Overview of the Hemostasis Research Program: Advances and Future Directions

DTIC Science & Technology

2004-09-01

Gauze sponges - Clamps ◆ Noncompressible - Intracavitary hemostatic agent - High Intensity Focused Ultrasound ( HIFU ) - Drugs to enhance hemostatic...7 2.6 High Intensity Focused Ultrasound ( HIFU ) Device In addition to screening potential hemostatic agents, the ISR is currently evaluating...Drugs to Treat Coagulopathy High Intensity Focused Ultrasound Self/Buddy Aid Battalion Surgeon Scenario One: Bullet Wound to Thigh (Femoral

Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration.

PubMed

Lukasiewicz, A; Lebkowska, U; Galar, M

2012-01-01

Some of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties. Hemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent. There was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters. We found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.

Ankaferd hemostat in the management of gastrointestinal hemorrhages

PubMed Central

Beyazit, Yavuz; Kekilli, Murat; Haznedaroglu, Ibrahim C; Kayacetin, Ertugrul; Basaranoglu, Metin

2011-01-01

Gastrointestinal (GI) bleeding refers to any hemorrhage ascribed to the pathologies of the gastrointestinal tract, extending from the mouth to the anal canal. Despite the recent improvements in the endoscopic, hemostatic and adjuvant pharmacologic techniques, the reported mortality is still around 5%-10% for peptic ulcer bleeding and about 15%-20% for variceal hemorrhages. Although endoscopic management reduces the rates of re-bleeding, surgery, and mortality in active bleeding; early recurrence ratios still occur in around 20% of the cases even with effective initial hemostatic measures. In this quest for an alternative pro-hemostatic agent for the management of GI bleedings, Ankaferd blood stopper (ABS) offers a successful candidate, specifically for “difficult-to-manage” situations as evidenced by data presented in several studies. ABS is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica. It is effective in both bleeding individuals with normal hemostatic parameters and in patients with deficient primary and/or secondary hemostasis. ABS also modulates the cellular apoptotic responses to hemorrhagic stress, as well as hemostatic hemodynamic activity. Through its effects on the endothelium, blood cells, angiogenesis, cellular proliferation, vascular dynamics, and wound healing, ABS is now becoming an effective alternative hemostatic medicine for gastrointestinal bleedings that are resistant to conventional anti-hemorrhagic measurements. The aim of this review is to outline current literature experience suggesting the place of ABS in the management of GI bleeding, and potential future controlled trials in this complicated field. PMID:22046083

Marginal integrity of low-shrinkage and methacrylate-based composite resins: Effect of three different hemostatic agents

PubMed Central

Khoroushi, Maryam; Sahraneshin-Samani, Mahsa

2016-01-01

Background Moisture control is very important in restorative procedures in dentistry. Use of hemostatic agents helps control moisture; however, they might result in changes on enamel and dentin surfaces, affecting composite resin bond quality. The aim of this in vitro study was to evaluate the marginal microleakage of two different composite resins with the use of three different hemostatic agents. Material and Methods Standardized Class V cavities were prepared on the buccal and lingual surfaces of 48 premolars with cervical margins 1 mm apical to the cementoenamel junction (CEJ). The samples were randomly divided into 8 groups. In groups 1 to 4, an etch-and-rinse adhesive (Adper Single Bond) was applied as the bonding system, followed by exposure to different hemostatic agent: group 1: no hemostatic agent (control); group 2: ViscoStat; group 3: ViscoStat Clear; and group 4: trichloracetic acid, as hemostatic agents. The cavities were restored with Z-250 composite resin. In group 5 to 8 Silorane System Adhesive (Filtek P90 Adhesive) was applied as a bonding agent, followed by exposure to different hemostatic agents in a manner similar to that in groups 1to 4. The cavities were restored with Filtek P90, a low-shrinkage composite resin. The samples in each group were evaluated for dye penetration under a stereomicroscope at ×36 after 24 hours and a 500-round thermocycling procedure at enamel and dentin margins. Statistical analysis was carried out using Kruskal-Wallis and Mann-Whitney tests (α=0.05). Results Z-250 composite resin exhibited significantly higher dentin microleakage scores compared to Filtek P90 (P = 0.004). Trichloracetic acid increased dentin microleakage with Filtek P90 (P=0.033). Conclusions Under the limitations of this in vitro study, application of hemostatic agents did not affect microleakage of the two tested composite resins except for trichloracetic acid that increased marginal microleakage when used with Filtek P90. Key words:Composite resin, dental leakage, hemostatics, silorane system adhesive. PMID:27034759

Hemostasis in a noncompressible hemorrhage model: an end-user evaluation of hemostatic agents in a proximal arterial injury.

PubMed

Satterly, Steven; Nelson, Daniel; Zwintscher, Nathan; Oguntoye, Morohunranti; Causey, Wayne; Theis, Bryan; Huang, Raywin; Haque, Mohamad; Martin, Matthew; Bickett, Gerald; Rush, Robert M

2013-01-01

1. Evaluate hemostatic bandages by the end user using subjective and objective criteria. 2. Determine if user training and education level impact overall hemostatic outcomes. 3. Our hypothesis was that prior medical training would be directly linked to improved hemostatic outcomes in noncompressible hemorrhage indepen- dent of dressing used. Military personnel were given standardized instruction on hemostatic dressings as part of a tactical combat casualty care course (TC3). Soldiers were randomized to a hemostatic dressing. Proximal arterial (femoral and axillary) injuries were created in extremities of live tissue models (goat or pig). Participants attempted hemostasis through standardized dressing application. Evaluation of hemostasis was performed at 2- and 4-minute intervals by physicians blinded to participants' training level. Military personnel that are due to deploy are given "refresher" instruction by their units as well as participating in the TC3 to further hone their medical skills prior to deployment. The TC3 is simulation training designed to simulate combat environments and real-life trauma scenarios. Military personnel due to deploy, physicians (residents and board certified surgeons), animal care technicians, and veterinarian support. Celox 42 (33%), ChitoGauze 11 (9%), Combat Gauze 45 (35%), and HemCon wafer 28 (22%) bandages were applied in 126 arterial injuries created in 45 animals in a standardized model of hemorrhage. Overall, no significant difference in hemostasis and volume of blood loss was seen between the 4 dressings at 2 or 4 minutes. Combat gauze was the most effective at controlling hemorrhage, achieving 83% hemostasis by 4 minutes. Combat gauze was also rated as the easiest dressing to use by the soldiers (p<0.05). When compared to nonmedical personnel, active duty soldiers with prior medical training improved hemostasis at 4 minutes by 20% (p = 0.05). There is no significant difference in hemostasis between hemostatic bandages for proximal arterial hemorrhage. Hemostasis significantly improves between 2 and 4 minutes using direct pressure and hemostatic agents. Prior medical training leads to 20% greater efficacy when using hemostatic dressings. Published by Elsevier Inc.

