. Autotransfusion includes any technique in which the patient's own blood is collected, processed and stored, followed by reinfusion when circumstances dictate. In the perioperative period of cardiac surgery, a number of techniques are recognized as useful in this context. Preoperative autologous donation, with or without erythropoietin supplementation, intraoperative acute normovolaemic haemodilution, intraoperative cell salvage, postoperative cell salvage (reinfusion of shed mediastinal blood) and platelet rich plasmapheresis are all techniques which are used with more or less enthusiasm to reduce the need for an allogeneic blood transfusion. Modification of the priming technique of the cardiopulmonary bypass circuit using an autologous blood prime is included in this review even though it does not fall strictly within the definition of autotransfusion. Although autotransfusion is not the answer to every problem, there is no doubt that it should play a significant part in the strategy of blood conservation.

Procoagulant Platelets Form an α-Granule Protein-covered “Cap” on Their Surface That Promotes Their Attachment to Aggregates*

PubMed Central

Abaeva, Anastasia A.; Canault, Matthias; Kotova, Yana N.; Obydennyy, Sergey I.; Yakimenko, Alena O.; Podoplelova, Nadezhda A.; Kolyadko, Vladimir N.; Chambost, Herve; Mazurov, Aleksei V.; Ataullakhanov, Fazoil I.; Nurden, Alan T.; Alessi, Marie-Christine; Panteleev, Mikhail A.

2013-01-01

Strongly activated “coated” platelets are characterized by increased phosphatidylserine (PS) surface expression, α-granule protein retention, and lack of active integrin αIIbβ3. To study how they are incorporated into thrombi despite a lack of free activated integrin, we investigated the structure, function, and formation of the α-granule protein “coat.” Confocal microscopy revealed that fibrin(ogen) and thrombospondin colocalized as “cap,” a single patch on the PS-positive platelet surface. In aggregates, the cap was located at the point of attachment of the PS-positive platelets. Without fibrin(ogen) retention, their ability to be incorporated in aggregates was drastically reduced. The surface fibrin(ogen) was strongly decreased in the presence of a fibrin polymerization inhibitor GPRP and also in platelets from a patient with dysfibrinogenemia and a fibrinogen polymerization defect. In contrast, a fibrinogen-clotting protease ancistron increased the amount of fibrin(ogen) and thrombospondin on the surface of the PS-positive platelets stimulated with collagen-related peptide. Transglutaminases are also involved in fibrin(ogen) retention. However, platelets from patients with factor XIII deficiency had normal retention, and a pan-transglutaminase inhibitor T101 had only a modest inhibitory effect. Fibrin(ogen) retention was normal in Bernard-Soulier syndrome and kindlin-3 deficiency, but not in Glanzmann thrombasthenia lacking the platelet pool of fibrinogen and αIIbβ3. These data show that the fibrin(ogen)-covered cap, predominantly formed as a result of fibrin polymerization, is a critical mechanism that allows coated (or rather “capped”) platelets to become incorporated into thrombi despite their lack of active integrins. PMID:23995838

Pathogen inactivation efficacy of Mirasol PRT System and Intercept Blood System for non-leucoreduced platelet-rich plasma-derived platelets suspended in plasma.

PubMed

Kwon, S Y; Kim, I S; Bae, J E; Kang, J W; Cho, Y J; Cho, N S; Lee, S W

2014-10-01

This study was conducted to evaluate the efficacy of pathogen inactivation (PI) in non-leucoreduced platelet-rich plasma-derived platelets suspended in plasma using the Mirasol PRT System and the Intercept Blood System. Platelets were pooled using the Acrodose PL system and separated into two aliquots for Mirasol and Intercept treatment. Four replicates of each viral strain were used for the evaluation. For bacteria, both low-titre (45-152 CFU/unit) inoculation and high-titre (7·34-10·18 log CFU/unit) inoculation with two replicates for each bacterial strain were used. Platelets with non-detectable bacterial growth and platelets inoculated with a low titre were stored for 5 days, and culture was performed with the BacT/ALERT system. The inactivation efficacy expressed as log reduction for Mirasol and Intercept systems for viruses was as follows: human immunodeficiency virus 1, ≥4·19 vs. ≥4·23; bovine viral diarrhoea virus, 1·83 vs. ≥6·03; pseudorabies virus, 2·73 vs. ≥5·20; hepatitis A virus, 0·62 vs. 0·76; and porcine parvovirus, 0·28 vs. 0·38. The inactivation efficacy for bacteria was as follows: Escherichia coli, 5·45 vs. ≥9·22; Staphylococcus aureus, 4·26 vs. ≥10·11; and Bacillus subtilis, 5·09 vs. ≥7·74. Postinactivation bacterial growth in platelets inoculated with a low titre of S. aureus or B. subtilis was detected only with Mirasol. Pathogen inactivation efficacy of Intercept for enveloped viruses was found to be satisfactory. Mirasol showed satisfactory inactivation efficacy for HIV-1 only. The two selected non-enveloped viruses were not inactivated by both systems. Inactivation efficacy of Intercept was more robust for all bacteria tested at high or low titres. © 2014 International Society of Blood Transfusion.

Impact of glucose and acetate on the characteristics of the platelet storage lesion in platelets suspended in additive solutions with minimal plasma.

PubMed

Saunders, C; Rowe, G; Wilkins, K; Collins, P

2013-07-01

Glucose and acetate have been proposed to be required elements in platelet storage media. This study investigated the role of these compounds on the varied elements that comprise the platelet storage lesion. For each replicate, four pooled and split ABO group-specific buffy coat-derived platelet concentrates were suspended in an in-house additive solution with minimal plasma and varying final concentrations of acetate or glucose. Units were sampled on days 2, 3, 6, 8 and 10 and tested for markers of platelet morphology, activation, function, metabolism and indicators of cell death. The absence of glucose was associated with a decrease in ATP, falling to a mean of 1·1 ± 0·1 μmol/10(11) plts in units with no added glucose compared with 4·2 ± 0·6 μmol/10(11) plts (P < 0·001) in units with 30 mm glucose. As glucose became depleted, the decrease in ATP to levels below 3 μmol/10(11) plts was associated with an increase in both annexin V binding and intracellular free calcium. In units lacking exogenous acetate, ATP levels on day 10 were 5·2 ± 1·5 μmol/10(11) plts compared with 2·7 ± 0·9 μmol/10(11) plts in units with 56 mm acetate (P = 0·006). Higher concentrations of exogenous acetate were associated with a lower hypotonic shock response and higher surface expression of CD62P suggestive of a dose dependency. Under current physical storage conditions, glucose appears necessary for the maintenance of platelets stored as concentrates in minimal volumes of plasma. The addition of acetate was associated with increased platelet activation and reduced ATP levels. © 2013 International Society of Blood Transfusion.

A PC-PU nanoparticle/PU/decellularized scaffold composite vascular patch: Synergistically optimized overall performance promotes endothelialization.

PubMed

Zhang, Jun; Liu, Cheng; Feng, Fuling; Wang, Dawei; Lu, Shuaishuai; Wei, Guo; Mo, Hong; Qiao, Tong

2017-12-01

Composite vascular patches have gained increasingly attention due to the limited availability of autologous patches (vascular graft materials made from the blood vessels of the same recipient), the lack of growth capability of nonautologous patches (vascular graft materials made from the blood vessels of a different donor) and the disadvantages of synthetic patches. In this study, we report a highly biocompatible phosphatidylcholine-polyurethane nanoparticle/polyurethane/decellularized scaffold composite vascular patch (PCVP). It was fabricated by a facile method - cosedimentation. Its in vitro blood and cell compatibility including hemolysis, plasma recalcification time, coagulation time, platelet adhesion and cytotoxicity was evaluated. The surface modified with phosphatidylcholine-polyurethane (PC-PU) nanoparticles exhibited the improved anticoagulation activity. The in vivo performance of the PCVP was investigated in a mouse model. The nanopatterned surface that resembled the concave-convex structure of the luminal surface of native blood vessels enhanced cell attachment, proliferation, migration and differentiation. The decellularized scaffold had the mechanical property similar to that of the targeted blood vessels, which could withstand in vivo dynamic blood pressure. The overall performance of the PCVP was synergistically optimized by each layer of the multilayer design. The patched artery remained patent and the formation of endothelial tissue - endothelialization was achieved 30days after the in vivo implantation in a mouse model. Copyright © 2017 Elsevier B.V. All rights reserved.

A proteomic approach reveals the variation in human platelet protein composition after storage at different temperatures.

