[Quantitative studies on reversible thrombocyte aggregation during exertion].

PubMed

Haber, P; Silberbauer, K; Sinzinger, H

1980-10-11

In 8 oarsmen aged 19 to 31 years a symptom-limited rectangular-progressive bicycle stress test has been conducted. Venous blood was taken before and at the end of the test, and 30 and 60 minutes afterwards. pH, base excess, pCO2, platelet count and platelet count ratio (WU and HOAK) were measured or calculated, the last in order to quantify the tendency of the platelets to form reversible aggregates. At the point of exhaustion there is a highly significant (p < 0.001) decrease in the platelet cunt ratio (= increase in reversible platelet aggregates). A highly significant correlation exists between base excess and the platelet count ratio. The regression line does not fall below the normal value of the platelet count ratio until the delta-base excess is -4 mval/l. This means that an increase in the tendency to form reversible platelet aggregates is not typical of the range of aerobic metabolism but of muscular work in the anaerobic range with high exercise-induced metabolic acidosis. The basis for sudden death in sport due to internal reasons is not uncommonly an unknown and asymptomatic coronary disease and platelet aggregates. Persons aged over 30 years and sports in which competition is also inherent (soccer, tennis) are often involved. Acute cardiac death in sport is not very frequent. Nevertheless, the following recomendation seems to be warranted: persons aged over 30 years in bad condition should not start competitive sports or other intensive muscular exercise. Before they do so, low-intensive, controlled, aerobic endurance training is necessary.

[Megakaryocytic leukemia with thrombocytosis].

PubMed

Nakajima, M; Fukunaga, H; Amano, M; Fukuda, T; Ryo, R

1989-07-01

A 62-year-old man was admitted to our hospital with exertional dyspnea. On admission, neither hepatosplenomegaly nor lymphadenopathy were noted. Laboratory data revealed anemia (Hb, 4.8 g/dl), leukopenia (2,800 microliters) and a normal platelet count (21 X 10(4)/microliters). The immature blast cells in the peripheral blood were 15%, which increased to 32% during his clinical course. On cytochemical studies, the blast cells had no staining with peroxidase, alpha-naphthyl-butyrate esterase and PAS, although acid phosphatase was positive. More than 58% of the blasts were identified as being of megakaryocytic lineage by platelet peroxidase and by tests with monoclonal GP IIb/IIIa antibody. Bone marrow biopsy disclosed marked fibrosis. However, the patient constantly had normal counts of platelets ranging from 21 X 10(4) to 63 X 10(4)/microliters. This case provides evidence that the megakaryocytic leukemias can be categorized into two types, which are characterized by either undifferentiated or differentiated megakaryocytic leukemia cells.

Protein A immunoadsorption therapy in HIV-related immune thrombocytopenia: a preliminary report.

PubMed

Bertram, J H; Snyder, H W; Gill, P S; Shulman, I; Henry, D H; Jenkins, D; Kiprov, D D

1988-12-01

Nine homosexual patients with immune thrombocytopenia were treated with autologous plasma that had been perfused over silica-immobilized Staphylococcus aureus protein A (SpA). Pretreatment platelet counts ranged from 10,000 to 98,000 cells/mm3 (mean: 54,000 cells/mm3). Six patients responded to therapy. Platelets increased by a mean of 95,000 cells/mm3 (p less than 0.007) and reached normal levels (greater than 150,000 cells/mm3) in four patients. Increased platelet counts are presently sustained in these four individuals after 5 months of follow-up. Increases in platelet counts significantly correlated with decreases in platelet-associated IgG (PAIgG), platelet-directed IgG (PDIgG), and immune complexes (CIC). PAIgG and PDIgG declined by a mean of 67% (p less than 0.003) and 58% (p less than 0.007), respectively. CIC decreased by a mean of 37% (p = 0.02). Complement was concomitantly activated in all four examined patients. C3a and C5a increased 23-fold and 2.6-fold, respectively, while total hemolytic complement decreased by 50%. Activated complement components and removal of CIC and IgG thus may contribute to the platelet-enhancing activity of SpA immunoadsorption therapy.

Abnormal Whole Blood Thrombi in Humans with Inherited Platelet Receptor Defects

PubMed Central

Castellino, Francis J.; Liang, Zhong; Davis, Patrick K.; Balsara, Rashna D.; Musunuru, Harsha; Donahue, Deborah L.; Smith, Denise L.; Sandoval-Cooper, Mayra J.; Ploplis, Victoria A.; Walsh, Mark

2012-01-01

To delineate the critical features of platelets required for formation and stability of thrombi, thromboelastography and platelet aggregation measurements were employed on whole blood of normal patients and of those with Bernard-Soulier Syndrome (BSS) and Glanzmann’s Thrombasthenia (GT). We found that separation of platelet activation, as assessed by platelet aggregation, from that needed to form viscoelastic stable whole blood thrombi, occurred. In normal human blood, ristocetin and collagen aggregated platelets, but did not induce strong viscoelastic thrombi. However, ADP, arachidonic acid, thrombin, and protease-activated-receptor-1 and -4 agonists, stimulated both processes. During this study, we identified the genetic basis of a very rare double heterozygous GP1b deficiency in a BSS patient, along with a new homozygous GP1b inactivating mutation in another BSS patient. In BSS whole blood, ADP responsiveness, as measured by thrombus strength, was diminished, while ADP-induced platelet aggregation was normal. Further, the platelets of 3 additional GT patients showed very weak whole blood platelet aggregation toward the above agonists and provided whole blood thrombi of very low viscoelastic strength. These results indicate that measurements of platelet counts and platelet aggregability do not necessarily correlate with generation of stable thrombi, a potentially significant feature in patient clinical outcomes. PMID:23300803

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.

Autologous Platelet-Rich Plasma Preparations

PubMed Central

Schippinger, Gert; Prüller, Florian; Divjak, Manuela; Mahla, Elisabeth; Fankhauser, Florian; Rackemann, Steve; Raggam, Reinhard Bernd

2015-01-01

Background Autologous platelet-rich plasma (PRP) has been widely used for the treatment of sports injuries. It has been associated with improved healing and regeneration of soft tissues in elite athletes. Athletes are commonly receiving nonsteroidal anti-inflammatory drugs (NSAIDs). As yet, the effect of these drugs on platelet function in PRP formulations has not been taken into consideration. Hypothesis The function of platelets in PRP produced under the influence of NSAIDs is inhibited and may lessen a possible healing effect on the site of injury. Study Design Controlled laboratory study. Methods PRP was collected from patients receiving NSAIDs after elective orthopaedic surgery, and platelet function was evaluated using light transmission aggregometry (LTA). Results were compared with those obtained from healthy volunteers without a history of NSAID intake during the previous 2 weeks. Two different systems for blood collection and PRP production (Arthrex ACP double-syringe system and standard 4.5-mL sodium citrate blood collection tubes) were used and compared regarding the quality of PRP that was produced. Results For both groups, the baseline platelet counts of whole blood and the platelet counts of PRP formulations were found to be in the normal range. Both collection systems for PRP produced comparable results without significant differences between the groups. Platelet function testing with LTA revealed significantly impaired platelet aggregation in both PRP preparations, obtained from patients taking NSAIDs, irrespective of the type of NSAID (P < .001). All subjects from the control group showed normal platelet aggregation patterns when tested with LTA. Conclusion Autologous PRP produced from subjects after NSAID medication shows significantly impaired platelet function and may result in lower quality regarding the content of bioactive compounds. Clinical Relevance If required, the administration of NSAIDs should be performed after blood collection for preparation of autologous PRP; otherwise, the therapeutic effect may be limited. PMID:26665098

Nonhuman primate model of polytraumatic hemorrhagic shock recapitulates early platelet dysfunction observed following severe injury in humans.

PubMed

Schaub, Leasha J; Moore, Hunter B; Cap, Andrew P; Glaser, Jacob J; Moore, Ernest E; Sheppard, Forest R

2017-03-01

Platelet dysfunction has been described as an early component of trauma-induced coagulopathy. The platelet component of trauma-induced coagulopathy remains to be fully elucidated and translatable animal models are required to facilitate mechanistic investigations. We sought to determine if the early platelet dysfunction described in trauma patients could be recapitulated in a nonhuman primate model of polytraumatic hemorrhagic shock. Twenty-four male rhesus macaques weighting 7 to 14 kg were subjected to 60 minutes (min) of severe pressure-targeted controlled hemorrhagic shock (HS) with and without other injuries. After 60 min, resuscitation with 0.9% NaCl and whole blood was initiated. Platelet counts and platelet aggregation assays were performed at baseline (BSLN), end of shock (EOS; T = 60 min), end of resuscitation (EOR; T = 180 min), and T = 360 min on overall cohort. Results are reported as mean ± standard deviation (SD) or median (interquartile range). Statistical analysis was conducted using Spearmen correlation, one-way analysis of variance, two-way repeated-measures analysis of variance, paired t-test or Wilcoxon nonparametric test, with p < 0.05 considered significant. Platelet count in all injury cohorts decreased over time, but no animals developed thrombocytopenia. Correlations were observed between platelet aggregation and platelet count for all agonists: adenosine diphosphate, thrombin recognition-activating peptide-6, collagen, and arachidonic acid. Overall, compared to BSLN, platelet aggregation decreased for all agonist at EOS, EOR, and T = 360 min. When normalized to platelet count, platelet aggregation in response to agonist thrombin recognition-activating peptide-6 demonstrated no change from BSLN at subsequent time points. Aggregation to adenosine diphosphate was significantly less at EOR but not EOS or T = 360 min compared to BSLN. Platelet aggregation to collagen and arachidonic acid was not significantly different at EOS compared to BSLN but was significantly less at EOR and T = 360 min. Nonhuman primates manifest early platelet dysfunction in response to polytraumatic hemorrhagic shock, consistent with that reported in severely injured human patients. Nonhuman primate models potentially are translationally valuable for understanding the mechanisms and pathophysiology of trauma-induced platelet dysfunction.

Effects of isotretinoin on the platelet counts and the mean platelet volume in patients with acne vulgaris.

PubMed

Ataseven, Arzu; Ugur Bilgin, Aynur

2014-01-01

Aim. The aim of this study was to evaluate the platelet counts and the mean platelet volume in patients who received isotretinoin for the treatment of acne vulgaris. Method. A total of 110 patients were included in this retrospective study. Complete blood count parameters were recorded prior to and three-months following the treatment. Results. Both platelet counts and the mean platelet volume were significantly decreased following the treatment. No significant differences were noted on the levels of hemoglobin, hematocrit, and white blood cell count. Conclusion. Platelet counts and mean platelet volume significantly decreased following isotretinoin treatment. Since the decrease of platelet counts and the mean platelet volume was seen concomitantly, it is concluded that the effect of isotretinoin was through the suppression of bone marrow.

Mean Platelet Volume (MPV), Platelet Distribution Width (PDW), Platelet Count and Plateletcrit (PCT) as predictors of in-hospital paediatric mortality: a case-control Study.

PubMed

Golwala, Zainab Mohammedi; Shah, Hardik; Gupta, Neeraj; Sreenivas, V; Puliyel, Jacob M

2016-06-01

Thrombocytopenia has been shown to predict mortality. We hypothesize that platelet indices may be more useful prognostic indicators. Our study subjects were children one month to 14 years old admitted to our hospital. To determine whether platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) and their ratios can predict mortality in hospitalised children. Children who died during hospital stay were the cases. Controls were age matched children admitted contemporaneously. The first blood sample after admission was used for analysis. Receiver operating characteristic (ROC) curve was used to identify the best threshold for measured variables and the ratios studied. Multiple regression analysis was done to identify independent predictors of mortality. Forty cases and forty controls were studied. Platelet count, PCT and the ratios of MPV/Platelet count, MPV/PCT, PDW/Platelet count, PDW/PCT and MPV × PDW/Platelet count × PCT were significantly different among children who survived compared to those who died. On multiple regression analysis the ratio of MPV/PCT, PDW/Platelet count and MPV/Platelet count were risk factors for mortality with an odds ratio of 4.31(95% CI, 1.69-10.99), 3.86 (95% CI, 1.53-9.75), 3.45 (95% CI, 1.38-8.64) respectively. In 67% of the patients who died MPV/PCT ratio was above 41.8 and PDW/Platelet count was above 3.86. In 65% of patients who died MPV/Platelet count was above 3.45. The MPV/PCT, PDW/Platelet count and MPV/Platelet count, in the first sample after admission in this case control study were predictors of mortality and could predict 65% to 67% of deaths accurately.

Haematological values in pregnant women in Port Harcourt, Nigeria II: Serum iron and transferrin, total and unsaturated iron binding capacity and some red cell and platelet indices.

PubMed

Amah-Tariah, F S; Ojeka, S O; Dapper, D V

2011-12-20

Previous studies on the normal values of serum iron, unsaturated iron binding capacity, total iron binding capacity, serum transferrin, percent transferrin saturation, red cell distribution width, and various platelet indices: Platelet count, mean platelet volume, platelet distribution width, plateletcrit and platelet larger cell ratio in pregnant subjects in Nigeria are relatively scanty. Present study aims to determine the values of these parameters in apparently healthy pregnant subjects residing in Port Harcourt south eastern Nigeria; and help establish normal reference ranges of these parameters for the population under reference. Cross sectional prospective study involving 220 female subjects attending for the first time, the ante-natal clinics of a tertiary health care facility in Port Harcourt. Subjects were divided into 73, 75 and 72 subjects in the first, second and third trimester of pregnancy respectively. Serum iron and unsaturated iron binding capacity, red cell distribution width, platelet count and platelet distribution width were determined by automated methods; total iron binding capacity, serum transferrin concentrations, percent transferrin saturation, mean platelet volume and plateletcrit were calculated using appropriate formulas. The values of serum iron, unsaturated iron binding capacity, total iron binding capacity and serum transferrin concentrations were found to show significant variations between the various trimesters of pregnancy. However, while serum iron showed significant decreases during pregnancy; unsaturated iron binding capacity, total iron binding capacity and serum transferrin concentrations were found to show significant increases during pregnancy amongst our subjects (p<0.05). By contrast the values of red cell distribution width, platelet count, mean platelet volume, platelet distribution width, plateletcrit and platelet larger cell ratio did not show any significant differences at the different trimesters of pregnancy in our subjects (p>0.05). The present study reports, for the first time, normative values for these parameters in apparently healthy pregnant subjects in Port Harcourt south eastern Nigeria. Apparently, increases in unsaturated and total iron binding capacity and serum transferrin values seen amongst our subjects with increasing gestation may perhaps be a mechanism to ensure a fetal adequate iron delivery on account of the decreasing serum iron concentration with gestation in our subjects. The study suggests that values of serum transferrin are perhaps a more useful screening tool for iron deficiency anemia during pregnancy amongst our subjects.

Idiopathic thrombocytopenic purpura diagnosed during the second decade of life.

PubMed

Lowe, Eric J; Buchanan, George R

2002-08-01

To retrospectively review our institutional experience of adolescents with idiopathic thrombocytopenic purpura (ITP). Medical record review of all patients diagnosed with ITP between the ages of 10 and 18 years seen at our center from January 1976 to March 2000. Data were collected from 126 patients. Of the evaluable 110 cases, 63 (57%) satisfied the criteria for chronic ITP, 30 (27%) for acute ITP, and 17 (15%) were uncertain. Sex distribution and mean ages were similar in all 3 groups. Platelet count at presentation was higher in patients with chronic ITP. Splenectomy was performed in 24 patients, with 17 (77%) of 22 having normal platelet counts at last follow-up. Outcome for the nonsplenectomized patients with chronic ITP included normalization of platelet count (n = 4), minimal or no bleeding without treatment (n = 29), treatment for ongoing symptoms (n = 5), and unknown (n = 1). Two patients died, 1 from intracranial hemorrhage and 1 from Escherichia coli sepsis and pulmonary hemorrhage. Patients 10 to 18 years of age with ITP are more likely than younger children to have chronic disease. Many patients with ITP recover without drug therapy or need for splenectomy. ITP in adolescents shares features of both childhood and adult ITP.

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.

Lesson of the month 1: To stop a fit, but swinging low.

PubMed

Ogbebor, Osakpolor; Agrawal, Ankit; Yegneswaran, Balaji

2018-06-01

This is a case of an elderly woman who presented to our emergency room with an episode of a witnessed fall. The past medical history of the patient was significant for post-stroke epilepsy for which she was on oxcarbazepine. Initial blood work showed a white cell count of 4.5, haemoglobin of 12.4, and platelet count of 15,000. Peripheral blood smear showed normal platelet and red cell morphology without clumping. The patient's history suggested that she was recently started on oxcarbazepine prompting discontinuing of the drug. The platelet count improved from 15,000 cells/mL to 80,000 cells/mL on discharge.Antiepileptic medications have been reported to cause various blood dyscrasias in the literature. There are few studies that report the association of carbamazepine and thrombocytopenia and much fewer written about oxcarbazepine. Thrombocytopenia appears to be an uncommon reported side effect of oxcarbazepine; more commonly reported side effects include dizziness, tiredness, memory problems and headache. The treatment of antiepileptic drug-associated thrombocytopenia is discontinuing the medication and monitoring the platelet counts. In few cases, immunoglobulin infusion is required. Antiepileptic drug-associated thrombocytopenia is difficult to predict and so it is imperative to monitor the platelet level when antiepileptic drugs are started and even after the medication is switched to a different one. © Royal College of Physicians 2018. All rights reserved.

Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia

PubMed Central

Howard, M; Ashwell, S; Bond, L; Holbrook, I

2000-01-01

Aim—To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. Methods—24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 109/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. Results—At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. Conclusions—Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia. Key Words: thrombocythaemia • hypercalcaemia • hyperkalaemia PMID:10767824

Intratumoral consumption of indium-111-labeled platelets in a child with splenic hemangioma and thrombocytopenia.

PubMed

Pampin, C; Devillers, A; Treguier, C; Fremond, B; Moisan, A; Goasguen, J; Le Gall, E

2000-01-01

The authors report Kasabach-Merritt syndrome (KMS) in a patient with thrombocytopenia and splenic hemangioma. A 13-month-old boy with a history of anemia, thrombocytopenia, and abdominal mass was admitted to the hospital. The scintigraphic studies showed that a large mass contiguous to the spleen was responsible for the platelet uptake. After partial splenectomy, the platelet count returned to normal. This report of KMS in a child with splenic hemangioma suggests that the scintigraphic studies are mandatory to confirm diagnosis. Indium-111-labeled platelets are useful in identifying hemangiomatous sequestration of platelets in patients with thrombocytopenia.

Essential Thrombocythaemia and Peripheral Gangrene

PubMed Central

Preston, F. E.; Emmanuel, I. G.; Winfield, D. A.; Malia, R. G.

1974-01-01

Six patients are described in whom gangrene of one or more toes occurred as the presenting feature of essential thrombocythaemia. Spontaneous platelet aggregation was observed in platelet-rich plasma from four patients and platelet aggregation after the addition of adenosine diphosphate and collagen was highly abnormal in samples from all six. All of the patients described dramatic relief of pain within six hours of ingestion of aspirin and this coincided with disappearance of the spontaneous platelet aggregation and collagen-induced platelet aggregation. Treatment with phosphorus-32 corrected the platelet count and there were no further recurrences of peripheral vascular disease. Platelet function tests performed at the time all gave normal results. It is concluded that essential thrombocythaemia is an important and treatable cause of peripheral vascular disease. PMID:4472103

[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.

Platelet participation in the pathogenesis of dermonecrosis induced by Loxosceles gaucho venom.

PubMed

Tavares, F L; Peichoto, M E; Marcelino, J R; Barbaro, K C; Cirillo, M C; Santoro, M L; Sano-Martins, I S

2016-06-01

Loxosceles gaucho spider venom induces in vitro platelet activation and marked thrombocytopenia in rabbits. Herein, we investigated the involvement of platelets in the development of the dermonecrosis induced by L. gaucho venom, using thrombocytopenic rabbits as a model. L. gaucho venom evoked a drop in platelet and neutrophil counts 4 h after venom injection. Ecchymotic areas at the site of venom inoculation were noticed as soon as 4 h in thrombocytopenic animals but not in animals with initial normal platelet counts. After 5 days, areas of scars in thrombocytopenic animals were also larger, evidencing the marked development of lesions in the condition of thrombocytopenia. Histologically, local hemorrhage, collagen fiber disorganization, and edema were more severe in thrombocytopenic animals. Leukocyte infiltration, predominantly due to polymorphonuclears, was observed in the presence or not of thrombocytopenia. Thrombus formation was demonstrated by immunohistochemistry at the microvasculature, and it occurred even under marked thrombocytopenia. Taken together, platelets have an important role in minimizing not only the hemorrhagic phenomena but also the inflammatory and wound-healing processes, suggesting that cutaneous loxoscelism may be aggravated under thrombocytopenic conditions. © The Author(s) 2015.

Platelet Counts in Insoluble Platelet-Rich Fibrin Clots: A Direct Method for Accurate Determination.

PubMed

Kitamura, Yutaka; Watanabe, Taisuke; Nakamura, Masayuki; Isobe, Kazushige; Kawabata, Hideo; Uematsu, Kohya; Okuda, Kazuhiro; Nakata, Koh; Tanaka, Takaaki; Kawase, Tomoyuki

2018-01-01

Platelet-rich fibrin (PRF) clots have been used in regenerative dentistry most often, with the assumption that growth factor levels are concentrated in proportion to the platelet concentration. Platelet counts in PRF are generally determined indirectly by platelet counting in other liquid fractions. This study shows a method for direct estimation of platelet counts in PRF. To validate this method by determination of the recovery rate, whole-blood samples were obtained with an anticoagulant from healthy donors, and platelet-rich plasma (PRP) fractions were clotted with CaCl 2 by centrifugation and digested with tissue-plasminogen activator. Platelet counts were estimated before clotting and after digestion using an automatic hemocytometer. The method was then tested on PRF clots. The quality of platelets was examined by scanning electron microscopy and flow cytometry. In PRP-derived fibrin matrices, the recovery rate of platelets and white blood cells was 91.6 and 74.6%, respectively, after 24 h of digestion. In PRF clots associated with small and large red thrombi, platelet counts were 92.6 and 67.2% of the respective total platelet counts. These findings suggest that our direct method is sufficient for estimating the number of platelets trapped in an insoluble fibrin matrix and for determining that platelets are distributed in PRF clots and red thrombi roughly in proportion to their individual volumes. Therefore, we propose this direct digestion method for more accurate estimation of platelet counts in most types of platelet-enriched fibrin matrix.

Platelet Counts in Insoluble Platelet-Rich Fibrin Clots: A Direct Method for Accurate Determination

PubMed Central

Kitamura, Yutaka; Watanabe, Taisuke; Nakamura, Masayuki; Isobe, Kazushige; Kawabata, Hideo; Uematsu, Kohya; Okuda, Kazuhiro; Nakata, Koh; Tanaka, Takaaki; Kawase, Tomoyuki

2018-01-01

Platelet-rich fibrin (PRF) clots have been used in regenerative dentistry most often, with the assumption that growth factor levels are concentrated in proportion to the platelet concentration. Platelet counts in PRF are generally determined indirectly by platelet counting in other liquid fractions. This study shows a method for direct estimation of platelet counts in PRF. To validate this method by determination of the recovery rate, whole-blood samples were obtained with an anticoagulant from healthy donors, and platelet-rich plasma (PRP) fractions were clotted with CaCl2 by centrifugation and digested with tissue-plasminogen activator. Platelet counts were estimated before clotting and after digestion using an automatic hemocytometer. The method was then tested on PRF clots. The quality of platelets was examined by scanning electron microscopy and flow cytometry. In PRP-derived fibrin matrices, the recovery rate of platelets and white blood cells was 91.6 and 74.6%, respectively, after 24 h of digestion. In PRF clots associated with small and large red thrombi, platelet counts were 92.6 and 67.2% of the respective total platelet counts. These findings suggest that our direct method is sufficient for estimating the number of platelets trapped in an insoluble fibrin matrix and for determining that platelets are distributed in PRF clots and red thrombi roughly in proportion to their individual volumes. Therefore, we propose this direct digestion method for more accurate estimation of platelet counts in most types of platelet-enriched fibrin matrix. PMID:29450197

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.

Calcium - ionized

MedlinePlus

... diuretics Thrombocytosis (high platelet count) Tumors Vitamin A excess Vitamin D excess Lower-than-normal levels may be due to: Hypoparathyroidism Malabsorption Osteomalacia Pancreatitis Renal failure Rickets Vitamin D deficiency Alternative Names Free calcium; Ionized calcium ...

Influences of red blood cell and platelet counts on the distribution and elimination of crystalloid fluid.

PubMed

Hahn, Robert G

2017-01-01

A high number of blood cells increases the viscosity of the blood. The present study explored whether variations in blood cell counts are relevant to the distribution and elimination of infused crystalloid fluid. On three different occasions, 10 healthy male volunteers received an intravenous infusion of 25mL/kg of Ringer's acetate, Ringer's lactate, and isotonic saline over 30min. Blood hemoglobin and urinary excretion were monitored for 4h and used as input in a two-volume kinetic model, using nonlinear mixed effects software. The covariates used in the kinetic model were red blood cell and platelet counts, the total leukocyte count, the use of isotonic saline, and the arterial pressure. Red blood cell and platelet counts in the upper end of the normal range were associated with a decreased rate of distribution and redistribution of crystalloid fluid. Simulations showed that high counts were correlated with volume expansion of the peripheral (interstitial) fluid space, while the plasma volume was less affected. In contrast, the total leukocyte count had no influence on the distribution, redistribution, or elimination. The use of isotonic saline caused a transient reduction in the systolic arterial pressure (P<0.05) and doubled the half-life of infused fluid in the body when compared to the two Ringer solutions. Isotonic saline did not decrease the serum potassium concentration, despite the fact that saline is potassium-free. High red blood cell and platelet counts are associated with peripheral accumulation of infused crystalloid fluid. Copyright © 2017 The Lithuanian University of Health Sciences. Production and hosting by Elsevier Sp. z o.o. All rights reserved.

Platelet counting using the Coulter electronic counter.

PubMed

Eggleton, M J; Sharp, A A

1963-03-01

A method for counting platelets in dilutions of platelet-rich plasm using the Coulter electronic counter is described.(1) The results obtained show that such platelet counts are at least as accurate as the best methods of visual counting. The various technical difficulties encountered are discussed.

Correlation of platelet count and acute ST-elevation in myocardial infarction.

PubMed

Paul, G K; Sen, B; Bari, M A; Rahman, Z; Jamal, F; Bari, M S; Sazidur, S R

2010-07-01

The role of platelets in the pathogenesis of ST-elevation myocardial infarction (STEMI) has been substantiated by studies that demonstrated significant clinical benefits associated with antiplatelet therapy. Initial platelet counts in Acute Myocardial Infarction (AMI) may be a useful adjunct for identifying those patients who may or may not respond to fibrinolytic agents. Patient with acute STEMI has variable level of platelet count and with higher platelet count have poor in hospital outcome. There are many predictors of poor outcome in Acute Myocardial Infarction (AMI) like cardiac biomarkers (Troponin I, Troponin T and CK-MB), C-Reactive Protien (CRP) and WBC (White Blood Cell) counts. Platelet count on presentation of STEMI is one of them. Higher platelet count is associated with higher rate of adverse clinical outcome in ST-Elevation Myocardial Infarction (STEMI), like heart failure, arrhythmia, re-infarction & death. So, categorization of patient with STEMI on the basis of platelet counts may be helpful for risk stratification and management of these patients.

Platelet counting using the Coulter electronic counter

PubMed Central

Eggleton, M. J.; Sharp, A. A.

1963-01-01

A method for counting platelets in dilutions of platelet-rich plasm using the Coulter electronic counter is described.1 The results obtained show that such platelet counts are at least as accurate as the best methods of visual counting. The various technical difficulties encountered are discussed. PMID:16811002

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.

An Evaluation of the Accuracy of the Subtraction Method Used for Determining Platelet Counts in Advanced Platelet-Rich Fibrin and Concentrated Growth Factor Preparations

PubMed Central

Watanabe, Taisuke; Isobe, Kazushige; Suzuki, Taiji; Kawabata, Hideo; Nakamura, Masayuki; Tsukioka, Tsuneyuki; Okudera, Toshimitsu; Okudera, Hajime; Uematsu, Kohya; Okuda, Kazuhiro; Nakata, Koh; Kawase, Tomoyuki

2017-01-01

Platelet concentrates should be quality-assured of purity and identity prior to clinical use. Unlike for the liquid form of platelet-rich plasma, platelet counts cannot be directly determined in solid fibrin clots and are instead calculated by subtracting the counts in other liquid or semi-clotted fractions from those in whole blood samples. Having long suspected the validity of this method, we herein examined the possible loss of platelets in the preparation process. Blood samples collected from healthy male donors were immediately centrifuged for advanced platelet-rich fibrin (A-PRF) and concentrated growth factors (CGF) according to recommended centrifugal protocols. Blood cells in liquid and semi-clotted fractions were directly counted. Platelets aggregated on clot surfaces were observed by scanning electron microscopy. A higher centrifugal force increased the numbers of platelets and platelet aggregates in the liquid red blood cell fraction and the semi-clotted red thrombus in the presence and absence of the anticoagulant, respectively. Nevertheless, the calculated platelet counts in A-PRF/CGF preparations were much higher than expected, rendering the currently accepted subtraction method inaccurate for determining platelet counts in fibrin clots. To ensure the quality of solid types of platelet concentrates chairside in a timely manner, a simple and accurate platelet-counting method should be developed immediately. PMID:29563413

Antiplatelet drug induced isolated profound thrombocytopenia in interventional cardiology: a review based on individual case reports.

PubMed

Höchtl, Thomas; Pachinger, Linda; Unger, Gerhard; Geppert, Alexander; Wojta, Johann; Harenberg, Job; Huber, Kurt

2007-08-01

A combination antithrombotic and antiplatelet therapy with clopidogrel, aspirin, glycoprotein IIb/IIIa receptor inhibitors and heparins is routinely used as adjunct therapy in patients undergoing percutaneous coronary intervention (PCI). As all substances inhibit platelet function, bleeding and thrombocytopenia may occur. We report on three patients who developed isolated profound thrombocytopenia (platelet count of < 20,000/mm(3)) within 24 h after initiation of combination antiplatelet and antithrombotic therapy during a 1 year observation period in 443 consecutive patients undergoing PCI and stent implantation. The data from our cardiology unit revealed an incidence of an isolated profound thrombocytopenia in 0.7% of all patients on combination antithrombotic therapy and in 1.5% of patients with GPIIb/IIIa-blockers. In all three cases with isolated profound thrombocytopenia GPIIb/IIIa-blockers were found to be the causative agents. Negative results of HIT-assays excluded heparin induced thrombocytopenia type II. Despite the extremely low platelet count no severe bleeding was observed and in all cases platelet counts normalized within 3-4 days without specific interventions except discontinuation of the responsible agent. These findings are discussed in conjunct with an overview of the recent literature.

The Relationship of Mean Platelet Volume/Platelet Distribution Width and Duodenal Ulcer Perforation.

PubMed

Fan, Zhe; Zhuang, Chengjun

2017-03-01

Duodenal ulcer perforation (DUP) is a severe acute abdominal disease. Mean platelet volume (MPV) and platelet distribution width (PDW) are two platelet parameters, participating in many inflammatory processes. This study aims to investigate the relation of MPV/PDW and DUP. A total of 165 patients were studied retrospectively, including 21 females and 144 males. The study included two groups: 87 normal patients (control group) and 78 duodenal ulcer perforation patients (DUP group). Routine blood parameters were collected for analysis including white blood cell count (WBC), neutrophil ratio (NR), platelet count (PLT), MPV and PDW. Receiver operating curve (ROC) analysis was applied to evaluate the parameters' sensitivity. No significant differences were observed between the control group and DUP group in age and gender. WBC, NR and PDW were significantly increased in the DUP group ( P <0.001, respectively); PLT and MPV were significantly decreased in the DUP group ( P <0.001, respectively) compared to controls. MPV had the high sensitivity. Our results suggested a potential association between MPV/PDW and disease activity in DUP patients, and high sensitivity of MPV. © 2017 by the Association of Clinical Scientists, Inc.

Treatment with Huisheng oral solution inhibits the development of pulmonary thromboembolism and metastasis in mice with Lewis lung carcinoma

PubMed Central

WANG, WEI; WANG, HONG; WANG, CHUN-MEI; GOU, SI; CHEN, ZHONG-HUA; GUO, JIE

2014-01-01

The aim of this study was to investigate whether Huisheng oral solution (HSOS) has an inhibitory effect on the development of pulmonary thrombosis and metastasis in mice with Lewis lung carcinoma (LLC), and to explore the possible mechanisms involved. A mouse model of LLC was developed, and model mice were divided into either a treatment group or a control group to undergo treatment with HSOS or normal saline. Normal mice treated with saline were used as normal controls. On day 25 after treatment, blood samples were drawn from the eyes of half the mice in each group to determine blood cell counts and plasma levels of D-Dimer and vascular endothelial growth factor (VEGF), while heart blood samples were collected from the remaining mice to measure the rate of thrombin-induced platelet aggregation. For all mice, pathological analyses of the cerebrum, lung, mesentery, femoral vein, external iliac vein and spleen were performed. Tumors were weighed to assess the impact of HSOS treatment on tumor growth, and the number of thrombi, metastatic nodules and neovessels in the tumor tissue were counted. In addition, 24 normal New Zealand rabbits were divided into two groups and treated with either HSOS or normal saline to determine the rates of ADP-, collagen- or thrombin-induced platelet aggregation. Compared with the model group, HSOS treatment decreased the incidence of pulmonary thromboembolism and metastasis, the number of metastatic nodules, the plasma levels of D-dimer and VEGF, the rate of collagen-induced platelet aggregation in rabbits and the numbers of leukocytes and tumor neovessels (P<0.05 for all). It increased the thymus and spleen coefficients and the number of platelets (P<0.05 for all), but had no significant effect on thrombin-induced platelet aggregation in mice and rabbits, ADP-induced platelet aggregation in rabbits, or the number of red blood cells. The reduced rate of tumor growth was 9.7% in mice treated with HSOS. HSOS treatment effectively reduced the development of pulmonary thromboembolism and metastasis in mice bearing LLC via mechanisms possibly associated with ameliorating a blood hypercoagulable state, decreasing tumor angiogenesis and enhancing immunity. PMID:24348827

Management of adult patients with persistent idiopathic thrombocytopenic purpura following splenectomy: a systematic review.

PubMed

Vesely, Sara K; Perdue, Jedidiah J; Rizvi, Mujahid A; Terrell, Deirdra R; George, James N

2004-01-20

Treatment of chronic refractory idiopathic thrombocytopenic purpura is a dilemma because many patients have minimal symptoms, response to treatment is uncertain, and treatments may have serious adverse effects. To determine the effectiveness of treatments for adult patients with idiopathic thrombocytopenic purpura who have not responded to splenectomy. English-language reports from 1966 through 2003 that were retrieved from MEDLINE and Reference Update and bibliographies of retrieved articles. Articles reporting 5 or more total patients were reviewed to select eligible patients. Patients were eligible for inclusion if they were more than 16 years of age, had idiopathic thrombocytopenic purpura for more than 3 months, had a previous splenectomy, and had a platelet count less than 50 x 10(9) cells/L. Patients were assessed for platelet count response, bleeding complications, duration of follow-up, and death. Complete remission was defined as a normal platelet count with no treatment for more than 3 months and for the duration of follow-up. 90 articles with 656 patients treated with 22 therapies met selection criteria. Azathioprine, cyclophosphamide, and rituximab had the most reported complete responses, but they were reported in only 41 to 109 patients. Reported complete response rates ranged from 17% to 27%, but 36% to 42% of patients had no response with these 3 treatments. Most reports described only platelet count responses; bleeding outcomes were reported in only 63 patients (10%). Only 111 (17%) of the 656 eligible patients had pretreatment platelet counts of less than 10 x 10(9) cells/L. No treatment method was reported in more than 20 patients. Evidence for the effectiveness of any treatment for patients with idiopathic thrombocytopenic purpura and persistent severe thrombocytopenia after splenectomy is minimal. Potentially effective treatments must be evaluated by randomized, controlled trials to determine both benefit and safety.

Can Eosinophil Count, Platelet Count, and Mean Platelet Volume Be a Positive Predictive Factor in Penile Arteriogenic Erectile Dysfunction Etiopathogenesis?

PubMed Central

Sönmez, Mehmet Giray; Göğer, Yunus Emre; Sönmez, Leyla Öztürk; Aydın, Arif; Balasar, Mehmet; Kara, Cengiz

2016-01-01

Blood count parameters of patients referring with erectile dysfunction (ED) were examined in this study and it was investigated whether eosinophil count (EC), platelet count (PC), and mean platelet volume values among the suspected predictive parameters which may play a role in especially penile arteriogenic ED etiopathogenesis had a contribution on pathogenesis. Patients referring with ED complaint were evaluated. Depending on the medical story, ED degree was determined by measuring International Index of Erectile Function. Penile Doppler ultrasonography was taken in patients suspected to have vasculogenic ED. According to penile Doppler ultrasonography result, patients with arterial deficiency were included in the penile arteriogenic ED group and the patients with normal results were included in the nonvasculogenic ED group. A total of 36 patients participated in the study from the penile arteriogenic ED group and 32 patients from the nonvasculogenic ED group. Compared with the nonvasculogenic ED group, the penile arteriogenic ED group’s low International Index of Erectile Function score, high EC, mean platelet volume and PC values were detected to be statistically significant (p < .001, p = .021, p = .018, p = .034, respectively). No statistically significant difference was observed among the two groups when age, white blood cells, red blood cells, and hemoglobin values were considered. Pansystolic volume velocities were detected as statistically significantly low compared with the nonvasculogenic ED group in the measurements made in 5th, 10th, 15th, and 20th minutes on the right and left sides in the penile arteriogenic ED group. High MPV value and PC is a significant predictive factor for penile arteriogenic ED and vasculogenic ED and high EC is specifically predictive of arteriogenic ED. PMID:27895254

Comparison of point-of-care methods for preparation of platelet concentrate (platelet-rich plasma).

PubMed

Weibrich, Gernot; Kleis, Wilfried K G; Streckbein, Philipp; Moergel, Maximilian; Hitzler, Walter E; Hafner, Gerd

2012-01-01

This study analyzed the concentrations of platelets and growth factors in platelet-rich plasma (PRP), which are likely to depend on the method used for its production. The cellular composition and growth factor content of platelet concentrates (platelet-rich plasma) produced by six different procedures were quantitatively analyzed and compared. Platelet and leukocyte counts were determined on an automatic cell counter, and analysis of growth factors was performed using enzyme-linked immunosorbent assay. The principal differences between the analyzed PRP production methods (blood bank method of intermittent flow centrifuge system/platelet apheresis and by the five point-of-care methods) and the resulting platelet concentrates were evaluated with regard to resulting platelet, leukocyte, and growth factor levels. The platelet counts in both whole blood and PRP were generally higher in women than in men; no differences were observed with regard to age. Statistical analysis of platelet-derived growth factor AB (PDGF-AB) and transforming growth factor β1 (TGF-β1) showed no differences with regard to age or gender. Platelet counts and TGF-β1 concentration correlated closely, as did platelet counts and PDGF-AB levels. There were only rare correlations between leukocyte counts and PDGF-AB levels, but comparison of leukocyte counts and PDGF-AB levels demonstrated certain parallel tendencies. TGF-β1 levels derive in substantial part from platelets and emphasize the role of leukocytes, in addition to that of platelets, as a source of growth factors in PRP. All methods of producing PRP showed high variability in platelet counts and growth factor levels. The highest growth factor levels were found in the PRP prepared using the Platelet Concentrate Collection System manufactured by Biomet 3i.

Effective estimation of correct platelet counts in pseudothrombocytopenia using an alternative anticoagulant based on magnesium salt

PubMed Central

Schuff-Werner, Peter; Steiner, Michael; Fenger, Sebastian; Gross, Hans-Jürgen; Bierlich, Alexa; Dreissiger, Katrin; Mannuß, Steffen; Siegert, Gabriele; Bachem, Maximilian; Kohlschein, Peter

2013-01-01

Pseudothrombocytopenia remains a challenge in the haematological laboratory. The pre-analytical problem that platelets tend to easily aggregate in vitro, giving rise to lower platelet counts, has been known since ethylenediamine-tetra acetic acid EDTA and automated platelet counting procedures were introduced in the haematological laboratory. Different approaches to avoid the time and temperature dependent in vitro aggregation of platelets in the presence of EDTA were tested, but none of them proved optimal for routine purposes. Patients with unexpectedly low platelet counts or flagged for suspected aggregates, were selected and smears were examined for platelet aggregates. In these cases patients were asked to consent to the drawing of an additional sample of blood anti-coagulated with a magnesium additive. Magnesium was used in the beginning of the last century as anticoagulant for microscopic platelet counts. Using this approach, we documented 44 patients with pseudothrombocytopenia. In all cases, platelet counts were markedly higher in samples anti-coagulated with the magnesium containing anticoagulant when compared to EDTA-anticoagulated blood samples. We conclude that in patients with known or suspected pseudothrombocytopenia the magnesium-anticoagulant blood samples may be recommended for platelet counting. PMID:23808903

Hematologic adverse effects of 2 different polyclonal antilymphocyte preparations in de novo kidney transplant patients.

PubMed

Rostaing, Lionel; Lavayssière, Laurence; Kamar, Nassim

2010-06-01

To evaluate the hematologic adverse effects of polyclonal antilymphocyte globulins within the first month after surgery in kidney transplant recipients. In this prospective, randomized trial, we included 16 adult-sensitized (panel-reactive antibodies > 30%) recipients of a kidney from a deceased donor. Eight patients received therapy with Genzyme (Thymoglobulin: ATG-G; 6.2 +/- 2.9 mg/kg for 7 days), and 8 patients received Fresenius (Lymphoglobulin: ATG-F; 22.6 +/- 7.9 mg/kg for 6 days). Other immunosuppressants included mycophenolate mofetil, tacrolimus, and steroids. Platelet counts were normal before transplant and significantly reduced after transplant; however, this was more pronounced in ATG-F patients, and had normalized by day 7 in the ATG-G and by day 10 in the ATG-F groups. Mean leukocyte/polymorphonuclear cell counts remained within the normal range in both groups through follow-up. Hemoglobin levels were similar at approximately 10 g/dL for both groups, up to day 10. However, erythropoietin-stimulating-agent therapy had been given to more patients in the ATG-F group than patients in the ATG-G group. Reticulocyte counts were significantly lower in ATG-F patients by days 3, 5, 7, and 10. From day 14 onwards, reticulocyte counts were similar in both groups. With regard to lymphocyte counts, these were normal in both groups before transplant and then significantly decreased afterward. No patient presented with acute rejection or serum-sickness disease. Reduced platelet and reticulocyte counts occur more frequently immediately after transplant when using ATG-F compared with ATG-G therapy. Consequently, erythropoietin-stimulating-agent therapy was needed more often for ATG-F patients.

Immunopathology of thrombocytopenia in experimental malaria.

PubMed

Grau, G E; Piguet, P F; Gretener, D; Vesin, C; Lambert, P H

1988-12-01

An early thrombocytopenia was observed in CBA mice during acute infection with Plasmodium berghei. This was associated with an increase in bone marrow megakaryocytes and a reduction of normal syngeneic 111Indium-labelled platelet life span. Malaria-induced thrombocytopenia was thus considered to be the result of increased peripheral platelet destruction rather than central hypoproduction. The occurrence of thrombocytopenia was modulated by T-cell depletion. Indeed, thymectomized, irradiated or anti-CD4 monoclonal antibody-treated mice failed to develop thrombocytopenia, although they were infected to the same extent. Conversely, a significant thrombocytopenia was observed in thymectomized mice reconstituted with CD4+ T cells. During the course of infection, a significant inverse correlation was found between platelet counts and platelet-associated IgG. Normal mice passively transferred with serum from syngeneic malaria-infected mice developed thrombocytopenia. The possibility to raise monoclonal anti-platelet antibodies from P. berghei-infected animals further suggested a role for an antibody-mediated platelet destruction during acute murine malaria infection. These results indicate that in murine malaria, thrombocytopenia is mediated by immune mechanisms and that CD4+ T cells might be significantly involved.

Immunopathology of thrombocytopenia in experimental malaria.

PubMed Central

Grau, G E; Piguet, P F; Gretener, D; Vesin, C; Lambert, P H

1988-01-01

An early thrombocytopenia was observed in CBA mice during acute infection with Plasmodium berghei. This was associated with an increase in bone marrow megakaryocytes and a reduction of normal syngeneic 111Indium-labelled platelet life span. Malaria-induced thrombocytopenia was thus considered to be the result of increased peripheral platelet destruction rather than central hypoproduction. The occurrence of thrombocytopenia was modulated by T-cell depletion. Indeed, thymectomized, irradiated or anti-CD4 monoclonal antibody-treated mice failed to develop thrombocytopenia, although they were infected to the same extent. Conversely, a significant thrombocytopenia was observed in thymectomized mice reconstituted with CD4+ T cells. During the course of infection, a significant inverse correlation was found between platelet counts and platelet-associated IgG. Normal mice passively transferred with serum from syngeneic malaria-infected mice developed thrombocytopenia. The possibility to raise monoclonal anti-platelet antibodies from P. berghei-infected animals further suggested a role for an antibody-mediated platelet destruction during acute murine malaria infection. These results indicate that in murine malaria, thrombocytopenia is mediated by immune mechanisms and that CD4+ T cells might be significantly involved. PMID:3065215

Safety and efficacy of oral DMSA therapy for children with autism spectrum disorders: Part A - Medical results

PubMed Central

Adams, James B; Baral, Matthew; Geis, Elizabeth; Mitchell, Jessica; Ingram, Julie; Hensley, Andrea; Zappia, Irene; Newmark, Sanford; Gehn, Eva; Rubin, Robert A; Mitchell, Ken; Bradstreet, Jeff; El-Dahr, Jane

2009-01-01

Background This study investigated the effect of oral dimercapto succinic acid (DMSA) therapy for children with autism spectrum disorders ages 3-8 years. Methods Phase 1 involved 65 children who received one round of DMSA (3 days). Participants who had high urinary excretion of toxic metals were selected to continue on to phase 2. In phase 2, 49 participants were randomly assigned in a double-blind design to receive an additional 6 rounds of either DMSA or placebo. Results DMSA greatly increased the excretion of lead, substantially increased excretion of tin and bismuth, and somewhat increased the excretion of thallium, mercury, antimony, and tungsten. There was some increase in urinary excretion of essential minerals, especially potassium and chromium. The Phase 1 single round of DMSA led to a dramatic normalization of RBC glutathione in almost all cases, and greatly improved abnormal platelet counts, suggesting a significant decrease in inflammation. Conclusion Overall, DMSA therapy seems to be reasonably safe, effective in removing several toxic metals (especially lead), dramatically effective in normalizing RBC glutathione, and effective in normalizing platelet counts. Only 1 round (3 days) was sufficient to improve glutathione and platelets. Additional rounds increased excretion of toxic metals. PMID:19852789

Mechanism Underlying Linezolid-induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

PubMed Central

Nishijo, Nao; Tsuji, Yasuhiro; Matsunaga, Kazuhisa; Kutsukake, Masahiko; Okazaki, Fumiyasu; Fukumori, Shiro; Kasai, Hidefumi; Hiraki, Yoichi; Sakamaki, Ippei; Yamamoto, Yoshihiro; Karube, Yoshiharu; To, Hideto

2017-01-01

Objective: To investigate the relationship between renal function and linezolid (LZD)-induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5-week-old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2-14C-thymidine (0.185 MBq) was administrated intravenously to LZD-administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD-administered CRD group than in the LZD-nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD-administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD-administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD-induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD-induced thrombocytopenia is not caused by nonimmune-mediated bone marrow suppression. PMID:28405130

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.

Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

PubMed

Sallmon, Hannes; Weber, Sven C; Dirks, Juliane; Schiffer, Tamara; Klippstein, Tamara; Stein, Anja; Felderhoff-Müser, Ursula; Metze, Boris; Hansmann, Georg; Bührer, Christoph; Cremer, Malte; Koehne, Petra

2018-01-01

The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated. Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure ( p  < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

Women with Red Hair Report A Slightly Increased Rate of Bruising, but Have Normal Coagulation Tests

PubMed Central

Liem, Edwin B.; Hollensead, Sandra C.; Joiner, Teresa V.

2005-01-01

There is an anecdotal impression that redheads experience more perioperative bleeding complications than those with other hair colors. We, therefore, tested the hypothesis that perceived problems with hemostasis could be detected with commonly used coagulation tests. Se studied healthy female Caucasian volunteers, 18 to 40 years, comparable in terms of height, weight, and age, with natural bright red (n = 25) or black or dark brown (n = 26) hair. Volunteers were questioned about their bleeding history and the following tests were performed: complete blood count, prothrombin time/international normalized ratio, activated partial thromboplastin time, platelet function analysis (PFA-100), and platelet aggregation using standard turbidimetric methodology. Agonists for aggregation were adenosine diphosphate, arachidonic acid, collagen, epinephrine, and two concentrations of ristocetin. The red-haired volunteers reported significantly more bruising, but there were no significant differences between the red- and dark-haired groups in hemoglobin concentration, platelet numbers, prothrombin time/international normalized ratio, or activated partial thromboplastin time. Furthermore, no significant differences in platelet function, as measured with the PFA-100 or with platelet aggregometry, were observed. We conclude that if redheads have hemostasis abnormalities, they are subtle. PMID:16368849

Platelet count and total and cause-specific mortality in the Women's Health Initiative.

PubMed

Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lin, Juan; Lessin, Lawrence; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

2017-04-01

We used data from the Women's Health Initiative to examine the association of platelet count with total mortality, coronary heart disease (CHD) mortality, cancer mortality, and non-CHD/noncancer mortality. Platelet count was measured at baseline in 159,746 postmenopausal women and again in year 3 in 75,339 participants. Participants were followed for a median of 15.9 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline platelet count and of the mean of baseline + year 3 platelet count. Low and high deciles of both baseline and mean platelet count were positively associated with total mortality, CHD mortality, cancer mortality, and non-CHD/noncancer mortality. The association was robust and was not affected by adjustment for a number of potential confounding factors, exclusion of women with comorbidity, or allowance for reverse causality. Low- and high-platelet counts were associated with all four outcomes in never smokers, former smokers, and current smokers. In this large study of postmenopausal women, both low- and high-platelet counts were associated with total and cause-specific mortality. Copyright © 2017 Elsevier Inc. All rights reserved.

The Radiologist Is in, but Was it Worth the Wait? Radiology Resident Note Quality in an Outpatient Interventional Radiology Clinic.

PubMed

Abboud, Salim E; Soriano, Stephanie; Abboud, Rayan; Patel, Indravadan; Davidson, Jon; Azar, Nami R; Nakamoto, Dean A

Preprocedural evaluation of patients in an interventional radiology (IR) clinic is a complex synthesis of physical examination and imaging findings, and as IR transitions to an independent clinical specialty, such evaluations will become an increasingly critical component of a successful IR practice and quality patient care. Prior research suggests that preprocedural evaluations increased patient's perceived quality of care and may improve procedural technical success rates. Appropriate documentation of a preprocedural evaluation in the medical record is also paramount for an interventional radiologist to add value and function as an effective member of a larger IR service and multidisciplinary health care team. The purpose of this study is to examine the quality of radiology resident notes for patients seen in an outpatient IR clinic at a single academic medical center before and after the adoption of clinic note template with reminders to include platelet count, international normalized ratio, glomerular filtration rate, and plan for periprocedural coagulation status. Before adoption of the template, platelet count, international normalized ratio, glomerular filtration rate and an appropriate plan for periprocedural coagulation status were documented in 72%, 82%, 42%, and 33% of patients, respectively. After adoption of the template, appropriate documentation of platelet count, international normalized ratio, and glomerular filtration rate increased to 96%, and appropriate plan for periprocedural coagulation status was documented in 83% of patients. Patient evaluation and clinical documentation skills may not be adequately practiced during radiology residency, and tools such as templates may help increase documentation quality by radiology residents. Copyright © 2017 Elsevier Inc. All rights reserved.

Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis.

PubMed

Ranganathan, Usha; Kaunzner, Ulrike; Foster, Stacyann; Vartanian, Timothy; Perumal, Jai S

2018-04-01

Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). Although Immune thrombocytopenia (ITP) has been reported as a secondary autoimmune phenomenon following alemtuzumab infusion, immediate thrombocytopenia during the infusion has not been reported. We report transient, reversible, self-limiting acute-onset thrombocytopenia during the first course with alemtuzumab. In total, 3 of 22 paitents developed mild self-limited bruising associated with a drop in platelet count from their baseline during the intial 5-day course of alemtuzumab. Upon chart review, all 22 patients who received alemtuzumab developed an immediate mostly asymptomatic drop in platelet count which returned to normal within 2 months post-infusion.

Plasma glycoprotein V levels in the general population: normal distribution, associated parameters and implications for clinical studies.

PubMed

Aleil, Boris; Meyer, Nicolas; Wolff, Valérie; Kientz, Daniel; Wiesel, Marie-Louise; Gachet, Christian; Cazenave, Jean-Pierre; Lanza, François

2006-10-01

Soluble glycoprotein V (sGPV) is a new plasma marker of thrombosis released from the platelet surface by thrombin. sGPV levels are increased in patients with atherothrombotic diseases, but the determinants of sGPV levels are unknown in the general population. Identification of these potential confounding factors is needed for correct design and analysis of clinical studies on cardiovascular diseases. The aim of this study was to determine the normal range of plasma values and the factors controlling sGPV levels in a population of normal individuals. Three hundred blood donors were recruited at the Etablissement Français du Sang-Alsace for the measurement of plasma levels of sGPV, platelet factor 4 (PF4), thrombin-antithrombin complexes (TAT) and D-dimers. The plasma level of sGPV was (median [interquartile range]) 27.5 [23.5-34.4] microg/l and displayed a Gaussian distribution. sGPV had a lower interindividual coefficient of variation (33%) than PF4 (176%), TAT (87%) or D-dimers (82%). sGPV levels were independent of age and sex but sensitive to red cell (r = 0.412; p < 0.0001) and platelet counts (r = 0.267; p = 0.001), total cholesterol (r = -0.313; p < 0.0001), food intake (r = 0.184; p = 0.0014) and smoking (r = -0.154; p = 0.039). Contrary to PF4 and TAT, sGPV did not differ between venous and arterial blood samples of 12 healthy individuals. Red cell and platelet counts, total cholesterol, current smoking and recent food intake are important determinants of sGPV levels and must be taken into account in clinical studies using sGPV as a thrombosis marker. Normal distribution of sGPV levels in the general population supports its use in clinical applications.

The platelet count in EDTA-anticoagulated blood from patients with thrombocytopenia may be underestimated when measured in routine laboratories.

PubMed

Podda, Gian Marco; Pugliano, Mariateresa; Femia, Eti Alessandra; Mezzasoma, Anna Maria; Gresele, Paolo; Carpani, Giovanni; Cattaneo, Marco

2012-07-01

Spuriously low platelet counts (PCs) can be observed in normal blood samples anticoagulated with ethylenediamine tetra-acetic acid (EDTA)and, much less frequently, with citrate-tris-pyridossalphosphate (CPT),due to time-dependent in vitro platelet agglutination. Accuracy in PC determination is essential as PC is one of the parameters that usually guides treatment for thrombocytopenic patients. PCs of 93 thrombocy to penic patients were measured in EDTA- or CPT-anticoagulated blood samples immediately after sampling (t0) and 90 min (t90) after storage at room temperature. The presence of platelet agglutinates in blood samples was determined by examining blood smears using optical microscopy.PCs decreased at t90 with both anticoagulants. Platelet agglutinates were present at t90 in 27% of EDTA-samples vs. 2% of CPT-samples with decreased PCs (P < 0.001). Based on PCs in EDTA-samples, 15 patients (16%) shifted from a lower bleeding risk at t0 to a higher bleeding risk category at t90 (P 5 0.019), compared to 5 (5%) patients, based on PCs in CPT-samples. Therefore, time-dependent in vitro platelet agglutination in EDTA-blood samples may cause underestimation of PCs in thrombocytopenic patients, possibly leading to improper management.

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

Improvement of thrombocytopenia following bone marrow transplantation by pegylated recombinant human megakaryocyte growth and development factor in mice.

PubMed

Kabaya, K; Shibuya, K; Torii, Y; Nitta, Y; Ida, M; Akahori, H; Kato, T; Kusaka, M; Miyazaki, H

1996-12-01

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.

Improvement in platelet count after 3rd-line and 4th-line eradication therapy for Helicobacter pylori in patients with immune thrombocytopenia.

PubMed

Jomen, Wataru; Sato, Takashi; Maesawa, Chihaya

2017-01-01

Case 1: A 78-year-old woman was diagnosed with H. pylori positive gastritis at a previous hospital in April 2012 and received 3rd-line H. pylori eradication therapy, which ended in failure. She was referred to our department due to oral hemorrhage, petechiae involving all four extremities, and thrombocytopenia in January 2016. She was hospitalized with a diagnosis of ITP and received inpatient treatment. While receiving outpatient prednisolone (PSL) treatment, we administered 4th-line eradication therapy in March. Her platelet levels have since returned to normal, and PSL treatment has been discontinued. She is currently followed without treatment. Case 2: A 65-year-old woman was diagnosed with ITP at a previous hospital in June 2013 and received 2nd-line eradication therapy, which ended in failure. Thereafter, PSL treatment was continued but she was later referred to our department in March 2016. Since 3rd-line eradication therapy was successful, her platelet count normalized and PSL treatment has been discontinued. She is currently followed without treatment. Based on our observations in these two cases, third-line H. pylori eradication therapy is potentially effective in ITP patients.

Postoperative Decrease in Platelet Counts Is Associated with Delayed Liver Function Recovery and Complications after Partial Hepatectomy.

PubMed

Takahashi, Kazuhiro; Kurokawa, Tomohiro; Oshiro, Yukio; Fukunaga, Kiyoshi; Sakashita, Shingo; Ohkohchi, Nobuhiro

2016-05-01

Peripheral platelet counts decrease after partial hepatectomy; however, the implications of this phenomenon are unclear. We assessed if the observed decrease in platelet counts was associated with postoperative liver function and morbidity (complications grade ≤ II according to the Clavien-Dindo classification). We enrolled 216 consecutive patients who underwent partial hepatectomy for primary liver cancers, metastatic liver cancers, benign tumors, and donor hepatectomy. We classified patients as either low or high platelet percentage (postoperative platelet count/preoperative platelet count) using the optimal cutoff value calculated by a receiver operating characteristic (ROC) curve analysis, and analyzed risk factors for delayed liver functional recovery and morbidity after hepatectomy. Delayed liver function recovery and morbidity were significantly correlated with the lowest value of platelet percentage based on ROC analysis. Using a cutoff value of 60% acquired by ROC analysis, univariate and multivariate analysis determined that postoperative lowest platelet percentage ≤ 60% was identified as an independent risk factor of delayed liver function recovery (odds ratio (OR) 6.85; P < 0.01) and morbidity (OR, 4.90; P < 0.01). Furthermore, patients with the lowest platelet percentage ≤ 60% had decreased postoperative prothrombin time ratio and serum albumin level and increased serum bilirubin level when compared with patients with platelet percentage ≥ 61%. A greater than 40% decrease in platelet count after partial hepatectomy was an independent risk factor for delayed liver function recovery and postoperative morbidity. In conclusion, the decrease in platelet counts is an early marker to predict the liver function recovery and complications after hepatectomy.

Analysis of Platelet-Rich Plasma Extraction

PubMed Central

Fitzpatrick, Jane; Bulsara, Max K.; McCrory, Paul Robert; Richardson, Martin D.; Zheng, Ming Hao

2017-01-01

Background: Platelet-rich plasma (PRP) has been extensively used as a treatment in tissue healing in tendinopathy, muscle injury, and osteoarthritis. However, there is variation in methods of extraction, and this produces different types of PRP. Purpose: To determine the composition of PRP obtained from 4 commercial separation kits, which would allow assessment of current classification systems used in cross-study comparisons. Study Design: Controlled laboratory study. Methods: Three normal adults each donated 181 mL of whole blood, some of which served as a control and the remainder of which was processed through 4 PRP separation kits: GPS III (Biomet Biologics), Smart-Prep2 (Harvest Terumo), Magellan (Arteriocyte Medical Systems), and ACP (Device Technologies). The resultant PRP was tested for platelet count, red blood cell count, and white blood cell count, including differential in a commercial pathology laboratory. Glucose and pH measurements were obtained from a blood gas autoanalyzer machine. Results: Three kits taking samples from the “buffy coat layer” were found to have greater concentrations of platelets (3-6 times baseline), while 1 kit taking samples from plasma was found to have platelet concentrations of only 1.5 times baseline. The same 3 kits produced an increased concentration of white blood cells (3-6 times baseline); these consisted of neutrophils, leukocytes, and monocytes. This represents high concentrations of platelets and white blood cells. A small drop in pH was thought to relate to the citrate used in the sample preparation. Interestingly, an unexpected increase in glucose concentrations, with 3 to 6 times greater than baseline levels, was found in all samples. Conclusion: This study reveals the variation of blood components, including platelets, red blood cells, leukocytes, pH, and glucose in PRP extractions. The high concentrations of cells are important, as the white blood cell count in PRP samples has frequently been ignored, being considered insignificant. The lack of standardization of PRP preparation for clinical use has contributed at least in part to the varying clinical efficacy in PRP use. Clinical Relevance: The variation of platelet and other blood component concentrations between commercial PRP kits may affect clinical treatment outcomes. There is a need for standardization of PRP for clinical use. PMID:28210651

[Occurence, etiology and clinical significance of trombocytopenia in pregnancy].

PubMed

Brychtová, P; Procházka, M; Lattová, V; Lubušký, M; Procházková, J; Slavík, L; Úlehlová, J; Simetka, O

2013-12-01

The principal objective of the study is to compare results from the experimental group of pregnant women suffering from thrombocytopenia in pregnancy with results from the control group of pregnant women with normal physiologic blood platelet count. Department of Obstetrics and Gynaecology of the Tomas Bata Regional Hospital Zlín, Obstetrics and Gynaecology Clinic, Haematology and Oncology Clinic of the Palacky University Teaching Hospital and Medical School in Olomouc, Obstetrics and Gynaecology Clinic of the Ostrava Teaching Hospital. A group of 200 pregnant women suffering from thrombocytopenia underwent thorough medical tests. The level of platelets, presence of anti-platelets agents, liver function (LFT), anti-phospholipid antibodies, complete blood count with differential, specific antibodies for hepatitis B and C, Lyme borreliosis and cytomegalovirus were determined from venous blood using the EIA, ELISA methods. Medical articles and books about thrombocytopenia divide the causes for thrombocytopenia as follows: 79.5% benign gestational thrombocytopenia, 16% preeclampsia, 2.5% HELLP syndrome, 1% immune thrombocytopenia, 1% HVC. The number of women who developed physiological anaemia in pregnancy and were overweight is identical in the experimental group of pregnant women suffering from thrombocytopenia and in the control group of pregnant women with normal physiologic blood platelet count, and the proportion of the different age groups in the two groups of pregnant women is also identical. 32% of pregnancies in the experimental group ended in a caesarean section, of which 13.5% in a group of 127 pregnant women suffering from mild thrombocytopenia, 17.5% in a group of 71 pregnant women suffering from moderate thrombocytopenia and 1% in a group of 2 pregnant women suffering from severe thrombocytopenia. 20.5% pregnancies in the control group ended in caesarean section.

Platelet count recovery and seroreversion in immune HIT despite continuation of heparin: further observations and literature review.

PubMed

Shih, Andrew W; Sheppard, Jo-Ann I; Warkentin, Theodore E

2017-10-05

One of the standard distinctions between type 1 (non-immune) and type 2 (immune-mediated) heparin-induced thrombocytopenia (HIT) is the transience of thrombocytopenia: type 1 HIT is viewed as early-onset and transient thrombocytopenia, with platelet count recovery despite continuing heparin administration. In contrast, type 2 HIT is viewed as later-onset (i. e., 5 days or later) thrombocytopenia in which it is generally believed that platelet count recovery will not occur unless heparin is discontinued. However, older reports of type 2 HIT sometimes did include the unexpected observation that platelet counts could recover despite continued heparin administration, although without information provided regarding changes in HIT antibody levels in association with platelet count recovery. In recent years, some reports of type 2 HIT have confirmed the observation that platelet count recovery can occur despite continuing heparin administration, with serological evidence of waning levels of HIT antibodies ("seroreversion"). We now report two additional patient cases of type 2 HIT with platelet count recovery despite ongoing therapeutic-dose (1 case) or prophylactic-dose (1 case) heparin administration, in which we demonstrate concomitant waning of HIT antibody levels. We further review the literature describing this phenomenon of HIT antibody seroreversion and platelet count recovery despite continuing heparin administration. Our observations add to the concept that HIT represents a remarkably transient immune response, including sometimes even when heparin is continued.

The effects of hypobaric hypoxia (50.6 kPa) on blood components in guinea-pigs.

PubMed

Osada, H

1991-06-01

One hundred and five male (Hartley) guinea-pigs weighing 350-380 g and 30 splenectomized guinea-pigs were exposed to simulated hypobaric hypoxia of 50.6 kPa (equal to an altitude of 5486 m) for 14 days. The partial pressure of oxygen was set at half that at sea level. The white blood cell count increased significantly on day 3 of the simulated high altitude experiment but returned to normal on day 7, whereas the red blood cell count increased continuously. To study the effect of high altitude exposure on platelets, the platelet count in the splenectomized group was compared to that in a non-splenectomized group. Investigation of the resistance of red blood cell membranes to osmotic pressure under hypobaric conditions revealed a shift of the onset of haemolysis in the hyperosmotic direction. These findings may help to increase our understanding of the biochemical mechanisms of adaptation to hypobaric hypoxia.

Unusual Presentation of Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Madhusudhanan, M.; Yusuff, Ali M.

2008-01-01

A snakebite victim presented with normal clotting profile and a low platelet count. A routine CBC in his past records (February 2004) showed a platelet count of 20,000/microlitre, but the patient was not symptomatic. We report a case of chronic idiopathic thrombocytopenic purpura, incidentally found in a patient presenting with snakebite. The patient also has acquired primary testicular failure. After the diagnosis the patient was on regular follow up. He caused trauma to the right external auditory canal and perforated his tympanic membrane. His left tympanic membrane was also scarred and retracted. Establishing a diagnosis of an ITP early is important so that the patient can take precaution to avoid undue trauma and monitor proper follow up. PMID:22567212

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

Platelet Kinetics in Idiopathic Thrombocytopenic Purpura Patients Treated with Thrombopoietin Receptor Agonists

PubMed Central

Meyer, Oliver; Herzig, Eric; Salama, Abdulgabar

2012-01-01

Aim Thrombopoietin receptor agonists (Tpo RA) increase platelet counts in the majority of chronic autoimmune thrombocytopenia (idiopathic thrombocytopenic purpura; ITP) patients. It is unknown whether this treatment may also improve platelet survival (PS) in these patients. Methods In order to determine platelet survival (PS), autologous platelets were labeled with 111In oxine and retransfused in six patients under treatment with Tpo RA (romiplostim n = 3; eltrombopag n = 3). Results Stable platelet counts of greater than 100 × 103/μl were observed in all 6 patients. Platelet survival was decreased in all cases (mean 2.10 days; range 0.13–3.73 days). No correlation was found between platelet count and PS. Similarly, there was no significant relationship between platelet turnover and platelet count. However, a high platelet turnover, exceeding 25 or three times the norm was observed in 2 patients who presented the lowest PS (0.13 or 0.83 days). Two patients had a moderately shortened PS (1.91 or 2.42 days), and, correspondingly, a moderately increased platelet turnover rate (63,072 or 72,872 platelets/μl/day). Conclusion These results indicate that Tpo RA may not only overcompensate platelet destruction in ITP, but may interfere with other mechanisms, which, in some cases, results in a reduced platelet destruction rate. PMID:22896760

Leptospirosis in Spanish travelers returning from Chiang Mai: A case series.

PubMed

Rodriguez-Valero, Natalia; Moriñigo, Helena Moza; Martínez, Miguel J; Peiró, Aida; Oliveira, Ines; Bodro, Marta; Gómez-Junyent, Joan; Gascon, Joaquim; Muñoz, Jose

Leptospirosis is an important zoonosis worldwide, nevertheless is often poor recognized in non tropical settings. In Thailand is becoming an emerging disease and Chiang Mai could become a popular spot to acquire the disease amongst travelers. We describe three cases of imported leptospirosis undifferentiated fever after travelling to Thailand during the summer of 2015 diagnosed at two Spanish hospitals. Our three patients probably acquired leptospirosis while swimming in freshwater around Chiang Mai, a Thailand's northern region with moderate incidence of leptopirosis. Travelers had normal white blood cell counts and low platelets, suggesting leptospirosis after ruling out other imported diseases such as malaria, dengue or typhoid. As recent findings point out, low platelets and normal white blood cell counts are clinical features that could help the clinician to suspect Leptospirosis infection. It should be always considered as a cause of fever, particularly if travelers come from a tropical country and have had contact with water or flooding, especially during rainy season. Copyright © 2018 Elsevier Ltd. All rights reserved.

A large kindred with X-linked neutropenia with an I294T mutation of the Wiskott-Aldrich syndrome gene.

PubMed

Beel, Karolien; Cotter, Melanie M; Blatny, Jan; Bond, Jonathan; Lucas, Geoff; Green, Frances; Vanduppen, Vik; Leung, Daisy W; Rooney, Sean; Smith, Owen P; Rosen, Michael K; Vandenberghe, Peter

2009-01-01

X-linked neutropenia (XLN, OMIM #300299) is a rare form of severe congenital neutropenia. It was originally described in a three-generation family with five affected members that had an L270P mutation in the GTP-ase binding domain (GBD) of the Wiskott-Aldrich syndrome protein (WASP) [Devriendt et al (2001) Nature Genetics, Vol. 27, 313-317]. Here, we report and describe a large three-generation family with XLN, with 10 affected males and eight female carriers. A c.882T>C mutation was identified in the WAS gene, resulting in an I294T mutation. The infectious course is variable and mild in view of the profound neutropenia. In addition to the original description, low-normal IgA levels, low to low-normal platelet counts and reduced natural killer (NK)-cell counts also appear as consistent XLN features. However, inverted CD4/CD8 ratios were not found in this family, nor were cases identified with myelodysplastic syndrome or acute myeloid leukaemia. Female carriers exhibited a variable attenuated phenotype. Like L270P WASP, I294T WASP is constitutively active towards actin polymerization. In conclusion, this largest XLN kindred identified to date provides new independent genetic evidence that mutations disrupting the auto-inhibitory GBD of WASP are the cause of XLN. Reduced NK cells, low to low normal platelet counts and low to low-normal IgA levels are also features of XLN.

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.

Immature platelet fraction in bacterial sepsis severity assessment

NASA Astrophysics Data System (ADS)

Djuang, M. H.; Ginting, F.; Hariman, H.

2018-03-01

Sepsis is an infection-induced syndrome, mostly caused by bacteria, of organ dysfunctions that caused by host response dysregulations. One of the simplest sepsis-indicator is platelet and its indexes. A new platelet parameter called immature platelet count (IPF) became theinterest in this study. The study aims to see whether IPF could assess sepsis severity by procalcitonin (PCT).Sixty-four of seventy-one patients with increased PCT were included in this cross-sectional study and separated into three groups based on their PCT levels. IPF showed no significance among the three groups (p-value>0.05) while platelet count was significant (p-value<0.05). Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) showed a strongpositive correlation with IPF. Higher sepsis severity based on PCT showed larger platelet count, as the result of platelet destructions caused by pro-inflammatory cytokines and endotoxins.

Corticosteroids compared with intravenous immunoglobulin for the treatment of immune thrombocytopenia in pregnancy.

PubMed

Sun, Dongmei; Shehata, Nadine; Ye, Xiang Y; Gregorovich, Sandra; De France, Bryon; Arnold, Donald M; Shah, Prakesh S; Malinowski, Ann Kinga

2016-09-08

Treatment options for immune thrombocytopenia (ITP) in pregnancy are limited, and evidence to guide management decisions is lacking. This retrospective study of singleton pregnancies from 2 tertiary centers compared the effectiveness of intravenous immunoglobulin (IVIg) and corticosteroids in treatment of ITP. Data from 195 women who had 235 pregnancies were reviewed. Treatment was not required in 137 pregnancies (58%). Of the remaining 98 pregnancies in 91 women, 47 (48%) were treated with IVIg and 51 were treated with corticosteroids as the initial intervention. Mean maternal platelet count at birth did not differ between groups (IVIg 69 × 10(9)/L vs corticosteroids 77 × 10(9)/L; P = .71) nor did the proportion of mothers who achieved a platelet count response (IVIg 38% vs corticosteroids 39%; P = .85). There were no fatal or severe maternal, fetal, or neonatal hemorrhages. Of 203 neonates in whom platelet counts were available, 56 (28%) had a birth platelet count <150 × 10(9)/L and 18 (9%) had platelet counts <50 × 10(9)/L. Nadir platelet counts for most affected neonates occurred at birth, although for some neonates, nadir platelet counts occurred up to 6 days postnatally. Intracranial hemorrhage was noted in 2 neonates (nadir platelet counts were 135 and 18 × 10(9)/L). There were no neonatal deaths. The majority of pregnant women with a history of ITP did not require treatment, and neonatal outcomes were comparable for mothers who received IVIg or corticosteroids for treatment of maternal ITP. © 2016 by The American Society of Hematology.

Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

PubMed

Zaccardi, F; Rocca, B; Rizzi, A; Ciminello, A; Teofili, L; Ghirlanda, G; De Stefano, V; Pitocco, D

2017-10-01

The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 10 9 /L (95%CI: 9.8-29.3; p < 0.001) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Allogeneic blood stem cell transplantation: considerations for donors.

PubMed

Anderlini, P; Körbling, M; Dale, D; Gratwohl, A; Schmitz, N; Stroncek, D; Howe, C; Leitman, S; Horowitz, M; Gluckman, E; Rowley, S; Przepiorka, D; Champlin, R

1997-08-01

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

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.

Sphingosine 1-phosphate release from platelets during clot formation: close correlation between platelet count and serum sphingosine 1-phosphate concentration

PubMed Central

2013-01-01

Background Sphingosine 1-phosphate (Sph-1-P), abundantly stored in platelets and released extracellularly upon activation, plays important roles as an extracellular mediator by interacting with specific cell surface receptors, especially in the area of vascular biology and immunology/hematology. Although the plasma Sph-1-P level is reportedly determined by red blood cells (RBCs), but not platelets, this may not be true in cases where the platelets have been substantially activated. Methods and results We measured the Sph-1-P and dihydrosphingosine 1-phosphate (DHSph-1-P) levels in serum samples (in which the platelets had been fully activated) from subjects with (n = 21) and without (n = 33) hematological disorders. We found that patients with essential thrombocythemia exhibited higher serum Sph-1-P and DHSph-1-P concentrations. The serum Sph-1-P concentration was closely correlated with the platelet count but was very weakly correlated with the RBC count. Similar results were obtained for DHSph-1-P. The serum Sph-1-P and DHSph-1-P levels were inversely correlated with the level of autotaxin (ATX), a lysophosphatidic acid-producing enzyme. A multiple regression analysis also revealed that the platelet count had the greatest explanatory impact on the serum Sph-1-P level. Conclusions Our present results showed close correlations between both the serum Sph-1-P and DHSph-1-P levels and the platelet count (but not the RBC count); these results suggest that high concentrations of these sphingoid base phosphates may be released from platelets and may mediate cross talk between platelet activation and the formation of atherosclerotic lesions. PMID:23418753

Carica papaya Leaves Juice Significantly Accelerates the Rate of Increase in Platelet Count among Patients with Dengue Fever and Dengue Haemorrhagic Fever

PubMed Central

Subenthiran, Soobitha; Choon, Tan Chwee; Cheong, Kee Chee; Thayan, Ravindran; Teck, Mok Boon; Muniandy, Prem Kumar; Afzan, Adlin; Abdullah, Noor Rain; Ismail, Zakiah

2013-01-01

The study was conducted to investigate the platelet increasing property of Carica papaya leaves juice (CPLJ) in patients with dengue fever (DF). An open labeled randomized controlled trial was carried out on 228 patients with DF and dengue haemorrhagic fever (DHF). Approximately half the patients received the juice, for 3 consecutive days while the others remained as controls and received the standard management. Their full blood count was monitored 8 hours for 48 hours. Gene expression studies were conducted on the ALOX 12 and PTAFR genes. The mean increase in platelet counts were compared in both groups using repeated measure ANCOVA. There was a significant increase in mean platelet count observed in the intervention group (P < 0.001) but not in the control group 40 hours since the first dose of CPLJ. Comparison of mean platelet count between intervention and control group showed that mean platelet count in intervention group was significantly higher than control group after 40 and 48 hours of admission (P < 0.01). The ALOX 12 (FC  =  15.00) and PTAFR (FC  =  13.42) genes were highly expressed among those on the juice. It was concluded that CPLJ does significantly increase the platelet count in patients with DF and DHF. PMID:23662145

Advances and controversies in neonatal ICU platelet transfusion practice.

PubMed

Christensen, Robert D

2008-01-01

Some of the platelet transfusions currently given to NICU patients are unnecessary and convey no benefits. Although ordered with good intentions, unnecessary platelet transfusions carry known and unknown risks. Identifying and eliminating any unnecessary platelet transfusions in NICUs would be a step toward better care, lower costs, and more careful preservation of blood component resources. A renewed interest in platelet transfusion studies is needed, if essential data is to be gathered to improve NICU platelet transfusion practice. Retrospective studies can be of value: for instance, seeking associations between bleeding events and platelet counts can suggest the possibility of cause and effect relationships. Such studies might identify approximate platelet count levels that convey high hemorrhagic risk and might help focus future prospective trials. Prospective indirect studies also can be of value, for instance, measuring the template bleeding time and the PFA-100 closure time as a function of platelet count and perhaps as a function of circulating platelet mass, and would provide new information with relevance to platelet transfusion benefits. Such studies might give a better awareness of how low the platelet count can fall before platelet plug formation is impaired. It seems inescapable, however, that new, multicentered, randomized, prospective studies are needed, where NICU patients are assigned different platelet transfusion triggers and then carefully tracked for bleeding events and long-term neurodevelopmental outcomes. Only that type of study is likely to generate the evidence base needed for widespread implementation of improvements in NICU platelet transfusion practice.

Equiosmolar Solutions of Hypertonic Saline and Mannitol Do Not Impair Blood Coagulation During Elective Intracranial Surgery.

PubMed

Hernández-Palazón, Joaquín; Fuentes-García, Diego; Doménech-Asensi, Paloma; Piqueras-Pérez, Claudio; Falcón-Araña, Luis; Burguillos-López, Sebastián

2017-01-01

The authors investigated the effect of equiosmolar, equivolemic solutions of 3% hypertonic saline (HS) and 20% mannitol on blood coagulation assessed by rotational thromboelastometry (ROTEM) and standard coagulation tests during elective craniotomy. In a prospective, randomized, double-blind trial, 40 patients undergoing elective craniotomy were randomized to receive 5 mL/kg of either 20% mannitol or 3% HS for intraoperative brain relaxation. Fibrinogen, activated partial thromboplastin time, prothrombin time, hemoglobin, hematocrit, and platelet count were simultaneously measured intraoperatively with ROTEM for EXTEM, INTEM, and FIBTEM analysis. ROTEM parameters were: clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and α-angle. No significant differences between groups were found in ROTEM variables CT, CFT, MCF, α-angle (EXTEM and INTEM), and MCF (FIBTEM) nor standard coagulation tests. ROTEM parameters did not show changes after administration of hyperosmolar solutions relating to basal values, except for an increase of CFT EXTEM (118±28 vs. 128±26 s) and decrease of CT INTEM (160±18 vs. 148±15 s) with values within normal range. Significant decreases from baseline levels were observed for hematocrit (-7%), platelet count (-10%), and fibrinogen (-13%) after HS infusion, and hematocrit (-9%), platelet count (-13%), and fibrinogen (-9%) after mannitol infusion, but remaining normal. The use of 5 mL/kg of equiosmolar solutions of 3% HS and 20% mannitol applied to reach a brain relaxation during elective craniotomy does not induce coagulation impairment as evidenced by ROTEM and standard coagulation tests.

Complete blood count reference values of cord blood in Taiwan and the influence of gender and delivery route on them.

PubMed

Chang, Yu-Hsun; Yang, Shang-Hsien; Wang, Tso-Fu; Lin, Teng-Yi; Yang, Kuo-Liang; Chen, Shu-Huey

2011-06-01

Cord blood banking has become more popular in recent years. Checking cord blood complete blood count (CBC) and white blood cell (WBC) differential counts (DCs) is essential before cryopreserving the cord blood units. Therefore, establishing the normal reference values of cord blood CBC and WBC DC is important in clinical practice and research. To obtain a large-scale population-based normal CBC and WBC DC reference values of healthy neonates' cord blood from a public cord blood bank and to investigate the influence of the gender and delivery route. From September 2001 to November 2006, the cord blood of healthy Taiwanese neonates with gestational age 36 weeks and more were collected by Tzu Chi Cord Blood Bank with written informed consents. All cord blood samples were analyzed by Sysmex XE2100 automated hematology analyzer (Sysmex Corporation, Kobe, Japan) to obtain the CBC. The WBC DC was calculated by manual method. We used Student's t test and Mann-Whitney U test for investigating the influences of gender and delivery route on the CBC and WBC DC reference values. The results were presented by mean±standard deviation or 2.5-97.5th percentiles. In the study period, totally 5602 cord blood samples were collected eligibly for analysis. The cord blood CBC and WBC DC normal reference values were calculated. The female neonates had significantly higher mean corpuscular volume, platelet count, and WBC count, but lower red blood cell (RBC) count, hemoglobin (Hb), hematocrit, and mean corpuscular Hb concentration values (p<0.001). Newborns through vaginal delivery had significantly higher RBC count, Hb, hematocrit, platelet count, and WBC count (p<0.001). The percentages of some different types WBC were significantly influenced by gender and delivery routes. Male babies had higher lymphocyte, monocyte, eosinophil, basophil, and nucleated RBC ratios than the female neonates. Newborns through cesarean section had significantly lower neutrophil, monocyte, and nucleated RBC ratios, but higher lymphocyte and eosinophil ratios, than newborns through vaginal delivery. We successfully obtained the normal CBC and WBC DC reference values of the cord blood in Taiwan. Gender and delivery routes were important confounding factors that influenced the cord blood CBC and WBC DC values. Copyright © 2011. Published by Elsevier B.V.

Thrombocytopenia following implantation of the stentless biological sorin freedom SOLO valve.

PubMed

Gersak, Borut; Gartner, Urska; Antonic, Miha

2011-07-01

Stentless biological valves have proven advantages in hemodynamic performance and left ventricular function compared to stented biological valves. Following a marked postoperative fall in the platelet count of patients after implantation of the Freedom SOLO valve, the study aim was to confirm clinical observations that this effect was more severe in patients receiving Freedom SOLO valves than in those receiving St. Jude Medical (SJM) mechanical aortic valves. Preoperative and postoperative platelet counts were compared in two groups of patients who underwent aortic valve replacement (AVR) without any concomitant procedures between January and December 2007. Patients received either a Freedom SOLO valve (n = 28) or a SJM mechanical valve (n = 41). Mean values of platelet counts were compared using three multiple linear regression models. Platelet counts were significantly lower in the Freedom SOLO group than in the SJM group from the first postoperative day (POD 1) up to POD 6 (p <0.001). In three patients of the Freedom SOLO group the platelet count fell below 30x10(9)/l, while the lowest level in the SJM group was 75x10(9)/l. Based on multiple linear regression models, the type of valve implanted had a statistically significant influence on postoperative platelet counts on POD 1, POD 3, and POD 5 (p <0.001). Whilst the reason for this phenomenon is unknown, the use of consistent monitoring should prevent severe falls in platelet count from becoming dangerous for the patient. Further studies are required to investigate the phenomenon since, despite a shorter cardiopulmonary bypass time, the fall in platelet count was more profound in the Freedom SOLO group.

One Year Follow-Up of Children and Adolescents With Chronic Immune Thrombocytopenic Purpura (ITP) Treated With Rituximab

PubMed Central

Mueller, Brigitta U.; Bennett, Carolyn M.; Feldman, Henry A.; Bussel, James B.; Abshire, Thomas C.; Moore, Theodore B.; Sawaf, Hadi; Loh, Mignon L.; Rogers, Zora R.; Glader, Bertil E.; McCarthy, Maggie C.; Mahoney, Donald H.; Olson, Thomas A.; Feig, Stephen A.; Lorenzana, Adonis N.; Mentzer, William C.; Buchanan, George R.; Neufeld, Ellis J.

2017-01-01

Background We previously showed in a prospective study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts over 50,000/mm3 within the first 12 weeks. These patients were followed for the next year. Methods Platelet counts were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. Results Eight of the 11 initial responders maintained a platelet count over 150,000/mm3 without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm3 without the need for further intervention. Conclusions Rituximab resulted in sustained efficacy with platelet counts of 50,000/mm3 or higher in 11 of 36 patients (31%). PMID:18937333

White blood cell and platelet count as adjuncts to standard clinical evaluation for risk assessment in patients at low probability of acute aortic syndrome.

PubMed

Morello, Fulvio; Cavalot, Giulia; Giachino, Francesca; Tizzani, Maria; Nazerian, Peiman; Carbone, Federica; Pivetta, Emanuele; Mengozzi, Giulio; Moiraghi, Corrado; Lupia, Enrico

2017-08-01

Pre-test probability assessment is key in the approach to suspected acute aortic syndromes (AASs). However, most patients with AAS-compatible symptoms are classified at low probability, warranting further evaluation for decision on aortic imaging. White blood cell count, platelet count and fibrinogen explore pathophysiological pathways mobilized in AASs and are routinely assayed in the workup of AASs. However, the diagnostic performance of these variables for AASs, alone and as a bundle, is unknown. We tested the hypothesis that white blood cell count, platelet count and/or fibrinogen at presentation may be applied as additional tools to standard clinical evaluation for pre-test risk assessment in patients at low probability of AAS. This was a retrospective observational study conducted on consecutive patients managed in our Emergency Department from 2009 to 2014 for suspected AAS. White blood cell count, platelet count and fibrinogen were assayed during evaluation in the Emergency Department. The final diagnosis was obtained by computed tomography angiography. The pre-test probability of AAS was defined according to guidelines. Of 1210 patients with suspected AAS, 1006 (83.1%) were classified at low probability, and 271 (22.4%) were diagnosed with AAS. Within patients at low probability, presence of at least one alteration among white blood cell count >9*10 3 /µl, platelet count <200*10 3 /µl and fibrinogen <350 mg/dl was associated with a sensitivity of 95.5% (89.7-98.5%) and a specificity of 18.3% (15.6-21.2%). In patients at low probability, white blood cell count >9*10 3 /µl and platelet count <200*10 3 /µl were found as independent predictors of AAS beyond established clinical risk markers. Within patients at low probability, the estimated risk of AAS based on the number of alterations amongst white blood cell count >9*10 3 /µl and platelet count <200*10 3 /µl was 2.7% (1.2-5.7%) with zero alterations, 11.3% (8.8-14.3%) with one alteration and 31.9% (24.8-40%) with two alterations ( p<0.001). In addition to standard clinical evaluation, white blood cell count and platelet count may be used in patients at low pre-test probability to fine-tune risk assessment of AAS.

The effect of molar pregnancies on platelet parameters.

PubMed

Soylu Karapınar, Oya; Benk Şilfeler, Dilek; Dolapçıoğlu, Kenan; Keskin Kurt, Raziye; Beyazıt, Ahmet

2016-10-01

The aim of this study was to compare platelet parameters between abortus groups with gestational trophoblastic disease (GTD) (molar pregnancy, invasive mole, choriocarcinoma, etc) and without disease according to pathological result. The study population consisted of patients with GTD (n = 53) and aborted patients without disease as a control group (n = 53) who were seen in our clinic between January 2010 and December 2013. In this retrospective study, age, gravidity, levels of haemoglobin, white blood cell count, platelets, platelet parameters (mean platelet volume (MPV), platelet distrubition width (PDW), platelet crit (PCT), which shows platelet functions were recorded. The pathological diagnosis of GTD was recorded. The mean platelet count, MPV, PDW and PCT levels were similar between the groups. There is no statistically significiant difference between types of GTN in these parameters according to pathological diagnosis. According to our study results, platelet count and levels of MPV, PDW ve PCT in GTD patients were similar to aborted patients without disease.

Increased circulating blood cell counts in combat-related PTSD: Associations with inflammation and PTSD severity.

PubMed

Lindqvist, Daniel; Mellon, Synthia H; Dhabhar, Firdaus S; Yehuda, Rachel; Grenon, S Marlene; Flory, Janine D; Bierer, Linda M; Abu-Amara, Duna; Coy, Michelle; Makotkine, Iouri; Reus, Victor I; Aschbacher, Kirstin; Bersani, F Saverio; Marmar, Charles R; Wolkowitz, Owen M

2017-12-01

Inflammation is reported in post-traumatic stress disorder (PTSD). Few studies have investigated circulating blood cells that may contribute to inflammation. We assessed circulating platelets, white blood cells (WBC) and red blood cells (RBC) in PTSD and assessed their relationship to inflammation and symptom severity. One-hundred and sixty-three male combat-exposed veterans (82 PTSD, 81 non-PTSD) had blood assessed for platelets, WBC, and RBC. Data were correlated with symptom severity and inflammation. All cell counts were significantly elevated in PTSD. There were small mediation effects of BMI and smoking on these relationships. After adjusting for these, the differences in WBC and RBC remained significant, while platelet count was at trend level. In all subjects, all of the cell counts correlated significantly with inflammation. Platelet count correlated with inflammation only in the PTSD subjects. Platelet count, but none of the other cell counts, was directly correlated with PTSD severity ratings in the PTSD group. Combat PTSD is associated with elevations in RBC, WBC, and platelets. Dysregulation of all three major lineages of hematopoietic cells in PTSD, as well as their significant correlation with inflammation, suggest clinical significance of these changes. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Basic characteristics of plasma rich in growth factors (PRGF): blood cell components and biological effects.

PubMed

Nishiyama, Kazuhiko; Okudera, Toshimitsu; Watanabe, Taisuke; Isobe, Kazushige; Suzuki, Masashi; Masuki, Hideo; Okudera, Hajime; Uematsu, Kohya; Nakata, Koh; Kawase, Tomoyuki

2016-11-01

Platelet-rich plasma (PRP) is widely used in regenerative medicine because of its high concentrations of various growth factors and platelets. However, the distribution of blood cell components has not been investigated in either PRP or other PRP derivatives. In this study, we focused on plasma rich in growth factors (PRGF), a PRP derivative, and analyzed the distributions of platelets and white blood cells (WBCs). Peripheral blood samples were collected from healthy volunteers ( N  = 14) and centrifuged to prepare PRGF and PRP. Blood cells were counted using an automated hematology analyzer. The effects of PRP and PRGF preparations on cell proliferation were determined using human periosteal cells. In the PRGF preparations, both red blood cells and WBCs were almost completely eliminated, and platelets were concentrated by 2.84-fold, whereas in the PRP preparations, both platelets and WBCs were similarly concentrated by 8.79- and 5.51-fold, respectively. Platelet counts in the PRGF preparations were positively correlated with platelet counts in the whole blood samples, while the platelet concentration rate was negatively correlated with red blood cell counts in the whole blood samples. In contrast, platelet counts and concentration rates in the PRP preparations were significantly influenced by WBC counts in whole blood samples. The PRP preparations, but not the PRGF preparations, significantly suppressed cell growth at higher doses in vitro. Therefore, these results suggest that PRGF preparations can clearly be distinguished from PRP preparations by both inclusion of WBCs and dose-dependent stimulation of periosteal cell proliferation in vitro.

Impact of Helicobacter pylori Eradication Therapy on Platelet Counts in Patients With Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Amiri, Mohamadreza

2016-01-01

This study was a before and after clinical evaluation of Helicobacter pylori eradication on platelet counts in a group of 23 patients with chronic Idiopathic (Autoimmune) thrombocytopenic purpura (CITP). H. pylori infection was identified in patients by a 13C-urea breath test and confirmed by an H. pylori stool antigen test. Eradication was conducted in patients testing positive. Infected (n = 10) and uninfected (n = 13) patient groups did not differ with respect to age, gender, history of previous splenectomy, treatment with anti-D, current treatment with corticosteroids, or initial platelet counts. H. pylori eradication was successful in eight infected CITP patients, with two patients not responsive to treatment. Compared to the uninfected group, patients in the infected group who responded to eradication therapy had significantly increased platelet counts after six months (56.2 ± 22.2 vs. 233 ± 85.6 ×103 million cells/L; P < 0.01), whereas platelet counts in the non-responding patients and uninfected group did not differ after this period of time. H. pylori eradication promotes significant platelet count improvement in patients with CITP. Thus, all patients with CITP should be tested and treated for H. pylori infections. PMID:26925898

Pseudothrombocytopenia or platelet clumping as a possible cause of low platelet count in patients with viral infection: a case series from single institution focusing on hepatitis A virus infection.

PubMed

Choe, W-H; Cho, Y-U; Chae, J-D; Kim, S-H

2013-02-01

Pseudothrombocytopenia (PTCP) is the phenomenon of ethylenediaminetetraacetic acid anticoagulant-activated platelet clumping, which results in artificially low platelet counts. Other investigators have reported a few cases of PTCP associated with viral infections. The objective of this study was to demonstrate the association of viral infection with PTCP. Medical records of patients with thrombocytopenia who were tested for peripheral blood smear examination between March 2009 and February 2011 were reviewed for platelet clumping and viral infection. Thrombocytopenic patients with viral infection had a higher frequency of platelet clumping than those with other diseases, which was statistically significant (13.8% vs. 6.5%, respectively: P = 0.003). Among the 18 cases where PTCP or platelet clumping was related to viral infection, hepatitis A virus infection (72.2%) was most common, followed by cytomegalovirus (11.1%) and influenza A H1N1 infections (5.6%). A third (33.3%) of the patients had platelet counts <100 × 10⁹/L. Pseudothrombocytopenia or platelet clumping should be considered in patients with acute viral infection, particularly if the platelet count is unexpectedly low, because failure to recognize PTCP may lead to unnecessary diagnostic tests and patient mismanagement. © 2012 Blackwell Publishing Ltd.

The use of regression analysis in determining reference intervals for low hematocrit and thrombocyte count in multiple electrode aggregometry and platelet function analyzer 100 testing of platelet function.

PubMed

Kuiper, Gerhardus J A J M; Houben, Rik; Wetzels, Rick J H; Verhezen, Paul W M; Oerle, Rene van; Ten Cate, Hugo; Henskens, Yvonne M C; Lancé, Marcus D

2017-11-01

Low platelet counts and hematocrit levels hinder whole blood point-of-care testing of platelet function. Thus far, no reference ranges for MEA (multiple electrode aggregometry) and PFA-100 (platelet function analyzer 100) devices exist for low ranges. Through dilution methods of volunteer whole blood, platelet function at low ranges of platelet count and hematocrit levels was assessed on MEA for four agonists and for PFA-100 in two cartridges. Using (multiple) regression analysis, 95% reference intervals were computed for these low ranges. Low platelet counts affected MEA in a positive correlation (all agonists showed r 2 ≥ 0.75) and PFA-100 in an inverse correlation (closure times were prolonged with lower platelet counts). Lowered hematocrit did not affect MEA testing, except for arachidonic acid activation (ASPI), which showed a weak positive correlation (r 2 = 0.14). Closure time on PFA-100 testing was inversely correlated with hematocrit for both cartridges. Regression analysis revealed different 95% reference intervals in comparison with originally established intervals for both MEA and PFA-100 in low platelet or hematocrit conditions. Multiple regression analysis of ASPI and both tests on the PFA-100 for combined low platelet and hematocrit conditions revealed that only PFA-100 testing should be adjusted for both thrombocytopenia and anemia. 95% reference intervals were calculated using multiple regression analysis. However, coefficients of determination of PFA-100 were poor, and some variance remained unexplained. Thus, in this pilot study using (multiple) regression analysis, we could establish reference intervals of platelet function in anemia and thrombocytopenia conditions on PFA-100 and in thrombocytopenia conditions on MEA.

Arsenic trioxide at conventional dosage does not aggravate hemorrhage in the first-line treatment of adult acute promyelocytic leukemia.

PubMed

Cui, Wen; Wang, Jin; Nie, Rui-Min; Zhao, Ling-Ling; Gao, Meng-Qing; Zhu, Hong-Ming; Chen, Li; Hu, Jiong; Li, Jun-Min; Shen, Zhi-Xiang; Wang, Zhen-Yi; Chen, Sai-Juan; Chen, Zhu; Wang, Kan-Kan; Xi, Xiao-Dong; Mi, Jian-Qing

2018-04-01

The arsenic trioxide (ATO) plus all-trans retinoic acid (ATRA) therapy has demonstrated a tremendous success in the first-line treatment of acute promyelocytic leukemia (APL). Actually, early death (ED) is currently thought as a major challenge in APL. ATO has been reported to inhibit platelet function in vitro, and whether it increases the ED rate by exacerbating the hemorrhagic symptoms remains to be investigated. Effects of ATO on platelet aggregation and adhesion were evaluated in vitro and in thirty-two complete remission (CR) and four newly diagnosed APL patients. Furthermore, concentrations of plasma total arsenic were monitored in APL patients via ICP-MS. The inhibition of platelet function, either aggregation or adhesion, did occur in vitro when the concentration of ATO reached 2 μmol/L. However, in CR APL patients receiving ATO with normal platelet count, the platelets responded normally when being activated and so did those in the newly diagnosed patients with thrombocytopenia. Our data further showed that the conventional dosage of ATO reached a plasma concentration substantially below the required concentration to inhibit platelets. In the first-line treatment of APL, the use of ATO is safe and effective and does not compromise the hemostatic potential that may eventually increase ED rate. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests.

PubMed

Ho, Kimberly K; Abrams-Ogg, Anthony C G; Wood, R Darren; O'Sullivan, M Lynne; Kirby, Gordon M; Blois, Shauna L

2015-05-01

The objectives of this study were to establish feline references intervals for 3 commercial whole blood platelet function test analyzer systems: Multiplate analyzer (MP; Roche Diagnostics International Ltd., Rotkreuz, Switzerland), Platelet Function Analyzer-100 (PF: Siemens Canada, Mississauga, Ontario, Canada), and Plateletworks Combo-25 kit (PW; Helena Laboratories, Beaumont, TX). Venipuncture was performed on 55 healthy sedated cats, and platelet aggregation in response to adenosine diphosphate (ADP), collagen (COL), and arachidonic acid (AA; MP only) was assessed using citrated blood. For the MP analyzer, median (95% confidence intervals [CIs]) area under curve (Units) for ADP, COL, and AA agonists were 87 (11-176), 81 (32-129), and 91 (59-129), respectively. For the PF analyzer, median (95% CIs) closure time, using COL-ADP cartridges, was 69 (46-89) sec. For the PW assay, median (95% CIs) percent aggregations for ADP and COL agonists were 71 (18-92) and 49 (9-96), respectively, using impedance hematology analyzer platelet counts, and 94 (25-98) and 68 (14-119), respectively, using flow cytometry hematology analyzer platelet counts. There were low correlations between the PF analyzer (COL-ADP cartridge) and MP analyzer (COL agonist; ρ = 0.11), and between the PF analyzer (COL-ADP cartridge) and PW assay (COL agonist using impedance platelet counts; ρ = 0.14). The PW assay percent aggregations using impedance and flow cytometric platelet counts were correlated for both ADP (ρ = 0.64) and COL (ρ = 0.64) agonists. Platelet function testing using these tests are feasible in cats, but 95% CIs are wide, so single results may be difficult to interpret. Platelet counting by impedance or flow cytometry may be used for the PW assay but are not interchangeable. © 2015 The Author(s).

Effects of sodium citrate and acid citrate dextrose solutions on cell counts and growth factor release from equine pure-platelet rich plasma and pure-platelet rich gel.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2015-03-14

There is a lack information on the effects of the most commonly used anticoagulants for equine platelet rich plasmas (PRPs) elaboration on cell counts and growth factor release from platelet rich gels (PRGs). The aims of this study were 1) to compare the effects of the anticoagulants sodium citrate (SC), acid citrate dextrose solution A (ACD-A) and ACD-B on platelet (PLT), leukocyte (WBC) and on some parameters associated to platelet activation including mean platelet volume (MPV) and platelet distribution width (PDW) between whole blood, pure PRP (P-PRP) and platelet-poor plasma (PPP); 2) to compare transforming growth factor beta 1 (TGF-β(1)) and platelet-derived growth factor isoform BB (PDGF-BB) concentrations in supernatants from pure PRG (P-PRG), platelet-poor gel (PPG), P-PRP lysate (positive control) and plasma (negative control); 3) to establish the possible correlations between all the studied cellular and molecular parameters. In all cases the three anticoagulants produced P-PRPs with significantly higher PLT counts compared with whole blood and PPP. The concentrations of WBCs were similar between P-PRP and whole blood, but significantly lower in PPP. The type of anticoagulant did not significantly affect the cell counts for each blood component. The anticoagulants also did not affect the MPV and PDW parameters. Independently of the anticoagulant used, all blood components presented significantly different concentrations of PDGF-BB and TGF-β(1). The highest growth factor (GF) concentrations were observed from P-PRP lysates, followed by PRG supernatants, PPP lysates, PPG supernatants and plasma. Significant correlations were observed between PLT and WBC counts (ρ = 0.80), PLT count and TGF-β(1) concentration (ρ = 0.85), PLT count and PDGF-BB concentration (ρ = 0.80) and PDGF-BB and TGF-β(1) concentrations (ρ = 0.75). The type of anticoagulant was not correlated with any of the variables evaluated. The anticoagulants did not significantly influence cell counts or GF concentrations in equine PRP. However, ACD-B was apparently the worst anticoagulant evaluated. It is necessary to perform additional research to determine the effect of anticoagulants on the kinetics of GF elution from P-PRG.

Immune Thrombocytopenic Purpura Detected with Oral Hemorrhage: a Case Report

PubMed Central

Sugiura, Tsutomu; Yamamoto, Kazuhiko; Murakami, Kazuhiro; Horita, Satoshi; Matsusue, Yumiko; Nakashima, Chie; Kirita, Tadaaki

2018-01-01

Immune thrombocytopenic purpura (ITP) is an immune-mediated acquired disease found in both adults and children. It is characterized by transient or persistent decreases in the platelet count. We report a case of ITP detected based on oral hemorrhagic symptoms. The patient was a 79-year-old female with no significant past medical history. She presented with sudden onset of gingival bleeding and hemorrhagic bullae on the buccal mucosa. Gingival bleeding was difficult to control. Laboratory tests revealed severe thrombocytopenia with a platelet count as low as 2000/μL. Under a provisional diagnosis of a hematological disorder, she was referred to a hematologist. A peripheral smear showed normal-sized platelets. A bone marrow examination revealed increased numbers of megakaryocytes without morphologic abnormalities. The patient was diagnosed with ITP and treated with a combination of pulsed steroid therapy and high-dose immunoglobulin therapy. However, her severe thrombocytopenia was refractory to these treatments. Then, a thrombopoietin receptor agonist was begun as a second-line treatment. Her platelets rapidly increased, and no bleeding complications were reported. Because oral symptoms can be one of the initial manifestations of ITP, dentists should be familiar with the clinical appearance of ITP, and attention must be paid to detect and diagnose unidentified cases. PMID:29854891

Thrombocytopenia in neonates with polycythemia: incidence, risk factors and clinical outcome.

PubMed

Vlug, Roos D; Lopriore, Enrico; Janssen, Marleen; Middeldorp, Johanna M; Rath, Mirjam E A; Smits-Wintjens, Vivianne E H J

2015-02-01

Polycythemia occurs in 1 to 5% of neonates and is associated with complications, including an increased risk of thrombocytopenia. To evaluate incidence, risk factors, management and outcome of thrombocytopenia in neonates with polycythemia. All neonates with polycythemia admitted to our neonatal intensive care unit between 2006 and 2013 were included in this retrospective study. We evaluated the incidence of thrombocytopenia (platelet count <150 × 10(9)/l) and severe thrombocytopenia (platelet count <50 × 10(9)/l) and the correlation between platelet counts and hematocrit values. The incidence of thrombocytopenia and severe thrombocytopenia was 51 (71/140) and 9% (13/140), respectively. Platelet count was negatively correlated with hematocrit (spearman correlation coefficient -0.233, p = 0.007). After multiple regression analysis, we found an independent association between thrombocytopenia and being small for gestational age (OR: 10.0; 95%; CI: 1.2-81.7; p = 0.031). Thrombocytopenia occurs in 51% of neonates with polycythemia and is independently associated with growth restriction. Increased hematocrit is associated with decreased platelet count.

Long-term exposure to ambient particulate matter (PM2.5) is associated with platelet counts in adults.

PubMed

Zhang, Zilong; Chan, Ta-Chien; Guo, Cui; Chang, Ly-Yun; Lin, Changqing; Chuang, Yuan Chieh; Jiang, Wun Kai; Ho, Kin Fai; Tam, Tony; Woo, Kam S; Lau, Alexis K H; Lao, Xiang Qian

2018-05-09

The prothrombotic effects of particulate matter (PM) may underlie the association of air pollution with increased risks of cardiovascular disease. This study aimed to investigate the association between long-term exposure to PM with an aerodynamic diameter ≤2.5 μm (PM 2.5 ) and platelet counts, a marker of coagulation profiles. The study participants were from a cohort consisting of 362,396 Taiwanese adults who participated in a standard medical examination program between 2001 and 2014. Platelet counts were measured through Complete Blood Count tests. A satellite-based spatio-temporal model was used to estimate 2-year average ambient PM 2.5 concentration at each participant's address. Mixed-effects linear regression models were used to investigate the association between PM 2.5 exposure and platelet counts. This analysis included 175,959 men with 396,248 observations and 186,437 women with 397,877 observations. Every 10-μg/m 3 increment in the 2-year average PM 2.5 was associated with increases of 0.42% (95% CI: 0.38%, 0.47%) and 0.49% (95% CI: 0.44%, 0.54%) in platelet counts in men and women, respectively. A series of sensitivity analyses, including an analysis in participants free of cardiometabolic disorders, confirmed the robustness of the observed associations. Baseline data analyses showed that every 10-μg/m 3 increment in PM 2.5 was associated with higher risk of 17% and 14% of having elevated platelet counts (≥90th percentile) in men and women, respectively. Long-term exposure to PM 2.5 appears to be associated with increased platelet counts, indicating potential adverse effects on blood coagulability. Copyright © 2018 Elsevier Ltd. All rights reserved.

Basic characteristics of plasma rich in growth factors (PRGF): blood cell components and biological effects

PubMed Central

Nishiyama, Kazuhiko; Okudera, Toshimitsu; Watanabe, Taisuke; Isobe, Kazushige; Suzuki, Masashi; Masuki, Hideo; Okudera, Hajime; Uematsu, Kohya; Nakata, Koh

2016-01-01

Abstract Platelet‐rich plasma (PRP) is widely used in regenerative medicine because of its high concentrations of various growth factors and platelets. However, the distribution of blood cell components has not been investigated in either PRP or other PRP derivatives. In this study, we focused on plasma rich in growth factors (PRGF), a PRP derivative, and analyzed the distributions of platelets and white blood cells (WBCs). Peripheral blood samples were collected from healthy volunteers (N = 14) and centrifuged to prepare PRGF and PRP. Blood cells were counted using an automated hematology analyzer. The effects of PRP and PRGF preparations on cell proliferation were determined using human periosteal cells. In the PRGF preparations, both red blood cells and WBCs were almost completely eliminated, and platelets were concentrated by 2.84‐fold, whereas in the PRP preparations, both platelets and WBCs were similarly concentrated by 8.79‐ and 5.51‐fold, respectively. Platelet counts in the PRGF preparations were positively correlated with platelet counts in the whole blood samples, while the platelet concentration rate was negatively correlated with red blood cell counts in the whole blood samples. In contrast, platelet counts and concentration rates in the PRP preparations were significantly influenced by WBC counts in whole blood samples. The PRP preparations, but not the PRGF preparations, significantly suppressed cell growth at higher doses in vitro. Therefore, these results suggest that PRGF preparations can clearly be distinguished from PRP preparations by both inclusion of WBCs and dose‐dependent stimulation of periosteal cell proliferation in vitro. PMID:29744155

Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia.

PubMed

Gadhwal, Ajeet Kumar; Ankit, B S; Chahar, Chitresh; Tantia, Pankaj; Sirohi, P; Agrawal, R P

2016-06-01

Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients. All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed. On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value < 0.01). On 4th and 5th day platelet count of study group (122.43±19.36 and 112.47±17.49 thousands respectively) was also significantly higher than the control group (88.75±21.65 and 102.59±19.35 thousands) (p value < 0.01). On 7th day platelet count of study group and control group were not significantly different (124.47±12.35 and 122.46±19.76 thousands respectively, p value 0.08). Average hospitalization period of study group v/s control group was 3.65±0.97 v/s 5.42±0.98 days (p value < 0.01). Average platelet transfusion requirement in study group was significantly less than control group (0.685 units per patient v/s 1.19 units per patient) (p value <0.01). It is concluded that Carica papaya leaf extract increases the platelet count in dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.

Adjusting MtDNA Quantification in Whole Blood for Peripheral Blood Platelet and Leukocyte Counts.

PubMed

Hurtado-Roca, Yamilee; Ledesma, Marta; Gonzalez-Lazaro, Monica; Moreno-Loshuertos, Raquel; Fernandez-Silva, Patricio; Enriquez, Jose Antonio; Laclaustra, Martin

2016-01-01

Alterations of mitochondrial DNA copy number (mtDNAcn) in the blood (mitochondrial to nuclear DNA ratio) appear associated with several systemic diseases, including primary mitochondrial disorders, carcinogenesis, and hematologic diseases. Measuring mtDNAcn in DNA extracted from whole blood (WB) instead of from peripheral blood mononuclear cells or buffy coat may yield different results due to mitochondrial DNA present in platelets. The aim of this work is to quantify the contribution of platelets to mtDNAcn in whole blood [mtDNAcn(WB)] and to propose a correction formula to estimate leukocytes' mtDNAcn [mtDNAcn(L)] from mtDNAcn(WB). Blood samples from 10 healthy adults were combined with platelet-enriched plasma and saline solution to produce artificial blood preparations. Aliquots of each sample were combined with five different platelet concentrations. In 46 of these blood preparations, mtDNAcn was measured by qPCR. MtDNAcn(WB) increased 1.07 (95%CI 0.86, 1.29; p<0.001) per 1000 platelets present in the preparation. We proved that leukocyte count should also be taken into account as mtDNAcn(WB) was inversely associated with leukocyte count; it increased 1.10 (95%CI 0.95, 1.25, p<0.001) per unit increase of the ratio between platelet and leukocyte counts. If hematological measurements are available, subtracting 1.10 the platelets/leukocyte ratio from mtDNAcn(WB) may serve as an estimation for mtDNAcn(L). Both platelet and leukocyte counts in the sample are important sources of variation if comparing mtDNAcn among groups of patients when mtDNAcn is measured in DNA extracted from whole blood. Not taking the platelet/leukocyte ratio into account in whole blood measurements, may lead to overestimation and misclassification if interpreted as leukocytes' mtDNAcn.

FlnA-null megakaryocytes prematurely release large and fragile platelets that circulate poorly

PubMed Central

Jurak Begonja, Antonija; Hoffmeister, Karin M.; Hartwig, John H.

2011-01-01

Filamin A (FlnA) is a large cytoplasmic protein that crosslinks actin filaments and anchors membrane receptors and signaling intermediates. FlnAloxP PF4-Cre mice that lack FlnA in the megakaryocyte (MK) lineage have a severe macrothrombocytopenia because of accelerated platelet clearance. Macrophage ablation by injection of clodronate-encapsulated liposomes increases blood platelet counts in FlnAloxP PF4-Cre mice and reveals the desintegration of FlnA-null platelets into microvesicles, a process that occurs spontaneously during storage. FlnAloxP PF4-Cre bone marrows and spleens have a 2.5- to 5-fold increase in MK numbers, indicating increased thrombopoiesis in vivo. Analysis of platelet production in vitro reveals that FlnA-null MKs prematurely convert their cytoplasm into large CD61+ platelet-sized particles, reminiscent of the large platelets observed in vivo. FlnA stabilizes the platelet von Willebrand factor receptor, as surface expression of von Willebrand factor receptor components is normal on FlnA-null MKs but decreased on FlnA-null platelets. Further, FlnA-null platelets contain multiple GPIbα degradation products and have increased expression of the ADAM17 and MMP9 metalloproteinases. Together, the findings indicate that FlnA-null MKs prematurely release large and fragile platelets that are removed rapidly from the circulation by macrophages. PMID:21652675

Potential Harm of Prophylactic Platelet Transfusion in Adult Dengue Patients.

PubMed

Lee, Tau-Hong; Wong, Joshua G X; Leo, Yee-Sin; Thein, Tun-Linn; Ng, Ee-Ling; Lee, Linda K; Lye, David C

2016-03-01

Thrombocytopenia is a hallmark of dengue infection, and bleeding is a dreaded complication of dengue fever. Prophylactic platelet transfusion has been used to prevent bleeding in the management of dengue fever, although the evidence for its benefit is lacking. In adult dengue patients with platelet count <20,000/mm3 without bleeding, we aimed to assess if prophylactic platelet transfusion was effective in reducing clinical bleeding and other outcomes. We conducted a retrospective non-randomised observational study of dengue patients with platelet count < 20,000/mm3 without bleeding (except petechiae) admitted to Tan Tock Seng Hospital from January 2005 to December 2008. Baseline characteristics and clinical outcomes were compared between the non-transfused vs. transfused groups. Outcomes studied were clinical bleeding, platelet increment, hospital length of stay, intensive care unit admission and death. Of the 788 patients included, 486 received prophylactic platelet transfusion. There was no significant difference in the presence of clinical bleeding in the two groups (18.2% in non-transfused group vs. 23.5% in transfused group; P = 0.08). Patients in the transfused group took a median of 1 day longer than the non-transfused group to increase their platelet count to 50,000/mm3 or more (3 days vs. 2 days, P <0.0001). The median duration of hospital stay in the non-transfused group was 5 days vs. 6 days in the transfused group (P< 0.0001). There was no significant difference in the proportion requiring ICU admission (non-transfused 0.66% vs. transfused 1.23%, P = 0.44) and death (non-transfused 0% vs. transfused 0.2%, P = 0.43). Platelet transfusion in absence of bleeding in adult dengue with platelet count <20,000/mm3 did not reduce bleeding or expedite platelet recovery. There was potential harm by slowing recovery of platelet count to >50,000/mm3 and increasing length of hospitalization.

Measurement of immature platelets with Abbott CD-Sapphire and Sysmex XE-5000 in haematology and oncology patients.

PubMed

Meintker, Lisa; Haimerl, Maria; Ringwald, Jürgen; Krause, Stefan W

2013-11-01

Measurement of immature platelets was introduced into routine diagnostics by Sysmex as immature platelet fraction (IPF) some years ago and recently by Abbott as reticulated platelet fraction (rPT). Here, we compare both methods. We evaluated the precision and agreement of these parameters between Sysmex XE-5000 and Abbott CD-Sapphire in three distinct thrombocytopaenic cohorts: 30 patients with beginning thrombocytopaenia and 64 patients with recovering platelets (PLT) after chemotherapy, 16 patients with immune thrombocytopaenia (ITP) or heparin-induced thrombocytopaenia type 2 (HIT) and 110 additional normal controls. Furthermore, we analysed, how IPF/rPT differed between these thrombocytopaenic cohorts and controls. Both analysers demonstrated acceptable overall precision (repeatability) of IPF/rPT with lower precision at low PLT counts. IPF/rPT artificially increased during storage of blood samples overnight. Inter-instrument comparison showed a moderate correlation (Pearson r²=0.38) and a systematic bias of 1.04 towards higher IPF-values with the XE-5000. IPF/rPT was highest in recovering thrombopoesis after chemotherapy and moderately increased in ITP/HIT. The normal range deduced from control samples was much narrower with CD-Sapphire (1.0%-3.8%, established here for the first time) in comparison to XE-5000 (0.8%-7.9%) leading to a smaller overlap of samples with increased PLT turnover and normal controls. IPF and rPT both give useful information on PLT turnover, although the two analysers only show a moderate inter-instrument correlation and have different reference ranges. A better separation of patient groups with high PLT turnover like ITP/HIT from normal controls is obtained by CD-Sapphire.

Platelet indices and netrophil to lymphocyte ratio in adults with acute appendicitis.

PubMed

Kostakis, I D; Machairas, N; Damaskos, C; Doula, C; Tsaparas, P; Charalampoudis, P; Spartalis, E; Sotiropoulos, G C; Kouraklis, G

2016-03-01

A study was performed in adults with acute appendicitis and matched controls to assess the utility of the platelet indices and neutrophil to lymphocyte ratio, as a diagnostic adjunct. Data were retrospectively collected from a complete blood count test of 155 adult patients (72 men and 83 women) with histologically proven acute appendicitis upon admission, and of 50 healthy adults (20 men and 30 women). The parameters for white blood cells and platelets were compared between the two groups, and for each gender separately. A higher white blood cell count, neutrophil count, neutrophil percentage, neutrophil to lymphocyte ratio and lower lymphocyte percentage was reported in patients with acute appendicitis than that in the healthy controls, with high areas under the curve (AUC), sensitivities, specifi cities, positive predictive values (PPVs) and moderate negative predictive values (NPVs). The lymphocyte count was lower in patients than it was in the healthy controls. The platletcrit was lower in the female patients than that in the female controls, whereas a difference was not detected in the male participants. Differences were not detected with regard to platelet count, mean platelet volume and platelet distribution width for both genders. The neutrophil to lymphocyte ratio increases and lymphocyte percentage decreases in acute appendicitis, and can be used as an additional diagnostic marker. Plateletcrit, and therefore total platelet mass, is reduced in women with acute appendicitis, indicating the involvement of platelets in its pathophysiology. However, it is neither a reliable predictor or excluder of the disease.

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.

C-reactive protein, platelets, and patent ductus arteriosus.

PubMed

Meinarde, Leonardo; Hillman, Macarena; Rizzotti, Alina; Basquiera, Ana Lisa; Tabares, Aldo; Cuestas, Eduardo

2016-12-01

The association between inflammation, platelets, and patent ductus arteriosus (PDA) has not been studied so far. The purpose of this study was to evaluate whether C-reactive protein (CRP) is related to low platelet count and PDA. This was a retrospective study of 88 infants with a birth weight ≤1500 g and a gestational age ≤30 weeks. Platelet count, CRP, and an echocardiogram were assessed in all infants. The subjects were matched by sex, gestational age, and birth weight. Differences were compared using the χ 2 , t-test, or Mann-Whitney U-test, as appropriate. Significant variables were entered into a logistic regression model. The association between CRP and platelets was evaluated by correlation and regression analysis. Platelet count (167 000 vs. 213 000 µl -1 , p = 0.015) was lower and the CRP (0.45 vs. 0.20 mg/dl, p = 0.002) was higher, and the platelet count correlated inversely with CRP (r = -0.145, p = 0.049) in the infants with vs. without PDA. Only CRP was independently associated with PDA in a logistic regression model (OR 64.1, 95% confidence interval 1.4-2941, p = 0.033).

The clinical significance of platelet counts in the first 24 hours after severe injury.

PubMed

Stansbury, Lynn G; Hess, Aaron S; Thompson, Kwaku; Kramer, Betsy; Scalea, Thomas M; Hess, John R

2013-04-01

Admission platelet (PLT) counts are known to be associated with all-cause mortality for seriously injured patients admitted to a trauma center. The course of subsequent PLT counts, their implications, and the effects of PLT therapy are less well known. Trauma center patients who were directly admitted from the scene of injury, received 1 or more units of uncrossmatched red blood cells in the first hour of care, survived for at least 15 minutes, and had a PLT count measured in the first hour were analyzed for the association of their admission and subsequent PLT counts in the first 24 hours with injury severity and hemorrhagic and central nervous system (CNS) causes of in-hospital mortality. Over an 8.25-year period, 1292 of 45,849 direct trauma admissions met entry criteria. Admission PLT counts averaged 228×10(9) ±90×10(9) /L and decreased by 104×10(9) /L by the second hour and 1×10(9) /L each hour thereafter. The admission count was not related to time to admission. Each 1-point increase in the injury severity score was associated with a 1×10(9) /L decrease in the PLT count at all times in the first 24 hours of care. Admission PLT counts were strongly associated with hemorrhagic and CNS injury mortality and subsequent PLT counts. Effects of PLT therapy could not be ascertained. Admission PLT counts in critically injured trauma patients are usually normal, decreasing after admission. Low PLT counts at admission and during the course of trauma care are strongly associated with mortality. © 2012 American Association of Blood Banks.

Analytical variability of estimated platelet counts on canine blood smears.

PubMed

Paltrinieri, Saverio; Paciletti, Veronica; Zambarbieri, Jari

2018-06-04

The analytical variability of estimated platelet counts in dogs has not been reported. The purpose of this study was to assess the magnitude of analytical imprecision of platelet estimates and the possible impact of this imprecision on clinical decisions. Three independent observers counted the number of platelets in 3 different areas (LE = lateral edge; CM = central monolayer; FE = feathered edge) of 30 canine blood smears with different instrumental platelet counts. The coefficient of variation (CV) for each observer was calculated in different areas of each smear (intra-observer variability), among different regions of each smear (inter-area variability), and among different observers in each area (inter-observer variability). The influence of these variabilities on the classification of platelet estimates as adequate, increased, or decreased was also assessed. The CVs recorded in the different areas by each observer ranged from 8% to 88% and were negatively correlated (P < .001, r = -.65) with the mean number of platelets per field. The mean platelet number was significantly lower in the FE and significantly higher in the CM compared with the LE, but the magnitude of this difference varied with the operators. The concordance among operators regarding platelet estimates was fair (k = 0.36) to substantial (k = 0.71) depending on the area. The overall inter-area concordance was moderate (k = 0.59). Platelet estimates suffer from high variability that could lead to patient misclassification. Therefore, guidelines to standardize the platelet estimate are needed. © 2018 American Society for Veterinary Clinical Pathology.

Rapid Evaluation of Platelet Function With T2 Magnetic Resonance

PubMed Central

Cuker, Adam; Husseinzadeh, Holleh; Lebedeva, Tatiana; Marturano, Joseph E.; Massefski, Walter; Lowery, Thomas J.; Lambert, Michele P.; Abrams, Charles S.; Weisel, John W.

2016-01-01

Objectives: The clinical diagnosis of qualitative platelet disorders (QPDs) based on light transmission aggregometry (LTA) requires significant blood volume, time, and expertise, all of which can be barriers to utilization in some populations and settings. Our objective was to develop a more rapid assay of platelet function by measuring platelet-mediated clot contraction in small volumes (35 µL) of whole blood using T2 magnetic resonance (T2MR). Methods: We established normal ranges for platelet-mediated clot contraction using T2MR, used these ranges to study patients with known platelet dysfunction, and then evaluated agreement between T2MR and LTA with arachidonic acid, adenosine diphosphate, epinephrine, and thrombin receptor activator peptide. Results: Blood from 21 healthy donors was studied. T2MR showed 100% agreement with LTA with each of the four agonists and their cognate inhibitors tested. T2MR successfully detected abnormalities in each of seven patients with known QPDs, with the exception of one patient with a novel mutation leading to Hermansky-Pudlak syndrome. T2MR appeared to detect platelet function at similar or lower platelet counts than LTA. Conclusions: T2MR may provide a clinically useful approach to diagnose QPDs using small volumes of whole blood, while also providing new insight into platelet biology not evident using plasma-based platelet aggregation tests. PMID:28028118

The association of platelets with failed patent ductus arteriosus closure after a primary course of indomethacin or ibuprofen: a systematic review and meta-analysis.

PubMed

Mitra, Souvik; Chan, Anthony K; Paes, Bosco A

2017-01-01

To conduct a meta-analysis of the association of platelet counts and pharmacotherapeutic failure in preterms with a patent ductus arteriosus (PDA). MEDLINE, Embase, Science Citation Index, abstracts and conference proceedings were searched, and principal authors contacted. Included studies reported indomethacin or ibuprofen use for PDA closure, compared a group which failed treatment versus a group which did not and reported the association between platelet counts and indomethacin or ibuprofen failure. Two reviewers independently screened results and assessed methodological quality using the Newcastle-Ottawa Scale. Results are expressed as mean difference in platelet counts and summary odds ratios (OR) using a random effects model. 1105 relevant studies were identified; eight involving 1087 preterms were included. Platelet counts were significantly lower in infants who failed pharmacotherapy (Meandifference:-30.88 × 10 9 /L; 95% CI:-45.69 × 10 9 ,-16.07 × 10 9 /L; I2 = 24%; p heterogeneity  =   0.24). Similar results were obtained based on either pharmacotherapeutic agent. Treatment failure was also significantly associated with pre-treatment thrombocytopenia (summary OR:1.75; 95% CI:1.23-2.49, I2 = 36%, p heterogeneity  =   0.20). Platelet counts are significantly lower in preterms who fail primary treatment for PDA. Pre-treatment thrombocytopenia is associated with higher odds of failure. Further cohort studies reporting platelet counts in prostaglandin inhibitor failure are needed for meta-analyses to firmly establish or refute a stronger association.

Does platelet mass influence the effectiveness of ibuprofen treatment for patent ductus arteriosus in preterm infants?

PubMed

Akar, Selahattin; Karadag, Nilgun; Gokmen Yildirim, Tulin; Toptan, Handan Hakyemez; Dincer, Emre; Tuten, Abdulhamit; Yavuz, Taner; Topcuoglu, Sevilay; Karatepe, Hande Ozgun; Ozalkaya, Elif; Karatekin, Guner; Ovali, Fahri

2016-12-01

The aim of this study is to evaluate whether the platelet mass in the first 24 h of life is effective on closure of patent ductus arteriosus (PDA) or not. Preterm infants with a gestational age of < 32 weeks, hospitalized at a tertiary neonatal intensive care unit (NICU) and requiring medical treatment (intravenous or oral ibuprofen) for hemodinamically significant PDA (hsPDA) were enrolled in this study. The patients were divided into two groups after first course of pharmacologic treatment according to closure of PDA (Group 1: PDA closure, Group 2: PDA without closure). Groups were compared in terms of demographics findings, morbidities, platelet measurements like counts, mean platelet volume (MPV) and platelet mass (platelet count × mean platelet volume). The study included 77 preterm newborns in Group 1, and 30 preterms in Group 2. There were no differences in birth weight, gestational age, gender and maternal risk factors between the study groups. The mean platelet count in the first postnatal blood count was in Group 1: 211.3 ± 89.2 × 10(3)/mm(3) and in Group 2: 216.5 ± 26 × 10(3)/mm(3), respectively (p = 0.783). The mean platelet volumes (MPV) were similar in both groups (p = 0.535). No statistically significant difference between platelet mass values was detected (Group 1: 1811 ± 884 fl/nl, Group 2: 1868 ± 717 fl/nl) (p = 0.753). Our data suggest that platelet count, MPV and platelet mass did not affect the closure of hsPDA with ibuprofen.

Effects of immunosuppressive agents on the hemostatic system in normal dogs.

PubMed

Thomason, John M; Archer, Todd M; Wills, Robert W; Mackin, Andrew J

2018-05-10

In dogs, the effects of immunosuppressive medications on hemostasis are not well known. The objective was to determine the effects of immunosuppressive medications on primary and secondary hemostasis. Our hypothesis was that cyclosporine and prednisone would increase markers of hypercoagulability and thromboxane synthesis, while azathioprine, mycophenolate mofetil, and leflunomide would have minimal effects on hemostasis. Eight healthy dogs. A randomized, cross-over study used aggregometry, the PFA-100 platelet function analyzer, viscoelastometry, platelet count, and prothrombin and activated partial thromboplastin times to evaluate hemostasis during the administration of prednisone, azathioprine, cyclosporine, mycophenolate mofetil, and leflunomide for 1 week each at standard oral doses. Urine 11-dehydro-thromboxane-B 2 (11-dTXB 2 ) and 6-keto-prostaglandin-F 1α (6-keto-PGF 1α ) concentrations, normalized to urine creatinine concentration, were measured. The aggregometry amplitude decreased from 51 ± 21 to 27 ± 14 (P = .002) during leflunomide treatment (ADP activation), but there were no differences in amplitude (P = .240) for any medications when platelets were activated with collagen. For all medications, there were no significant differences in viscoelastometry indices (ACT, P = .666; ClotRate, P = .340; and platelet function, P = .411) and platelet count (P = .552). Compared with pretreatment values, urinary 11-dTXB 2 -to-creatinine ratio increased (P = .001) after drug administration (from 3.7 ± 0.6 to 5.6 ± 1.1). Cyclosporine was associated with an increase (P < .001) in the 6-keto-PGF 1α -to-creatinine ratio (from 10.3 ± 4.6 to 22.1 ± 5.3). Most immunosuppressive drugs do not enhance platelet function or coagulation in healthy dogs, suggesting that these medications might not predispose hypercoagulable dogs to thromboembolism. The results of our study need to be correlated with the clinical outcomes of hypercoagulable dogs. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Portal hypertension and hypersplenism in extrahepatic portal venous obstruction: Are they related?

PubMed

Kilambi, Ragini; Singh, Anand Narayan; Madhusudhan, Kumble Seetharama; Pal, Sujoy; Saxena, Renu; Shalimar; Dash, Nihar Ranjan; Sahni, Peush

2018-06-23

Portal hypertension (PHT) due to extrahepatic portal venous obstruction (EHPVO) is common in developing countries. Hypersplenism is a near-constant feature of EHPVO, but its significance, unlike in cirrhotics, is unknown. We aimed to study the relationship between hypersplenism and the severity of PHT in patients with EHPVO. This prospective study was done at a tertiary care center from January 2014 to August 2015. All patients with EHPVO who underwent a splenectomy and a shunt or devascularization were included. Data regarding clinical profile, preoperative parameters, and intraoperative details were recorded. The correlation was studied between hypersplenism and the intraoperatively measured portal pressures and markers of PHT. Of the 40 patients studied (mean [SD] age 22.4 [8.4] years), hematological hypersplenism was present in 39 (97.5%). The mean (SD) hemoglobin, total leukocyte counts (TLC), and platelet counts were 9.9 (2.4) g/dL, 2971 (1239) cells/mm 3 , and 66,400 (32047) cells/mm 3 , respectively. The mean (SD) sonographic spleen volume (SV), splenic weight, and intraoperative portal pressure were 1084.7 (553.9) cm 3 , 1088.7 (454.7) g, and 35.6 (5.1) mmHg, respectively. The TLC and platelet counts correlated inversely with the portal pressure. Additionally, the platelet counts correlated negatively with eradicated variceal status, SV, and weight; hemoglobin with SV and weight; and TLC with SV. Multivariate analysis showed the platelet counts were an independent predictor of portal pressures and platelet counts ≤ 53,500 cells/mm 3 indicated significantly high portal pressures. The platelet counts showed a significant inverse correlation with portal pressures in patients with EHPVO and may be used as surrogate markers of PHT. A platelet count ≤ 53,500 cells/mm 3 is predictive of significantly high pressures.

New oral anticoagulants in the treatment of heparin-induced thrombocytopenia.

PubMed

Sharifi, Mohsen; Bay, Curt; Vajo, Zoltan; Freeman, Wilbur; Sharifi, Mirali; Schwartz, Frederic

2015-04-01

Heparin induced thrombocytopenia (HIT) is a potentially catastrophic syndrome with a high incidence of vascular thrombosis. There are little data on the efficacy of new oral anticoagulants (NOAC) in this setting. This study reports on the outcome of patients with HIT, treated with NOAC. We retrospectively identified 22 patients with HIT who were treated by our group with a combination of NOAC and a short course of argatroban. These patients were evaluated in a prospective fashion for development of outcomes at a mean follow up of 19±3 months. There were a total of 5 deep and 2 superficial vein thromboses diagnosed at index hospitalization. No patient developed arterial thrombosis. All patients tolerated NOAC and their platelet count normalized before discharge. At 19 months of follow-up, 6 patients had died of non-thrombotic causes. There was no bleeding, limb loss or recurrent venous thromboembolism in any patient. In patients with HIT, a short course of parenteral treatment with argatroban followed by administration of a NOAC is highly safe and effective in prevention of thrombosis and normalization of platelet count. Development of HIT however, portends a poor prognosis independent of vascular thrombosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chicken pox associated thrombocytopenia in adults.

PubMed

Ali, Nadir; Anwar, Masood; Majeed, Irfan; Tariq, Waheed Uz Zaman

2006-04-01

To determine the frequency and magnitude of thrombocytopenia associated with chicken pox in adults. Observational descriptive study. Combined Military Hospital, Attock, from July 2003 to June 2004. All patients of age 15 years and above with history of fever, followed by appearance of the typical vesicular chicken pox rash, were inducted after informed consent. Two milliliters of whole blood was collected on day 1 of admission, and blood counts were performed. Patients were admitted and given 800 mg oral acyclovir, 5 times/day, for 7 days, in addition to symptomatic treatment. Patients were followed till 8 weeks. A total of 410 patients of chicken pox were received, out of which 270 were included. Age of patients ranged between 15 and 40 years with median age of 21 years. Platelet count on the day of admission ranged between 29 x 10(9)/L to 513 x 10(9)/L, mean platelet count 178 x 10(9)/L. Platelet count < 150 x 10(9)/L was detected in 80/270 (30%) patients. Platelet count in thrombocytopenia patients was from 29 x 10(9)/L to 149 x 10(9)/L with mean 121 x 10(9)/L. Thrombocytopenia recovered within 02 weeks in 78/80 (97%) patients. In 2 patients, thrombocytopenia recovered in 3 weeks. None of the patients developed purpuric spots, ecchymosis or bleeding manifestations. Thrombocytopenia in chicken pox is a common entity. Platelet count remains above 25 x 10(9) /L, which is usually not associated with bleeding manifestations. None of the patients in this series developed purpura. No specific pattern of total leukocyte counts was predictive of the progression or regression in platelet count.

Platelet counts on admission affect coronary flow, myocardial perfusion and left ventricular systolic function after primary percutaneous coronary intervention.

PubMed

Sharif, Dawod; Abu-Salem, Mira; Sharif-Rasslan, Amal; Rosenschein, Uri

2017-10-01

Patients with acute ST-elevation myocardial infarction (STEMI) and increased platelet count treated by fibrinolysis have worse outcomes. The aim of this study was to test the hypothesis that platelet blood count at admission in patients with acute STEMI treated by primary percutaneous coronary intervention affects coronary flow, myocardial perfusion and recovery of left ventricular systolic function. A total of 174 patients presenting with acute anterior STEMI and treated with primary percutaneous coronary intervention were included and divided into subgroups of admission platelet blood count of <200 K, 200-300 K, 300-400 K and >400 K. Evaluation of coronary artery flow and myocardial blush grade was performed according to the TIMI criteria. Electrocardiographic ST elevation resolution post-primary percutaneous coronary intervention was evaluated. Doppler echocardiographic evaluation of left anterior descending coronary artery velocities early and late after primary percutaneous coronary intervention and assessment of left ventricular ejection fraction and wall motion score index (WMSI) of left ventricular and left anterior descending coronary artery territory were performed. Post-primary percutaneous coronary intervention TIMI, myocardial blush grade and ST elevation resolution were similar in all groups. Patients with platelet counts <200 K had higher peak diastolic left anterior descending coronary artery velocity both early and late after primary percutaneous coronary intervention, and higher prevalence of left anterior descending coronary artery velocity deceleration time exceeding 600 ms, (45.5% vs. 40%, P<0.05). Patients with platelet counts >400 K presented with worse left ventricular ejection fraction, left ventricular WMSI and left anterior descending coronary artery WMSI, and before discharge this subgroup had worse left ventricular WMSI and left anterior descending coronary artery WMSI, P<0.01. Patients with anterior STEMI treated by primary percutaneous coronary intervention with lower admission platelet count had higher left anterior descending coronary artery diastolic velocities, better myocardial perfusion with more patients having left anterior descending coronary artery-descending coronary artery velocity deceleration time >600 ms. Patients with higher platelet counts had lower left ventricular systolic function both at admission and before discharge.

Influence of a cyclic combination chemotherapeutic protocol on primary haemostasis in dogs suffering from malignant lymphoma.

PubMed

Eberle, N; Mischke, R

2010-03-01

The purpose of this study was to examine the influence of cyclic combination chemotherapy on primary haemostasis in dogs with malignant lymphoma. Seventeen dogs receiving cytostatic treatment for high-grade lymphoma were included in the study. The dogs were treated with a Madison-Wisconsin derived protocol, which included asparaginase, vincristine, doxorubicin and prednisolone. At different time points during the first 4 weeks of induction, platelet count, capillary bleeding time, analysis of the platelet function using the platelet function analyser PFA-100, and platelet aggregation by the Born-method were measured. The most obvious changes were found for median values of the platelet count, which increased significantly from 210,000/microL before induction to 349,000/microL during the second week of induction (P=0.0010). Median platelet count subsequently decreased by the fourth week of treatment (Friedman-test: P<0.0001). None of the parameters of platelet function (capillary bleeding time, automatic platelet function analysis, aggregation maximum) showed significant changes with time (P>0.05, Friedman-test). The results did not suggest that significant platelet dysfunction was induced by the chemotherapeutic protocol used in the study. 2009 Elsevier Ltd. All rights reserved.

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.

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.

Efficacy of and risk of bleeding during pegylated interferon plus ribavirin treatment in HIV/HCV-coinfected patients with pretreatment thrombocytopenia.

PubMed

Mira, J A; Neukam, K; López-Cortés, L F; Rivero-Juárez, A; Téllez, F; Girón-González, J A; de los Santos-Gil, I; Ojeda-Burgos, G; Merino, D; Ríos-Villegas, M J; Collado, A; Torres-Cornejo, A; Macías, J; Rivero, A; Pérez-Pérez, M; Pineda, J A

2015-09-01

The aim of this study was to assess the efficacy of and the risk of major bleeding during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients according to the pretreatment platelet count. Two hundred and seventy-four HCV/HIV-coinfected, previously naïve individuals with compensated cirrhosis enrolled in one Spanish prospective cohort who received peg-IFN/RBV were included in this study. The frequency of severe bleeding and sustained virological response (SVR) rate were compared between patients with a pretreatment platelet count ≤70,000/mm(3) and >70,000/mm(3), respectively. Sixty-one (22 %) patients had a baseline platelet count ≤70,000/mm(3). The median (Q1-Q3) pretreatment platelet count was 58,000 (49,000-65,000) cells/mm(3) in the platelet ≤70,000 group and 129,000 (102,500-166,000) cells/mm(3) in the platelet >70,000 group (p < 0.0001). Seventeen (28 %) subjects of the platelet ≤70,000 group and 71 (33 %) patients of the platelet >70,000 group achieved SVR (p = 0.4). Only 2 (3.2 %) patients in the platelet ≤70,000 group developed a severe hemorrhagic event, specifically esophageal variceal bleeding. The efficacy of therapy with peg-IFN/RBV in HIV/HCV-coinfected patients with low pretreatment platelet counts is comparable to that found in the overall subset of subjects with compensated cirrhosis. The frequency of severe hemorrhagic events related with this therapy is low in this population.

Oscillatory haematopoiesis in adults with sickle cell disease treated with hydroxycarbamide.

PubMed

Baird, John H; Minniti, Caterina P; Lee, Jung-Min; Tian, Xin; Wu, Colin; Jackson, Mary; Alam, Shoaib; Taylor, James G; Kato, Gregory J

2015-03-01

Hydroxycarbamide therapy has been associated with significant oscillations in peripheral blood counts from myeloid, lymphoid and erythroid lineages in patients with polycythaemia vera and chronic myeloid leukaemia. We retrospectively evaluated serial blood counts over an 8-year period from 44 adult patients with sickle cell disease receiving hydroxycarbamide. Platelet counts, leucocyte counts, haemoglobin values and reticulocyte counts, apportioned by hydroxycarbamide status, were analysed using a Lomb-Scargle periodogram algorithm. Significant periodicities were present in one or more counts in 38 patients receiving hydroxycarbamide for a mean duration of 4·81 years. Platelet and leucocyte counts oscillated in 56·8% and 52·3% of patients, respectively. These oscillations generally became detectable within days of initiating therapy. During hydroxycarbamide therapy, the predominant periods of oscillation were 27 ± 1 d for platelet counts and 15 ± 1 d for leucocyte counts. Despite an absolute decrease in leucocyte and platelet counts during hydroxycarbamide treatment, the amplitudes between nadirs and zeniths remained similar regardless of exposure. Our observations appear consistent with previously proposed models of cyclic haematopoiesis, and document that hydroxycarbamide-induced oscillations in blood counts are innocuous phenomena not limited to myeloproliferative disorders as described previously. We speculate the known cell cycle inhibitory properties of hydroxycarbamide may accentuate otherwise latent constitutive oscillatory haematopoiesis. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

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.

Evidence for Radiation-Induced Disseminated Intravascular Coagulation as a Major Cause of Radiation-Induced Death in Ferrets

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

Krigsfeld, Gabriel S.; Savage, Alexandria R.; Billings, Paul C.

Purpose: The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Methods and Materials: Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. Results: The lethal dose of radiation to 50% of the population (LD{sub 50}) of the ferrets was established at ∼1.5 Gy, with 100%more » mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Conclusions: Data presented here provide evidence that death at the LD{sub 50} in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals.« less

Evidence for radiation-induced disseminated intravascular coagulation as a major cause of radiation-induced death in ferrets.

PubMed

Krigsfeld, Gabriel S; Savage, Alexandria R; Billings, Paul C; Lin, Liyong; Kennedy, Ann R

2014-03-15

The studies reported here were performed as part of a program in space radiation biology in which proton radiation like that present in solar particle events, as well as conventional gamma radiation, were being evaluated in terms of the ability to affect hemostasis. Ferrets were exposed to 0 to 2 Gy of whole-body proton or gamma radiation and monitored for 30 days. Blood was analyzed for blood cell counts, platelet clumping, thromboelastometry, and fibrin clot formation. The lethal dose of radiation to 50% of the population (LD50) of the ferrets was established at ∼ 1.5 Gy, with 100% mortality at 2 Gy. Hypocoagulability was present as early as day 7 postirradiation, with animals unable to generate a stable clot and exhibiting signs of platelet aggregation, thrombocytopenia, and fibrin clots in blood vessels of organs. Platelet counts were at normal levels during the early time points postirradiation when coagulopathies were present and becoming progressively more severe; platelet counts were greatly reduced at the time of the white blood cell nadir of 13 days. Data presented here provide evidence that death at the LD50 in ferrets is most likely due to disseminated intravascular coagulation (DIC). These data question the current hypothesis that death at relatively low doses of radiation is due solely to the cell-killing effects of hematopoietic cells. The recognition that radiation-induced DIC is the most likely mechanism of death in ferrets raises the question of whether DIC is a contributing mechanism to radiation-induced death at relatively low doses in large mammals. Copyright © 2014 Elsevier Inc. All rights reserved.

Changes in haematology measurements with the Sysmex XT-2000iV during storage of feline blood sampled in EDTA or EDTA plus CTAD.

PubMed

Granat, Fanny; Geffré, Anne; Bourgès-Abella, Nathalie; Braun, Jean-Pierre; Trumel, Catherine

2013-06-01

In veterinary medicine a complete blood cell count (CBC) cannot always be performed within 24 h as usually recommended, particularly for specimens shipped to a reference laboratory. This raises the question of the stability of the variables, especially in ethylenediamine tetra-acetic acid (EDTA) feline blood specimens, known to be prone to in vitro platelet aggregation. Citrate, theophylline, adenosine and dipyridamole (CTAD) has been reported to limit platelet aggregation in feline blood specimens. The aim of this study was to measure the stability of the haematological variables and the platelet aggregation score in EDTA and EDTA plus CTAD (EDCT) feline blood specimens during 48 h of storage at room temperature. Forty-six feline EDTA and EDCT blood specimens were analysed with a Sysmex XT-2000iV analyser, and the platelet count and score of platelet aggregation were estimated immediately and after 24 and 48 h of storage. A significant increase in mean corpuscular volume, haematocrit, reticulocyte and eosinophil counts, and a significant decrease in mean corpuscular haemoglobin concentration and monocyte count were observed. Haemoglobin, mean corpuscular haemoglobin, and red blood cell, white blood cell, neutrophil and lymphocyte counts remained stable. Changes in reticulocyte indexes with time (low fluorescence ratio, medium fluorescence ratio, high fluorescence ratio and immature reticulocyte fraction) were not significant. Changes were generally more pronounced in EDTA than in EDCT. Platelet aggregation decreased markedly in initially highly aggregated EDTA specimens, and increased slightly in initially non- or mildly-aggregated EDTA or EDCT specimens. Platelet counts increased and decreased, or remained stable, respectively. CTAD can reduce storage-induced changes of the haematological variables in feline samples, thus improving the reliability of a CBC and limiting clinical misinterpretations.

Correlation of platelet count and acute ST-elevation myocardial infarction.