Synthetic Strategies for Engineering Intravenous Hemostats

PubMed Central

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

2015-01-01

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

Longitudinal association of hemostatic factors with risk for cancers of the breast, colorectum, and lung among postmenopausal women.

PubMed

Kabat, Geoffrey C; Salazar, Christian R; Zaslavsky, Oleg; Lane, Dorothy S; Rohan, Thomas E

2016-09-01

The aim of this study was to examine whether hemostatic factors associated with coagulation and inflammation pathways are associated with cancer risk in postmenopausal women. We used data from the Women's Health Initiative study to examine the association of plasma fibrinogen levels, factor VII antigen activity, and factor VII concentration measured at baseline and during follow-up with the risk for cancers of the breast, colorectum, and lung. Among 5287 women who were followed up for a median of 11.4 years, 275 cases of breast cancer, 102 cases of colorectal cancer, and 90 cases of lung cancer were identified. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for the association of hemostatic factors with each cancer. Hemostatic factors were not associated with breast cancer in either baseline or longitudinal analyses. Baseline hemostatic factors showed weak associations with colorectal cancer; however, no association was seen in longitudinal analyses. Fibrinogen was positively associated with lung cancer in both baseline and longitudinal analyses; the association was seen only in never and former smokers, not in current smokers. We found no evidence of an association between hemostatic factors and breast or colorectal cancer in postmenopausal women. The positive association of fibrinogen levels with lung cancer requires confirmation in larger studies.

Comparative evaluation of absorbable hemostats: advantages of fibrin-based sheets.

PubMed

Krishnan, Lissy K; Mohanty, Mira; Umashankar, P R; Lal, Arthur Vijayan

2004-11-01

Bioactive hemostats and wound dressings consist of either inherently active materials or act as delivery vehicles which contain such materials. Fibrin is a natural hemostat and scaffold, guiding the direction of wound contraction and closure. In order to improve the ease of application of liquid fibrin glue, we have made a freeze-dried form of polymerized fibrin that supports hemostasis and wound healing. The bleeding from the middle ear artery of rabbits was found to be arrested instantaneously on application of fibrin sheets, even when the animal was heparinized systemically. As the fibrin sheet was found to be fragile, gelatin was incorporated to the sheet and thus the mechanical stability was improved without compromising the hemostatic effect. The efficacy of the fabricated fibrin and fibrin-gelatin sheets to seal traumatized rat liver was compared with commercially available hemostats, Abgel (cross-linked gelatin) and Surgicel (cross-linked cellulose). Tissue compatibility of all the hemostats was studied by analyzing the liver tissue 15 days after application. While the hemostatic effect was best with fibrin and fibrin-gelatin sheets, both Surgicel and Abgel were not capable of arresting the bleeding quickly. Gross analysis of tissue on the 15th day of application, visibly, Abgel was not only degraded but resulted in severe adhesions of internal organs and histologically capsule formation around the implant was evident. Though Surgicel was also seen as cream soft material on the site of application that joined two pieces of liver, there was no adhesion of other internal organs and histologically, immune reaction and foreign-body-type giant cells were present in large amounts. Fibrin was not found grossly on application site whereas fibrin-gelatin was seen as a small white spot. Granulation tissue formation and cell migration into the fibrin-based sheets were evident, and therefore, fibrin-based sheets are not only efficient hemostats but showed optimum degradation and wound healing.

Embolization with ethylene vinyl alcohol copolymer (Onyx®) for peripheral hemostatic and non-hemostatic applications: a feasibility and safety study

PubMed Central

Né, Romaric; Chevallier, Olivier; Falvo, Nicolas; Facy, Olivier; Berthod, Pierre-Emmanuel; Galland, Christophe; Gehin, Sophie; Midulla, Marco

2018-01-01

Background Onyx® is a liquid embolic agent, which is approved for the treatment of cerebral vascular lesions but still rarely used in peripheral interventional radiology. The goal of this study is to report the feasibility and safety of embolization with Onyx® for peripheral hemostatic and non-hemostatic endovascular procedures. Methods Retrospective study of all consecutive patients who underwent visceral or peripheral embolization with Onyx® for hemostatic or non-hemostatic purpose in our department between May 2014 and November 2016. Demographic data, clinical presentation, underlying etiology, culprit vessel, endovascular procedure, pain during embolization, outcomes, and follow-up data were collected. Results Fifty patients (males, 34; females, 16; mean age, 56±18 years; range, 15–89 years) were included. Twenty-nine (58%) of patients underwent hemostatic embolization for arterial (n=22, 44%) or venous (n=7, 14%) bleeding lesions, whereas 21 (42%) of patients underwent non-hemostatic embolization for arterial aneurysms (n=8, 16%), preoperative portal vein deprivation (n=6, 12%) or other indications (n=7, 14%). Onyx-18 was used in 37 (74%) patients, Onyx-34 in 9 (18%) patients, and a combination of both in 4 (8%) patients. Onyx was used alone in 25 (50%) patients and in combination with other agent in 25 (50%) patients. Mean number of Onyx® vials used was 3.7 (range, 1–17). Immediate technical success rate was 100%. Primary clinical success was achieved in all patients. Recurrent bleeding occurred in two patients. Significant pain (pain score ≥3) was noted during injection in 10 (20%) patients. No major complication or side effects were noted within 1 month. Conclusions Transcatheter embolization with Onyx® is feasible and safe in the peripheral arterial or venous vasculature for both bleeding and non-bleeding patients whatever the anatomic site. PMID:29774181

Embolization with ethylene vinyl alcohol copolymer (Onyx®) for peripheral hemostatic and non-hemostatic applications: a feasibility and safety study.