PubMed

Wang, Shichun; Jiang, Tianlun; Fan, Yahan; Zhao, Shuming

2018-03-29

Cryopreservation can slow down the metabolism and decrease the risk of bacterial contamination. But, chilled platelets (PLTs) show a reduced period in circulation due to the rapid clearance by hepatic cells or spleen macrophages after transfusion. The deleterious changes that PLTs undergo are mainly considered the result of PLT protein variation. However, the basis for proteomic variation of stored PLTs remains poorly understood. Besides count, activation markers (CD62P and Annexin V), and aggregation, we used quantitative mass spectrometry to create the first comprehensive and quantitative human PLT proteome of samples stored at different temperatures (22°C, 10°C and -80°C). We found different conditions caused different platelet storage lesion (PSL). PLT count was decreased no matter at what temperature stored. PLTs viability at low temperature dropped by 21.78% and 11.21%, respectively, as compared 10.26% at room temperature, there were no significant differences between the storage methods. Membrane expression of CD62P gradually increased in all groups especially stored at 22°C up to 40% and 10°C up to 30%. However, exposure of PS on the PLT membrane was below 1% in every group. The PLT proteome showed there were 575 and 454 potential proteins identified by general iTRAQ analysis and phosphorylation iTRAQ a nalysis, respectively, among them, 33 common differentially expressed proteins caused by storage time and 44 caused by storage temperature Especially, membrane-bound proteins (such as FERMT3, STX4, MYL9 and TAGLN2) played key roles in PLT storage lesion. The pathways "Endocytosis", "Fc gamma R-mediated phagocytosis" and "Regulation of actin cytoskeleton" were affected predominantly by storage time. And the pathways "SNARE interactions in vesicular transport" and "Vasopressin-regulated water reabsorption" were affected by cold storage in our study. Proteomic results can help us to understand PLT biochemistry and physiology and thus unravel the mechanisms of PSL in time and space for more successful PLT transfusion therapy.

Effect of platelet-rich plasma and porcine dermal collagen graft augmentation for rotator cuff healing in a rabbit model.

PubMed

Chung, Seok Won; Song, Byung Wook; Kim, Yeun Ho; Park, Kyoung Un; Oh, Joo Han

2013-12-01

The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. To verify the effect of platelet-rich plasma (PRP) with and without porcine dermal collagen graft augmentation on tendon-to-bone healing, using the rabbit supraspinatus tendon. Controlled laboratory study. A total of 80 rabbits were randomly allocated into 4 groups (20 rabbits per group: 12 for histological and 8 for mechanical testing): repair (R), repair + patch augmentation (RPa), repair + PRP (RPr), and repair + patch + PRP (RPaPr). The right shoulder was used for experimental interventions, and the left served as a control. Six weeks after the detachment of the supraspinatus, the torn tendon was repaired in a transosseous manner, simulating double-row repair in all groups. Platelet-rich plasma was prepared and applied onto the repair site in the RPr and RPaPr groups, and the patch was used to augment the repair in the RPa and RPaPr groups. The mechanical tensile strength test was performed at 8 weeks after repair and the histological evaluation at 4 and 8 weeks. At 4 weeks, the collagen fibers were poorly organized, and fiber continuity was not established in all groups. However, vascularity and cellularity were higher with granulation tissue formation in the PRP-treated groups (RPr and RPaPr) than the nontreated groups (R and RPa). At 8 weeks, tendon-to-bone integration was much improved with more collagen fibers, and longitudinally oriented collagen fibers were visible in all groups. The PRP-treated groups showed better collagen fiber continuity and orientation than the nontreated groups; however, no distinctive difference was found between the patch-augmented groups (RPa and RPaPr) and nonaugmented groups (R and RPr). The mean load-to-failure results were 61.57 ± 29.99 N, 76.84 ± 16.08 N, 105.35 ± 33.82 N, and 117.93 ± 12.60 N for the R, RPa, RPr, and RPaPr groups, respectively, and they were significantly different between the R and RPr (P = .018), R and RPaPr (P = .002), and RPa and RPaPr (P = .029) groups. This animal study showed the enhancement of tendon-to-bone healing after local administration of autologous PRP assessed by histological and biomechanical testing in a rabbit model of chronic rotator cuff tears. However, there was little additive effect of the patch graft. The use of PRP might be a biological supplement to increase the rotator cuff healing rate, which still remains low even after successful cuff repair, but this result should be interpreted with caution regarding clinical applications.

Point of care hemoglobin testing in plateletpheresis donors: Noninvasive versus invasive methods.

PubMed

Mallhi, R S; Pawar, Amit; Kushwaha, Neerja; Kumar, Sudeep; Dimri, Ujjwal

2016-10-01

Predonation hemoglobin (Hb) for plateletpheresis donors is estimated by presently available invasive methods. Venous samples of only those donors whose Hb is more than 12.5 g/dl are screened for complete blood count and transfusion transmissible infections. There is a pressing need to substitute this invasive Hb test with noninvasive one to reduce donor discomfort and avoid further pricking the donor. We therefore went ahead with the aim of comparing a noninvasive Hb estimation method NBM 200 with the invasive method - Hemocue, taking SYSMEX KX-21 as a gold standard. 500 voluntary consenting plateletpheresis donors qualifying the laid down criteria for platelet donation were included in the study. Hb readings obtained by the NBM 200 and Hemocue were compared to those obtained from the fully automated hematology analyzer SYSMEX KX-21. Coefficients of correlation were found to be statistically significant at <0.0001 level of confidence. Results of Friedman's test on the three methods also showed significant difference in means. Bland-Altman plots and mountain plots also confirm the same. NBM 200 was found to be more sensitive, specific, and precise than Hemocue in detecting ineligible donors. NBM 200 was found to be more sensitive, specific, and precise as compared to Hemocue for predonation screening of Hb in plateletpheresis donors and the prime benefit it offers is that it is 'noninvasive' thereby assisting in stemming the platelet donor pool. The onus lies on the blood transfusion services to make use of appropriately validated gadgets that reduce the donor discomfort.

Undetected Severe Fetal Myelosuppression following Administration of High-Dose Cytarabine for Acute Myeloid Leukemia: Is More Frequent Surveillance Necessary?

PubMed Central

Holland, Marium

2017-01-01

Background Cytarabine use during pregnancy carries a 5–7% risk of neonatal cytopenia. We report two cases of fetal myelosuppression following high-dose cytarabine administration for acute myeloid leukemia (AML). Case 1 A 36-year-old G9P6 diagnosed with AML at 21 weeks was monitored for fetal anemia weekly and growth monthly. At 33 weeks (after 2 cycles), BPP was 2/10 and MCA PSV was elevated at 1.51 MoM. Urgent cesarean section was performed. The infant had an initial pH of 6.78 and pancytopenia (hematocrit 13.3%, platelets 3 K/UL, and white blood cell count 2.0 K/UL). Initially transfusion dependent, the neonate had count recovery by 3 weeks. Case 2 A 30-year-old G4P3 with AML at 26 weeks was monitored for fetal anemia twice weekly and growth monthly. At 34 weeks (after cycle 1), she was admitted with neutropenic fever. The fetal MCA PSV was borderline at 1.48 MoM. It improved to 1.38 MoM at 35 weeks but the fetal tracing worsened. At delivery the fetus was found to have a hematocrit of 30%, but with normal platelet and WBC. The fetus did not require any transfusions. Conclusion Cytarabine use during pregnancy may cause neonatal myelosuppression. We recommend monitoring for fetal anemia with MCA Dopplers twice weekly. PMID:29075543

A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus via zoonotic food-borne route.

PubMed

Matsubayashi, Keiji; Kang, Jong-Hon; Sakata, Hidekatsu; Takahashi, Kazuaki; Shindo, Motohiro; Kato, Masaru; Sato, Shinichiro; Kato, Toshiaki; Nishimori, Hiroyuki; Tsuji, Kunihiko; Maguchi, Hiroyuki; Yoshida, Jun-Ichi; Maekubo, Hiroshi; Mishiro, Shunji; Ikeda, Hisami

2008-07-01

Five cases of transfusion transmission of hepatitis E virus (HEV) have been reported so far. The infection routes of the causative donors remain unclear, however. Also, the progress of virus markers in the entire course of HEV infection has not been well documented. Nucleic acid testing was performed by real-time reverse transcription-polymerase chain reaction targeting the open reading frame 2 region of HEV. Full-length nucleotide sequences of HEV RNA were detected by direct sequencing. Lookback study of a HEV-positive donor revealed that the platelets (PLTs) donated from him 2 weeks previously contained HEV RNA and were transfused to a patient. Thirteen relatives including the donor were ascertained to enjoy grilled pork meats together in a barbecue restaurant 23 days before the donation. Thereafter, his father died of fulminant hepatitis E and the other 6 members showed serum markers of HEV infection. In the recipient, HEV was detected in serum on Day 22 and reached the peak of 7.2 log copies per mL on Day 44 followed by the steep increase of alanine aminotransferase. Immunoglobulin G anti-HEV emerged on Day 67; subsequently, hepatitis was resolved. HEV RNA sequences from the donor and recipient were an identical, Japan-indigenous strain of genotype 4. HEV RNA was detectable up to Day 97 in serum, Day 85 in feces, and Day 71 in saliva. A transfusion-transmitted hepatitis E case by blood from a donor infected via the zoonotic food-borne route and the progress of HEV markers in the entire course are demonstrated. Further studies are needed to clarify the epidemiology and the transfusion-related risks for HEV even in industrialized countries.