PubMed

Paul, G K; Sen, B; Rahman, M Z; Ali, M; Rahman, M M; Rokonuzzaman, S M

2014-10-01

The study was conducted in the Department of cardiology, NICVD Dhaka during the period January 2006 to December 2007 to assess the impact of platelet on ST-elevation myocardial infarction (STEMI). To perform this prospective study 200 patients with STEMI within 72 hours of chest pain of both sexes were randomly selected and were evaluated by clinical history, physical examination and with the help of ECG, Echocardiography and others cardiac risk factors analysis. Heparin therapy before admission, previously documented thrombocytopenia (<140,000/cmm), history of previous or current haemostatic disorder, renal impairment (Creatinine >1.6mg/dl) and history of PCI & CABG were excluded in this study. Patient of Platelet count (PC) ≤200000/cubic millimeter (cmm) in Group I and patient of Group II, platelet counts were PC >200000/cmm. Follow up period was 3 days to 7 days after hospital admission. Primary outcome heart failure (any Killip class) was significantly more in Group II than Group I (40.0% vs. 23.0%; p=0.009). Though the incidence of Killip class I and cardiogenic shock were not significant between these two groups but Killip class II (18.0% vs. 8.0%; p=0.036) and Killip class III (15.0% vs. 6.0%; p=0.037) heart failure were significantly more among the patient with higher platelet counts. In-hospital mortality, one of the primary outcomes of this study, was significantly higher in Group II (13.0%) than Group I (5.0 %) and p value was 0.048. Re-infarction was more in patient with higher platelet counts group (Group II) than patients with lower platelet count (Group I) but statistically was not significant (16.0% vs.11.0%; p=0.300).

Evaluation of Plasma Platelet Microparticles in Thrombotic Thrombocytopenic Purpura.

PubMed

Tahmasbi, Leila; Karimi, Mehran; Kafiabadi, Sedigheh Amini; Nikougoftar, Mahin; Haghpanah, Sezaneh; Ranjbaran, Reza; Moghadam, Mohamad

2017-01-01

Platelet microparticles (PMPs) have a procoagulant activity about 50-100 times greater than active platelets due to high expression of negatively charged phospholipids on their surfaces. In this study, we evaluated microparticle immunophenotyping and also plasma PMPs level in patients with Thrombotic Thrombocytopenic Purpura (TTP) in Southern Iran. We had two study groups: 15 TTP patients and 15 healthy control group and PMPs from platelet concentrate (PC) at the 5 th day of storage. Microparticles were prepared in two steps, by low and high centrifugation followed by size confirmation via 'Dynamic Light Scattering (DLS)' Zetasizer. Immunophenotyping of PMPs was done via flow cytometry, using a FACS Calibur flow cytometer (BD, USA). PMPs counts were obtained using Partec-cyflow and Polysciences Microbeads (1 micron in diameter). Results were analyzed using FlowJo 7.6 (Treestar, USA) and Partec FlowMax software. Our results showed that the majority of microparticles in TTP patients and normal individuals were PMPs and also demonstrated that the plasma PMPs level in TTP patients was higher than the normal control group ( P -value<0.001). It seems that elevated PMPs level in TTP patients could be related to thrombotic events. Nevertheless, more studies are needed to confirm these results. © 2017 by the Association of Clinical Scientists, Inc.

The effect of variation in donor platelet function on transfusion outcome: a semirandomized controlled trial.

PubMed

Kelly, Anne M; Garner, Stephen F; Foukaneli, Theodora; Godec, Thomas R; Herbert, Nina; Kahan, Brennan C; Deary, Alison; Bakrania, Lekha; Llewelyn, Charlotte; Ouwehand, Willem H; Williamson, Lorna M; Cardigan, Rebecca A

2017-07-13

The effect of variation in platelet function in platelet donors on patient outcome following platelet transfusion is unknown. This trial assessed the hypothesis that platelets collected from donors with highly responsive platelets to agonists in vitro assessed by flow cytometry (high-responder donors) are cleared more quickly from the circulation than those from low-responder donors, resulting in lower platelet count increments following transfusion. This parallel group, semirandomized double-blinded trial was conducted in a single center in the United Kingdom. Eligible patients were those 16 or older with thrombocytopenia secondary to bone marrow failure, requiring prophylactic platelet transfusion. Patients were randomly assigned to receive a platelet donation from a high- or low-responder donor when both were available, or when only 1 type of platelet was available, patients received that. Participants, investigators, and those assessing outcomes were masked to group assignment. The primary end point was the platelet count increment 10 to 90 minutes following transfusion. Analysis was by intention to treat. Fifty-one patients were assigned to receive platelets from low-responder donors, and 49 from high-responder donors (47 of which were randomized and 53 nonrandomized). There was no significant difference in platelet count increment 10 to 90 minutes following transfusion in patients receiving platelets from high-responder (mean, 21.0 × 10 9 /L; 95% confidence interval [CI], 4.9-37.2) or low-responder (mean, 23.3 × 10 9 /L; 95% CI, 7.8-38.9) donors (mean difference, 2.3; 95% CI, -1.1 to 5.7; P = .18). These results support the current policy of not selecting platelet donors on the basis of platelet function for prophylactic platelet transfusion. © 2017 by The American Society of Hematology.

Stability of selected hematology variables in canine blood kept at room temperature in EDTA for 24 and 48 hours.

PubMed

Médaille, C; Briend-Marchal, A; Braun, J P

2006-03-01

Most hematologic analyses are performed within a short time of blood sampling, but samples collected at the end of a week may have to be stored for up to 2 days. The stability of hematologic constituents is poorly documented. The objective of this study was to compare the results of RBC, WBC and platelet counts, hemoglobin (Hgb) concentration, and MCV before and after storage of canine blood at room temperature for 24 and 48 hours. One hundred fifty-two K3-EDTA canine blood specimens from 2 veterinary hospitals were analyzed within 4 hours of collection, then 24 and 48 hours later with a Coulter T540 hematology analyzer. Results were compared by Passing-Bablock agreement, difference plots, and according to their classification as normal or abnormal based on reference intervals. RBC count and Hgb concentration were stable for the duration of the study. Differences in WBC and platelet counts varied with the specimen, independently of the initial value. MCV increased consistently over the 2 days. However, only a few results were misclassified. Whole blood specimens stored for up to 2 days at room temperature are suitable for cell counts and Hgb measurement. However, potential variations have to be known to avoid misinterpretations, especially near the decision limits.

Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease.

PubMed

Borges, Álvaro H; Lundgren, Jens D; Ridolfo, Annalisa; Katlama, Christine; Antunes, Francisco; Grzeszczuk, Anna; Blaxhult, Anders; Mitsura, Viktar M; Doroana, Manuela; Battegay, Manuel; Gargalianos, Panagiotis; Mocroft, Amanda

2014-11-13

To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events. Prospective cohort. EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events. There were 62 898 person-years of follow-up (PYFU) among 12 279 patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS-defining events [adjusted incidence rate ratio (aIRR) 1.42, 95% CI 1.07-1.86], when compared to those with platelet counts 101-200 × 10/l, whereas the incidence of non-AIDS-defining events was more than two-fold higher (aIRR 2.66, 95% CI 2.17-3.26). Among non-AIDS-defining events, the adjusted incidence of cancer (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm thrombocytopenia and lagging platelets by 1 year prior to clinical events. Patients with thrombocytopenia had increased incidence of AIDS-defining and non-AIDS-defining events, but the association with the latter, in particular cancer, was stronger. Future studies should investigate whether the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease.

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis.

PubMed

Padmanabhan, Anand; Jones, Curtis G; Bougie, Daniel W; Curtis, Brian R; McFarland, Janice G; Wang, Demin; Aster, Richard H

2015-01-01

Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain "delayed HIT" seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. © 2015 by The American Society of Hematology.

Heparin-independent, PF4-dependent binding of HIT antibodies to platelets: implications for HIT pathogenesis

PubMed Central

Jones, Curtis G.; Bougie, Daniel W.; Curtis, Brian R.; McFarland, Janice G.; Wang, Demin; Aster, Richard H.

2015-01-01

Antibodies specific for platelet factor 4 (PF4)/heparin complexes are the hallmark of heparin-induced thrombocytopenia and thrombosis (HIT), but many antibody-positive patients have normal platelet counts. The basis for this is not fully understood, but it is believed that antibodies testing positive in the serotonin release assay (SRA) are the most likely to cause disease. We addressed this issue by characterizing PF4-dependent binding of HIT antibodies to intact platelets and found that most antibodies testing positive in the SRA, but none of those testing negative, bind to and activate platelets when PF4 is present without any requirement for heparin (P < .0001). Binding of SRA-positive antibodies to platelets was inhibited by chondroitinase ABC digestion (P < .05) and by the addition of chondroitin-4-sulfate (CS) or heparin in excess quantities. The findings suggest that although all HIT antibodies recognize PF4 in a complex with heparin, only a subset of these antibodies recognize more subtle epitopes induced in PF4 when it binds to CS, the major platelet glycosaminoglycan. Antibodies having this property could explain “delayed HIT” seen in some individuals after discontinuation of heparin and the high risk for thrombosis that persists for weeks in patients recovered from HIT. PMID:25342714

Effect of carprofen on hemostatic variables in dogs.

PubMed

Hickford, F H; Barr, S C; Erb, H N

2001-10-01

To evaluate the effect of carprofen on hemostatic variables in clinically normal dogs. 12 clinically normal Labrador Retrievers. 10 dogs (6 females, 4 males) received carprofen (2.2 mg/kg of body weight, PO, q 12 h) for 5 days. Two dogs (untreated control group; 1 female, 1 male) did not receive carprofen. Hemostatic variables (platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen, platelet aggregation, and bleeding time) were assessed for all dogs prior to treatment, on day 5 of treatment, and 2 and 7 days after discontinuation of the drug (days 7 and 12). Serum biochemical variables and Hct were assessed prior to treatment and on days 5 and 12. In dogs receiving carprofen, platelet aggregation was significantly decreased, and onset of aggregation was significantly delayed on days 5, 7, and 12, compared with pretreatment values. Activated partial thromboplastin time was significantly increased on days 5, 7, and 12 over pretreatment values in treated dogs, but values remained within reference ranges. Significant differences were not detected in buccal mucosal bleeding time, other serum biochemical and hemostatic variables, or Hct, compared with pretreatment values and the internal control group. Administration of carprofen for 5 days causes minor but not clinically important alterations in hemostatic and serum biochemical variables in clinically normal Labrador Retrievers. Carprofen is commonly used to treat osteoarthritis and chronic pain in dogs, but prior to this study, its effect on platelet aggregation and hemostatic variables was unknown.

The role of transforming growth factor-beta in PEG-rHuMGDF-induced reversible myelofibrosis in rats.

PubMed

Yanagida, M; Ide, Y; Imai, A; Toriyama, M; Aoki, T; Harada, K; Izumi, H; Uzumaki, H; Kusaka, M; Tokiwa, T

1997-12-01

Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.

Origin-Specific Adhesive Interactions of Mesenchymal Stem Cells with Platelets Influence Their Behavior After Infusion.

PubMed

Sheriff, Lozan; Alanazi, Asma; Ward, Lewis S C; Ward, Carl; Munir, Hafsa; Rayes, Julie; Alassiri, Mohammed; Watson, Steve P; Newsome, Phil N; Rainger, G E; Kalia, Neena; Frampton, Jon; McGettrick, Helen M; Nash, Gerard B

2018-02-28

We investigated the adhesive behavior of mesenchymal stem cells (MSC) in blood, which might influence their fate when infused as therapy. Isolated human bone marrow MSC (BMMSC) or umbilical cord MSC (UCMSC) adhered efficiently from flow to the matrix proteins, collagen, or fibronectin, but did not adhere to endothelial selectins. However, when suspended in blood, BMMSC no longer adhered to collagen, while UCMSC adhered along with many aggregated platelets. Neither MSC adhered to fibronectin from flowing blood, although the fibronectin surface did become coated with a platelet monolayer. UCMSC induced platelet aggregation in platelet rich plasma, and caused a marked drop in platelet count when mixed with whole human or mouse blood in vitro, or when infused into mice. In contrast, BMMSC did not activate platelets or induce changes in platelet count. Interestingly, isolated UCMSC and BMMSC both adhered to predeposited platelets. The differences in behavior in blood were attributable to expression of podoplanin (an activating ligand for the platelet receptor CLEC-2), which was detected on UCMSC, but not BMMSC. Thus, platelets were activated when bound to UCMSC, but not BMMSC. Platelet aggregation by UCMSC was inhibited by recombinant soluble CLEC-2, and UCMSC did not cause a reduction in platelet count when mixed with blood from mice deficient in CLEC-2. We predict that both MSC would carry platelets in the blood, but their interaction with vascular endothelium would depend on podoplanin-induced activation of the bound platelets. Such interactions with platelets might target MSC to damaged tissue, but could also be thrombotic. Stem Cells 2018. © 2018 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Comparison of Immature Platelet Count to Established Predictors of Platelet Reactivity During Thienopyridine Therapy.

PubMed

Stratz, Christian; Bömicke, Timo; Younas, Iris; Kittel, Anja; Amann, Michael; Valina, Christian M; Nührenberg, Thomas; Trenk, Dietmar; Neumann, Franz-Josef; Hochholzer, Willibald

2016-07-19

Previous data suggest that reticulated platelets significantly affect antiplatelet response to thienopyridines. It is unknown whether parameters describing reticulated platelets can predict antiplatelet response to thienopyridines. The authors sought to determine the extent to which parameters describing reticulated platelets can predict antiplatelet response to thienopyridine loading compared with established predictors. This study randomized 300 patients undergoing elective coronary stenting to loading with clopidogrel 600 mg, prasugrel 30 mg, or prasugrel 60 mg. Adenosine diphosphate (ADP)-induced platelet reactivity was assessed by impedance aggregometry before loading (intrinsic platelet reactivity) and again on day 1 after loading. Multiple parameters of reticulated platelets were assessed by automated whole blood flow cytometry: absolute immature platelet count (IPC), immature platelet fraction, and highly fluorescent immature platelet fraction. Each parameter of reticulated platelets correlated significantly with ADP-induced platelet reactivity (p < 0.01 for all 3 parameters). In a multivariable model including all 3 parameters, only IPC remained a significant predictor of platelet reactivity (p < 0.001). In models adjusting each of the 3 parameters for known predictors of on-treatment platelet reactivity including cytochrome P450 2C19 (CYP2C19) polymorphisms, age, body mass index, diabetes, and intrinsic platelet reactivity, only IPC prevailed as an independent predictor (p = 0.001). In this model, IPC was the strongest predictor of on-treatment platelet reactivity followed by intrinsic platelet reactivity. IPC is the strongest independent platelet count-derived predictor of antiplatelet response to thienopyridine treatment. Given its easy availability, together with its even stronger association with on-treatment platelet reactivity compared with known predictors, including the CYP2C19*2 polymorphism, IPC may become the preferred predictor of antiplatelet response to thienopyridine treatment. (Impact of Extent of Clopidogrel-Induced Platelet Inhibition During Elective Stent Implantation on Clinical Event Rate-Advanced Loading Strategies [ExcelsiorLOAD]; DRKS00006102). Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Validity of Particle-Counting Method Using Laser-Light Scattering for Detecting Platelet Aggregation in Diabetic Patients

NASA Astrophysics Data System (ADS)

Nakadate, Hiromichi; Sekizuka, Eiichi; Minamitani, Haruyuki

We aimed to study the validity of a new analytical approach that reflected the phase from platelet activation to the formation of small platelet aggregates. We hoped that this new approach would enable us to use the particle-counting method with laser-light scattering to measure platelet aggregation in healthy controls and in diabetic patients without complications. We measured agonist-induced platelet aggregation for 10 min. Agonist was added to the platelet-rich plasma 1 min after measurement started. We compared the total scattered light intensity from small aggregates over a 10-min period (established analytical approach) and that over a 2-min period from 1 to 3 min after measurement started (new analytical approach). Consequently platelet aggregation in diabetics with HbA1c ≥ 6.5% was significantly greater than in healthy controls by both analytical approaches. However, platelet aggregation in diabetics with HbA1c < 6.5%, i.e. patients in the early stages of diabetes, was significantly greater than in healthy controls only by the new analytical approach, not by the established analytical approach. These results suggest that platelet aggregation as detected by the particle-counting method using laser-light scattering could be applied in clinical examinations by our new analytical approach.

Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.

PubMed

Bedet, Alexandre; Razazi, Keyvan; Boissier, Florence; Surenaud, Mathieu; Hue, Sophie; Giraudier, Stéphane; Brun-Buisson, Christian; Mekontso Dessap, Armand

2018-06-01

Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. Prospective, observational study. Thrombocytopenia was defined as an absolute platelet count <100 G/L or a 50% relative decrease in platelet count during the first week of septic shock. Plasma concentrations of 27 endogenous mediators involved in sepsis and platelet pathophysiology were assessed at day-1 using a multi-analyte Milliplex human cytokine kit. Patients with underlying diseases at risk of thrombocytopenia (hematological malignancies, chemotherapy, cirrhosis, and chronic heart failure) were excluded. Thrombocytopenia occurred in 33 (55%) of 60 patients assessed. Patients with thrombocytopenia were more prone to present with extrapulmonary infections and bacteremia. Disseminated intravascular coagulation was frequent (81%) in these patients. Unbiased hierarchical clustering identified five different clusters of sepsis mediators, including one with markers of platelet activation (e.g., thrombospondin-1) positively associated with platelet count, one with markers of inflammation (e.g., tumor necrosis factor alpha and heat shock protein 70), and endothelial dysfunction (e.g., intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) negatively associated with platelet count, and another involving growth factors of thrombopoiesis (e.g., thrombopoietin), also negatively associated with platelet count. Surrogates of hemodilution (e.g., hypoprotidemia and higher fluid balance) were also associated with thrombocytopenia. Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.

[Effects of lysine clonixinate on platelet function. Comparison with other non-steroidal anti-inflammatory agents].

PubMed

Kramer, E H; Sassetti, B; Kaminker, A J; De Los Santos, A R; Martí, M L; Di Girolamo, G

2001-01-01

One of the mechanisms of action of non steroid antiinflammatory drugs (NSAIDs) consists of inhibition of prostaglandin synthesis. This explains many of the pharmacological effects and adverse events observed in medical practice. Administration of NSAIDs to patients with hemostatic disorders or perioperative conditions entails the risk of bleeding due to inhibition of platelet function. This study deals with platelet changes induced by lysine clonixinate vs diclofenac, ibuprofen and aspirin in classical tests such as platelet count, platelet factor 3 (PF3) activity and platelet aggregation with various inductors and more recent procedures such as P-selectin measurement by flow cytometry. Unlike control drugs, lysine clonixinate did not induce changes in platelet count or function when administered to healthy volunteers at the commonly used therapeutic doses.

Bone marrow vascular endothelial growth factor level per platelet count might be a significant predictor for the treatment outcomes of patients with diffuse large B-cell lymphomas.

PubMed

Kim, Jung Sun; Gang, Ga Won; Lee, Se Ryun; Sung, Hwa Jung; Park, Young; Kim, Dae Sik; Choi, Chul Won; Kim, Byung Soo

2015-10-01

Developing a parameter to predict bone marrow invasion by non-Hodgkin's lymphoma is an important unmet medical need for treatment decisions. This study aimed to confirm the validity of the hypothesis that bone marrow plasma vascular endothelial growth factor level might be correlated with the risk of bone marrow involvement and the prognosis of patients with diffuse large B-cell non-Hodgkin's lymphoma. Forty-nine diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone regimen were enrolled. Vascular endothelial growth factor level was measured with enzyme-linked immunosorbent assay. The validity of bone marrow plasma vascular endothelial growth factor level and bone marrow vascular endothelial growth factor level per platelet count for predicting treatment response and survival after initial rituximab, cyclophosphamide, daunorubicin, vincristine and prednisolone combined chemotherapy was assessed. Bone marrow plasma vascular endothelial growth factor level per platelet count was significantly associated with old age (≥ 65 years), poor performance score (≥ 2), high International prognosis index (≥ 3) and bone marrow invasion. The patients with high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) showed a significantly lower complete response rate than the others. On Kaplan-Meier survival curves, the patients with high bone marrow plasma vascular endothelial growth factor levels (≥ 655 pg/ml) or high bone marrow plasma vascular endothelial growth factor level per platelet count (≥ 3.01) demonstrated a significantly shorter overall survival and progression-free survival than the others. In the patients without bone marrow involvement, bone marrow plasma vascular endothelial growth factor level per platelet count had a significant relationship with overall survival and progression-free survival. Multivariate analysis revealed that the patients without BM invasion showing high level of bone marrow plasma vascular endothelial growth factor per platelet count had significantly shorter progression-free survival and overall survival. Bone marrow plasma vascular endothelial growth factor level per platelet count might be associated with bone marrow invasion by diffuse large B-cell lymphoma and is correlated with clinical outcomes after treatment. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Anti-aggregatory effect of boswellic acid in high-fat fed rats: involvement of redox and inflammatory cascades

PubMed Central

2016-01-01

Introduction A high-fat diet is one of the main dietary factors promoting platelet aggregation. The present study was conducted to elucidate the involvement of boswellic acid (BA) on the platelet hyperaggregability in HFD-fed rats. As platelet hyperaggregability in HFD rats is closely linked to inflammation and enhanced free radical production, the present study was extended to evaluate the anti-inflammatory and anti-oxidative effect of BA on HFD-promoted platelet aggregation. Material and methods Rats were assigned to normal, HFD-fed, aspirin-treated (30 mg/kg), and BA-treated (250 and 500 mg/kg) groups. Results Boswellic acid administration in a high dose was effective in attenuating the severity of hyperlipidemia and platelet aggregation, indicated by lower collagen/epinephrine-induced platelet aggregation, as evidenced by the significant increase (p < 0.05) in the circulating platelet count and reduction in the number of thrombi in the lungs. Moreover, it attenuated the oxidative stress and the intensity of inflammatory mediators associated with platelet hyperaggregability, as evidenced by the inhibitory effects on interlukin-1β, COX-2 and tumor necrosis factor-α, indicating that the antiplatelet activity of BA is likely a consequence of controlling oxidative stress and inflammation. Conclusions The present data suggest that BA shows a promising anti-aggregatory effect by attenuating the enhanced hyperlipidemia, oxidative stress and inflammation associated with HFD. PMID:27904529

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.

Prognostic Impact of Neutrophil/Lymphocyte Ratio, Platelet Count, CRP, and Albumin Levels in Metastatic Colorectal Cancer Patients Treated with FOLFIRI-Bevacizumab.

PubMed

Artaç, Mehmet; Uysal, Mükremin; Karaağaç, Mustafa; Korkmaz, Levent; Er, Zehra; Güler, Tunç; Börüban, Melih Cem; Bozcuk, Hakan

2017-06-01

Metastatic colorectal cancer (mCRC) is a lethal disease and fluorouracil-leucovorin-irinotecan (FOLFIRI) plus bevacizumab (bev) is a standard approach. Hence, there is a strong need for identifying new prognostic factors to show the efficacy of FOLFIRI-bev. This is a retrospective study including patients (n = 90) with mCRC from two centers in Turkey. Neutrophil/lymphocyte (N/L) ratio, platelet count, albumin, and C-reactive protein (CRP) were recorded before FOLFIRI-bev therapy. The efficacy of these factors on progression-free survival (PFS) was analyzed with Kaplan Meier and Cox regression analysis. And the cutoff value of N/L ratio was analyzed with ROC analysis. The median age was 56 years (range 21-80). Forty-seven percent of patients with N/L ratio >2.5 showed progressive disease versus 43 % in patients with N/L ratio <2.5 (p = 0.025). The median PFS was 8.1 months for the patients with N/L ratio >2.5 versus 13.5 months for the patients with N/L ratio <2.5 (p = 0.025). At univariate Cox regression analysis, high baseline neutrophil count, LDH, N/L ratio, and CRP were all significantly associated with poor prognosis. At multivariate Cox regression analysis, CRP was confirmed to be a better independent prognostic factor. CRP variable was divided into above the upper limit of normal (ULN) and normal value. The median PFSs of the patients with normal and above ULN were 11.3 versus 5.8 months, respectively (p = 0.022). CRP and N/L ratio are potential predictors for advanced mCRC treated with FOLFIRI-bev.

[Influence of raising oxygen content on function of platelet concentrate during preservation].

PubMed

Zhan, Tong; Xiao, Jian-Yu; Tao, Jing; Miao, Xi-Feng; Liu, Yan-Cun; Tang, Rong-Cai

2006-08-01

To explore the influence of raising oxygen (dissolved oxygen) content on function of platelet concentrate, the platelet concentrate was prepared by a CS-3000 plus blood cell separator. Experiments were divided into 2 groups: test group and control group. After raising oxygen content in platelet plasma under sterile operation, the platelet samples of two groups were preserved in oscillator with horizontal oscillation at 22 +/- 2 degrees C. The platelet count, platelet aggregation rate, lactic acid content and CD62p expression level of platelet were detected on 0, 1, 2, 3, 4, 5 days of platelet preservation. The results showed that the platelet count and platelet aggregation rate decreased with prolongation of preserved time, while the lactic acid content and CD62p expression level of platelet increased gradually. Compared with control group, there were significant differences in aggregation rate of platelet preserved for 2-3 days, and in CD62p expression level of platelet preserved for 1-3 days, while significant difference was found in lactic acid content of platelet preserved for 1-3 days. It is concluded that raising content of oxygen in platelet plasma can provide more oxygen to compensate oxygen supply deficiency for platelet metabolism and improve the efficiency of platelet oxygenic metabolism and the quality of platelet during preservation.

Immune Thrombocytopenic Purpura Presenting as Unprovoked Gingival Hemorrhage: a Case Report

PubMed Central

Bal, Mehmet V; Koyuncuoglu, Cenker Z; Saygun, Işıl

2014-01-01

Immune thrombocytopenic purpura is an autoimmune disease characterized by auto-antibody induced platelet destruction and reduced platelet production, leading to low blood platelet count. In this case report, the clinical diagnose of a patient with immune thrombocytopenic purpura and spontaneous gingival hemorrhage by a dentist is presented. The patient did not have any systemic disease that would cause any spontaneous hemorrhage. The patient was referred to a hematologist urgently and her thrombocyte number was found to be 2000/μL. Other test results were in normal range and immune thrombocytopenic purpura diagnose was verified. Then hematological treatment was performed and patient’s health improved without further problems. Hematologic diseases like immune thrombocytopenic purpura, in some cases may appear firstly in the oral cavity and dentists must be conscious of unexplained gingival hemorrhage. In addition, the dental treatment of immune thrombocytopenic purpura patients must be planned with a hematologist. PMID:25317211

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.

Determinants of the Thrombogenic Potential of Multiwalled Carbon Nanotubes

PubMed Central

Burke, Andrew; Singh, Ravi; Carroll, David L.; Owen, John; Kock, Nancy D.; D’Agostino, Ralph; Torti, Frank M.; Torti, Suzy V.

2011-01-01

Multiwalled carbon nanotubes (MWCNTs) are cylindrical tubes of graphitic carbon with unique physical and electrical properties. MWCNTs are being explored for a variety of diagnostic and therapeutic applications. Successful biomedical application of MWCNTs will require compatibility with normal circulatory components, including constituents of the hemostatic cascades. In this manuscript, we compare the thrombotic activity of MWCNTs in vitro and in vivo. We also assess the influence of functionalization of MWCNTs on thrombotic activity. In vitro, MWCNT activate the intrinsic pathway of coagulation as measured by activated partial thromboplastin time (aPTT) assays. Functionalization by amidation or carboxylation enhances this procoagulant activity. Mechanistic studies demonstrate that MWCNTs enhance propagation of the intrinsic pathway via a non-classical mechanism strongly dependent on factor IX. MWCNTs preferentially associate with factor IXa and may provide a platform for its activation. In addition to their effects on the coagulation cascade, MWCNTs activate platelets in vitro, with amidated MWCNTs exhibiting greater platelet activation than carboxylated or pristine MWCNTs. However, contrasting trends are obtained in vivo, where functionalization tends to diminish rather than enhance pro-coagulant activity. Thus, following systemic injection of MWCNTs in mice, pristine MWCNTs decreased platelet counts, increased vWF, and increased D-dimers. In contrast, carboxylated MWCNTS exhibited little procoagulant tendency in vivo, eliciting only a mild and transient decrease in platelets. Amidated MWCNTs elicited no statistically significant change in platelet count. Further, neither carboxylated nor amidated MWCNTs increased vWF or D-dimers in mouse plasma. We conclude that the pro-coagulant tendencies of MWCNTs observed in vitro are not necessarily recapitulated in vivo. Further, functionalization can markedly attenuate the procoagulant activity of MWCNTs in vivo. This work will inform the rational development of biocompatible MWCNTs for systemic delivery. PMID:21663954

Relationship between platelet count and hemodialysis membranes

PubMed Central

Nasr, Rabih; Saifan, Chadi; Barakat, Iskandar; Azzi, Yorg Al; Naboush, Ali; Saad, Marc; Sayegh, Suzanne El

2013-01-01

Background One factor associated with poor outcomes in hemodialysis patients is exposure to a foreign membrane. Older membranes are very bioincompatible and increase complement activation, cause leukocytosis by activating circulating factors, which sequesters leukocytes in the lungs, and activates platelets. Recently, newer membranes have been developed that were designed to be more biocompatible. We tested if the different “optiflux” hemodialysis membranes had different effects on platelet levels. Methods Ninety-nine maintenance hemodialysis patients with no known systemic or hematologic diseases affecting their platelets had blood drawn immediately prior to, 90 minutes into, and immediately following their first hemodialysis session of the week. All patients were dialyzed using a Fresenius Medical Care Optiflux polysulfone membrane F160, F180, or F200 (polysulfone synthetic dialyzer membranes, 1.6 m2, 1.8 m2, and 2.0 m2 surface area, respectively, electron beam sterilized). Platelet counts were measured from each sample by analysis using a CBC analyzer. Results The average age of the patients was 62.7 years; 36 were female and 63 were male. The mean platelet count pre, mid, and post dialysis was 193 (standard deviation ±74.86), 191 (standard deviation ±74.67), and 197 (standard deviation ±79.34) thousand/mm3, respectively, with no statistical differences. Conclusion Newer membranes have no significant effect on platelet count. This suggests that they are, in fact, more biocompatible than their predecessors and may explain their association with increased survival. PMID:23983482

Factors influencing platelet clumping during peripheral blood hematopoietic stem cell collection

PubMed Central

Mathur, Gagan; Bell, Sarah L.; Collins, Laura; Nelson, Gail A.; Knudson, C. Michael; Schlueter, Annette J.

2018-01-01

BACKGROUND Platelet clumping is a common occurrence during peripheral blood hematopoietic stem cell (HSC) collection using the Spectra Optia mononuclear cell (MNC) protocol. If clumping persists, it may prevent continuation of the collection and interfere with proper MNC separation. This study is the first to report the incidence of clumping, identify precollection factors associated with platelet clumping, and describe the degree to which platelet clumping interferes with HSC product yield. STUDY DESIGN AND METHODS In total, 258 HSC collections performed on 116 patients using the Optia MNC protocol were reviewed. Collections utilized heparin in anticoagulant citrate dextrose to facilitate large-volume leukapheresis. Linear and logistic regression models were utilized to determine which precollection factors were predictive of platelet clumping and whether clumping was associated with product yield or collection efficiency. RESULTS Platelet clumping was observed in 63% of collections. Multivariable analysis revealed that a lower white blood cell count was an independent predictor of clumping occurrence. Chemotherapy mobilization and a lower peripheral blood CD34+ cell count were predictors of the degree of clumping. Procedures with clumping had higher collection efficiency but lower blood volume processed on average, resulting in no difference in collection yields. Citrate toxicity did not correlate with clumping. CONCLUSION Although platelet clumping is a common technical problem seen during HSC collection, the total CD34+ cell-collection yields were not affected by clumping. WBC count, mobilization approach, and peripheral blood CD34+ cell count can help predict clumping and potentially drive interventions to proactively manage clumping. PMID:28150319

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.

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.

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.

Differential changes in platelet VEGF, Tsp, CXCL12, and CXCL4 in patients with metastatic cancer.

PubMed

Wiesner, Tina; Bugl, Stefanie; Mayer, Frank; Hartmann, Jörg T; Kopp, Hans-Georg

2010-03-01

Data from animal studies indicate that platelets play a key role in tumor dissemination and metastasis. We therefore hypothesized that metastastic cancer patients may display a specific platelet phenotype. Percentage of activated, p-selectin positive platelets as well as platelet contents (i.e., plasma and platelet count-corrected serum levels of VEGF-A, CXCL12, CXCL4, and thrombospondin-1) were analyzed in 43 patients with newly diagnosed metastatic disease prior to treatment. Tumor patients had increased platelet counts and significantly elevated percentages of activated platelets. Moreover, the platelet content of VEGF-A in cancer patients was significantly increased compared to healthy controls, while thrombospondin-1, CXCL12 and CXCL4 were significantly decreased. Our data contain several unexpected results: firstly, CXCL12 was found in minute quantities in the serum as compared with murine studies. Secondly, CXCL4, which was found by mass spectrometry to be the single massively upregulated intraplatelet chemokine in mice after tumor xenotransplantation, was decreased in tumor patient platelets. While increased contents of VEGF-A have been attributed to platelet scavenger activity, the differential decrease of specific platelet contents may be due to differential secretion or altered megakaryopoiesis in metastatic cancer patients.

Association of Platelet Serotonin Levels in Alzheimer's Disease with Clinical and Cerebrospinal Fluid Markers.

PubMed

Tajeddinn, Walid; Fereshtehnejad, Seyed-Mohammad; Seed Ahmed, Mohammed; Yoshitake, Takashi; Kehr, Jan; Shahnaz, Tasmin; Milovanovic, Micha; Behbahani, Homira; Höglund, Kina; Winblad, Bengt; Cedazo-Minguez, Angel; Jelic, Vesna; Järemo, Petter; Aarsland, Dag

2016-05-04

Serotonin (5-HT) is involved in the pathology of Alzheimer's disease (AD). We aimed to measure 5-HT level in platelets in AD and explore its association with cerebrospinal fluid (CSF), AD biomarkers (amyloid-β 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau)), and clinical symptoms. 15 patients with AD and 20 patients with subjective cognitive impairment (SCI) were included. 5-HT metabolites were measured, in a specific fraction, using high performance liquid chromatography with electrochemical detection (HPLC-ECD). Significantly lower 5-HT concentrations were observed in AD patients compared to SCI patients both after normalization against total protein (p = 0.008) or platelet count (p = 0.019). SCI patients with lower 5-HT level have higher AD CSF biomarkers, total tau (p = 0.026) and tau/Aβ42 ratio (p = 0.001), compared to those with high 5-HT levels. AD patients have reduced platelet 5-HT levels. In SCI, lower 5-HT content was associated with a higher AD-CSF biomarker burden.

Evaluation of the platelet counting by Abbott CELL-DYN SAPPHIRE haematology analyser compared with flow cytometry.

PubMed

Grimaldi, E; Del Vecchio, L; Scopacasa, F; Lo Pardo, C; Capone, F; Pariante, S; Scalia, G; De Caterina, M

2009-04-01

The Abbot Cell-Dyn Sapphire is a new generation haematology analyser. The system uses optical/fluorescence flow cytometry in combination with electronic impedance to produce a full blood count. Optical and impedance are the default methods for platelet counting while automated CD61-immunoplatelet analysis can be run as selectable test. The aim of this study was to determine the platelet count performance of the three counting methods available on the instrument and to compare the results with those provided by Becton Dickinson FACSCalibur flow cytometer used as reference method. A lipid interference experiment was also performed. Linearity, carryover and precision were good, and satisfactory agreement with reference method was found for the impedance, optical and CD61-immunoplatelet analysis, although this latter provided the closest results in comparison with flow cytometry. In the lipid interference experiment, a moderate inaccuracy of optical and immunoplatelet counts was observed starting from a very high lipid value.

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.

[A report of two children with fever, headache, and purpura].

PubMed

Xu, Hong-Bo; Tan, Mei; Lu, Jian; Tian, Mao-Qiang; Chen, Yan

2017-09-01

In this study, two school-aged children had an acute onset in spring and had the manifestations of fever, headache, vomiting, disturbance of consciousness, purpura and ecchymosis, and positive meningeal irritation sign. There were increases in peripheral white blood cells and neutrophils, but reductions in the hemoglobin level and platelet count in the two children. They had a significant increase in C-reactive protein. There were hundreds or thousands of white blood cells in the cerebrospinal fluid, mainly neutrophils. Increased protein contents but normal levels of glucose and chloride in the cerebrospinal fluid were found. Head CT scan showed multiple hematomas in the right cerebellum and both hemispheres in one child. Bone marrow cytology indicated infection in the bone marrow, and both blood culture and bone marrow culture showed methicillin-resistant Staphylococcus aureus (MRSA). Both patients had cardiac murmurs and progressive reductions in the hemoglobin level and platelet count during treatment, and echocardiography showed the formation of vegetation in the aortic valve. Therefore, the patients were diagnosed with infectious endocarditis (IE). Vancomycin was used as the anti-infective therapy based on the results of drug sensitivity test. One child was cured after 6 weeks, and the other child was withdrawn from the treatment and then died. Dynamic monitoring of cardiac murmurs should be performed for children with unexplained fever, and echocardiography should be performed in time to exclude IE. IE should also be considered for children with purulent meningitis and skin and mucosal bleeding which cannot be explained by the reduction in platelet count.

Magnitude of reactive thrombocytosis and associated clinical conditions in dogs.

PubMed

Athanasiou, Labrini V; Polizopoulou, Zoe S; Papavasileiou, Eleftheria G; Mpairamoglou, Efstathios L; Kantere, Maria C; Rousou, Xanthi A

2017-09-09

Previous studies on the underlying causes of thrombocytosis have raised scientific interest in its clinical relevance in dogs. The purpose of this study was: (1) to explore the clinical conditions associated with thrombocytosis; (2) to compare platelet counts among these conditions; and (3) to identify possible interactions with other haematological variables and associated conditions. Medical records of 195 dogs with thrombocytosis (platelet count >500×10 3 /μL) were reviewed for signalment, complete blood count results and definitive diagnosis. The prevalence of thrombocytosis was 6.02%. All cases included had reactive thrombocytosis, with non-neoplastic, non-inflammatory underlying conditions in 48.2%, inflammatory processes in 34.4% and neoplastic processes in 17.4%. Haemoglobin and white blood cell counts were negatively and positively associated with platelet count, respectively. This study revealed that mean platelet count in dogs with neoplasia and a packed cell volume of 35% or below was significantly higher than that for dogs with other disease categories. Therefore, for dogs with marked thrombocytosis and anaemia, it is recommended that neoplasia should be included in the list of differential diagnoses. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Mitochondrial dysfunction in blood cells from amyotrophic lateral sclerosis patients.

PubMed

Ehinger, Johannes K; Morota, Saori; Hansson, Magnus J; Paul, Gesine; Elmér, Eskil

2015-06-01

Mitochondrial dysfunction is implicated in amyotrophic lateral sclerosis, where the progressive degeneration of motor neurons results in muscle atrophy, paralysis and death. Abnormalities in both central nervous system and muscle mitochondria have previously been demonstrated in patient samples, indicating systemic disease. In this case-control study, venous blood samples were acquired from 24 amyotrophic lateral sclerosis patients and 21 age-matched controls. Platelets and peripheral blood mononuclear cells were isolated and mitochondrial oxygen consumption measured in intact and permeabilized cells with additions of mitochondrial substrates, inhibitors and titration of an uncoupler. Respiratory values were normalized to cell count and for two markers of cellular mitochondrial content, citrate synthase activity and mitochondrial DNA, respectively. Mitochondrial function was correlated with clinical staging of disease severity. Complex IV (cytochrome c-oxidase)-activity normalized to mitochondrial content was decreased in platelets from amyotrophic lateral sclerosis patients both when normalized to citrate synthase activity and mitochondrial DNA copy number. In mononuclear cells, complex IV-activity was decreased when normalized to citrate synthase activity. Mitochondrial content was increased in amyotrophic lateral sclerosis patient platelets. In mononuclear cells, complex I activity declined and mitochondrial content increased progressively with advancing disease stage. The findings are, however, based on small subsets of patients and need to be confirmed. We conclude that when normalized to mitochondria-specific content, complex IV-activity is reduced in blood cells from amyotrophic lateral sclerosis patients and that there is an apparent compensatory increase in cellular mitochondrial content. This supports systemic involvement in amyotrophic lateral sclerosis and suggests further study of mitochondrial function in blood cells as a future biomarker for the disease.

Long-term increases in lymphocytes and platelets in human T-lymphotropic virus type II infection

PubMed Central

Bartman, Melissa T.; Kaidarova, Zhanna; Hirschkorn, Dale; Sacher, Ronald A.; Fridey, Joy; Garratty, George; Gibble, Joan; Smith, James W.; Newman, Bruce; Yeo, Anthony E.

2008-01-01

Human T-lymphotropic viruses types I and II (HTLV-I and HTLV-II) cause chronic infections of T lymphocytes that may lead to leukemia and myelopathy. However, their long-term effects on blood counts and hematopoiesis are poorly understood. We followed 151 HTLV-I–seropositive, 387 HTLV-II–seropositive, and 799 HTLV-seronegative former blood donors from 5 U.S. blood centers for a median of 14.0 years. Complete blood counts were performed every 2 years. Multivariable repeated measures analyses were conducted to evaluate the independent effect of HTLV infection and potential confounders on 9 hematologic measurements. Participants with HTLV-II had significant (P < .05) increases in their adjusted lymphocyte counts (+126 cells/mm3; approximately +7%), hemoglobin (+2 g/L [+0.2 g/dL]) and mean corpuscular volume (MCV; 1.0 fL) compared with seronegative participants. Participants with HTLV-I and HTLV-II had higher adjusted platelet counts (+16 544 and +21 657 cells/mm3; P < .05) than seronegatives. Among all participants, time led to decreases in platelet count and lymphocyte counts, and to increases in MCV and monocytes. Sex, race, smoking, and alcohol consumption all had significant effects on blood counts. The HTLV-II effect on lymphocytes is novel and may be related to viral transactivation or immune response. HTLV-I and HTLV-II associations with higher platelet counts suggest viral effects on hematopoietic growth factors or cytokines. PMID:18755983

Flow cytometric analysis of platelet cyclooxygenase-1 and -2 and surface glycoproteins in patients with immune thrombocytopenia and healthy individuals.

PubMed

Rubak, Peter; Kristensen, Steen D; Hvas, Anne-Mette

2017-06-01

Immature platelets may contain more platelet enzymes such as cyclooxygenase (COX)-1 and COX-2 than mature platelets. Patients with immune thrombocytopenia (ITP) have a higher fraction of immature platelets and can therefore be utilized as a biological model for investigating COX-1 and COX-2 platelet expression. The aims were to develop flow cytometric assays for platelet COX-1 and COX-2 and to investigate the COX-1 and COX-2 platelet expression, platelet turnover, and platelet glycoproteins in ITP patients (n = 10) compared with healthy individuals (n = 30). Platelet count and platelet turnover parameters (mean platelet volume (MPV), immature platelet fraction (IPF), and immature platelet count (IPC)) were measured by flow cytometry (Sysmex XE-5000). Platelet COX-1, COX-2, and the glycoproteins (GP)IIb, IX, Ib, Ia, and IIIa were all analyzed by flow cytometry (Navios) and expressed as median fluorescence intensity. COX analyses were performed in both whole blood and platelet rich plasma (PRP), whereas platelet glycoproteins were analyzed in whole blood only. ITP patients had significantly lower platelet count (55 × 10 9 /L) than healthy individuals (240 × 10 9 /L, p < 0.01), but a higher MPV (p = 0.03) and IPF (p < 0.01). IPC was similar for the two groups (p = 0.74). PRP had significantly lower MPV (p < 0.01) and significantly higher platelet count and IPC (both p-values <0.03) when compared with whole blood. IPF was similar for PRP and whole blood (p = 0.18). COX-1 expression was 10 times higher and COX-2 expression was 50% higher in PRP than in whole blood (p COX-1 < 0.01, p COX-2 < 0.01). Platelet COX-1 expression was higher in ITP patients than healthy individuals using whole blood (p COX-1 < 0.01) and PRP, though this was nonsignificant in PRP (p COX-1 = 0.17). In ITP patients, positive correlations were found between platelet turnover and COX-1 expression (all p-values <0.01, rho = 0.80-0.94), whereas healthy individuals showed significant though weaker correlations between platelet turnover and COX-1 and COX-2 expressions (all p-values <0.03, rho = 0.44-0.71). GPIIb, IX, and Ib expression was increased in ITP patients compared with healthy individuals (all p-values < 0.03). GPIIb, IX, Ib, and IIIa showed positive correlations with platelet turnover in ITP patients (all p-values <0.02, rho = 0.71-0.94), but weak and nonsignificant correlations in healthy individuals (all p-values >0.14, rho = 0.11-0.28). In conclusion, ITP patients expressed higher COX-1 and platelet glycoprotein levels than healthy individuals. COX-1 and platelet glycoproteins demonstrated positive correlations with platelet turnover in ITP patients. In healthy individuals, COX-1 and COX-2 expression correlated positively with platelet turnover. PRP was more sensitive compared with whole blood as regards determination of COX. Therefore, PRP is the recommended matrix for investigating COX-1 and COX-2 in platelets.

21 CFR 864.8175 - Calibrator for platelet counting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calibrator for platelet counting. 864.8175 Section 864.8175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8175 Calibrator for...

21 CFR 864.8175 - Calibrator for platelet counting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Calibrator for platelet counting. 864.8175 Section 864.8175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8175 Calibrator for...

21 CFR 864.8175 - Calibrator for platelet counting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Calibrator for platelet counting. 864.8175 Section 864.8175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8175 Calibrator for...

21 CFR 864.8175 - Calibrator for platelet counting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Calibrator for platelet counting. 864.8175 Section 864.8175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8175 Calibrator for...

21 CFR 864.8175 - Calibrator for platelet counting.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Calibrator for platelet counting. 864.8175 Section 864.8175 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8175 Calibrator for...

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.

First comparative analysis concerning the plasma platelet contamination during MNC collection.

PubMed

Pfeiffer, Hella; Achenbach, Susanne; Strobel, Julian; Zimmermann, Robert; Eckstein, Reinhold; Strasser, Erwin F

2017-08-01

Monocytes can be cultured into dendritic cells with addition of autologous plasma, which is highly prone to platelet contamination due to the apheresis process. Since platelets affect the maturation process of monocytes into dendritic cells and might even lead to a diminished harvest of dendritic cells, it is very important to reduce the platelet contamination. A new collection device (Spectra Optia) was analyzed, compared to two established devices (COM.TEC, Cobe Spectra) and evaluated regarding the potential generation of source plasma. Concurrent plasma collected during leukapheresis was analyzed for residual cell contamination in a prospective study with the new Spectra Optia apheresis device (n=24) and was compared with COM.TEC and Cobe Spectra data (retrospective analysis, n=72). Donor pre-donation counts of platelets were analyzed for their predictive value of contaminating PLTs in plasma harvests. The newest apheresis device showed the lowest residual platelet count of the collected concurrent plasma (median 3.50×10 9 /l) independent of pre-donation counts. The other two devices and sets had a higher platelet contamination. The contamination of the plasma with leukocytes was very low (only 2.0% were higher than 0.5×10 9 /l). This study showed a significant reduction of platelet contamination of the concurrent plasma collected with the new Spectra Optia device. This plasma product with low residual platelets and leukocytes might also be used as plasma for fractionation. Copyright © 2017 Elsevier Ltd. All rights reserved.

A pilot study evaluating the prognostic utility of platelet indices in dogs with septic peritonitis.

PubMed

Llewellyn, Efa A; Todd, Jeffrey M; Sharkey, Leslie C; Rendahl, Aaron

2017-09-01

To characterize platelet indices at time of diagnosis of septic peritonitis in dogs and to assess the relationship between platelet parameter data and survival to discharge in dogs treated surgically. Retrospective, observational, descriptive pilot study from 2009 to 2014. University teaching hospital. Forty-eight dogs diagnosed with septic peritonitis were included in this study. Thirty-six dogs had surgical source control. Blood samples from 46 healthy control dogs were used for reference interval (RI) generation. None. Dogs with septic peritonitis had significantly increased mean values for mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) with increased proportions of dogs having values above the RI compared to healthy dogs. A significantly increased proportion of dogs with septic peritonitis had platelet counts above (12.5%) and below (8.3%) the RI, with no significant difference in mean platelet count compared to healthy dogs. No significant differences in the mean platelet count, MPV, PCT, or PDW were found between survivors and nonsurvivors in dogs with surgical source control; however, dogs with MPV values above the RI had significantly increased mortality compared to dogs within the RI (P = 0.025). Values outside the RI for other platelet parameters were not associated with significant differences in mortality. Dogs with septic peritonitis have increased frequency of thrombocytosis and thrombocytopenia with increased MPV, PCT, and PDW. An increased MPV may be a useful indicator of increased risk of mortality in dogs treated surgically. © Veterinary Emergency and Critical Care Society 2017.

[Changes and significance of peripheral blood platelet count in tumor shrinkage induced by a low dose of CTX in T739 mice].

PubMed

Li, Mo-lin; Jia, Yu-jie; Jiang, Miao-na; Shu, Xiao-hong; Li, Chuan-gang

2008-06-01

To establish a mouse model for BTT739 tumor-bearing mice cured by a low dose of cyclophosphamide (CTX). And then to observe the dynamic changes and significance of peripheral blood counts especially blood platelet count during tumor shrinkage induced by a low dose of CTX in T739 mice. Mouse bladder carcinoma tissues were inoculated subcutaneously into T739 mice. Seven days later, different doses of CTX or the same volume of NS were administered intraperitoneally to treat these tumor-bearing T739 mice. Tumor sizes were observed and recorded subsequently to find out the minimal dose of CTX that could cure most of these tumor-bearing mice. Then another 12 tumor-bearing mice were randomly divided into 15 mg/kg CTX treatment group and control group. Blood samples were obtained from orbital venous sinus on different times after CTX treatment. Complete blood counts were performed and the relationship between peripheral blood platelet counts and tumor shrinkage was analyzed. Within 2 weeks after CTX treatment, the speed of tumor shrinkage had a positive relationship with the dose of CTX used; but the survival rate of the tumor-bearing mice had a negative relationship with the dose of CTX used in 2 months after CTX treatment. 15 mg/kg CTX could cure most of the tumor bearing mice, while it had no remarkably inhibitive effects on peripheral blood cells. The perpherial platelet count increased to (1483.4+/-184.4)x10(9)/L in mice 6 h after CTX treatment. There was significant difference compared with that in mice of control group (1086.6+/-81.0)x10(9)/L (P<0.01). During the 2nd to 14th day after CTX treatment, there was no obvious difference in the platelet count between treatment group and control group (P>0.05). CTX 15 mg/kg could cure most of bladder tumor-bearing T739 mice. The transient increase of the peripheral platelet count in 6 h after CTX treatment may relate to the antitumor effects of CTX.

Influence of calcium salts and bovine thrombin on growth factor release from equine platelet-rich gel supernatants.

PubMed

Giraldo, Carlos E; Álvarez, María E; Carmona, Jorge U

2017-01-16

To compare five activation methods in equine platelet-rich plasma (PRP) by determination of platelet-derived growth factor BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) concentrations in platelet-rich gel (PRG) supernatants. Platelet-rich plasma from 20 horses was activated by calcium chloride (CC), calcium gluconate (CG), bovine thrombin (BT), and their combinations, BTCC and BTCG. Both growth factor concentrations in PRG supernatants were measured by ELISA and compared with plasma and platelet lysates (PL) over time. Growth factor concentrations were significantly lower in plasma and higher for all PRG supernatants. Platelet lysates contained a significantly lower concentration of PDGF-BB than PRG supernatants and a significantly higher concentration of TGF-β1 than PRG supernatants. Clots from PRP activated with sodium salts were more stable over time and had significant growth factor release, whereas CC produced gross salt deposition. Significant correlations were noticed for platelet with leukocyte concentrations in PRP (r s : 0.76), platelet counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.86), platelet counts in PRP with PDGF-BB concentrations in PRG supernatants (r s : 0.78), leukocyte counts in PRP with TGF-β1 concentrations in PRG supernatants (r s : 0.76), and PDGF-BB concentrations with activating substances (r s : 0.72). Calcium gluconate was the better substance to induce PRP activation. It induced growth factor release free from calcium precipitates in the clots. Use of BT alone or combined with calcium salts was not advantageous for growth factor release.

Leukocyte and platelet changes following low-dose lipopolysaccharide administration in five dogs.

PubMed

Flatland, B; Fry, M M; LeBlanc, C J; Rohrbach, B W

2011-02-01

Effects of low-dose LPS (0.1 μg/kg i.v.) on leukocyte and platelet parameters measured using an Advia 120 hematology analyzer were investigated. Five dogs received a saline sham treatment prior to LPS, and blood was collected before and 3, 6, and 24 h post-treatment. LPS-treated dogs had mild neutrophil toxic change and increased neutrophil bands at 3 and 6 h. Compared to saline-treated controls, total leukocyte, neutrophil, and monocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Compared to baseline, total leukocyte counts of LPS-treated dogs were significantly decreased at 3 h and increased at 24 h. Mean platelet volume was significantly increased and mean platelet component concentration was decreased at 3 h compared to baseline. Platelet count was significantly decreased at 3 and 6 h; plateletcrit did not change significantly. High dosage is not required in order to detect LPS-mediated hematologic effects in dogs. Low-dose LPS administration causes significant changes in leukocyte and platelet indices in dogs without causing severe clinical signs or death. Copyright © 2010 Elsevier Ltd. All rights reserved.

Postinfluenza Vaccination Idiopathic Thrombocytopenic Purpura in Three Elderly Patients

PubMed Central

Nagasaki, Joji; Manabe, Masahiro; Ido, Kentaro; Ichihara, Hiroyoshi; Aoyama, Yasutaka; Ohta, Tadanobu; Furukawa, Yoshio; Mugitani, Atsuko

2016-01-01

The etiologies of secondary idiopathic thrombocytopenic purpura (ITP) include infection, autoimmune disease, and immunodeficiency. We report the cases of three elderly patients who developed ITP after receiving influenza vaccinations. The platelet count of an 81-year-old woman fell to 27,000/μL after she received an influenza vaccination. A 75-year-old woman developed thrombocytopenia (5,000 platelets/μL) after receiving an influenza vaccination. An 87-year-old woman whose laboratory test values included a platelet count of 2,000/μL experienced genital bleeding after receiving an influenza vaccination. After Helicobacter pylori (HP) eradication or corticosteroid treatment, all of the patients' platelet counts increased. Influenza vaccination is an underlying etiology of ITP in elderly patients. HP eradication or corticosteroid treatment is effective for these patients. Clinicians should be aware of the association between ITP and influenza vaccinations. PMID:26998369

Splenic artery pseudoaneurysm due to seatbelt injury in a glucose-6-phosphate dehydrogenase-deficient adult.

PubMed

Lau, Yu Zhen; Lau, Yuk Fai; Lai, Kang Yiu; Lau, Chu Pak

2013-11-01

A 23-year-old man presented with abdominal pain after suffering blunt trauma caused by a seatbelt injury. His low platelet count of 137 × 10(9)/L was initially attributed to trauma and his underlying hypersplenism due to glucose-6-phosphate dehydrogenase (G6PD) deficiency. Despite conservative management, his platelet count remained persistently reduced even after his haemoglobin and clotting abnormalities were stabilised. After a week, follow-up imaging revealed an incidental finding of a pseudoaneurysm (measuring 9 mm × 8 mm × 10 mm) adjacent to a splenic laceration. The pseudoaneurysm was successfully closed via transcatheter glue embolisation; 20% of the spleen was also embolised. A week later, the platelet count normalised, and the patient was subsequently discharged. This case highlights the pitfalls in the detection of a delayed occurrence of splenic artery pseudoaneurysm after blunt injury via routine delayed phase computed tomography. While splenomegaly in G6PD may be a predisposing factor for injury, a low platelet count should arouse suspicion of internal haemorrhage rather than hypersplenism.

Analysis of Consequences of Birth Asphyxia in Infants: A Regional Study in Southern Punjab, Pakistan.

PubMed

Samad, Noreen; Farooq, Samia; Hafeez, Kinza; Maryam, Mukharma; Rafi, Muhammad Aftab

2016-12-01

To evaluate the biochemical consequences and platelet counts of birth asphyxia in neonates. Cohort study. Department of Child Health, Nishter Medical College and Hospital, Multan, from September to November 2015. The data of 50 (50%) asphyxiated neonates and 50 (50%) non-asphyxiated neonates, with age range less than 1 month, was collected from Children Ward of Nishtar Hospital, Multan, Pakistan. Data on platelet count in blood, kidney function tests (creatinine, urea), liver function tests (bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST)) and cardiac enzyme test (lactate dehydrogenase (LDH)) were analysed by paired sample t-test by SPSS software. Sociodemographic data of those neonate's mothers was also collected. In asphyxiated neonates LDH, ALT, AST, creatinine, bilirubin, urea levels were higher than healthy infants, while the platelet count was smaller in asphyxiated neonates than healthy infants. There was a higher rate of alteration in platelet count, levels of LDH, AST, ALT, urea creatinine and bilirubin in asphyxiated infants. These alterations may be correlated with damage of vital organ of asphyxiated neonates.

Modified combination of platelet count and neutrophil "to" lymphocyte ratio as a prognostic factor in patients with advanced head and neck cancer.

PubMed

Nakayama, Masahiro; Gosho, Masahiko; Hirose, Yuki; Nishimura, Bungo; Tanaka, Shuho; Tabuchi, Keiji; Okubo, Hideki; Wada, Tetsuro; Hara, Akira

2018-06-01

We evaluated the prognostic potential of the combination of platelet count and neutrophil to lymphocyte ratio (COP-NLR) in patients with advanced head and neck cancer. We proposed a modified COP-NLR scoring system defined as follows: score 0 (platelet count level <300 × 10 9 /L and NLR <3); score 1 (platelet count level ≥300 × 10 9 /L and NLR <3); and score 2 (NLR ≥3). We assessed whether the modified scoring system had better performance as an indicator of prognosis than the existing COP-NLR scoring system (original and 4-group scores). A total of 248 patients were enrolled. The Akaike Information Criterion value with the modified COP-NLR score was the smallest among the 3 models. The 3-year survival rates according to the modified COP-NLR scores of 0, 1, and 2 were 80.6%, 59.9%, and 23.8%, respectively. The modified COP-NLR score is a useful prognostic marker in patients with advanced head and neck cancer. © 2018 Wiley Periodicals, Inc.

Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial.

PubMed

Bussel, James B; Provan, Drew; Shamsi, Tahir; Cheng, Gregory; Psaila, Bethan; Kovaleva, Lidia; Salama, Abdulgabar; Jenkins, Julian M; Roychowdhury, Debasish; Mayer, Bhabita; Stone, Nicole; Arning, Michael

2009-02-21

Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg. In this phase III, randomised, double-blind, placebo-controlled study, adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura (ITP), platelet counts less than 30 000 per muL of blood, and one or more previous ITP treatment received standard care plus once-daily eltrombopag 50 mg (n=76) or placebo (n=38) for up to 6 weeks. Patients were randomly assigned in a 2:1 ratio of eltrombopag:placebo by a validated randomisation system. After 3 weeks, patients with platelet counts less than 50 000 per microL could increase study drug to 75 mg. The primary endpoint was the proportion of patients achieving platelet counts 50 000 per microL or more at day 43. All participants who received at least one dose of their allocated treatment were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT00102739. 73 patients in the eltrombopag group and 37 in the placebo group were included in the efficacy population and were evaluable for day-43 analyses. 43 (59%) eltrombopag patients and six (16%) placebo patients responded (ie, achieved platelet counts >/=50 000 per microL; odds ratio [OR] 9.61 [95% CI 3.31-27.86]; p<0.0001). Response to eltrombopag compared with placebo was not affected by predefined study stratification variables (baseline platelet counts, concomitant ITP drugs, and splenectomy status) or by the number of previous ITP treatments. Of the 34 patients in the efficacy analysis who increased their dose of eltrombopag, ten (29%) responded. Platelet counts generally returned to baseline values within 2 weeks after the end of treatment. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo (OR 0.49 [95% CI 0.26-0.89]; p=0.021). The frequency of grade 3-4 adverse events during treatment (eltrombopag, two [3%]; placebo, one [3%]) and adverse events leading to study discontinuation (eltrombopag, three [4%]; placebo, two [5%]), were similar in both groups. Eltrombopag is an effective treatment for managment of thrombocytopenia in chronic ITP.

Effect of quinine and artesunate combination therapy on platelet count of children with severe malaria.

PubMed

Gupta, Parul; Narang, Manish; Gomber, Sunil; Saha, Rumpa

2017-05-01

There are several case reports of quinine-induced thrombocytopenia but no clinical trials to ascertain its incidence and significance in severe malaria. The primary objective was to assess the effect of quinine on the platelet count in children with severe malaria and to compare it with artesunate combination therapy (ACT), and the secondary objective was to assess outcome of treatment with quinine and ACT. An open-labelled, randomised, controlled trial was undertaken in 100 children aged 6 months to 12 years who were diagnosed with malaria by microscopy and/or rapid diagnostic test kits with at least one WHO clinical or laboratory criterion for severe malaria. All subjects were commenced on either quinine or ACT. Clindamycin was added to artesunate as a combination drug (ACT). It was also given to patients on quinine to avoid its confounding effect on the results. Platelet counts were undertaken every 24 hours for 7 consecutive days, temperature and coma score (Blantyre coma score ≥3 in children <4 years or Glasgow coma score ≥13 in children >4 years) was recorded 6-hourly and peripheral smears were taken 12-hourly until two consecutively negative smears were obtained. The primary outcome was a fall in the platelet count by ≥20% from the time of drug initiation until day 7. The secondary outcome was comparison of the efficacy, parasite clearance time, fever clearance time, coma recovery time and adverse effects of quinine vs ACT. 30.4% patients in the quinine group (n = 48) had ≥20% fall in platelet count and 10.8% of patients in the ACT group (n = 46) (P = 0.02). Despite the fall in platelet count, there was no bleeding. The efficacy of ACT was significantly better than quinine but the other treatment outcomes showed insignificant difference. Quinine should be used with caution in patients with severe malaria because of the potential risk of quinine-induced thrombocytopenia.

The effects of residual platelets in plasma on plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays.

PubMed

Pieters, Marlien; Barnard, Sunelle A; Loots, Du Toit; Rijken, Dingeman C

2017-01-01

Due to controversial evidence in the literature pertaining to the activity of plasminogen activator inhibitor-1 in platelets, we examined the effects of residual platelets present in plasma (a potential pre-analytical variable) on various plasminogen activator inhibitor-1 and plasminogen activator inhibitor-1-related assays. Blood samples were collected from 151 individuals and centrifuged at 352 and 1500 g to obtain plasma with varying numbers of platelet. In a follow-up study, blood samples were collected from an additional 23 individuals, from whom platelet-poor (2000 g), platelet-containing (352 g) and platelet-rich plasma (200 g) were prepared and analysed as fresh-frozen and after five defrost-refreeze cycles (to determine the contribution of in vitro platelet degradation). Plasminogen activator inhibitor-1 activity, plasminogen activator inhibitor-1 antigen, tissue plasminogen activator/plasminogen activator inhibitor-1 complex, plasma clot lysis time, β-thromboglobulin and plasma platelet count were analysed. Platelet α-granule release (plasma β-thromboglobulin) showed a significant association with plasminogen activator inhibitor-1 antigen levels but weak associations with plasminogen activator inhibitor-1 activity and a functional marker of fibrinolysis, clot lysis time. Upon dividing the study population into quartiles based on β-thromboglobulin levels, plasminogen activator inhibitor-1 antigen increased significantly across the quartiles while plasminogen activator inhibitor-1 activity and clot lysis time tended to increase in the 4th quartile only. In the follow-up study, plasma plasminogen activator inhibitor-1 antigen was also significantly influenced by platelet count in a concentration-dependent manner. Plasma plasminogen activator inhibitor-1 antigen levels increased further after complete platelet degradation. Residual platelets in plasma significantly influence plasma plasminogen activator inhibitor-1 antigen levels mainly through release of latent plasminogen activator inhibitor-1 with limited effects on plasminogen activator inhibitor-1 activity, tissue plasminogen activator/plasminogen activator inhibitor-1 complex or plasma clot lysis time. Platelets may however also have functional effects on plasma fibrinolytic potential in the presence of high platelet counts, such as in platelet-rich plasma.

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

PubMed Central

Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

2013-01-01

The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

[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.

Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia.

PubMed

Dasouki, Majed J; Rafi, Syed K; Olm-Shipman, Adam J; Wilson, Nathan R; Abhyankar, Sunil; Ganter, Brigitte; Furness, L Mike; Fang, Jianwen; Calado, Rodrigo T; Saadi, Irfan

2013-11-14

We recently identified 2 siblings afflicted with idiopathic, autosomal recessive aplastic anemia. Whole-exome sequencing identified a novel homozygous missense mutation in thrombopoietin (THPO, c.112C>T) in both affected siblings. This mutation encodes an arginine to cysteine substitution at residue 38 or residue 17 excluding the 21-amino acid signal peptide of THPO receptor binding domain (RBD). THPO has 4 conserved cysteines in its RBD that form 2 disulfide bonds. Our in silico modeling predicts that introduction of a fifth cysteine may disrupt normal disulfide bonding to cause poor receptor binding. In functional assays, the mutant-THPO-containing media shows two- to threefold reduced ability to sustain UT7-TPO cells, which require THPO for proliferation. Both parents and a sibling with heterozygous R17C change have reduced platelet counts, whereas a sibling with wild-type sequence has normal platelet count. Thus, the R17C partial loss-of-function allele results in aplastic anemia in the homozygous state and mild thrombocytopenia in the heterozygous state in our family. Together with the recent identification of THPO receptor (MPL) mutations and the effects of THPO agonists in aplastic anemia, our results have clinical implications in the diagnosis and treatment of patients with aplastic anemia and highlight a role for the THPO-MPL pathway in hematopoiesis in vivo.

Mutation Analysis of IDH1/2 Genes in Unselected De novo Acute Myeloid Leukaemia Patients in India - Identification of A Novel IDH2 Mutation.

PubMed

Raveendran, Sureshkumar; Sarojam, Santhi; Vijay, Sangeetha; Geetha, Aswathy Chandran; Sreedharan, Jayadevan; Narayanan, Geetha; Sreedharan, Hariharan

2015-01-01

IDH1/2 mutations which result in alternation in DNA methylation pattern are one of the most common methylation associated mutations in Acute myeloid leukaemia. IDH1/2 mutations frequently associated with higher platelet level, normal cytogentics and NPM1 mutations. Here we analyzed IDH1/2 mutations in 200 newly diagnosed unselected Indian adult AML patients and investigated their correlation with clinical, cytogenetic parameters along with cooperating NPM1 mutation. We detected 5.5% and 4% mutations in IDH1/2 genes, respectively. Except IDH2 c.515_516GG>AA mutation, all the other identified mutations were reported mutations. Similar to reported c.515G>A mutation, the novel c.515_516GG>AA mutation replaces 172nd arginine to lysine in the active site of the enzyme. Even though there was a preponderance of IDH1/2 mutations in NK-AML, cytogenetically abnormal patients also harboured IDH1/2 mutations. IDH1 mutations showed significant higher platelet count and NPM1 mutations. IDH2 mutated patients displayed infrequent NPM1 mutations and lower WBC count. All the NPM1 mutations in the IDH1/2 mutated cases showed type A mutation. The present data suggest that IDH1/2 mutations are associated with normal cytogenetics and type A NPM1 mutations in adult Indian AML patients.

A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF).

PubMed

Abe, Yasunori; Wada, Hideo; Tomatsu, Hiroaki; Sakaguchi, Akane; Nishioka, Junji; Yabu, Yasunori; Onishi, Katsuya; Nakatani, Kaname; Morishita, Yoshitaka; Oguni, Shinichiro; Nobori, Tsutomu

2006-01-01

Immature platelet fraction (IPF) has been measured by fully automated analyzer (XE-2100) as reticulated platelet (RP) which is reflected with thrombopoiesis in bone marrow. IPF value in the healthy volunteers was 3.3% (1.0-10.3) and upper 95% confidential interval (95% CI) of IPF was determined as 7.7%. IPF was significantly high in the patients with idiopathic thrombocytopenic purpura (ITP; 17.4%, 1.2-53.2%) and recovery phase of post-chemotherapy, and significantly low in nadir phase of post-chemotherapy, and within normal range in the patients with ITP in complete remission (CR) and with aplastic anemia (AA). Total count of IPF was significantly low in patients with ITP, AA or post-chemotherapy. Mean platelet volume (MPV) was significantly high in only patients with ITP. IPF 7.7% is best point for highest sensitivity (86.8%) and specificity (92.6%) in diagnosis of ITP and recovery phase of post-chemotherapy. In receiver operating characteristic curve for diagnosis of ITP and recovery phase of post-chemotherapy, IPF was significantly more useful than MPV. These results show that IPF reflects the pathology of thrombocytopenic disorders, and that measurement of IPF is useful for the differential diagnosis and analysis of platelet kinetics.

Short-Term Storage of Platelet-Rich Plasma at Room Temperature Does Not Affect Growth Factor or Catabolic Cytokine Concentration.

PubMed

Wilson, Brooke H; Cole, Brian J; Goodale, Margaret B; Fortier, Lisa A

2018-04-01

The aim of this study was to provide clinical recommendations about the use of platelet-rich plasma (PRP) that was subjected to short-term storage at room temperature. We determined bioactive growth factor and cytokine concentrations as indicators of platelet and white blood cell degranulation in blood and PRP. Additionally, this study sought to validate the use of manual, direct smear analysis as an alternative to automated methods for platelet quantification in PRP. Blood was used to generate low-leukocyte PRP (Llo PRP) or high-leukocyte PRP (Lhi PRP). Blood was either processed immediately or kept at room temperature for 2 or 4 hours prior to generation of PRP, which was then held at room temperature for 0, 1, 2, or 4 hours. Subsequently, bioactive transforming growth factor beta-1 and matrix metalloproteinase-9 were measured by ELISA (enzyme-linked immunosorbent assay). Manual and automated platelet counts were performed on all blood and PRP samples. There were no differences in growth factor or cytokine concentration when blood or Llo PRP or Lhi PRP was retained at room temperature for up to 4 hours. Manual, direct smear analysis for platelet quantification was not different from the use of automated machine counting for PRP samples, but in the starting blood samples, manual platelet counts were significantly higher than those generated using automated technology. When there is a delay of up to 4 hours in the generation of PRP from blood or in the application of PRP to the patient, bioactive growth factor and cytokine concentrations remain stable in both blood and PRP. A manual direct counting method is a simple, cost-effective, and valid method to measure the contents of the PRP product being delivered to the patient.

Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model

PubMed Central

Chrom, Pawel; Stec, Rafal; Bodnar, Lubomir; Szczylik, Cezary

2018-01-01

Purpose The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy. Materials and Methods This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R2, Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups. Results Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R2, 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R2, 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups). Conclusion Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice. PMID:28253564

Incorporating Neutrophil-to-lymphocyte Ratio and Platelet-to-lymphocyte Ratio in Place of Neutrophil Count and Platelet Count Improves Prognostic Accuracy of the International Metastatic Renal Cell Carcinoma Database Consortium Model.

PubMed

Chrom, Pawel; Stec, Rafal; Bodnar, Lubomir; Szczylik, Cezary

2018-01-01

The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy. This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R 2 , Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups. Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R 2 , 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R 2 , 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups). Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

Diagnostic validity of hematologic parameters in evaluation of massive pulmonary embolism.

PubMed

Ates, Hale; Ates, Ihsan; Kundi, Harun; Yilmaz, Fatma Meric

2017-09-01

The aim of this study was to determine the hematologic parameter with the highest diagnostic differentiation in the identification of massive acute pulmonary embolism (APE). A retrospective study was performed on patients diagnosing with APE between June 2014 and June 2016. All radiological and laboratory parameters of patients were scanned through the electronic information management system of the hospital. PLR was obtained from the ratio of platelet count to lymphocyte count, NLR was obtained from the ratio of neutrophil count to lymphocyte count, WMR was obtained from white blood cell in mean platelet volume ratio, MPR was obtained from the ratio of mean platelet volume to platelet count, and RPR was obtained from the ratio of red distribution width to platelet count. Six hundred and thirty-nine patients consisting of 292 males (45.7%) and 347 females (54.3%) were included in the research. Independent predictors of massive risk as compared to sub-massive group were; pulmonary arterial systolic pressure (PASP) (OR=1.40; P=.001), PLR (OR=1.59; P<.001), NLR (OR=2.22; P<.001), WMR (OR=1.22; P<.001), MPR (OR=0.33; P<.001), and RPR (OR=0.68; P<.001). Upon evaluation of the diagnostic differentiation of these risk factors for massive APE by employing receiver operating characteristic curve analysis, it was determined that PLR (AUC±SE=0.877±0.015; P<.001), and NLR (AUC±SE=0.893±0.013; P<.001) have similar diagnostic differentiation in diagnosing massive APE and these two parameters are superior over PASP, MPR, WMR, and RPR. We determined that the levels of NLR and PLR are superior to other parameters in the determination of clinical severity in APE cases. © 2016 Wiley Periodicals, Inc.

Aging stability of complete blood count and white blood cell differential parameters analyzed by Abbott CELL-DYN Sapphire hematology analyzer.