PubMed

Né, Romaric; Chevallier, Olivier; Falvo, Nicolas; Facy, Olivier; Berthod, Pierre-Emmanuel; Galland, Christophe; Gehin, Sophie; Midulla, Marco; Loffroy, Romaric

2018-04-01

Onyx ® is a liquid embolic agent, which is approved for the treatment of cerebral vascular lesions but still rarely used in peripheral interventional radiology. The goal of this study is to report the feasibility and safety of embolization with Onyx ® for peripheral hemostatic and non-hemostatic endovascular procedures. Retrospective study of all consecutive patients who underwent visceral or peripheral embolization with Onyx ® for hemostatic or non-hemostatic purpose in our department between May 2014 and November 2016. Demographic data, clinical presentation, underlying etiology, culprit vessel, endovascular procedure, pain during embolization, outcomes, and follow-up data were collected. Fifty patients (males, 34; females, 16; mean age, 56±18 years; range, 15-89 years) were included. Twenty-nine (58%) of patients underwent hemostatic embolization for arterial (n=22, 44%) or venous (n=7, 14%) bleeding lesions, whereas 21 (42%) of patients underwent non-hemostatic embolization for arterial aneurysms (n=8, 16%), preoperative portal vein deprivation (n=6, 12%) or other indications (n=7, 14%). Onyx-18 was used in 37 (74%) patients, Onyx-34 in 9 (18%) patients, and a combination of both in 4 (8%) patients. Onyx was used alone in 25 (50%) patients and in combination with other agent in 25 (50%) patients. Mean number of Onyx ® vials used was 3.7 (range, 1-17). Immediate technical success rate was 100%. Primary clinical success was achieved in all patients. Recurrent bleeding occurred in two patients. Significant pain (pain score ≥3) was noted during injection in 10 (20%) patients. No major complication or side effects were noted within 1 month. Transcatheter embolization with Onyx ® is feasible and safe in the peripheral arterial or venous vasculature for both bleeding and non-bleeding patients whatever the anatomic site.

Effect of aluminum chloride hemostatic agent on microleakage of class V composite resin restorations bonded with all-in-one adhesive

PubMed Central

Mohammadi, Narmin; Bahari, Mahmood; Pournaghi-Azar, Fatemeh; Mozafari, Aysan

2012-01-01

Objectives: Since hemostatic agents can induce changes on enamel and dentin surfaces and influence composite resin adhesion, the aim of the present study was to evaluate the effect of the aluminum chloride hemostatic agent on the gingival margin microleakage of class V (Cl V) composite resin restorations bonded with all-in-one adhesive. Study design: Cl V cavities were prepared on the buccal surfaces of 60 sound bovine permanent incisors. Gingival margins of the cavities were placed 1.5 mm apical to the cemento-enamel junction (CEJ). The teeth were randomly divided into two groups of 30. In group 1, the cavities were restored without the application of a hemostatic agent; in group 2, the cavities were restored after the application of the hemostatic agent. In both groups all-in-one adhesive and Z250 composite resin were used to restore the cavities with the incremental technique. After finishing and polishing, the samples underwent a thermocycling procedure, followed by immersion in 2% basic fuschin solution for 24 hours. The samples were sectioned and gingival microleakage was evaluated under a stereomicroscope. The non-parametric Mann-Whitney U test was used to compare microleakage between the two groups. Statistical significance was defined at P<0.05. Results: A statistically significant difference was observed in microleakage between the two groups (P<0.001). Conclusions: Contamination of Cl V composite resin restorations bonded with all-in-one adhesive with aluminum chloride hemostatic agent significantly increases restoration gingival margin microleakage. Key words:All-in-one adhesive resin, composite resin restoration, hemostatic agent, microleakage. PMID:22322497

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

Usefulness of hemostatic sealants for minimizing ovarian damage during laparoscopic cystectomy for endometriosis.

PubMed

Choi, Chahien; Kim, Woo Young; Lee, Dong Hee; Lee, San Hui

2018-03-01

We aimed to evaluate the impact of topical hemostatic sealants and bipolar coagulation during laparoscopic ovarian endometriotic cyst resection on ovarian reserve by comparing the rates of decrease in anti-Müllerian hormone (AMH). A randomized prospective data collection was made on women aged 19-45 years who planned to have laparoscopic ovarian cystectomy at one of two institutions (n = 80), Kangbuk Samsung Hospital, Seoul, Korea or National Health Insurance Service Ilsan Hospital, Goyang, Korea, from January 2014 to April 2016. Patients were randomly divided into two groups treated with either a topical hemostatic sealant or bipolar coagulation for hemostasis. The hemostatic group was randomized to the FloSeal or TachoSil subgroups. Preoperative and 3-month postoperative AMH levels were checked and the rates of decrease of AMH were compared. All patients enrolled were treated with dienogest (Visanne) for 6-12 months. None were lost to follow-up at postoperative 3 months, but about one-third of the patients had been lost to follow-up by 6-12 months. AMH was significantly decreased in both groups 3 months postoperatively; however, the rate of decrease in the bipolar coagulation group was greater than that in the hemostatic sealant group, 41.9% (interquartile range [IQR], 22.29-65.24) versus 18.1% (IQR, 10.94-29.90), P = 0.007. Between the two hemostatic subgroups, there was no significant difference in AMH decrease rate, 14.95% (IQR, 11.34-21.21) versus 18.1% (IQR 9.76-40.70), P = 0.204. Hemostatic sealants may be an alternative to bipolar coagulation for preservation of ovarian reserve after laparoscopic ovarian cystectomy for endometriosis. © 2017 Japan Society of Obstetrics and Gynecology.

Highly Absorbent Antibacterial Hemostatic Dressing for Healing Severe Hemorrhagic Wounds

PubMed Central

Li, Ting-Ting; Lou, Ching-Wen; Chen, An-Pang; Lee, Mong-Chuan; Ho, Tsing-Fen; Chen, Yueh-Sheng; Lin, Jia-Horng

2016-01-01

To accelerate healing of severe hemorrhagic wounds, a novel highly absorbent hemostatic dressing composed of a Tencel®/absorbent-cotton/polylactic acid nonwoven base and chitosan/nanosilver antibacterial agent was fabricated by using a nonwoven processing technique and a freeze-drying technique. This study is the first to investigate the wicking and water-absorbing properties of a nonwoven base by measuring the vertical wicking height and water absorption ratio. Moreover, blood agglutination and hemostatic second tests were conducted to evaluate the hemostatic performance of the resultant wound dressing. The blending ratio of fibers, areal weight, punching density, and fiber orientation, all significantly influenced the vertical moisture wicking property. However, only the first two parameters markedly affected the water absorption ratio. After the nonwoven base absorbed blood, scanning electron microscope (SEM) observation showed that erythrocytes were trapped between the fibrin/clot network and nonwoven fibers when coagulation pathways were activated. Prothrombin time (PT) and activated partial thromboplastin time (APTT) blood agglutination of the resultant dressing decreased to 14.34 and 50.94 s, respectively. In the femoral artery of the rate bleeding model, hemostatic time was saved by 87.2% compared with that of cotton cloth. Therefore, the resultant antibacterial wound dressing demonstrated greater water and blood absorption, as well as hemostatic performance, than the commercially available cotton cloth, especially for healing severe hemorrhagic wounds. PMID:28773912

Hemostatic granules and dressing prepared from formulations of carboxymethyl cellulose, kappa-carrageenan and polyethylene oxide crosslinked by gamma radiation

NASA Astrophysics Data System (ADS)

Barba, Bin Jeremiah D.; Aranilla, Charito T.; Relleve, Lorna S.; Cruz, Veriza Rita C.; Vista, Jeanina Richelle; Abad, Lucille V.