Hematological complications in children subjected to extracorporeal membrane oxygenation.

PubMed

Santiago, M J; Gómez, C; Magaña, I; Muñoz, V; Saiz, P; Sánchez, A; López-Herce, J

2018-03-29

To analyze the hematological complications and need for transfusions in children receiving extracorporeal life support (ECLS). A retrospective study was carried out. A pediatric intensive care unit. Children under 18 years of age treated with ECLS between September 2006 and November 2015. None. Patient and ECLS characteristics, anticoagulation, hematological and coagulation parameters, transfusions and clinical course. A total of 100 patients (94 with heart disease) with a median age of 11 months were studied. Seventy-six patients presented bleeding. The most frequent bleeding point being the mediastinum and 39 patients required revision surgery. In the first 3days, 97% of the patients required blood transfusion (34.4ml/kg per day), 94% platelets (21.1ml/kg per day) and 90% plasma (26.6ml/kg per day). Patients who were in the postoperative period, those who were bleeding at the start of ECLS, those requiring revision surgery, those who could not suspend extracorporeal circulation, and those subjected to transthoracic cannulation required a greater volume of transfusions than the rest of the patients. Thromboembolism occurred in 14 patients and hemolysis in 33 patients. Mortality among the children who were bleeding at the start of ECLS (57.6%) was significantly higher than in the rest of the patients (37.5%) (P=0.048). Children treated with ECLS present high blood product needs. The main factors related to transfusions were postoperative period, bleeding at the start of ECLS, revision surgery, transthoracic cannulation, and the impossibility of suspending extracorporeal circulation. Children with bleeding suffered greater mortality than the rest of the patients. Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

Clinicians' satisfaction with a hospital blood transfusion service: a marketing analysis of a monopoly supplier.

PubMed Central

Pennington, S J; McClelland, D B; Murphy, W G

1993-01-01

One of the objectives of the NHS reforms is to improve customer focus within the health service. In a study to assess the quality of customer service provided by the Edinburgh and South East Scotland Blood Transfusion Service a 19 item questionnaire survey of the main clinical users of the service was performed to ascertain their satisfaction, measured on a 5 point anchored scale, with important aspects of the service, including medical consultation, diagnostic services, blood and blood components or products and their delivery, and general satisfaction with the service. Of 122 clinicians in medical and surgical disciplines in five hospitals in Edinburgh, 72 (59%) replied. Fourteen (22%) indicated dissatisfaction with any aspect of the medical consultation service, owing to inadequate follow up of clinical contacts and unsatisfactory routing of incoming calls. Diagnostic services were criticised for the presentation, communication, and interpretation of results. The restricted availability of whole blood, the necessity to order platelets and plasma through the duty blood transfusion service doctor, and the use of a group and screen policy, attracted criticism from a small number of clinicians. Ten of 68 respondents expressed dissatisfaction with delivery of blood and components to the wards and theatres. The findings indicate that the clinicians served by this blood transfusion service are largely satisfied with the service. Changes are being implemented to improve reporting of laboratory results and measures taken to improve liaison with clinicians. PMID:10132458

Role of transfused red blood cells for shock and coagulopathy within remote damage control resuscitation.

PubMed

Spinella, Philip C; Doctor, Allan

2014-05-01

The philosophy of damage control resuscitation (DCR) and remote damage control resuscitation (RDCR) can be summarized by stating that the goal is to prevent death from hemorrhagic shock by "staying out of trouble instead of getting out of trouble." In other words, it is preferred to arrest the progression of shock, rather than also having to reverse this condition after significant tissue damage and organ injury cascades are established. Moreover, to prevent death from exsanguination, a balanced approach to the treatment of both shock and coagulopathy is required. This was military doctrine during World War II, but seemed to be forgotten during the last half of the 20th century. Damage control resuscitation and RDCR have revitalized the approach, but there is still more to learn about the most effective and safe resuscitative strategies to simultaneously treat shock and hemorrhage. Current data suggest that our preconceived notions regarding the efficacy of standard issue red blood cells (RBCs) during the hours after transfusion may be false. Standard issue RBCs may not increase oxygen delivery and may in fact decrease it by disturbing control of regional blood flow distribution (impaired nitric oxide processing) and failing to release oxygen, even when perfusing hypoxic tissue (abnormal oxygen affinity). Standard issue RBCs may assist with hemostasis but appear to have competing effects on thrombin generation and platelet function. If standard issue or RBCs of increased storage age are not optimal, then are there alternatives that will allow for an efficacious and safe treatment of shock while also supporting hemostasis? Studies are required to determine if fresh RBCs less than 7 to 10 days provide an outcome advantage. A resurgence in the study of whole blood stored at 4°C for up to 10 days also holds promise. Two randomized controlled trials in humans have indicated that following transfusion with either whole blood stored at 4°C or platelets stored at 4°C there was less clinical bleeding than when blood was reconstituted with components or when platelets were stored at 22°C. Early reversal of shock is essential to prevent exacerbation of coagulopathy and progression of cell death cascades in patients with severe traumatic injuries. Red blood cell storage solutions have evolved to accommodate the needs of non-critically ill patients yet may not be optimal for patients in hemorrhagic shock. Continued focus on the recognition and treatment of shock is essential for continued improvement in outcomes for patients who require damage control resuscitation and RDCR.

Epsilon aminocaproic acid reduces blood transfusion and improves the coagulation test after pediatric open-heart surgery: a meta-analysis of 5 clinical trials.

PubMed

Lu, Jun; Meng, Haoyu; Meng, Zhaoyi; Sun, Ying; Pribis, John P; Zhu, Chunyan; Li, Quan

2015-01-01

Excessive postoperative blood loss after cardiopulmonary bypass is a common problem, especially in patients suffering from congenital heart diseases. The efficacy of epsilon aminocaproic acid (EACA) as a prophylactic treatment for postoperative bleeding after pediatric open-heart surgery has not been determined. This meta-analysis investigates the efficacy of EACA in the minimization of bleeding and blood transfusion and the maintenance of coagulation tests after pediatric open-heart surgery. A comprehensive literature search was performed to identify all randomized clinical trials on the subject. PubMed, Embase, the Cochrane Library, and the Chinese Medical Journal Network were screened. The primary outcome used for the analysis was postoperative blood loss. Secondary outcomes included postoperative blood transfusion, re-exploration rate and postoperative coagulation tests. The mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) were used as summary statistics. Five trials were included in this meta-analysis of 515 patients. Prophylactic EACA was associated with a reduction in postoperative blood loss, but this difference did not reach statistical significance (MD: -7.08; 95% CI: -16.11 to 1.95; P = 0.12). Patients treated with EACA received fewer postoperative blood transfusions, including packed red blood cells (MD: -8.36; 95% CI: -12.63 to -4.09; P = 0.0001), fresh frozen plasma (MD: -3.85; 95% CI: -5.63 to -2.08; P < 0.0001), and platelet concentrate (MD: -10.66; 95% CI: -18.45 to -2.87; P = 0.007), and had a lower re-exploration rate (RR: 0.46; 95% CI: 0.23 to 0.92; P = 0.03). Prophylactic EACA also improved coagulation tests 6 hours after open-heart surgery. Prophylactic EACA minimizes postoperative blood transfusion and helps maintain coagulation in pediatric patients undergoing open-heart surgery. Therefore, the results of this study indicate that adjunctive EACA is a good choice for the prevention of postoperative blood transfusion following pediatric cardiac surgery.

Transient spontaneous engraftment of CD34 hematopoietic cord blood stem cells as seen in peripheral blood: treatment of leprosy patients with anemia by placental umbilical cord whole blood transfusion.

PubMed

Bhattacharya, N

2006-01-01

Cord blood, because of its rich mix of fetal and adult hemoglobin, high platelet and white blood cell (WBC) counts, and a plasma filled with cytokine and growth factors, as well as its hypoantigenic nature and altered metabolic profile, has all the potential of a real and safe alternative to adult blood transfusion. Our experience of 74 units (50 ml-146 ml mean, 86 ml +/- 7.6 ml SD, median 80 ml, mean packed cell volume 48 +/- 4.1 SD, mean percent hemoglobin concentration 16.2 g/dl +/- 1.8 g/dl of placental umbilical cord whole blood collection (from 1 April 1999) after lower uterine cesarean section (LUCS) from consenting mothers and transfusion of the same to 16 informed, consenting patients with percent plasma hemoglobin 8 g/dl or less, is presented here. After collection the blood was immediately preserved in the refrigerator and transfused within 72 hours of collection. Fifteen males and one female, aged 12-72 yrs (mean 48.4 yrs) participated: five cases were pausibacillary type (PB) and 11 cases were multibacillary type (MB). The clinical spectrum of the cases varied widely from the tuberculoid to the lepromatous type and one patient presented with gangrene of the leg preceding an auto amputation which was infested with maggots. Each case was approved by the institutional ethical committee and received two to eight units of freshly collected placental umbilical cord blood in one transfusion without encountering any clinical, immunological or non-immunological reaction. Seven days after completion of the placental umbilical cord blood transfusion, the peripheral blood hematopoietic stem cell (CD34) estimation revealed a rise from the pretransfusion base level (.09%), varying from 3.6% to 16.2%, in 75% of the cases, without provoking any clinical graft vs host reaction in any of the leprosy victims. This value returned to normal within three months in most cases.