PubMed

Hedberg, P; Lehto, T

2009-02-01

This study presents the results of an aging stability study of complete blood count (CBC) and leukocyte differential parameters using the Abbott CELL-DYN Sapphire hematology analyzer. Stability studies showed no substantial change in CBC parameters up to 24-48 h at +23 +/- 2 degrees C (room temperature), except for optical platelet count (PLTo). For specimens aged over 24, the value of impedance platelet count yielded more reliable results than the routine PLTo. White blood cell (WBC) differential parameters, except eosinophils, were stable for up to 48 h at +23 +/- 2 degrees C. CBC parameters were stable for 72 h, except mean platelet volume, which slightly increased between 48 and 72 h, at +4 degrees C. WBC differentials were stable 48-72 h, with a slight decrease observed in absolute neutrophils and lymphocytes at +4 degrees C.

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

PubMed Central

Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

1978-01-01

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

[Assessment of local and systemic inflammatory parameters of peripheral burn in an animal model].

PubMed

Torres, Wilmary; Mendoza, Liseth; Vicci, Hember; Eblen-Zajjur, Antonio; Navarro, María

2016-01-01

To evaluate the edema volume and leukocyte, platelet, and fibrinogen count of peripheral burn in an animal model. The back left leg of Rattus norvegicus (experimental group) was placed in water at 60 °C for 60 seconds or at room temperature (control group). An analysis was carried out before and after the induced burn (at 4, 8, 12, and 24 h). The edema volume was determined by an orthogonal photo, the leukocyte and platelet counts were determined using automated equipment, and the fibrinogen count was determined using the gravimetric method. The maximum value of the edema was recorded at 4 h and leukocytes at 24 h. The platelet count did not vary at different post-edema time intervals. The fibrinogen level increased at 4 h and 24 h. In this animal model we induced systemic inflammation characterized by leukocytosis and elevated fibrinogen levels, combined with edema located at the induction area.

Acute immune thrombocytopenic purpura as adverse reaction to oral polio vaccine (OPV).

PubMed

Jin, Cheng-qiang; Dong, Hai-xin; Sun, Zhuo-xiang; Zhou, Jian-wei; Dou, Cui-yun; Lu, Shu-hua; Yang, Rui-rui

2013-08-01

A case of acute immune thrombocytopenic purpura following oral polio vaccine (OPV) is reported. An 82-d-old infant developed purpura at the same day after the second dose of oral polio vaccine. Until the time of hospital admission, the male infant had been in good health and had not received any drugs, and the possible causes of this condition were excluded. His platelet count was 13×10(9)/L. Platelet-associated IgG was elevated, but the amount of megakaryocytes in bone marrow aspirates was within the normal range, suggesting immune mechanism-associated thrombocytopenia. The infant recovered with the proper treatment within 30 d. Attention should be paid to OPV-associated thrombocytopenia, though it seems to be less frequent than after natural infections.

An Inherited Platelet Function Defect in Basset Hounds

PubMed Central

Johnstone, I. B.; Lotz, F.

1979-01-01

An inherited platelet function defect occurring in a family of basset hounds has been described. The trait is transmitted as an autosomal characteristic and appears to be expressed clinically only in the homozygous state. The characteristics of this platelet defect include: 1) marked bleeding tendencies and prolonged skin bleeding times in either male or female dogs. 2) normal blood coagulation mechanism. 3) adequate numbers of circulating platelets which appear morphologically normal by light microscopy. 4) normal whole blood clot retraction. 5) deficient in vivo platelet consumption and in vitro platelet retention in glass bead columns. 6) defective ADP-induced platelet aggregation in homozygotes, apparently normal ADP response in heterozygotes, and defective collagen-induced platelet aggregation in both. PMID:509382

[In-line leukocyte depletion ov thrombocytapheresis concentrates with the Fresenius-AS-104 cell separator].

PubMed

Zeiler, T; Kretschmer, V

1997-01-01

This study reports on in-line filtration of 72 platelet concentrates (PC) collected by the Fresenius AS 104 cell separator, using the new C4F sets with integrated leukocyte filters (Biofil P plus). 72 volunteer donors, automatic counts of platelets, microscopical counting of residual leukocytes with the Nageotte chamber, GMP-140 by flow cytometrie, beta-thromboglobulin release, platelet aggregation (ADP, collagen). Filtration reduced leukocytes by 98.5%. Residual leukocyte contamination remained clearly below 5 x 10(6) (mean 0.5 +/- 0.6 x 10(6), maximum 2.8 x 10(6). Platelet loss by filtration was found to be between 27.4 and 0.7% (median 8.5%). Filtration caused a significant decrease of platelet aggregability (p < 0.005), but no significant increase of beta-thromboglobulin release and only a slight decrease of GMP-140 expression. From these data can be concluded that in-line filtration was highly efficient with acceptable platelet retention. No significant platelet activation could be observed in the PC. The decrease of platelet aggregability have been due to the reduction of activated platelets which are believed to show reduced in vivo survival.

Determinants of platelet aggregation in 50-70-year-old men from three Japanese communities.

PubMed

Imano, Hironori; Iso, Hiroyasu; Sato, Shinichi; Kitamura, Akihiko; Okamura, Tomonori; Tanigawa, Takeshi; Ohira, Tetsuya; Kudo, Minako; Naito, Yoshihiko; Iida, Minoru; Shimamoto, Takashi

2002-12-01

To investigate the association of lifestyle and constitutional variables with platelet aggregation, we examined the platelet aggregation, serum fatty acid composition, alcohol intake, smoking, and dietary intake of seafood and soybean estimated by a 1-week dietary record in 448 males aged 50-70 in three rural Japanese communities: Ikawa, Akita prefecture (northeast coast), Noichi, Kochi prefecture (southwest coast), and Kyowa, Ibaraki prefecture (central inland). Platelet aggregatory threshold index (PATI) was used to determine the minimum concentration of adenosine 5'-diphosphate (ADP) that caused a non-reversible aggregation of platelets. Intake of seafood and n3-polyunsaturated fatty acid and ingestion of ethanol were higher in the northeast coastal community than in the other two communities. Mean platelet and white blood cell counts were lower in northeast coastal community than in the other two communities. The geometric mean PATI was higher (i.e. platelet aggregation was lower) in the northeast coastal community than the other two communities. Within the entire sample, platelet aggregation correlated inversely with serum level of n3-polyunsaturated fatty acids and gamma-glutamyl transpeptidase, an index of alcohol consumption, and positively with platelet and white blood cell counts. Platelet aggregation tended to correlate positively with serum arachidonic acid. There was no correlation between smoking and platelet aggregation. Our results suggest that seafood intake and moderate alcohol consumption reduce platelet aggregation.

Childhood immune thrombocytopenia: Clinical presentation and management

PubMed Central

2012-01-01

Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1–6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2–0.9%) [7–12]. Childhood primary ITP usually runs a benign, self-limiting course, with or without treatment. Complete remission occurs within six months from diagnosis, commonly within 6–12 weeks, in the majority of children with the diagnosis of ITP. However, 20–30% of children will continue to have persistent low platelets count with bleeding symptoms beyond six months from diagnosis [4, 12–18]. The diagnosis of ITP in children is essentially one of exclusion. The child is usually one to seven years old, develops skin bruises, petechiae, or mucosal bleeding, who is otherwise healthy and having no lymphadenopathy or organomegally. Full blood count reveals isolated thrombocytopenia with normal hemoglobin (Hb) level, white blood count (WBC) and normal peripheral blood smear. Initial management options for newly diagnosed childhood ITP include; observation only, the use of intravenous immunoglobulin (IVIG), steroids, anti-D immunoglobulin, each alone or in combination [6, 19.] Children who develop chronic ITP may benefit from splenectomy [19, 20–24]. Rituximab, a chimeric monoclonal antibody (anti-CD20), may lead to complete remission, and defers the need for splenectomy [25–27]. Recently, the thrombopoietin (TPO) agonists (Romiplostim and Eltrombopag) produced very good response in adult and pediatric patients with severe chronic ITP [28–30]. PMID:27493327

Reprint of "Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump".

PubMed

Schiariti, Michele; Saladini, Patrizia; Cuturello, Domenico; Iannetta, Loredana; Torromeo, Concetta; Puddu, Paolo Emilio

2014-04-01

Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes. Copyright © 2014 Elsevier Inc. All rights reserved.

Decline in platelet count and long-term post-PCI ischemic events: implication of the intra-aortic balloon pump.

PubMed

Schiariti, Michele; Saladini, Patrizia; Cuturello, Domenico; Iannetta, Loredana; Torromeo, Concetta; Puddu, Paolo Emilio

2014-01-01

Thrombocytopenia (TC) following a percutaneous coronary intervention (PCI) has been associated not only with hemorrhagic, but also with ischemic outcomes. The purpose of this study was to re-examine the relationship of TC with ischemic events at a 1-year follow-up, and investigate the possible associations. We studied a real-world, unselected population of ischemic patients undergoing PCI, totaling 861 patients-year, and divided into two groups: with TC (delta platelet count ≥25% from baseline to post-PCI during the hospital admission) and without TC. Compared with patients without TC, patients with TC had a higher and earlier incidence of both hemorrhagic and ischemic events. In them, the use of intra-aortic balloon pump (IABP) was ten-fold higher. In Kaplan-Meier curves assessing the contribution of both TC and IABP to outcome, IABP was a univariate detrimental factor additive to the role of TC. In a forced Cox model, the relative decline (delta) in platelet count (p=0.05) and the use of IABP (p=0.0001) were both associated with ischemic outcomes. After excluding all patients with IABP, the delta platelet count was no longer significantly associated with ischemic outcomes (p=0.66). After excluding all patients with shock and all those who undergone thrombolysis, there was still a relationship (p=0.0042) between the delta platelet count and ischemic events. In this patient population the use of IABP, but not thrombocytopenia per se, is a possible primary cause of worse ischemic outcomes. Copyright © 2013 Elsevier Inc. All rights reserved.

Patterns and influences in health-related quality of life in children with immune thrombocytopenia: A study from the Dallas ITP Cohort.

PubMed

Flores, Adolfo; Klaassen, Robert J; Buchanan, George R; Neunert, Cindy E

2017-08-01

Relationships between clinical/demographic factors and health-related quality of life (HRQoL) in childhood immune thrombocytopenia (ITP) remain poorly understood. Recent studies reveal conflicting information about factors that contribute to HRQoL. This was a prospective, single-institution, cohort study of newly diagnosed children with ITP. Serial evaluations of HRQoL were performed using the Kid's ITP Tools (KIT), scored from 0 (worst) to 100 (best), at enrollment and 1 week, 6 months, and 12 months following diagnosis. All visits included bleeding severity grading. Relationships between HRQoL and platelet count, treatment, bleeding severity, and course of disease were examined. A total of 99 children with newly diagnosed ITP were evaluable for analysis. KIT scores were low at diagnosis for parents (median 26, range 15-43) and children (median 65, range 55-81) and were not influenced by age or platelet count. At diagnosis, children who received treatment had lower platelet counts (P = 0.005), more severe hemorrhage (P < 0.0125), and lower HRQoL by parent, child, and proxy reporting (P < 0.05). Oral bleeding negatively impacted proxy-reported disease burden at diagnosis (P = 0.01). Persistence of disease and lower platelet counts at 6 and 12 month visits were the only factors noted to consistently impact quality of life beyond diagnosis for both parents and children. HRQoL is low at diagnosis but significantly improves over time. Patients with ongoing disease and lower platelet counts continue to have significant disease burden. © 2017 Wiley Periodicals, Inc.

Platelets Cellular and Functional Characteristics in Patients with Atrial Fibrillation: A Comprehensive Meta-Analysis and Systematic Review

PubMed Central

Weymann, Alexander; Ali-Hasan-Al-Saegh, Sadeq; Sabashnikov, Anton; Popov, Aron-Frederik; Mirhosseini, Seyed Jalil; Nombela-Franco, Luis; Testa, Luca; Lotfaliani, Mohammadreza; Zeriouh, Mohamed; Liu, Tong; Dehghan, Hamidreza; Yavuz, Senol; de Oliveira Sá, Michel Pompeu Barros; Baker, William L.; Jang, Jae-Sik; Gong, Mengqi; Benedetto, Umberto; Dohmen, Pascal M.; D’Ascenzo, Fabrizio; Deshmukh, Abhishek J.; Biondi-Zoccai, Giuseppe; Calkins, Hugh; Stone, Gregg W.

2017-01-01

Background This systematic review with meta-analysis aimed to determine the strength of evidence for evaluating the association of platelet cellular and functional characteristics including platelet count (PC), MPV, platelet distribution width (PDW), platelet factor 4, beta thromboglobulin (BTG), and p-selectin with the occurrence of atrial fibrillation (AF) and consequent stroke. Material/Methods We conducted a meta-analysis of observational studies evaluating platelet characteristics in patients with paroxysmal, persistent and permanent atrial fibrillations. A comprehensive subgroup analysis was performed to explore potential sources of heterogeneity. Results Literature search of all major databases retrieved 1,676 studies. After screening, a total of 73 studies were identified. Pooled analysis showed significant differences in PC (weighted mean difference (WMD)=−26.93 and p<0.001), MPV (WMD=0.61 and p<0.001), PDW (WMD=−0.22 and p=0.002), BTG (WMD=24.69 and p<0.001), PF4 (WMD=4.59 and p<0.001), and p-selectin (WMD=4.90 and p<0.001). Conclusions Platelets play a critical and precipitating role in the occurrence of AF. Whereas distribution width of platelets as well as factors of platelet activity was significantly greater in AF patients compared to SR patients, platelet count was significantly lower in AF patients. PMID:28302997

Pneumatic tube system transport does not alter platelet function in optical and whole blood aggregometry, prothrombin time, activated partial thromboplastin time, platelet count and fibrinogen in patients on anti-platelet drug therapy

PubMed Central

Enko, Dietmar; Mangge, Harald; Münch, Andreas; Niedrist, Tobias; Mahla, Elisabeth; Metzler, Helfried; Prüller, Florian

2017-01-01

Introduction The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ≤ 25%. Conclusions Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced. PMID:28392742

The effect of smoking on neutrophil/lymphocyte and platelet/lymphocyte ratio and platelet ındices: a retrospective study.

PubMed

Tulgar, Y K; Cakar, S; Tulgar, S; Dalkilic, O; Cakiroglu, B; Uyanik, B S

2016-07-01

Smoking commonly leads to death. Although the neutrophil/lymphocyte Ratio, platelet/lymphocyte ratio and platelet indices have been shown to be important for the diagnosis, prognosis and severity of some diseases, the smoking status of patients in these studies has not been well defined. In this study, we compared ratios derived from complete blood count and platelet indices to smoking status and length in smokers and non-smokers. The data of healthy males and females aged between 18-60 years who presented to our institute for a routine check-up were collected, and subjects were divided in two groups - smokers and non-smokers. The presence of medical history or laboratory results which could affect inflammatory response, formed our exclusion criteria. All complete blood count results were noted and persons' smoking habits were calculated as pack/years. White blood cell, neutrophil, basophil and eosinophil counts; mean corpuscular volume, red cell distribution width and neutrophil/lymphocyte ratio were significantly higher in smokers when compared to non-smokers (p<0.05). When smokers were grouped according to smoking habits; positive linear correlations were detected between pack/year and Neutrophil/lymphocyte ratio and also pack/year and plateletcrit in smokers (p<0.05). Neutrophil/lymphocyte ratio increases in correlation with pack/year while platelet/lymphocyte ratio is not affected and platelet distribution width is increased in smokers. If smokers are not excluded from studies evaluating neutrophil/lymphocyte ratio and platelet distribution width, the relationship between smoking status as well as pack/year must be determined and reported.

[Adjusting Platelet Counts for Platelet Aggregation Tests].

PubMed

Ling, Li-Qin; Yang, Xin-Chun; Chen, Hao; Liu, Chao-Nan; Chen, Si; Jiang, Hong; Jin, Ya-Xiong; Zhou, Jing

2018-03-01

To explore a better method to adjust platelet counts for light transmission aggregometry (LTA). Blood samples from 36 healthy participants aged from 18 to 50 yr. were collected.Platelet-rich plasma (PRP) was diluted using platelet-poor plasma (PPP) and physiological saline (PS),respectively,in a ratio of 1.5,2,2.5 and 3 times. Platelet aggregation was induced by adenosine diphosphate (ADP),arachidonic acid (ARA),collagen (COL), epinephrine (EPI),or ristocetin (RIS). The maximal aggregation rates (MAs) of different approaches were compared. We also compared the MAs induced by RIS between PRP-obtained-PPP and whole blood-obtained-PPP (2 100× g, 5 min). Compared with the original PRP,the MAs induced by ADP,ARA,and EPI decreased in PPP-adjusted PRP (significant at 2-3 times dilution ratio, P <0.05),but not in PS-adjusted PRP ( P >0.05). The MA induced by RIS decreased in PS-adjusted PRP (significant at all dilution ratios, P <0.05),but not in PPP-adjusted PRP ( P >0.05). No changes in the MA induced by COL were found in PS-adjusted PRP and PPP-adjusted PRP ( P >0.05). Whole blood-obtained-PPP (2 100× g, 5 min) had the same MA induced by ristocetin compared with PRP-obtained-PPP ( P >0.05). PS is recommended for adjusting platelets counts for platelet aggregation induced by ADP,ARA,COL and EPI. Whole blood-obtained-PPP (2 100 × g, 5 min) is recommended for RIS-induced aggregation as a matter of convenience. Copyright© by Editorial Board of Journal of Sichuan University (Medical Science Edition).

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.

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.

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

PubMed Central

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

2014-01-01

This is the protocol for a review and there is no abstract. The objectives are as follows: 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 patients with haematological disorders after chemotherapy with or without stem cell transplantation. PMID:25722651

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

PubMed Central

2013-01-01

Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects were observed in either patient. Conclusions In our two case reports, we found an association between vitamin D deficiency and immune thrombocytopenia where platelet levels responded to vitamin D treatment and hydroxychloroquine but not to prednisone. We believe there may be synergism between vitamin D supplementation and hydroxychloroquine. The mechanism by which high-dose vitamin D results in increased platelet counts in immune thrombocytopenia patients is unknown. However, vitamin D has long been thought to play an immunomodulatory role, which may include a dampened immune response in patients with immune thrombocytopenia or other autoimmune diseases. PMID:23556539

All Plasma Products Are Not Created Equal: Characterizing Differences Between Plasma Products

DTIC Science & Technology

2015-06-01

2011;6(4):e18812. 24. Chandler WL. Microparticle counts in platelet - rich and platelet -free plasma , effect of centrifugation and sample-processing protocols...used throughout the article for this product. Laboratory Methods Platelet -Poor Plasma Preparation Platelet -poor plasma (PPP) was prepared by centrifuga... platelets , respectively. Flow cytometry was performed as described by Matijevic et al.4 Briefly, 10 KL of each plasma product was incubated with

Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy.

PubMed

Veena, Ravindran Kalathil; Ajith, Thekkuttuparambil Ananthanarayanan; Janardhanan, Kainoor Krishnankutty; Antonawich, Francis

2016-01-01

Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton's lymphoma ascites (DLA) and Ehrlich's ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co. Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count. The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.

The value of daily platelet counts for predicting dengue shock syndrome: Results from a prospective observational study of 2301 Vietnamese children with dengue.

PubMed

Lam, Phung Khanh; Ngoc, Tran Van; Thu Thuy, Truong Thi; Hong Van, Nguyen Thi; Nhu Thuy, Tran Thi; Hoai Tam, Dong Thi; Dung, Nguyen Minh; Hanh Tien, Nguyen Thi; Thanh Kieu, Nguyen Tan; Simmons, Cameron; Wills, Bridget; Wolbers, Marcel

2017-04-01

Dengue is the most important mosquito-borne viral infection to affect humans. Although it usually manifests as a self-limited febrile illness, complications may occur as the fever subsides. A systemic vascular leak syndrome that sometimes progresses to life-threatening hypovolaemic shock is the most serious complication seen in children, typically accompanied by haemoconcentration and thrombocytopenia. Robust evidence on risk factors, especially features present early in the illness course, for progression to dengue shock syndrome (DSS) is lacking. Moreover, the potential value of incorporating serial haematocrit and platelet measurements in prediction models has never been assessed. We analyzed data from a prospective observational study of Vietnamese children aged 5-15 years admitted with clinically suspected dengue to the Hospital for Tropical Diseases in Ho Chi Minh City between 2001 and 2009. The analysis population comprised all children with laboratory-confirmed dengue enrolled between days 1-4 of illness. Logistic regression was the main statistical model for all univariate and multivariable analyses. The prognostic value of daily haematocrit levels and platelet counts were assessed using graphs and separate regression models fitted on each day of illness. Among the 2301 children included in the analysis, 143 (6%) progressed to DSS. Significant baseline risk factors for DSS included a history of vomiting, higher temperature, a palpable liver, and a lower platelet count. Prediction models that included serial daily platelet counts demonstrated better ability to discriminate patients who developed DSS from others, than models based on enrolment information only. However inclusion of daily haematocrit values did not improve prediction of DSS. Daily monitoring of platelet counts is important to help identify patients at high risk of DSS. Development of dynamic prediction models that incorporate signs, symptoms, and daily laboratory measurements, could improve DSS prediction and thereby reduce the burden on health services in endemic areas.

Platelet storage in Fresenius/NPBI polyolefin and BTHC-PVC bags: a direct comparison.

PubMed

Hornsey, V S; McColl, K; Drummond, O; Macgregor, I R; Prowse, C V

2008-08-01

New platelet storage systems, such as changes in the plastic of the storage bags, require validation. In this study, pooled buffy coat platelets stored in Fresenius/NPBI polyolefin bags were compared with those stored in Fresenius/NPBI butyryl-trihexyl citrate (BTHC) plasticized polyvinyl chloride (PVC). The CompoSelect thrombocyte polishing filter system (1000 mL polyolefin bag) and the CompoStop F730 system (1300 mL BTHC-PVC bag) were used to prepare paired, plasma-suspended, buffy coat platelet concentrates. Samples were taken up to day 7 for in vitro analysis. In a separate experiment, 12 units were prepared using the CompoStop F730 system and samples taken after leucofiltration for FXIIa assay. By day 7, platelet concentrates stored in BTHC-PVC demonstrated significantly higher pH levels (7.32 +/- 0.05 vs. 7.26 +/- 0.05) and a greater degree of cell lysis as shown by increased lactate dehydrogenase levels (497 +/- 107 vs. 392 +/- 81 U L(-1)). The supernatants contained higher concentrations of soluble P-selectin and the chemokine 'regulated on activation, normal T-cell expressed and presumably secreted', which are released from the alpha-granules during activation. The ATP concentrations were significantly lower in BTHC-PVC. Platelet counts, mean platelet volume and hypotonic shock response were similar for both bags. FXIIa antigen concentrations were 0.6 +/- 0.2 ng mL(-1) indicating that activation of the contact factor pathway had not occurred. Although the CompoStop F730 leucoreduction filter did not activate the contact system, platelets stored in 100% plasma in BTHC-PVC bags demonstrated different in vitro characteristics from those stored in polyolefin. Further work is required to demonstrate whether these differences will affect in vivo recovery and survival.

EFFECT OF THE TREATMENT WITH P-32 ON BLOOD COAGULATION FACTORS IN POLYCYTHEMIA VERA (in Italian)

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

Austoni, M.; Masetto, I.; Butto, M.

1961-01-01

Blood coagulation factors were investigated in 14 patients with polycythemia vera, before and after P/sup 32/ treatment. In connection with the improvement of clinical signs of thrombosis or hemorrhage and with the red cell count decrease, significant changes were observed, especially in the platelet sector. A general normalization of the platelet function occurred with a decrease from 420000 before to 186200/cmm after the therapy. This was evident with the Heparin tolerance test in vitro: the mean values, which were 6'39"/3 heparin Units/ml, 8'57"/7 heparin U/ml, and 12'31"/10 heparin U/ml before treatment, passed to 7'36", 11'10", and 16'08", in connection withmore » the improvement of the plasmatic thrombogenic diathesis. (P.C.H.)« less

Depressed reticuloendothelial clearance of platelets in rats after trauma.

PubMed

Kaplan, J E; Moon, D G; Minnear, F L; Saba, T M

1984-02-01

Platelet microembolization may contribute to microcirculatory and organ damage following trauma and shock. It is hypothesized that posttraumatic reticuloendothelial depression predisposes to such microembolization by failure to clear altered platelets from the circulation. The present study evaluated the short-term (1 h) clearance and organ localization of radiolabeled homologous damaged platelets in normal rats and in rats following sublethal Noble-Collip drum trauma. Platelets were collected in citrated platelet-rich plasma from normal rats and labeled with 51Cr in citrated saline. Platelets were altered by repeated centrifugation in protein-free medium. These platelets differed functionally and morphologically from normal platelets. Disappearance of iv injected damaged platelets conformed to a two-compartment exponential clearance. Velocity of clearance in the rapid compartment correlated with hepatic platelet localization, whereas velocity of clearance in the second compartment correlated with splenic platelet localization. Clearance rate of the rapid compartment was depressed at 1 h after trauma and elevated at 24 h. These changes were associated with a decrease in hepatic platelet localization at 1 h and an increase above normal at 24 h. Splenic platelet localization was decreased by 3 h following trauma. Pulmonary platelet localization was increased at all times following trauma. It is concluded that the posttrauma state is associated with a defect in the reticuloendothelial system clearance of altered platelets, which may augment embolization of platelets in the lung.

Dose of Prophylactic Platelet Transfusions and Prevention of Hemorrhage

PubMed Central

Slichter, Sherrill J.; Kaufman, Richard M.; Assmann, Susan F.; McCullough, Jeffrey; Triulzi, Darrell J.; Strauss, Ronald G.; Gernsheimer, Terry B.; Ness, Paul M.; Brecher, Mark E.; Josephson, Cassandra D.; Konkle, Barbara A.; Woodson, Robert D.; Ortel, Thomas L.; Hillyer, Christopher D.; Skerrett, Donna L.; McCrae, Keith R.; Sloan, Steven R.; Uhl, Lynne; George, James N.; Aquino, Victor M.; Manno, Catherine S.; McFarland, Janice G.; Hess, John R.; Leissinger, Cindy; Granger, Suzanne

2010-01-01

BACKGROUND We conducted a trial of prophylactic platelet transfusions to evaluate the effect of platelet dose on bleeding in patients with hypoproliferative thrombocytopenia. METHODS We randomly assigned hospitalized patients undergoing hematopoietic stem-cell transplantation or chemotherapy for hematologic cancers or solid tumors to receive prophylactic platelet transfusions at a low dose, a medium dose, or a high dose (1.1×1011, 2.2×1011, or 4.4×1011 platelets per square meter of body-surface area, respectively), when morning platelet counts were 10,000 per cubic millimeter or lower. Clinical signs of bleeding were assessed daily. The primary end point was bleeding of grade 2 or higher (as defined on the basis of World Health Organization criteria). RESULTS In the 1272 patients who received at least one platelet transfusion, the primary end point was observed in 71%, 69%, and 70% of the patients in the low-dose group, the medium-dose group, and the high-dose group, respectively (differences were not significant). The incidences of higher grades of bleeding, and other adverse events, were similar among the three groups. The median number of platelets transfused was significantly lower in the low-dose group (9.25×1011) than in the medium-dose group (11.25×1011) or the high-dose group (19.63×1011) (P = 0.002 for low vs. medium, P<0.001 for high vs. low and high vs. medium), but the median number of platelet transfusions given was significantly higher in the low-dose group (five, vs. three in the medium-dose and three in the high-dose group; P<0.001 for low vs. medium and low vs. high). Bleeding occurred on 25% of the study days on which morning platelet counts were 5000 per cubic millimeter or lower, as compared with 17% of study days on which platelet counts were 6000 to 80,000 per cubic millimeter (P<0.001). CONCLUSIONS Low doses of platelets administered as a prophylactic transfusion led to a decreased number of platelets transfused per patient but an increased number of transfusions given. At doses between 1.1×1011 and 4.4×1011 platelets per square meter, the number of platelets in the prophylactic transfusion had no effect on the incidence of bleeding. (ClinicalTrials.gov number, NCT00128713.) PMID:20164484

Matrix metalloproteinase content and activity in low-platelet, low-leukocyte and high-platelet, high-leukocyte platelet rich plasma (PRP) and the biologic response to PRP by human ligament fibroblasts.

PubMed

Pifer, Matthew A; Maerz, Tristan; Baker, Kevin C; Anderson, Kyle

2014-05-01

Recent work has shown the presence of catabolic cytokines in platelet-rich plasma (PRP), but little is known about endogenous catabolic proteases such as matrix metalloproteinases (MMPs). Hypothesis/ To quantify MMP content in 2 commercially available PRP preparation systems: Arthrex Double Syringe System autologous conditioned plasma (ACP) and Biomet GPS (GPS). The hypothesis was that MMPs are actively secreted from PRP immediately after preparation. Controlled laboratory study. PRP was prepared using either ACP (low platelet, low leukocyte) or GPS (high platelet, high leukocyte). MMP-2, MMP-3, and MMP-9 concentrations were measured using multiplex enzyme-linked immunosorbent assays for up to 6 days in 2 donors, and MMP activity was measured in 3 donors using kinetic activity kits able to detect the enzymatic cleavage of a fluorogenic peptide. Human ligament fibroblasts were cultured and exposed to both ACP and GPS from 1 donor each. MMP-2, -3, and -9 concentrations were assayed in culture media at 24 and 48 hours after exposure. GPS exhibited higher total MMP-2, -3, and -9 concentrations for up to 144 hours of release, while ACP had higher platelet-normalized MMP-2 and MMP-3 concentrations. GPS had significantly higher total and endogenous MMP-2 activity (P = .004 and .014, respectively), MMP-3 activity (P = .020 and .015, respectively), and MMP-9 activity (P = .004 and .002, respectively) compared with ACP. Once normalized to platelet count, differences in MMP activity were not significant between ACP and GPS. Compared with controls, cells stimulated with interleukin-1 beta (IL-1β) and treated with ACP showed significantly higher fold changes of MMP-2 (P = .001) and MMP-3 (P = .003) concentrations at 24 hours than did cells treated with GPS. Total MMP-9 content was higher in the media of GPS-treated, IL-1β-stimulated cells compared with ACP-treated cells (P = .001). At 48 hours, IL-1β-stimulated cells treated with GPS exhibited higher fold changes of MMP-2 concentration (P = .002) compared with controls, but no difference in MMP-3 concentration was found. At 48 hours, there was a significantly higher concentration of MMP-9 in the cell culture media of ACP-treated cells compared with GPS-treated cells (P = .003). PRP prepared as both ACP and GPS contains MMP-2, -3, and -9, which is released over a period of at least 6 days. Furthermore, a large proportion of these MMPs are in their active form, and MMP activity is dependent on platelet count within the PRP preparation. Once exposed to ligament fibroblasts, both ACP and GPS cause the fibroblasts to release MMPs, most notably 24 hours after PRP exposure, and this release is dependent on prior IL-1β stimulation. The results of this study demonstrate that PRP therapy delivers ng/mL-range concentrations of catabolic proteases, which could perpetuate inflammation and inhibit tissue healing.

Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura

PubMed Central

Noonavath, Ravinder Naik; Lakshmi, Chandrasekharan Padma; Dutta, Tarun Kumar; Kate, Vikram

2014-01-01

AIM: To assess the effect of Helicobacter pylori (H. pylori) eradication on platelet counts in patients with chronic immune thrombocytopenic purpura (cITP). METHODS: A total of 36 cITP patients were included in the study. The diagnosis of H. pylori was done by rapid urease test and Giemsa staining of the gastric biopsy specimen. All H. pylori positive patients received standard triple therapy for 14 d and were subjected for repeat endoscopy at 6 wk. Patients who continued to be positive for H. pylori on second endoscopy received second line salvage therapy. All the patients were assessed for platelet response at 6 wk, 3rd and 6th months. RESULTS: Of the 36 patients, 17 were positive for H. pylori infection and eradication was achieved in 16 patients. The mean baseline platelet count in the eradicated patients was 88615.38 ± 30117.93/mm3 and platelet count after eradication at 6 wk, 3 mo and 6 mo was 143230.77 ± 52437.51/mm3 (P = 0.003), 152562.50 ± 52892.3/mm3 (P = 0.0001), 150187.50 ± 41796.68/mm3 (P = 0.0001) respectively and in the negative patients, the mean baseline count was 71000.00 ± 33216.46/mm3 and at 6 wk, 3rd and 6th month follow up was 137631.58 ± 74364.13/mm3 (P = 0.001), 125578.95 ± 71472.1/mm3 (P = 0.005), 77210.53 ± 56892.28/mm3 (P = 0.684) respectively. CONCLUSION: Eradication of H. pylori leads to increase in platelet counts in patients with cITP and can be recommended as a complementary treatment with conventional therapy. PMID:24944483

Evaluation of the Value of d-Dimer, P-Selectin, and Platelet Count for Prediction of Portal Vein Thrombosis After Devascularization.

PubMed

Fei, Yang; Zong, Guang-Quan; Chen, Jian; Liu, Ren-Min

2016-07-01

To evaluate the value of d-dimer, P-selectin, and platelet count in patients with cirrhotic portal hypertension (PHT) for prediction of portal vein thrombosis (PVT) after devascularization. A total of 137 patients with cirrhotic PHT who undergone devascularization from January 2012 to April 2014 were retrospectively reviewed, all of them were divided into 2 groups (PVT group and non-PVT group) by Doppler ultrasonography (DU) examination. The level of d-dimer, P-selectin, and platelet count was tested during the perioperative period. In all, 38 (27.7%) patients were found to have PVT by DU examination postoperatively. In contrast to the non-PVT group, the level of d-dimer, P-selectin, and platelet count in the PVT group was much higher significantly at 1, 3, and 7 days after devascularization. (P < .05). However, in the 15 days after surgery, the difference in P-selectin between the 2 groups was not significant (P = .260). It was shown that the highest sensitivity of the 3 markers for PVT was d-dimer, the highest specificity belonged to P-selectin. The area under receiver-operating characteristic (ROC) curve of P-selectin was the biggest of the 3 markers. When the 3 markers were combined to be used to diagnose PVT, the sensitivity was increased to 0.907, with a slight drop of specificity to 0.693, the area under the ROC curve was 0.927. The level of d-dimer, P-selectin, and platelet count might be good candidate predictive markers for PVT in patients with cirrhotic PHT after devascularization. The combined test of the 3 markers can increase the value of prediction. © The Author(s) 2015.

Platelet count recovery after intravenous immunoglobulin predicts a favorable outcome in children with immune thrombocytopenia

PubMed Central

Ji, Mi Hong; Kim, Sung Jin; Ahn, Hyo Seop

2016-01-01

Background Childhood immune thrombocytopenic purpura (ITP) is a common acquired bleeding disorder. Even though most children recover, either spontaneously or with therapy, 10-20% of newly diagnosed ITP cases have a chronic course beyond 12 months. This study evaluated whether clinical and laboratory findings can predict the response to intravenous immunoglobulin (IVIG) and progression to persistent or chronic ITP in children. Methods During the period between March 2003 and June 2015, we retrospectively analyzed 72 children, newly diagnosed with ITP, who received IVIG treatment. Peripheral blood counts were obtained at diagnosis and at 1, 3, 6, and 12 months after IVIG treatment. Results After 6 months of IVIG treatment, 14 of 72 patients (19.4%) had persistent ITP, and after 12 months, 7 of 40 patients (17.5%) had chronic ITP. Age at diagnosis, gender, history of viral infection, or vaccination before disease onset were not statistically correlated with platelet recovery at 6 and 12 months. However, a platelet count recovery of ≥100×103/µL at 1 and 3 months was significantly correlated with platelet recovery at 6 (P<0.001 and P<0.001, respectively) and 12 (P=0.007 and P=0.004, respectively) months. Conclusion This study demonstrated that early platelet count recovery, at 1 and 3 months after IVIG treatment, predicts a short disease duration and a favorable outcome in children with newly diagnosed ITP. Further investigation in a larger group of patients is warranted to validate these findings. PMID:27382553

2-O, 3-O desulfated heparin mitigates murine chemotherapy- and radiation-induced thrombocytopenia

PubMed Central

Tkaczynski, Elizabeth; Arulselvan, Abinaya; Tkaczynski, John; Avery, Stephen; Xiao, Liqing; Torok-Storb, Beverly; Abrams, Kraig; Rao, Narayanam V.; Johnson, Gregory; Poncz, Mortimer

2018-01-01

Thrombocytopenia is a significant complication of chemotherapy and radiation therapy. Platelet factor 4 (PF4; CXCL4) is a negative paracrine of megakaryopoiesis. We have shown that PF4 levels are inversely related to steady-state platelet counts, and to the duration and severity of chemotherapy- and radiation-induced thrombocytopenia (CIT and RIT, respectively). Murine studies suggest that blocking the effect of PF4 improves megakaryopoiesis, raising nadir platelet counts and shortening the time to platelet count recovery. We examined the ability of 2-O, 3-O desulfated heparin (ODSH), a heparin variant with little anticoagulant effects, to neutralize PF4’s effects on megakaryopoiesis. Using megakaryocyte colony assays and liquid cultures, we show that ODSH restored megakaryocyte proliferation in PF4-treated Cxcl4−/− murine and human CD34+-derived megakaryocyte cultures (17.4% megakaryocyte colonies, P < .01 compared with PF4). In murine CIT and RIT models, ODSH, started 24 hours after injury, was examined for the effect on hematopoietic recovery demonstrating higher platelet count nadirs (9% ± 5% treated vs 4% ± 4% control) and significantly improved survival in treated animals (73% treated vs 36% control survival). Treatment with ODSH was able to reduce intramedullary free PF4 concentrations by immunohistochemical analysis. In summary, ODSH mitigated CIT and RIT in mice by neutralizing the intramedullary negative paracrine PF4. ODSH, already in clinical trials in humans as an adjuvant to chemotherapy, may be an important, clinically relevant therapeutic for CIT and RIT. PMID:29599195

Study of a Two-Step Centrifugation Protocol for Concentrating Cells and Growth Factors in Bovine Platelet-Rich Plasma

PubMed Central

Gutiérrez, Claudia M.; López, Catalina

2017-01-01

There is a lack of information about the methods used for bovine platelet-rich plasma (PRP)/platelet-rich gel (PRG) procurement, including information on platelet (PLT), white blood cell (WBC) in PRP, and growth factor release from PRG supernatants. The aims of this study were to compare and to correlate the PLT, WBC, transforming growth factor beta-1 (TGF-β1), and platelet-derived growth factor BB (PDGF-BB) concentrations in bovine whole blood, plasma, and four PRP layers and their respective PRG supernatants: A and B (obtained by a single centrifugation tube method at 720g/5 min) and C and D (obtained by a double centrifugation tube method, by using two centrifugation episodes at 720g/5 min). PLT and WBC counts were significantly higher in PRP-C, followed by whole blood, PRP-A, PRP-B, and PRP-D. TGF-β1 concentrations were significantly higher in PRG-B supernatants and its correspondent PRP-B lysate when compared to the other PRG supernatants and plasma. Supernatants from PRG-A, PRG-B, and PRG-D had equivalent TGF-β1 concentrations. PDGF-BB concentrations were not statistically different between the hemoderivatives. Significant Pearson correlations were noted between PLT counts and WBC counts (0.8) and between PLT counts and PLT distribution width (0.6). Further studies should be performed to assess the potential clinical applications of these PRPs. PMID:29214094

Can mean platelet volume and neutrophil-to-lymphocyte ratio be biomarkers of acute exacerbation of bronchiectasis in children?

PubMed Central

Erdem, Semiha Bahceci; Karaman, Sait; Yazici, Selcuk; Can, Demet

2017-01-01

Introduction Bronchiectasis (BE) is a parenchymal lung disease evolving as a result of recurrent lung infections and chronic inflammation. Although it has been shown in adult studies that mean platelet volume (MPV) and neutrophil-to-lymphocyte ratio (NLR) can be used as biomarkers of airway inflammation, knowledge is limited in the paediatric age group. The aim of our study is to investigate the potential of MPV and NLR as biomarkers that may indicate acute exacerbations of non-cystic fibrosis BE in children. Material and methods Children with non-cystic fibrosis BE (n = 50), who were followed in the division of Paediatric Pulmonology of our hospital between June 2010 and July 2015, were involved in the present retrospective cross-sectional study. Haemogram values during acute exacerbations and non-exacerbation periods, and a control group were compared. Results In children with bronchiectasis, the average leukocyte count (p < 0.001), platelet count (p = 0.018), absolute neutrophil count (p < 0.001), and NLR (p < 0.001) were higher, as expected, when compared with the control group. NLR values, in the period of acute exacerbation were significantly higher than the values of both the non-exacerbation periods (p = 0.02) and the control group (p < 0.001). In contrast, MPV values in the period of acute exacerbation did not exhibit a significant difference from those of non-exacerbation periods (p = 0.530) and the control group (p = 0.103). Conclusions It was concluded that leukocyte count, platelet count, absolute neutrophil count, and NLR can be used to show chronic inflammation in BE, but only NLR and absolute neutrophil count can be used as biomarkers to show acute exacerbations. PMID:29472813

Mean platelet volume is elevated in patients with patent foramen ovale.

PubMed

Demir, Bulent; Caglar, Ilker Murat; Ungan, Ismail; Ugurlucan, Murat; Tureli, Hande Oktay; Karakaya, Osman

2013-12-30

Platelets play a major role in thromboembolic events. Increased mean platelet volume (MPV) indicates higher platelet reactivity and also a tendency to thrombosis. Patent foramen ovale (PFO), persistence of the fetal anatomic shunt between right and left atria, is strongly associated with cryptogenic stroke. The aim of this study is to determine the relationship between MPV and PFO and if such an association exists, whether higher MPV levels may require antiplatelet therapy before a thromboembolic event happens, together with a literature review. Thirty patients (15 women, 15 men), free of any cerebrovascular events, were diagnosed with PFO by transesophageal echocardiography (TEE), enrolled as the study group. Thirty consecutive patients (16 women and 14 men), who were diagnosed as normal in TEE, were enrolled as the control group. These two groups were compared according to MPV and anatomical features of the right atrium. There was no significant difference between study and control groups in clinical features and also no difference was observed in platelet counts; however, MPV in the PFO group was significantly higher than the control group (8.38 ±0.93 fl and 7.45 ±0.68 fl respectively). Our results indicate that elevated MPV may be detected in patients with PFO. This might be one of the explanations for the relationship between PFO and cryptogenic stroke; however, larger cohorts are warranted in order to define further mechanisms.

Premature aging of cardiovascular/platelet function in polycystic ovarian syndrome.

PubMed

Chan, Wai Ping A; Ngo, Doan T; Sverdlov, Aaron L; Rajendran, Sharmalar; Stafford, Irene; Heresztyn, Tamila; Chirkov, Yuliy Y; Horowitz, John D

2013-07-01

The objective of this study was to compare the impact of aging on nitric oxide (NO) modulation of platelet and vascular function in healthy women and women with polycystic ovary syndrome. A case-control study of women ages 18 to 60 years, comparing women with polycystic ovarian syndrome against age-matched healthy controls, was performed. A total of 242 women, of whom 109 had polycystic ovarian syndrome (based on Rotterdam criteria), participated in the study. Women who were pregnant or on clopidogrel were excluded from the study. Inhibition of platelet aggregation by nitric oxide (primary outcome measure), vascular endothelial function, plasma concentrations of N(G), N(G)-dimethyl-L-arginine (ADMA), endothelial progenitor cell count, and high-sensitivity C-reactive protein (markers of endothelial dysfunction and inflammation) were assessed. With increasing age in control women, there was progressive attenuation of platelet responses to NO, impairment of endothelial function, and elevation of ADMA levels (P ≤.001). Irrespective of age, women with polycystic ovarian syndrome exhibited greater impairment of all these parameters (all P <.05, 2-way analysis of variance) and demonstrated these anomalies earlier in life. Normal aging in women is associated with attenuation of NO-based signaling in platelets and blood vessels. In women with polycystic ovarian syndrome, these changes are present from early adult life and may contribute to premature atherogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

Acute effects of 30 minutes of exposure to a smartphone call on in vitro platelet function

PubMed Central

Lippi, Giuseppe; Danese, Elisa; Brocco, Giorgio; Gelati, Matteo; Salvagno, Gian Luca; Montagnana, Martina

2017-01-01

Background Significant concerns are now regularly raised about the safety of excessive mobile phone use. This study was aimed to assess the acute effects of radiofrequency waves emitted by a commercial smartphone on platelet function. Materials and methods Two sequential citrated blood samples were collected from 16 healthy volunteers recruited from laboratory staff. The first sample was placed in a plastic rack, 1 cm distant from a commercial smartphone receiving a 30-min call and emitting 900 MHz radiofrequency waves. The second sample was placed in another plastic rack, isolated from radiofrequency wave sources, for the same period. The platelet count and the mean platelet volume were then assessed in all blood samples, whereas platelet function was evaluated using the platelet function analyser-100 (PFA-100). Results A 30-min exposure of citrated blood to smartphone radiofrequency waves induced significant prolongation of collagen-epinephrine aggregation (median increase, 10%) and a considerable increase of mean platelet volume (median increase, 5%), whereas collagen-adenosine diphosphate aggregation and platelet count remained unchanged. Discussion This study demonstrates that smartphone radiofrequency waves induce significant perturbation of platelet structure and function, thus providing further support to concerns regarding excessive use of mobile phones. Caution should also be taken with regards to blood products containing platelets, which should be kept far away from mobile phones and smartphones throughout the production pipeline and storage period. PMID:27177410

Effects of Nd:YAG laser-heated metal cap on human platelets in vitro

NASA Astrophysics Data System (ADS)

Liu, Xia; Guo, You-chi

1993-03-01

Human platelet-rich plasma (PRP) was irradiated in vitro with a fiberoptic Nd:YAG laser-heated metal cap to study its effects on platelets. The energy of the laser was 5 and 10 watts with an irradiation time of 0, 3, 6, and 9 seconds and 14 watts with an irradiation time of 0, 3, 4, and 5 seconds, respectively. The irradiated PRPs were analyzed for platelet count, aggregation reaction, thromboxane (TX)B2 measurement and electron microscopy. Various degrees of decrease in platelet count were observed in all groups. Except the 5Wx3S group, the other groups showed an increase in the maximum aggregation rate of platelets, which corresponded to the enhancement of TXB2 formation. It was also demonstrated by a transmission electron microscopy in 10Wx3S, 10Wx6S, 10Wx9S, 14Wx3S, 14Wx4S, and 14Wx5S energy groups that alpha- and dense-particles in irradiated platelets became sparse in number or even disappeared, less electron density, irregularity in size and shape, and a tendency for these particles to cluster around platelet membranes and open canalicular systems, which dilated apparently. Furthermore, scanning electron microscopy depicted the appearance of short and thick pseudopods on the surfaces of some irradiated platelets and an increase in the axis rate in most of the irradiated platelets.

Acute effects of 30 minutes of exposure to a smartphone call on in vitro platelet function.

PubMed

Lippi, Giuseppe; Danese, Elisa; Brocco, Giorgio; Gelati, Matteo; Salvagno, Gian Luca; Montagnana, Martina

2017-05-01

Significant concerns are now regularly raised about the safety of excessive mobile phone use. This study was aimed to assess the acute effects of radiofrequency waves emitted by a commercial smartphone on platelet function. Two sequential citrated blood samples were collected from 16 healthy volunteers recruited from laboratory staff. The first sample was placed in a plastic rack, 1 cm distant from a commercial smartphone receiving a 30-min call and emitting 900 MHz radiofrequency waves. The second sample was placed in another plastic rack, isolated from radiofrequency wave sources, for the same period. The platelet count and the mean platelet volume were then assessed in all blood samples, whereas platelet function was evaluated using the platelet function analyser-100 (PFA-100). A 30-min exposure of citrated blood to smartphone radiofrequency waves induced significant prolongation of collagen-epinephrine aggregation (median increase, 10%) and a considerable increase of mean platelet volume (median increase, 5%), whereas collagen-adenosine diphosphate aggregation and platelet count remained unchanged. This study demonstrates that smartphone radiofrequency waves induce significant perturbation of platelet structure and function, thus providing further support to concerns regarding excessive use of mobile phones. Caution should also be taken with regards to blood products containing platelets, which should be kept far away from mobile phones and smartphones throughout the production pipeline and storage period.

Growth factor and pro-inflammatory cytokine contents in platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), advanced platelet-rich fibrin (A-PRF), and concentrated growth factors (CGF).

PubMed

Masuki, Hideo; Okudera, Toshimitsu; Watanebe, Taisuke; Suzuki, Masashi; Nishiyama, Kazuhiko; Okudera, Hajime; Nakata, Koh; Uematsu, Kohya; Su, Chen-Yao; Kawase, Tomoyuki

2016-12-01

The development of platelet-rich fibrin (PRF) drastically simplified the preparation procedure of platelet-concentrated biomaterials, such as platelet-rich plasma (PRP), and facilitated their clinical application. PRF's clinical effectiveness has often been demonstrated in pre-clinical and clinical studies; however, it is still controversial whether growth factors are significantly concentrated in PRF preparations to facilitate wound healing and tissue regeneration. To address this matter, we performed a comparative study of growth factor contents in PRP and its derivatives, such as advanced PRF (A-PRF) and concentrated growth factors (CGF). PRP and its derivatives were prepared from the same peripheral blood samples collected from healthy donors. A-PRF and CGF preparations were homogenized and centrifuged to produce extracts. Platelet and white blood cell counts in A-PRF and CGF preparations were determined by subtracting those counts in red blood cell fractions, supernatant acellular serum fractions, and A-PRF/CGF exudate fractions from those counts of whole blood samples. Concentrations of growth factors (TGF-β1, PDGF-BB, VEGF) and pro-inflammatory cytokines (IL-1β, IL-6) were determined using ELISA kits. Compared to PRP preparations, both A-PRF and CGF extracts contained compatible or higher levels of platelets and platelet-derived growth factors. In a cell proliferation assay, both A-PRF and CGF extracts significantly stimulated the proliferation of human periosteal cells without significant reduction at higher doses. These data clearly demonstrate that both A-PRF and CGF preparations contain significant amounts of growth factors capable of stimulating periosteal cell proliferation, suggesting that A-PRF and CGF preparations function not only as a scaffolding material but also as a reservoir to deliver certain growth factors at the site of application.

Whole blood flow cytometry measurements of in vivo platelet activation in critically-Ill patients are influenced by variability in blood sampling techniques.

PubMed

Rondina, Matthew T; Grissom, Colin K; Men, Shaohua; Harris, Estelle S; Schwertz, Hansjorg; Zimmerman, Guy A; Weyrich, Andrew S

2012-06-01

Flow cytometry is often used to measure in vivo platelet activation in critically-ill patients. Variability in blood sampling techniques, which may confound these measurements, remains poorly characterized. Platelet activation was measured by flow cytometry performed on arterial and venous blood from 116 critically-ill patients. We determined how variability in vascular sampling site, processing times, and platelet counts influenced levels of platelet-monocyte aggregates (PMA), PAC-1 binding (for glycoprotein (GP) IIbIIIa), and P-selectin (P-SEL) expression. Levels of PMA, but not PAC-1 binding or P-SEL expression, were significantly affected by variability in vascular sampling site. Average PMA levels were approximately 60% higher in whole blood drawn from an arterial vessel compared to venous blood (16.2±1.8% vs. 10.7±1.2%, p<0.05). Levels of PMA in both arterial and venous blood increased significantly during ex vivo processing delays (1.7% increase for every 10 minute delay, p<0.05). In contrast, PAC-1 binding and P-SEL expression were unaffected by processing delays. Levels of PMA, but not PAC-1 binding or P-SEL expression, were correlated with platelet count quartiles (9.4±1.6% for the lowest quartile versus 15.4±1.6% for the highest quartile, p<0.05). In critically-ill patients, variability in vascular sampling site, processing times, and platelet counts influence levels of PMA, but not PAC-1 binding or P-SEL expression. These data demonstrate the need for rigorous adherence to blood sampling protocols, particularly when levels of PMA, which are most sensitive to variations in blood collection, are measured for detection of in vivo platelet activation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Mean Platelet Volume, Red Cell Distribution Width to Platelet Count Ratio, Globulin Platelet Index, and 16 Other Indirect Noninvasive Fibrosis Scores: How Much Do Routine Blood Tests Tell About Liver Fibrosis in Chronic Hepatitis C?

PubMed

Thandassery, Ragesh B; Al Kaabi, Saad; Soofi, Madiha E; Mohiuddin, Syed A; John, Anil K; Al Mohannadi, Muneera; Al Ejji, Khalid; Yakoob, Rafie; Derbala, Moutaz F; Wani, Hamidullah; Sharma, Manik; Al Dweik, Nazeeh; Butt, Mohammed T; Kamel, Yasser M; Sultan, Khaleel; Pasic, Fuad; Singh, Rajvir

2016-07-01

Many indirect noninvasive scores to predict liver fibrosis are calculated from routine blood investigations. Only limited studies have compared their efficacy head to head. We aimed to compare these scores with liver biopsy fibrosis stages in patients with chronic hepatitis C. From blood investigations of 1602 patients with chronic hepatitis C who underwent a liver biopsy before initiation of antiviral treatment, 19 simple noninvasive scores were calculated. The area under the receiver operating characteristic curves and diagnostic accuracy of each of these scores were calculated (with reference to the Scheuer staging) and compared. The mean age of the patients was 41.8±9.6 years (1365 men). The most common genotype was genotype 4 (65.6%). Significant fibrosis, advanced fibrosis, and cirrhosis were seen in 65.1%, 25.6, and 6.6% of patients, respectively. All the scores except the aspartate transaminase (AST) alanine transaminase ratio, Pohl score, mean platelet volume, fibro-alpha, and red cell distribution width to platelet count ratio index showed high predictive accuracy for the stages of fibrosis. King's score (cutoff, 17.5) showed the highest predictive accuracy for significant and advanced fibrosis. King's score, Göteborg university cirrhosis index, APRI (the AST/platelet count ratio index), and Fibrosis-4 (FIB-4) had the highest predictive accuracy for cirrhosis, with the APRI (cutoff, 2) and FIB-4 (cutoff, 3.25) showing the highest diagnostic accuracy.We derived the study score 8.5 - 0.2(albumin, g/dL) +0.01(AST, IU/L) -0.02(platelet count, 10/L), which at a cutoff of >4.7 had a predictive accuracy of 0.868 (95% confidence interval, 0.833-0.904) for cirrhosis. King's score for significant and advanced fibrosis and the APRI or FIB-4 score for cirrhosis could be the best simple indirect noninvasive scores.

Relationship between platelet-to-lymphocyte ratio and coronary slow flow.

PubMed

Oylumlu, Muhammed; Doğan, Adnan; Oylumlu, Mustafa; Yıldız, Abdülkadir; Yüksel, Murat; Kayan, Fethullah; Kilit, Celal; Amasyalı, Basri

2015-05-01

The coronary slow flow phenomenon (CSFP), which is characterized by delayed distal vessel opacification in the absence of significant epicardial coronary disease, is an angiographic finding. The aim of this study is to investigate the association between platelet-to-lymphocyte ratio (PLR) and coronary blood flow rate. This is a retrospective observational study. It was based on two medical centers. A total of 197 patients undergoing coronary angiography were included in the study, 95 of whom were patients with coronary slow flow without stenosis in coronary angiography and 102 of whom had normal coronary arteries and normal flow. The PLR was higher in the coronary slow flow group compared with the control groups (p=0.001). In the correlation analysis, PLR showed a significant correlation with left anterior descending (LAD) artery thrombolysis in myocardial infarction (TIMI) frame count. After multiple logistic regression, high levels of PLR were independently associated with coronary slow flow, together with hemoglobin. PLR was higher in patients with CSFP, and we also showed that PLR was significantly and independently associated with CSFP.

Platelet Dynamics during Natural and Pharmacologically Induced Torpor and Forced Hypothermia

PubMed Central

de Vrij, Edwin L.; Vogelaar, Pieter C.; Goris, Maaike; Houwertjes, Martin C.; Herwig, Annika; Dugbartey, George J.; Boerema, Ate S.; Strijkstra, Arjen M.; Bouma, Hjalmar R.; Henning, Robert H.

2014-01-01

Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5′-AMP in mice did not induce thrombocytopenia, possibly because 5′-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets, dependent on intrinsic platelet functionality, governs clearance of circulating platelets during torpor. PMID:24722364

Levofloxacin-Induced Acute Immune-Mediated Thrombocytopenia of Rapid-Onset.

PubMed

Shih, Andrew W; Lam, Andy S; Warkentin, Theodore E

2018-04-01

Drug-induced immune thrombocytopenia (D-ITP) typically occurs after the patient has been receiving the implicated drug for at least 1 week, due to newly forming drug-dependent antibodies ("typical-onset" D-ITP). A "rapid-onset" form of D-ITP can occur when previous sensitization has occurred, where antibodies have thus already been formed, and a precipitous platelet count fall occurs upon reexposure. Typical-onset D-ITP has been reported after levofloxacin, but the rapid-onset form with a well-documented previous exposure has not been described. We report a 76-year-old male treated with levofloxacin for acute exacerbation of chronic obstructive pulmonary disease. After a single 750 mg oral dose of levofloxacin, his platelet count fell from 187 to 5 × 10 9 /L (nadir) over 4 days. Other causes of thrombocytopenia were ruled out. He had received a previous course of levofloxacin 6 months earlier. Discontinuation of levofloxacin and treatment with intravenous immunoglobulin and dexamethasone resulted in platelet count recovery. Levofloxacin-dependent antibodies were not detectable, consistent with the known low sensitivity of laboratory tests for drug-dependent antibodies, presumably indicating antibodies against levofloxacin metabolites, as is indirectly supported by the abrupt but relatively slow platelet count decline observed. This case illustrates a rapid-onset presentation of levofloxacin-induced D-ITP in the setting of previous drug exposure.

Evaluation of mouse red blood cell and platelet counting with an automated hematology analyzer.

PubMed

Fukuda, Teruko; Asou, Eri; Nogi, Kimiko; Goto, Kazuo

2017-10-07

An evaluation of mouse red blood cell (RBC) and platelet (PLT) counting with an automated hematology analyzer was performed with three strains of mice, C57BL/6 (B6), BALB/c (BALB) and DBA/2 (D2). There were no significant differences in RBC and PLT counts between manual and automated optical methods in any of the samples, except for D2 mice. For D2, RBC counts obtained using the manual method were significantly lower than those obtained using the automated optical method (P<0.05), and PLT counts obtained using the manual method were higher than those obtained using the automated optical method (P<0.05). An automated hematology analyzer can be used for RBC and PLT counting; however, an appropriate method should be selected when D2 mice samples are used.

Intracellular activation of the fibrinolytic cascade in the Quebec Platelet Disorder.

PubMed

Sheth, Prameet M; Kahr, Walter H A; Haq, M Anwar; Veljkovic, Dragoslava Kika; Rivard, Georges E; Hayward, Catherine P M

2003-08-01

The Quebec Platelet Disorder (QPD) is an unusual bleeding disorder associated with increased platelet stores of urokinase-type plasminogen activator (u-PA) and proteolysis of platelet alpha-granule proteins. The increased u-PA and proteolyzed plasminogen in QPD platelets led us to investigate possible contributions of intracellular plasmin generation to QPD alpha-granule proteolysis. ELISA indicated there were normal amounts of plasminogen and plasmin-alpha(2)-antiplasmin (PAP) complexes in QPD plasmas. Like normal platelets, QPD platelets contained only a small proportion of the blood plasminogen, however, they contained an increased amount of PAP complexes compared to normal platelets (P < 0.005). The quantities of plasminogen stored in platelets were important to induce QPD-like proteolysis of normal alpha-granule proteins by two chain u-PA (tcu-PA) in vitro. Moreover, adding supplemental plasminogen to QPD, but not to control, platelet lysates, triggered further alpha-granule protein proteolysis to forms that comigrated with plasmin degraded proteins. These data suggest the generation of increased but limiting amounts of plasmin within platelets is involved in producing the unique phenotypic changes to alpha-granule proteins in QPD platelets. The QPD is the only known bleeding disorder associated with chronic, intracellular activation of the fibrinolytic cascade.

Relations of Platelet Indices with Endometrial Hyperplasia and Endometrial Cancer.

PubMed

Karateke, Atilla; Kaplanoglu, Mustafa; Baloglu, Ali

2015-01-01

Platelets are blood elements thought to play a role in the immune system and therefore tumor development and metastasis. Platelet activation parameters such as mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) can be easily evaluated with the whole blood count and have been studied as markers of systemic inflammatory responses in various cancer types. Our aim in this study was to evaluate the correlation between endometrial pathologies and MPV, PDW and PCT. A total of 194 patients who presented to our clinic with abnormal vaginal bleeding were included in our study. The patients were divided into 3 groups (endometrial hyperplasia, endometrial cancer, control) according to their pathology results. The groups were compared for MPV, PDW, and PCT values obtained from the blood samples taken on endometrial biopsy day. The endometrial cancer patients were the oldest group (p=0.04). There was no significant difference between the three groups in terms of white blood cell count (WBC), platelet count (PC), and hemoglobin (Hb) level. The highest MPV (p<0.001), PDW (p=0.002), and PCT (p<0.001) levels were in the endometrial cancer group, and the lowest levels were in the control group. The easy evaluation of platelet parameters in patients who are suspected of having endometrial pathology is a significant advantage. We found MPV, PDW, and PCT to be correlated with the severity of endometrial pathology with the highest values in endometrial cancer. Studies to be conducted together with different laboratory parameters will further help evaluate the diagnosis and severity of endometrial cancer and precursor lesions.

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.

Platelet closure time in anesthetized Greyhounds with hemorrhagic shock treated with hydroxyethyl starch 130/0.4 or 0.9% sodium chloride infusions.

PubMed

McBride, Duana; Hosgood, Giselle; Raisis, Anthea; Smart, Lisa

2016-07-01

To measure platelet closure time (PCT) in dogs during controlled hemorrhagic shock and after fluid resuscitation with hydroxyethyl starch (HES) 130/0.4 or 0.9% sodium chloride. Experimental interventional study. University veterinary teaching hospital. Eleven healthy Greyhounds. Dogs were anesthetized and had 48 mL/kg of blood removed to induce hemorrhagic shock. Dogs received 20 mL/kg of HES 130/0.4 (n = 6) or 80 mL/kg of 0.9% sodium chloride (NaCl; n = 5) intravenously over 20 minutes. PCT was measured using the Platelet Function Analyzer-100 with collagen and adenosine-diphosphate cartridges at: T0 = 60 minutes after induction of anesthesia prior to hemorrhage, T1 = during hemorrhagic shock, and T2 = 40 minutes after completion of fluid bolus. Packed cell volume and platelet count were concurrently measured. Hemorrhagic shock did not significantly change PCT, with no difference between T0 and T1. Both the HES 130/0.4 and 0.9% NaCl group had a significantly increased mean PCT at T2 of 91.4 seconds (95% CI 69.3-113.4) and 95.5 seconds (95% CI 78.2-112.8), respectively, compared to T1. The magnitude of change was significantly greater for the 0.9% NaCl group than the HES 130/0.4 group. There was no difference in the magnitude of change in PCV and platelet count between the 2 groups. The PCV and platelet count were >25% and >100,000/μL, respectively, in all dogs, except for dogs in the HES 130/0.4 group at T2 where platelet counts were <100,000/μL. Controlled hemorrhagic shock in Greyhounds under anesthesia did not cause a significant change in PCT. Both HES 130/0.4 and 0.9% NaCl administration after induction of shock increased PCT. These results do not support that HES 130/0.4 causes relevant platelet dysfunction beyond hemodilution. © Veterinary Emergency and Critical Care Society 2016.

Enhancing the Accuracy of Platelet to Lymphocyte Ratio after Adjustment for Large Platelet Count: A Pilot Study in Breast Cancer Patients

PubMed Central

Seretis, Charalampos; Seretis, Fotios; Lagoudianakis, Emmanuel; Politou, Marianna; Gemenetzis, George; Salemis, Nikolaos S.

2012-01-01

Background. The objective of our study is to investigate the potential effect of adjusting preoperative platelet to lymphocyte ratio, an emerging biomarker of survival in cancer patients, for the fraction of large platelets. Methods. A total of 79 patients with breast neoplasias, 44 with fibroadenomas, and 35 with invasive ductal carcinoma were included in the study. Both conventional platelet to lymphocyte ratio (PLR) and the adjusted marker, large platelet to lymphocyte ratio (LPLR), were correlated with laboratory and histopathological parameters of the study sample. Results. LPLR elevation was significantly correlated with the presence of malignancy, advanced tumor stage, metastatic spread in the axillary nodes and HER2/neu overexpression, while PLR was only correlated with the number of infiltrated lymph nodes. Conclusions. This is the first study evaluating the effect of adjustment for large platelet count on improving PLR accuracy, when correlated with the basic independent markers of survival in a sample of breast cancer patients. Further studies are needed in order to assess the possibility of applying our adjustment as standard in terms of predicting survival rates in cancer. PMID:23304480

Enhancing the accuracy of platelet to lymphocyte ratio after adjustment for large platelet count: a pilot study in breast cancer patients.

PubMed

Seretis, Charalampos; Seretis, Fotios; Lagoudianakis, Emmanuel; Politou, Marianna; Gemenetzis, George; Salemis, Nikolaos S

2012-01-01

Background. The objective of our study is to investigate the potential effect of adjusting preoperative platelet to lymphocyte ratio, an emerging biomarker of survival in cancer patients, for the fraction of large platelets. Methods. A total of 79 patients with breast neoplasias, 44 with fibroadenomas, and 35 with invasive ductal carcinoma were included in the study. Both conventional platelet to lymphocyte ratio (PLR) and the adjusted marker, large platelet to lymphocyte ratio (LPLR), were correlated with laboratory and histopathological parameters of the study sample. Results. LPLR elevation was significantly correlated with the presence of malignancy, advanced tumor stage, metastatic spread in the axillary nodes and HER2/neu overexpression, while PLR was only correlated with the number of infiltrated lymph nodes. Conclusions. This is the first study evaluating the effect of adjustment for large platelet count on improving PLR accuracy, when correlated with the basic independent markers of survival in a sample of breast cancer patients. Further studies are needed in order to assess the possibility of applying our adjustment as standard in terms of predicting survival rates in cancer.

Big spleens and hypersplenism: fix it or forget it?

PubMed

Boyer, Thomas D; Habib, Shahid

2015-05-01

Hypersplenism is a common manifestation of portal hypertension in the cirrhotic. More than half of cirrhotics will have low platelet counts, but neutropenia is much less common. Despite being common in the cirrhotic population, the presence of hypersplenism is of little clinical consequence. The presence of hypersplenism suggests more advanced liver disease and an increase in risk of complications, but there is no data showing that correcting the hypersplenism improves patient survival. In most series, the most common indications for treating the hypersplenism is to increase platelet and white blood cell counts to allow for use of drugs that suppress the bone marrow such as interferon alpha and chemotherapeutic agents. There are several approaches used to treat hypersplenism. Portosystemic shunts are of questionable benefit. Splenectomy, either open or laparoscopically, is the most effective but is associated with a significant risk of portal vein thrombosis. Partial splenic artery embolization and radiofrequency ablation are effective methods for treating hypersplenism, but counts tend to fall back to baseline long-term. Pharmacological agents are also effective in increasing platelet counts. Development of direct acting antivirals against hepatitis C will eliminate the most common indication for treatment. We lack controlled trials designed to determine if treating the hypersplenism has benefits other than raising the platelet and white blood cell counts. In the absence of such studies, hypersplenism in most patients should be considered a laboratory abnormality and not treated, in other words forget it. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparative Analysis of Various Aspects of Plateletpheresis on the Fenwal Amicus and Fresenius COM.TEC Cell Separator Instruments.

PubMed

Philip, Joseph; Biswas, Amit Kumar; Chatterjee, Tathagata; Mallhi, Rajiv Singh

2014-01-01

To compare the Fenwal Amicus and the Fresenius COM.TEC apheresis instruments regarding donor peripheral blood parameters, operational variables of the instruments, and quality control parameters of the product obtained. We performed 100 platelet collections from 100 voluntary donors using the 2 studied devices. We measured platelet count using an automated analyzer and analyzed the activation statuses using a flow cytometer. The median time needed to perform the procedures was significantly longer with the COM.TEC. However, the product we obtained using the Amicus instrument showed higher degrees of platelet-activation. All products we obtained with both instruments had white blood cell counts of less than 5 × 10(6) per bag. We observed no statistical difference regarding collection efficiency and collection rates between the devices. Both instruments collected platelets efficiently, with minimal donor discomfort. Compared with the COM.TEC instrument, the Amicus reached the platelet target yield more quickly; however, it displayed an increase in platelet activation. Copyright© by the American Society for Clinical Pathology (ASCP).

Low-level light treatment ameliorates immune thrombocytopenia

PubMed Central

Yang, Jingke; Zhang, Qi; Li, Peiyu; Dong, Tingting; Wu, Mei X.

2016-01-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP. PMID:27901126

Low-level light treatment ameliorates immune thrombocytopenia

NASA Astrophysics Data System (ADS)

Yang, Jingke; Zhang, Qi; Wu, Mei X.

2017-02-01

Immune thrombocytopenia (ITP) is an immune-mediated acquired bleeding disorder characterized by abnormally low platelet counts. We reported here the ability of low-level light treatment (LLLT) to alleviate ITP in mice. The treatment is based on noninvasive whole body illumination 30 min a day for a few consecutive days by near infrared light (830 nm) transmitted by an array of light-emitting diodes (LEDs). LLLT significantly lifted the nadir of platelet counts and restored tail bleeding time when applied to two passive ITP models induced by anti-CD41 antibody. The anti-platelet antibody hindered megakaryocyte differentiation from the progenitors, impaired proplatelet and platelet formation, and induced apoptosis of platelets. These adverse effects of anti-CD41 antibody were all mitigated by LLLT to varying degrees, owing to its ability to enhance mitochondrial biogenesis and activity in megakaryocytes and preserve mitochondrial functions in platelets in the presence of the antibody. The observations argue not only for contribution of mitochondrial stress to the pathology of ITP, but also clinical potentials of LLLT as a safe, simple, and cost-effective modality of ITP.

Immature platelet fraction (IPF) as a predictive value for thrombopoietic recovery after allogeneic stem cell transplantation.

PubMed

Sakuragi, Mikiko; Hayashi, Satoru; Maruyama, Miho; Kiyokawa, Tomoko; Nagamine, Keisuke; Fujita, Jiro; Maeda, Tetsuo; Kato, Hisashi; Kashiwagi, Hirokazu; Kanakura, Yuzuru; Tomiyama, Yoshiaki

2018-03-01

We consecutively examined the utility of measurements of percentage of immature platelet fraction (IPF%) and absolute IPF number (A-IPF) in predicting thrombopoietic recovery in 15 adult patients who underwent allogeneic hematopoietic stem cell transplantation (allo-SCT). Four patients were excluded from the evaluation due to insufficient data. Platelet count and IPF were measured by Sysmex XN-1000 (XN), a newer generation analyzer. First, we confirmed that platelet count measured by XN was more accurate than by XE-2100 (XE). IPF measurement was effective to predict the recovery in 7 of the 11 patients examined. Moreover, IPF measurement, especially IPF% measurement, suggested accelerated platelet turnover in two patients who failed to achieve platelet recovery by day 60. In addition to IPF%, A-IPF showed a complementary role on the prediction of thrombopoietic recovery. The increase in IPF% was only transient, while A-IPF values showed lasting increase during platelet recovery. In two patients (cases 6 and 7) an increase in A-IPF, but not in IPF%, was observed during platelet recovery. Our data suggest that IPF% and A-IPF measured by XN are useful for the prediction of thrombopoietic recovery and the assessment of pathogenesis of thrombocytopenia in patients after allo-SCT.

Von Willebrand's disease with spontaneous platelet aggregation induced by an abnormal plasma von Willebrand factor.

PubMed Central

Grainick, H R; Williams, S B; McKeown, L P; Rick, M E; Maisonneuve, P; Jenneau, C; Sultan, Y

1985-01-01

We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia. Images PMID:2932469

Performance evaluation of the new hematology analyzer Sysmex XN-series.

PubMed

Seo, J Y; Lee, S-T; Kim, S-H

2015-04-01

The Sysmex XN-series is a new automated hematology analyzer designed to improve the accuracy of cell counts and the specificity of the flagging events. The basic characteristics and the performance of new measurement channels of the XN were evaluated and compared with the Sysmex XE-2100 and the manual method. Fluorescent platelet count (PLT-F) was compared with the flow cytometric method. The low WBC mode and body fluid mode were also evaluated. For workflow analysis, 1005 samples were analyzed on both the XN and the XE-2100, and manual review rates were compared. All parameters measured by the XN correlated well with the XE-2100. PLT-F showed better correlation with the flow cytometric method (r(2)  = 0.80) compared with optical platelet count (r(2)  = 0.73) for platelet counts <70 × 10(9) /L. The low WBC mode reported accurate leukocyte differentials for samples with a WBC count <0.5 × 10(9) /L. Relatively good correlation was found for WBC counts between the manual method and the body fluid mode (r = 0.88). The XN made less flags than the XE-2100, while the sensitivities of both instruments were comparable. The XN provided reliable results on low cell counts, as well as reduced manual blood film reviews, while maintaining a proper level of diagnostic sensitivity. © 2014 John Wiley & Sons Ltd.

Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca−/− mice

PubMed Central

Pawlikowska, Patrycja; Fouchet, Pierre; Vainchenker, William; Rosselli, Filippo

2014-01-01

Fanconi anemia (FA) is an inherited chromosomal instability syndrome that is characterized by progressive bone marrow failure. One of the main causes of morbidity and mortality in FA is a bleeding tendency, resulting from low platelet counts. Platelets are the final products of megakaryocyte (MK) maturation. Here, we describe a previously unappreciated role of Fanconi anemia group A protein (Fanca) during the endomitotic process of MK differentiation. Fanca deficiency leads to the accumulation of MKs with low nuclear ploidy and to decreased platelet production. We show, for the first time, that Fanca−/− mice are characterized by limited number and proliferative capacity of MK progenitors. Defective megakaryopoiesis of Fanca−/− cells is associated with the formation of nucleoplasmic bridges and increased chromosomal instability, indicating that inaccurate endoreplication and karyokinesis occur during MK polyploidization. Sustained DNA damage forces Fanca−/− MKs to enter a senescence-like state. Furthermore, inhibition of the Rho-associated kinase, a regulator of cytokinesis, improves the polyploidization of Fanca−/− MKs but greatly increases their genomic instability and diminishes their differentiation potential, supporting the notion that accumulation of DNA damage through endomitotic cycles affects MK maturation. Our study indicates that Fanca expression during endomitosis is crucial for normal megakaryopoiesis and platelet production. PMID:25261197

Defective endomitosis during megakaryopoiesis leads to thrombocytopenia in Fanca-/- mice.

PubMed

Pawlikowska, Patrycja; Fouchet, Pierre; Vainchenker, William; Rosselli, Filippo; Naim, Valeria

2014-12-04

Fanconi anemia (FA) is an inherited chromosomal instability syndrome that is characterized by progressive bone marrow failure. One of the main causes of morbidity and mortality in FA is a bleeding tendency, resulting from low platelet counts. Platelets are the final products of megakaryocyte (MK) maturation. Here, we describe a previously unappreciated role of Fanconi anemia group A protein (Fanca) during the endomitotic process of MK differentiation. Fanca deficiency leads to the accumulation of MKs with low nuclear ploidy and to decreased platelet production. We show, for the first time, that Fanca(-/-) mice are characterized by limited number and proliferative capacity of MK progenitors. Defective megakaryopoiesis of Fanca(-/-) cells is associated with the formation of nucleoplasmic bridges and increased chromosomal instability, indicating that inaccurate endoreplication and karyokinesis occur during MK polyploidization. Sustained DNA damage forces Fanca(-/-) MKs to enter a senescence-like state. Furthermore, inhibition of the Rho-associated kinase, a regulator of cytokinesis, improves the polyploidization of Fanca(-/-) MKs but greatly increases their genomic instability and diminishes their differentiation potential, supporting the notion that accumulation of DNA damage through endomitotic cycles affects MK maturation. Our study indicates that Fanca expression during endomitosis is crucial for normal megakaryopoiesis and platelet production. © 2014 by The American Society of Hematology.

Heparin-associated thrombocytopenia: antibody binding specificity to platelet antigens.

PubMed

Lynch, D M; Howe, S E

1985-11-01

Sera from four patients with heparin-associated thrombocytopenia (HAT) were evaluated by a quantitative enzyme-linked immunosorbent assay (ELISA) to detect heparin-dependent serum platelet-bindable immunoglobulin (S-PBIg) and by Western blotting and immunoprecipitation to investigate the specificity of the antibody binding. All HAT sera showed mildly increased S-PBIg (mean, 7.8 fg per platelet; normal, less than 6.0 fg per platelet) to intact target platelets in the ELISA, which was markedly increased in the presence of heparin (mean, 20.9 fg per platelet). This increase was 20-fold greater than normal control sera, which showed a mean differential increase of only 0.5 fg per platelet. Immunoglobulin binding specificity to platelet antigens was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of platelet lysate with transfer of the platelet fractions onto nitrocellulose strips (Western blotting) and subsequent immunoassay using HAT and normal sera. In the presence of heparin, the four HAT patients demonstrated increased binding of immunoglobulin to platelet antigens of apparent molecular weights of 180, 124, and 82 kd. Radiolabeled heparin when incubated with HAT sera, normal sera, or albumin blanks bound to platelet proteins of the same apparent molecular weights. These observations are consistent with current hypotheses suggesting that HAT antibody is directed to heparin-platelet complexes or, alternatively, that heparin induces conformational change of antigenic sites on the platelet membrane.

Predictors of successful closure of patent ductus arteriosus with indomethacin.

PubMed

Ahamed, M F; Verma, P; Lee, S; Vega, M; Wang, D; Kim, M; Fuloria, M

2015-09-01

To determine whether platelet counts can predict the likelihood of successful closure of patent ductus arteriosus (PDA) with indomethacin. This was a retrospective cohort study of infants <32 weeks' gestational age (GA) and birth weight <1500 g with PDA. Clinical characteristics between infants who achieved ductal closure with indomethacin and those who failed were compared. Multivariable logistic regression was used to identify predictors of successful ductal closure. In infants with hemodynamically significant PDA, older GA (odds ratio=1.54; 95% confidence interval: 1.12 to 2.13), male gender (odds ratio=3.02; 95% confidence interval: 1.08 to 8.49) and higher platelet count (odds ratio=1.5; 95% confidence interval: 1.04 to 2.17) prior to indomethacin treatment were associated with successful ductal closure with indomethacin. Older GA, male gender and higher platelet count at time of treatment of hemodynamically significant PDA are predictors of successful ductal closure with indomethacin.

Successful replantation of 2 digits in a patient with thrombocytosis after splenectomy: A case report.

PubMed

Hwang, Jae Ha; Kim, Dong Wan; Kim, Kwang Seog; Lee, Sam Yong

2018-06-01

Thrombosis is the most common complication of thrombocytosis, which can be particularly damaging to reattached digits. We present a guideline about digital replantation when thrombocytosis is expected. We report a case of an 18-year-old man who sustained a traumatic amputation of two fingers and splenic rupture in a traffic accident. He underwent digital replantation the day after splenectomy when life-threatening conditions had been managed. The platelet count increased to over 1,300,000/mm and post-splenectomy reactive thrombocytosis was diagnosed. Hydroxyurea and anagrelide were administered to control the platelet count after consultation with a hematologist. The reattached fingers survived without any complication. In patients with digital amputation, replantation can be attempted, even when thrombocytosis is expected, when requested by the patient. Furthermore, the platelet count should be actively controlled with medication to improve the survival rate of the reattached finger.

Elevated platelet count as predictor of recurrence in rectal cancer patients undergoing preoperative chemoradiotherapy followed by surgery.

PubMed

Toiyama, Yuji; Inoue, Yasuhiro; Kawamura, Mikio; Kawamoto, Aya; Okugawa, Yoshinaga; Hiro, Jyunichiro; Saigusa, Susumu; Tanaka, Koji; Mohri, Yasuhiko; Kusunoki, Masato

2015-02-01

The impact of systemic inflammatory response (SIR) on prognostic and predictive outcome in rectal cancer after neoadjuvant chemoradiotherapy (CRT) has not been fully investigated. This retrospective study enrolled 89 patients with locally advanced rectal cancer who underwent neoadjuvant CRT and for whom platelet (PLT) counts and SIR status [neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR)] were available. Both clinical values of PLT and SIR status in rectal cancer patients were investigated. Elevated PLT, NLR, PLR, and pathologic TNM stage III [ypN(+)] were associated with significantly poor overall survival (OS). Elevated PLT, NLR, and ypN(+) were shown to independently predict OS. Elevated PLT and ypN(+) significantly predicted poor disease-free survival (DFS). Elevated PLT was identified as the only independent predictor of DFS. PLT counts are a promising pre-CRT biomarker for predicting recurrence and poor prognosis in rectal cancer.

New gene functions in megakaryopoiesis and platelet formation

PubMed Central

Gieger, Christian; Radhakrishnan, Aparna; Cvejic, Ana; Tang, Weihong; Porcu, Eleonora; Pistis, Giorgio; Serbanovic-Canic, Jovana; Elling, Ulrich; Goodall, Alison H.; Labrune, Yann; Lopez, Lorna M.; Mägi, Reedik; Meacham, Stuart; Okada, Yukinori; Pirastu, Nicola; Sorice, Rossella; Teumer, Alexander; Voss, Katrin; Zhang, Weihua; Ramirez-Solis, Ramiro; Bis, Joshua C.; Ellinghaus, David; Gögele, Martin; Hottenga, Jouke-Jan; Langenberg, Claudia; Kovacs, Peter; O’Reilly, Paul F.; Shin, So-Youn; Esko, Tõnu; Hartiala, Jaana; Kanoni, Stavroula; Murgia, Federico; Parsa, Afshin; Stephens, Jonathan; van der Harst, Pim; van der Schoot, C. Ellen; Allayee, Hooman; Attwood, Antony; Balkau, Beverley; Bastardot, François; Basu, Saonli; Baumeister, Sebastian E.; Biino, Ginevra; Bomba, Lorenzo; Bonnefond, Amélie; Cambien, François; Chambers, John C.; Cucca, Francesco; D’Adamo, Pio; Davies, Gail; de Boer, Rudolf A.; de Geus, Eco J. C.; Döring, Angela; Elliott, Paul; Erdmann, Jeanette; Evans, David M.; Falchi, Mario; Feng, Wei; Folsom, Aaron R.; Frazer, Ian H.; Gibson, Quince D.; Glazer, Nicole L.; Hammond, Chris; Hartikainen, Anna-Liisa; Heckbert, Susan R.; Hengstenberg, Christian; Hersch, Micha; Illig, Thomas; Loos, Ruth J. F.; Jolley, Jennifer; Khaw, Kay Tee; Kühnel, Brigitte; Kyrtsonis, Marie-Christine; Lagou, Vasiliki; Lloyd-Jones, Heather; Lumley, Thomas; Mangino, Massimo; Maschio, Andrea; Leach, Irene Mateo; McKnight, Barbara; Memari, Yasin; Mitchell, Braxton D.; Montgomery, Grant W.; Nakamura, Yusuke; Nauck, Matthias; Navis, Gerjan; Nöthlings, Ute; Nolte, Ilja M.; Porteous, David J.; Pouta, Anneli; Pramstaller, Peter P.; Pullat, Janne; Ring, Susan M.; Rotter, Jerome I.; Ruggiero, Daniela; Ruokonen, Aimo; Sala, Cinzia; Samani, Nilesh J.; Sambrook, Jennifer; Schlessinger, David; Schreiber, Stefan; Schunkert, Heribert; Scott, James; Smith, Nicholas L.; Snieder, Harold; Starr, John M.; Stumvoll, Michael; Takahashi, Atsushi; Tang, W. H. Wilson; Taylor, Kent; Tenesa, Albert; Thein, Swee Lay; Tönjes, Anke; Uda, Manuela; Ulivi, Sheila; van Veldhuisen, Dirk J.; Visscher, Peter M.; Völker, Uwe; Wichmann, H.-Erich; Wiggins, Kerri L.; Willemsen, Gonneke; Yang, Tsun-Po; Zhao, Jing Hua; Zitting, Paavo; Bradley, John R.; Dedoussis, George V.; Gasparini, Paolo; Hazen, Stanley L.; Metspalu, Andres; Pirastu, Mario; Shuldiner, Alan R.; van Pelt, L. Joost; Zwaginga, Jaap-Jan; Boomsma, Dorret I.; Deary, Ian J.; Franke, Andre; Froguel, Philippe; Ganesh, Santhi K.; Jarvelin, Marjo-Riitta; Martin, Nicholas G.; Meisinger, Christa; Psaty, Bruce M.; Spector, Timothy D.; Wareham, Nicholas J.; Akkerman, Jan-Willem N.; Ciullo, Marina; Deloukas, Panos; Greinacher, Andreas; Jupe, Steve; Kamatani, Naoyuki; Khadake, Jyoti; Kooner, Jaspal S.; Penninger, Josef; Prokopenko, Inga; Stemple, Derek; Toniolo, Daniela; Wernisch, Lorenz; Sanna, Serena; Hicks, Andrew A.; Rendon, Augusto; Ferreira, Manuel A.; Ouwehand, Willem H.; Soranzo, Nicole

2012-01-01

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function. PMID:22139419

The association between hematological parameters and metabolic syndrome in Iranian men: A single center large-scale study.

PubMed

Ahmadzadeh, Jamal; Mansorian, Behnam; Attari, Mohammad Mirza-Aghazadeh; Mohebbi, Ira; Naz-Avar, Raha; Moghadam, Karaim; Ghareh-Bagh, Seyyed Adel Khoshbou

Some studies have demonstrated that metabolic syndrome is associated with hematological parameters. The present study explores the relationship between hematological parameters and numbers of metabolic syndrome conditions in Iranian men. This cross-sectional study included 11,114 participants who were professional drivers of commercial motor vehicles, and were enrolled in the Iranian Health Surveys between 2014 and 2016. Diagnosis of metabolic syndrome was made according to International Diabetes Federation criteria. Clinical data, including anthropometric measurements and serum parameters, were collected. Odds ratios for hematological parameters and metabolic syndrome were calculated using binary logistic regression models. We found that hemoglobin; platelet, and white blood cell counts increased with increasing numbers of metabolic syndrome components (p<0.05 for all). The odds ratio of metabolic syndrome significantly increased across successive quartiles of platelet (1.00, 1.25, 1.29, and 1.51) and white blood cell counts (1.00, 1.51, 1.79, and 2.11) with the lowest quartile as the referent group. Similar associations for hemoglobin and hematocrit in the top quartile were also observed. We did not observe any significant difference in the mean of neutrophil count, mean platelet volume (MPV), red cell distribution width, or platelet distribution width among participants with or without metabolic syndrome. Our findings indicate that high levels of major hematological parameters such as hemoglobin, hematocrit, as well as platelet and white blood cell counts could be novel indicators for the development of metabolic syndrome. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Clinical course and prognostic factors of childhood immune thrombocytopenia: single center experience of 10 years

PubMed Central

Jung, Jae Yeob; O, A Rum; Kim, Je Keong

2016-01-01

Purpose This study aimed to evaluate the clinical course of childhood immune thrombocytopenia (ITP) and to assess the risk factors for developing chronic ITP. Methods The records of 64 children diagnosed with ITP from November 2005 and December 2014 at single center were retrospectively analyzed. Results The median age at diagnosis and the median platelet count were 1 year (range, 1 month to 15 years) and 9×109/L (range, 0–84×109/L), respectively. No patient experienced severe bleeding. Nineteen children (29.7%) spontaneously recovered their platelet count to ≥100×109/L at a median of 10 days. In total 45 patients (70.3%) received intravenous immunoglobulin (IVIG) as first-line therapy, and showed platelet recovery at 1 week. The final diagnosis of 55 (85.9%) and 9 patients (14.1%) was acute and chronic ITP, respectively. Older age, absence of prior infection and insidious onset of symptoms were significantly associated with the development of chronic ITP. Among the patients who received IVIG, those with platelet count <45×109/L at 1 month after IVIG showed a significantly higher incidence of chronic ITP compared to those with platelet count ≥45×109/L (88.8% vs. 44.4%, P<0.01). Conclusion In most patients, ITP runs a benign course and approximately 86% of them recover within 1 year of their initial diagnosis. The potential impact of the risk factors of chronic ITP on clinical practice needs to be explored and further studies are warranted to determine whether IVIG influences the course of ITP. PMID:27610182

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.

An enzyme-linked immunosorbent assay for the evaluation of thrombocytopenia induced by heparin.

PubMed

Howe, S E; Lynch, D M

1985-05-01

Five patients with heparin-associated thrombocytopenia (HAT) were evaluated by platelet aggregation and quantitation of immunoglobulin binding to intact target platelets in both the presence and absence of heparin. These patients developed thrombocytopenia (12,000 to 70,000 platelets/microliter) 7 to 15 days and embolic and hemorrhagic complications 9 to 15 days after the initiation of heparin therapy. Platelet aggregation after the addition of heparin was demonstrated in two of four HAT serum samples, whereas normal serum samples showed no significant platelet aggregation. The five HAT serum samples showed normal to elevated baseline serum platelet-bindable immunoglobulin (SPBIg) with a range of 4.3 to 11.4 fg/platelet (normal less than or equal to 1.0 to 6.5 fg/platelet). When HAT sera were incubated with target platelets and heparin (5 U/ml), the SPBIg increased to 8.5 to 37.5 fg/platelet, a mean increase of 148% in the presence of heparin. Normal and control serum samples (from 10 normal laboratory volunteers, nine patients without thrombocytopenia receiving heparin, nine patients with autoimmune thrombocytopenic purpura, and nine patients with nonimmune thrombocytopenia not receiving heparin) showed only a slight increase in SPBIg of 0 to 2.8 fg/platelet above baseline, a mean increase of 15% after heparin incubation with the serum samples. The measurement of SPBIg of washed platelets incubated with test serum samples in the presence and absence of heparin is potentially a specific and sensitive in vitro test for the diagnosis of HAT and may prove more sensitive than platelet aggregation studies with heparin.

Role of Tumor Suppressor P53 in Megakaryopoiesis and Platelet Function

PubMed Central

Apostolidis, Pani A.; Woulfe, Donna S.; Chavez, Massiel; Miller, William M.; Papoutsakis, Eleftherios T.

2011-01-01

The pathobiological role of p53 has been widely studied, however its role in normophysiology is relatively unexplored. We previously showed that p53 knock-down increased ploidy in megakaryocytic cultures. This study aims to examine the effect of p53 loss on in vivo megakaryopoiesis, platelet production and function, and to investigate the basis for greater ploidy in p53−/− megakaryocytic cultures. Here, we used flow cytometry to analyze ploidy, DNA synthesis and apoptosis in murine cultured and bone marrow megakaryocytes following thrombopoietin administration and to analyze fibrinogen binding to platelets in vitro. Culture of p53−/− marrow cells for 6 days with thrombopoietin gave rise to 1.7-fold more megakaryocytes, 26.1±3.6% of which reached ploidy classes ≥64N compared to 8.2±0.9% of p53+/+ megakaryocytes. This was due to 30% greater DNA synthesis in p53−/− megakaryocytes and 31% greater apoptosis in p53+/+ megakaryocytes by day 4 of culture. Although the bone marrow and spleen steady-state megakaryocytic content and ploidy were similar in p53+/+ and p53−/− mice, thrombopoietin administration resulted in increased megakaryocytic polyploidization in p53−/− mice. Although their platelet counts were normal, p53−/− mice exhibited significantly longer bleeding times and p53−/− platelets were less sensitive than p53+/+ platelets to agonist-induced fibrinogen binding and P-selectin secretion. In summary, our in vivo and ex-vivo studies indicate that p53 loss leads to increased polyploidization during megakaryopoiesis. Our findings also suggest for the first time a direct link between p53 loss and the development of fully functional platelets resulting in hemostatic deficiencies. PMID:22024107

The Use of Platelets to Affect Functional Healing of an Anterior Cruciate Ligament (ACL) Autograft in a Caprine ACL Reconstruction Model

PubMed Central

Spindler, Kurt P.; Murray, Martha M.; Carey, James L.; Zurakowski, David; Fleming, Braden C.

2009-01-01

Many anterior cruciate ligament (ACL) reconstructions have increased laxity postoperatively. We hypothesized that enhancing an ACL graft with a collagen-platelet composite (CPC) would improve knee laxity and graft structural properties. We also hypothesized the platelet concentration in the CPC would affect these parameters. Twelve goats underwent ACL reconstruction with autologous patellar tendon graft. In six goats, a collagen-platelet composite was placed around the graft (CPC group). In the remaining six goats, the collagen scaffold only was used (COLL group). Three goats were excluded due to complications. After 6 weeks in vivo, anterior–posterior (AP) laxity and tensile properties of the ACL reconstructed knees were measured and normalized against the contralateral intact knee. At a knee flexion angle of 30°, the average increase in AP laxity was 40% less in the CPC group than the COLL group (p = 0.045). At 60°, the AP laxity was 30% less in the CPC group, a difference that was close to statistical significance (p = 0.080). No differences were found between treatment groups with respect to the structural properties (p > 0.30). However, there were significant correlations between serum platelet concentration and AP laxity (R2 = 0.643; p = 0.009), maximum load (R2 = 0.691; p = 0.006), and graft stiffness (R2 = 0.840; p < 0.001). In conclusion, use of a CPC to enhance healing of an allograft ACL reconstruction inversely correlated with early sagittal plane laxity and the systemic platelet count was highly predictive of ACL reconstruction graft strength and stiffness at 6 weeks. These findings emphasize the importance of further research on delineating the effect of platelets in treating of ACL injuries. PMID:19009602

21 CFR 864.6160 - Manual blood cell counting device.

Code of Federal Regulations, 2012 CFR

2012-04-01

... blood cell counting device. (a) Identification. A manual blood cell counting device is a device used to count red blood cells, white blood cells, or blood platelets. (b) Classification. Class I (general... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Manual blood cell counting device. 864.6160...

21 CFR 864.6160 - Manual blood cell counting device.

Code of Federal Regulations, 2013 CFR

2013-04-01

... blood cell counting device. (a) Identification. A manual blood cell counting device is a device used to count red blood cells, white blood cells, or blood platelets. (b) Classification. Class I (general... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Manual blood cell counting device. 864.6160...

21 CFR 864.6160 - Manual blood cell counting device.

Code of Federal Regulations, 2011 CFR

2011-04-01

... blood cell counting device. (a) Identification. A manual blood cell counting device is a device used to count red blood cells, white blood cells, or blood platelets. (b) Classification. Class I (general... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Manual blood cell counting device. 864.6160...

21 CFR 864.6160 - Manual blood cell counting device.

Code of Federal Regulations, 2014 CFR

2014-04-01

... blood cell counting device. (a) Identification. A manual blood cell counting device is a device used to count red blood cells, white blood cells, or blood platelets. (b) Classification. Class I (general... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Manual blood cell counting device. 864.6160...

21 CFR 864.6160 - Manual blood cell counting device.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Manual blood cell counting device. 864.6160... blood cell counting device. (a) Identification. A manual blood cell counting device is a device used to count red blood cells, white blood cells, or blood platelets. (b) Classification. Class I (general...

Platelet size and density affect shear-induced thrombus formation in tortuous arterioles

NASA Astrophysics Data System (ADS)

Chesnutt, Jennifer K. W.; Han, Hai-Chao

2013-10-01

Thrombosis accounts for 80% of deaths in patients with diabetes mellitus. Diabetic patients demonstrate tortuous microvessels and larger than normal platelets. Large platelets are associated with increased platelet activation and thrombosis, but the physical effects of large platelets in the microscale processes of thrombus formation are not clear. Therefore, the objective of this study was to determine the physical effects of mean platelet volume (MPV), mean platelet density (MPD) and vessel tortuosity on platelet activation and thrombus formation in tortuous arterioles. A computational model of the transport, shear-induced activation, collision, adhesion and aggregation of individual platelets was used to simulate platelet interactions and thrombus formation in tortuous arterioles. Our results showed that an increase in MPV resulted in a larger number of activated platelets, though MPD and level of tortuosity made little difference on platelet activation. Platelets with normal MPD yielded the lowest amount of mural thrombus. With platelets of normal MPD, the amount of mural thrombus decreased with increasing level of tortuosity but did not have a simple monotonic relationship with MPV. The physical mechanisms associated with MPV, MPD and arteriole tortuosity play important roles in platelet activation and thrombus formation.

Exposure from the Chernobyl accident had adverse effects on erythrocytes, leukocytes, and, platelets in children in the Narodichesky region, Ukraine: A 6-year follow-up study

PubMed Central

Stepanova, Eugenia; Karmaus, Wilfried; Naboka, Marina; Vdovenko, Vitaliy; Mousseau, Tim; Shestopalov, Viacheslav M; Vena, John; Svendsen, Erik; Underhill, Dwight; Pastides, Harris

2008-01-01

Background After the Chernobyl nuclear accident on April 26, 1986, all children in the contaminated territory of the Narodichesky region, Zhitomir Oblast, Ukraine, were obliged to participate in a yearly medical examination. We present the results from these examinations for the years 1993 to 1998. Since the hematopoietic system is an important target, we investigated the association between residential soil density of 137Caesium (137Cs) and hemoglobin concentration, and erythrocyte, platelet, and leukocyte counts in 1,251 children, using 4,989 repeated measurements taken from 1993 to 1998. Methods Soil contamination measurements from 38 settlements were used as exposures. Blood counts were conducted using the same auto-analyzer in all investigations for all years. We used linear mixed models to compensate for the repeated measurements of each child over the six year period. We estimated the adjusted means for all markers, controlling for potential confounders. Results Data show a statistically significant reduction in red and white blood cell counts, platelet counts and hemoglobin with increasing residential 137Cs soil contamination. Over the six-year observation period, hematologic markers did improve. In children with the higher exposure who were born before the accident, this improvement was more pronounced for platelet counts, and less for red blood cells and hemoglobin. There was no exposure×time interaction for white blood cell counts and not in 702 children who were born after the accident. The initial exposure gradient persisted in this sub-sample of children. Conclusion The study is the first longitudinal analysis from a large cohort of children after the Chernobyl accident. The findings suggest persistent adverse hematological effects associated with residential 137Cs exposure. PMID:18513393

Thrombocytopenia in Small for Gestational Age Infants

PubMed Central

Christensen, Robert D.; Baer, Vickie L.; Henry, Erick; Snow, Gregory L.; Butler, Allison; Sola-Visner, Martha C.

2016-01-01

BACKGROUND Thrombocytopenia is common among small for gestational age neonates (SGA; birth weight <10th % reference range) but several aspects of this thrombocytopenia are unclear, including the incidence, typical nadir, duration, association with preeclampsia, mechanism, and risk of death. METHODS Using nine years of multihospital records we studied SGA neonates with ≥2 platelet counts <150,000/μL in their first week. RESULTS We found first-week thrombocytopenia in 31% (905 of 2891) of SGA neonates vs. 10% of non-SGA matched-controls (p<0.0001). One hundred-two of the 905 had a recognized cause of thrombocytopenia (DIC, early-onset sepsis, ECMO). This group had a 65% mortality rate. The remaining 803 did not have an obvious cause for their thrombocytopenia. We termed these the “thrombocytopenia of SGA”. They had a mortality rate of 2% (p<0.0001) and a mean nadir count on day 4 of 93,000/μL (standard deviation, 51,580/μL, 10th % 50,000/μL, 90th % 175,000/μL). By day 14, platelet counts were ≥150,000/μL in >half of the patients. Severely SGA neonates (<1st %) had lower counts and longer thrombocytopenia duration (p<0.001). High nucleated red cell counts at birth correlated with low platelets (p<0.0001). Platelet transfusions were given to 23% and counts typically >tripled. Thrombocytopenia was associated with SGA status more so than with the diagnosis of maternal preeclampsia. CONCLUSIONS SGA neonates with clearly recognized varieties of thrombocytopenia have a high mortality rate. In contrast the “thrombocytopenia of SGA” is a hyporegenerative condition of moderate severity and two weeks duration, associated with evidence of intrauterine hypoxia, and associated with a low mortality rate. PMID:26216323

Imputation of Exome Sequence Variants into Population- Based Samples and Blood-Cell-Trait-Associated Loci in African Americans: NHLBI GO Exome Sequencing Project

PubMed Central

Auer, Paul L.; Johnsen, Jill M.; Johnson, Andrew D.; Logsdon, Benjamin A.; Lange, Leslie A.; Nalls, Michael A.; Zhang, Guosheng; Franceschini, Nora; Fox, Keolu; Lange, Ethan M.; Rich, Stephen S.; O’Donnell, Christopher J.; Jackson, Rebecca D.; Wallace, Robert B.; Chen, Zhao; Graubert, Timothy A.; Wilson, James G.; Tang, Hua; Lettre, Guillaume; Reiner, Alex P.; Ganesh, Santhi K.; Li, Yun

2012-01-01

Researchers have successfully applied exome sequencing to discover causal variants in selected individuals with familial, highly penetrant disorders. We demonstrate the utility of exome sequencing followed by imputation for discovering low-frequency variants associated with complex quantitative traits. We performed exome sequencing in a reference panel of 761 African Americans and then imputed newly discovered variants into a larger sample of more than 13,000 African Americans for association testing with the blood cell traits hemoglobin, hematocrit, white blood count, and platelet count. First, we illustrate the feasibility of our approach by demonstrating genome-wide-significant associations for variants that are not covered by conventional genotyping arrays; for example, one such association is that between higher platelet count and an MPL c.117G>T (p.Lys39Asn) variant encoding a p.Lys39Asn amino acid substitution of the thrombpoietin receptor gene (p = 1.5 × 10−11). Second, we identified an association between missense variants of LCT and higher white blood count (p = 4 × 10−13). Third, we identified low-frequency coding variants that might account for allelic heterogeneity at several known blood cell-associated loci: MPL c.754T>C (p.Tyr252His) was associated with higher platelet count; CD36 c.975T>G (p.Tyr325∗) was associated with lower platelet count; and several missense variants at the α-globin gene locus were associated with lower hemoglobin. By identifying low-frequency missense variants associated with blood cell traits not previously reported by genome-wide association studies, we establish that exome sequencing followed by imputation is a powerful approach to dissecting complex, genetically heterogeneous traits in large population-based studies. PMID:23103231

Prognostic significance of platelet count changes during hospitalization for community-acquired pneumonia.

PubMed

Gorelik, Oleg; Izhakian, Shimon; Barchel, Dana; Almoznino-Sarafian, Dorit; Tzur, Irma; Swarka, Muhareb; Beberashvili, Ilia; Feldman, Leonid; Cohen, Natan; Shteinshnaider, Miriam

2017-06-01

The prognostic significance of platelet count (PC) changes during hospitalization for community-acquired pneumonia (CAP) has not been investigated. For 976 adults, clinical data during hospitalization for CAP and all-cause mortality following discharge were compared according to ΔPC (PC on discharge minus PC on admission): groups A (declining PC, ΔPC < -50 × 10 9 /l), B (stable PC, ΔPC ± 50 × 10 9 /l), and C (rising PC, ΔPC >50 × 10 9 /l), and according to the presence of thrombocytopenia, normal PC, and thrombocytosis on admission/discharge. Groups A, B, and C comprised 7.9%, 46.5%, and 45.6% of patients, respectively. On hospital admission/discharge, thrombocytopenia, normal PC, and thrombocytosis were observed in 12.8%/6.4%, 84.1%/84.4%, and 3.1%/9.2% of patients, respectively. The respective 90-day, 3-year, and total (median follow-up of 54 months) mortality rates were significantly higher: in group A (40.3%, 63.6%, and 72.7%), compared to groups B (12.3%, 31.5%, and 39.0%) and C (4.9%, 17.3%, and 25.4%), p < 0.001; and in patients with thrombocytopenia at discharge (27.4%, 48.4%, and 51.6%), compared to those with normal PC (10.2%, 26.9%, and 35.4%) and thrombocytosis (8.9%, 17.8%, and 24.4%) at discharge (p < 0.001). Mortality rates were comparable among groups with thrombocytopenia, normal PC, and thrombocytosis at admission (p = 0.6). In the entire sample, each 100 × 10 9 /l increment of ΔPC strongly predicted lower mortality (p < 0.001, relative risk 0.73, 95% confidence interval 0.64-0.83). In conclusion, PC changes are common among CAP inpatients. Rising PC throughout hospitalization is a powerful predictor of better survival, while declining PC predicts poor outcome. Evaluation of PC changes during hospitalization for CAP may provide useful prognostic information.

Classical management of refractory adult immune (idiopathic) thrombocytopenic purpura.

PubMed

McMillan, R

2002-03-01

Treatment of chronic immune (idiopathic) thrombocytopenic purpura with corticosteroids and/or splenectomy results in safe platelet counts in over 70% of patients without additional treatment. Therapy of patients who are refractory to these two treatments may be difficult. The treatment approach to refractory ITP patients, described in this report, is arbitrarily divided into four levels: levels 1 through 3 represent treatments with increasing side effects; level 4 therapy may be tried when the others have failed. Patients undergoing these treatments may require concomitant intravenous gammaglobulin, high-dose corticosteroids or platelets, to maintain the platelet count in the setting of mucosal bleeding or severe thrombocytopenia. Copyright 2002, Elsevier Science Ltd. All rights reserved.

A prospective randomized clinical trial of vincristine versus human intravenous immunoglobulin for acute adjunctive management of presumptive primary immune-mediated thrombocytopenia in dogs.

PubMed

Balog, K; Huang, A A; Sum, S O; Moore, G E; Thompson, C; Scott-Moncrieff, J C

2013-01-01

Dogs with immune-mediated thrombocytopenia (ITP) are at risk of hemorrhage when platelet count is <50,000/μL. Treatment with vincristine (VINC) or human intravenous immunoglobulin (hIVIG) decreases platelet recovery time compared with treatment with corticosteroids alone. To compare the effect of hIVIG versus VINC on platelet recovery in dogs with ITP. Prospective, randomized study. Twenty dogs with idiopathic ITP (platelet count <16,000/μL) were enrolled. All dogs were treated with corticosteroids. Dogs were randomly assigned to receive a single dose of hIVIG (0.5 g/kg) or VINC (0.02 mg/kg). Outcome measures were platelet recovery time, duration of hospitalization, and survival to discharge. There was no significant difference in age, sex, weight, or initial platelet count between dogs treated with hIVIG (n = 10) and dogs treated with VINC (n = 10). Median platelet recovery time for both groups was 2.5 days (P = .51). Median hospitalization time for all dogs that survived to discharge was 4 days and not different between groups (P = .29). Seven of 10 dogs in the hIVIG group and 10 of 10 in the VINC group survived to discharge. Survival analysis did not identify any significant difference between the groups at discharge, 6 months, and 1 year after entry into the study. No adverse effects were reported in either group. Vincristine should be the first-line adjunctive treatment for the acute management of canine ITP because of lower cost and ease of administration compared with human intravenous immunoglobulin (hIVIG). Copyright © 2013 by the American College of Veterinary Internal Medicine.

Platelet Transfusion Practices in Critically Ill Children.

PubMed

Nellis, Marianne E; Karam, Oliver; Mauer, Elizabeth; Cushing, Melissa M; Davis, Peter J; Steiner, Marie E; Tucci, Marisa; Stanworth, Simon J; Spinella, Philip C

2018-05-04

Little is known about platelet transfusions in pediatric critical illness. We sought to describe the epidemiology, indications, and outcomes of platelet transfusions among critically ill children. Prospective cohort study. Multicenter (82 PICUs), international (16 countries) from September 2016 to April 2017. Children ages 3 days to 16 years prescribed a platelet transfusion in the ICU during screening days. None. Over 6 weeks, 16,934 patients were eligible, and 559 received at least one platelet transfusion (prevalence, 3.3%). The indications for transfusion included prophylaxis (67%), minor bleeding (21%), and major bleeding (12%). Thirty-four percent of prophylactic platelet transfusions were prescribed when the platelet count was greater than or equal to 50 × 10 cells/L. The median (interquartile range) change in platelet count post transfusion was 48 × 10 cells/L (17-82 × 10 cells/L) for major bleeding, 42 × 10 cells/L (16-80 × 10 cells/L) for prophylactic transfusions to meet a defined threshold, 38 × 10 cells/L (17-72 × 10 cells/L) for minor bleeding, and 25 × 10 cells/L (10-47 × 10 cells/L) for prophylaxis in patients at risk of bleeding from a device. Overall ICU mortality was 25% but varied from 18% to 35% based on indication for transfusion. Upon adjusted analysis, total administered platelet dose was independently associated with increased ICU mortality (odds ratio for each additional 1 mL/kg platelets transfused, 1.002; 95% CI, 1.001-1.003; p = 0.005). The majority of platelet transfusions are given as prophylaxis to nonbleeding children, and significant variation in platelet thresholds exists. Studies are needed to clarify appropriate indications, with focus on prophylactic transfusions.

Comprehensive haematological indices reference intervals for a healthy Omani population: First comprehensive study in Gulf Cooperation Council (GCC) and Middle Eastern countries based on age, gender and ABO blood group comparison.

PubMed

Al-Mawali, Adhra; Pinto, Avinash Daniel; Al-Busaidi, Raiya; Al-Lawati, Rabab H; Morsi, Magdi

2018-01-01

Reference intervals for venous blood parameters differs with age, gender, geographic region, and ethnic groups. Hence local laboratory reference intervals are important to improve the diagnostic accuracy of health assessments and diseases. However, there have been no comprehensive published reference intervals established in Oman, the Gulf Cooperation Council or Middle Eastern countries. Hence, the aim of this study was to establish reference intervals for full blood count in healthy Omani adults. Venous blood specimens were collected from 2202 healthy individuals aged 18 to 69 years from January 2012 to April 2017, and analysed by Sysmex XS-1000i and Cell-Dyn Sapphire automated haematology analysers. Results were statistically analysed and compared by gender, age, and ABO blood group. The lower and upper reference limits of the haematology reference intervals were established at the 2.5th and 97.5th percentiles respectively. Reference intervals were calculated for 17 haematology parameters which included red blood cell, white blood cell, and platelet parameters. Red blood cell (RBC), haemoglobin (HGB), haematocrit (HCT), platelet and platelet haematocrit counts of the healthy donors were significantly different between males and females at all ages (p < 0.05), with males having higher mean values of RBC, HGB and HCT than females. Other complete blood count parameters showed no significant differences between genders, age groups, instruments, or blood groups. Our study showed a lower haemoglobin limit for the normal reference interval in males and females than the currently used in Oman. Data from this study established specific reference intervals which could be considered for general use in Oman. The differences in haematology reference intervals highlights the necessity to establish reference intervals for venous blood parameters among the healthy population in each country or at least in each region.

Concentration-dependent effect of hypocalcaemia on in vitro clot strength in patients at risk of bleeding: a retrospective cohort study.

PubMed

Ho, K M; Yip, C B

2016-02-01

It is uncertain whether hypocalcaemia is associated with an increased risk of bleeding. This study assessed the dose-related relationship between ionised calcium concentrations and in vitro clot strength measured by maximum amplitude (MA) on the thromboelastograph (TEG). A total of 610 patients who were at risk of bleeding or had active bleeding between 2010 and 2014 were considered in this retrospective cohort study. A scatter plot with Pearson correlation coefficient (r) and multiple linear regression was used to assess the dose-related relationship between ionised calcium concentrations and MA on the TEG. The mean ionised calcium of the patients was 1·10 mmol L(-1) (interquartile range: 1·04-1·17) and 235 (38·5%) of them had hypocalcaemia (<1·1 mmol L(-1) ). Hypocalcaemia was more common in patients with significant coexisting coagulopathy. Ionised calcium concentrations (r = 0·285, 95% confidence interval (CI) 0·211-0·356, P = 0·001), as well as fibrinogen concentrations, platelet counts, international normalised ratio (INR) and activated Partial Thromboplastin Time (aPTT), had a significant linear correlation with the MA on the TEG. Ionised calcium concentrations and its interaction term with platelet count were both significantly associated with the MA on the TEG (slope of the regression line 1·1 per 0·1 mmol L(-1) increment, 95%CI 0·3 to 1·9, P = 0·011), after adjusting for fibrinogen concentrations, platelet counts, INR and aPTT. Ionised calcium concentrations had a concentration-dependent association with in vitro clot strength after adjusting for other coagulation abnormalities in patients with coexisting coagulopathy. Maintaining a normal ionised calcium concentration, >1 mmol L(-1) , during critical bleeding is recommended. © 2016 British Blood Transfusion Society.

Thrombopoietic effects of interleukin-6 in long-term administration in mice.

PubMed

Ishibashi, T; Shikama, Y; Kimura, H; Kawaguchi, M; Uchida, T; Yamamoto, T; Okano, A; Akiyama, Y; Hirano, T; Kishimoto, T

1993-05-01

To further investigate the thrombopoietic and adverse effects of interleukin-6 (IL-6), 2 or 10 micrograms/day of recombinant human (rh) IL-6 was administered intraperitoneally (i.p.) to mice for up to 30 days. IL-6 increased platelet count, which plateaued at a level 30 to 40% higher than control after 5 days of treatment. This cytokine also maintained the high platelet count for the duration of treatment. The count exceeded normal levels 7 days after cessation of the 30-day treatment. IL-6 also induced a remarkable increase in the size but not the frequency of megakaryocytes in bone marrow sections. The number of bone marrow colony-forming units megakaryocyte (CFU-MK) and colony-forming units granulocyte-macrophage (CFU-GM) was not augmented by the administration of IL-6 in this protocol, while spleen progenitors were significantly stimulated. Small but significant increases did occur in the number of bone marrow megakaryocytes and CFU-MK, and in the proportion of CFU-MK in the DNA synthetic phase in mice treated with 10 micrograms/day of IL-6 for 30 days. Electron microscopic examination of bone marrow demonstrated that IL-6 remarkably developed the distribution of the demarcation membrane system (DMS) in mice treated for 30 days, with little change in mice treated for 5 days. The administration of 2 micrograms/day for 30 days induced a 2.2-fold increase in fibrinogen. No changes were observed in the hepatic or renal functions. Histologic and immunofluorescence studies on the kidneys revealed no significant changes compared with controls, indicating that proliferation of the glomerular mesangium did not occur. No neutralizing antibodies were detected in mice treated for 30 days. We conclude that the long-term administration of IL-6 in mice stimulates megakaryocyte maturation and platelet production with few adverse effects, and that this cytokine may be a candidate for the treatment of thrombocytopenia in humans.

Thrombocyte counts in mice after the administration of papaya leaf suspension.

PubMed

Sathasivam, Kathiresan; Ramanathan, Surash; Mansor, Sharif M; Haris, Mas Rosemal M H; Wernsdorfer, Walther H

2009-10-01

Following up a popular use of crude leaf preparations from Carica papaya for the treatment of dengue infections, a suspension of powdered Carica papaya leaves in palm oil has been investigated for its effect on thrombocyte counts in mice, administering by gavage 15 mg of powdered leaves per kg body weight to 5 mice. Equal numbers of animals received corresponding volumes of either palm oil alone or physiological saline solution. Thrombocyte counts before and at 1, 2, 4, 8, 10, 12, 24, 48 and 72 hours after dosing revealed significantly higher mean counts at 1, 2, 4, 8, 10 and 12 after dosing with the C. papaya leaf formulation as compared to the mean count at hour 0. There was only a non-significant rise of thrombocyte counts in the group having received saline solution, possibly the expression of a normal circadian rhythm in mice. The group having received palm oil only showed a protracted increase of platelet counts that was significant at hours 8 and 48 and obviously the result of a hitherto unknown stimulation of thrombocyte release. The results call for a dose-response investigation and for extending the studies to the isolation and identification of the C. papaya substances responsible for the release and/or production of thrombocytes.

Flow rate calibration to determine cell-derived microparticles and homogeneity of blood components.

PubMed

Noulsri, Egarit; Lerdwana, Surada; Kittisares, Kulvara; Palasuwan, Attakorn; Palasuwan, Duangdao

2017-08-01

Cell-derived microparticles (MPs) are currently of great interest to screening transfusion donors and blood components. However, the current approach to counting MPs is not affordable for routine laboratory use due to its high cost. The current study aimed to investigate the potential use of flow-rate calibration for counting MPs in whole blood, packed red blood cells (PRBCs), and platelet concentrates (PCs). The accuracy of flow-rate calibration was investigated by comparing the platelet counts of an automated counter and a flow-rate calibrator. The concentration of MPs and their origins in whole blood (n=100), PRBCs (n=100), and PCs (n=92) were determined using a FACSCalibur. The MPs' fold-changes were calculated to assess the homogeneity of the blood components. Comparing the platelet counts conducted by automated counting and flow-rate calibration showed an r 2 of 0.6 (y=0.69x+97,620). The CVs of the within-run and between-run variations of flow-rate calibration were 8.2% and 12.1%, respectively. The Bland-Altman plot showed a mean bias of -31,142platelets/μl. MP enumeration revealed both the difference in MP levels and their origins in whole blood, PRBCs, and PCs. Screening the blood components demonstrated high heterogeneity of the MP levels in PCs when compared to whole blood and PRBCs. The results of the present study suggest the accuracy and precision of flow-rate calibration for enumerating MPs. This flow-rate approach is affordable for assessing the homogeneity of MPs in blood components in routine laboratory practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as Empirical Therapy for Thrombocytopenia associated with Dengue Fever.

PubMed

Kasture, Prabhu Nagnathappa; Nagabhushan, K H; Kumar, Arun

2016-06-01

Dengue is a rapidly expanding global health problem. Approximately 2.5 billion people live in dengue-risk regions with about 100 million new cases each year worldwide. The cumulative dengue diseases burden has attained an unprecedented proportion in recent times with sharp increase in the size of human population at risk. The management of dengue virus infection is essentially supportive and symptomatic and no specific treatment is available for increasing the fallen platelets, which have a significant role in causing the mortality of dengue patient.This study was conducted to evaluate the platelet increasing efficacy of Carica papaya leaf extract (CPLE) in patients with dengue fever (DF). The administration of Carica papaya leaf extract should significantly increase the platelet count in cases of thrombocytopenia associated with dengue, preventing the patient to go in DHF or DSS conditions. A Multi-centric, Double blind, Placebo controlled, Randomized, prospective study was conducted in 300 patients across 5 centres', to evaluate the Efficacy and Safety of Carica Papaya Leaf Extract, as empirical therapy for thrombocytopenia associated with dengue fever. The subjects were randomized into two groups, as control and intervention group. Both the groups were managed by the standard management guidelines for dengue except steroid administration. In addition to this, the intervention group received CPLE tablet three times daily for five days. All of them were followed daily with platelet monitoring. This study has been registered in the clinical trial registry-India (CTRI Registration number: CTRI/2015/05/005806). The results indicate that CPLE had significant increase(p< 0.01) in the platelet count over the therapy duration, in dengue fever patients, confirming CPLE accelerates the increase in platelet count compared to the control group. There were few adverse events related to GI disturbance like nausea and vomiting which were similar in both groups. Thus this study concluded that Carica papaya leaf extract (CPLE) does significantly increase the platelet count in patients with thrombocytopenia associated with dengue with fewer side effects and good tolerability.

A mild transient decrease of peripheral red blood cell counts induced by a suprapharmacological dose of pegylated human megakaryocyte growth and development factor in rats.

PubMed

Harada, K; Ide, Y; Tazunoki, Y; Imai, A; Yanagida, M; Kikuchi, Y; Imai, A; Ishii, H; Kawahara, J; Izumi, H; Kusaka, M; Tokiwa, T

1999-07-01

Previous studies have shown that pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) at suprapharmacological dose induces a mild transient decrease of red blood cell counts according to thrombopoiesis in normal mice. To unravel the mechanism underlying this mild transient decrease of red blood cells, we have studied the effect of PEG-rHuMGDF on the circulating plasma and blood volume, and the serum biochemical parameters of anaemia and splenectomy. Also, we have performed histological studies of the bone marrow and the spleen of PEG-rHuMGDF-treated rats. PEG-rHuMGDF (300 microg kg(-1)]) or vehicle was subcutaneously administered to rats once a day for up to five days. From day 6 after the start of PEG-rHuMGDF administration, the platelet counts and plateletcrit levels were significantly increased, reaching peak values on day 10, and recovering to normal by day 20. The red blood cell counts and the haematocrit levels were significantly decreased on day 6 to 13. The decreases in red blood cell levels and haematocrit produced by PEG-rHuMGDF treatment were mild and had recovered by day 15. The plasma and blood volumes were significantly increased on day 10 in PEG-rHuMGDF-treated rats. No alteration of the serum biochemical parameters for anaemia, iron or total bilirubin, were observed on day 10. The histological examination on day 10 revealed a marked increase in megakaryocytes and a slight decrease in erythropoiesis in the bone marrow of rats that received PEG-rHuMGDF (300 microg kg(-1)). There was also a slight increase in splenic megakaryocytes and erythropoiesis. The decrease of red blood cells by PEG-rHuMGDF was not affected by splenectomy. These results suggest that the mild transient decrease of red blood cells induced by PEG-rHuMGDF treatment for up to five days is based mainly on the increases in the plasma and blood volume. These events are secondary changes due to the regulation of the excess production of megakaryocytes in the marrow and the peripheral platelets.

[Protective effect of arctigenin in GK rats combined with hypertension macroangiopathy].

PubMed

Feng, Qin; Sun, Bao-cun; Xia, Wen-kai

2015-03-01

To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.

Effects of saline or albumin resuscitation on standard coagulation tests.

PubMed

Bellomo, Rinaldo; Morimatsu, Hiroshi; Presneill, Jeff; French, Craig; Cole, Louise; Story, David; Uchino, Shigehiko; Naka, Toshio; Finfer, Simon; Cooper, D James; Myburgh, John

2009-12-01

To explore whether fluid resuscitation with normal saline or 4% albumin is associated with differential changes in routine clinical coagulation tests. Substudy from a large double-blind randomised controlled trial, the SAFE (Saline versus Albumin Fluid Evaluation) study. Three general intensive care units. Cohort of 687 critically ill patients. We randomly allocated patients to receive either 4% human albumin or normal saline for fluid resuscitation, and collected demographic and haematological data. Albumin was administered to 338 patients and saline to 349. At baseline, the two groups had similar mean activated partial thromboplastin time (APTT) of 37.2 s (albumin) v 39.1 s (saline); mean international normalised ratio (INR) of 1.38 v 1.34, and mean platelet count of 244 x 10(9)/L v 249 x 10(9)/L. After randomisation, during the first day of treatment, the APTT in the albumin group was prolonged by a mean of 2.7 s, but shortened slightly by a mean of -0.9 s in the saline group. The INR did not change in either group, while the platelet count decreased transiently in both groups. Using multivariate analysis of covariance to account for baseline coagulation status, albumin fluid resuscitation (P = 0.01) and a greater overall volume of resuscitation (P = 0.03) were independently associated with prolongation of APTT during the first day. Administration of albumin or of larger fluid volumes is associated with a prolongation of APTT. In ICU patients, the choice and amount of resuscitation fluid may affect a routinely used coagulation test.

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.

The relation of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mean platelet volume with the presence and severity of Behçet's syndrome.

PubMed

Alan, Sevil; Tuna, Serpil; Türkoğlu, Elif Betül

2015-12-01

Behçet's syndrome (BS) is associated with chronic inflammation and endothelial dysfunction. Although there have been extensive investigations on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV) in many diseases, their roles in BS is unclear. The purpose of the present study was to evaluate NLR, PLR, and MPV levels in BS patients and explore their clinical significance. The study included 254 patients with BS and 173 healthy individuals. Age, sex, age of onset, duration of disease, smoking, Behçet activity score, total white blood counts, neutrophil, platelet, and T lymphocyte counts of the patients were recorded. White blood cell (WBC), neutrophil, platelet, NLR, and PLR were significantly higher in patients with BS when compared with healthy controls (all p < 0.001). Lymphocyte counts and MPVs of the BS group were not statistically different from healthy controls (all p > 0.05). In the BS group, PLR and MPV were significantly different among the three severity groups (p = 0.037 and p = 0.016, respectively). We showed that any laboratory markers were not associated with joint, eye, central nervous system, large vessel, or gastrointestinal involvement in BS. NLR was shown to be an independent factor for BS by multivariate analysis. We suggest that NLR can be considered to be a diagnostic criterion of BS given the support of the findings from larger prospective studies. Copyright © 2015. Published by Elsevier Taiwan.

Utility of the immature platelet fraction in pediatric immune thrombocytopenia: Differentiating from bone marrow failure and predicting bleeding risk.

PubMed

McDonnell, Alicia; Bride, Karen L; Lim, Derick; Paessler, Michele; Witmer, Char M; Lambert, Michele P

2018-02-01

Differentiating childhood immune thrombocytopenia (ITP) from other cause of thrombocytopenia remains a diagnosis of exclusion. Additionally factors that predict bleeding risk for those patients with ITP are currently not well understood. Previous small studies have suggested that immature platelet fraction (IPF) may differentiate ITP from other causes of thrombocytopenia and in combination with other factors may predict bleeding risk. We performed a retrospective chart review of thrombocytopenic patients with an IPF measured between November 1, 2013 and July 1, 2015. Patients were between 2 months and 21 years of age with a platelet count <50 × 10 9 /l. Each patient chart was reviewed for final diagnosis and bleeding symptoms. A bleeding severity score was retrospectively assigned. Two hundred seventy two patients met inclusion criteria, 97 with ITP, 11 with bone marrow failure (BMF), 126 with malignancy, and 38 with other causes of thrombocytopenia. An IPF > 5.2% differentiated ITP from BMF with 93% sensitivity and 91% specificity. Absolute immature platelet number (AIPN) was significantly lower in ITP patients with severe to life-threatening hemorrhage than those without, despite similar platelet counts. On multivariate analysis, an IPF < 10.4% was confirmed as an independent predictor of bleeding risk at platelet counts <10 × 10 9 /l in patients with ITP. IPF measurement alone has utility in both the diagnosis of ITP and identifying patients at increased risk of hemorrhage. Further study is required to understand the pathophysiological differences of ITP patients with lower IPF/AIPN. © 2017 Wiley Periodicals, Inc.

Hematological Alterations on Sub-acute Exposure to Flubendiamide in Sprague Dawley Rats.

PubMed

Vemu, Bhaskar; Dumka, Vinod Kumar

2014-01-01

Pesticide poisoning is a common occurrence around the world. Pesticides can act on various body systems resulting in toxicity. Flubendiamide is a new generation pesticide, reported to have better activity against Lepidopteran insects. The present study was carried out with an objective to analyze the effects of flubendiamide sub-acute exposure on hematology of rats. Male and female Sprague Dawley (SD) rats (9-11 weeks) were divided into five groups with six animals in each group. First group served as control, while the rest were exposed to ascending oral doses of flubendiamide (125, 250, 500 and 1000 mg/kg) for 28 days. After the trial period, blood was collected in heparinized vials and analyzed using Siemens ADVIA 2120(®) autoanalyzer. Various erythrocytic, platelet and leukocyte parameters were measured and analyzed using statistical tests by one-way analysis of variance (ANOVA) and t-test using Statistical Package for Social Sciences (SPSS)(®) 20 software. After processing the data through statistical analysis, it was observed that the effect of flubendiamide exposure on female rats was negligible. The only significant change observed in the female rats was that in total erythrocytic count, while rest of the parameters showed non-significant bidirectional changes. In males, many parameters viz., total leukocyte count (TLC), total erythrocyte count (TEC), packed cell volume (PCV), mean corpuscular volume (MCV), platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), hemoglobin distribution width (HDW), large platelets (LPT) and plateletcrit (PCT) expressed significant difference when compared to control. Many of the changes were dose independent, but sex specific. This lead to the hypothesis that saturation toxicokinetics might be one of the reasons for this varied response, which can only be evaluated after further testing.

The Effects of Helicobacter pylori Eradication Therapy for Chronic Idiopathic Thrombocytopenic Purpura

PubMed Central

Hwang, Jae Jin; Lee, Dong Ho; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

2016-01-01

Background/Aims The aim of this study was to evaluate the ability of Helicobacter pylori eradication treatment to increase platelet counts in Korean patients with chronic idiopathic thrombocytopenic purpura (ITP). Methods A total of 102 patients were evaluated against two criteria. First, those diagnosed with H. pylori infections in whom eradication was successful were assigned to the H. pylori-positive and -eradicated group (n=39), whereas those diagnosed with H. pylori infections in whom eradication failed were assigned to the H. pylori-positive and -non-eradicated group (n=3), and those without H. pylori infections were assigned to the H. pylori-negative group (n=60). Second, patients with complete remission in whom the platelet recovery effect was maintained over the average follow-up period of 6 months after eradication therapy were defined as the responder group (n=58), whereas those with partial or no response were defined as the nonresponder group (n=44). Results The platelet counts of the H. pylori-positive and -eradicated group were significantly increased 6 months after eradication therapy compared to those of the H. pylori-positive and -non-eradicated group and the H. pylori-negative group (43.2±29.1 to 155.3±68.7×103/μL vs 42.5±28.1 to 79.8±59.7×103/μL vs 43.1±28.9 to 81.2±62.2×103/μL; p=0.041). The eradication therapy success rate in the responder group was 100.0% (39/39), in contrast to the nonresponder group (0%, 0/3) (p<0.001). Conclusions H. pylori eradication therapy was related to increased platelet count, and successful eradication affected the increased platelet count in Korean patients with chronic ITP. PMID:26347517

Delayed fertilization of anuran amphibian (Xenopus) eggs leads to reduced numbers of primordial germ cells

NASA Technical Reports Server (NTRS)

Wakahara, M.; Neff, A. W.; Malacinski, G. M.

1984-01-01

Several media were tested for the extent to which they promoted high fertilization efficiencies in ovulated, stripped Xenopus eggs. One medium was selected for maintaining eggs in a 'delayed fertilization' (DelF) condition. DelF eggs displayed several unusual characteristics, including shift of the center of gravity, prominent sperm entrance site, and occasional polyspermy. The frequency of normal pattern formation varied according to the length of time eggs were maintained in the DelF condition. Various developmental abnormalities were observed during gastrulation, neurulation, and organogenesis. Most abnormalities appeared, however, to be related to morphogenesis of the endoderm. Primordial germ cell (PGC) development was examined in DelF eggs which displayed normal external morphological features at the swimming tadpole stage. PGC counts were usually normal in short-duration (eg, 5 hr) DelF eggs, but frequently substantially reduced or completely diminished in longer-duration (eg, 25h) tadpoles. Six spawnings were compared and shown to exhibit considerable variability in fertility, morphogenesis, and PGC development. Yolk platelet shifts and developmental parameters were examined in two additional spawnings. The subcortical cytoplasm in which the germ plasm is normally localized appeared to be disrupted in longer duration DelF eggs. That observation may account for low PGC counts in DelF tadpoles.

[Role of anti c-mpl antibody in systemic lupus erythematosus with thrombocytopenia].

PubMed

Yang, Tuo; Huang, Ci Bo; Lai, Bei; Zhao, Li Ke; Chen, Ying Juan; Zhao, Yue Tao; Zhang, Chun Mei; Zeng, Xiao Feng

2012-04-18

To determine whether anti-thrompoietin receptor (TPO-R, c-mpl) antibody contributes to thrombocytopenia in systemic lupus erytematosus (SLE) and explore the pathogenic role of this antibody. Sera from 24 SLE patients with thrombocytopenia, 27 SLE patients having normal platelet counts with a history of thrombocytopenia, 18 SLE patients with neither thrombocytopenia nor post thrombocytopenia and 18 healthy controls were collected. Anti c-mpl antibodies were detected by an indirected ELISA assay. The serum TPO levels were measured by an ELISA assay. Clinical findings, autoantibody profiles, and SLEDAI were evaluated. Serum anti c-mpl antibodies were detected in 18.8% of the SLE patientis. The frequency of this antibody in SLE with thrombocytopenia, SLE with a history of thrombocytopenia and SLE without thrombocytopenia were of no difference (P=0.600). In the patients with anti c-mpl antibodies, their platelet counts were decreased(P=0.025) and serum TPO levels elevated(P=0.038) than those in the patients without, while there were no differences between the two groups in C3, C4, ESR, CRP level, the frequency of ANA, dsDNA, ANCA and SLEDAI. Anti c-mpl antibody contributes to SLE-associated thrombocytopenia by functionally blocking an interaction between thrombopoietin and c-mpl, which might inhibit TPO-dependent megakaryocyte proliferation and differentiation.

21 CFR 864.8625 - Hematology quality control mixture.

Code of Federal Regulations, 2011 CFR

2011-04-01

... parameters such as white cell count (WBC), red cell count (RBC), platelet count (PLT), hemoglobin, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). (b) Classification. Class II (performance standards). [45 FR 60637, Sept. 12...

Platelet abnormalities in adults with severe pulmonary arterial hypertension related to congenital heart defects (Eisenmenger syndrome).

PubMed

Remková, Anna; Šimková, Iveta; Valkovičová, Tatiana; Kaldarárová, Monika

2016-12-01

Patients with severe pulmonary arterial hypertension suffer from life-threatening thrombotic and bleeding complications. The aim of this study was to compare selected platelet, endothelial, and coagulation parameters in healthy volunteers and patients with severe pulmonary arterial hypertension because of congenital heart defects. The study included healthy volunteers (n = 50) and patients with cyanotic congenital heart defects classified as Eisenmenger syndrome (n = 41). We investigated platelet count, mean platelet volume, and platelet aggregation - spontaneous and induced by various concentrations of five agonists. Von Willebrand factor (vWF), fibrinogen, factor VIII and XII, plasminogen activator inhibitor, antithrombin, D-dimer, and antiphospholipid antibodies were also investigated. We found a decreased platelet count [190 (147-225) vs. 248 (205-295) 10 l, P < 0.0001], higher mean platelet volume [10.9 (10.1-12.0) vs. 10.2 (9.4-10.4) fl, P < 0.0001], and significantly decreased platelet aggregation (induced by five agonists, in various concentrations) in patients with Eisenmenger syndrome compared with controls. These changes were accompanied by an increase of plasma vWF antigen [141.6 (108.9-179.1) vs. 117.4 (9.2-140.7) IU/dl, P = 0.022] and serum anti-β2-glycoprotein [2.07 (0.71-3.41) vs. 0.47 (0.18-0.99) U/ml, P < 0.0001]. Eisenmenger syndrome is accompanied by platelet abnormalities. Thrombocytopenia with increased platelet size is probably due to a higher platelet turnover associated with platelet activation. Impaired platelet aggregation can reflect specific platelet behaviour in patients with Eisenmenger syndrome. These changes can be related both to bleeding and to thrombotic events. A higher vWF antigen may be a consequence of endothelial damage in Eisenmenger syndrome, but the cause for an increase of anti-β2-glycoprotein is unknown.

Platelets from patients with the Quebec platelet disorder contain and secrete abnormal amounts of urokinase-type plasminogen activator.

PubMed

Kahr, W H; Zheng, S; Sheth, P M; Pai, M; Cowie, A; Bouchard, M; Podor, T J; Rivard, G E; Hayward, C P

2001-07-15

The Quebec platelet disorder (QPD) is an autosomal dominant platelet disorder associated with delayed bleeding and alpha-granule protein degradation. The degradation of alpha-granule, but not plasma, fibrinogen in patients with the QPD led to the investigation of their platelets for a protease defect. Unlike normal platelets, QPD platelets contained large amounts of fibrinolytic serine proteases that had properties of plasminogen activators. Western blot analysis, zymography, and immunodepletion experiments indicated this was because QPD platelets contained large amounts of urokinase-type plasminogen activator (u-PA) within a secretory compartment. u-PA antigen was not increased in all QPD plasmas, whereas it was increased more than 100-fold in QPD platelets (P <.00009), which contained increased u-PA messenger RNA. Although QPD platelets contained 2-fold more plasminogen activator inhibitor 1 (PAI-1) (P <.0008) and 100-fold greater u-PA-PAI-1 complexes (P <.0002) than normal platelets, they contained excess u-PA activity, predominantly in the form of two chain (tcu-PA), which required additional PAI-1 for full inhibition. There was associated proteolysis of plasminogen in QPD platelets, to forms that comigrated with plasmin. When similar amounts of tcu-PA were incubated with normal platelet secretory proteins, many alpha-granule proteins were proteolyzed to forms that resembled degraded QPD platelet proteins. These data implicate u-PA in the pathogenesis of alpha-granule protein degradation in the QPD. Although patients with the QPD have normal to increased u-PA levels in their plasma, without evidence of systemic fibrinogenolysis, their increased platelet u-PA could contribute to bleeding by accelerating fibrinolysis within the hemostatic plug. QPD is the only inherited bleeding disorder in humans known to be associated with increased u-PA.

Utility of a Fluorescence Microscopy Imaging System for Analyzing the DNA Ploidy of Pathological Megakaryocytes Including 5q- Syndrome.

PubMed

Nakahara, Takako; Suemori, Shinichiro; Tsujioka, Takayuki; Kataoka, Mikio; Kataoka, Hiromi; Shibakura, Misako; Tohyama, Kaoru

2018-06-01

To investigate megakaryocyte (MK) DNA ploidy in various hematological diseases, fluorescence microscopy imaging system (FMI) can be used to analyze DNA ploidy with cell morphology at the single-cell level by using specialized image-processing software. Here we compared DNA ploidy obtained by FMI measured with that obtained flow cytometry (FCM). With FMI, we could evaluate the DNA ploidy in long-term preserved bone marrow smear samples after staining. We next analyzed the MK DNA ploidy in 42 bone marrow smear samples including 26 myeloid neoplasm cases, and we compared the DNA ploidy and platelet counts in the patients' peripheral blood; the production of platelets was significantly high compared to DNA ploidy in the myeloproliferative neoplasms group. The FMI method revealed that the patients with 5q- syndrome exhibited relatively low DNA ploidy despite high platelet counts, and this result suggested that increased DNA ploidy is not indispensable to abundant platelet production. The FMI method for DNA ploidy will be a useful tool to clarify the relationship between DNA ploidy and platelet production by MKs.

Blood Count Tests

MedlinePlus

... white blood cells (WBC), and platelets. Blood count tests measure the number and types of cells in ... helps doctors check on your overall health. The tests can also help to diagnose diseases and conditions ...

Microparticles from splenectomized β-thalassemia/HbE patients play roles on procoagulant activities with thrombotic potential.

PubMed

Klaihmon, Phatchanat; Phongpao, Kunwadee; Kheansaard, Wasinee; Noulsri, Egarit; Khuhapinant, Archrob; Fucharoen, Suthat; Morales, Noppawan Phumala; Svasti, Saovaros; Pattanapanyasat, Kovit; Chaichompoo, Pornthip

2017-02-01

Thromboembolic events including cerebral thrombosis, deep vein thrombosis, and pulmonary embolism are major complications in β-thalassemia. Damaged red blood cells and chronic platelet activation in splenectomized β-thalassemia/HbE patients were associated with increased microparticles (MPs) releases into blood circulation. MPs are small membrane vesicles, which play important roles on coagulation. However, the role of MP in thalassemia is poorly understood. In this study, the effects of splenectomized-MPs on platelet activation and aggregation were investigated. The results showed that isolated MPs from fresh platelet-free plasma of patients and normal subjects directly induce platelet activation, platelet aggregation, and platelet-neutrophil aggregation in a dose-dependent manner. Interestingly, MPs obtained from splenectomized patients are more efficient in induction of platelet activation (P-selectin + ) when compared to MPs from normal subjects (P < 0.05), tenfold lower than pathophysiological level, at 1:0.1 platelet MP ratio. Co-incubation of splenectomized-MPs with either normal-, non-splenectomized- or splenectomized-platelets at 1:10 platelet MP ratio increased platelet activation up to 5.1 ± 2.2, 5.6 ± 3.7, and 9.5 ± 3.0%, respectively, when normalized with individual baseline. These findings suggest that splenectomized patients were proned to be activated by MPs, and splenectomized-MPs could play an important role on chronic platelet activation and aggregation, leading to thrombus formation in β-thalassemia/HbE patients.

A Novel Automated Slide-Based Technology for Visualization, Counting, and Characterization of the Formed Elements of Blood: A Proof of Concept Study.

PubMed

Winkelman, James W; Tanasijevic, Milenko J; Zahniser, David J

2017-08-01

- A novel automated slide-based approach to the complete blood count and white blood cell differential count is introduced. - To present proof of concept for an image-based approach to complete blood count, based on a new slide preparation technique. A preliminary data comparison with the current flow-based technology is shown. - A prototype instrument uses a proprietary method and technology to deposit a precise volume of undiluted peripheral whole blood in a monolayer onto a glass microscope slide so that every cell can be distinguished, counted, and imaged. The slide is stained, and then multispectral image analysis is used to measure the complete blood count parameters. Images from a 600-cell white blood cell differential count, as well as 5000 red blood cells and a variable number of platelets, that are present in 600 high-power fields are made available for a technologist to view on a computer screen. An initial comparison of the basic complete blood count parameters was performed, comparing 1857 specimens on both the new instrument and a flow-based hematology analyzer. - Excellent correlations were obtained between the prototype instrument and a flow-based system. The primary parameters of white blood cell, red blood cell, and platelet counts resulted in correlation coefficients (r) of 0.99, 0.99, and 0.98, respectively. Other indices included hemoglobin (r = 0.99), hematocrit (r = 0.99), mean cellular volume (r = 0.90), mean corpuscular hemoglobin (r = 0.97), and mean platelet volume (r = 0.87). For the automated white blood cell differential counts, r values were calculated for neutrophils (r = 0.98), lymphocytes (r = 0.97), monocytes (r = 0.76), eosinophils (r = 0.96), and basophils (r = 0.63). - Quantitative results for components of the complete blood count and automated white blood cell differential count can be developed by image analysis of a monolayer preparation of a known volume of peripheral blood.

Thrombocytopenia in pregnancy with different diagnoses

PubMed Central

Wang, Xiaoyue; Xu, Yan; Luo, Wenxiang; Feng, Hui; Luo, Yizhou; Wang, Yanli; Liao, Hui

2017-01-01

Abstract To investigate the clinical features and perinatal treatment of thrombocytopenia induced by different causes during pregnancy. Clinical data from 195 pregnant women with thrombocytopenia attending 2 tertiary hospitals from January 2014 to October 2016 were retrospectively studied. The obtained data were analyzed with SPSS 19.0 software. There were 117 (60.0%), 55 (28.2%), and 23 cases (11.8%) of pregnancy-associated thrombocytopenia (PAT), idiopathic thrombocytopenia (ITP), and hypertensive disorder in pregnancy (PIH), respectively. The percentage of nulliparous women, gestational age at delivery, date of diagnosis of thrombocytopenia, and delivery mode significantly differed between the patients in these 3 groups (P < .05). Patients with PIH had a higher percentage of premature delivery and of lower birth weight infants than patients in the other 2 groups. The 3 groups had similar incidences of postpartum hemorrhage, rates of stillbirth, and neonatal Apgar scores at 5 minutes. PAT and PIH patients had different platelet counts after delivery compared with at diagnosis, whereas the platelet counts of the ITP patients were similar at diagnosis and after delivery. ITP patients in the nontreatment group and the treatment group had significantly different platelet counts (P < .05), and in the treatment group, the maternal platelet count did not differ for treatment with intravenous immunoglobulin (IVIg) versus corticosteroids. The causes of thrombocytopenia in pregnancy are diverse, and the clinical features vary widely. Timely analysis is needed to determine the primary cause of thrombocytopenia, and appropriate therapy should then be selected to effectively improve the prognosis of pregnancies. PMID:28723784

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.

The effect of prolactin levels on MPV in women with PCOS.

PubMed

Yilmaz, Özgür; Calan, Mehmet; Kume, Tuncay; Temur, Muzaffer; Yesil, Pınar; Senses, Mehmet Y

2015-05-01

Polycystic ovary syndrome (PCOS) is associated with cardiovascular risk factors including hypertension, obesity, hyperlipidaemia and glucose intolerance. Several studies demonstrated the link between PCOS and an increased risk of cardiovascular disease. Platelets play a crucial role in the development of atherothrombotic disease. Mean platelet volume (MPV) is a marker of platelet size that reflects its activity. Research points to a link between prolactin (PRL) and platelet activation. The purpose of this study was to investigate whether prolactin levels are associated with MPV in women with PCOS. The research was designed as a cross-sectional study. Participants were divided into three groups-PCOS patients with mildly elevated PRL levels (n = 72), patients with PCOS with normal PRL levels (n = 207) and healthy controls (n = 90). They were body mass index and age-matched and consecutively recruited. Complete blood counts, serum glucose, prolactin, insulin, lipids, high-sensitivity C-reactive protein and free-testosterone levels were measured. Among the three groups, MPV levels were higher in women with PCOS having mildly elevated PRL levels (P < 0·001) and MPV was found to be correlated with PRL levels (r = 0·387, P < 0·001). Multiple regression analysis showed that PRL levels were associated with MPV levels (R(2) = 0·239, β = 0·354, P < 0·001). Mean platelet volume levels are significantly increased in women with PCOS having mildly elevated PRL. Our results suggest that there is a link between prolactin and MPV levels. In women with PCOS, elevated PRL levels may increase the risk of developing atherothrombotic events via the activation of platelets. © 2014 John Wiley & Sons Ltd.

Branched-chain amino acid-enriched nutrient increases blood platelet count in patients after endoscopic injection sclerotherapy.

PubMed

Furuichi, Yoshihiro; Imai, Yasuharu; Miyata, Yuki; Sugimoto, Katsutoshi; Sano, Takatomo; Taira, Junichi; Kojima, Mayumi; Kobayashi, Yoshiyuki; Nakamura, Ikuo; Moriyasu, Fuminori

2016-10-01

Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated. A total of 61 LC patients were randomly divided into an EIS monotherapy group (non-BCAA group, n = 31) and an EIS combined with BCAA therapy group (n = 30). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points. The platelet counts before treatment were at the same level in both groups (P = 0.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P = 0.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P < 0.01). The skeletal muscle volume measured by InBody720 significantly decreased in the non-BCAA group (P < 0.001). EIS induced protein-energy malnutrition, however, skeletal muscle volume was maintained by taking BCAA. Administration of BCAA had some effect in maintaining the nutritional state, and may improve the platelet count. Taking a greater amount of nutrients and shorter dietary restriction period or hospitalization was desirable. © 2016 The Japan Society of Hepatology.