2018-03-01

Uncontrolled hemorrhage remains a persistent problem especially in anatomical areas where compression and tourniquet cannot be applied. Hemostatic agents are materials which can achieve control of bleeding in acute, life-threatening traumatic coagulopathy. In this study, we prepared biocompatible hydrogel-based hemostat crosslinked by ionizing radiation. Granules made from carboxymethyl cellulose and dressing from kappa carrageenan and polyethylene oxide were characterized by FT-IR, SEM, and gel analysis. Gamma radiation with a dose of 25 kGy was used for sterilization process. Stability studies indicate that the products remain effective with a shelf life of up to 18 months based on accelerated aging. Both hemostatic agents were demonstrated to be effective in vitro blood clotting assays showing a low blood clotting index, high platelet adhesion capacity and accelerated clotting time. Hemostat granules and dressing were also used in a femoral artery rat bleeding model where hemorrhage control was achieved in 90 s without compression and resulted in 100% survival rate after a 7 and 14-day observation.

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.

Safety and hemostatic efficacy of fibrin pad in partial nephrectomy: Results of an open-label Phase I and a randomized, standard-of-care-controlled Phase I/II study

PubMed Central

2012-01-01

Background Bleeding severity, anatomic location, tissue characteristics, and visibility are common challenges encountered while managing intraoperative bleeding, and conventional hemostatic measures (suture, ligature, and cautery) may sometimes be ineffective or impractical. While topical absorbable hemostats (TAH) are useful hemostatic adjuvants, each TAH has associated disadvantages. Methods We evaluated the safety and hemostatic efficacy of a new advanced biologic combination product―fibrin pad―to potentially address some gaps associated with TAHs. Fibrin pad was assessed as adjunctive hemostat in open partial nephrectomy in single-center, open-label, Phase I study (N = 10), and as primary hemostat in multicenter, single-blind, randomized, standard-of-care (SOC)-controlled Phase I/II study (N = 7) in Israel. It was used to control mild-to-moderate bleeding in Phase I and also spurting arterial bleeding in Phase I/II study. Phase I study assessed safety and Phase I/II study, proportion of successes at 10 min following randomization, analyzed by Fisher exact tests at 5% significance level. Results Phase I (N = 10): All patients completed the study. Hemostasis was achieved within 3–4 min (average = 3.1 min) of a single application in all patients. Fibrin pad was found to be safe for human use, with no product-related adverse events reported. Phase I/II (N = 7): Hemostatic success at 10 min (primary endpoint) was achieved in 3/4 patients treated with fibrin pad versus 0/3 patients treated with SOC. No clinically significant change in laboratory or coagulation parameters was recorded, except a case of post-procedural hemorrhage with fibrin pad, which was considered serious and related to the fibrin pad treatment, and required re-operation. Although Data Safety Monitoring Board authorized trial continuation, the sponsor decided against proceeding toward an indication for primary treatment of severe arterial hemorrhage as a replacement for sutures. The study was suspended after 7/30 planned subjects were enrolled. Conclusions The first-in-man trial of fibrin pad demonstrated its safety and efficacy as an adjunctive hemostatic technique for mild-to-moderate bleeding in partial nephrectomy. The study also suggested that the product should not replace sutures or meticulous surgical techniques for the treatment of severe arterial hemorrhage. Trial registration Phase I/II trial, NCT00598130 PMID:23137020

[Bed-side management of post-operative bleeding in transurethral resection of the prostate--hemostatic trial with thrombin solution injected into the resected cavity of the prostate].

PubMed

Hasegawa, S; Nakashima, J; Kimura, S

1987-08-01

To control post-operative bleeding from the resected cavity in transurethral resection of the prostate (TUR-P), 20,000 units of thrombin dissolved in 5-20 ml of physiological saline was injected into the cavity in one shot with a new type of 3-way Foley catheter. The catheter has two holes close to the balloon, and the holes provide outlets through which the solution is directly injected into the cavity. Out of 23 patients between 58 and 87 years old, 11 were given thrombin and 12 were control cases. In each case, urine blood volume (ml/hr) was determined before (a) and after (b) injection. The hemostatic effect was assessed with a "hemostatic index" of b/a. There was a statistically significant difference in the hemostatic indices between thrombin group and the control. (p less than 0.02) This new hemostatic method proved to be a very useful easy bed-side technique to control bleeding even in sudden bleeding after TUR-P. No serious side effects were found during the course of this study.

Graphene-Montmorillonite Composite Sponge for Safe and Effective Hemostasis.

PubMed

Li, Guofeng; Quan, Kecheng; Liang, Yuping; Li, Tianyi; Yuan, Qipeng; Tao, Lei; Xie, Qian; Wang, Xing

2016-12-28

Montmorillonite (MMT) is considered to be the most effective hemostat among natural phyllosilicates. However, there is a barrier against using MMT for the commercial hemostatics because the invaded MMT powders might cause thrombosis in vessel. Until now, it is still a challenge to manage the release of MMT and eliminate its side effect. Herein, we present a graphene-MMT composite sponge (GMCS), synthesized under a hydrothermal reaction, fixing MMT powders into the cross-linked graphene sheets. We demonstrate that only a few embedded MMT can evoke remarkable platelet stimulation at the sponge interface, while maintaining fast plasma absorbency of the innate sponge. In the synergy of the above hemostatic mechanisms, the GMCS can rapidly stop bleeding in approximately 85 s in rabbit artery injury test. More importantly, computed tomography angiography certifies that the GMCS does not cause thrombus or blood clot in vessels. Cytotoxicity assay further highlights its biocompatibility. In-depth analysis proposes that two-dimensional graphene overmatches one-dimensional linear polymers in the composite construction, and dimension transformation of blood distribution plays a crucial role for reinforcing the hemostatic performance. This GMCS hemostat not only opens a new perspective for graphene composite, but also makes a new chance of using clays for trauma therapy.