Cumulative inhibitory effect of low-dose aspirin on vascular prostacyclin and platelet thromboxane production in patients with atherosclerosis.

PubMed

Weksler, B B; Tack-Goldman, K; Subramanian, V A; Gay, W A

1985-02-01

The relationship between the antithrombotic and antiplatelet effects of aspirin is complex, since aspirin influences other systems that protect against thrombosis as well as inhibiting platelet function. We investigated possible cumulative effects of low-dose aspirin on vascular production of prostacyclin in patients with documented atherosclerotic cardiovascular disease. Candidates for coronary artery vein graft bypass ingested 20 mg of aspirin daily during the week before surgery, and platelet aggregation, platelet formation of thromboxane A2 (TXA2), aortic and saphenous vein production of prostacyclin (PGI2), and hemostatic status were measured at the time of the bypass surgery. Low-dose aspirin markedly inhibited platelet aggregation responses and reduced TXA2 generation by greater than 90%, effects similar to those observed with much higher doses of aspirin. Both aortic and saphenous vein production of PGI2 were inhibited by 50% compared with PGI2 produced by vascular tissues of control subjects who received no aspirin preoperatively (51 +/- 10 pg 6-keto-PGF1 alpha/mg aortic wet weight [mean +/- SEM] in aspirin-treated subjects vs 130 +/- 16 pg/mg in control subjects, and 71 +/- 8 pg/mg saphenous vein wet weight vs 131 +/- 17 pg/mg). Blood loss at surgery was not significantly increased by preoperative low-dose aspirin as measured by chest tube drainage (754 +/- 229 ml in aspirin-treated subjects vs 645 +/- 271 ml in control subjects), hematocrit nadir (31.2 +/- 1.9% vs 31.8 +/- 1.7%), or transfusions (2.2 +/- 1.3 units of red blood cells vs 2.2 +/- 1.7 units).(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemorrhagic dengue and vertical transmission to the newborn: a case report and literature review].

PubMed

Morgan-Ortiz, Fred; Rodríguez-Lugo, Silvia Mirelle; León-Gil, María del Socorro; Gaxiola-Villa, Marisela; Martínez-Félix, Nora Selene; Lara-Avila, Leticia

2014-06-01

To describe the case of a patient with term pregnancy and infection with hemorrhagic dengue and vertical transmission to the newborn. Thirty-two year old patient with pregnancy at 38 weeks was admitted with fever 2 days earlier (38 degrees C). During her stay she continued with fever of 39 degrees C and platelets of 85,000/mm3. Serology for dengue NS1 antigen was reported positive. Labor was induced getting a new-born, male, 3,220 g, who breathed and cried at birth. During the postpartum period continued with fever, malaise, retro-ocular pain, generalized rash in upper and lower limbs, bleeding gums and petechial on the soft palate and thrombocytopenia of 5,000/mm3, later. At 8 days of stay, platelet concentration increased to 42,000/mm3 without requiring platelet concentrates and she was discharged after ten days in hospital with platelets of 94,000/mm3. The 4th day of extra-uterine live (EUL), neonate shows generalized rash over the trunk; The 5th day starts with 38 degrees C fever and thrombocytopenia (78,000/mm3). Dengue serological tests reported positive for Ag NS1 and negative for Abs IgM and IgG. Neonate was admitted to NICU, he continued with a decrease in platelet of 14,000/mm3- and ecchymotic areas by pressure and veno-punction sites. Four platelet concentrates were transfused. At 10th day of EUL platelet count was reported with 387,000/mm3. In an endemic area, such as Sinaloa state, in a pregnant woman with fever and thrombocytopenia, we should be alert to possibility of a DV infection and its complications. Although rare, such as this case, infection can be transmitted to fetus (vertical transmission) and produce a primary congenital dengue, even in its severe hemorrhagic types.

Evaluation of the 3D BacT/ALERT automated culture system for the detection of microbial contamination of platelet concentrates.

PubMed

McDonald, C P; Rogers, A; Cox, M; Smith, R; Roy, A; Robbins, S; Hartley, S; Barbara, J A J; Rothenberg, S; Stutzman, L; Widders, G

2002-10-01

Bacterial transmission remains the major component of morbidity and mortality associated with transfusion-transmitted infections. Platelet concentrates are the most common cause of bacterial transmission. The BacT/ALERT 3D automated blood culture system has the potential to screen platelet concentrates for the presence of bacteria. Evaluation of this system was performed by spiking day 2 apheresis platelet units with individual bacterial isolates at final concentrations of 10 and 100 colony-forming units (cfu) mL-1. Fifteen organisms were used which had been cited in platelet transmission and monitoring studies. BacT/ALERT times to detection were compared with thioglycollate broth cultures, and the performance of five types of BacT/ALERT culture bottles was evaluated. Sampling was performed immediately after the inoculation of the units, and 10 replicates were performed per organism concentration for each of the five types of BacT/ALERT bottles. The mean times for the detection of these 15 organisms by BacT/ALERT, with the exception of Propionibacterium acnes, ranged from 9.1 to 48.1 h (all 10 replicates were positive). In comparison, the time range found using thioglycollate was 12.0-32.3 h (all 10 replicates were positive). P. acnes' BacT/ALERT mean detection times ranged from 89.0 to 177.6 h compared with 75.6-86.4 h for the thioglycollate broth. BacT/ALERT, with the exception of P. acnes, which has dubious clinical significance, gave equivalent or shorter detection times when compared with the thioglycollate broth system. The BacT/ALERT system detected a range of organisms at levels of 10 and 100 cfu mL-1. This study validates the BacT/ALERT microbial detection system for screening platelets. Currently, the system is the only practically viable option available for routinely screening platelet concentrates to prevent bacterial transmission.

Electrospun silk fibroin fibers for storage and controlled release of human platelet lysate.

PubMed

Pignatelli, Cataldo; Perotto, Giovanni; Nardini, Marta; Cancedda, Ranieri; Mastrogiacomo, Maddalena; Athanassiou, Athanassia

2018-04-17

Human platelet lysate (hPL) is a pool of growth factors and cytokines able to induce regeneration of different tissues. Despite its good potentiality as therapeutic tool for regenerative medicine applications, hPL has been only moderately exploited in this field. A more widespread adoption has been limited because of its rapid degradation at room temperature that decreases its functionality. Another limiting factor for its extensive use is the difficulty of handling the hPL gels. In this work, silk fibroin-based patches were developed to address several points: improving the handling of hPL, enabling their delivery in a controlled manner and facilitating their storage by creating a device ready to use with expanded shelf life. Patches of fibroin loaded with hPL were synthesized by electrospinning to take advantage of the fibrous morphology. The release kinetics of the material was characterized and tuned through the control of fibroin crystallinity. Cell viability assays, performed with primary human dermal fibroblasts, demonstrated that fibroin is able to preserve the hPL biological activity and prolong its shelf-life. The strategy of storing and preserving small active molecules within a naturally-derived, protein-based fibrous scaffold was successfully implemented, leading to the design of a biocompatible device, which can potentially simplify the storage and the application of the hPL on a human patient, undergoing medical procedures such as surgery and wound care. Human platelets lysate (hPL) is a mixture of growth factors and cytokines able to induce the regeneration of damaged tissues. This study aims at enclosing hPL in a silk fibroin electrospun matrix to expand its utilization. Silk fibroin showed the ability to preserve the hPL activity at temperature up to 60 °C and the manipulation of fibroin's crystallinity provided a tool to modulate the hPL release kinetic. This entails the possibility to fabricate the hPL silk fibroin patches in advance and store them, resulting in an easy and fast accessibility and an expanded use of hPL for wound healing. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hepatitis-associated aplastic anaemia: a poor prognosis.

PubMed

Gonçalves, Vivian; Calado, Rita; Palaré, Maria João; Ferrão, Anabela; Morais, Anabela

2013-02-13

A 13-year-old boy presented with spontaneous skin and mucosal bleeds 3 weeks after acute hepatitis of unknown aetiology. Laboratory analyses revealed pancytopenia and bone marrow biopsy that confirmed the diagnosis of aplastic anaemia. Other causes of congenital and acquired aplastic anaemia were excluded. He was diagnosed with hepatitis-associated aplastic anaemia. He developed a critical clinical condition, becoming totally dependent on erythrocyte and platelet transfusions, and severe neutropenia, which led to invasive bacterial infection. He died due to sepsis with multiple organ failure 3 months after admission.