Thrombocytopenia associated with the induction of neonatal tolerance to alloantigens: immunopathogenic mechanisms.

PubMed

Merino, J; Qin, H Y; Schurmans, S; Gretener, D; Grau, G E; Lambert, P H

1989-09-01

BALB/c mice rendered tolerant to alloantigens by neonatal injection of semi-allogeneic (C57BL/6 x BALB/c)F1 spleen cells develop a thrombocytopenia in association with an autoimmune lupus-like syndrome. The possible mechanisms involved in the thrombocytopenia were investigated. The development of thrombocytopenia was first detected at 3 weeks of age coinciding with the start of the other autoimmune manifestations and was always related to a state of tolerance and B cell chimerism. There was a significant increase of megakaryocytes in bone marrow and spleens from thrombocytopenic tolerant mice and radiolabeled platelets from these mice were more rapidly eliminated from the bloodstream than normal platelets when injected into normal recipients. A significant correlation between the spleen weight and the decrease of the circulating platelets was observed, although some mice with severe thrombocytopenia had only a moderate spleen enlargement. Thrombocytopenia significantly correlates with the levels of platelet-associated IgG (PAIgG) but not with anti-single-stranded DNA antibodies or circulating immune complexes. Platelets from mice with high levels of PAIgG had a shorter life-span when injected into normal mice than those from mice with low or normal PAIgG. The possibility that PAIgG are partially due to antibodies reacting specifically with platelet membrane components was analyzed. First, F(ab')2 Ig fragments from tolerant mice were shown to bind to normal platelets, in contrast to F(ab')2 Ig fragments from normal mice. Second, some monoclonal antibodies produced by hybridomas derived from tolerant mice reacted in vitro with platelets and induced a transient thrombocytopenia after i.v. injection into normal mice. These data suggest that the thrombocytopenia observed in tolerant mice is the result of a peripheral hyperdestruction of platelets associated with (a) hypersplenism, (b) nonspecific fixation of immunoglobulins, probably as immune complexes and (c) with autoantibodies reacting specifically with platelets. It may represent an interesting model for human chronic idiopathic thrombocytopenia.

Lnk regulates integrin αIIbβ3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo

PubMed Central

Takizawa, Hitoshi; Nishimura, Satoshi; Takayama, Naoya; Oda, Atsushi; Nishikii, Hidekazu; Morita, Yohei; Kakinuma, Sei; Yamazaki, Satoshi; Okamura, Satoshi; Tamura, Noriko; Goto, Shinya; Sawaguchi, Akira; Manabe, Ichiro; Takatsu, Kiyoshi; Nakauchi, Hiromitsu; Takaki, Satoshi; Eto, Koji

2009-01-01

The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk–/– mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin αIIbβ3–mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk–/– mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk–/– platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the β3 integrin subunit, and reduced binding of Fyn to integrin αIIbβ3. These results provide new insight into the mechanism of αIIbβ3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. PMID:20038804

Standardization of a Protocol for Obtaining Platelet Rich Plasma from blood Donors; a Tool for Tissue Regeneration Procedures.

PubMed

Gómez, Lina Andrea; Escobar, Magally; Peñuela, Oscar

2015-01-01

To develop a protocol for obtaining autologous platelet rich plasma in healthy individuals and to determine the concentration of five major growth factors before platelet activation. This protocol could be integrated into the guidelines of good clinical practice and research in regenerative medicine. Platelet rich plasma was isolated by centrifugation from 38 healthy men and 42 women ranging from 18 to 59 years old. The platelet count and quantification of growth factors were analyzed in eighty samples, stratified for age and gender of the donor. Analyses were performed using parametric the t-test or Pearson's analysis for non-parametric distribution. P < 0.05 was considered statistically significant. Our centrifugation protocol allowed us to concentrate basal platelet counts from 1.6 to 4.9 times (mean = 2.8). There was no correlation between platelet concentration and the level of the following growth factors: VEGF-D (r = 0.009, p = 0.4105), VEGF-A (r = 0.0068, p = 0.953), PDGF subunit AA (p = 0.3618; r = 0.1047), PDGF-BB (p = 0.5936; r = 0.6095). In the same way, there was no correlation between donor gender and growth factor concentrations. Only TGF-β concentration was correlated to platelet concentration (r = 0.3163, p = 0.0175). The procedure used allowed us to make preparations rich in platelets, low in leukocytes and red blood cells, and sterile. Our results showed biological variations in content of growth factors in PRP. The factors influencing these results should be further studied.

Molecular mimicry by Helicobacter pylori CagA protein may be involved in the pathogenesis of H. pylori-associated chronic idiopathic thrombocytopenic purpura.

PubMed

Takahashi, Toru; Yujiri, Toshiaki; Shinohara, Kenji; Inoue, Yusuke; Sato, Yutaka; Fujii, Yasuhiko; Okubo, Masashi; Zaitsu, Yuzuru; Ariyoshi, Koichi; Nakamura, Yukinori; Nawata, Ryouhei; Oka, Yoshitomo; Shirai, Mutsunori; Tanizawa, Yukio

2004-01-01

The eradication of Helicobacter pylori often leads to platelet recovery in patients with chronic idiopathic thrombocytopenic purpura (cITP). Although this clinical observation suggests the involvement of H. pylori, little is known about the pathogenesis of cITP. We initially examined the effect of H. pylori eradication on platelet counts in 20 adult Japanese cITP patients. Then, using platelet eluates as the probe in immunoblot analyses, we examined the role of molecular mimicry in the pathogenesis of cITP. Helicobacter pylori infection was detected in 75% (15 of 20) of cITP patients. Eradication was achieved in 13 (87%) of the H. pylori-positive patients, seven (54%) of which showed increased platelet counts within the 4 months following treatment. Completely responsive patients also showed significant declines in platelet-associated immunoglobulin G (PAIgG) levels. Platelet eluates from 12 (nine H. pylori-positive and three H. pylori-negative) patients recognized H. pylori cytotoxin-associated gene A (CagA) protein, and in three completely responsive patients, levels of anti-CagA antibody in platelet eluates declined after eradication therapy. Cross-reactivity between PAIgG and H. pylori CagA protein suggests that molecular mimicry by CagA plays a key role in the pathogenesis of a subset of cITP patients.

Lymphocyte-platelet crosstalk in Graves' disease.

PubMed

Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

2014-03-01

Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

Platelets and Multi-Organ Failure in Sepsis.

PubMed

Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

2017-10-20

Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models.

Platelets and Multi-Organ Failure in Sepsis

PubMed Central

Greco, Elisabetta; Lupia, Enrico; Bosco, Ornella; Vizio, Barbara; Montrucchio, Giuseppe

2017-01-01

Platelets have received increasing attention for their role in the pathophysiology of infectious disease, inflammation, and immunity. In sepsis, a low platelet count is a well-known biomarker for disease severity and more recently authors have focused their attention on the active role of platelets in the pathogenesis of multi-organ failure. Septic shock is characterised by a dysregulated inflammatory response, which can impair the microcirculation and lead to organ injury. Being at the crossroads between the immune system, clotting cascade, and endothelial cells, platelets seem to be an appealing central mediator and possible therapeutic target in sepsis. This review focuses on the pathogenic role of platelets in septic organ dysfunction in humans and animal models. PMID:29053592

Platelet Distribution Width to Platelet Count Ratio as an Index of Severity of Illness.

PubMed

Purbiya, Pragati; Golwala, Zainab Mohammedi; Manchanda, Ayush; Sreenivas, V; Puliyel, Jacob M

2018-01-01

To prospectively validate association between the ratio of platelet distribution width (PDW)/platelet count (PCT) and pediatric intensive care unit (PICU) mortality. The study was done in the pediatric intensive care unit (PICU). Platelet indices in the first sample taken after admission were used. In this case control analysis, cases were the patients who died in PICU and the survivors served as controls. Consecutive 209 eligible patients over a period of 15 mo from January 2014 through March 2015 were included. Exposure was PDW/PC above 0.07. Of them 174 survived and 35 died. The mean PDW for survivors was 16.77 (±0.92) and for those who died it was 17.33 (±1.03) (p 0.0015). Mean platelet count (PC) for survivors was 3,46,000 (±1,64,700) and for those who died it was 1,75,800 (±1,61,500) (p < 0.001). PDW/PC for survivors was 0.12 (±0.46) and for those who died it was 0.336 (±0.53) (p 0.0014). Using the cut-off of 0.07 for PDW/PC described by Golwala et al., 77.14% above the cut-off died, compared to 22.85% below that cut-off. The odds ratio (OR) for death was 10.6 (95% CI: 4.48 to 25.12). The area under the receiver operating curve (ROC) curve for PDW/PC ratio was 0.81. The ratio of PDW/PC, higher than 0.07 in the first sample after admission can be considered as an independent predictor of mortality with sensitivity and specificity of 77.1% and 77.5%, respectively. It may be a useful component for inclusion in composite scores for predicting mortality.

RhoG protein regulates platelet granule secretion and thrombus formation in mice.

PubMed

Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

2013-11-22

Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

Platelet ERK5 is a Redox Switch and Triggers Maladaptive Platelet Responses and Myocardial Infarct Expansion

PubMed Central

Cameron, Scott J.; Ture, Sara K.; Mickelsen, Deanne; Chakrabarti, Enakshi; Modjeski, Kristina L.; McNitt, Scott; Seaberry, Micheal; Field, David J.; Le, Nhat-Tu; Abe, Jun-ichi; Morrell, Craig N.

2015-01-01

Background Platelets have a pathophysiologic role in the ischemic microvascular environment of acute coronary syndromes (ACS). Compared to platelet activation in normal healthy conditions, less attention is given to mechanisms of platelet activation in diseased states. Platelet function and mechanisms of activation in ischemic and reactive oxygen species (ROS) rich environments may not be the same as in normal healthy conditions. Extracellular Regulated Protein Kinase 5 (ERK5) is a Mitogen Activated Protein Kinase (MAPK) family member activated in hypoxic, ROS rich environments, and in response to receptor signaling mechanisms. Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells following ischemia. We present evidence that platelets express ERK5 and platelet ERK5 has an adverse effect on platelet activation via selective receptor-dependent and receptor-independent ROS mediated mechanisms in ischemic myocardium. Methods and Results Using isolated human platelets and a mouse model of myocardial infarction (MI), we found that platelet ERK5 is activated post-MI and platelet specific ERK5−/− mice have less platelet activation, reduced MI size, and improved post-MI heart function. Furthermore, the expression of downstream ERK5 regulated proteins is reduced in ERK5−/− platelets post-MI. Conclusions ERK5 functions as a platelet activator in ischemic conditions and platelet ERK5 maintains the expression of some platelet proteins following MI, leading to infarct expansion. This demonstrates that platelet function in normal healthy conditions is different from platelet function in chronic ischemic and inflammatory conditions. Platelet ERK5 may be a target for acute therapeutic intervention in the thrombotic and inflammatory post-MI environment. PMID:25934838

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

PubMed Central

Ambler, Kimberley L. S.; Vickars, Linda M.; Leger, Chantal S.; Foltz, Lynda M.; Montaner, Julio S. G.; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A.

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed. PMID:22693513

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era.

PubMed

Ambler, Kimberley L S; Vickars, Linda M; Leger, Chantal S; Foltz, Lynda M; Montaner, Julio S G; Harris, Marianne; Dias Lima, Viviane; Leitch, Heather A

2012-01-01

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 10(9)/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 10(9)/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed.

Platelet-rich plasma as treatment for persistent ocular epithelial defects.

PubMed

Ronci, Corrado; Ferraro, Angelo Salvatore; Lanti, Alessandro; Missiroli, Filippo; Sinopoli, Silvia; Del Proposto, Gianpaolo; Cipriani, Chiara; De Felici, Cecilia; Ricci, Federico; Ciotti, Marco; Cudillo, Laura; Arcese, William; Adorno, Gaspare

2015-06-01

Platelet- rich plasma (PRP) exhibits regenerative proprieties in wound healing but the biochemical mechanisms are unclear. In this study, autologous PRP with a mean value of 338 × 10(3) platelets/µL was used to treat corneal lesions of different aetiology, while homologous PRP with 1 × 10(6) platelets/µL was used to treat cornel lesions induced by a graft versus host disease. The impact of platelet count on the levels of PDGF AA and BB, VEGF, and EGF in the two PRPs was evaluated after a cycle of freezing/thawing. Treated corneal lesions healed or improved. The levels of PDGF AA and BB, VEGF, and EGF in the autologous PRP raised from 296 ± 61; 201.8 ± 24; 53 ± 14 and 8.9 ± 2 to 1017 ± 253; 924.7 ± 222; 101 ± 46.5 and 174 ± 15.5 pg/mL, while in the homologous PRP were 3.4, 4.5, 3.2 and 2 folds higher, respectively. High level of platelet counts seems not required to treat corneal lesions. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Mean Platelet Volume in Patients with Retinal Vein Occlusion

PubMed Central

Şahin, Muhammed; Yüksel, Harun; Türkcü, Fatih Mehmet; Çınar, Yasin; Cingü, Abdullah Kürşat; Arı, Şeyhmus; Çaça, İhsan

2013-01-01

Background. The aim of this study was to investigate the mean platelet volume (MPV) of patients with retinal vein occlusion (RVO). Methods. Hundred and ninty-three patients with the diagnosis of RVO and 83 healthy control subjects were included in this retrospective study. Retinal vein occlusion was diagnosed based on clinical examination. All patients and control subjects underwent complete ocular examination. MPV, hematocrit, hemoglobin, and platelet count of the participants were recorded. The data of patients with RVO was compared with the control subjects. Results. Patients with RVO had significantly higher MPV values (8.19 ± 1.22 fL) compared with the control subjects (7.68 ± 1.11 fL) (P = 0.004). No significant difference was found in platelet counts between RVO group and the control group (275.77 ± 70.87 109/L and 261.96 ± 59.40 109/L, resp., P = 0.161), Mean platelet volume was an independent predictor of RVO (odds ratio (OR) = 1.43; 95% confidence interval (CI) = 1.09–1.89; P = 0.011). Conclusion. Our results demonstrated that the MPV values were significantly higher in patients with RVO, suggesting that larger platelets may contribute to the pathogenesis of the RVOs. PMID:23781328

The mean platelet volume in patients with retinal vein occlusion.

PubMed

Sahin, Alparslan; Sahin, Muhammed; Yüksel, Harun; Türkcü, Fatih Mehmet; Cınar, Yasin; Cingü, Abdullah Kürşat; Arı, Seyhmus; Caça, Ihsan

2013-01-01

Background. The aim of this study was to investigate the mean platelet volume (MPV) of patients with retinal vein occlusion (RVO). Methods. Hundred and ninty-three patients with the diagnosis of RVO and 83 healthy control subjects were included in this retrospective study. Retinal vein occlusion was diagnosed based on clinical examination. All patients and control subjects underwent complete ocular examination. MPV, hematocrit, hemoglobin, and platelet count of the participants were recorded. The data of patients with RVO was compared with the control subjects. Results. Patients with RVO had significantly higher MPV values (8.19 ± 1.22 fL) compared with the control subjects (7.68 ± 1.11 fL) (P = 0.004). No significant difference was found in platelet counts between RVO group and the control group (275.77 ± 70.87 10(9)/L and 261.96 ± 59.40 10(9)/L, resp., P = 0.161), Mean platelet volume was an independent predictor of RVO (odds ratio (OR) = 1.43; 95% confidence interval (CI) = 1.09-1.89; P = 0.011). Conclusion. Our results demonstrated that the MPV values were significantly higher in patients with RVO, suggesting that larger platelets may contribute to the pathogenesis of the RVOs.

Natural history of severe thrombocytopenia in infectious mononucleosis

PubMed Central

Wong, Su Yong; Bennett, Bruce

1982-01-01

The natural history of severe thrombocytopenia in two patients with infectious mononucleosis (minimum platelet counts under 10 × 109 and 17 × 109/l respectively) is described. In both, the platelet count rose rapidly and spontaneously, reaching approximately 100 × 109/l on the seventh day. Bleeding symptoms were also transient and never life-threatening. The possibility of very rapid spontaneous recovery from severe thrombocytopenia must be borne in mind in assessing the effect of any drug in the management of this complication of infectious mononucleosis. PMID:7111109

Blood platelets: computerized morphometry applied on optical images

NASA Astrophysics Data System (ADS)

Korobova, Farida V.; Ivanova, Tatyana V.; Gusev, Alexander A.; Shmarov, Dmitry A.; Kozinets, Gennady I.

2000-11-01

The new technology of computerized morphometric image analysis of platelets on blood smears was developed. In a basis of the device is included analysis of cytophotometric and morphometric parameters of platelets. Geometrical and optical parameters of platelets on 35 donors, platelet concentrates and 15 patients with haemorrhagic thrombocythaemia were investigated, average meanings for the area, diameter, its logarithms and optical density of platelets in norm were received. Distribution of the areas, diameters and optical densities of platelets of patients with haemorrhagic thrombocythaemia differed from those at the healthy people. After a course of treatment these meanings came nearer to normal. The important characteristics of platelets in platelet concentrates after three days of storage were in limits of normal meanings, but differed from those in whole blood platelets. Obtained data allow to enter the quantitative standards into investigation of platelets of the healthy people and at various alteration of thrombocytopoieses.

Diagnosis and Prognosis of the Arbovirus-Dengue using Intelligent Algorithm

NASA Astrophysics Data System (ADS)

Jiji, G. Wiselin; Lakshmi, V. Selva; Lakshmi, K. Vathsala; Priya, S. Shunmuga

2016-06-01

Dengue is the most common and widespread arthropod-borne viral infection in the world. It was carried by mosquitoes and this disease used to be called break-bone fever. Dengue is a quite dangerous febrile disease transmitted by aedus aegypti mosquito that can even cause death. In this paper, we proposed new fusion architecture to support the diagnosis of Arbovirus-Dengue. The architecture combines features of platelets and Case-Based Reasoning (CBR) technology together to facilitate medical diagnosis. Along with these features and platelet count, CBR is incorporated which contains symptoms of the disease and platelet count. Experiments on a set of 10 images yielded a balanced accuracy of 86.95 %. This was a superior diagnosis performance in comparison with the state-of-the-art works.

Safety of immediate endoscopic sphincterotomy in acute suppurative cholangitis caused by choledocholithiasis

PubMed Central

Ito, Tomoyasu; Sai, Jin Kan; Okubo, Hironao; Saito, Hiroaki; Ishii, Shigeto; Kanazawa, Ryo; Tomishima, Ko; Watanabe, Sumio; Shiina, Shuichiro

2016-01-01

AIM: To examine the safety of immediate endoscopic sphincterotomy (EST) in patients with acute suppurative cholangitis (ASC) caused by choledocholithiasis, as compared with elective EST. METHODS: Patients with ASC due to choledocholithiasis were allocated to two groups: Those who underwent EST immediately and those who underwent EBD followed by EST 1 wk later because they were under anticoagulant therapy, had a coagulopathy (international normalized ratio > 1.3, partial thromboplastin time greater than twice that of control), or had a platelet count < 50000 × 103/μL. One of four trainees [200-400 cases of endoscopic retrograde cholangiopancreatography (ERCP)] supervised by a specialist (> 10000 cases of ERCP) performed the procedures. The success and complication rates associated with EST in each group were examined. RESULTS: Of the 87 patients with ASC, 59 were in the immediate EST group and 28 in the elective EST group. EST was successful in all patients in both groups. There were no complications associated with EST in either group of patients, although white blood cell count, C-reactive protein, total bilirubin, and serum concentrations of liver enzymes just before EST were significantly higher in the immediate EST group than in the elective EST group. CONCLUSION: Immediate EST can be as safe as elective EST for patients with ASC associated with choledocholithiasis provided they are not under anticoagulant therapy, or do not have a coagulopathy or a platelet count < 50000 × 103/μL. Moreover, the procedure was safely performed by a trainee under the supervision of an experienced specialist. PMID:26862368

Deletion of RUNX1 exons 1 and 2 associated with familial platelet disorder with propensity to acute myeloid leukemia.

PubMed

Cavalcante de Andrade Silva, Marcela; Krepischi, Ana Cristina Victorino; Kulikowski, Leslie Domenici; Zanardo, Evelin Aline; Nardinelli, Luciana; Leal, Aline Medeiros; Costa, Silvia Souza; Muto, Nair Hideki; Rocha, Vanderson; Velloso, Elvira Deolinda Rodrigues Pereira

2018-04-01

Familial platelet disorder with propensity to acute myeloid leukemia (FPD/AML) associated with RUNX1 mutations is an autosomal dominant disorder included in the group of the myeloid neoplasms with germ line predisposition. We describe two brothers who were diagnosed with hematological malignancies (one with AML and the other with T-cell lymphoblastic lymphoma). There was a history of leukemia in the paternal family and two of their siblings presented with low platelet counts and no history of significant bleeding. A microdeletion encompassing exons 1-2 of RUNX1 (outside the cluster region of the Runt Homology domain and the transactivation domain) was detected in six family members using array-CGH and MLPA validation. A low platelet count was not present in all deletion carriers and, therefore, it should not be used as an indication for screening in suspected families and family members. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of Complete Blood Count Indices (NLR, PLR, MPV/PLT, and PLCRi) in Healthy Dogs, Dogs With Periodontitis, and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response.

PubMed

Rejec, Ana; Butinar, Janos; Gawor, Jerzy; Petelin, Milan

2017-12-01

The aim of the study was to retrospectively assess complete blood count (CBC) indices of dogs with periodontitis (PD; n = 73) and dogs with oropharyngeal tumors (OT; n = 92) in comparison to CBC indices of healthy dogs (HD; n = 71). Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet ratio, and platelet large cell ratio index (PLCRi) were evaluated as biomarkers of systemic inflammatory response provoked by PD and OT. Results of multivariable polytomous logistic regression analysis indicated no significant associations between CBC indices and PD. Both NLR and PLCRi were significantly higher in dogs with OT when compared to HD and dogs with PD and could, therefore, indicate a tumor-associated systemic inflammatory response. Additional studies of CBC indices, along with other biomarkers of systemic inflammatory response, are recommended to validate them as reliable indicators of clinical disease activity.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

PubMed

Saito, Shunnichi; Nollet, Kenneth E; Ngoma, Alain M; Ono, Takako; Ohto, Hitoshi

2018-02-01

Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

Laboratory signs of aspirin response in haemodialysis patients.

PubMed

Kilickesmez, Kadriye O; Kocas, Cuneyt; Okcun, Baris; Abaci, Okay; Kaya, Aysem; Arat, Alev; Gorcin, Bilal; Gurmen, Tevfik

2011-09-01

Aspirin is effective in the secondary prevention and high-risk primary prevention of cardiovascular events. However, clinical and laboratory evidence demonstrates diminished or no response to aspirin in some patients. This study was designed to assess aspirin response in haemodialysis patients. We prospectively enrolled 78 haemodialysis patients (28 female; 58.4 ± 12.6 years old) and 79 patients (29 female; 58.4 ± 10.6 years old) with normal renal function (glomerular filtration rate (GFR) >60 mL/min/1.73 m(2)). All subjects in both the haemodialysis patient group and the control group were taking aspirin (80-300 mg) for at least 30 days and were not taking other antiplatelet agents. Platelet function was assessed by arachidonic acid-induced aggregometry with a Multiplate analyser (Dynabyte Medical, Munich, Germany). Multiplate electrode aggregometry values below 300 AU were applied as a cut-off for response to aspirin. Aspirin non-response was two-fold more prevalent in haemodialysis patients (42.3%) than in patients with normal renal function (21.5%), and this difference was statistically significant (p = 0.005). The two groups were similar in terms of sex, age, tobacco use, the presence of diabetes mellitus, and platelet count. The frequency of aspirin non-response as defined in this study was higher in haemodialysis patients than in patients with normal renal function. However, larger subsets of patients are needed to confirm the present study.

The effects of vincristine on platelet aggregation studied by a filter loop technique in the rat.

PubMed Central

Bee, D.; Leach, E.; Martin, J. F.; Suggett, A. J.

1980-01-01

1 A method for measuring aggregation of platelets of adenosine diphosphate (ADP) is described using a filter inserted into the flowing aortic blood in the rat. 2 Repeated infusions of ADP resulted in a fall in the calculated aggregation index without significant changes in the platelet count. 3 Vincristine (0.05 mg/kg) intravenously caused significant inhibition of ADP-induced platelet aggregation. 4 Infusion of ADP caused some peripheral vasodilatation though it is unlikely that this contributed to the effects seen to any great extent. PMID:7437636

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.

Effect of Physical Exercise on Platelet Reactivity in Patients with Dual Antiplatelet Therapy.

PubMed

Brunner, Stefan; Rizas, Konstantinos; Hamm, Wolfgang; Mehr, Michael; Lackermair, Korbinian

2018-06-14

It is known that physical exercise may increase platelet activity. However, the effect of exercise on platelet reactivity in patients on dual antiplatelet therapy has not been investigated yet. In our study, 21 patients with coronary artery disease on dual antiplatelet therapy and 10 controls were enrolled. We performed an exercise test using a cycle ergometer and determined the adenosine diphosphate-induced platelet reactivity before and immediately after exercise testing. Additionally, we analysed maximal exercise capacity and an electrocardiogram. Further, we assessed chromogranin A and P-selectin levels and platelet counts. © Georg Thieme Verlag KG Stuttgart · New York.

Differential proteomics study of platelets in asymptomatic constitutional macrothrombocytopenia: altered levels of cytoskeletal proteins.

PubMed

Karmakar, Shilpita; Saha, Sutapa; Banerjee, Debasis; Chakrabarti, Abhijit

2015-01-01

Harris platelet syndrome (HPS), also known as asymptomatic constitutional macrothrombocytopenia (ACMT), is an autosomal dominant platelet disorder characterized by mild-to-severe thrombocytopenia and giant platelets with normal platelet aggregation and absence of bleeding symptoms. We have attempted a comparative proteomics study for profiling of platelet proteins in healthy vs. pathological states to discover characteristic protein expression changes in macrothrombocytes and decipher the factors responsible for the functionally active yet morphologically distinct platelets. We have used 2-D gel-based protein separation techniques coupled with MALDI-ToF/ToF-based mass spectrometric identification and characterization of the proteins to investigate the differential proteome profiling of platelet proteins isolated from the peripheral blood samples of patients and normal volunteers. Our study revealed altered levels of actin-binding proteins such as myosin light chain, coactosin-like protein, actin-related protein 2/3 complex, and transgelin2 that hint toward the cytoskeletal changes necessary to maintain the structural and functional integrity of macrothrombocytes. We have also observed over expressed levels of peroxiredoxin2 that signifies the prevailing oxidative stress in these cells. Additionally, altered levels of protein disulfide isomerase and transthyretin provide insights into the measures adapted by the macrothrombocytes to maintain their normal functional activity. This first proteomics study of platelets from ACMT may provide an understanding of the structural stability and normal functioning of these platelets in spite of their large size. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of Spectra Optia and COBE Spectra apheresis systems' performances for red blood cell exchange procedures.

PubMed

Kim, Jaehyup; Joseph, Ranjit; Matevosyan, Karen; Sarode, Ravi

2016-12-01

Spectra Optia (Terumo BCT, Lakewood, CO) was FDA approved for red blood cell exchange (RBCx) procedures in January 2014 and is expected to replace COBE spectra (Terumo BCT) very soon in the USA. The performance characteristics of these devices for Isovolemic Hemodilution (IHD-RBCx) procedure were compared in this study. A total of 114 IHD-RBCx procedures from 19 patients were analyzed. For every patient, three procedures on each device with similar pre-procedure hematocrits were compared. Pre and post procedure laboratory parameters compared were hemoglobin S (HbS), hematocrits (Hct), platelet counts and fraction of cells remaining (FCR). Statistical analysis was performed using t-test adjusted by the Holm-Bonferroni method to reduce family-wise error rate. There were no significant differences between these two devices in regards to HbS, Hct, FCR and platelet counts (p = > 0.05). However, rinseback volume (124.2 ± 8.9 ml) and normal saline replacement volume during IHD phase (296.1 ± 97.2 ml) were lower in Spectra Optia as compared to COBE Spectra (337 ± 33.8 ml and 326.6 ± 105.2 ml, p value <0.001 and 0.030 respectively). Spectra Optia had a longer run time (107.1 ± 15.9 min vs 123.8 ± 19.6 min, p value <0.001) overall. Performance characteristics of Spectra Optia for HbS, Hct and FCR were similar to COBE Spectra for IHD-RBCx. IHD-RBCx procedure on Optia required less normal saline replacement volume and rinse back volume but with overall longer procedure run time. Copyright © 2016. Published by Elsevier Ltd.

Microfluidic assay of platelet deposition on collagen by perfusion of whole blood from healthy individuals taking aspirin.

PubMed

Li, Ruizhi; Fries, Susanne; Li, Xuanwen; Grosser, Tilo; Diamond, Scott L

2013-08-01

Microfluidic devices can create hemodynamic conditions for platelet assays. We validated an 8-channel device in a study of interdonor response to acetylsalicylic acid (ASA, aspirin) with whole blood from 28 healthy individuals. Platelet deposition was assessed before treatment or 24 h after ingestion of 325 mg ASA. Whole blood (plus 100 μmol/L H-d-Phe-Pro-Arg-chloromethylketone to inhibit thrombin) was further treated ex vivo with ASA (0-500 μmol/L) and perfused over fibrillar collagen for 300 s at a venous wall shear rate (200 s(-1)). Ex vivo ASA addition to blood drawn before aspirin ingestion caused a reduction in platelet deposition [half-maximal inhibitory concentration (IC50) approximately 10-20 μmol/L], especially between 150 and 300 s of perfusion, when secondary aggregation mediated by thromboxane was expected. Twenty-seven of 28 individuals displayed smaller deposits (45% mean reduction; range 10%-90%; P < 0.001) from blood obtained 24 h after ASA ingestion (no ASA added ex vivo). In replicate tests, an R value to score secondary aggregation [deposition rate from 150 to 300 s normalized by rate from 60 to 150 s] showed R < 1 in only 2 of 28 individuals without ASA ingestion, with R > 1 in only 3 of 28 individuals after 500 μmol/L ASA addition ex vivo. At 24 h after ASA ingestion, 21 of 28 individuals displayed poor secondary aggregation (R < 1) without ex vivo ASA addition, whereas the 7 individuals with residual secondary aggregation (R > 1) displayed insensitivity to ex vivo ASA addition. Platelet deposition was not correlated with platelet count. Ex vivo ASA addition caused similar inhibition at venous and arterial wall shear rates. Microfluidic devices quantified platelet deposition after ingestion or ex vivo addition of aspirin.

Effects of baseline and early acquired thrombocytopaenia on long-term mortality in patients undergoing percutaneous coronary intervention with bivalirudin.

PubMed

Ali, Ziad A; Qureshi, Yasir H; Karimi Galougahi, Keyvan; Poludasu, Shyam; Roye, Swathi; Krishnan, Prakash; Zalewski, Adrian; Shah, Zainab Z; Bhatti, Navdeep; Kalapatapu, Kumar; Mehran, Roxana; Dangas, George; Kini, Annapoorna S; Sharma, Samin K

2016-04-08

Bivalirudin use as a procedural anticoagulant in patients undergoing percutaneous coronary intervention (PCI) is associated with a lower incidence of thrombocytopaenia compared to other antithrombotic agents. We aimed to evaluate the prognostic impact of baseline thrombocytopaenia and early changes in platelet counts among patients undergoing PCI with exclusive use of bivalirudin. We evaluated 7,505 patients who underwent PCI over a period of eight years. Patients who received unfractionated heparin and glycoprotein IIb/IIIa receptor inhibitors were specifically excluded. Eight hundred and fifty-eight (11.4%) patients had baseline thrombocytopaenia and 451 (6.0%) developed acquired thrombocytopaenia. After adjustment for potential covariates, moderate to severe acquired thrombocytopaenia was the strongest independent predictor (HR 4.34, 95% CI: 2.13-8.84; p<0.001) of in-hospital net adverse clinical events, which included major adverse cardiac events and major bleeding complications. Age, male gender, baseline platelet count and intra-aortic balloon pump (IABP) insertion were independent predictors of in-hospital acquired thrombocytopaenia. After a mean follow-up of 2.6±1.7 years, moderate to severe baseline thrombocytopaenia (HR 2.42, 95% CI: 1.79-3.29; p<0.001), moderate to severe acquired thrombocytopaenia (HR 2.37, 95% CI: 1.13-4.97; p=0.02) and severe changes in platelet count (>67 k) were significant predictors of mortality. In patients undergoing PCI with bivalirudin, moderate to severe baseline and acquired thrombocytopaenia along with severe changes in platelet count are associated with higher long-term mortality.

Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases.

PubMed

Perricone, Carlo; Ceccarelli, Fulvia; Nesher, Gideon; Borella, Elisabetta; Odeh, Qasim; Conti, Fabrizio; Shoenfeld, Yehuda; Valesini, Guido

2014-12-01

Immune thrombocytopenic purpura (ITP) is an autoimmune condition characterized by low platelet count with mucocutaneous and other bleedings. Clinical manifestations may range from spontaneous formation of purpura and petechiae, especially on the extremities, to epistaxis, bleeding at the gums or menorrhagia, any of which occur usually if the platelet count is below 20,000 per μl. A very low count may result in the spontaneous formation of hematomas in the mouth or on other mucous membranes. Fatal complications, including subarachnoid or intracerebral, lower gastrointestinal or other internal bleeding can arise due to an extremely low count. Vaccines may induce ITP by several mechanisms. Vaccine-associated autoimmunity may stem not only from the antigen-mediated responses but also from other constituents of the vaccine, such as yeast proteins, adjuvants, and preservatives diluents. The most likely is through virally induced molecular mimicry. The binding of pathogenic autoantibodies to platelet and megakaryocytes may cause thrombocytopenia by different mechanisms, such as opsonization, direct activation of complement, or apoptotic pathways. The autoantibodies hypothesis is not sufficient to explain all ITP cases: In the anti-platelet antibody-negative cases, a complementary mechanism based on T cell immune-mediated mechanism has been suggested. In particular, T cell subsets seem dysregulated with an increased production of pro-inflammatory cytokines, as IFN-γ and TNF, and chemokines, as CXCL10. Vaccines are one of the most striking discoveries in human history that changed dramatically life expectancy. Nonetheless, the occurrence of adverse events and autoimmune phenomena has been described following vaccination, and ITP may represent one of this.

Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis.

PubMed Central

Freedman, J E; Loscalzo, J; Benoit, S E; Valeri, C R; Barnard, M R; Michelson, A D

1996-01-01

Highly reactive oxygen species rapidly inactivate nitric oxide (NO), and endothelial product which inhibits platelet activation. We studied platelet inhibition by NO in two brothers with a cerebral thrombotic disorder. Both children had hyperreactive platelets, as determined by whole blood platelet aggregometry and flow cytometric analysis of the platelet surface expression of P-selectin. Mixing experiments showed that the patients'platelets behaved normally in control plasma; however, control platelets suspended in patient plasma were not inhibited by NO. As determined by flow cytometry, in the presence of plasma from either patient there was normal inhibition of the thrombin-induced expression of platelet surface P-selectin by prostacyclin, but not NO. Using a scopoletin assay, we measured a 2.7-fold increase in plasma H2O2 generation in one patient and a 3.4-fold increase in the second patient, both compared woth control plasma. Glutathione peroxidase (GSH-Px) activity was decreased in the patients' plasmas compared with control plasma. The addition of exogenous GSH-Px led to restoration of platelet inhibition by NO. These data show that, in these patients' plasmas, impaired metabolism of reactive oxygen species reduces the bioavailability of NO and impairs normal platelet inhibitory mechanisms. These findings suggest that attenuated NO-mediated platelet inhibition produced by increased reactive oxygen species or impaired antioxidant defense may cause a thrombotic disorder in humans. PMID:8613552

Hypoxia increases erythropoiesis and decreases thrombocytopoiesis in mice: a comparison of two mouse strains.

PubMed

Cottrell, M B; Jackson, C W; McDonald, T P

1991-07-01

Several previous studies have shown that hypoxia increases erythropoiesis and decreases thrombocytopoiesis in mice. It has been postulated that the thrombocytopenia is caused by stem cell competition between the erythrocytic and megakaryocytic cell lines. In the present work, we compared the effects of severe hypoxia (5.5-6.0% O2) in both male and female C3H and BALB/c mice by measuring their abilities to produce red blood cells and platelets. All mice had significant increases in packed cell volumes and marked decreases in platelet production after hypoxia; however, there were significant differences in the degree of stimulation in the two mouse strains. After 14 days of hypoxia, the percentage of 35S incorporation into platelets, total circulating platelet counts and total circulating platelet masses were lower in C3H mice than in BALB/c mice, but platelet sizes were larger. Also, hypoxia caused greater changes in male mice than in female mice, with male C3H mice showing the greatest increase in packed cell volumes and the lowest platelet counts of all mice tested. The least responses were observed in female BALB/c mice. BALB/c mice had higher P50 (right-shifted O2 dissociation curves) and lower erythrocyte 2,3-diphosphoglycerate values than C3H mice, indicating a lower hemoglobin O2 affinity for BALB/c mice. The results indicate that the effects of hypoxia are not direct upon platelet production, but that the thrombocytopenia is a result of stimulation of erythropoiesis. These data support the stem cell competition hypothesis and illustrate that the degree of the inverse relationship between red blood cells and platelet production of hypoxic mice is dependent, to a large degree, upon the sex and strain of mice that are used.

Hydroxysafflor yellow A of Carthamus tinctorius attenuates lung injury of aged rats exposed to gasoline engine exhaust by down-regulating platelet activation.

PubMed

Wang, Chaoyun; Wang, Chunhua; Ma, Chunlei; Huang, Qingxian; Sun, Hongliu; Zhang, Xiaomin; Bai, Xianyong

2014-02-15

Long-term inhalation of gasoline engine exhaust (GEE) increases the risk of respiratory disease. Studies have suggested involvement of platelets in the development of some lung diseases. Hydroxysafflor yellow A (HSYA), a flavonoid compound, prevents hemostasis. Therefore, we investigated its effects on GEE-induced lung injury, and role of platelets in injury. Sixty-week-old male Sprague-Dawley rats were exposed to GEE for 4h/day for 6 weeks, and then grouped as follows: control, GEE, GEE+HSYA, GEE+HSYA+GW9662, and GEE+GW9662. Arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2), pH, and the PaO2/fraction of inspired oxygen ratio (PaO2/FiO2) in the blood were detected using a blood gas analyzer. Wet/dry lung weight ratio, total protein in bronchoalveolar lavage fluid (BALF), and cytokine concentrations in serum and BALF were determined. Furthermore, cyclic adenosine monophosphate (cAMP) level and expression levels of target proteins were analyzed. Platelets were counted and their state was evaluated. HSYA attenuated GEE-mediated decreases in PaO2, PaO2/FiO2, platelet cAMP level, protein kinase A (PKA) activity, and peroxisome proliferator-activated receptor γ (PPARγ) expression. HSYA also attenuated GEE-mediated increases in lung permeability, cytokine levels in serum and BALF, plasma platelet count, and ADP-mediated platelet aggregation. Moreover, it suppressed GEE-induced increases in the expression of adhesion molecules and proinflammatory cytokines in platelets and lung tissue. Therefore, HSYA is therapeutically effective for GEE-mediated lung injury and acts by enhancing PKA activity and inhibiting platelet activation. Copyright © 2013 Elsevier GmbH. All rights reserved.

Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model.

PubMed

Dharmarathna, Sinhalagoda Lekamlage Chandi Asoka; Wickramasinghe, Susiji; Waduge, Roshitha Nilmini; Rajapakse, Rajapakse Peramune Veddikkarage Jayanthe; Kularatne, Senanayake Abeysinghe Mudiyanselage

2013-09-01

To investigate the potential role of fresh Carica papaya (C. papaya) leaf extract on haematological and biochemical parameters and toxicological changes in a murine model. In total 36 mice were used for the trial. Fresh C. papaya leaf extract [0.2 mL (2 g)/mouse] was given only to the test group (18 mice). General behavior, clinical signs and feeding patterns were recorded. Blood and tissue samples were collected at intervals. Haematological parameters including platelet, red blood cell (RBC), white blood cell (WBC), packed cell volume (PCV), serum biochemistry including serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were determined. Organs for possible histopathological changes were examined. Neither group exhibited alteration of behavior or reduction in food and water intake. Similarly, no significant changes in SGOT, SGPT and serum creatinine levels were detected in the test group. Histopathological organ changes were not observed in either group of mice except in three liver samples of the test group which had a mild focal necrosis. The platelet count (11.33±0.35)×10⁵/µL (P=0.00004) and the RBC count (7.97±0.61)×10⁶/µL (P=0.00003) were significantly increased in the test group compared to that of the controls. However, WBC count and PCV (%) values were not changed significantly in the test group. The platelet count in the test group started to increase significantly from Day 3 (3.4±0.18×10⁵/µL), reaching almost a fourfold higher at Day 21 (11.3×10⁵/µL), while it was 3.8×10⁵/µL and 5.5×10⁵/µL at Day 3 and Day 21 respectively in the control. Likewise, the RBC count in the test group increased from 6×10⁶/µL to 9×10⁶/ µL at Day 21 while it remained near constant in the control group (6×10⁶/µL). Fresh C. papaya leaf extract significantly increased the platelet and RBC counts in the test group as compared to controls. Therefore, it is very important to identify those chemicals of C. papaya leaves as it can be recommended to be used as a medication to boost thrombopoiesis and erythropoiesis in humans and in animals in which these cell lineages have been compromised.

Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model

PubMed Central

Dharmarathna, Sinhalagoda Lekamlage Chandi Asoka; Wickramasinghe, Susiji; Waduge, Roshitha Nilmini; Rajapakse, Rajapakse Peramune Veddikkarage Jayanthe; Kularatne, Senanayake Abeysinghe Mudiyanselage

2013-01-01

Objective To investigate the potential role of fresh Carica papaya (C. papaya) leaf extract on haematological and biochemical parameters and toxicological changes in a murine model. Methods In total 36 mice were used for the trial. Fresh C. papaya leaf extract [0.2 mL (2 g)/mouse] was given only to the test group (18 mice). General behavior, clinical signs and feeding patterns were recorded. Blood and tissue samples were collected at intervals. Haematological parameters including platelet, red blood cell (RBC), white blood cell (WBC), packed cell volume (PCV), serum biochemistry including serum creatinine, serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT) were determined. Organs for possible histopathological changes were examined. Results Neither group exhibited alteration of behavior or reduction in food and water intake. Similarly, no significant changes in SGOT, SGPT and serum creatinine levels were detected in the test group. Histopathological organ changes were not observed in either group of mice except in three liver samples of the test group which had a mild focal necrosis. The platelet count (11.33±0.35)×105/µL (P=0.000 04) and the RBC count (7.97±0.61)×106/µL (P=0.000 03) were significantly increased in the test group compared to that of the controls. However, WBC count and PCV (%) values were not changed significantly in the test group. The platelet count in the test group started to increase significantly from Day 3 (3.4±0.18×105/µL), reaching almost a fourfold higher at Day 21 (11.3×105/µL), while it was 3.8×105/µL and 5.5×105/µL at Day 3 and Day 21 respectively in the control. Likewise, the RBC count in the test group increased from 6×106/µL to 9×106/ µL at Day 21 while it remained near constant in the control group (6×106/µL). Conclusions Fresh C. papaya leaf extract significantly increased the platelet and RBC counts in the test group as compared to controls. Therefore, it is very important to identify those chemicals of C. papaya leaves as it can be recommended to be used as a medication to boost thrombopoiesis and erythropoiesis in humans and in animals in which these cell lineages have been compromised. PMID:23998013

Comparison between human and porcine thromboelastograph parameters in response to ex-vivo changes to platelets, plasma, and red blood cells.

PubMed

Sondeen, Jill L; de Guzman, Rodolfo; Amy Polykratis, Irene; Dale Prince, Malcolm; Hernandez, Orlando; Cap, Andrew P; Dubick, Michael A

2013-12-01

In the acute care setting, both the tracings and numeric outputs (R time, angle, and MA) of thrombelastography (TEG) may be used to inform treatment decisions. The objective was to determine the sensitivity of TEG to isolated changes in platelet count, hematocrit and fibrinogen concentration in human blood. As pigs have a similar coagulation system, we also compared the responses of the pig blood. Eight volunteers (>18 years of age, no anticoagulation or nonsteroidal anti-inflammatory therapy, not pregnant) were enrolled into this study. Four female anesthetized donor pigs were instrumented percutaneously with a catheter for blood collection. All blood was collected into sodium citrate. The concentration of each component (platelets, fibrinogen, and red blood cells) was changed while keeping the other components constant by use of centrifugation or preparation of each individual's plasma into platelet poor plasma, platelet rich plasma, cryoprecipitate, purified washed platelets, and packed red blood cells as appropriate. TEG (Haemoscope) analysis was performed and compared with the patients' whole blood diluted with lactated Ringer's solution. We demonstrated that the major factor affecting the MA and angle was the platelet count. In fact, reducing platelets alone resulted in TEG profiles and parameters that were similar to lactated Ringer's dilution profiles. Swine blood responses were parallel to that of human blood, although there were offsets especially of TEG-R and angle that confirmed that the swine are hypercoagulable compared with humans. Superficially similar TEG tracing patterns can be produced by divergent mechanisms associated with altered concentrations of blood components.

An adolescent girl with abnormal liver profile.

PubMed

Nair, S; Pitchumoni, C S

1998-04-01

A 17-year-old previously healthy high school student who lived in a dormitory was referred to our office by her private physician for evaluation of abnormal liver function tests. She was sexually active with one partner but denied any current or past substance abuse. The patient was not taking any medications or nutritional supplements. Family history was unremarkable. Physical examination revealed scleral icterus and minimal hepatomegaly. Spleen was not palpable. The liver function tests are shown in table 1. Total leucocyte count was 6.3 x 10(9)/1 with 53% lymphocytes. The platelet count was normal. Anti-Hbc IgM antibody was negative, so were anti-HAV IgM and anti-HCV antibodies. HBsAg was negative and anti-HBs antibody was positive. Erythrocyte sedimentation rate was 16 mm in the first hour. An abdominal sonogram was done to evaluate a persistent elevation in alkaline phosphatase and it showed only hepatomegaly.

Calcium supplementation during pregnancy for preventing hypertensive disorders is not associated with changes in platelet count, urate, and urinary protein: a randomized control trial.

PubMed

Hofmeyr, G J; Mlokoti, Z; Nikodem, V C; Mangesi, L; Ferreira, S; Singata, M; Jafta, Z; Merialdi, M; Hazelden, C; Villar, J

2008-01-01

To test the hypothesis that calcium supplementation inhibits the underlying pathological processes in women with preeclampsia. Seven hundred and eight nulliparous women were enrolled in a WHO randomized double-blind trial, who received 1.5 g of calcium or placebo from 20 weeks of pregnancy or earlier. Platelet count, serum urate, and urinary protein/creatinine ratio were measured at or near 35 gestational weeks. No difference was detected in rates of abnormal platelet count (relative risk [RR] 1.18; 95% confidence interval [CI], 0.63 to 2.18), serum urate level (1.0; 0.64 to 1.57) or urine protein/creatinine ratio (1.01; 0.76 to 1.34). This was consistent with the main trial finding of no difference in the incidence of 'dipstick' proteinuria between women receiving calcium and those receiving placebo (8312 women; RR, 1.01; 95% CI, 0.88 to 1.15). An effect of calcium supplementation in the second half of pregnancy on the rate of abnormal laboratory measures associated with preeclampsia was not demonstrated.

Plasma serotonin in patients with chronic tension headaches.

PubMed

Anthony, M; Lance, J W

1989-02-01

Previous reports have suggested that platelet level of serotonin in chronic tension headache (CTH) is lower than in normal control subjects, and that there is continuous activation of platelets both in migraine and in CTH. In this study we compared platelet serotonin concentration in 95 patients with CTH, 166 patients with migraine and 35 normal control subjects. Mean platelet serotonin (ng/10(9) platelets) was 310 for the CTH group, 384 during migraine headache, 474 for normal control subjects and 514 in headache-free migrainous patients. There was significant statistical difference of values between CTH patients and those of normal control subjects as well as headache-free migrainous patients, but not of those of migrainous patients during headache. It is suggested that CTH is a low serotonin syndrome, representing one end of the spectrum of idiopathic headache, the other end being represented by migraine.

Human platelet lysate as a promising growth-stimulating additive for culturing of stem cells and other cell types.

PubMed

Shanskii, Ya D; Sergeeva, N S; Sviridova, I K; Kirakozov, M S; Kirsanova, V A; Akhmedova, S A; Antokhin, A I; Chissov, V I

2013-11-01

We compared the composition and biological activity of fetal calf serum and platelet lysate from donor platelet concentrate. In platelet lysate, the concentrations of alkaline phosphatase, lactate dehydrogenase, creatinine, and mineral metabolism parameters were lower, while parameters of lipid and protein metabolism were higher than in fetal calf serum. The concentrations of growth factors (platelet-derived (AA, AB, BB), vascular endothelial, insulin-like, and transforming growth factor β) in platelet lysate 1.7-148.7-fold surpassed the corresponding parameters in fetal calf serum. After replacement of fetal calf serum with platelet lysate in the culture medium (0, 25, 50, 75, and 100%), the count of multipotent mesenchymal stromal cells on day 7 (in comparison with day 1) increased by 154.8, 206.6, 228.2, 367.7, and 396.5%, respectively. Thus, platelet lysate can be an adequate non-xenogenic alternative for fetal calf serum.

Examining platelet-fibrin interactions during traumatic shock in a swine model using platelet contractile force and clot elastic modulus.

PubMed

White, Nathan J; Martin, Erika J; Brophy, Donald F; Ward, Kevin R

2011-07-01

A significant proportion of severely injured patients develop early coagulopathy, characterized by abnormal clot formation, which impairs resuscitation and increases mortality. We have previously demonstrated an isolated decrease in clot strength by thrombelastography in a swine model of nonresuscitated traumatic shock. In order to more closely examine platelet-fibrin interactions in this setting, we define the observed decrease in clot strength in terms of platelet-induced clot contraction and clot elastic modulus using the Hemostasis Analysis System (HAS) (Hemodyne Inc., Richmond, Virginia, USA). Whole blood was sampled for HAS measurements, metabolic measurements, cell counts, and fibrinogen concentration at baseline prior to injury and again at a predetermined level of traumatic shock defined by oxygen debt. Male swine (N=17) received femur fracture and controlled arterial hemorrhage to achieve an oxygen debt of 80 ml/kg. Platelet counts were unchanged, but fibrinogen concentration was reduced significantly during shock (167.6 vs. 66.7 mg/dl, P=0.0007). Platelet contractile force generated during clot formation did not change during shock (11.7 vs. 10.4 kdynes, P=0.41), but clot elastic modulus was dynamically altered, resulting in a lower final value (22.9 vs. 17.3 kdynes/cm, P<0.0001). In this model of traumatic shock, platelet function was preserved, whereas terminal clot elastic modulus was reduced during shock in a manner most consistent with early changes in the mechanical properties of the developing fibrin fiber network.

Attenuation of Thrombosis by Crude Rice (Oryza sativa) Bran Policosanol Extract: Ex Vivo Platelet Aggregation and Serum Levels of Arachidonic Acid Metabolites

PubMed Central

Ismail, Maznah; Tohit, Eusni Rahayu Mohd; Abdullah, Rasedee; Zhang, Yi-Da

2016-01-01

Background. Vascular occlusion or thrombosis was often attributed to uncontrolled platelet activation. Influence of sugarcane policosanol extract on platelet was reported but little was known of rice bran policosanol, particularly its mechanisms of actions on platelet activities. Objective. Antiplatelet mechanisms of rice bran policosanol extract (RBE) were studied using hyperlipidemic Sprague Dawley rats. Ex vivo platelet aggregation, platelet count (PC), bleeding time (BT), and coagulation time were assayed. Serum eicosanoids and other aggregation-related metabolites levels were quantified. Design. Rats were divided into 6 groups for comparisons (vehicle control Tween 20/H2O, high dose policosanol 500 mg/kg, middle dose policosanol 250 mg/kg, low dose policosanol 100 mg/kg, and positive control aspirin 30 mg/kg). Results. Low dose 100 mg/kg of RBE inhibited aggregation by 42.32 ± 4.31% and this was comparable with the effect of 30 mg/kg aspirin, 43.91 ± 5.27%. Results showed that there were no significant differences in PC, BT, and coagulation time among various groups after RBE treatment. Serum thromboxane A2 was attenuated while prostacyclin level increased upon RBE treatment. Conclusions. RBE reduced ex vivo ADP-induced platelet aggregation without giving adverse effects. No changes in full blood count suggested that rice bran policosanol did not disturb biological blood cell production and destruction yet it reduced aggregation through different mechanisms. PMID:27800004

Neutrophil-lymphocyte ratio in patients with pesticide poisoning.

PubMed

Dundar, Zerrin Defne; Ergin, Mehmet; Koylu, Ramazan; Ozer, Rasit; Cander, Basar; Gunaydin, Yahya Kemal

2014-09-01

Pesticides are highly toxic to human beings, and pesticide poisoning is associated with high morbidity and mortality. The identification of powerful prognostic markers is important for the management of patients with pesticide poisoning in emergency settings. To investigate the prognostic value of the neutrophil-lymphocyte ratio and hematological parameters measured in patients with pesticide poisoning within the first 24 h after admission to the emergency department (ED). All patients (≥15 years old) admitted to the ED from July 2008 through February 2013 due to pesticide poisoning were enrolled in the study. The written and electronic medical charts of patients were reviewed. Neutrophil-lymphocyte ratio and platelet-lymphocyte ratio were calculated for each patient using absolute neutrophil, lymphocyte, and platelet counts. Mechanical ventilation requirement and mortality were used as the primary endpoints. A total of 189 patients were included in the study. The mechanically ventilated patients had significantly higher leukocyte and neutrophil counts, and neutrophil-lymphocyte and platelet-lymphocyte ratios (p < 0.001, p < 0.001, p < 0.001, p = 0.003, respectively), whereas they had significantly lower lymphocyte counts compared to nonventilated patients (p = 0.011). Survivors had significantly higher leukocyte and neutrophil counts, and neutrophil-lymphocyte ratios (p < 0.001, p < 0.001, p = 0.002, respectively), whereas there was no significant difference between groups in terms of lymphocyte counts (p = 0.463), compared to nonsurvivors. Leukocyte counts, neutrophil counts, and neutrophil-lymphocyte ratios measured within the first 24 h after admission to the ED are useful and easy-to-use parameters for estimating prognosis in the follow-up of patients with pesticide poisoning. Copyright © 2014 Elsevier Inc. All rights reserved.

[The occurrence and impact on survival of type 2 diabetes mellitus and thrombocytosis in colorectal cancer, before and after the surgical resection of the primary tumor].

PubMed

Herold, Zoltán; Ambrus, Viktória; Herold, Magdolna; Herczeg, György; Igaz, Péter; Harsányi, László; Somogyi, Anikó

2018-05-01

The relationship between platelets and metastatic tumor cells is an ongoing research area. Pre- and postoperative thrombocytosis are suggested predictive survival markers. Colorectal cancer and type 2 diabetes are characterized by various changes to platelets. The occurrence of colorectal cancer is more frequent in diabetes. Our aim was to determine the occurrence of type 2 diabetes in colorectal cancer patients, who attended the Semmelweis University 2nd Department of Internal Medicine's Oncology Department in the last three years. Further goals included the evaluation of anamnestic, pre- and postoperative laboratory data, and whether diabetes can be a significant survival factor. A retrospective study was conducted with 86 randomly selected colorectal cancer patients' preoperative (86 patients) and paired postoperative (66, who were operable) data. Patients were monitored no later than September 30, 2017 or until their death. Preoperatively, elevated (over 400 Giga/L) platelet counts were present in 22.1% of the patients (323.5 ± 128.63 Giga/L, mean ± SD) which decreased to 10.6% postoperatively (χ 2 : p = 0.0351; 289.2 ± 82.45 Giga/L, p = 0.0232). Negative correlation was found between platelet counts and overall survival (R: -0.35, p = 0.0085). One third of the patients had diabetes. Laboratory results (i.e., blood counts, creatinine) between diabetic and non-diabetic patients were not significant. Diabetes is a significant five-fold postoperative risk factor for shorter overall survival (relative risk: 5.1612, p = 0.0165). Average survival was 30.6 ± 26.78 months. Persistent consequential postoperative thrombocytosis may indicate shorter survival time. Our observations suggest elevated platelet counts and type 2 diabetes as prognostic markers for survival at the recognition of colorectal tumors. Orv Hetil. 2018; 159(19): 756-767.

Bleeding frequency and characteristics among hematologic malignancy inpatient rehabilitation patients with severe thrombocytopenia.

PubMed

Fu, Jack B; Tennison, Jegy M; Rutzen-Lopez, Isabel M; Silver, Julie K; Morishita, Shinichiro; Dibaj, Seyedeh S; Bruera, Eduardo

2018-03-28

To identify the frequency and characteristics of bleeding complications during acute inpatient rehabilitation of hematologic malignancy patients with severe thrombocytopenia. Retrospective descriptive analysis. Comprehensive cancer center acute inpatient rehabilitation unit. Consecutive hematologic malignancy patients with a platelet count of less than or equal to 20,000/microliter (μL) on the day of acute inpatient rehabilitation admission from 1/1/2005 through 8/31/2016. Medical records were retrospectively analyzed for demographic, laboratory, and medical data. Patients were rehabilitated using the institutional exercise guidelines for thrombocytopenic patients. Bleeding events noted in the medical record. Out of 135 acute inpatient rehabilitation admissions, 133 unique patients were analyzed with a total of 851 inpatient rehabilitation days. The mean platelet count was 14,000/μL on the day of admission and 22,000/μL over the course of the rehabilitation admission. There were 252 days of inpatient rehabilitation where patients had less than 10,000/μL platelets. A total of 97 bleeding events were documented in 77/135 (57%) admissions. Of the 97 bleeding events, 72 (74%), 14 (14%), and 11 (11%) were considered to be of low, medium, and high severity, respectively. There were 4/97 (4%) bleeding events that were highly likely attributable to physical activity but only 1/4 was considered high severity. Bleeding rates were .09, .08, .17, and .37 for > 20,000, 15-20,000, 10-15,000, and < 10,000/μL mean platelet counts respectively (p = .003). Forty-four percent of patients were transferred back to the primary acute care service with infection being the most common reason for transfer. This study is the first to examine exercise-related bleeding complications during acute inpatient rehabilitation in severely thrombocytopenic hematologic cancer patients. Bleeding rates increased with lower platelet counts. However, using the exercise guidelines for severely thrombocytopenic patients, the risk of severe exercise-related bleeding events was low.

Relationship between hepatic CTGF expression and routine blood tests at the time of liver transplantation for biliary atresia: hope or hype for a biomarker of hepatic fibrosis.

PubMed

Haafiz, Allah; Farrington, Christian; Andres, Joel; Islam, Saleem

2011-01-01

Progressive hepatic fibrosis (HF) is a prominent feature of biliary atresia (BA), the most common indication for liver transplantation (LT) in children. Despite its importance in BA, HF is not evaluated in routine patient care because the invasiveness of liver biopsy makes histologic monitoring of fibrosis unfeasible. Therefore, the identification of noninvasive markers to assess HF is desirable especially in children. The main goal of this pilot project was to establish an investigational framework correlating hepatic expression of fibrogenic markers with routine blood tests in BA. Using liver explants from patients with BA (n = 26), immune-expression of connective tissue growth factor (CTGF), a key fibrogenic cytokine was determined using horseradish-labeled antibodies. Expression intensities of lobular (L-CTGF) and portal (P-CTGF) CTGF were determined by using ImageJ software. These CTGF intensities were correlated with blood tests performed at the time of LT. Correlation coefficients were determined for each blood test variable versus mean L-CTGF and P-CTGF expression intensities. A P-value of less than 0.05 was considered statistically significant. All patients had end-stage liver disease and persistent cholestasis at the time of LT. Kendall tau (τ) rank correlation coefficient for L-CTGF and white blood cell (WBC) was inversed (-0.52; P ≤ 0.02). Similar but statistically nonsignificant inverse relationships were noted between L-CTGF and prothrombin time (PT) (-0.15; P ≤ 0.4), international normalized ratio (INR) (-0.14; P ≤ 0.5), and platelet count (-0.36; P ≤ 0.09). Inversed (τ) rank correlation coefficients were also evident between P-CTGF expression and gamma-glutamyl transpeptidase (GGT), PT, INR, and platelet count. Pearson correlation coefficients for combinational analysis of standardized total bilirubin (TB), alkaline phosphatase, GGT, and platelet count with L-CTGF (0.33; P = 0.3) and P-CTGF (0.06; P = 0.8), were not significant. Similar analysis for alanine aminotransferase, TB, and GGT combination (L-CTGF, 0.16; P = 0.5; P-CTGF -0.3; P = 0.2) as well as WBC, platelet count, and TB (L-CTGF: -0.36; P = 0.09; P-CTGF -0.33; P = 0.13) also revealed nonsignificant results. Hepatic expression of fibrogenic markers can be correlated with routinely performed blood tests in patients with BA. We document that although a trend of inverse relationship is noted, hepatic CTGF expression does not correlate well with routinely performed blood tests in advanced BA. Further work is required to determine more reliable ways of noninvasive diagnosis of HF.

Genome-wide Association Study of Platelet Count Identifies Ancestry-Specific Loci in Hispanic/Latino Americans

PubMed Central

Schick, Ursula M.; Jain, Deepti; Hodonsky, Chani J.; Morrison, Jean V.; Davis, James P.; Brown, Lisa; Sofer, Tamar; Conomos, Matthew P.; Schurmann, Claudia; McHugh, Caitlin P.; Nelson, Sarah C.; Vadlamudi, Swarooparani; Stilp, Adrienne; Plantinga, Anna; Baier, Leslie; Bien, Stephanie A.; Gogarten, Stephanie M.; Laurie, Cecelia A.; Taylor, Kent D.; Liu, Yongmei; Auer, Paul L.; Franceschini, Nora; Szpiro, Adam; Rice, Ken; Kerr, Kathleen F.; Rotter, Jerome I.; Hanson, Robert L.; Papanicolaou, George; Rich, Stephen S.; Loos, Ruth J.F.; Browning, Brian L.; Browning, Sharon R.; Weir, Bruce S.; Laurie, Cathy C.; Mohlke, Karen L.; North, Kari E.; Thornton, Timothy A.; Reiner, Alex P.

2016-01-01

Platelets play an essential role in hemostasis and thrombosis. We performed a genome-wide association study of platelet count in 12,491 participants of the Hispanic Community Health Study/Study of Latinos by using a mixed-model method that accounts for admixture and family relationships. We discovered and replicated associations with five genes (ACTN1, ETV7, GABBR1-MOG, MEF2C, and ZBTB9-BAK1). Our strongest association was with Amerindian-specific variant rs117672662 (p value = 1.16 × 10−28) in ACTN1, a gene implicated in congenital macrothrombocytopenia. rs117672662 exhibited allelic differences in transcriptional activity and protein binding in hematopoietic cells. Our results underscore the value of diverse populations to extend insights into the allelic architecture of complex traits. PMID:26805783

Use of the Heimlich valve in a compact autotransfusion device.

PubMed

Schweitzer, E J; Hauer, J M; Swan, K G; Bresch, J R; Harmon, J W; Graeber, G M

1987-05-01

A compact device which evacuates blood from a hemothorax and facilitates rapid autotransfusion was evaluated in dogs. Experimental hemothorax was established surgically by incising the internal mammary artery through a thoracotomy with the animals under general anesthesia. Postoperatively the blood was drained by one of two methods. In the Heimlich valve group (n = 5), blood was drained by a chest tube through a one-way flutter valve into a collapsible plastic bag. In the Sorenson group (n = 5), blood was drained by a chest tube into the Sorenson Autotransfusion System. Blood from these two groups was then autotransfused. In the control group (n = 5), the drained blood was not autotransfused. Results showed no statistical difference between the two autotransfusion groups in the volume of blood collected, circulating fibrinogen levels, platelet counts, stroma-free hemoglobin levels, prothrombin time, or 51Cr-labeled RBC survival. There was a significant drop in the circulating platelet count, which returned to normal by 24 hours, in both groups of dogs which were autotransfused. We conclude that autotransfusion of blood collected by a compact device which utilizes a Heimlich valve and requires no suction is similar to using the Sorenson Autotransfusion System. It may be safe to use the Heimlich valve to collect blood for autotransfusion in clinical situations, where its qualities of simplicity, portability and a minimum requirement for storage space are desirable.

Cytogenetic abnormalities and their prognostic significance in idiopathic myelofibrosis: a study of 106 cases.

PubMed

Reilly, J T; Snowden, J A; Spearing, R L; Fitzgerald, P M; Jones, N; Watmore, A; Potter, A

1997-07-01

The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).

Management of antithrombotic therapy in adults with immune thrombocytopenia (ITP): a survey of ITP specialists and general hematologist-oncologists.

PubMed

Pishko, Allyson M; Misgav, Mudi; Cuker, Adam; Cines, Douglas B; George, James N; Vesely, Sara K; Terrell, Deirdra R

2018-07-01

While patients with immune thrombocytopenia (ITP) and low platelet counts are at risk for bleeding, they are not protected against arterial and venous thrombotic events. Frequently, hematologists are asked to consult on a patient with ITP requiring an antiplatelet (AP) agent or anticoagulant (AC). No direct evidence exists to guide hematologists in weighing the risk of thrombosis against the risk of bleeding in patients with ITP. Therefore, we performed a survey to determine the preferred management of AP/AC therapy in ITP patients. The survey described hypothetical patient scenarios and asked respondents to recommend a minimum platelet count for initiation of AP/AC therapy. We surveyed both hematologists with an international reputation in treatment of ITP (n = 48) and also general hematologist-oncologists in Oklahoma (n = 97). Response rates were 38/48 (79%) for the ITP specialists and 46/97 (47%) for general hematologist-oncologists. Overall, recommended platelet thresholds for antithrombotic therapy were similar between ITP specialists and general hematologist-oncologists. Although both groups recommended a minimum platelet count of 50 × 10 9 /L for AP and AC therapy in most scenarios, there was great variability in individual practice patterns among respondents. This study highlights the need for studies of patients with ITP who require AP/AC therapy to provide high-quality evidence for establishing optimal management strategies.

Ratio of mean platelet volume to platelet count is a potential surrogate marker predicting liver cirrhosis.

PubMed

Iida, Hiroya; Kaibori, Masaki; Matsui, Kosuke; Ishizaki, Morihiko; Kon, Masanori

2018-01-27

To provide a simple surrogate marker predictive of liver cirrhosis (LC). Specimens from 302 patients who underwent resection for hepatocellular carcinoma between January 2006 and December 2012 were retrospectively analyzed. Based on pathologic findings, patients were divided into groups based on whether or not they had LC. Parameters associated with hepatic functional reserve were compared in these two groups using Mann-Whitney U -test for univariate analysis. Factors differing significantly in univariate analyses were entered into multivariate logistic regression analysis. There were significant differences between the LC group ( n = 100) and non-LC group ( n = 202) in prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, cholinesterase, type IV collagen, hyaluronic acid, indocyanine green retention rate at 15 min, maximal removal rate of technitium-99m diethylene triamine penta-acetic acid-galactosyl human serum albumin and ratio of mean platelet volume to platelet count (MPV/PLT). Multivariate analysis showed that prothrombin activity, concentrations of alanine aminotransferase, aspartate aminotransferase, total bilirubin and hyaluronic acid, and MPV/PLT ratio were factors independently predictive of LC. The area under the curve value for MPV/PLT was 0.78, with a 0.8 cutoff value having a sensitivity of 65% and a specificity of 78%. The MPV/PLT ratio, which can be determined simply from the complete blood count, may be a simple surrogate marker predicting LC.

Plasma-derived microparticles in polycythaemia vera.

PubMed

Ahadon, M; Abdul Aziz, S; Wong, C L; Leong, C F

2018-04-01

Microparticles are membrane bound vesicles, measuring less than 1.0 um, which are released during cellular activation or during apoptosis. Studies have shown that these circulating microparticles play a role in coagulation, cell signaling and cellular interactions. Increased levels of circulating microparticles have been observed in a number of conditions where there is vascular dysfunction, thrombosis and inflammation. The objective of this study was to determine the various plasma-derived microparticles in patients with polycythaemia vera (PV) in Universiti Kebangsaan Malaysia Medical Centre and to compare them with normal control. A total of 15 patients with PV and 15 healthy volunteers were included in this cross-sectional descriptive study. Plasma samples from both patients and healthy volunteers were prepared and further processed for isolation of microparticles. Flow cytometry analyses were then carried out in all samples to determine the cellular origin of the microparticles. Full blood count parameters for both groups were also collected. Data collected were analyzed using SPSS version 12.0. Patients with PV had a significantly higher percentage of platelet derived microparticles compared to healthy controls (P <0.05). The control group had a higher level of endothelial derived microparticles but the differences were not statistically significant (P > 0.05). The median percentage of positive events for platelet derived microparticles was higher in patients with PV compared to normal healthy controls.

Update on thrombopoietin in preclinical and clinical trials.

PubMed

Miyazaki, H

1998-05-01

Thrombopoietin, also termed the c-Mpl ligand, is a lineage-dominant hematopoietic factor that primarily regulates megakaryopoiesis and thrombopoiesis. Treatment of normal animals with recombinant human megakaryocyte growth and development factor, a truncated molecule of the c-Mpl ligand, which is modified with polyethylene glycol (PEG-rHuMGDF), and glycosylated recombinant thrombopoietin stimulates the expansion of bone marrow megakaryocytes and their progenitors, and greatly enhances the production of morphologically and functionally normal platelets. In contrast, this cytokine has only minimal effects on peripheral leukocyte and erythrocyte counts. In myelosuppressed animals, PEG-rHuMGDF or glycosylated thrombopoietin accelerates multilineage hematopoietic recovery effectively improving thrombocytopenia and, in most models, leukopenia (or neutropenia) and anemia. In addition to daily multiple injections, even a single injection of PEG-rHuMGDF after myelosuppressive treatment is fully effective for hematopoietic recovery. In clinical trials, PEG-rHuMGDF or glycosylated recombinant human thrombopoietin potently stimulates thrombopoiesis in cancer patients before chemotherapy. The administration of PEG-rHuMGDF alone or in combination with recombinant human granulocyte colony-stimulating factor (rhG-CSF) reduces the duration of severe thrombocytopenia and in some cases platelet nadirs in patients with advanced cancers after dose-intensive chemotherapy. The recombinant hormone is well-tolerated with little drug-related toxicity.

Arterial thrombosis associated with immune thrombocytopenia: presence of a platelet aggregating IgG synergistic with thrombin and adrenalin.

PubMed

Jackson, S P; Jane, S M; Mitchell, C A; Fernando Cortizo, W; Hau, L; Pfueller, S L; Salem, H H

1989-11-24

We report the case of a 50-year-old lady who presented with arterial thrombosis in the setting of thrombocytopenia. Investigations confirmed the diagnosis of idiopathic thrombocytopenic purpura. A spontaneous platelet aggregating factor (SPAF) was isolated from the immunoglobulin fraction of the patient's plasma. The isolated IgG irreversibly aggregated platelet-rich plasma and washed platelets, an effect abolished by pretreating the platelets with aspirin. The activity of the IgG was greatly enhanced by subaggregatory concentrations of thrombin and adrenalin and was localized to the F(ab')2 of the molecule. Plasmapheresis in combination with anti-platelet therapy resulted in an increase in the patient's platelet count, reduced platelet aggregating activity of plasma and significant clinical improvement. We suggest that the presence of this platelet aggregating IgG contributed to the development of thrombosis in our patient and postulate that a similar factor may explain the paradox of thrombosis observed in a select group of thrombocytopenic patients.

Medical examination of Rongelap people six months after exposure to fallout

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

Bond, V.P.; Conard, R.A.; Robertson, J.S.

1955-04-01

Follow-up medical examinations were made of the Marshallese inhabitants of Rongelap Atoll 6 months after they had been exposed to atomic bomb fallout radiation during the Operation CASTLE test series in March, 1954. During the early acute period following exposure, these people had shown systemic effects and marked hematological changes resulting from penetrating gamma radiation; extensive superficial skin lesions and epilation associated principally with beta and soft gamma radiation from fallout material deposited on uncovered skin areas; and minimal internal contamination with fission products, resulting principally from ingestion of fallout material. At the time of the 6-month resurvey the individuals,more » in general, appeared healthy and normally active, and no deaths had occurred in the interim period. Chest X-rays of all individuals revealed no abnormalities ascribable to the fallout radiation. Analysis of hematological data obtained failed to demonstrate a significant effect of measles on the peripheral blood count. Neutrophile, lymphocyte, and platelet counts were not significantly different from counts taken on the 74th post-exposure day, and none of these values had returned to control levels.« less

Fragmented red cells reference range for the Sysmex XN®-series of automated blood cell counters.