Hemostatic powder spray: a new method for managing gastrointestinal bleeding

PubMed Central

Papafragkakis, Haris; Ofori, Emmanuel; Ona, Mel A.; Krishnaiah, Mahesh; Duddempudi, Sushil; Anand, Sury

2015-01-01

Gastrointestinal bleeding is a leading cause of morbidity and mortality in the United States. The management of gastrointestinal bleeding is often challenging, depending on its location and severity. To date, widely accepted hemostatic treatment options include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as photodynamic therapy and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips. These approaches, albeit effective in achieving hemostasis, are associated with a 5–10% rebleeding risk. New simple, effective, universal, and safe methods are needed to address some of the challenges posed by the current endoscopic hemostatic techniques. The use of a novel hemostatic powder spray appears to be effective and safe in controlling upper and lower gastrointestinal bleeding. Although initial reports of hemostatic powder spray as an innovative approach to manage gastrointestinal bleeding are promising, further studies are needed to support and confirm its efficacy and safety. The aim of this study was to evaluate the technical feasibility, clinical efficacy, and safety of hemostatic powder spray (Hemospray, Cook Medical, Winston-Salem, North Carolina, USA) as a new method for managing gastrointestinal bleeding. In this review article, we performed an extensive literature search summarizing case reports and case series of Hemospray for the management of gastrointestinal bleeding. Indications, features, technique, deployment, success rate, complications, and limitations are discussed. The combined technical and clinical success rate of Hemospray was 88.5% (207/234) among the human subjects and 81.8% (9/11) among the porcine models studied. Rebleeding occurred within 72 hours post-treatment in 38 patients (38/234; 16.2%) and in three porcine models (3/11; 27.3%). No procedure-related adverse events were associated with the use of Hemospray. Hemospray appears to be a safe and effective approach in the management of gastrointestinal bleeding. PMID:26082803

Hemostatic powder spray: a new method for managing gastrointestinal bleeding.

PubMed

Changela, Kinesh; Papafragkakis, Haris; Ofori, Emmanuel; Ona, Mel A; Krishnaiah, Mahesh; Duddempudi, Sushil; Anand, Sury

2015-05-01

Gastrointestinal bleeding is a leading cause of morbidity and mortality in the United States. The management of gastrointestinal bleeding is often challenging, depending on its location and severity. To date, widely accepted hemostatic treatment options include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as photodynamic therapy and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips. These approaches, albeit effective in achieving hemostasis, are associated with a 5-10% rebleeding risk. New simple, effective, universal, and safe methods are needed to address some of the challenges posed by the current endoscopic hemostatic techniques. The use of a novel hemostatic powder spray appears to be effective and safe in controlling upper and lower gastrointestinal bleeding. Although initial reports of hemostatic powder spray as an innovative approach to manage gastrointestinal bleeding are promising, further studies are needed to support and confirm its efficacy and safety. The aim of this study was to evaluate the technical feasibility, clinical efficacy, and safety of hemostatic powder spray (Hemospray, Cook Medical, Winston-Salem, North Carolina, USA) as a new method for managing gastrointestinal bleeding. In this review article, we performed an extensive literature search summarizing case reports and case series of Hemospray for the management of gastrointestinal bleeding. Indications, features, technique, deployment, success rate, complications, and limitations are discussed. The combined technical and clinical success rate of Hemospray was 88.5% (207/234) among the human subjects and 81.8% (9/11) among the porcine models studied. Rebleeding occurred within 72 hours post-treatment in 38 patients (38/234; 16.2%) and in three porcine models (3/11; 27.3%). No procedure-related adverse events were associated with the use of Hemospray. Hemospray appears to be a safe and effective approach in the management of gastrointestinal bleeding.

Use of a contoured bioresorbable plate with a hemostatic plug to control life-threatening bleeding from the superior sagittal sinus during hemispherotomy: technical note.

PubMed

Tuite, Gerald F; Carey, Carolyn M; Nelson, William W; Raffa, Scott J; Winesett, S Parrish

2016-10-01

Profuse bleeding originating from an injured cerebral sinus can be a harrowing experience for any surgeon, particularly during an operation on a young child. Common surgical remedies include sinus ligation, primary repair, placement of a hemostatic plug, and patch or venous grafting that may require temporary stenting. In this paper the authors describe the use of a contoured bioresorbable plate to hold a hemostatic plug in place along a tear in the inferomedial portion of a relatively inaccessible part of the posterior segment of the superior sagittal sinus in an 11-kg infant undergoing hemispherotomy for epilepsy. This variation on previously described hemostatic techniques proved to be easy, effective, and ultimately lifesaving. Surgeons may find this technique useful in similar dire circumstances when previously described techniques are ineffective or impractical.

The hemostatic activity of cryopreserved platelets is mediated by phosphatidylserine-expressing platelets and platelet microparticles.

PubMed

Johnson, Lacey; Coorey, Craig P; Marks, Denese C

2014-08-01

Cryopreservation of platelets (PLTs) at -80°C with dimethyl sulfoxide (DMSO) can extend the shelf life from 5 days to 2 years. Cryopreserved PLTs are reported to have a greater in vivo hemostatic effect than liquid-stored PLTs. As such, the aim of this study was to understand the mechanisms responsible for the hemostatic potential of cryopreserved PLTs and the contribution of the reconstitution solution to this activity. DMSO (5% final concentration) was added to buffy coat-derived PLTs, followed by prefreeze removal of DMSO and storage at -80°C. Cryopreserved PLTs (n=8 per group) were thawed at 37°C, reconstituted with either 1 unit of thawed frozen plasma or PLT additive solution (PAS-G). In vitro assays were performed before freezing and after thawing to assess the hemostatic activity of PLTs. Cryopreserved PLTs expressed high levels of phosphatidylserine and contained significantly more phosphatidylserine-positive PLT microparticles than liquid-stored PLTs. This was accompanied by a significant decrease in the time to clot formation and clot strength, as measured by thromboelastography. The supernatant from cryopreserved PLTs was sufficient to reduce the phosphatidylserine-dependent clotting time and increase the thrombin generation potential. Overall, plasma-reconstituted cryopreserved PLTs were more procoagulant than those reconstituted in PAS-G. PLT cryopreservation results in the generation of phosphatidylserine-expressing PLT microparticles which contribute to the hemostatic activity. Understanding the hemostatic activity of these components may assist in extending the use of these specialized components beyond military applications. © 2014 Australian Red Cross Blood Service. Transfusion © 2014 AABB.