Circulating microparticles, protein C, free protein S and endothelial vascular markers in children with sickle cell anaemia

PubMed Central

Piccin, Andrea; Murphy, Ciaran; Eakins, Elva; Kunde, Jan; Corvetta, Daisy; Di Pierro, Angela; Negri, Giovanni; Guido, Mazzoleni; Sainati, Laura; Mc Mahon, Corrina; Smith, Owen Patrick; Murphy, William

2015-01-01

Introduction Circulating microparticles (MP) have been described in sickle cell anaemia (SCA); however, their interaction with endothelial markers remains unclear. We investigated the relationship between MP, protein C (PC), free protein S (PS), nitric oxide (NO), endothelin-1 (ET-1) and adrenomedullin (ADM) in a large cohort of paediatric patients. Method A total of 111 children of African ethnicity with SCA: 51 in steady state; 15 in crises; 30 on hydroxyurea (HU) therapy; 15 on transfusion; 17 controls (HbAA) of similar age/ethnicity. MP were analysed by flow cytometry using: Annexin V (AV), CD61, CD42a, CD62P, CD235a, CD14, CD142 (tissue factor), CD201 (endothelial PC receptor), CD62E, CD36 (TSP-1), CD47 (TSP-1 receptor), CD31 (PECAM), CD144 (VE-cadherin). Protein C, free PS, NO, pro-ADM and C-terminal ET-1 were also measured. Results Total MP AV was lower in crisis (1.26×106 ml−1; 0.56–2.44×106) and steady state (1.35×106 ml−1; 0.71–3.0×106) compared to transfusion (4.33×106 ml−1; 1.6–9.2×106, p<0.01). Protein C levels were significantly lower in crisis (median 0.52 IU ml−1; interquartile range 0.43–0.62) compared with all other groups: HbAA (0.72 IU ml−1; 0.66–0.82, p<0.001); HU (0.67 IU ml−1; 0.58–0.77, p<0.001); steady state (0.63 IU ml−1; 0.54–0.70, p<0.05) and transfusion (0.60 IU ml−1; 0.54–0.70, p<0.05). In addition, levels were significantly reduced in steady state (0.63 IU ml−1; 0.54–0.70) compared with HbAA (0.72 IU ml−1; 0.66–0.80, p<0.01). PS levels were significantly higher in HbAA (0.85 IU ml−1; 0.72–0.97) compared with crisis (0.49 IU ml−1; 0.42–0.64, p<0.001), HU (0.65 IU ml−1; 0.56–0.74, p<0.01) and transfusion (0.59 IU ml−1; 0.47–0.71, p<0.01). There was also a significant difference in crisis patients compared with steady state (0.49 IU ml−1; 0.42–0.64 vs. 0.68 IU ml−1; 0.58–0.79, p<0.05). There was high correlation (R>0.9, p<0.05) between total numbers of AV-positive MP (MP AV) and platelet MP expressing non-activation platelet markers. There was a lower correlation between MP AV and MP CD62P (R=0.73, p<0.05) (platelet activation marker), and also a lower correlation between percentage of MP expressing CD201 (%MP CD201) and %MP CD14 (R=0.627, p<0.001). %MP CD201 was higher in crisis (11.6%) compared with HbAA (3.2%, p<0.05); %MP CD144 was higher in crisis (7.6%) compared with transfusion (2.1%, p<0.05); %CD14 (0.77%) was higher in crisis compared with transfusion (0.0%, p<0.05) and steady state (0.0%, p<0.01); MP CD14 was detectable in a higher number of samples (92%) in crisis compared with the rest (40%); %MP CD235a was higher in crisis (17.9%) compared with transfusion (8.9%), HU (8.7%) and steady state (9.9%, p<0.05); %CD62E did not differ significantly across the groups and CD142 was undetectable. Pro-ADM levels were raised in chest crisis: 0.38 nmol L−1 (0.31–0.49) versus steady state: 0.27 nmol L−1 (0.25–0.32; p<0.01) and control: 0.28 nmol L−1 (0.27–0.31; p<0.01). CT-proET-1 levels were reduced in patients on HU therapy: 43.6 pmol L−1 (12.6–49.6) versus control: 55.1 pmol L−1 (45.2–63.9; p<0.05). NO levels were significantly lower in chest crisis (19.3 mmol L−1 plasma; 10.7–19.9) compared with HU (22.2 mmol L−1 plasma; 18.3–28.4; p<0.05), and HbSC (30.6 mmol L−1 plasma; 20.8–39.5; p<0.05) and approach significance when compared with steady state (22.5mmol L−1 plasma; 16.9–28.2; p=0.07). Conclusion Protein C and free PS are reduced in crisis with lower numbers of platelet MP and higher percentage of markers of endothelial damage and of red cell origin. During chest crisis, ADM and ET-1 were elevated suggesting a role for therapy inhibiting ET-1 in chest crisis. PMID:26609806

Does Platelet Reactivity Predict Bleeding in Patients Needing Urgent Coronary Artery Bypass Grafting During Dual Antiplatelet Therapy?

PubMed

Mahla, Elisabeth; Prueller, Florian; Farzi, Sylvia; Pregartner, Gudrun; Raggam, Reinhard B; Beran, Elisabeth; Toller, Wolfgang; Berghold, Andrea; Tantry, Udaya S; Gurbel, Paul A

2016-12-01

Up to 15% of patients require coronary artery bypass grafting (CABG) during dual antiplatelet therapy. Available evidence suggests an association between platelet reactivity and CABG-related bleeding. However, platelet reactivity cutoffs for bleeding remain elusive. We sought to explore the association between platelet reactivity and bleeding. Patients on aspirin and a P2Y 12 receptor inhibitor within 48 hours before isolated CABG (n = 149) were enrolled in this prospective study. Blood was drawn 2 to 4 hours preoperatively and platelet reactivity assessed by light transmittance aggregometry (LTA), vasodilator-stimulated phosphoprotein (VASP) assay, Multiplate analyzer and Innovance PFA2Y. The primary endpoint was calculated red blood cell loss computed as follows: (blood volume × preoperative hematocrit × 0.91) - (blood volume × hematocrit × 0.91 on postoperative day 5) + (mL of transfused red blood cells × 0.59). Preoperative platelet reactivity was low [median (interquartile range): LTA: 20 (9-28)%; VASP-PRI: 39 (15-73)%; Multiplate adenosine phosphate test: 16 (12-22) U∗min]. Innovance PFA2Y ≥300 seconds, 72%. Median (IQR) red blood cell loss in patients in first the LTA tertile was 1,449 (1,020 to 1,754) mL compared with 1,107 (858 to 1,512) mL and 1,075 (811 to 1,269) mL in those in the second and third tertiles, respectively (p < 0.004). Bleeding Academic Research Consortium (BARC)-4 bleeding differed between tertiles (62% versus 46% versus 36%; p = 0.037). In a multivariable linear regression model, aspirin dose ≥300 mg, cardiopulmonary bypass time, EuroSCORE, and tertile distribution of platelet reactivity were significantly associated with red blood cell loss. A gradual decrease in red blood cell loss and BARC-4 bleeding occurs with increasing platelet reactivity in patients on antiplatelet therapy undergoing CABG. Our findings support current guidelines to determine time of surgery based on an objective measurement of platelet function (Platelet Inhibition and Bleeding in Patients Undergoing Emergent Cardiac Surgery; clinicaltrials.gov NCT01468597). Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

CANINE HEMOPHILIA

PubMed Central

Graham, John B.; Buckwalter, Joseph A.; Hartley, L. J.; Brinkhous, Kenneth M.

1949-01-01

A study was made of the clotting defect and the course of the malady in a group of male dogs with an inherited, sex-linked bleeding disease. The clotting defect is characterized by a prolonged clotting time and a delayed prothrombin utilization, and is corrected by the addition either of thromboplastin or of normal plasma. A plasma protein fraction, fraction I, also corrects the defect. The defect appears to be due to a deficiency of a plasma factor, which normally, in the presence of platelets, makes thromboplastin available in shed blood. The clotting anomaly appears to be identical with that found in human hemophilia. The hemostatic defect is characterized by repeated hemorrhages, usually without obvious relationship to trauma. Hemarthroses occur frequently and may result in permanent joint deformity. The animals usually die early in life from massive hemorrhage. Transfusions with normal blood or plasma correct the clotting defect and readily control the hemorrhagic phenomena. By the use of transfusions, these dogs have been reared to maturity. PMID:18136192

A point-of-care assessment of the effects of desmopressin on impaired platelet function using multiple electrode whole-blood aggregometry in patients after cardiac surgery.