PubMed

Lesesve, J-F; Speyer, E; Perol, J-P

2015-10-01

Fragmented red cells (FRCs) are a new parameter determined automatically by the latest generation of blood cell counters. FRC counts may be of interest as they may reflect schistocyte counts measured on a stained peripheral blood smear observed under the microscope. However, FRC counts depend on the technical procedure used to detect them so that reference ranges are device dependent. The XN-9000® is one of the latest models from the Sysmex series of analysers. We aimed to establish a reference range for FRCs based on 1366 normal patient samples. The mean ± SD was 0.14 ± 0.35% and the median was 0% (95% confidence interval of the mean: 0.12-0.16%). We observed that the percentage of red blood cells with <17 pg of haemoglobin content (Hypo-He) was correlated to an FRC increase and that flagged results relating to red blood cells, reticulocytes or platelets might have presented with artefactually increased FRCs. The FRCs reference range (healthy subjects) should be useful for laboratory staff for selecting which blood smears to check optically. © 2015 John Wiley & Sons Ltd.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation

PubMed Central

Saito, Shunnichi; Ngoma, Alain M.; Ono, Takako; Ohto, Hitoshi

2018-01-01

Background Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Materials and methods Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Results Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. Discussion This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis. PMID:27893349

Phosphatidylserine-mediated platelet clearance by endothelium decreases platelet aggregates and procoagulant activity in sepsis.

PubMed

Ma, Ruishuang; Xie, Rui; Yu, Chengyuan; Si, Yu; Wu, Xiaoming; Zhao, Lu; Yao, Zhipeng; Fang, Shaohong; Chen, He; Novakovic, Valerie; Gao, Chunyan; Kou, Junjie; Bi, Yayan; Thatte, Hemant S; Yu, Bo; Yang, Shufen; Zhou, Jin; Shi, Jialan

2017-07-10

The mechanisms that eliminate activated platelets in inflammation-induced disseminated intravascular coagulation (DIC) in micro-capillary circulation are poorly understood. This study explored an alternate pathway for platelet disposal mediated by endothelial cells (ECs) through phosphatidylserine (PS) and examined the effect of platelet clearance on procoagulant activity (PCA) in sepsis. Platelets in septic patients demonstrated increased levels of surface activation markers and apoptotic vesicle formation, and also formed aggregates with leukocytes. Activated platelets adhered were and ultimately digested by ECs in vivo and in vitro. Blocking PS on platelets or αvβ3 integrin on ECs attenuated platelet clearance resulting in increased platelet count in a mouse model of sepsis. Furthermore, platelet removal by ECs resulted in a corresponding decrease in platelet-leukocyte complex formation and markedly reduced generation of factor Xa and thrombin on platelets. Pretreatment with lactadherin significantly increased phagocytosis of platelets by approximately 2-fold, diminished PCA by 70%, prolonged coagulation time, and attenuated fibrin formation by 50%. Our results suggest that PS-mediated clearance of activated platelets by the endothelium results in an anti-inflammatory, anticoagulant, and antithrombotic effect that contribute to maintaining platelet homeostasis during acute inflammation. These results suggest a new therapeutic target for impeding the development of DIC.

Decreased prothrombotic effects of pegylated recombinant human megakaryocyte growth and development factor in thrombocytopenic state in a rat thrombosis model.

PubMed

Nishiyama, U; Kuwaki, T; Akahori, H; Kato, T; Ikeda, Y; Miyazaki, H

2005-02-01

Previous in vitro studies demonstrated that thrombopoietin (TPO) acts on platelets to activate a variety of intracellular signaling pathways and to enhance platelet sensitivity to multiple agonists. Little is known, however, about whether TPO exerts prothrombotic effects in vivo. The aim of this study was to examine the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a pegylated N-terminal domain of human TPO, in a rat model of venous thrombosis. A microthrombus was photochemically induced on the vessel wall of a mesenteric venule, but the vessel was not occluded by it. A single intravenous injection of PEG-rHuMGDF (3 microg kg(-1)) after the thrombus generation into normal rats enhanced the thrombus size, resulting in transient thrombotic occlusion in the majority of rats. Stimulatory effects on thrombus growth were also observed following administration of glycosylated recombinant human full-length TPO (6 microg kg(-1)). In rats rendered thrombocytopenic by total body irradiation, however, PEG-rHuMGDF, even at 300 microg kg(-1), did not induce a significant increase in thrombus size or thrombotic occlusion. Platelets from thrombocytopenic rats had decreased surface levels of c-Mpl and decreased sensitivity to PEG-rHuMGDF in an in vitro aggregation response. Thus, decreased prothrombotic effects of PEG-rHuMGDF in thrombocytopenic rats might be the result not only of low platelet counts but also of decreased platelet reactivity to PEG-rHuMGDF. These results indicate that PEG-rHuMGDF has little effect on venous thrombus formation in thrombocytopenic states associated with high endogenous TPO levels.

[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.

Inhibitory effects of ethyl pyruvate on platelet aggregation and phosphatidylserine exposure.

PubMed

Li, Wenjin; Yang, Xinyu; Peng, Minyuan; Li, Can; Mu, Guangfu; Chen, Fangping

2017-06-03

Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression. The underlying mechanism of action may involve the inhibition of platelet PI3K/Akt and Protein Kinase C (PKC) signaling pathways. Additionally, EP dose dependently inhibited platelet PS exposure induced by high concentration thrombin. Lactate dehydrogenase (LDH) activity assay and mice platelet count implied that EP may have no toxic effect on platelets. Therefore, we are the first to report that EP has potent anti-platelet activity and attenuates platelet PS exposure in vitro, suggesting that the inhibitory effects of EP on platelets may also play important roles in improvement of inflammation and coagulation disorder in related animal models. Copyright © 2017 Elsevier Inc. All rights reserved.

Platelet activation suppresses HIV-1 infection of T cells

PubMed Central

2013-01-01

Background Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. Results We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Conclusions Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens. PMID:23634812

Platelet activation suppresses HIV-1 infection of T cells.

PubMed

Solomon Tsegaye, Theodros; Gnirß, Kerstin; Rahe-Meyer, Niels; Kiene, Miriam; Krämer-Kühl, Annika; Behrens, Georg; Münch, Jan; Pöhlmann, Stefan

2013-05-01

Platelets, anucleate cell fragments abundant in human blood, can capture HIV-1 and platelet counts have been associated with viral load and disease progression. However, the impact of platelets on HIV-1 infection of T cells is unclear. We found that platelets suppress HIV-1 spread in co-cultured T cells in a concentration-dependent manner. Platelets containing granules inhibited HIV-1 spread in T cells more efficiently than degranulated platelets, indicating that the granule content might exert antiviral activity. Indeed, supernatants from activated and thus degranulated platelets suppressed HIV-1 infection. Infection was inhibited at the stage of host cell entry and inhibition was independent of the viral strain or coreceptor tropism. In contrast, blockade of HIV-2 and SIV entry was less efficient. The chemokine CXCL4, a major component of platelet granules, blocked HIV-1 entry and neutralization of CXCL4 in platelet supernatants largely abrogated their anti-HIV-1 activity. Release of CXCL4 by activated platelets inhibits HIV-1 infection of adjacent T cells at the stage of virus entry. The inhibitory activity of platelet-derived CXCL4 suggests a role of platelets in the defense against infection by HIV-1 and potentially other pathogens.

A prospective cohort study of light transmission platelet aggregometry for bleeding disorders: is testing native platelet-rich plasma non-inferior to testing platelet count adjusted samples?

PubMed

Castilloux, Jean Francois; Moffat, Karen A; Liu, Yang; Seecharan, Jodi; Pai, Menaka; Hayward, Catherine P M

2011-10-01

Light transmission platelet aggregometry (LTA) is important to diagnose bleeding disorders. Experts recommend testing LTA with native (N) rather than platelet count adjusted (A) platelet-rich plasma (PRP), although it is unclear if this provides non-inferior, or superior, detection of bleeding disorders. Our goal was to determine if LTA with NPRP is non-inferior to LTA with APRP for bleeding disorder assessments. A prospective cohort of patients, referred for bleeding disorder testing, and healthy controls, were evaluated by LTA using common agonists, NPRP and APRP (adjusted to 250 x 10⁹ platelets/l). Recruitment continued until 40 controls and 40 patients with definite bleeding disorders were tested. Maximal aggregation (MA) data were assessed for the detection of abnormalities from bleeding disorders (all causes combined to limit bias), using sample-type specific reference intervals. Areas under receiver-operator curves (AUROC) were evaluated using pre-defined criteria (area differences: < 0.15 for non-inferiority, > 0 for superiority). Forty-four controls and 209 patients were evaluated. Chart reviews for 169 patients indicated 67 had bleeding disorders, 28 from inherited platelet secretion defects. Mean MA differences between NPRP and APRP were small for most agonists (ranges, controls: -3.3 to 5.8; patients: -3.0 to 13.7). With both samples, reduced MA with two or more agonists was associated with a bleeding disorder. AUROC differences between NPRP and APRP were small and indicated that NPRP were non-inferior to APRP for detecting bleeding disorders by LTA, whereas APRP met superiority criteria. Our study validates using either NPRP or APRP for LTA assessments of bleeding disorders.

Head-out immersion in hot water increases serum BDNF in healthy males.

PubMed

Kojima, Daisuke; Nakamura, Takeshi; Banno, Motohiko; Umemoto, Yasunori; Kinoshita, Tokio; Ishida, Yuko; Tajima, Fumihiro

2017-11-20

Brain-derived neurotrophic factor (BDNF) is an important neurotrophin. The present study investigated the effects of head-out water immersion (HOI) on serum BDNF concentrations. Eight healthy men performed 20 min head-out water immersion at 42 °C (hot-HOI) and 35 °C (neutral-HOI). These experimental trials were administered in a randomised order separated by at least 7 days. Venous blood samples were withdrawn at rest, immediately after the 20-min HOI, as well as at 15 and 30 min after the end of the HOI. Serum BDNF and S100β, plasma cortisol, platelet and monocyte counts, and core body temperature (T cb ) were measured. T cb was higher at the end of the hot-HOI and 15 min after hot-HOI (p < 0.01), but recovered to pre-HOI level at 30 min after hot-HOI. No change in T cb was recorded during neutral-HOI. BDNF level was higher (p < 0.05) at the end of the hot-HOI and at 15 min after the end of hot-HOI, and returned to the baseline at 30 min after hot-HOI. S100β, platelet count and monocyte count remained stable throughout the study. Cortisol level was lower at the end of the hot-HOI and returned to pre-HOI level during the recovery period. BDNF and S100β, cortisol, and platelet and monocyte counts did not change throughout the neutral-HOI study. The present findings suggested that the increase in BDNF during 20-min hot-HOI was induced by hyperthermia through enhanced production, rather than by changes in permeability of the blood-brain barrier (BBB), platelet clotting mechanisms or secretion from monocytes.

Is Thrombocytopenia an Early Prognostic Marker in Septic Shock?

PubMed

Thiery-Antier, Nadiejda; Binquet, Christine; Vinault, Sandrine; Meziani, Ferhat; Boisramé-Helms, Julie; Quenot, Jean-Pierre

2016-04-01

To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. Prospective, multicenter, observational cohort study. Fourteen ICUs from 10 French university teaching and nonacademic hospitals. Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. None. Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p ≤ 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p < 0.0001). This is the first study to investigate thrombocytopenia within the first 24 hours of septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

PubMed

Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

2009-02-01

Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

[Influence of cytostatic combination therapy with vincristine sulphate and iphosphamide on blood coagulation].

PubMed

Neidhardt, B; Hartwich, G

1975-02-28

Disorders of blood coagulation were investigated before and during a cytostatic combination therapy with vincristine sulphate and iphosphamide (Asta Z 4942) in 12 patients with malignant tumours or haemoblastoses. Thromboplastin time, partial thromboplastin time, thrombin time, heat-dependent fibrin, clot retraction, and clotting factors II, V, VIII, IX, X, and the platelet count were determined. A change in the plasmatic coagulation system attributable to the combination therapy could not be demonstrated in any patient. The influence of the cytostatic combination on the platelet-dependent haemostasis was small; a decrease in platelet count could be observed in only one patient, in whom an additional causative damage to thrombopoiesis due to the underlying disease could be assumed. Regardless of the cytostatic therapy there were indications of a hypercoagulability in 10 patients. This explains the increased susceptibility of such patients for thromboses or consumption coagulopathy.

[Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits].

PubMed

Gong, Min; Lin, Huan-bing; Wang, Qian; Xu, Jiang-ping

2008-08-01

To investigate the effect of nattokinase on intimal hyperplasia in rabbit abdominal artery after balloon injury and explore a novel strategy for the preventing restenosis after percutaneous transluminal angioplasty. Fifty-six New Zealand rabbits were randomly divided into 7 groups, namely the solvent control group, model group, natto extract lavage group, refined nattokinse lavage group, intravenous refined nattokinse injection group, clopidogrel group and clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter through the femoral artery into the thoracic aorta of the rabbits. The platelet counts were notad and platelet aggregation was observed, and the abdominal artery was taken for pathological analysis. The expressions of MMP-2 and -9 in the abdominal artery were detected immunohistochemically. There was no significant difference in the platelet counts, platelet aggregation rate or MMP-2 and -9 expression between the model group and the nattokinse-treated groups (P>0.05). The stenosis index in each nattokinse-treated group was significantly greater and the neointimal proliferation index smaller than that of the model group (P<0.01 or 0.05). Nattokinse can inhibit restenosis of rabbit abdominal artery after percutaneous transluminal angioplasty, which is independent of its actions on the platelet or MMP-2 and -9 expressions.

Coagulation parameters in copperhead compared to other Crotalinae envenomation: secondary analysis of the F(ab')2 versus Fab antivenom trial.

PubMed

Gerardo, Charles J; Vissoci, Joao R Nickenig; Brown, Michael W J; Bush, Sean P

2017-02-01

Coagulation derangements in copperhead envenomation are considered less severe than other crotaline envenomations, resulting in recommendations to limit both coagulation testing and antivenom treatment. A prospective, blinded, multicenter, randomized clinical trial comparing the effectiveness of F(ab') 2 versus Fab antivenom in crotaline envenomation patients was completed in 2011. We determined the difference between coagulation parameters in copperhead compared to other crotaline envenomations. We performed a post hoc analysis comparing the coagulation parameters (platelets and fibrinogen) prospectively obtained in the aforementioned trial. All the patients received antivenom in one of three treatment arms [F(ab') 2 with maintenance, F(ab') 2 with placebo maintenance, or Fab with maintenance]. Coagulation parameters were measured at pretreatment baseline, during acute hospitalization, day 5, day 8, and day 15 post-envenomation. Mean platelet count and fibrinogen levels for the copperhead and other crotaline groups were compared. The platelet and fibrinogen point estimates with distribution are presented graphically over time. 122 patients were enrolled in the study. There were 22 patients with copperhead envenomation, 93 with other crotaline envenomations, and 7 that could not be definitively determined. The mean age was 42 (SD 20) years. There was a minor pretreatment difference in mean baseline platelet count between the copperhead group (246 × 109/L 95% CI 215, 277) compared to other crotaline envenomation patients (184 × 109/L 95% CI 167, 202). There was a modest pretreatment difference in mean fibrinogen level between copperhead patients (345 mg/dL 95% CI 277, 415) and other crotaline patients (261mg/dL 95% CI 241, 281). Pretreatment coagulation parameter means were normal and converged post treatment. On average, copperhead envenomations have less severe initial coagulation derangements. However, in mild envenomations, differences in laboratory values are minimal and there is substantial variation in individual patients regardless of species. Species alone should not be used to determine the need for laboratory testing or treatment in crotaline snakebite.

Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus.

PubMed

Sallmon, Hannes; Weber, Sven C; Hüning, Britta; Stein, Anja; Horn, Peter A; Metze, Boris C; Dame, Christof; Bührer, Christoph; Felderhoff-Müser, Ursula; Hansmann, Georg; Koehne, Petra

2012-09-01

Experimental studies suggest that platelet-triggered ductal sealing is critically involved in definite ductus arteriosus closure. Whether thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in humans is controversial. This was a retrospective study of 1350 very low birth weight (VLBW; <1500 g) infants, including 592 extremely low birth weight (ELBW; <1000 g) infants. All infants who had a platelet count in the first 24 hours after birth and an echocardiogram performed on day of life 4 to 5 were included. The incidence of thrombocytopenia was analyzed in infants with and without PDA, and in those who did or did not undergo PDA intervention. The impact of thrombocytopenia, gestational age, birth weight, gender, and sepsis on PDA was determined by receiver operating characteristic curve, odds ratio, and regression analyses. Platelet numbers within the first 24 hours after birth did not differ between VLBW/ELBW infants with and without spontaneous ductal closure. Platelet numbers were not associated with subsequent PDA treatment. Low platelet counts were not related to failure of pharma-cologic PDA treatment and the need for subsequent surgical ligation. Lower gestational age or birth weight, male gender, and sepsis were linked to the presence of PDA in VLBW infants on day of life 4 to 5. Thrombocytopenia in the first 24 hours after birth was not associated with PDA in this largest VLBW/ELBW infant cohort studied to date. Impaired platelet function, due to immaturity and critical illness, rather than platelet number, might play a role in ductus arteriosus patency.

The superiority of indium ratio over blood pool subtraction in analysis of indium-111 platelet deposition on thoraco-abdominal prosthetic grafts

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

Ripley, S.; Wakefield, T.; Spaulding, S.

1985-05-01

In this investigation platelet deposition in polytetrafluroethylene (PTFE) thoracoabdominal grafts (TAC's) was evaluated using two different semi-quantitative techniques. Ten PTFE TAG's 6 mm in diameter and 30 cm in length were inserted into 10 mongrel dogs. One, 4 and 6 weeks after graft implantation the animals were injected with autologous In-111 platelets labelled by a modified Thakur technique. Platelet imaging in grafts was performed 48 hrs after injection. Blood pool was determined by Tc99m labelled RBC's (in vivo/in vitro technique). Semi-quantitative analysis was performed by subdividing the imaged graft into three major regions and selecting a reference region from eithermore » the native aorta or common iliac artery. Excess platelet deposition was determined by two methods: 1) the ratio of In-111 counts in the graft ROI''s to the reference region and 2) the percent In-111 excess using the Tc99m blood pool subtraction technique (TBPST). Animals were sacrificed 7 weeks after implantation and radioactivity in the excised grafts was determined using a well counter. A positive correlation was found to exist between the In-111 ratio percent analysis (IRPA) and the direct gamma counting (DCC) for all three segments of the prosthetic graft. Correlation coefficients for the thorax, midsegment and abdominal segments were 0.80, 0.73 and 0.48 respectivly. There was no correlation between TBPST and DGC. Using the IRPA technique the thrombogenicity of TAG's can be routinely assessed and is clinically applicable for patient use. TBPST should probably be limited to the extremities to avoid error due to free Tc99m counts from kidneys and ureters.« less

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

PubMed

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Comparison of the platelet-rich plasma and buffy coat protocols for preparation of canine platelet concentrates.

PubMed

Hoareau, Guillaume L; Jandrey, Karl E; Burges, Julie; Bremer, Daphne; Tablin, Fern

2014-12-01

Platelet (PLT) concentrates (PC) can be produced via the buffy coat (BC) or platelet-rich plasma (PRP) protocols. The 2 methods have not been compared with canine blood. The aims of the study were to compare the PLT, WBC, and RBC concentrations, in vitro PLT function, and markers of platelet storage lesion (PSL) in canine PC generated by 2 different protocols, and determine microbial growth throughout storage. PC from 8 healthy donor dogs were produced using 2 standard protocols, PRP and BC. PLT, WBC, and RBC counts, optical aggregometry assays, and PSL markers (pH, pCO2 , HCO3 , lactate and glucose concentrations, and LDH activity) were determined on storage days 0, 1, 3, 5, and 7. Aerobic and anaerobic bacterial cultures were also performed. Mean PLT counts were comparable between protocols and remained stable throughout storage up to day 7, while median WBC and RBC counts on day 0 were significantly higher in the BC-PC group (17,800 WBCs/μL; 195,000 RBCs/μL) than in the PRP-PC group (200 WBCs/μL; 10,000 RBCs/μL) (P = .012). In PRP-PC aggregometry, the median slope and amplitude in response to γ-thrombin and convulxin (+ ADP) were significantly decreased, and virtually absent in BC-PC during storage. PSL markers (lactate, LDH activity) were higher in BC-PC. Aerobic bacterial growth was observed in 2 PRP-PC and 1 BC-PC. This in vitro study suggests that PRP-PC had lesser WBC and RBC contamination and superior PLT function compared with BC-PC. In vivo studies are required to address safety and efficacy of PRP-PC. © 2014 American Society for Veterinary Clinical Pathology.

Relationships of inflammatory and haemostatic markers with social class: results from a population-based study of older men.

PubMed

Ramsay, Sheena; Lowe, Gordon D O; Whincup, Peter H; Rumley, Ann; Morris, Richard W; Wannamethee, S Goya

2008-04-01

Haemostatic and inflammatory markers have been hypothesised to mediate the relationship of social class and cardiovascular disease (CVD). We investigated whether a range of inflammatory/haemostatic markers are associated with social class independent of chronic diseases and behavioural risk factors in a population-based sample of 2682 British men aged 60-79 without a physician diagnosis of CVD, diabetes or musculoskeletal disease requiring anti-inflammatory medications. Men in lower social classes had higher mean levels of C-reactive protein, fibrinogen, interleukin-6, white blood cell count, von Willebrand factor (vWF), factor VIII, activated protein C (APC) resistance, plasma viscosity, fibrin D-dimer and platelet count, compared to higher social class groups; but not of tissue plasminogen activator antigen, haematocrit or activated partial prothrombin time. After adjustment for behavioural risk factors (smoking, alcohol, physical activity and body mass), the associations of social class with vWF, factor VIII, APC resistance, plasma viscosity, and platelet count though weakened, remained statistically significant, while those of other markers were considerably attenuated. In this study of older men without CVD, the social gradient in inflammatory and haemostatic markers was substantially explained by behavioural risk factors. The effect of socio-economic gradient on the factor VIII-vWF complex, APC resistance, plasma viscosity and platelet count merits further study.

[The oxidative stress in platelets of patients with ovary cancer as observed at chemotherapy].

PubMed

Zubrikhina, G N; Davydova, T V; Kormosh, N G; Gorozhanskaia, E G

2004-12-01

Disorders in the main chains of platelet antioxidant protection were examined in 32 patients with primarily-diagnosed ovary cancer who were postoperatively receiving chemotherapy according to PC. The activity of antioxidant-protection enzymes (superoxide dismutase, catalase, glutation-S-transferase) as well as the content of malonic dialdehyde (MDA) and glutathione were examined after each course of chemotherapy. The data obtained were compared with the aggregation ability of platelets, with the content of fibrinogen and with the count of platelets. The parameters of the antioxidant system in platelets were examined for control in 30 virtually healthy women. The results denote that the oxidant stress progression in the body due to the growing tumor and aggravating because of chemodrugs deregulates the free-radical processes in platelets, which can affect their functional properties or rheological blood properties.

Autonomous role of Wiskott-Aldrich syndrome platelet deficiency in inducing autoimmunity and inflammation.

PubMed

Sereni, Lucia; Castiello, Maria Carmina; Marangoni, Francesco; Anselmo, Achille; di Silvestre, Dario; Motta, Sara; Draghici, Elena; Mantero, Stefano; Thrasher, Adrian J; Giliani, Silvia; Aiuti, Alessandro; Mauri, Pierluigi; Notarangelo, Luigi D; Bosticardo, Marita; Villa, Anna

2018-02-06

Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency characterized by eczema, infections, and susceptibility to autoimmunity and malignancies. Thrombocytopenia is a constant finding, but its pathogenesis remains elusive. To dissect the basis of the WAS platelet defect, we used a novel conditional mouse model (CoWas) lacking Wiskott-Aldrich syndrome protein (WASp) only in the megakaryocytic lineage in the presence of a normal immunologic environment, and in parallel we analyzed samples obtained from patients with WAS. Phenotypic and functional characterization of megakaryocytes and platelets in mutant CoWas mice and patients with WAS with and without autoantibodies was performed. Platelet antigen expression was examined through a protein expression profile and cluster proteomic interaction network. Platelet immunogenicity was tested by using ELISAs and B-cell and platelet cocultures. CoWas mice showed increased megakaryocyte numbers and normal thrombopoiesis in vitro, but WASp-deficient platelets had short lifespan and high expression of activation markers. Proteomic analysis identified signatures compatible with defects in cytoskeletal reorganization and metabolism yet surprisingly increased antigen-processing capabilities. In addition, WASp-deficient platelets expressed high levels of surface and soluble CD40 ligand and were capable of inducing B-cell activation in vitro. WASp-deficient platelets were highly immunostimulatory in mice and triggered the generation of antibodies specific for WASp-deficient platelets, even in the context of a normal immune system. Patients with WAS also showed platelet hyperactivation and increased plasma soluble CD40 ligand levels correlating with the presence of autoantibodies. Overall, these findings suggest that intrinsic defects in WASp-deficient platelets decrease their lifespan and dysregulate immune responses, corroborating the role of platelets as modulators of inflammation and immunity. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Short term effects of reduced exposure to cigarette smoke on white blood cells, platelets and red blood cells in adult cigarette smokers.

PubMed

Roethig, Hans J; Koval, Tamara; Muhammad-Kah, Raheema; Jin, Yan; Mendes, Paul; Unverdorben, Martin

2010-01-01

Previous studies indicate that cigarette smokers have a 5-30% higher white blood cell counts (WBC) compared to non-smokers and higher red blood cell counts. This study was to pool hematology data from three similar studies and analyze the data for effects on WBC, its subpopulations, platelets, red blood cell count (RBC) and hematocrit in adult cigarette smokers three days after using an electrically heated cigarette smoking system (EHCSS) as a potential reduced exposure product (PREP) or no-smoking compared to smoking a conventional cigarette. Lower exposure to cigarette smoke in adult, long term smokers, by using an EHCSS or stopping smoking, leads to statistically significant decreases of up to 9% in WBC, neutrophils, lymphocytes, platelets, RBC and hematocrit within three days. Switching from CC-smoking to EHCSS-smoking or no-smoking resulted in lower WBC and vice versa within 3 days. This clinical model may be used as a screening tool to find new technologies that could provide insights on changes in inflammation resulting from the change in cigarette smoke. Copyright 2010 Elsevier Inc. All rights reserved.

Retrospective Analysis of the Risk Factors for Grade IV Neutropenia in Oesophageal Cancer Patients Treated with a Docetaxel, Cisplatin, and 5-Fluorouracil Regimen.

PubMed

Naito, Masahito; Yamamoto, Tomoya; Shimamoto, Chikao; Miwa, Yoshihiro

2017-01-01

Previous Japanese trials of the docetaxel, cisplatin, and 5-fluorouracil regimen for oesophageal cancer have demonstrated that a large proportion of patients also develop grade IV neutropenia. Our aim was to examine the risk factors for neutropenia in patients treated with this regimen. We retrospectively analysed the risk factors for developing grade IV neutropenia in 66 patients with oesophageal cancer using a multivariate analysis. After administering the docetaxel, cisplatin, and 5-fluorouracil regimen, 49 patients (74.2%) developed grade IV neutropenia. Grade IV neutropenia was significantly associated with platelet count (p < 0.01), alanine transaminase level (p = 0.05), and proton-pump inhibitor administration (p < 0.05). Receiver operating characteristic curve analysis confirmed a platelet count of 290 × 103/μL as the optimal diagnostic cut-off value for grade IV neutropenia. The receiver operating characteristic area for grade IV neutropenia was increased by including patients that were administered a proton-pump inhibitor and alanine transaminase level (updated model; sensitivity and specificity, 75.5 and 88.2%, respectively). Our findings suggest that a platelet count is the most significant predictor of grade IV neutropenia. © 2017 S. Karger AG, Basel.

Intermittent versus continuous oxaliplatin and fluoropyrimidine combination chemotherapy for first-line treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

PubMed Central

Adams, Richard A; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Madi, Ayman; Fisher, David; Kenny, Sarah L; Kay, Edward; Hodgkinson, Elizabeth; Pope, Malcolm; Rogers, Penny; Wasan, Harpreet; Falk, Stephen; Gollins, Simon; Hickish, Tamas; Bessell, Eric M; Propper, David; Kennedy, M John; Kaplan, Richard; Maughan, Timothy S

2011-01-01

Summary Background When cure is impossible, cancer treatment should focus on both length and quality of life. Maximisation of time without toxic effects could be one effective strategy to achieve both of these goals. The COIN trial assessed preplanned treatment holidays in advanced colorectal cancer to achieve this aim. Methods COIN was a randomised controlled trial in patients with previously untreated advanced colorectal cancer. Patients received either continuous oxaliplatin and fluoropyrimidine combination (arm A), continuous chemotherapy plus cetuximab (arm B), or intermittent (arm C) chemotherapy. In arms A and B, treatment continued until development of progressive disease, cumulative toxic effects, or the patient chose to stop. In arm C, patients who had not progressed at their 12-week scan started a chemotherapy-free interval until evidence of disease progression, when the same treatment was restarted. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and B is described in a companion paper. Here, we compare arms A and C, with the primary objective of establishing whether overall survival on intermittent therapy was non-inferior to that on continuous therapy, with a predefined non-inferiority boundary of 1·162. Intention-to-treat (ITT) and per-protocol analyses were done. This trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to continuous and 815 to intermittent therapy). Median survival in the ITT population (n=815 in both groups) was 15·8 months (IQR 9·4–26·1) in arm A and 14·4 months (8·0–24·7) in arm C (hazard ratio [HR] 1·084, 80% CI 1·008–1·165). In the per-protocol population (arm A, n=467; arm C, n=511), median survival was 19·6 months (13·0–28·1) in arm A and 18·0 months (12·1–29·3) in arm C (HR 1·087, 0·986–1·198). The upper limits of CIs for HRs in both analyses were greater than the predefined non-inferiority boundary. Preplanned subgroup analyses in the per-protocol population showed that a raised baseline platelet count, defined as 400 000 per μL or higher (271 [28%] of 978 patients), was associated with poor survival with intermittent chemotherapy: the HR for comparison of arm C and arm A in patients with a normal platelet count was 0·96 (95% CI 0·80–1·15, p=0·66), versus 1·54 (1·17–2·03, p=0·0018) in patients with a raised platelet count (p=0·0027 for interaction). In the per-protocol population, more patients on continuous than on intermittent treatment had grade 3 or worse haematological toxic effects (72 [15%] vs 60 [12%]), whereas nausea and vomiting were more common on intermittent treatment (11 [2%] vs 43 [8%]). Grade 3 or worse peripheral neuropathy (126 [27%] vs 25 [5%]) and hand–foot syndrome (21 [4%] vs 15 [3%]) were more frequent on continuous than on intermittent treatment. Interpretation Although this trial did not show non-inferiority of intermittent compared with continuous chemotherapy for advanced colorectal cancer in terms of overall survival, chemotherapy-free intervals remain a treatment option for some patients with advanced colorectal cancer, offering reduced time on chemotherapy, reduced cumulative toxic effects, and improved quality of life. Subgroup analyses suggest that patients with normal baseline platelet counts could gain the benefits of intermittent chemotherapy without detriment in survival, whereas those with raised baseline platelet counts have impaired survival and quality of life with intermittent chemotherapy and should not receive a treatment break. Funding Cancer Research UK. PMID:21641867

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.

Cathepsin G-Dependent Modulation of Platelet Thrombus Formation In Vivo by Blood Neutrophils

PubMed Central

Faraday, Nauder; Schunke, Kathryn; Saleem, Sofiyan; Fu, Juan; Wang, Bing; Zhang, Jian; Morrell, Craig; Dore, Sylvain

2013-01-01

Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies. PMID:23940756

Alteration of mean platelet volume in the pathogenesis of acute ischemic stroke: cause or consequence?

PubMed

Ayas, Zeynep Özözen; Can, Ufuk

2018-01-30

Platelets have a crucial role on vascular disease which are involved in pathogenesis of ischemic stroke. Platelet size is measured as mean platelet volume (MPV) and is a marker of platelet activity. Platelets contain more dense granules as the size increases and produce more serotonin and tromboglobulin (b-TG) than small platelets. In this study, the alteration of MPV values were investigated in patients with acute stroke, who had MPV values before stroke, during acute ischemic stroke and 7 days after the stroke. The relationship between this alteration and risk factors, etiology and localization of ischemic stroke were also investigated. Sixty-seven patients with clinically and radiologically established diagnoses of ischemic stroke were enrolled into the study and stroke etiology was classified by modified Trial of Org 10 172 in Acute Stroke Treatment (TOAST) classification and, modified Bamford classification was used for localization and stroke risk factors were also evaluated. The platelet counts and MPV values from patient files in patients who had values before stroke (at examination for another diseases), within 24 hours of symptom onset and after 7 further days were analysed. MPV values increased after stroke (10.59±2.26) compared with acute stroke values (9.84±1.64) and the values before stroke (9.59±1.72) (p<0.0001); this alteration of MPV values occured 7 days after stroke (p<0.016). There was a positive correlation between age and MPV values during acute stroke (r=0.270; p<0.05). Patients with atrial fibrillation had higher alteration in the time of MPV compared with patients without atrial fibrillation (p>0.006). We assessed for gender, men (n=38) had a higher alteration in the time of MPV compared with women (n=29) (p=0.013). Although there was no alteration of platelet counts, MPV values were increased 7 days after stroke in patients with acute ischemic stroke.

Effects of desmopressin on platelet function under conditions of hypothermia and acidosis: an in vitro study using multiple electrode aggregometry*.

PubMed

Hanke, A A; Dellweg, C; Kienbaum, P; Weber, C F; Görlinger, K; Rahe-Meyer, N

2010-07-01

Hypothermia and acidosis lead to an impairment of coagulation. It has been demonstrated that desmopressin improves platelet function under hypothermia. We tested platelet function ex vivo during hypothermia and acidosis. Blood samples were taken from 12 healthy subjects and assigned as follows: normal pH, pH 7.2, and pH 7.0, each with and without incubation with desmopressin. Platelet aggregation was assessed by multiple electrode aggregometry. Baseline was normal pH and 36 degrees C. The other samples were incubated for 30 min and measured at 32 degrees C. Acidosis significantly impaired aggregation. Desmopressin significantly increased aggregability during hypothermia and acidosis regardless of pH, but did not return it to normal values at low pH. During acidosis and hypothermia, acidosis should be corrected first; desmopressin can then be administered to improve platelet function as a bridge until normothermia can be achieved.

Studies of Platelet 5-Hydroxytryptamine (Serotonin) in Storage Pool Disease and Albinism

PubMed Central

Weiss, Harvey J.; Tschopp, Thomas B.; Rogers, John; Brand, Harvey

1974-01-01

Platelets in patients with storage pool disease are markedly deficient in a nonmetabolic (storage) pool of ADP that is important in platelet aggregation. They are also deficient in ATP, although to a lesser degree. In seven patients with this disorder, including one with albinism, platelet 5-hydroxytryptamine (5-HT) levels were reduced in proportion to the reduction in ATP (r = 0.94). Their platelets show diminished capacity to absorb [14C]5-HT, and the type of defect was similar to that produced in normal platelets by reserpine, a drug known to inhibit the uptake of 5-HT by the platelet dense granules. Storage pool-deficient platelets also converted more [3H]5-HT to [3H]5-hydroxyindoleacetic acid than did normal platelets, and the platelets in one of two patients studied contained increased amounts of 5-HT metabolites. The above findings, together with those reported previously, support the conclusion that the capacity of the dense granules (which may be either diminished or functionally abnormal) for storing 5-HT is decreased in storage pool disease; as a result, the 5-HT that enters the platelet may be more exposed to monoamine oxidases present on mitochondrial membranes. This diminished storage capacity (for 5-HT) may also explain why preincubating platelet-rich plasma with 5-HT for 45 min without stirring inhibits subsequent platelet aggregation by 5-HT to a greater degree in patients with storage pool disease than in normal subjects. The latter finding is also consistent with the theory that the aggregation of platelets by 5-HT is mediated by the same receptors on the plasma membrane that are involved in its uptake. The diminished release of platelet-bound [14C]5-HT by collagen that we found in these patients, as well as findings in previous studies, suggests that the release reaction may also be abnormal in storage pool disease. Images PMID:4847252

Changes in thrombin-stimulated platelet malondialdehyde production during the menstrual cycle.

PubMed Central

Tindall, H; Zuzel, M; Paton, R C; McNicol, G P

1981-01-01

Forty normal women had thrombin-stimulated platelet malondialdehyde (MDA) production measured during their menstrual cycle. Twenty women in this group were taking the combined oral contraceptive pill (OCP). Platelet MDA production was found to fall by 30% during normal menstruation and the week when the subjects were not taking a combined OCP, but it remained constant throughout the remainder of the cycle. No significant change in initial platelet aggregation response to stimulation by thrombin, change in plasma thrombin clotting time, plasma heparin neutralising activity (HNA), or plasma antithrombin III (AT-III) activity was seen when the platelet MDA production was reduced. The bleeding time results showed some variation throughout the menstrual cycle but these did not appear to be related to the variation in platelet MDA production. PMID:7251901

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.

Onlay bone augmentation on mouse calvarial bone using a hydroxyapatite/collagen composite material with total blood or platelet-rich plasma.

PubMed

Ohba, Seigo; Sumita, Yoshinori; Umebayashi, Mayumi; Yoshimura, Hitoshi; Yoshida, Hisato; Matsuda, Shinpei; Kimura, Hideki; Asahina, Izumi; Sano, Kazuo

2016-01-01

The aim of this study was to assess newly formed onlay bone on mouse calvarial bone using a new artificial bone material, a hydroxyapatite/collagen composite, with total blood or platelet-rich plasma. The hydroxyapatite/collagen composite material with normal saline, total blood or platelet-rich plasma was transplanted on mouse calvarial bone. The mice were sacrificed and the specimens were harvested four weeks after surgery. The newly formed bone area was measured on hematoxylin and eosin stained specimens using Image J software. The hydroxyapatite/collagen composite materials with total blood or platelet-rich plasma induced a significantly greater amount of newly formed bone than that with normal saline. Moreover, bone marrow was observed four weeks after surgery in the transplanted materials with total blood or platelet-rich plasma but not with normal saline. However, there were no significant differences in the amount of newly formed bone between materials used with total blood versus platelet-rich plasma. The hydroxyapatite/collagen composite material was valid for onlay bone augmentation and this material should be soaked in total blood or platelet-rich plasma prior to transplantation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Functional expression of cysteinyl leukotriene receptors on human platelets.

PubMed

Hasegawa, Shunji; Ichiyama, Takashi; Hashimoto, Kunio; Suzuki, Yasuo; Hirano, Reiji; Fukano, Reiji; Furukawa, Susumu

2010-01-01

Normal peripheral blood leukocytes, such as basophils, eosinophils, B lymphocytes and monocytes/macrophages, have a cysteinyl leukotriene 1 (CysLT1) receptor, while the cysteinyl leukotriene 2 (CysLT2) receptor is expressed in cardiac Purkinje cells, endothelium, brain and leukocytes. However, it is unknown whether or not platelets express the CysLT1 or CysLT2 receptor. In this study we identify and characterize the biological function of the CysLT receptor of human platelets. We determined the CysLT1 or CysLT2 receptor mRNA expression in normal human platelets by RT-PCR and determined protein expression by Western blotting and flow cytometry. Moreover, we examined the effect of cysteinyl leukotrienes (CysLTs) in platelets on the induction of RANTES (Regulated on Activation, Normal T Expressed, and presumably Secreted). We also investigated whether the CysLT1 receptor antagonist pranlukast inhibits CysLT-induced RANTES release. In conclusion, we showed the functional expression of CysLT receptors on human platelets and demonstrated that CysLTs induced the release of significant amounts of RANTES, which suggests a novel role for human platelets in CysLT-mediated allergic inflammation.

Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.

PubMed

Cloutier, Nathalie; Allaeys, Isabelle; Marcoux, Genevieve; Machlus, Kellie R; Mailhot, Benoit; Zufferey, Anne; Levesque, Tania; Becker, Yann; Tessandier, Nicolas; Melki, Imene; Zhi, Huiying; Poirier, Guy; Rondina, Matthew T; Italiano, Joseph E; Flamand, Louis; McKenzie, Steven E; Cote, Francine; Nieswandt, Bernhard; Khan, Waliul I; Flick, Matthew J; Newman, Peter J; Lacroix, Steve; Fortin, Paul R; Boilard, Eric

2018-02-13

There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.

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.

The importance of platelets in the expression of monocyte tissue factor antigen measured by a new whole blood flow cytometric assay.

PubMed

Amirkhosravi, A; Alexander, M; May, K; Francis, D A; Warnes, G; Biggerstaff, J; Francis, J L

1996-01-01

Previous methods for the determination of monocyte tissue factor (TF) have been technically complex, difficult to standardize, prone to spuriously elevated results and difficult to implement in a clinical laboratory environment. We report the development of a two-color whole blood cytometric technique that overcomes many of these disadvantages. The assay uses small volumes of citrated blood (1.0 ml), can be performed in under one hour (if endotoxin stimulation is not performed), is reproducible (CV = 5%) and uses methodology commonly available in clinical laboratories. Baseline (mean +/- SD) expression of monocyte TF in normal subjects was very low (1.1 +/- 0.95%, Mean Fluorescence [Mean FL] 0.20 +/- 0.01) making relatively small increases easy to detect. Monocyte TF expression following endotoxin (LPS) stimulation for 1 h was 34.6 +/- 11.2% (Mean FL 0.32 +/- 0.04). LPS-stimulated activity varied between subjects (21-68%) but was remarkably consistent for individual subjects (CV = 5.4%). Stimulated monocyte TF expression was directly proportional to the platelet count and was reduced by platelet protective anticoagulants and by ingestion of aspirin. Non LPS-stimulated monocyte TF was markedly increased, in a dose-dependent manner, by adding collagen to whole blood. This was apparently associated with platelet-monocyte binding and could be abolished by anti-P-Selectin. We conclude that the whole blood flow cytometric assay of monocyte TF may be a valuable tool for clinical use and a useful model system for evaluating the humoral and cellular factors governing monocyte TF expression in a natural environment.

Pentadecapeptide BPC 157 reduces bleeding time and thrombocytopenia after amputation in rats treated with heparin, warfarin or aspirin.

PubMed

Stupnisek, Mirjana; Franjic, Sandra; Drmic, Domagoj; Hrelec, Masa; Kolenc, Danijela; Radic, Bozo; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2012-05-01

Recently, in rat abdominal aorta terminoterminal-anastomosis the stable gastric pentadecapeptide BPC 157 prevents obstructive thrombus formation and rapidly destroys already formed obstructive thrombus. Also, BPC 157 wound healing may signify the clot as conductive matrix or "scaffold" to speed up wound healing process, and decrease bleeding. Here, in rats, BPC 157 (10 μg/kg, 10 ng/kg) improved always reduced bleeding time and amount of bleeding after (tail) amputation only, heparin (250 mg/kg, 25mg/kg, 10mg/kg i.v.), warfarin (1.5mg/kg i.g. once daily for 3 consecutive days), aspirin (0.1g/kg i.g. (once daily/3 consecutive days) or 1.0 g/kg i.p. once), and amputation associated with those agents application. BPC 157 counteracting regimens (i.v., i.p., i.g. (immediately after any challenge)) correspondingly follow the route of bleeding-agents application. All heparin-, warfarin-, and aspirin-rats and normal-rats that received BPC 157 exhibited lesser fall in platelets count. BPC 157 attenuated over-increased APTT-, TT-values in 10mg/kg heparin-rats, but did not influence heparin activity (anti-Xa test). Indicatively, unless counteracted in BPC 157 rats, excessive bleeding-acute thrombocytopenia (<20% of initial values in heparin-rats) approaches substantial fall in platelets count known in type II HIT. Also, BPC 157 markedly prolongs the survival time (heparin-rats, 25mg/kg, right foot amputation). Copyright © 2011 Elsevier Ltd. All rights reserved.

Thromboelastographic evaluation of dogs with congenital portosystemic shunts.

PubMed

Kelley, D; Lester, C; DeLaforcade, A; Webster, C R L

2013-01-01

On plasma-based assays, dogs with congenital portosystemic shunts (CPSS) have changes in serum concentrations of both pro- and anticoagulant proteins, but how these abnormalities affect whole blood coagulation assays (eg, thromboelastography) are unknown. To conduct kaolin-activated thromboelastography (TEG) analysis in dogs with CPSS and to compare TEG coagulation status with clinical presentation, routine serum biochemistry, and plasma-based coagulation tests. Twenty-one client-owned dogs with CPSS confirmed by ultrasound examination or nuclear scintigraphy. In a prospective study, signalment, clinical presentation, TEG analysis, CBC, serum biochemistry, and hemostatic tests (platelet count, prothrombin time [PT], activated partial thromboplastin time [aPTT], quantitative fibrinogen, antithrombin [AT] activity, protein C [PC] activity, d-dimers, and factor VIII activity) were analyzed in dogs with CPSS. Dogs with CPSS had significantly shorter K values and increased angle, maximum amplitude (MA), and G values compared with the reference population. On plasma-based coagulation testing, dogs with CPSS had significantly prolonged PT, lower platelet counts, lower AT and PC activities, and increased d-dimers and factor VIII activity. Evaluation of G value defined 9/21 dogs with CPSS as hypercoagulable. These dogs were more likely to have hepatic encephalopathy (HE) than CPSS dogs that had normal coagulation. TEG analysis detected hemostatic abnormalities consistent with a hypercoagulable state in some dogs with CPSS. The presence of a hypercoagulable state was 40 times more likely in dogs with symptomatic HE. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Prediction of early death among patients enrolled in phase I trials: development and validation of a new model based on platelet count and albumin.

PubMed

Ploquin, A; Olmos, D; Lacombe, D; A'Hern, R; Duhamel, A; Twelves, C; Marsoni, S; Morales-Barrera, R; Soria, J-C; Verweij, J; Voest, E E; Schöffski, P; Schellens, J H; Kramar, A; Kristeleit, R S; Arkenau, H-T; Kaye, S B; Penel, N

2012-09-25

Selecting patients with 'sufficient life expectancy' for Phase I oncology trials remains challenging. The Royal Marsden Hospital Score (RMS) previously identified high-risk patients as those with ≥ 2 of the following: albumin <35 g l(-1); LDH > upper limit of normal; >2 metastatic sites. This study developed an alternative prognostic model, and compared its performance with that of the RMS. The primary end point was the 90-day mortality rate. The new model was developed from the same database as RMS, but it used Chi-squared Automatic Interaction Detection (CHAID). The ROC characteristics of both methods were then validated in an independent database of 324 patients enrolled in European Organization on Research and Treatment of Cancer Phase I trials of cytotoxic agents between 2000 and 2009. The CHAID method identified high-risk patients as those with albumin <33 g l(-1) or ≥ 33 g l(-1), but platelet counts ≥ 400.000 mm(-3). In the validation data set, the rates of correctly classified patients were 0.79 vs 0.67 for the CHAID model and RMS, respectively. The negative predictive values (NPV) were similar for the CHAID model and RMS. The CHAID model and RMS provided a similarly high level of NPV, but the CHAID model gave a better accuracy in the validation set. Both CHAID model and RMS may improve the screening process in phase I trials.

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

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.

Platelet count and platelet indices in women with preeclampsia.

PubMed

AlSheeha, Muneera A; Alaboudi, Rafi S; Alghasham, Mohammad A; Iqbal, Javed; Adam, Ishag

2016-01-01

Although the exact pathophysiology of preeclampsia is not completely understood, the utility of different platelets indices can be utilized to predict preeclampsia. To compare platelet indices, namely platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and PC to MPV ratio in women with preeclampsia compared with healthy controls. Qassim Hospital, Kingdom of Saudi Arabia. A case-control study. Sixty preeclamptic women were the cases and an equal number of healthy pregnant women were the controls. There was no significant difference in age, parity, and body mass index between the study groups. Sixteen and 44 of the cases were severe and mild preeclampsia, respectively. There was no significant difference in PDW and MPV between the preeclamptic and control women. Both PC and PC to MPV ratios were significantly lower in the women with preeclampsia compared with the controls. There was no significant difference in the PC, PDW, MPV, and PC to MPV ratio when women with mild and severe preeclampsia were compared. Using receiver operating characteristic (ROC) curves, the PC cutoff was 248.0×10 3 /µL for diagnosis of pre-eclampsia ( P =0.019; the area under the ROC curve was 62.4%). Binary regression suggests that women with PC <248.010×10 3 /µL were at higher risk of preeclampsia (odds ratio =2.2, 95% confidence interval =1.08-4.6, P =0.03). The PC/MPV cutoff was 31.2 for diagnosis of preeclampsia ( P =0.035, the area under the ROC curve was 62.2%). PC <248.010×10 3 /µL and PC to MPV ratio 31.2 are valid predictors of preeclampsia.

Population pharmacokinetic/ pharmacodynamic modelling of eltrombopag in healthy volunteers and subjects with chronic liver disease

PubMed Central

Farrell, Colm; Hayes, Siobhan C; Wire, Mary; Zhang, Jianping

2014-01-01

Aims To characterize the pharmacokinetics (PK)/pharmacodynamics (PD) of eltrombopag in chronic liver disease (CLD). Methods The PK/PD model was developed using data from 79 CLD patients using nonlinear mixed-effects modelling. Results The PK of eltrombopag were described by a two-compartment model with dual sequential first-order absorption. Gender, race and severity of CLD were predictors of the apparent clearance of eltrombopag. The PD of eltrombopag in CLD were adequately described by a four-compartment lifespan model, in which eltrombopag stimulated platelet precursor production rate. East Asian CLD patients were less sensitive to the stimulatory effect of eltrombopag. Following a daily dose regimen of 50 mg eltrombopag, the time to achieve peak platelet counts was longer for the CLD population compared with patients who had immune thrombocytopenic purpura, but was comparable to patients with hepatitis C. Likewise, it took a longer time for platelet counts to rebound back to baseline once eltrombopag treatment was discontinued. Conclusions The time course of the platelet response in CLD was different from that in immune thrombocytopenic purpura but comparable to that in hepatitis C. PMID:24117976

Predilution versus postdilution during continuous venovenous hemofiltration: a comparison of circuit thrombogenesis.

PubMed

de Pont, Anne-Cornélie J M; Bouman, Catherine S C; Bakhtiari, Kamran; Schaap, Marianne C L; Nieuwland, Rienk; Sturk, Augueste; Hutten, Barbara A; de Jonge, Evert; Vroom, Margreeth B; Meijers, Joost C M; Büller, Harry R

2006-01-01

During continuous venovenous hemofiltration, predilution can prolong circuit survival time, but the underlying mechanism has not been elucidated. The aim of the present study was to compare predilution with postdilution, with respect to circuit thrombogenesis. Eight critically ill patients were treated with both predilutional and postdilutional continuous venovenous hemofiltration in a crossover fashion. A filtration flow of 60 ml/min was used in both modes. We chose blood flows of 140 and 200 ml/min during predilution and postdilution, respectively, to keep the total flow through the hemofilter constant. Extracorporeal circuit pressures were measured hourly, and samples of blood and ultrafiltrate were collected at five different time points. Thrombin-antithrombin complexes and prothrombin fragments F1 + 2 were measured by ELISA, and platelet activation was assessed by flow cytometry. No signs of thrombin generation or platelet activation were found during either mode. During postdilution, baseline platelet count and maximal prefilter pressure had a linear relation, whereas both parameters were inversely related with circuit survival time. In summary, predilution and postdilution did not differ with respect to extracorporeal circuit thrombogenesis. During postdilution, baseline platelet count and maximal prefilter pressure were inversely related with circuit survival time.

Antithrombotic therapy in patients with thrombocytopenic cancer: outcomes associated with reduced-dose, low-molecular-weight heparin during hospitalization.

PubMed

Babilonia, Katrina M; Golightly, Larry K; Gutman, Jonathan A; Hassell, Kathryn L; Kaiser, Jeffrey N; Kiser, Tyree H; Klem, Patrick M; Trujillo, Toby C

2014-11-01

Guidelines are discordant concerning management of patients having thrombocytopenia with cancer-associated thrombosis (CAT). Hospitalized adults with CAT and platelets ≤50 × 10(9) cells/L were managed with dalteparin 100 units/kg subcutaneously once daily. Comparator patients with CAT and platelets >50 × 10(9) cells/L were managed with dalteparin 200 units/kg/d. Outcomes of 35 patients with thrombocytopenia (mean platelet count 26 ± 8.3 × 10(9) cells/L) and 58 comparator patients (mean platelet count 155 ± 75 × 10(9) cells/L) were evaluated. In all, 2 (5.7%) patients in the thrombocytopenia group and 1 patient (1.9%) in the comparator group experienced new-onset venous thromboembolism (odds ratio 3.31, 95% confidence interval [CI] 0.29-37.90, P = .556). The incidence of bleeding in patients with thrombocytopenia (8.6%) was similar to that in comparator patients (9.4%; risk ratio 0.94, 95% CI 0.37-2.39, P = .607). In hospitalized patients having thrombocytopenia with CAT, reduced-dose low-molecular-weight heparin was generally efficacious. © The Author(s) 2014.

[Full blood count reference values in children of 8 to 12 years old residing at 2,760 m above sea level].

PubMed

Armando García-Miranda, L; Contreras, I; Estrada, J A

2014-04-01

To determine reference values for full blood count parameters in a population of children 8 to 12 years old, living at an altitude of 2760 m above sea level. Our sample consisted of 102 individuals on whom a full blood count was performed. The parameters included: total number of red blood cells, platelets, white cells, and a differential count (millions/μl and %) of neutrophils, lymphocytes, monocytes, eosinophils and basophils. Additionally, we obtained values for hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, concentration of corpuscular hemoglobin and red blood cell distribution width. The results were statistically analyzed with a non-parametric test, to divide the sample in quartiles and obtain the lower and upper limits for our intervals. Moreover, the values for the intervals obtained from this analysis were compared to intervals obtained estimating+- 2 standard deviations above and below from our mean values. Our results showed significant differences compared to normal interval values reported for the adult Mexican population in most of the parameters studied. The full blood count is an important laboratory test used routinely for the initial assessment of a patient. Values of full blood counts in healthy individuals vary according to gender, age and geographic location; therefore, each population should have its own reference values. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

The lung is a site of platelet biogenesis and a reservoir for hematopoietic progenitors

PubMed Central

Lefrançais, Emma; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; Mallavia, Beñat; Liu, Fengchun; Sayah, David M.; Thornton, Emily E.; Headley, Mark B.; David, Tovo; Coughlin, Shaun R.; Krummel, Matthew F.; Leavitt, Andrew D.; Passegué, Emmanuelle; Looney, Mark R.

2017-01-01

Platelets are critical for hemostasis, thrombosis, and inflammatory responses1,2, yet the events leading to mature platelet production remain incompletely understood3. The bone marrow (BM) is proposed to be a major site of platelet production although indirect evidence points towards a potential pulmonary contribution to platelet biogenesis4-7. By directly imaging the lung microcirculation in mice8, we discovered that a large number of megakaryocytes (MKs) circulate through the lungs where they dynamically release platelets. MKs releasing platelets in the lung are of extrapulmonary origin, such as the BM, where we observed large MKs migrating out of the BM space. The lung contribution to platelet biogenesis is substantial with approximately 50% of total platelet production or 10 million platelets per hour. Furthermore, we identified populations of mature and immature MKs along with hematopoietic progenitors that reside in the extravascular spaces of the lung. Under conditions of thrombocytopenia and relative stem cell deficiency in the BM9, these progenitors can migrate out of the lung, repopulate the BM, completely reconstitute blood platelet counts, and contribute to multiple hematopoietic lineages. These results position the lung as a primary site of terminal platelet production and an organ with considerable hematopoietic potential. PMID:28329764

Platelet parameters (PLT, MPV, P-LCR) in patients with schizophrenia, unipolar depression and bipolar disorder.

PubMed

Wysokiński, Adam; Szczepocka, Ewa

2016-03-30

There are no studies comparing platelet parameters platelet parameters (platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR)) between patients with schizophrenia, bipolar disorder and unipolar depression. Therefore, the aim of this study was to determine and compare differences in PLT, MPV and P-LCR in patients with schizophrenia, unipolar depression and bipolar disorder. This was a retrospective, cross-sectional, naturalistic study of 2377 patients (schizophrenia n=1243; unipolar depression n=791; bipolar disorder n=343, including bipolar depression n=259 and mania n=84). There were significant differences for PLT, MPV and P-LCR values between study groups. A significant percentage of patients with bipolar disorder had abnormal (too low or too high) number of platelets. Negative correlation between PLT and age was found in all study groups and positive correlation between age and MPV and P-LCR was found in patients with schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Three Adult Cases of HPV-B19 Infection with Concomitant Leukopenia and Low Platelet Counts

PubMed Central

Yaguchi, Daizo; Marui, Nobuyuki; Matsuo, Masaki

2015-01-01

We encountered three adult patients with flu-like symptoms diagnosed with human parvovirus B19 (HPV-B19) infection. Blood serum analysis also revealed leukopenia, with white blood cell counts (WBCs) of 1,000–2,000/mL and low platelet counts of 89–150 × 109/L. Typical skin rash was absent in one patient. Bone marrow examination of another patient showed hypoplastic marrow with <5% blast cells. All patients recovered without administration of granulocyte colony-stimulating factor (G-CSF). Therefore, HPV-B19 infection with leukopenia should be considered in adult patients with leukopenia during erythema infectiosum epidemics, even if typical clinical findings (ie, skin rash) are absent. Further, the fact that three cases were observed over the stated time period at our hospital, which is located in Nagoya city, showed a transition to a slightly higher level of incidence than the annual average. PMID:25780346

The counting of native blood cells by digital microscopy

NASA Astrophysics Data System (ADS)

Torbin, S. O.; Doubrovski, V. A.; Zabenkov, I. V.; Tsareva, O. E.

2017-03-01

An algorithm for photographic images processing of blood samples in its native state was developed to determine the concentration of erythrocytes, leukocytes and platelets without individual separate preparation of cells' samples. Special "photo templates" were suggested to use in order to identify red blood cells. The effect of "highlighting" of leukocytes, which was found by authors, was used to increase the accuracy of this type of cells counting. Finally to raise the resolution of platelets from leukocytes the areas of their photo images were used, but not their sizes. It is shown that the accuracy of cells counting for native blood samples may be comparable with the accuracy of similar studies for smears. At the same time the proposed native blood analysis simplifies greatly the procedure of sample preparation in comparison to smear, permits to move from the detection of blood cells ratio to the determination of their concentrations in the sample.

Comparison of plateletpheresis on the Fresenius AS.TEC 204 and Haemonetics MCS 3p.

PubMed

Ranganathan, Sudha

2007-02-01

This is an attempt at comparing two cell separators for plateletpheresis, namely the Fresenius AS.TEC 204 and Haemonetics MCS 3p, at a tertiary care center in India. Donors who weighed between 55-75 kg, who had a hematocrit of 41-43%, and platelet counts of 250x10(3)-400x10(3)/microl were selected for the study. The comparability of the donors who donated on the two cell separators were analysed by t-test independent samples and no significant differences were found (P>0.05). The features compared were time taken for the procedure, volume processed on the separators, adverse reactions of the donors, quality control of the product, separation efficiency of the separators, platelet loss in the donors after the procedure, and the predictor versus the actual yield of platelets given by the cell separator. The volume processed to get a target yield of >3x10(11) was equal to 2.8-3.2 l and equal in both the cell separators. Symptoms of citrate toxicity were seen in 4 and 2.5% of donors who donated on the MCS 3p and the AS.TEC 204, respectively, and 3 and 1% of donors, respectively, had vasovagal reactions. All the platelet products collected had a platelet count of >3x10(11); 90% of the platelet products collected on the AS.TEC 204 attained the predicted yield that was set on the cell separator where as 75% of the platelet products collected on the MCS 3p attained the target yield. Quality control of the platelets collected on both the cell separators complied with the standards except that 3% of the platelets collected on the MCS 3p had a visible red cell contamination. The separation efficiency of the MCS 3p was higher, 50-52% as compared to the 40-45% on the AS.TEC 204. A provision of double venous access, less adverse reactions, negligible RBC contamination with a better predictor yield of platelets makes the AS.TEC 204 a safer and more reliable alternative than the widely used Haemonetics MCS 3p. Copyright (c) 2006 Wiley-Liss, Inc.

A case of EDTA-dependent pseudothrombocytopenia: simple recognition of an underdiagnosed and misleading phenomenon

PubMed Central

2014-01-01

Background EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is a common laboratory phenomenon with a prevalence ranging from 0.1-2% in hospitalized patients to 15-17% in outpatients evaluated for isolated thrombocytopenia. Despite its harmlessness, EDTA-PTCP frequently leads to time-consuming, costly and even invasive diagnostic investigations. EDTA-PTCP is often overlooked because blood smears are not evaluated visually in routine practice and histograms as well as warning flags of hematology analyzers are not interpreted correctly. Nonetheless, EDTA-PTCP may be diagnosed easily even by general practitioners without any experiences in blood film examinations. This is the first report illustrating the typical patterns of a platelet (PLT) and white blood cell (WBC) histograms of hematology analyzers. Case presentation A 37-year-old female patient of Caucasian origin was referred with suspected acute leukemia and the crew of the emergency unit arranged extensive investigations for work-up. However, examination of EDTA blood sample revealed atypical lymphocytes and an isolated thrombocytopenia together with typical patterns of WBC and PLT histograms: a serrated curve of the platelet histogram and a peculiar peak on the left side of the WBC histogram. EDTA-PTCP was confirmed by a normal platelet count when examining citrated blood. Conclusion Awareness of typical PLT and WBC patterns may alert to the presence of EDTA-PTCP in routine laboratory practice helping to avoid unnecessary investigations and over-treatment. PMID:24808761

Effect of flomoxef on blood coagulation and alcohol metabolism.

PubMed

Uchida, K; Matsubara, T

1991-01-01

The effect of flomoxef, a newly developed oxacephem antibiotic with an N-hydroxyethyltetrazolethiol (HTT) side chain, on blood coagulation and alcohol metabolism was compared with that of a series of cephalosporin antibiotics with N-methyltetrazolethiol (NMTT), thiadiazolethiol (TDT) or methylthiadiazolethiol (MTDT) side chains in position 3' of the cephalosporin nucleus known to cause hypoprothrombinemia and bleeding in patients who are malnourished, debilitated and/or of high age. A disulfiram-like effect caused by inhibition of aldehyde dehydrogenase was observed for NMTT-containing antibiotics. Studies were carried out on healthy volunteers and on rats. Eight-day treatment with 2 g flomoxef i.v. once or twice daily in five and six healthy male volunteers, respectively, did not cause any significant changes in prothrombin time (PT), coagulation factors II, VII, IX or X, in hepaplastin values or fibrinogen levels, activated partial thromboplastin time (APTT), platelet counts, bleeding time, or collagen- and ADP-induced platelet aggregation. Inhibition of vitamin K epoxide reductase was observed in rats treated with flomoxef, yet to a much lesser extent than observed for cephalosporins with NMTT, TDT or MTDT side chains. This defect was quickly normalized by vitamin K injection. There were no differences between oxacephem (1-O) and cephem (1-S) compounds with respect to effects on blood clotting and platelet aggregation. Flomoxef and its side chain HTT showed no influence on alcohol metbolism.

Risk factors associated with severe scrub typhus in Shandong, northern China.

PubMed

Zhang, Luyan; Zhao, Zhongtang; Bi, Zhenwang; Kou, Zengqiang; Zhang, Meng; Yang, Li; Zheng, Li

2014-12-01

The aim of this study was to identify risk factors associated with severe scrub typhus, in order to provide a reference for clinical decision-making. A case-control study was conducted of scrub typhus patients who presented at local hospitals between 2010 and 2013. In total, 46 patients with severe scrub typhus complications (cases) and 194 without severe complications (controls) were included. There were significant differences in the duration of illness before effective antibiotic therapy, lymphadenopathy, rash, blood platelet count, white blood cell (WBC) count, percentage neutrophils, and percentage lymphocytes between the case and control groups. Multivariate analysis demonstrated that the following four factors were significantly associated with the severe complications of scrub typhus: (1) duration of illness before effective antibiotic therapy (odds ratio (OR) 2.287, 95% confidence interval (CI) 1.096-4.770); (2) the presence of a rash (OR 3.694, 95% CI 1.300-10.495); (3) lymphadenopathy (OR 2.438, 95% CI 1.090-5.458); (4) blood platelet count <100×10(9)/l (OR 2.226, 95% CI 1.002-4.946). This study indicates that improved diagnosis and timely treatment are important factors for the prevention of severe scrub typhus. When scrub typhus patients present with a rash, lymphadenopathy, or blood platelet count <100×10(9)/l, clinicians should be alert to the appearance of severe complications. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Hematologic variables associated with brain failure in patients with small-cell lung cancer.

PubMed

Suzuki, Ryoko; Wei, Xiong; Allen, Pamela K; Welsh, James W; Komaki, Ritsuko; Lin, Steven H

2018-06-12

We sought factors associated with the development of brain metastases after treatment of small cell lung cancer (SCLC) in patients without brain involvement at diagnosis. We analyzed 293 patients with SCLC without brain metastases who received chemotherapy, thoracic radiation therapy (TRT), or both in 2001-2015. Pretreatment hematologic markers (platelet count, neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lactate dehydrogenase) and other clinical characteristics were evaluated for correlation with brain metastases-free survival (BMFS). Cutoffs were established with receiver operating characteristics curves. Factors significant in univariate analysis were used to build a multivariate Cox model for BMFS. Median follow-up time was 14.3 months. Brain metastases developed in 115 patients (39%)-32% of those with low pretreatment platelet counts (PPC) (≤270 × 10 9 /L) and 46% of those with high PPC (>270 × 10 9 /L). Median BMFS time for all patients was 27.9 months. Two-year BMFS rates were worse for patients with high PPC (14.6% vs. 22.1% low, P = 0.009). High PPC was independently associated with inferior BMFS (P = 0.038), as were receipt of TRT <45 Gy and no prophylactic cranial irradiation (both P < 0.001). High PPC was associated with increased rates of brain metastasis in patients with SCLC with no evidence of brain disease at diagnosis. Copyright © 2018. Published by Elsevier B.V.

Cerebral Venous Sinus Thrombosis Due to Low-molecular-weight Heparin-induced Thrombocytopenia.

PubMed

Gleichgerrcht, Ezequiel; Lim, Ming Y; Turan, Tanya N

2017-11-01

Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis (CVST) as the presenting thrombotic event induced by HIT, only one of which occurred with exposure to low-molecular-weight heparin (LMWH), with death as outcome. Here, we present a unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome. A 52-year-old woman received subcutaneous LMWH for deep vein thrombosis prophylaxis while in rehabilitation following kyphoplasty for spinal fracture related to recent trauma. On postoperative day 15, she developed acute onset altered mental status with significant agitation and nonsensical speech and was found to have brain imaging findings suggestive of CVST. Work-up revealed a drop in platelets associated with HIT, which did not improve off heparin products and with steroids, requiring intravenous immunoglobulin therapy, likely due to an overlapping immune thrombocytopenic purpura. Patient was managed on an argatroban drip until platelet count normalized and was able to transition to warfarin. Her clinical outcome was very favorable with near-normal neurological exam except for subtle cognitive changes. This unique case of LMWH-induced HIT leading to CVST but resulting in good clinical outcome highlights the importance of linking CVST with HIT and of establishing the need for early alternative antithrombotic therapeutic strategies.

Potential Value of Coagulation Parameters for Suggesting Preeclampsia During the Third Trimester of Pregnancy.

PubMed

Chen, Ying; Lin, Li

2017-07-01

Preeclampsia is a relatively common complication of pregnancy and considered to be associated with different degrees of coagulation dysfunction. This study was developed to evaluate the potential value of coagulation parameters for suggesting preeclampsia during the third trimester of pregnancy. Data from 188 healthy pregnant women, 125 patients with preeclampsia in the third trimester and 120 age-matched nonpregnant women were analyzed. Prothrombin time, prothrombin activity, activated partial thromboplastin time, fibrinogen (Fg), antithrombin, platelet count, mean platelet volume, platelet distribution width and plateletcrit were tested. All parameters, excluding prothrombin time, platelet distribution width and plateletcrit, differed significantly between healthy pregnant women and those with preeclampsia. Platelet count, antithrombin and Fg were significantly lower and mean platelet volume and prothrombin activity were significantly higher in patients with preeclampsia (P < 0.001). Among these parameters, the largest area under the receiver operating characteristic curve for preeclampsia was 0.872 for Fg with an optimal cutoff value of ≤2.87g/L (sensitivity = 0.68 and specificity = 0.98). For severe preeclampsia, the area under the curve for Fg reached up to 0.922 with the same optimal cutoff value (sensitivity = 0.84, specificity = 0.98, positive predictive value = 0.96 and negative predictive value = 0.93). Fg is a biomarker suggestive of preeclampsia in the third trimester of pregnancy, and our data provide a potential cutoff value of Fg ≤ 2.87g/L for screening preeclampsia, especially severe preeclampsia. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Effect of Gender on the Radiation Sensitivity of Murine Blood Cells

PubMed Central

Billings, Paul C; Romero-Weaver, Ana L; Kennedy, Ann R

2014-01-01

Space travel beyond the Earth’s protective magnetosphere risks exposing astronauts to ionizing radiation, such as that generated during a solar particle event (SPE). Ionizing radiation has well documented effects on blood cells and it is generally assumed that these effects contribute to the hematopoietic syndrome (HS), observed in animals and humans, following exposure to total body irradiation (TBI). The purpose of the current study was to assess the role of gender on the effects of gamma radiation on blood cells. C3H/HeN mice were irradiated with a 137Cs gamma source. Radiation had similar effects on white blood cells (WBCs), lymphocytes, and granulocytes in male and female C3H/HeN mice, while red blood cell (RBC) counts and hematocrit values remained stable following radiation exposure. Non-irradiated male mice had 13% higher platelet counts, compared with their female counterparts, and showed enhanced recovery of platelets on day 16 following radiation exposure. Hence, gender differences influence the response of platelets to TBI exposure. PMID:25221782

Effects of a single bout of strenuous exercise on platelet activation in female ApoE/LDLR-/- mice.

PubMed

Przyborowski, K; Kassassir, H; Wojewoda, M; Kmiecik, K; Sitek, B; Siewiera, K; Zakrzewska, A; Rudolf, A M; Kostogrys, R; Watala, C; Zoladz, J A; Chlopicki, S

2017-11-01

Strenuous physical exercise leads to platelet activation that is normally counterbalanced by the production of endothelium-derived anti-platelet mediators, including prostacyclin (PGI 2 ) and nitric oxide (NO). However, in the case of endothelial dysfunction, e.g. in atherosclerosis, there exists an increased risk for intravascular thrombosis during exercise that might be due to an impairment in endothelial anti-platelet mechanisms. In the present work, we evaluated platelet activation at rest and following a single bout of strenuous treadmill exercise in female ApoE/LDLR - /- mice with early (3-month-old) and advanced (7-month-old) atherosclerosis compared to female age-matched WT mice. In sedentary and post-exercise groups of animals, we analyzed TXB 2 generation and the expression of platelet activation markers in the whole blood ex vivo assay. We also measured pre- and post-exercise plasma concentration of 6-keto-PGF 1α , nitrite/nitrate, lipid profile, and blood cell count. Sedentary 3- and 7-month-old ApoE/LDLR - /- mice displayed significantly higher activation of platelets compared to age-matched wild-type (WT) mice, as evidenced by increased TXB 2 production, expression of P-selectin, and activation of GPIIb/IIIa receptors, as well as increased fibrinogen and von Willebrand factor (vWf) binding. Interestingly, in ApoE/LDLR - /- but not in WT mice, strenuous exercise partially inhibited TXB 2 production, the expression of activated GPIIb/IIIa receptors, and fibrinogen binding, with no effect on the P-selectin expression and vWf binding. Post-exercise down-regulation of the activated GPIIb/IIIa receptor expression and fibrinogen binding was not significantly different between 3- and 7-month-old ApoE/LDLR - /- mice; however, only 7-month-old ApoE/LDLR - /- mice showed lower TXB 2 production after exercise. In female 4-6-month-old ApoE/LDLR - /- but not in WT mice, an elevated pre- and post-exercise plasma concentration of 6-keto-PGF 1α was observed. In turn, the pre- and post-exercise plasma concentrations of nitrite (NO 2 - ) and nitrate (NO 3 - ) were decreased in ApoE/LDLR - /- as compared to that in age-matched WT mice. In conclusion, we demonstrated overactivation of platelets in ApoE/LDLR - /- as compared to WT mice. However, platelet activation in ApoE/LDLR - /- mice was not further increased by strenuous exercise, but was instead attenuated, a phenomenon not observed in WT mice. This phenomenon could be linked to compensatory up-regulation of PGI 2 -dependent anti-platelet mechanisms in ApoE/LDLR - /- mice.

Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia.

PubMed

Norris, J W; Pombo, M; Shirley, E; Blevins, G; Tablin, F

2015-01-01

Two congenital bleeding diatheses have been identified in Thoroughbred horses: Glanzmann thrombasthenia (GT) and a second, novel diathesis associated with abnormal platelet function in response to collagen and thrombin stimulation. Platelet dysfunction in horses with this second thrombasthenia results from a secretory defect. Two affected and 6 clinically normal horses. Ex vivo study. Washed platelets were examined for (1) expression of the αIIb-β3 integrin; (2) fibrinogen binding capacity in response to ADP and thrombin; (3) secretion of dense and α-granules; (4) activation of the mammalian target of rapamycin (mTOR)-protein kinase B (AKT) signaling pathway; and (5) cellular distribution of phosphatidylinositol-4-phosphate-3-kinase, class 2B (PIK3C2B) and SH2 containing inositol-5'-phosphatase 1 (SHIP1). Platelets from affected horses expressed normal amounts of αIIb-β3 integrin and bound fibrinogen normally in response to ADP, but bound 80% less fibrinogen in response to thrombin. α-granules only released 50% as much Factor V as control platelets, but dense granules released their contents normally. Protein kinase B (AKT) phosphorylation was reduced after thrombin activation, but mTOR Complex 2 (mTORC2) and phosphoinositide-dependent kinase 1 (PDK1) signaling were normal. SH2-containing inositol-5'-phosphatase 1 (SHIP1) did not localize to the cytoskeleton of affected platelets and was decreased overall consistent with reduced AKT phosphorylation. Defects in fibrinogen binding, granule secretion, and signal transduction are unique to this thrombasthenia, which we designate as atypical equine thrombasthenia. Copyright © The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Internal Medicine.

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

Quantitative Characterization of Shear-Induced Platelet Receptor Shedding: Glycoprotein Ibα, Glycoprotein VI, and Glycoprotein IIb/IIIa.

PubMed

Chen, Zengsheng; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

2017-11-07

The structural integrity of platelet receptors is essential for platelets to play the normal hemostatic function. The high non-physiologic shear stress (NPSS) commonly exists in blood-contacting medical devices and has been shown to cause platelet receptor shedding. The loss of platelet receptors may impair the normal hemostatic function of platelets. The aim of this study was to quantify NPSS-induced shedding of three key receptors on the platelet surface. Human blood was subjected to the matrix of well-defined shear stresses and exposure times, generated by using a custom-designed blood-shearing device. The expression of three key platelet receptors, glycoprotein (GP) Ibα, GPVI, and GPIIb/IIIa, in sheared blood was quantified using flow cytometry. The quantitative relationship between the loss of each of the three receptors on the platelet surface and shear condition (shear stress level and exposure time) was explored. It was found that these relationships followed well the power law functional form. The coefficients of the power law models for the shear-induced shedding of these platelet receptors were derived with coefficients of determination (R) of 0.77, 0.73, and 0.78, respectively. The power law models with these coefficients may be potentially used to predict the shear-induced platelet receptor shedding of human blood.

Effects of first-line anti-retroviral therapy on blood coagulation parameters of HIV-infected patients attending a tertiary hospital at Abuja, Nigeria.

PubMed

Nasir, I A; Owolagba, A; Ahmad, A E; Barma, M M; Musa Po, P O; Bakare, M; Ibrahim, Y; Amadu, D O

2016-08-01

Blood coagulation abnormalities are common in persons infected with the human immunodeficiency virus (HIV). However, few studies showed the association of these abnormalities with anti-retroviral therapy (ART). This cross-sectional study investigated the effects of ART on blood coagulation parameters of patients infected with HIV attending HIV special clinics of the University of Abuja Teaching Hospital (UATH), Gwagwalada, Abuja, Nigeria. A total of 191 patients comprising 128 HIV subjects on ART (test subjects) and 63 other HIV patients not on ART (control subjects) were included in the study. CD4+ lymphocyte counts, platelet counts, prothrombin time (PT) and partial thromboplastin time with kaolin (PTTK) of subjects were determined using flow cytometry, automated hematology analyser and Quick one-stage methods respectively. Of the total test subjects, 21 (16.4%) were CD4 lymphopaenic, and the mean CD4+ cell count for the test subjects was statistically higher than that of the control subjects (578 versus 322 cells/ mm(3)) (p = 0.014). Eight (6.3%) of test subjects had prolong PTTK, and the mean values of PT and PTTK were statistically not significant between test subjects and control subjects (p = 0.358 and p= 0.141 respectively). Eight (6.3%) of test subjects had thrombocytopaenia, the mean platelet count was significantly lower than that of the control subjects (238 versus 278.6 x 10(9)/L, p = 0.001), and also varied significantly with the duration of ART (p = 0.0086). Findings from this study revealed ART decreased platelet counts of HIV-infected individuals, but did not affect the PT and PTTK results.

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

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

Hang, Bo; Snijders, Antoine M.; Huang, Yurong

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeksmore » after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.« less

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

DOE PAGES

Hang, Bo; Snijders, Antoine M.; Huang, Yurong; ...

2017-02-03

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeksmore » after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.« less

[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.

In vitro effect of sodium nitrite on platelet aggregation in human platelet rich plasma--preliminary report.

PubMed

Kadan, M; Doğanci, S; Yildirim, V; Özgür, G; Erol, G; Karabacak, K; Avcu, F

2015-10-01

The role of nitrates and nitric oxide on platelet functions has obtained an increasing attention with respect to their potential effects on cardiovascular disorders. In this study we aimed to analyze the effect of sodium nitrite on platelet functions in human platelets. This in vitro study was designed to show the effect of sodium nitrite on platelet functions in seven healthy volunteers. Blood samples were centrifuged to prepare platelet rich plasma and platelet poor plasma. Platelet rich plasma was diluted with the platelet poor plasma to have a final count of 300,000 ± 25,000 platelets. Platelet rich plasma was incubated with six different increasing doses (from 10 μM to 5 mM) of sodium nitrite for 1 hour at 37°C. Then stimulating agents including collagen (3 μg ml-1), adenosine diphosphate (10 μM), and epinephrine (10 μM) were added to the cuvette. Changes in light transmission were observed for 10 minutes. In addition spontaneous aggregation were performed in control group with all aggregating agents separately. Effect of sodium nitrite on agonist-induced platelet aggregation depends on the concentration of sodium nitrite. Compared with control group, agonist-induced platelet aggregations were significantly suppressed by sodium nitrite at the concentration of 5, 1.0 and 0.5 mM. Our results suggested that sodium nitrite has inhibitory effects in vitro on platelet aggregation in a dose-dependent manner.

Topical application of recombinant activated factor VII during cesarean delivery for placenta previa.

PubMed

Schjoldager, Birgit T B G; Mikkelsen, Emmeli; Lykke, Malene R; Præst, Jørgen; Hvas, Anne-Mette; Heslet, Lars; Secher, Niels J; Salvig, Jannie D; Uldbjerg, Niels

2017-06-01

During cesarean delivery in patients with placenta previa, hemorrhaging after removal of the placenta is often challenging. In this condition, the extraordinarily high concentration of tissue factor at the placenta site may constitute a principle of treatment as it activates coagulation very effectively. The presumption, however, is that tissue factor is bound to activated factor VII. We hypothesized that topical application of recombinant activated factor VII at the placenta site reduces bleeding without affecting intravascular coagulation. We included 5 cases with planned cesarean delivery for placenta previa. After removal of the placenta, the surgeon applied a swab soaked in recombinant activated factor VII containing saline (1 mg in 246 mL) to the placenta site for 2 minutes; this treatment was repeated once if the bleeding did not decrease sufficiently. We documented the treatment on video recordings and measured blood loss. Furthermore, we determined hemoglobin concentration, platelet count, international normalized ratio, activated partial thrombin time, fibrinogen (functional), factor VII:clot, and thrombin generation in peripheral blood prior to and 15 minutes after removal of the placenta. We also tested these blood coagulation variables in 5 women with cesarean delivery planned for other reasons. Mann-Whitney test was used for unpaired data. In all 5 cases, the uterotomy was closed under practically dry conditions and the median blood loss was 490 (range 300-800) mL. There were no adverse effects of recombinant activated factor VII and we did not measure factor VII to enter the circulation. Neither did we observe changes in thrombin generation, fibrinogen, activated partial thrombin time, international normalized ratio, and platelet count in the peripheral circulation (all P values >.20). This study indicates that in patients with placenta previa, topical recombinant activated factor VII may diminish bleeding from the placenta site without initiation of systemic coagulation. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Platelet count

MedlinePlus

... sample from one person than another. Other slight risks from having blood drawn may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection ( ...

Comparison between a new platelet count drop method PL-11, light transmission aggregometry, VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals.

PubMed

Guan, Jie; Cong, Yulong; Ren, Junwei; Zhu, Yuan; Li, Li; Deng, Xinli; Bai, Jie

2015-01-01

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow™ aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100 mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5 ± 1 days, 8 ± 1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100 mg/d aspirin intake and began to recover during 4-6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r = 0.614, p < 0.01); PL-11 vs. VerifyNow (r = 0.829, p < 0.01); PL-11 vs. TEG (r = 0.697, p < 0.001). There was no significant bias between PL-11 and LTA at baseline (bias = 1.94%, p = 0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias = 24.02%, p < 0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA > 20%, the cut-off values for each method were, respectively: PL-11 > 50%, VerifyNow > 533 ARU, TEG > 60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.

Fever, thrombocytopenia, and AKI-A profile of malaria, dengue, and leptospirosis with renal failure in a South Indian tertiary-care hospital.

PubMed

Prabhu, Mayoor V; S, Arun; Ramesh, Venkat

In the tropics, the triad of fever, thrombocytopenia, and AKI portends a grim prognosis with high mortality and a severe strain on already-stretched resources. Malaria, dengue, and leptospirosis account for most cases. We undertook a review of cases to determine factors accounting for adverse prognosis. All patients presenting to the emergency room (ER) with a history of fever, thrombocytopenia, and renal failure were included in the study. Patients were followed until discharge or death, and end points looked at were 1-week and 30-day mortality, and renal function upon discharge. Parameters like liver function test (LFT), renal function, and platelet count upon discharge were also documented. A total of 43 patients was included in the study. Mean age was 42.5 years with 86% males. Mean APACHE and SOFA scores on admission were 23.89 and 15.42, respectively. Mean admission platelet counts were 41,000. Mean serum creatinine was 4.1, and bilirubin was 9.94. A platelet count of < 34,000, serum creatinine of > 4, albumin of > 2.3, SOFA score of > 20, and APACHE score of > 32.2 were significantly predictive of 1 week mortality. Need for mechanical ventilation, oliguria on admission, and need for dialysis all were highly predictive of 30-day mortality. In addition, a serum bicarbonate of < 12, INR of > 1.5, hemoglobin of < 9.5 were highly predictive of higher 30 day mortality. Overall, 1-week mortality was 16.3%, of which 48% was accounted for by patients with leptospirosis. Factors like low platelet count, oliguria, need for dialysis, high APACHE and SOFA scores on admission, need for mechanical ventilation, and low serum albumin portend a grave prognosis. There is need for randomized control trials (RCT) to further determine adverse prognostic factors in this subsect of patients.

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs.

PubMed

Makielski, Kelly M; Brooks, Marjory B; Wang, Chong; Cullen, Jonah N; O'Connor, Annette M; LeVine, Dana N

2018-04-21

A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Client-owned dogs (n = 61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGiBAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P < .0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (r s  = -0.527, P < .0001), and DOGiBAT directly correlated with transfusion requirements (r s  = 0.512, P < .0001) and hospitalization duration (r s  = 0.35, P = .006). The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials. Copyright © 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Retrospective Review of Platelet Transfusion Practices during 2013 Dengue Epidemic of Delhi, India.

PubMed

Chaurasia, Rahul; Zaman, Shamsuz; Chatterjee, Kabita; Das, Bankim

2015-07-01

Dengue infection is a major public health problem. During explosive outbreaks, there is sudden surge in demands of platelet products. The present study was carried out in order to review platelet transfusion practices during the epidemic of dengue. We retrospectively reviewed the clinical details including the platelet counts and haemorrhagic tendencies of dengue patients as well as the transfusion requirements of diagnosed dengue cases admitted at our centre. A total of 1,750 random donor platelet and 114 single donor platelet units were transfused to 531 patients. 23.2% platelet transfusions were found to be inappropriate Mean dosage of platelets transfused was 2 × 10(11) platelets per patient. A total of 347 (65.3%) patients had bleeding diathesis at the time of presentation. Skin and the oropharynx were the most common bleeding sites. Major bleeding was seen in 119 (34.3%) patients, whereas 228 (65.7%) patients had minor bleeding episodes. The study emphasises the need for minimising unnecessary transfusions and for using this scarce resource judiciously, which can be achieved by strict adherence to evidence-based transfusion guidelines and regular review of the on-going transfusion practices.

Can Platelet and Leukocyte Indicators Give Us an Idea about Distant Metastasis in Nasopharyngeal Cancer?

PubMed

Arıcıgil, Mitat; Dündar, Mehmet Akif; Yücel, Abitter; Arbağ, Hamdi; Aziz, Suhayb Kuria

This study aimes to evaluate platelet and leucocyte indicators, such as the mean platelet volume, platelet distribution width, plateletcrit, white blood cell count, neutrophil to lymphocyte ratio in nasopharyngeal cancer patients and also to evaluate the relationship between these indicators and nasopharyngeal cancer with distant metastasis. The medical records of 118 patients diagnosed with nasopharyngeal cancer in our hospital between January 2006 and August 2015 were reviewed. The nasopharyngeal cancer group was further sub grouped according to the presence or absence of distant metastasis and TNM (tumour - T, node - N, metastasis - M) classification. A control group consisted of 120 healthy patients. The platelet and leucocyte values at the time of the initial diagnosis were recorded. Neutrophil to lymphocyte ratio and platelet distribution width values were significantly higher in the nasopharyngeal cancer group. But only platelet distribution width values were significantly higher in the nasopharyngeal cancer group with distant metastasis compared to the nasopharyngeal cancer group without distant metastasis. Neutrophil to lymphocyte ratio and platelet distribution width values may increase in nasopharyngeal cancer. But only the platelet distribution width values may give us an idea about the distant metastasis in nasopharyngeal cancer.

Atypical Hemolytic Uremic Syndrome: A Meta-Analysis of Case Reports Confirms the Prevalence of Genetic Mutations and the Shift of Treatment Regimens.

PubMed

Krishnappa, Vinod; Gupta, Mohit; Elrifai, Mohamed; Moftakhar, Bahar; Ensley, Michael J; Vachharajani, Tushar J; Sethi, Sidharth Kumar; Raina, Rupesh

2018-04-01

Atypical hemolytic uremic syndrome (aHUS) is a rare life-threatening thrombotic microangiopathy (TMA) affecting multiple organ systems. Recently, aHUS has been shown to be associated with uncontrolled complement activation due to mutations in the alternative pathway of complement components paving the way for targeted drug therapy. By meta-analysis of case reports, we discuss the impact of new treatment strategies on the resolution time of aHUS symptoms and mortality, and the distribution of genetic mutations. A PubMed/Medline search was conducted for "atypical hemolytic uremic syndrome" case reports published between November 2005 and November 2015. R Version 3.2.2 was used to calculate descriptive statistics and perform univariate analyses. Wilcoxon rank-sum test was used to compare time to symptoms resolution, creatinine and platelet count normalization across the treatment and mutation carrier groups. A total of 259 aHUS patients were reported in 176 articles between 2005 and 2015. In the last 5-year period compared to the precedent, there was an increase in the number of aHUS cases reported (180 vs. 79 cases) and the use of eculizumab also increased (6.3% to 46.1%, P < 0.000), although plasma exchange usage did not change (P = 0.281). CFH antibodies were present in a significantly higher number of patients treated with plasma exchange therapy (19.1%, P = 0.000) while none of the non-plasma exchange therapy group had CFH antibodies. Most common mutation was CFH (50%, 69/139) followed by CFHR1 (35%, 30/85), MCP (22.8%, 23/101) and CFI (16.6%, 17/102). Time to symptoms resolution and serum creatinine or platelet count normalization were not significantly different between eculizumab and non-eculizumab group (P = 0.166, P = 0.361, P = 0.834), and between plasma exchange and non-plasma exchange group (P = 0.150, P = 0.135, P = 0.784). However, both eculizumab and plasma exchange groups had early platelet recovery (22 vs. 30 days and 25.5 vs. 32.5 days), faster creatinine normalization (27 vs. 30.5 days and 27 vs. 37 days) and interestingly, a longer period for symptoms resolution (45.5 vs. 21 days and 30 vs. 18.5 days) compared to non-eculizumab and non-plasma exchange groups. Mortality rate decreased with the use of eculizumab significantly (P = 0.045) compared to non-eculizumab group and there was no change in mortality rate with the use of plasma exchange therapy (P = 0.760) compared to non-plasma exchange group. Plasma exchange continues to be the initial treatment of choice for aHUS. Although significant reduction in the mortality rate was noted with the use of eculizumab, there were no differences in time to resolution of symptoms or serum creatinine or platelet normalization with the use of either eculizumab or plasma therapy. Atypical HUS is acute and life-threatening, so plasma exchange may be initiated before the confirmed diagnosis and in patients positive for CFH antibodies. Eculizumab therapy should be considered once aHUS is confirmed by genetic testing. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets

PubMed Central

Naik, Meghna U.; Stalker, Timothy J.; Brass, Lawrence F.

2012-01-01

Mounting evidence suggests that agonist-initiated signaling in platelets is closely regulated to avoid excessive responses to injury. A variety of physiologic agonists induce a cascade of signaling events termed as inside-out signaling that culminate in exposure of high-affinity binding sites on integrin αIIbβ3. Once platelet activation has occurred, integrin αIIbβ3 stabilizes thrombus formation by providing agonist-independent “outside-in” signals mediated in part by contractile signaling. Junctional adhesion molecule A (JAM-A), a member of the cortical thymocyte marker of the Xenopus (CTX) family, was initially identified as a receptor for a platelet stimulatory mAb. Here we show that JAM-A in resting platelets functions as an endogenous inhibitor of platelet function. Genetic ablation of Jam-A in mice enhances thrombotic function of platelets in vivo. The absence of Jam-A results in increase in platelet aggregation ex vivo. This gain of function is not because of enhanced inside-out signaling because granular secretion, Thromboxane A2 (TxA2) generation, as well as fibrinogen receptor activation, are normal in the absence of Jam-A. Interestingly, integrin outside-in signaling such as platelet spreading and clot retraction is augmented in Jam-A–deficient platelets. We conclude that JAM-A normally limits platelet accumulation by inhibiting integrin outside-in signaling thus preventing premature platelet activation. PMID:22271446

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.

Tetraspanin Tspan9 regulates platelet collagen receptor GPVI lateral diffusion and activation

PubMed Central

Haining, Elizabeth J.; Matthews, Alexandra L.; Noy, Peter J.; Romanska, Hanna M.; Harris, Helen J.; Pike, Jeremy; Morowski, Martina; Gavin, Rebecca L.; Yang, Jing; Milhiet, Pierre-Emmanuel; Berditchevski, Fedor; Nieswandt, Bernhard; Poulter, Natalie S.; Watson, Steve P.; Tomlinson, Michael G.

2017-01-01

Abstract The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels. A GPVI activation defect was suggested by partially impaired GPVI-induced protein tyrosine phosphorylation. In mechanistic experiments, Tspan9 and GPVI co-immunoprecipitated and co-localised, but super-resolution imaging revealed no defects in collagen-induced GPVI clustering on Tspan9-deficient platelets. However, single particle tracking using total internal reflection fluorescence microscopy showed that GPVI lateral diffusion was reduced by approximately 50% in the absence of Tspan9. Therefore, Tspan9 plays a fine-tuning role in platelet activation by regulating GPVI membrane dynamics. PMID:28032533

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2010 CFR

2010-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2013 CFR

2013-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2014 CFR

2014-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

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.

Erythrocyte and platelet fatty acids in retinitis pigmentosa.

PubMed

Stanzial, A M; Bonomi, L; Cobbe, C; Olivieri, O; Girelli, D; Trevisan, M T; Bassi, A; Ferrari, S; Corrocher, R

1991-05-01

The fatty acid composition and the glutathione-peroxidase activity (GSH-Px) of erythrocytes and platelets, the production of malondialdehyde (MDA) by platelets and the activity of the main systems of transmembrane cation transport in erythrocyte have been studied in 12 patients (5 males and 7 females) affected by retinitis pigmentosa (RP). A remarkable increase of saturated fatty acids (SFA), particularly of stearic acid (C18:0), has been noted in these patients. The reduced unsaturated/saturated fatty acids ratio (PUFA/SFA) observed in both erythrocytes and platelets and the decrease of arachidonic acid in platelets may depend by an active peroxidation process as documented by the increase of MDA. Platelet glutathione-peroxidase (PTL-GSH-PX) and plasma retinol were in the normal range, whereas erythrocyte glutathione-peroxidase (E-GSH-PX), MDA and plasma alfa-toco-pherol were increased in patients with RP. The activities of Na(+)-K+ pump, cotransport and Na(+)-Li+ countertransport were normal in RP erythrocytes.

Does an alteration of dialyzer design and geometry affect biocompatibility parameters?

PubMed

Opatrný, Karel; Krouzzecký, Ales; Polanská, Kamila; Mares, Jan; Tomsů, Martina; Bowry, Sudhir K; Vienken, Jörg

2006-04-01

The aim of the study was to assess the biocompatibility profile of a newly developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class of dialyzers incorporates a number of novel design features (including a new membrane) that have been developed specifically in order to enhance the removal of small- and middle-size molecules. The new FX dialyzer series was compared with the classical routinely used high-flux polysulfone F series of dialyzers. In an open prospective, randomized, crossover clinical study, concentrations of the C5a complement component, and leukocyte count in blood and various thrombogenicity parameters were evaluated before, and at 15 and 60 min of hemodialysis at both dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S dialyzers and, after crossover, the classical F60S, while in another 9 patients, the evaluation was made with the dialyzers used in reverse order. The comparison of dialyzers based on evaluation of the group including all procedures with the FX60S and the group including procedures with the F60S did not reveal significant differences in platelet count, activated partial thromboplastin times, plasma heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point of the collecting period. Both dialyzer types showed a significant increase in the plasma levels of the thrombin-antithrombin III complexes; however, the measured levels were only slightly elevated compared with the upper end of the normal range. Biocompatibility parameters reflecting the behavior of platelets, fibrinolysis, complement activation, and leukopenia do not differ during dialysis with either the FX60S or the F60S despite their large differences in design and geometry features. Although coagulation activation, as evaluated by one of the parameters used, was slightly higher with the FX60S, it was still within the range seen with other highly biocompatible dialyzers and therefore is not indicative of any appreciable activation of the coagulation system. Thus, the incorporation of various performance-enhancing design features into the new FX class of dialyzers does not result in a deterioration of their biocompatibility profile, which is comparable to that of the classical F series of dialyzers.

Predictive value of some hematological parameters for non-invasive and invasive mole pregnancies.

PubMed

Abide Yayla, Cigdem; Özkaya, Enis; Yenidede, Ilter; Eser, Ahmet; Ergen, Evrim Bostancı; Tayyar, Ahter Tanay; Şentürk, Mehmet Baki; Karateke, Ates

2018-02-01

The aim of this study was to discriminate mole pregnancies and invasive forms among cases with first trimester vaginal bleeding by the utilization of some complete blood count parameters conjunct to sonographic findings and beta human chorionic gonadotropin concentration. Consecutive 257 cases with histopathologically confirmed mole pregnancies and 199 women without mole pregnancy presented with first trimester vaginal bleeding who admitted to Zeynep Kamil Women and Children's Health Training Hospital between January 2012 and January 2016 were included in this cross-sectional study. The serum beta HCG level at presentation, and beta hCG levels at 1st, 2nd and 3rd weeks of postevacuation with some parameters of complete blood count were utilized to discriminate cases with molar pregnancy and cases with invasive mole among first trimester pregnants presented with vaginal bleeding and abnormal sonographic findings. Levels of beta hCG at baseline (AUC = 0.700, p < 0.05) and 1st (AUC = 0.704, p < 0.05), 2nd (AUC = 0.870, p < 0.001) and 3rd (AUC = 0.916, p < 0.001) weeks of postevacuation period were significant predictors for the cases with persistent disease. While area under curve for mean platelet volume is 0.715, it means that mean platelet volume has 21.5% additional diagnostic value for predicting persistency in molar patients. For 8.55 cut-off point for mean platelet volume, sensitivity is 84.6% and specificity is 51.6%. Area under curve for platelet/lymphocyte ratio is 0.683 means that platelet/lymphocyte ratio has additional 18.3% diagnostic value. For 102.25 cut-off point sensitivity is 86.6% and specificity is 46.2. Simple, widely available complete blood count parameters may be used as an adjunct to other risk factors to diagnose molar pregnancies and predict postevacuation trophoblastic disease.

Platelets as delivery systems for disease treatments

PubMed Central

Shi, Qizhen; Montgomery, Robert R.

2010-01-01

Platelets are small, anucleate, discoid shaped blood cells that play a fundamental role in hemostasis. Platelets contain a large number of biologically active molecules within cytoplasmic granules that are critical to normal platelet function. Because platelets circulate in blood through out the body, release biological molecules and mediators on demand, and participate in hemostasis as well as many other pathophysiologic processes, targeting expression of proteins of interest to platelets and utilizing platelets as delivery systems for disease treatment would be a logical approach. This paper reviews the genetic therapy for inherited bleeding disorders utilizing platelets as delivery system, with a particular focus on platelet-derived FVIII for hemophilia A treatment. PMID:20619307

Human plasma platelet-derived exosomes: effects of aspirin.

PubMed

Goetzl, Edward J; Goetzl, Laura; Karliner, Joel S; Tang, Norina; Pulliam, Lynn

2016-05-01

Platelet-derived exosomes mediate platelet atherogenic interactions with endothelial cells and monocytes. A new method for isolation of plasma platelet-derived exosomes is described and used to examine effects of aging and aspirin on exosome cargo proteins. Exosome secretion by purified platelets in vitro did not increase after exposure to thrombin or collagen, as assessed by exosome counts and quantification of the CD81 exosome marker. Thrombin and collagen increased exosome content of α-granule chemokines CXCL4 and CXCL7 and cytoplasmic high-mobility group box 1 (HMGB1) protein, but not membrane platelet glycoprotein VI (GPVI), with dependence on extracellular calcium. Aspirin consumption significantly blocked thrombin- and collagen-induced increases in exosome cargo levels of chemokines and HMGB1, without altering total exosome secretion or GPVI cargo. Plasma platelet-derived exosomes, enriched by absorption with mouse antihuman CD42b [platelet glycoprotein Ib (GPIb)] mAb, had sizes and cargo protein contents similar to those of exosomes from purified platelets. The plasma platelet-derived exosome number is lower and its chemokine and HMGB1 levels higher after age 65 yr. Aspirin consumption significantly suppressed cargo protein levels of plasma platelet-derived exosomes without altering total levels of exosomes. Cargo proteins of human plasma platelet-derived exosomes may biomark platelet abnormalities and in vivo effects of drugs.- Goetzl, E. J., Goetzl, L., Karliner, J. S., Tang, N., Pulliam, L. Human plasma platelet-derived exosomes: effects of aspirin. © FASEB.

In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin

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

Pumphrey, C.W.; Chesebro, J.H.; Dewanjee, M.K.

Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with amore » gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.« less

Neutrophil, lymphocyte and platelet counts, and risk of prostate cancer outcomes in white and black men: results from the SEARCH database.

PubMed

Vidal, Adriana C; Howard, Lauren E; de Hoedt, Amanda; Cooperberg, Matthew R; Kane, Christopher J; Aronson, William J; Terris, Martha K; Amling, Christopher L; Taioli, Emanuela; Fowke, Jay H; Freedland, Stephen J

2018-06-01

Systemic inflammation, as measured by C-reactive protein, has been linked with poor prostate cancer (PC) outcomes, predominantly in white men. Whether other immune measures like white blood cell counts are correlated with PC progression and whether results vary by race is unknown. We examined whether complete blood count (CBC) parameters were associated with PC outcomes and whether these associations varied by race. Analyses include 1,826 radical prostatectomy patients from six VA hospitals followed through medical record review for biochemical recurrence (BCR). Secondary outcomes included castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific mortality (PCSM). Cox-proportional hazards were used to assess the associations between pre-operative neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with each outcome. We used a Bonferroni-corrected p-value of 0.05/5 = 0.01 as the threshold for statistical significance. Of 1,826 men, 794 (43%) were black and 1,032 (57%) white. Neutrophil count (p < 0.001), NLR (p < 0.001), and PLR (p < 0.001) were significantly lower, while lymphocyte count (p < 0.001) was significantly higher in black versus white men. After adjusting for clinicopathological features, no CBC measures were significantly associated with BCR. There were no interactions between CBC and race in predicting BCR. Similarly, no CBC values were significantly associated with CRPC, metastases, or PCSM either among all men or when stratified by race. However, higher neutrophil count was associated with higher ACM risk in white men (p = 0.004). Pre-operative CBC measures were not associated with PC outcomes in black or white men undergoing radical prostatectomy, except for neutrophils-positive association with risk of ACM in white men. Whether circulating immune cell markers provide insight to the pathophysiology of PC progression or adverse treatment outcomes requires further study.

Platelet activation and function in response to high intensity interval exercise and moderate continuous exercise in CABG and PCI patients.

PubMed

Ahmadizad, Sajad; Nouri-Habashi, Akbar; Rahmani, Hiwa; Maleki, Majid; Naderi, Nasim; Lotfian, Sara; Salimian, Morteza

2016-01-01

The effects of high intensity interval training (HIIT) on inflammatory markers and endothelial function have been extensively shown. However, the acute effect of HIIT on platelet activation and function in patients with recent revascularization is unclear. The purpose of present study was to compare the responses of platelet activation (CD62P) and function (platelet aggregation) to high intensity interval exercise (HIIE) and moderate continuous exercise (MCE) in coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) patients. Thirty patients who had CABG or PCI were randomly divided into HIIE, MCE and control groups. After determining the VO2peak, subjects in the MCE group carried out 30 min of continuous exercise at 60% of VO2peak, whereas, the subjects in HIIE group performed an interval protocol consisted of 8 repetitions of 2 min activity (running on treadmill) at 90% of VO2peak interspersed by 2 min of active recovery between repetitions at 30% of VO2peak .  Subjects in control group were seated and had no activity for the same period of time. Two blood samples were collected before and immediately after exercise and were analyzed for markers of platelet activation and function. Data analyzes revealed that increases in platelet aggregation induced by ADP and corrected for increases in platelet count in response to MCE trial was significantly lower than HIIE group (P < 0.05). In addition, responses of CD62P to MCE trial was significantly lower compared to HIIE group (P < 0.05). Changes in plateletcrit and platelet distribution width were significantly different among the three trials where the PCT and PDW following the HIIE were higher than MCE. Platelet count increased significantly (P < 0.05) by 13% following HIIE trial. Based on the findings of the present study it could be concluded that the risk of exercise-induced thrombosis is higher during HIIE than MCE in patients with recent revascularization.

Reactivity of mouse antibodies against bromelain-treated mouse erythrocytes with thrombin-treated mouse platelets.

PubMed Central

Kawaguchi, S

1989-01-01

The reactivity of mouse antibodies against bromelain-treated mouse erythrocytes (BrMRBC) with mouse platelets before and after thrombin treatment was assessed by flow cytometry. Anti-BrMRBC antibodies could bind to thrombin-treated platelets, although normal platelets were also weakly reactive with the antibodies. The binding of anti-BrMRBC antibodies to platelets was confirmed by complement-dependent lysis. It is suggested that thrombin-activated platelets may be a real target for anti-BrMRBC antibodies. PMID:2467876

Authorising bortezomib treatment prior to reviewing haematology results: a step toward home administration.

PubMed

Waight, Clinton C; Cain, Rebecca

2014-10-01

Bortezomib treatment requires four visits to a chemotherapy unit in each 21-day cycle. Analysis of the Day 1 full blood count could allow clinicians to predict the risk of Grade 4 thrombocytopenia, thus negating the need to review the full blood count prior to each dose. The freedom to administer bortezomib without reviewing full blood count results on each treatment day could minimise appointment times and be a step toward home administration. A prospective study of treatment authorisation following a full toxicity assessment and full blood count results from the previous treatment day was undertaken. The full blood count results from 27 patients, receiving 381 doses revealed 12 treatment episodes where bortezomib was administered in the presence of Grade 4 thrombocytopenia. One instance of bleeding and two episodes of neutropenic sepsis were detected during toxicity assessments and treatment was not administered. Only one instance of Grade 4 thrombocytopenia was reported on any other treatment day when the Day 1 platelet count was greater than 75 × 10(9) units/l. From this data, Day 1 full blood count parameters were derived, which minimise the risk of Grade 4 haematological toxicity on subsequent treatment days, allowing clinicians to identify suitable patients for administration of bortezomib prior to reviewing full blood count results. When platelet counts on Day 1 are greater than 75 × 10(9) units/l and neutrophil counts are greater than 1.0 × 10(9) units/l, the administration of bortezomib can be authorised without the need for review of the full blood count on subsequent days of that cycle. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Rho GTPases and their downstream effectors in megakaryocyte biology.

PubMed

Pleines, Irina; Cherpokova, Deya; Bender, Markus

2018-06-18

Megakaryocytes differentiate from hematopoietic stem cells in the bone marrow. The transition of megakaryocytes to platelets is a complex process. Thereby, megakaryocytes extend proplatelets into sinusoidal blood vessels, where the proplatelets undergo fission to release platelets. Defects in platelet production can lead to a low platelet count (thrombocytopenia) with increased bleeding risk. Rho GTPases comprise a family of small signaling G proteins that have been shown to be master regulators of the cytoskeleton controlling many aspects of intracellular processes. The generation of Pf4-Cre transgenic mice was a major breakthrough that enabled studies in megakaryocyte-/platelet-specific knockout mouse lines and provided new insights into the central regulatory role of Rho GTPases in megakaryocyte maturation and platelet production. In this review, we will summarize major findings on the role of Rho GTPases in megakaryocyte biology with a focus on mouse lines in which knockout strategies have been applied to study the function of the best-characterized members Rac1, Cdc42 and RhoA and their downstream effector proteins.

Cholesterol efflux in megakaryocyte progenitors suppresses platelet production and thrombocytosis

PubMed Central

Murphy, Andrew J.; Bijl, Nora; Yvan-Charvet, Laurent; Welch, Carrie B.; Bhagwat, Neha; Reheman, Adili; Wang, Yiming; Shaw, James A.; Levine, Ross L.; Ni, Heyu; Tall, Alan R.; Wang, Nan

2013-01-01

Platelets play a key role in atherogenesis and its complications. Both hypercholesterolemia and increased platelet production promote athero-thrombosis; however, a potential link between altered cholesterol homeostasis and platelet production has not been explored. Transplantation of bone marrow (BM) deficient in ABCG4, a transporter of unknown function, into Ldlr−/− mice resulted in thrombocytosis, accelerated thrombosis and atherosclerosis. While not detected in lesions, Abcg4 was highly expressed in BM megakaryocyte progenitors (MkP). Abcg4−/− MkPs displayed defective cholesterol efflux to HDL, increased cell surface levels of thrombopoietin (TPO) receptor (c-MPL) and enhanced proliferation. This appeared to reflect disruption of the negative feedback regulation of c-MPL levels and signaling by E3 ligase c-CBL and cholesterol-sensing LYN kinase. HDL infusions reduced platelet counts in Ldlr−/− mice and in a mouse model of myeloproliferative neoplasm, in a completely ABCG4-dependent fashion. HDL infusions may offer a novel approach to reducing athero-thrombotic events associated with increased platelet production. PMID:23584088

Heparin-induced thrombocytopenia: real-world issues.

PubMed

Linkins, Lori-Ann; Warkentin, Theodore E

2011-09-01

Heparin-induced thrombocytopenia (HIT) is a prothrombotic drug reaction caused by platelet-activating antibodies. HIT sera often activate platelets without needing heparin-such heparin-"independent" platelet activation can be associated with HIT beginning or worsening despite stopping heparin ("delayed-onset HIT"). We address important issues in HIT diagnosis and therapy, using a recent cohort of HIT patients to illustrate influences of heparin type; triggers for HIT investigation; serological features of heparin-independent platelet activation; and treatment. In our cohort of recent HIT cases ( N = 13), low-molecular-weight heparin (dalteparin) was a common causative agent ( N = 8, 62%); most patients were diagnosed after HIT-thrombosis had occurred; and danaparoid was the most frequently selected treatment. Heparin-independent platelet activation was common (7/13 [54%]) and predicted slower platelet count recovery (>1 week) among evaluable patients (5/5 vs 1/6; P = 0.015). In our experience with argatroban-treated patients, HIT-associated consumptive coagulopathy confounds anticoagulant monitoring. Our observations provide guidance on practical aspects of HIT diagnosis and management. Thieme Medical Publishers.

A microfluidic biochip for complete blood cell counts at the point-of-care

PubMed Central

Hassan, U.; Reddy, B.; Damhorst, G.; Sonoiki, O.; Ghonge, T.; Yang, C.; Bashir, R.

2016-01-01

Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world. PMID:26909365

A microfluidic biochip for complete blood cell counts at the point-of-care.

PubMed

Hassan, U; Reddy, B; Damhorst, G; Sonoiki, O; Ghonge, T; Yang, C; Bashir, R

2015-12-01

Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world.

Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome. A prospective randomized double-blind study.

PubMed

Everts, P A; Devilee, R J J; Brown Mahoney, C; van Erp, A; Oosterbos, C J M; Stellenboom, M; Knape, J T A; van Zundert, A

2008-01-01

Platelet-leukocyte gel (PLG) is being used during various surgical procedures in an attempt to enhance the healing process. We studied the effects of PLG on postoperative recovery of patients undergoing open subacromial decompression (OSD). PLG was produced from platelet-leukocyte-rich plasma (P-LRP), prepared from a unit of whole blood. Forty patients were included in the study. Self-assessed evaluations, using the American Shoulder and Elbow Surgeons scoring system of activities of daily living (ADL), joint instability, pain levels, pain medications, and clinical evaluations for range of motion were conducted. Platelet and leukocyte counts were significantly increased in the P-LRP compared to baseline counts. Treated patients demonstrated decreased visual analog scales for pain and used significantly less pain medication, had an improved range of motion during passive forward elevation, external rotation, external rotation with arm at 90 degrees abduction, internal rotation, and cross body adduction compared to control patients (p < 0.001). No differences in the instability score were observed between the groups. Furthermore, treated patients performed more ADL (p < 0.05). In the PLG-treated group, recovery was faster and patients returned earlier to daily activities and also took less pain medication than control subjects. Copyright 2008 S. Karger AG, Basel.

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.

The role of platelet and endothelial GARP in thrombosis and hemostasis.

PubMed

Vermeersch, Elien; Denorme, Frederik; Maes, Wim; De Meyer, Simon F; Vanhoorelbeke, Karen; Edwards, Justin; Shevach, Ethan M; Unutmaz, Derya; Fujii, Hodaka; Deckmyn, Hans; Tersteeg, Claudia

2017-01-01

Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice.

The role of platelet and endothelial GARP in thrombosis and hemostasis

PubMed Central

Vermeersch, Elien; Denorme, Frederik; Maes, Wim; De Meyer, Simon F.; Vanhoorelbeke, Karen; Edwards, Justin; Shevach, Ethan M.; Unutmaz, Derya; Fujii, Hodaka; Deckmyn, Hans; Tersteeg, Claudia

2017-01-01

Background Glycoprotein-A Repetitions Predominant protein (GARP or LRRC32) is present on among others human platelets and endothelial cells. Evidence for its involvement in thrombus formation was suggested by full knockout of GARP in zebrafish. Objectives To evaluate the role of GARP in platelet physiology and in thrombus formation using platelet and endothelial conditional GARP knock out mice. Methods Platelet and endothelial specific GARP knockout mice were generated using the Cre-loxP recombination system. The function of platelets without GARP was measured by flow cytometry, spreading analysis and aggregometry using PAR4-activating peptide and collagen related peptide. Additionally, clot retraction and collagen-induced platelet adhesion and aggregation under flow were analyzed. Finally, in vivo tail bleeding time, occlusion time of the mesenteric and carotid artery after FeCl3-induced thrombosis were determined in platelet and endothelial specific GARP knock out mice. Results Platelet specific GARP knockout mice had normal surface GPIb, GPVI and integrin αIIb glycoprotein expression. Although GARP expression was increased upon platelet activation, platelets without GARP displayed normal agonist induced activation, spreading on fibrinogen and aggregation responses. Furthermore, absence of GARP on platelets did not influence clot retraction and had no impact on thrombus formation on collagen-coated surfaces under flow. In line with this, neither the tail bleeding time nor the occlusion time in the carotid- and mesenteric artery after FeCl3-induced thrombus formation in platelet or endothelial specific GARP knock out mice were affected. Conclusions Evidence is provided that platelet and endothelial GARP are not important in hemostasis and thrombosis in mice. PMID:28278197

Evaluation of blood neutrophil-lymphocyte ratio and platelet distribution width as inflammatory markers in patients with fibromyalgia.

PubMed

Aktürk, Semra; Büyükavcı, Raikan

2017-08-01

Fibromyalgia syndrome (FMS) is characterized by chronic widespread pain and systemic symptoms. The aetiology and pathogenesis of fibromyalgia are not yet fully understood. Blood neutrophil/lymphocyte ratio (NLR) is a marker of systemic inflammatory response. Platelet distribution width (PDW) and mean platelet volume (MPV) are the determinants of platelet activation and studied as markers in inflammatory diseases. The aim of the present study was to evaluate levels of NLR,PDW and MPV in patients with fibromyalgia. A total of 197 FMS patients and 53 healthy controls are included in the study. Demographic characteristics, erythrocyte sedimentation rate, C-reactive protein, neutrophil, lymphocyte and platelet counts, platelet distribution width and mean platelet volume levels were recorded. In the patient group, the blood NLR and MPV were significantly higher and the PDW was significantly lower compared to the control group. In the roc curve analysis, blood PDW ≥had 90.4% sensitivity and 90% specificity in predicting fibromyalgia. The results of this study suggest NLR and PDW as promising inflammatory markers indicating fibromyalgia and may be beneficial in facilitating the diagnosis of FMS patients.

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.

Hemopoietic progenitor cell function after HLA-identical sibling bone marrow transplantation: influence of chronic graft-versus-host disease.

PubMed

Atkinson, K; Norrie, S; Chan, P; Zehnwirth, B; Downs, K; Biggs, J

1986-05-01

We examined hemopoietic reconstitution during the first 12 months post-transplant in 31 patients given high-dose cyclophosphamide, total body irradiation and an HLA-identical sibling marrow transplant for hematological malignancy. Unexpectedly, we found marrow CFU-gm and marrow CFU-e cells to be denser than normal throughout the first year post-transplant. While functionally adequate neutrophil and platelet counts were achieved in the first six weeks post-transplant, there were defects in hemopoietic progenitor cell function during the first year post-transplant. Although we could detect no influence from acute graft-versus-host disease (GVHD), chronic GVHD adversely affected the growth of both myeloid and erythroid blood progenitor cells.

[Isolated severe neurologic disorders in post-partum: posterior reversible encephalopathy syndrome].

PubMed

Wernet, A; Benayoun, L; Yver, C; Bruno, O; Mantz, J

2007-01-01

Just after Caesarean section for twin pregnancy and feto-pelvic dysproportion, a woman presented severe headaches and arterial hypertension, then blurred vision, then generalised seizures. There were no oedematous syndrome, proteinuria was negative, ASAT were 1.5 N and platelet count was 120,000/mm(3). Cerebral CT-scan was normal. Posterior reversible encephalopathy syndrome (PRES) was diagnosed on MRI. A second MRI performed at day 9 showed complete regression of cerebral lesions, while patient was taking anti-hypertensive and antiepileptic drugs. PRES has to be evoked in post-partum central neurological symptoms, even in absence of classical sign of pre-eclampsia, like proteinuria. PRES and eclampsia share probably common physiopathological pathways. There management and prognosis seems identical.

Mild thrombocytopenia as presenting symptom of type 1 Gauchers's disease.

PubMed

Müzes, G; Pitlik, E; Somogyi, A; Tulassay, Z

2001-06-01

A young woman was examined for a mild thrombocytopenia which was present for some months. No signs of bleeding had so far occurred. Physical examination was normal except for a moderately enlarged spleen. Laboratory investigations showed a low platelet count. There was no evidence of an autoimmune or hematologic disease. Bone narrow aspirate indicated Gaucher's-like cells raising the suspicion of Gaucher's disease. This was further supported by electron microscopic demonstration of Gaucher's bodies in crista biopsy specimens. However, the definitive diagnosis was obtained by verifying deficient lysosomal glucosylceramide-beta-D-glucosidase activity in peripheral blood leukocytes. Upon the absence of neurologic involvement the patient was typical for the adult-onset or type 1 form of Gaucher's disease.

Role for Neutrophil Extracellular Traps (NETs) and Platelet Aggregation in Early Sepsis-induced Hepatic Dysfunction.

PubMed

Sakurai, Kentaro; Miyashita, Tomoharu; Okazaki, Mitsuyoshi; Yamaguchi, Takahisa; Ohbatake, Yoshinao; Nakanuma, Shinichi; Okamoto, Koichi; Sakai, Seisho; Kinoshita, Jun; Makino, Isamu; Nakamura, Keishi; Hayashi, Hironori; Oyama, Katsunobu; Tajima, Hidehiro; Takamura, Hiroyuki; Ninomiya, Itasu; Fushida, Sachio; Harada, Kenichi; Harmon, John W; Ohta, Tetsuo

2017-01-01

Severe sepsis is associated with high morbidity and mortality rates. Inflammation and coagulation play pivotal roles in the pathogenesis of sepsis leading to multiple organ failure, especially in the liver. The aim of the present study was to assess the mechanism from sepsis to liver damage in a mouse model. We created a sepsis model by injecting lipopolysaccharide (LPS) intraperitoneally in mice. At 0, 6, 12, and 24 h following intraperitoneal injection of LPS, mice were euthanised and analyzed. Primary antibodies against myeloperoxidase (MPO), hepatic sinusoidal endothelial cells (SE-1), and P-selectin (CD62p) were used. Expression and localization in neutrophil, sinusoidal endothelial, and platelet cells were assessed by immunohistochemistry. Immunohistochemical analyses revealed a positive staining for MPO, most abundantly in neutrophil granulocytes, within the hepatic sinusoids immediately after injection. Neutrophil extracellular trap (NET)-like structures stained for MPO, indicating the presence of neutrophils undergoing NETosis, were confirmed at 6 h after LPS administration. SE-1 staining for liver sinusoidal endothelial cells was significantly reduced at 12 h post-LPS administration through sinusoidal endothelial injury or detachment. Furthermore, the presence of extravasated platelets was confirmed in the space of Disse at 24 h after LPS administration. Blood sample analyses showed that white blood cell counts and platelet counts decreased gradually, while MPO amounts increased until 12 h after LPS administration. We conclude that NET formation and intravasated platelet aggregation are the first steps from sepsis to liver damage, and that extravasated platelet aggregation promoted by NET-facilitated detachment of sinusoidal endothelial cells is the origin of sepsis-induced liver dysfunction. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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.

The feed gas composition determines the degree of physical plasma-induced platelet activation for blood coagulation

NASA Astrophysics Data System (ADS)

Bekeschus, Sander; Brüggemeier, Janik; Hackbarth, Christine; Weltmann, Klaus-Dieter; von Woedtke, Thomas; Partecke, Lars-Ivo; van der Linde, Julia

2018-03-01

Cold atmospheric (physical) plasma has long been suggested to be a useful tool for blood coagulation. However, the clinical applicability of this approach has not been addressed sufficiently. We have previously demonstrated the ability of a clinically accepted atmospheric pressure argon plasma jet (kINPen® MED) to coagulate liver incisions in mice with similar performance compared to the gold standard electrocauterization. We could show that plasma-mediated blood coagulation was dependent on platelet activation. In the present work, we extended on this by investigating kINPen®-mediated platelet activation in anticoagulated human donor blood ex vivo. With focus on establishing high-throughput, multi-parametric platelet activation assays and performing argon feed gas parameter studies we achieved the following results: (i) plasma activated platelets in heparinized but not in EDTA-anticoagulated blood; (ii) plasma decreased total platelet counts but increased numbers of microparticles; (iii) plasma elevated the expression of several surface activation markers on platelets (CD62P, CD63, CD69, and CD41/61); (iv) in platelet activation, wet and dry argon plasma outperformed feed gas admixtures with oxygen and/or nitrogen; (v) plasma-mediated platelet activation was accompanied by platelet aggregation. Platelet aggregation is a necessary requirement for blood clot formation. These findings are important to further elucidate molecular details and clinical feasibility of cold physical plasma-mediated blood coagulation.

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.

Comparative evaluation of antiplatelet effect of lycopene with aspirin and the effect of their combination on platelet aggregation: An in vitro study.

PubMed

Sawardekar, Swapna B; Patel, Tejal C; Uchil, Dinesh

2016-01-01

The objective was to compare antiplatelet effect of lycopene with aspirin and to study effect of combination of the two on platelet aggregation in vitro, using platelets from healthy volunteers. Platelets were harvested; platelet count of platelet-rich plasma adjusted to 2.5 Χ 10(5)/μL. Aspirin (140 μmol/L) and lycopene (4, 6, 8, 10, and 12 μmol/L) were studied in vitro against adenosine-5'- diphosphate (ADP) (2.5 μM/L) and collagen. All the concentrations of lycopene (4-12 μmol/L) exhibited reduction in maximum platelet aggregation induced by aggregating agents ADP and collagen (P < 0.01 vs. vehicle) and were comparable with aspirin. Lycopene at concentration 10 μmol/L showed maximum platelet inhibition (47.05% ± 19.56%) against ADP, whereas lycopene at concentration 8 μmol/L showed maximum platelet inhibition (54.26% ± 30.71%) against collagen. Four μmol/L of lycopene combined with 140 μmol/L and 70 μmol/L aspirin showed greater inhibition of platelets as compared to aspirin 140 μmol/L alone, against both ADP and collagen. The study favorably compares lycopene and aspirin with respect to their antiplatelet activities against ADP and collagen. Lycopene can be considered as a potential target for modifying the thrombotic and pro-inflammatory events associated with platelet activation.

Platelet activation in pregnancy-induced hypertension.

PubMed

Karalis, Ioannis; Nadar, Sunil K; Al Yemeni, Eman; Blann, Andrew D; Lip, Gregory Y H

2005-01-01

Although excess platelet activation, as indicated by increased plasma beta thromboglobulin (beta-TG), has been shown in pregnancy-induced hypertension (PIH), platelet adhesion, platelet morphology and a comparison of platelet and soluble (plasma) levels of the adhesion molecules P-selectin (pPsel and sPsel, respectively) have not been studied. We conducted a cross-sectional study of 35 consecutive women with PIH (age 31+/-6 years), 31 consecutive women with normotensive pregnancies (age 29+/-5 years) and 30 normotensive non pregnant women (age 30+/-5 years). Platelet adhesion was studied in vitro by binding to fibrinogen-coated microwells, platelet morphology [mass and volume by flow cytometry], whole-platelet P-selectin (pPsel) by ELISA of the lysate of 2 x 10(8) cells, and the plasma markers soluble P-selectin (sP-sel) and beta-TG, by ELISA. The women with PIH had significantly raised sPsel, pPsel and (as expected) beta-TG (all p<0.05), when compared to the normotensive pregnant women and controls. However, in PIH platelet adhesion was similar to that in the normotensive pregnancy, but still higher than the normal controls (p<0.001). There was no difference among the three groups with respect to platelet mass and volume. pPsel and platelet adhesion correlated with gestational age and with systolic and diastolic blood pressure (all p<0.05). Increased platelet activation and adhesion develop during normal pregnancy, with some indices being further altered in PIH.

Rebound coagulopathy in patients with snakebite presenting with marked initial coagulopathy.

PubMed

Witham, Willam R; McNeill, Cathy; Patel, Sunny

2015-06-01

An estimated 70% of patients with pit viper snakebites require antivenom to treat serious complications such as coagulopathy. Evidence-based guidance is limited for the appropriate administration of Crotalinae Polyvalent Immune Fab (FabAV) and the duration of laboratory follow-up. The objective of our study was to assess the incidence of marked and recurrent envenomation coagulopathy at our trauma center and identify practice patterns that may prevent serious complications. A retrospective case review was conducted over a 3-year period on patients treated for symptomatic snakebite injury. Case records were reviewed for the inclusion criteria of international normalized ratio (INR) greater than 2.0. The exclusion criterion was limited to patients receiving anticoagulant therapy. In all, 61 patients were identified on retrospective chart review and 3 patients (4.9%) met inclusion criteria. Two of the 3 patients had marked rebound coagulopathy requiring readmission and additional treatment. In our small series, 2 patients presenting after crotaline envenomation with increased INR (>6.0), decreased fibrinogen (<60 mg/dL), and decreased platelet count (<100,000/mL) had recurrent coagulopathy and were asymptomatic, and recurrence was noted only with follow-up laboratory testing. All patients responded positively within a matter of hours to repeat FabAV administration, with resolution of rebound coagulopathy. We recommend periodic monitoring of patients with increased INR, decreased fibrinogen, and decreased platelet count. Patients should be monitored for 10 to 14 days after envenomation to identify asymptomatic rebound coagulopathy. Prompt readministration of FabAV appears to correct the coagulopathy. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Durability of small-for-size living donor allografts.

PubMed

Au, Kin Pan; Chan, See Ching; Chok, Kenneth Siu Ho; Chan, Albert Chi Yan; Wong, Tiffany Cho Lam; Sharr, William Wei; Lo, Chung Mau

2015-11-01

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals. © 2015 American Association for the Study of Liver Diseases.

Treatment and Prevention of Heparin-Induced Thrombocytopenia

PubMed Central

Dans, Antonio L.; Moores, Lisa K.; Bona, Robert; Davidson, Bruce L.; Schulman, Sam; Crowther, Mark

2012-01-01

Background: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated adverse drug reaction that can lead to devastating thromboembolic complications, including pulmonary embolism, ischemic limb necrosis necessitating limb amputation, acute myocardial infarction, and stroke. Methods: The methods of this guideline follow the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Results: Among the key recommendations for this article are the following: For patients receiving heparin in whom clinicians consider the risk of HIT to be > 1%, we suggest that platelet count monitoring be performed every 2 or 3 days from day 4 to day 14 (or until heparin is stopped, whichever occurs first) (Grade 2C). For patients receiving heparin in whom clinicians consider the risk of HIT to be < 1%, we suggest that platelet counts not be monitored (Grade 2C). In patients with HIT with thrombosis (HITT) or isolated HIT who have normal renal function, we suggest the use of argatroban or lepirudin or danaparoid over other nonheparin anticoagulants (Grade 2C). In patients with HITT and renal insufficiency, we suggest the use of argatroban over other nonheparin anticoagulants (Grade 2C). In patients with acute HIT or subacute HIT who require urgent cardiac surgery, we suggest the use of bivalirudin over other nonheparin anticoagulants or heparin plus antiplatelet agents (Grade 2C). Conclusions: Further studies evaluating the role of fondaparinux and the new oral anticoagulants in the treatment of HIT are needed. PMID:22315270

[Rituximab as effective therapy in very severe thrombotic thrombocytopenic purpura (TTP)].

PubMed

Illner, N; Wolf, G

2010-05-01

A 26-year-old woman was admitted from another hospital because of an increased serum creatinine (170 micromol/l). She was found to have a thrombocytopenia (14Gpt/l, WHO grade IV) with anaemia and a raised lactate dehydrogenase (25.45 micromol/l). The patient was in a reduced general state when admitted to this hospital. Her mucosal membranes were pale and she had moderate scleral icterus. During the first few hours she became clearly less alert but without motor or sensory deficits. Laboratory tests showed an increased total bilirubin (73 micromol, decreased haptoglobin (< 0.08 g/l), free hemoglobin was raised (20.7 micromol/l) and the blood smear showed 5.5% fragmentocytes. Direct and indirect Coombs tests were negative. Thrombotic thrombocytic purpura (TTP) was diagnosed. Daily plasmapheresis with fresh plasma replacement and administration of corticosteroids was initiated. ADAMTS13 activity (reported later) was < 2 % and antibodies against this protease were demonstrated. After initial improvement a motor and sensory aphasia occurred. Because of progressive thrombocytopenia, immunosuppression with a total of four doses of 375 mg/m(2)/bsa rituximab was undertaken (640 mg each), every seven days. Over the next two to three weeks the platelet count very slowly rose. The plasmapheresis was ended after a total of 65 sessions. Nine months after the last plasmapheresis the platelet count and renal functions were normal. Severe autoantibody TTP can be successfully treated by administering rituximanb, an anti-CD20 antibody, in addition to the standard treatment with plasmapheresis. Georg Thieme Verlag KG Stuttgart.New York.

Insertion side, body position and circuit life during continuous renal replacement therapy with femoral vein access.

PubMed

Kim, In Byung; Fealy, Nigel; Baldwin, Ian; Bellomo, Rinaldo

2011-01-01

Choice of insertion side and patient position during continuous renal replacement therapy (CRRT) with femoral vein vascular access may affect circuit life. We investigated if there is an association between choice of insertion side and body position and its changes and circuit life during CRRT with femoral vein access. We studied 50 patients receiving CRRT via femoral vein access with a sequential retrospective study in a tertiary intensive care unit. We defined two groups: patients with right or left femoral vein access. We then obtained information on age, gender, circuit life, total heparin dose, hemoglobin concentration and coagulation variables (platelet count, international normalized ratio, and activated partial thromboplastin time) and percentage of time each patient spent in the supine, left lying, right lying, and sitting position during treatment. We studied 341 circuits in 50 patients. Mean circuit life was 13.9 h. Of these circuits, 251 (73.6%) were treated with right femoral vein access. Mean circuit life in this group was significantly longer compared with left femoral vein access (15.0 ± 14.3 vs. 10.6 ± 7.4; p = 0.019). Percentage spent in a particular position during CRRT was not significantly different between two groups. On multivariable linear regression analysis, mean circuit life was significantly and positively correlated with right vascular access site (p = 0.03) and lower platelet count (p = 0.03), but not with patient position. Right-sided insertion but not time spent in a particular position significantly affects circuit life during CRRT with femoral vein access. Copyright © 2010 S. Karger AG, Basel.

Acute Kidney Injury in Mechanically Ventilated Patients: The Risk Factor Profile Depends on the Timing of Aki Onset.

PubMed

Lombardi, Raúl; Nin, Nicolás; Peñuelas, Oscar; Ferreiro, Alejandro; Rios, Fernando; Marin, Maria Carmen; Raymondos, Konstantinos; Lorente, Jose A; Koh, Younsuck; Hurtado, Javier; Gonzalez, Marco; Abroug, Fekri; Jibaja, Manuel; Arabi, Yaseen; Moreno, Rui; Matamis, Dimitros; Anzueto, Antonio; Esteban, Andres

2017-10-01

Acute kidney injury (AKI) is a frequent complication in patients under mechanical ventilation (MV). We aimed to assess the risk factors for AKI with particular emphasis on those potentially preventable. Retrospective analysis of a large, multinational database of MV patients with >24 h of MV and normal renal function at admission. AKI was defined according to creatinine-based KDIGO criteria. Risk factors were analyzed according to the time point at which AKI occurred: early (≤48 h after ICU admission, AKIE) and late (day 3 to day 7 of ICU stay, AKIL). A conditional logistic regression model was used to identify variables independently associated with AKI. Three thousand two hundred six patients were included. Seven hundred patients had AKI (22%), the majority of them AKIE (547/704). The risk factor profile was highly dependent upon the timing of AKI onset. In AKIE risk factors were older age; SAPS II score; postoperative and cardiac arrest as the reasons for MV; worse cardiovascular SOFA, pH, serum creatinine, and platelet count; higher level of peak pressure and Vt/kg; and fluid overload at admission. In contrast, AKIL was linked mostly to events that occurred after admission (lower platelet count and pH; ICU-acquired sepsis; and fluid overload). None ventilation-associated parameters were identify as risk factors for AKIL. In the first 48 h, risk factors are associated with the primary disease and the patient's condition at admission. Subsequently, emergent events like sepsis and organ dysfunction appear to be predictive factors making prevention a challenge.

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

Prediction of esophageal varices and variceal hemorrhage in patients with acute upper gastrointestinal bleeding.

PubMed

Rockey, Don C; Elliott, Alan; Lyles, Thomas

2016-03-01

In patients with upper gastrointestinal bleeding (UGIB), identifying those with esophageal variceal hemorrhage prior to endoscopy would be clinically useful. This retrospective study of a large cohort of patients with UGIB used logistic regression analyses to evaluate the platelet count, aspartate aminotransferase (AST) to platelet ratio index (APRI), AST to alanine aminotransferase (ALT) ratio (AAR) and Lok index (all non-invasive blood markers) as predictors of variceal bleeding in (1) all patients with UGIB and (2) patients with cirrhosis and UGIB. 2233 patients admitted for UGIB were identified; 1034 patients had cirrhosis (46%) and of these, 555 patients (54%) had acute UGIB due to esophageal varices. In all patients with UGIB, the platelet count (cut-off 122,000/mm(3)), APRI (cut-off 5.1), AAR (cut-off 2.8) and Lok index (cut-off 0.9) had area under the curve (AUC)s of 0.80 0.82, 0.64, and 0.80, respectively, for predicting the presence of varices prior to endoscopy. To predict varices as the culprit of bleeding, the platelet count (cut-off 69,000), APRI (cut-off 2.6), AAR (cut-off 2.5) and Lok Index (0.90) had AUCs of 0.76, 0.77, 0.57 and 0.73, respectively. Finally, in patients with cirrhosis and UGIB, logistic regression was unable to identify optimal cut-off values useful for predicting varices as the culprit bleeding lesion for any of the non-invasive markers studied. For all patients with UGIB, non-invasive markers appear to differentiate patients with varices from those without varices and to identify those with a variceal culprit lesion. However, these markers could not distinguish between a variceal culprit and other lesions in patients with cirrhosis. Copyright © 2016 American Federation for Medical Research.

Thromboresistance Characterization of Extruded Nitric Oxide-Releasing Silicone Catheters

PubMed Central

Amoako, Kagya A.; Archangeli, Christopher; Handa, Hitesh; Major, Terry; Meyerhoff, Mark E.; Annich, Gail M.; Bartlett, Robert H.

2013-01-01

Intravascular catheters used in clinical practice can activate platelets, leading to thrombus formation and stagnation of blood flow. Nitric oxide (NO)-releasing polymers have been shown previously to reduce clot formation on a number of blood contacting devices. In this work, trilaminar NO-releasing silicone catheters were fabricated and tested for their thrombogenicity. All catheters had specifications of L = 6 cm, inner diameter = 21 gauge (0.0723 cm), outer diameter = 12 gauge (0.2052 cm), and NO-releasing layer thickness = 200 ± 11 μm. Control and NO-releasing catheters were characterized in vitro for their NO flux and NO release duration by gas phase chemiluminescence measurements. The catheters were then implanted in the right and left internal jugular veins of (N = 6 and average weight = 3 kg) adult male rabbits for 4 hours thrombogenicity testing. Platelet counts and function, methemoglobin (metHb), hemoglobin (Hb), and white cell counts and functional time (defined as patency time of catheter) were monitored as measured outcomes. Nitric oxide-releasing catheters (N = 6) maintained an average flux above (2 ± 0.5) × 10−10 mol/min/cm2 for more than 24 hours, whereas controls showed no NO release. Methemoglobin, Hb, white cell, and platelet counts and platelet function at 4 hours were not significantly different from baseline (α = 0.05). However, clots on controls were visibly larger and prevented blood draws at a significantly (p < 0.05) earlier time (2.3 ± 0.7 hours) into the experiment, whereas all NO-releasing catheters survived the entire 4 hours test period. Results indicate that catheter NO flux levels attenuated thrombus formation in a short-term animal model. PMID:22395119

The effect of calabash chalk on some hematological parameters in female adult Wistar rats.

PubMed

Akpantah, Amabe Otoabasi; Ibok, Ofon Samuel; Ekong, Moses Bassey; Eluwa, Mokutima Amarachi; Ekanem, Theresa Bassey

2010-09-05

Calabash chalk is a naturally occurring mineral consumed among the Nigerian community for pleasure and commonly by pregnant women as a remedy for morning sickness. Reports have shown that it contains different toxic substances, with lead being the most abundant. This study was therefore undertaken to ascertain the effect of two commonly available preparations of this chalk on some hematological parameters. Twenty-four adult female Wistar rats with average weight of 100 g were assigned into three groups (1, 2, 3). Group 1 served as the control and the animals received distilled water, while Groups 2 and 3 were treated by oral gavage with 40 mg/kg of non-salted (NSCC) and salted calabash chalk (SCC), respectively, for 14 days. The hemoglobin (Hb) concentration and red blood cell (RBC) count were significantly (p<0.05, 0.001 respectively) lower in the NSCC group, while erythrocyte sedimentation rate (ESR) was significantly (p<0.05) higher in the NSCC group compared to the control. There were no significant differences in packed cell volume (PCV), white blood cell (WBC) and platelet (Pl) counts compared to the control. The SCC group presented no significant difference in all blood count parameters compared to the control. This infers that calabash chalk, particularly the non-salted form, alters the normal concentration of Hb, RBC and Pl counts, and ESR, as observed in the female Wistar rats studied.

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

PubMed

Lopriore, E; Slaghekke, F; Oepkes, D; Middeldorp, J M; Vandenbussche, F P H A; Walther, F J

2010-03-01

To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01). TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia. Copyright (c) 2010 John Wiley & Sons, Ltd.

Frequent plateletpheresis does not clinically significantly decrease platelet counts in donors.

PubMed

Katz, Louis; Palmer, Kim; McDonnell, Emily; Kabat, Andy

2007-09-01

In October 2005, the US Food and Drug Administration (FDA) issued draft guidance on collecting platelets (PLTs) by automated methods. The FDA proposed limiting collections to 24 components, rather than 24 procedures, annually with up to 3 components per procedure. The rationale was from literature suggesting frequent PLT collection resulted in significant declines in donor PLT counts. Additional requirements for minimal interdonation intervals were proposed. Plateletpheresis records at a regional blood center with predonation PLT counts were used to assess the impact of the restriction on PLT collections. They were reviewed to demonstrate the effects of collection frequency, number of products collected, and interdonation interval on donor PLT counts. Total protein and albumin levels were compared in a subset of 24-times-per-year PLT donors and control whole-blood donors. A limit of 24 components would require replacement of approximately 20 percent of the donor base to recover lost components. No clinically important decrease in PLT counts before donation was seen in donors donating multiple PLT components up to 24 times per year, regardless of interdonation interval. No frequent donor was deferred for a PLT count less than 150 x 10(9) per L. Short interdonation intervals were associated with statistically but not clinically important decreases in PLT counts. Protein levels were not distinguishable between PLT donors and controls. The proposed restrictions are not required to prevent thrombocytopenia in frequent PLT donors and would adversely impact the supply of apheresis PLTs. Protein levels are maintained in these high-frequency donors.

A quantitative ELISA procedure for the measurement of membrane-bound platelet-associated IgG (PAIgG).

PubMed

Lynch, D M; Lynch, J M; Howe, S E

1985-03-01

A quantitative ELISA assay for the measurement of in vivo bound platelet-associated IgG (PAIgG) using intact patient platelets is presented. The assay requires quantitation and standardization of the number of platelets bound to microtiter plate wells and an absorbance curve using quantitated IgG standards. Platelet-bound IgG was measured using an F(ab')2 peroxidase labeled anti-human IgG and o-phenylenediamine dihydrochloride (OPD) as the substrate. Using this assay, PAIgG for normal individuals was 2.8 +/- 1.6 fg/platelet (mean +/- 1 SD; n = 30). Increased levels were found in 28 of 30 patients with clinical autoimmune thrombocytopenia (ATP) with a range of 7.0-80 fg/platelet. Normal PAIgG levels were found in 26 of 30 patients with nonimmune thrombocytopenia. In the sample population studied, the PAIgG assay showed a sensitivity of 93%, specificity of 90%, a positive predictive value of 0.90, and a negative predictive value of 0.93. The procedure is highly reproducible (CV = 6.8%) and useful in evaluating patients with suspected immune mediated thrombocytopenia.

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

Performance evaluation of the Abbott CELL-DYN Ruby and the Sysmex XT-2000i haematology analysers.

PubMed

Leers, M P G; Goertz, H; Feller, A; Hoffmann, J J M L

2011-02-01

Two mid-range haematology analysers (Abbott CELL-DYN Ruby and Sysmex XT-2000i) were evaluated to determine their analytical performance and workflow efficiency in the haematology laboratory. In total 418 samples were processed for determining equivalence of complete blood count (CBC) measurements, and 100 for reticulocyte comparison. Blood smears served for assessing the agreement of the differential counts. Inter-instrument agreement for most parameters was good although small numbers of discrepancies were observed. Systematic biases were found for mean cell volume, reticulocytes, platelets and mean platelet volume. CELL-DYN Ruby WBC differentials were obtained with all samples while the XT-2000i suppressed differentials partially or completely in 13 samples (3.1%). WBC subpopulation counts were otherwise in good agreement with no major outliers. Following first-pass CBC/differential analysis, 88 (21%) of XT-2000i samples required further analyser processing compared to 18 (4.3%) for the CELL-DYN Ruby. Smear referrals for suspected WBC/nucleated red blood cells and platelet abnormalities were indicated for 106 (25.4%) and 95 (22.7%) of the XT-2000i and CELL-DYN Ruby samples respectively. Flagging efficiencies for both analysers were found to be similar. The Sysmex XT-2000i and Abbott CELL-DYN Ruby analysers have broadly comparable analytical performance, but the CELL-DYN Ruby showed superior first-pass efficiency. © 2010 Blackwell Publishing Ltd.

Clinical Features of 294 Turkish Patients with Chronic Myeloproliferative Neoplasms

PubMed Central

Andıç, Neslihan; Ünübol, Mustafa; Yağcı, Eren; Akay, Olga Meltem; Yavaşoğlu, İrfan; Kadıköylü, Vefki Gürhan; Bolaman, Ali Zahit

2016-01-01

Objective: Myeloproliferative neoplasms (MPNs) share common clonal stem cells but show significant differences in their clinical courses. The aim of this retrospective study was to evaluate thrombotic and hemorrhagic complications, JAK2 status, gastrointestinal and cardiac changes, treatment modalities, and survival in MPNs in Turkish patients. Materials and Methods: Medical files of 294 patients [112 essential thrombocythemia (ET), 117 polycythemia vera (PV), 46 primary myelofibrosis, and 19 unclassified MPN cases] from 2 different universities in Turkey were examined. Results: Older age, higher leukocyte count at diagnosis, and JAK2 mutation positivity were risk factors for thrombosis. Platelet count over 1000x109/L was a risk factor for hemorrhagic episodes. Hydroxyurea treatment was not related to leukemic transformation. Median follow-up time was 50 months (quartiles: 22.2-81.75) in these patients. Patients with primary myelofibrosis had the shortest survival of 137 months when compared with 179 months for ET and 231 months for PV. Leukemic transformation, thromboembolic events, age over 60 years, and anemia were found to be the factors affecting survival. Conclusion: Thromboembolic complications are the most important preventable risk factors for morbidity and mortality in MPNs. Drug management in MPNs is done according to hemoglobin and platelet counts. Based on the current study population our results support the idea that leukocytosis and JAK2 positivity are more important risk factors for thrombosis than hemoglobin and platelet values. PMID:27094255

[Risk factors for patent ductus arteriosus in early preterm infants: a case-control study].

PubMed

Du, Jin-Feng; Liu, Tian-Tian; Wu, Hui

2016-01-01

To investigate the risk factors for the occurrence of patent ductus arteriosus (PDA) and to provide a clinical basis for reducing the occurrence of PDA in early preterm infants. A total of 136 early preterm infants (gestational age≤32 weeks) who were hospitalized between January 2013 and December 2014 and diagnosed with hemodynamicalhy significant PDA (hs-PDA) were enrolled as the case group. Based on the matched case-control principle, 136 early preterm infants without hs-PDA were selected among those who were hospitalized within the same period at a ratio of 1:1 and enrolled as the control group. The two groups were matched for sex and gestational age. The basic information of neonates and maternal conditions during the pregnancy and perinatal periods were collected. Logistic regression analysis was performed to identify the risk factors for the development of PDA. Univariate analysis showed that neonatal infectious diseases, neonatal respiratory distress syndrome, decreased platelet count within 24 hours after birth, and low birth weight were associated with the development of hs-PDA (P<0.05). Multivariate conditional logistic regression analysis revealed that neonatal infectious diseases (OR=2.368) and decreased platelet count within 24 hours after birth (OR=0.996) were independent risk factors for hs-PDA. Neonatal infectious diseases and decreased platelet count within 24 hours after birth increase the risk of hs-PDA in early preterm infants.