Different chemical groups modification on the surface of chitosan nonwoven dressing and the hemostatic properties.

PubMed

Yan, Dong; Hu, Shihao; Zhou, Zhongzheng; Zeenat, Shah; Cheng, Feng; Li, Yang; Feng, Chao; Cheng, Xiaojie; Chen, Xiguang

2018-02-01

The hemostatic properties of surface modified chitosan nonwoven had been investigated. The succinyl groups, carboxymethyl groups and quaternary ammonium groups were introduced into the surface of chitosan nonwoven (obtained NSCS, CMCS and TMCS nonwoven, respectively). For blood clotting, absorbance value (0.105±0.03) of NSCS1 nonwoven was the smallest (CS 0.307±0.002, NSCS2 0.148±0.002, CMCS1 0.195±0.02, CMCS2 0.233±0.001, TMCS1 0.191±0.002, TMCS2 0.345±0.002), which indicated the stronger hemostatic potential. For platelet aggregation, adenosine diphosphate agonist was added to induce the nonwoven to adhered platelets. The aggregation of platelet with TMCS2 nonwoven was highest (10.97±0.16%). Further research of blood coagulation mechanism was discussed, which indicated NSCS and CMCS nonwoven could activate the intrinsic pathway of coagulation to accelerate blood coagulation. NSCS1 nonwoven showed the shortest hemostatic time (147±3.7s) and the lowest blood loss (0.23±0.05g) in a rabbit ear artery injury model. These results demonstrated that these surface modified chitosan nonwoven dressings could use as a promising hemostatic intervention, especially NSCS nonwoven dressing. Copyright © 2017 Elsevier B.V. All rights reserved.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

PubMed

Hickman, DaShawn A; Pawlowski, Christa L; Sekhon, Ujjal D S; Marks, Joyann; Gupta, Anirban Sen

2018-01-01

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Variation in hospital resource use and cost among surgical procedures using topical absorbable hemostats

PubMed Central

Martyn, Derek; Meckley, Lisa M; Miyasato, Gavin; Lim, Sangtaeck; Riebman, Jerome B; Kocharian, Richard; Scaife, Jillian G; Rao, Yajing; Corral, Mitra

2015-01-01

Background Adjunctive hemostats are used to assist with the control of intraoperative bleeding. The most common types are flowables, gelatins, thrombins, and oxidized regenerated celluloses (ORCs). In the US, Surgicel® products are the only US Food and Drug Administration-approved ORCs. Objective To compare the outcomes of health care resource utilization (HRU) and costs associated with using ORCs compared to other adjunctive hemostats (OAHs are defined as flowables, gelatins, and topical thrombins) for surgical procedures in the US inpatient setting. Patients and methods A retrospective, US-based cohort study was conducted using hospital inpatient discharges from the 2011–2012 calendar years in the Premier Healthcare Database. Patients with either an ORC or an OAH who underwent a cardiovascular procedure (valve surgery and/or coronary artery bypass graft surgery), carotid endarterectomy, cholecystectomy, or hysterectomy were included. Propensity score matching was used to create comparable groups of ORC and OAH patients. Clinical, economic, and HRU outcomes were compared. Results The propensity score matching created balanced patient cohorts for cardiovascular procedure (22,718 patients), carotid endarterectomy (10,890 patients), cholecystectomy (6,090 patients), and hysterectomy (9,348 patients). In all procedures, hemostatic agent costs were 28%–56% lower for ORCs, and mean hemostat units per discharge were 16%–41% lower for ORCs compared to OAHs. Length of stay and total procedure costs for patients treated with ORCs were lower for carotid endarterectomy patients (0.3 days and US$700) and for cholecystectomy patients (1 day and US$3,350) (all P<0.001). Conclusion Costs and HRU for patients treated with ORCs were lower than or similar to patients treated with OAHs. Proper selection of the appropriate hemostatic agents has the potential to influence clinical outcomes and treatment costs. PMID:26604807

Hemostatic abnormalities in dogs with naturally occurring heatstroke.

PubMed

Bruchim, Yaron; Kelmer, Efrat; Cohen, Adar; Codner, Carolina; Segev, Gilad; Aroch, Itamar

2017-05-01

To investigate hemostatic analyte abnormalities and their association with mortality in dogs with naturally occurring heatstroke. Prospective observational study. University teaching hospital. Thirty client-owned dogs with naturally occurring heatstroke. None. Citrated and EDTA blood samples were collected at presentation and at 4, 12, 24, 36, and 48 hours postpresentation (PP). Hemostatic tests performed included platelet count, prothrombin and activated partial thromboplastin times (PT and aPTT, respectively), antithrombin activity (ATA), total protein C activity (tPCA), fibrinogen, and D-dimer concentrations. The overall survival rate was 60% (18/30 dogs). Older age, higher heart rate and rectal temperature at presentation, and time from onset of clinical signs to presentation were significantly associated with mortality. Hemostatic analytes at presentation were not associated with mortality. Prolonged PT and aPTT at 12-24 hours PP, lower tPCA at 12 hours PP, and hypofibrinogenemia at 24 hours PP were significantly (P < 0.05) associated with mortality. Increased D-dimer concentration and low ATA were common at all time points, but were not associated with mortality. The frequency of disseminated intravascular coagulation (DIC) increased in nonsurvivors throughout hospitalization, but the development of DIC was not associated with mortality. The number of abnormal coagulation disturbances during the first 24 hours was significantly higher in nonsurvivors (P = 0.04). Hemostatic derangements are common in dogs with naturally occurring heatstroke. Alterations in PT, aPTT, tPCA, and fibrinogen concentrations appear to be associated with the outcome at 12-24 hours PP, exemplifying the need for serial measurement of multiple laboratory hemostatic tests during hospitalization, even when within reference interval on presentation. The development of DIC, as defined in this cohort, was not associated with mortality; however, nonsurvivors had significantly more coagulation abnormalities during the first 24 hours PP. © Veterinary Emergency and Critical Care Society 2017.

Comparison of hemostatic properties between collagen and synthetic buttress materials used in staple line reinforcement in a swine splenic hemorrhage model.