PubMed

Weber, Christian F; Dietrich, Wulf; Spannagl, Michael; Hofstetter, Christian; Jámbor, Csilla

2010-03-01

Blood loss after cardiac surgery can be caused by acquired platelet dysfunction after cardiopulmonary bypass. Monitoring of platelet function is clinically important for the identification of patients experiencing such platelet dysfunction. 1-Deamino-8-D-arginine vasopressin (desmopressin acetate, DDAVP) has been shown to augment platelet function and to reduce blood loss in patients with platelet dysfunction. In this study, we examined the feasibility of whole blood multiple electrode aggregometry (MEA) for the detection of cardiopulmonary bypass-induced platelet dysfunction and investigated its ability to monitor DDAVP treatment. Fifty-eight consecutive patients with blood loss exceeding 150 mL/h in the first 2 consecutive hours after cardiac surgery were screened for suspected isolated platelet dysfunction. Twenty-two patients had suspected isolated platelet dysfunction and were enrolled in the study. Platelet dysfunction was assumed if conventional coagulation analyses (platelet count, activated partial thromboplastin time, international normalized ratio, and fibrinogen) did not show abnormal values as defined for transfusion of allogenic blood products, and no surgical cause of bleeding was suspected. Eleven patients received 0.3 microg/kg DDAVP, and 11 patients received no therapy in a nonrandomized manner. MEA was performed after stimulation with thrombin receptor-activating peptide (TRAPtest, 32 microM), adenosine diphosphate (ADPtest, 6.4 microM), and arachidonic acid (ASPItest, 0.5 mM) before and 2 hours after intervention. Conventional laboratory variables were recorded. The Mann-Whitney test was used to detect differences between the groups, and the Wilcoxon test was used to detect differences before and after intervention. All enrolled patients showed platelet dysfunction that manifested as impaired platelet aggregation in MEA before intervention. After the intervention, platelet function improved in the DDAVP group (49 U [30/72 U], median [25th/75th percentile] postintervention vs 15 U [8/21 U] preintervention for the ASPItest [P < 0.001]; 35 U [24/54 U] vs 14 U [7/28 U] for the ADPtest [P = 0.002]; and 85 U [66/115 U] vs 64 U [26/88 U] for the TRAPtest [P = 0.007]). In contrast, MEA remained unchanged in the control group (22 U [10/50 U] postintervention vs 33 U [14/57 U] preintervention for the ASPItest [P = 0.175]; 17 U [12/20 U] vs 14 U [10/28 U] for the ADPtest [P = 0.147]; and 65 U [41/89 U] vs 57 U [30/91 U] for the TRAPtest [P = 0.123]). Impaired platelet function after cardiac surgery can be assessed at the bedside using MEA. The effect of DDAVP on impaired platelet function can also be detected as significant improvement in platelet aggregation to all activators. This device might be helpful for the identification of patients who may benefit from DDAVP therapy.

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

PubMed

Naymagon, Leonard; Pendurti, Gopichand; Billett, Henny H

2015-01-01

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Rapid detection of contaminant bacteria in platelet concentrate using differential impedance.

PubMed

Zhao, Z; Chalmers, A; Rieder, R

2014-08-01

Current FDA-approved culture-based methods for the bacterial testing of platelet concentrate (PC) can yield false-negative results attributed to Poisson-limited sampling errors incurred near the time of collection that result in undetectable bacterial concentrations. Testing PC at the point of issue (POI) extends the incubation period for any contaminant bacteria increasing the probability of detection. Data are presented from time-course experiments designed to simulate POI testing of bacterially contaminated PCs at different stages of growth using differential impedance sensing. Whole-blood-derived PCs were typically spiked with low numbers of bacteria (approximately 100 CFU/ml) and incubated under standard PC storage conditions. Each infected unit was evaluated every two hours over a 12-h period. All samples were treated with a chemical compound that induces stress in the bacterial cells only. The development of any bacterial stress was monitored by detecting changes in the dielectric properties of the PC using differential impedance. Differential impedance measurements and corresponding cell counts at the different time-points are presented for six organisms implicated in post-transfusion-septic reactions. All infected PCs were detected once contaminant bacteria reached concentrations ranging between 0·6 × 10(3) and 6 × 10(3)  CFU/ml irrespective of the phase of growth. Results were obtained within 30 min after the start of the assay and without the need for cell lysis or centrifugation. Differential impedance sensing can detect bacterial contamination in PC rapidly at concentrations below clinical thresholds known to cause adverse effects. © 2014 International Society of Blood Transfusion.

Reducing the financial impact of pathogen inactivation technology for platelet components: our experience.

PubMed

Girona-Llobera, Enrique; Jimenez-Marco, Teresa; Galmes-Trueba, Ana; Muncunill, Josep; Serret, Carmen; Serra, Neus; Sedeño, Matilde

2014-01-01

Pathogen inactivation (PI) technology for blood components enhances blood safety by inactivating viruses, bacteria, parasites, and white blood cells. Additionally, PI for platelet (PLT) components has the potential to extend PLT storage time from 5 to 7 days. A retrospective analysis was conducted into the percentage of outdated PLT components during the 3 years before and after the adoption of PLT PI technology in our institution. The PLT transfusion dose for both pre-PI and post-PI periods was similar. A retrospective analysis to study clinical safety and component utilization was also performed in the Balearic Islands University Hospital. As a result of PI implementation in our institution, the PLT production cost increased by 85.5%. However, due to the extension of PLT storage time, the percentage of outdated PLT units substantially decreased (-83.9%) and, consequently, the cost associated with outdated units (-69.8%). This decrease represented a 13.7% reduction of the initial cost increase which, together with the saving in blood transportation (0.1%), led to a saving of 13.8% over the initial cost. Therefore, the initial 85.5% increase in the cost of PLT production was markedly reduced to 71.7%. The mean number of PLT concentrates per patient was similar during both periods. The extension of PLT storage time can substantially contribute to reducing the financial impact of PI by decreasing the percentage of outdated PLTs while improving blood safety. Since the adoption of PI, there have been no documented cases of PLT transfusion-related sepsis in our region. © 2013 American Association of Blood Banks.

Genotyping applications for transplantation and transfusion management: The Emory Experience

PubMed Central

Fasano, Ross M.; Sullivan, Harold Cliff; Bray, Bob; Gebel, Howie; Meyer, Erin K.; Winkler, Annie M.; Josephson, Cassandra D.; Stowell, Sean R.; Duncan, Sandy; Roback, John D.

2018-01-01

Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for the simultaneous detection of multiple human leukocyte antigens (HLA), human platelet antigens (HPA) and red blood cell (RBC) antigens. The development of high resolution molecular HLA typing has led to improved outcomes of unrelated hematopoietic stem cell transplants by better identifying suitable donors typed at the allele level for HLA-A, B, C, DRB1 and DQB1 antigens. In solid organ transplantation, the combination of high resolution HLA typing along with solid-phase antibody identification and the calculated PRA have shown to be of specific benefit to highly sensitized patients, and have resulted in significant reductions of incompatible crossmatches at the time of organ allocation. This database-driven combined HLA antigen/antibody testing has promoted the routine implementation of the virtual crossmatch, in which an electronic crossmatch is performed, and perhaps even obviates the need for a physical crossmatch. Additionally, DNA-based testing for RBC antigens provides as an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although there are many applications of RBC genotyping in various transfusion settings, it has arguably been most useful in the management of transfusion-dependent patients with sickle cell disease (SCD) and thalassemia to minimize alloimmunization. The availability of high-throughput RBC genotyping for both patients and large populations of donors, along with coordinated informatics systems to link patients’ antigen needs with available antigen-negative and/or rare blood-typed donors, offer promise toward improving the efficiency, reliability, and extent of RBC matching for this population. PMID:28234571

Riboflavin and ultraviolet light for pathogen reduction of murine cytomegalovirus in blood products.

PubMed

Keil, Shawn D; Saakadze, Natia; Bowen, Richard; Newman, James L; Karatela, Sulaiman; Gordy, Paul; Marschner, Susanne; Roback, John; Hillyer, Christopher D

2015-04-01

Two studies were performed to test the effectiveness of riboflavin and ultraviolet (UV) light treatment (Mirasol PRT, Terumo BCT) against murine cytomegalovirus (MCMV). The first study utilized immune-compromised mice to measure the reduction of cell-free MCMV. A second study used a murine model to evaluate the ability of Mirasol PRT to prevent transfusion-transmitted (TT)-MCMV infection. Human plasma was inoculated with MCMV and then treated with Mirasol PRT. The viral titer was measured using an infectious dose 50% assay in nude mice. Mice were euthanized on Day 10 posttransfusion, and their spleens were tested for the presence of MCMV DNA using polymerase chain reaction (PCR). Mirasol PRT was also evaluated to determine its effectiveness in preventing TT-MCMV in platelets (PLTs) stored in PLT additive solution. PLTs were inoculated with either cell-associated MCMV or cell-free MCMV and then treated with Mirasol PRT. Mice were transfused with treated or untreated product and were euthanized 14 days posttransfusion. Blood and spleens were assayed for MCMV DNA by real-time-PCR. Using nude mice to titer MCMV, a modest 2.1-log reduction was observed in plasma products after Mirasol PRT treatment. TT-MCMV was not observed in the mouse transfusion model when either cell-free or cell-associated MCMV was treated with Mirasol PRT; MCMV transmission was uniformly observed in mice transfused with untreated PLTs. These results suggest that using riboflavin and UV light treatment may be able to reduce the occurrence of transmission of human CMV from infectious PLTs and plasma units. © 2014 AABB.