PubMed

Spector, David; Perry, Zvi; Konobeck, Tracy; Mooradian, Daniel; Shikora, Scott

2011-04-01

The use of staplers in gastrointestinal surgery is widespread, especially in advanced laparoscopic procedures. Staple line reinforcement with a buttress reduces bleeding and associated complications through a combination of factors. The intrinsic hemostatic properties of buttress materials have not been examined. This study examined the intrinsic hemostatic properties of two different types of material used in buttressing in an accepted hemostasis model that does not involve stapling or its effects by compression. An acellular collagen buttress (Veritas) and a synthetic polymer buttress (Duet) were compared to two commonly used hemostatic agents, Syvek and Surgicel, with gauze as control. In a swine capsular stripping hemostasis model, a 1 × 1 cm section of spleen capsule was removed and used as a source of bleeding, with one patch of material tested per bleeding site. A total of 51 wounds were created in five pigs (each patch n = 10, control n = 11). Hemostatic efficacy was assessed by quantitating the number of applications and total time needed for bleeding to stop. The mean time needed for hemostasis for Syvek and Veritas patches was significantly less than gauze, Duet and Surgicel (4.02, 4.51 vs. 8.97, 9.22, and 10.30 min respectively; p < 0.05). The Syvek and Veritas patches required significantly fewer applications than gauze, Duet™ and Surgicel (1.7, 2.2 vs. 4.1, 4.6, and 4.9 respectively; p < 0.01). The intrinsic hemostatic properties of different buttressing materials vary widely. In this study, a collagen buttress was significantly better at promoting hemostasis than the synthetic buttress material in a nonstapling model. This could be another factor to consider when choosing a buttress for staple line reinforcement.

Structure/function relations of hemostatic nonwoven dressings based on greige cotton

USDA-ARS?s Scientific Manuscript database

A variety of natural and synthetic fibers are employed in hemostatic dressings. Here we demonstrate the use of greige cotton as a functional fiber, which when combined with hydrophilic and hydrophobic fibers in hydroentangled nonwoven materials, promotes accelerated clotting. A biophysical approach...

Use of absorbable hemostatic gauze with medical adhesive is effective for achieving hemostasis in presacral hemorrhage.

PubMed

Zhang, Chang-Hua; Song, Xin-Ming; He, Yu-Long; Han, Fanghai; Wang, Liang; Xu, Jian-Bo; Chen, Chuang-Qi; Cai, Shi-Rong; Zhan, Wen-Hua

2012-04-01

Management of presacral hemorrhage is always challenging. Herein we describe the use of an absorbable hemostatic gauze with α-cyanoacrylate medical adhesive to achieve hemostasis. In this study, we conducted total mesorectal excision for the treatment of rectal cancer in 258 patients from March 2006 to May 2009. Intraoperative presacral hemorrhage developed in 5 (2%) patients during rectal mobilization. In these 5 patients, massive bleeding could not be controlled by pressure and pelvic packing with gauze. An absorbable hemostatic gauze spread with medical adhesive was compressed onto the bleeding vessel for at least 20 minutes. Hemostasis was achieved successfully and was maintained during the surgery. Patients recovered uneventfully and no postoperative events were noted. The use of an absorbable hemostatic gauze with medical adhesive is a simple and effective method for achieving hemostasis when massive presacral hemorrhage occurs. However, its effectiveness needs to be confirmed in a controlled study in a properly selected patient population. Copyright © 2012. Published by Elsevier Inc.

Serological analysis of patients treated with a new surgical hemostat containing bovine proteins and autologous plasma.

PubMed

Nelson, P A; Powers, J N; Estridge, T D; Elder, E A; Alea, A D; Sidhu, P K; Sehl, L C; DeLustro, F A

2001-01-01

A randomized, controlled clinical study of the management of diffuse bleeding with CoStasis surgical hemostat, a new hemostat containing bovine thrombin and collagen with the patient's own plasma, included patients undergoing cardiac, hepatic, iliac, and general surgery. Sera from 92 patients treated with CoStasis and 84 control patients were collected preoperatively and at a post surgical follow-up of 8 weeks. Among the control group, 57 patients were treated with Instat collagen sponge in noncardiac indications. Results showed that antibody responses in the CoStasis clinical study were similar to the reported literature for all antigens screened and were not associated with any adverse reactions. The bovine thrombin preparations in CoStasis and other commercially available thrombins were compared with the use of SDS-PAGE and Western blot analyses. Within this clinical study, CoStasis was shown to be a safe and effective hemostatic product containing bovine thrombin and bovine collagen and no pooled human blood products. Copyright 2001 John Wiley & Sons, Inc.

Evaluation of Shear Bond Strength of Total- and Self-etching Adhesive Systems after Application of Chlorhexidine to Dentin Contaminated with a Hemostatic Agent

PubMed Central

Sharafeddin, Farahnaz; Farhadpour, Hajar

2015-01-01

Statement of the Problem Hemostatic agents may influence the bond strength of different bonding agents. Also, chlorhexidine has shown positive effects on bond strength values and their combination effect has not been reported yet. Purpose The aim of this study was to evaluate the effect of contamination with a hemostatic agent on shear bond strength (SBS) of total- and self-etching adhesive systems and the effect of chlorhexidine application after removal of the hemostatic agent. Materials and Method In this experimental study, the occlusal enamel of each sixty caries-free mandibular molars was removed and their midcoronal dentin was exposed. The specimens were then mounted in auto-polymerizing resin 1mm apical to CEJ. Then, the specimens were divided into 6 groups (n=10) based on contamination with a hemostatic agent (H), application of chlorhexidine (CHX) and the adhesive system used; and then were classified as Group 1: Adper Single Bond (ASB); Group 2: H+ASB; Group 3: H+0.2% CHX+ASB; Group 4: Clearfil SE Bond (CSB); Group 5: H+CSB; Group 6: H+0.2% CHX+CSB. Then, composite resin rods (4×2 mm) were built up on the dentin surfaces and after thermocycling, the SBS (MPa) was evaluated. Statistical analysis was performed using two-way ANOVA and post hoc Tukey tests (p< 0.05). Results There were statistically significant differences between bond strength values of group 1 (ASB) and group 2 (H+ASB) (p< 0.001) and group 1 (ASB) and group 3 (H+CHX+ASB) (p< 0.001). Similarly, significant differences were seen between group 4 (CSB) and group 5 (H+CSB) (p< 0.001) and between group 4 (CSB) and group 6 (H+CHX+CSB) (p< 0.001). Conclusion Contamination with hemostatic agent reduced the SBS of both total- and self-etching adhesive systems. In addition, application of chlorhexidine after the removal of hemostatic agent had a negative effect on SBS of total- and self-etching adhesive systems. PMID:26331146

Use of topical hemostatic agents in gynecologic surgery.