Massive Blood Transfusion in Patients with Ruptured Abdominal Aortic Aneurysm.

PubMed

Montan, C; Hammar, U; Wikman, A; Berlin, E; Malmstedt, J; Holst, J; Wahlgren, C M

2016-11-01

The aim was to study blood transfusions and blood product ratios in massively transfused patients treated for ruptured abdominal aortic aneurysms (rAAAs). This was a registry based cohort study of rAAA patients repaired at three major vascular centres between 2008 and 2013. Data were collected from the Swedish Vascular Registry, hospitals medical records, and local transfusion registries. The transfusion data were analysed for the first 24 h of treatment. Massive transfusion (MT) was defined as 4 or more units of red blood cell (RBC) transfused within 1 h, or 10 or more RBC units within 24 h. Logistic regression was used to calculate the odds ratio of 30 day mortality associated with the ratios of blood products and timing of first units of platelets (PLTs) and fresh frozen plasma (FFP) transfused. Three hundred sixty nine rAAA patients were included: 80% men; 173 endovascular aneurysm repairs (EVARs) and 196 open repairs (ORs) with median RBC transfusion 8 units (Q1-Q3, 4-14) and 14 units (Q1-Q3, 8-28), respectively. A total of 261 (71%) patients required MT. EVAR patients with MT (n = 96) required less transfusion than OR patients (n = 165): median RBC 10 units (Q1-Q3, 6-16.5) vs. 15 units (Q1-Q3, 9-26) (p = .002), FFP 6 units (Q1-Q3, 2-14.5) vs. 13 units (Q1-Q3, 7-24) (p < .001), and PLT 0 units (Q1-Q3, 0-2) vs. 2 units (Q1-Q3, 0-4) (p = .01). Median blood product ratios in MT patients were FFP/RBC (EVAR group 0.59 [0.33-0.86], OR group 0.84 [0.67-1.2]; p < .001], and PLT/RBC (EVAR 0 [0-0.17], OR 0.12 (0-0.18); p < .001]. In patients repaired by OR a FFP/RBC ratio close to 1 was associated with reduced 30 day mortality (p = .003). The median PLT/RBC ratio was higher during the later part of the study period (p < .001, median test), whereas there was no significant difference in median FFP/RBC ratio (p = .101, median test). The majority of rAAA patients undergoing EVAR required MT. EVAR patients treated with MT had lower FFP/RBC and PLT/RBC ratios than OR patients with MT. The mortality risk was lower with FFP/RBC ratio close to 1:1 in open repaired patients requiring MT. The 24 h PLT/RBC ratio increased over the study period. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Treatment of platelets with riboflavin and ultraviolet light mediates complement activation and suppresses monocyte interleukin-12 production in whole blood.

PubMed

Loh, Y S; Dean, M M; Johnson, L; Marks, D C

2015-11-01

Pathogen inactivation (PI) and storage may alter the immunomodulatory capacity of platelets (PLTs). The aim of this study was to examine the effect of PI (Riboflavin and ultraviolet light treatment) and storage on the capacity of PLTs to induce cytokine responses in recipient inflammatory cells. A pool and split design was used to prepare untreated and PI-treated buffy coat-derived platelet concentrates (PCs). Samples were taken on days 2 and 7 postcollection and incubated with ABO/RhD-matched fresh whole blood for 6 h with or without lipopolysaccharide (LPS). The intracellular production of IP-10, MCP-1, MIP-1α, IL-8, IL-6, IL-10, IL-12, TNF-α and MIP-1β in monocytes and neutrophils was assessed using flow cytometry. Complement proteins in PLT supernatants were measured using a cytometric bead array. PLTs and PLT supernatant (both untreated and PI-treated) resulted in modulation of intracellular MIP-1β and IL-12 production in monocytes. Compared to untreated PLTs, PI-treated PLTs resulted in significantly lower LPS-induced monocyte IL-12 production (day 7). The concentration of C3a and C5a (and their desArg forms) was significantly increased in PLT supernatants following PI. PI results in decreased LPS-induced monocyte IL-12 production and increased complement activation. The association between platelet-induced complement activation and IL-12 production warrants further investigation. © 2015 International Society of Blood Transfusion.

Refrigeration and cryopreservation of platelets differentially affect platelet metabolism and function: a comparison with conventional platelet storage conditions.

PubMed

Johnson, Lacey; Tan, Shereen; Wood, Ben; Davis, April; Marks, Denese C

2016-07-01

Alternatives to room temperature storage of platelets (PLTs) may be beneficial to extend the limited shelf life and support transfusion logistics in rural and military areas. The aim of this study was to assess the morphologic, metabolic, and functional aspects of PLTs stored at room temperature or in refrigerated conditions or cryopreserved. A three-arm pool-and-split study was carried out using buffy coat-derived PLTs stored in 30% plasma/70% SSP+. The three matched treatment arms were room temperature stored (20-24°C), cold-stored (2-6°C), and cryopreserved (-80°C with dimethyl sulfoxide). Liquid-stored PLTs were tested over a 21-day period, while cryopreserved PLTs were examined immediately after thawing and after 6 and 24 hours of storage at room temperature. Cold-stored and cryopreserved PLTs underwent a significant shape change, although the cryopreserved PLTs appeared to recover from this during subsequent storage. Glycolytic metabolism was reduced in cold-stored PLTs, but accelerated in cryopreserved PLTs, while oxidative phosphorylation was negatively affected by both storage conditions. PLT aggregation was potentiated by cold storage and diminished by cryopreservation in comparison to room temperature-stored PLTs. Cold storage and cryopreservation resulted in faster clot formation (R-time; thromboelastography), which was associated with an increase in microparticles. Cold storage and cryopreservation of PLTs led to morphologic and metabolic changes. However, storage under these conditions appears to maintain or even enhance certain aspects of in vitro PLT function. © 2016 AABB.

Factors associated with the effect of open splenectomy for immune thrombocytopenic purpura.

PubMed

Li, Ying; Zhang, Dawei; Hua, Fanli; Gao, Song; Wu, Yangjiong; Xu, Jianmin

2017-01-01

To assess the effect and complications of open splenectomy (OS) for immune thrombocytopenic purpura (ITP) and determine preoperative factors associated with surgical effect. This was a retrospective analysis of ITP patients who failed medical therapy and were treated with OS between 1997 and 2014 at the Jinshan Hospital, China. Follow-up was 60 months. Surgical effect was determined from platelet counts and bleeding episodes. Complications were assessed including bleeding episodes. Preoperative factors were identified by logistic regression analysis. Fifty-six patients (48.2 ± 16.2 yr old; 39 females) were included. Disease course was 31.2 ± 48.2 months; 91.1% patients had preoperative platelet count <20 × 10 9 /L. OS effect at 1 wk, 1 month, 1 yr, and 5 yrs was in 91.1%, 92.9%, 91.1%, and 89.3% patients, respectively. Pneumonia or lower extremity thrombosis occurred in 7.1% patients. Postoperative mild, moderate, and severe bleeding occurred in 33.9%, 50.0%, and 16.1% patients, respectively. No patients required blood transfusion. Mortality was zero. Larger spleen size associated with surgical effect at 1 wk, 1 month, and 1 yr, and lower preoperative minimum platelet count associated with effect at 5 yrs (P < 0.05). Open splenectomy is an effective treatment with less complications for the management of ITP. Lower preoperative minimum platelet count associated with successful OS at 5 yrs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Assessing anxiety levels and empathic tendency in blood and platelet donors.

PubMed

Kılıç, Suar Çakı; Doğan, Erdoğan; Sevimligül, Gülgün; Yücel, Birsen; Bolat, Fatih; Kavakçı, Onder; Sencan, Mehmet

2013-06-01

In spite of a constantly-increasing requirement for blood transfusion in the world, blood donation does not exhibit an increase at the same rate. In Turkey with a population of 74 million, only 15 per 10,000 people donate blood regularly and rate of voluntary blood donation is very low compared to developed countries. The aim of this study is to determine empathic level of donors and anxiety levels of blood and platelet donors and also to enable comfort and motivation of donors by taking precautions for reducing their anxieties. This prospective and descriptive study was conducted with 100 voluntary donors (50 blood donors, 50 platelet donors) who admitted to Blood Centre of Cumhuriyet University Hospital between 15 March 2012 and 30 April 2012. Average age of these donors was 27 (19-48)years. The mean scores of donors from Empathic Tendency Scale (ETS), State Anxiety Invertory (SAI) and Trait Anxiety Inventory (TAI) were 70 (49-83), 40 (33-45) and 34 (30-44), respectively. ETS score of those donating blood/platelet for the first time was low, >1 is higher in those who donated previously. SAI and TAI scores of blood donors were higher than those of platelet donors (p<0.001) and TAI score was higher in those who donate for the first time (p<0.007) compared to previously donated precipitants. In conclusion, this study underscores that the request of the donor to help others is the most important factor for donation. People frequently donate blood to unfamiliar people and recurring blood donations increase the level of empathy. Donation made during the continuous disclosure is an important factor for being a donor. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intravenous hemostats: challenges in translation to patients

NASA Astrophysics Data System (ADS)

Lashof-Sullivan, Margaret; Shoffstall, Andrew; Lavik, Erin

2013-10-01

Excessive bleeding and the resulting complications are a leading killer of young people globally. There are many successful methods to halt bleeding in the extremities, including compression, tourniquets, and dressings. However, current treatments for internal hemorrhage (including from head or truncal injuries), termed non-compressible bleeding, are inadequate. For these non-compressible injuries, blood transfusions are the current treatment standard. However, they must be refrigerated, may potentially transfer disease, and are of limited supply. In addition, time is of the essence for halting hemorrhage, since more than a third of civilian deaths due to hemorrhage from trauma occur before the patient even reaches the hospital. As a result, particles that can cross-link activated platelets through the glycoprotein IIb/IIIa receptor expressed on activated platelets are being investigated as an alternative treatment for non-compressible bleeding. Ideally, these particles would interact specifically with platelets to stabilize the platelet plug. Initial designs used biologically derived microparticles with red blood cell fragment or albumin cores decorated with RGD or fibrinogen, which bind to GPIIb/IIIa. More recently there has been research into the use of fully synthetic nanoparticles with liposomal or polymer cores that crosslink platelets through a targeting peptide bound to the surface. Some of the challenges for the development of these particles include appropriate sizing to prevent blocking the capillaries of the lungs, immune system evasion to prevent strong reactions and increase circulation time, and storage and resuspension so that first responders can easily use the particles. In addition, the effectiveness of the variety of animal bleeding models in predicting outcomes must be examined before test results can be fully understood. Progress has been made in the development of particles to combat hemorrhage, but issues of immune sensitivity and storage must be resolved before these types of particles can be translated for human use.

HETEROTYPIC INTERACTIONS ENABLED BY POLARIZED NEUTROPHIL MICRODOMAINS MEDIATE THROMBO-INFLAMMATORY INJURY

PubMed Central

Hidalgo, Andrés; Chang, Jungshan; Jang, Jung-Eun; Peired, Anna J.; Chiang, Elaine Y.; Frenette, Paul S.

2009-01-01

Selectins and their ligands mediate leukocyte rolling allowing interactions with chemokines that lead to integrin activation and arrest. Here, we demonstrate that E-selectin is critical to induce a secondary wave of activating signals transduced specifically by E-selectin ligand-1, that induces polarized, activated αMβ2 integrin clusters at the leading edge of crawling neutrophils, allowing the capture of circulating erythrocytes or platelets. In a humanized model of sickle cell disease (SCD), the capture of erythrocytes by αMβ2 microdomains leads to acute lethal vascular occlusions. In a model of transfusion-related acute lung injury, polarized neutrophils capture circulating platelets, resulting in the generation of oxidative species that produces vascular damage and lung injury. Inactivation of E-selectin or αMβ2 prevented tissue injury in both inflammatory models, suggesting broad implications of this paradigm in thrombo-inflammatory diseases. These results indicate that endothelial selectins can influence neutrophil behavior beyond its canonical rolling step through delayed, organ-damaging, polarized activation. PMID:19305412

Fatal thrombocytopenia: A rare case with possible explanation

PubMed Central

Barik, Ramachandra; Patnaik, A. N.; Gulati, A. S.

2012-01-01

A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow. PMID:22629036

Fatal thrombocytopenia: A rare case with possible explanation.

PubMed

Barik, Ramachandra; Patnaik, A N; Gulati, A S

2012-04-01

A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow.

Image-guided intervention in the coagulopathic patient.

PubMed

Kohli, Marc; Mayo-Smith, William; Zagoria, Ronald; Sandrasegaran, Kumar

2016-04-01

Determining practice parameters for interventional procedures is challenging due to many factors including unreliable laboratory tests to measure bleeding risk, variable usage of standardized terminology for adverse events, poorly defined standards for administration of blood products, and the growing numbers of anticoagulant and antiplatelet medications. We aim to address these and other issues faced by radiologists performing invasive procedures through a review of available literature, and experiential guidance from three academic medical centers. We discuss the significant limitations with respect to using prothrombin-time and international normalized ratio to measure bleeding risk, especially in patients with synthetic defects due to liver function. Factors affecting platelet function including the impact of uremia; recent advances in laboratory testing, including platelet function testing; and thromboelastography are also discussed. A review of the existing literature of fresh-frozen plasma replacement therapy is included. The literature regarding comorbidities affecting coagulation including malignancy, liver failure, and uremia are also reviewed. Finally, the authors present a set of recommendations for laboratory thresholds, corrective transfusions, as well as withholding and restarting medications.

Leucoreduction of blood components: an effective way to increase blood safety?

PubMed Central

Bianchi, Maria; Vaglio, Stefania; Pupella, Simonetta; Marano, Giuseppe; Facco, Giuseppina; Liumbruno, Giancarlo M.; Grazzini, Giuliano

2016-01-01

Over the past 30 years, it has been demonstrated that removal of white blood cells from blood components is effective in preventing some adverse reactions such as febrile non-haemolytic transfusion reactions, immunisation against human leucocyte antigens and human platelet antigens, and transmission of cytomegalovirus. In this review we discuss indications for leucoreduction and classify them into three categories: evidence-based indications for which the clinical efficacy is proven, indications based on the analysis of observational clinical studies with very consistent results and indications for which the clinical efficacy is partial or unproven. PMID:26710353

Allele frequencies of human platelet antigens in Banjar, Bugis, Champa, Jawa and Kelantan Malays in Peninsular Malaysia.

PubMed

Wan Syafawati, W U; Norhalifah, H K; Zefarina, Z; Zafarina, Z; Panneerchelvam, S; Norazmi, M N; Chambers, G K; Edinur, H A

2015-10-01

The major aims of this study are to characterise and compile allelic data of human platelet antigen (HPA)-1 to -6 and -15 systems in five Malay sub-ethnic groups in Peninsular Malaysia. HPAs are polymorphic glycoproteins expressed on the surface of platelet membranes and are genetically differentiated across ethnogeographically unrelated populations. Blood samples were obtained with informed consent from 192 volunteers: Banjar (n = 30), Bugis (n = 37), Champa (n = 51), Jawa (n = 39) and Kelantan (n = 35). Genotyping was done using polymerase chain reaction-sequence specific primer method. In general, frequencies of HPAs in the Malay sub-ethnic groups are more similar to those in Asian populations compared with other more distinct populations such as Indians, Australian Aborigines and Europeans. This study provides the first HPA datasets for the selected Malay sub-ethnic groups. Subsequent analyses including previously reported HPA data of Malays, Chinese and Indians revealed details of the genetic relationships and ancestry of various sub-populations in Peninsular Malaysia. Furthermore, the comprehensive HPA allele frequency information from Peninsular Malaysia provided in this report has potential applications for future study of diseases, estimating risks associated with HPA alloimmunization and for developing an efficient HPA-typed donor recruitment strategy. © 2015 British Blood Transfusion Society.

[Detection of antigen structures in blood cells in various prepared plasma transfusions].

PubMed

Barz, D

1994-01-01

We investigated the content of antigen-bearing cells and cell fragments in Fresh Frozen Plasma (FFP) from blood centers, in Octaplas (virus-inactivated fresh plasma produced with the solvent/detergent technique by the Octapharma Company) and in MB-plasma (virus-inactivated fresh plasma after photodynamic treatment with methylen blue coming from the German Red Cross in Springe, Lower Saxony). With the aid of an immunoassay (MAIPA-test) these plasmas were tested regarding Rhesus-D-antigen, HLA-class-I- and HLA-class-II-antigens, platelet specific antigens HPA-1a/HPA-1b and granulocyte specific antigens NA1/NA2. In Octaplas (n = 10) we did not find cells or cell fragments and no antigen-bearing blood cell structures. In FFP (n = 28) there were platelet specific antigens in 27 cases (96.4%) and HLA-class-I-antigens in 4 cases (14.3%). In MB-plasma (n = 14) we found platelet specific antigens in all cases, HLA-class-I-antigens in 4 cases (18.6%), HLA-class-II-antigens and granulocyte specific antigens in 1 case (7.1%) and Rhesus-D-antigen in 3 cases (21.4%). Plasma derived from whole blood showed lower levels of cells and antigens than plasma which was produced with the aid of the cell separator.