PubMed

Wysham, Weiya Z; Roque, Dario R; Soper, John T

2014-09-01

Sutures, hemoclips, and electrocautery are the primary mechanisms used to achieve hemostasis during gynecologic surgery, but in situations in which these are inadequate or not feasible, an array of hemostatic agents are available to help achieve hemostasis. These agents include physical agents such as cellulose, collagen, or gelatin products as well as biologic agents such as thrombin and fibrin products. Limited data are available on many of these agents, although their use is increasing, sometimes at high costs. In gynecologic surgery, hemostatic agents are likely most effective when used in areas of oozing or slow bleeding and as an adjunct to conventional surgical methods of hemostasis.

[Preliminary evaluation on seroma prevention and treatment with transposition of tissue flaps and arista hemostatic powder].

PubMed

Zhang, Ruming; Tan, Yiwen; Wang, Heqi

2006-12-01

To investigate and evaluate prevention and treatment of seroma by transposition of tissue flaps and Arista hemostatic powder after regional lymph node resection in patients with malignant tumors. Twelve patients (6 males, 6 females; aged 31-81 years, with metastatic tumors underwent prevention and treatment of seroma with the tissue flaps and Arista hemostatic powder spray after regional lymph node resection. The metastatic tumors involved the axilla in 1 patient with breast carcinoma, the iliac and inguinal regions in 2 patients with carcinomas of the uterine cervix and the rectum, and the inguinal region in 9 patients, including 4 patients with malignant fibrous histiocytoma(3 in the thigh, 1 in the leg), 2 patients with squamous carcinomas in the leg, 1 patient with synovial sarcoma in the knee, 1 patient with epithelioid sarcoma in the leg, and 1 patient with malignant melanoma in the foot. As for the lymph node removal therapy. 1 patient underwent axillary lymph node removal, 2 patients underwent lymph node removal in theiliac and inguinal regions, and 9 patients underwent lymph node removal in the inguinal region. Meanwhile, of the 12 patients, 6 patients underwent transposition of sartorius flaps with Arista hemostatic powder, 3 patients underwent transposition of the rectus abdominis myocutaneous flaps (including 2 patients treated with Arista spray befor the wound closure and 1 patient treated by transposition of local skin flaps with Arista spray used again),and 3 patients underwent only the suturing of the wounds combined with Arista. At the same time, of the 12 patients,only 4 patient underwent the transplantation of artificial blood vessels. The follow-up for 2-10 months after operation revealed that 10 patients, who had received the transposition of tissue flaps and the spray of Arista hemostatic powder, had the first intention of the incision heal with seroma cured. Nine patients were given a preventive use of Arista hemostatic powder and therefore no seroma developed. The combined use of the transposition of tissue flaps and Arista hemostatic powder spray achieved a success rate of 100% in the prevention or treatment of seroma. However, 1 patient developed microcirculation disturbance 24 hours after operation and underwent disarticulation of the hip; 1 patient developed pelvic cavity hydrops and died 10 months after operation. The combined use of transposition of tissue flaps and Arista hemostatic powder spray can effectively prevent or treat seroma after regional lymph node removal in a patient with malignant tumor.

Application of Absorbable Hemostatic Materials Observed in Thyroid Operation

NASA Astrophysics Data System (ADS)

Li, Yan-Ming; Liang, Zhen-Zhen; Song, Yan

2016-05-01

To observe the application effects of the absorbable hemostatic materials in thyroid operation. Methods: From May 2014 to January 2015, 100 patients with thyroid surgery in our university affiliated hospital were selected as the research object. Randomly divided into experimental group and control group, 50 cases in each group. Application of absorbable hemostatic hemostatic materials in the experimental group during the operation, the control group using the traditional mechanical methods of hemostasis hemostasis to observe the operation time, bleeding volume, postoperative drainage volume, complications and hospital stay of the two groups. Results: The operation time, bleeding volume, postoperative drainage and hospital stay in the experimental group were significantly lower in the study group than in the control group, and the difference between the two groups was statistically significant (P< 0.05); The satisfaction of patients in the experimental group was significantly higher than that in the control group, the difference was statistically significant in the two groups (P < 0.05); There was no significant difference in the incidence of wound bleeding complications between the study group and the control group (P > 0.05). Conclusion: Absorbable hemostatic materials can effectively shorten the operation time, reduce intraoperative blood loss and postoperative drainage, reduce the length of hospital stay and improve the success rate of surgery and patient satisfaction, which is worthy to be popularized in clinical thyroid surgery.

Properties of novel bone hemostat prepared using sugar-modified hydroxyapatite, phosphoryl oligosaccharides of calcium and thermoplastic resin

NASA Astrophysics Data System (ADS)

Mimira, Tokio; Umeda, Tomohiro; Musha, Yoshiro; Itatani, Kiyoshi

2013-12-01

A novel hemostatic agent was prepared using phosphoryl oligosaccharides of calcium (POs-Ca), hydroxyapatite (Ca10(PO4)6(OH)2; HAp) obtained by the hydrolysis of POs-Ca or sugar-containing HAp (s-HAp; 60.3 mass% calcium-deficient HAp and 39.5 mass% organic materials, Ca/P ratio = 1.56) and thermoplastic resin (the mixture of random copolymer of ethylene oxide/propylene oxide (EPO) and polyethylene oxide (EO); EPO : EO : water = 25 : 15 : 60 (mass ratio); 25EPO-15EO). The gel formed by mixing 25EPO-15EO with water (25EPO-15EO/water mass ratio: 0.20) was flash frozen at -80°C, freeze-dried at -50°C for 15 h and then ground using mixer. The consistency conditions of hemostats mixed with POs-Ca or s-HAp were optimized for the practical uses. The mean stanching times of hemostats were: s-HAp/25EPO-15EO (8.2 h; s-HAp/25EPO-15EO = 0.20) > 25EPO-15EO (5.3 h) > POs-Ca/25EPO-15EO (4.7 h; POs-Ca/25EPO-15EO = 0.20). The gentamicin, a typical antibiotic agent, loaded s-HAp/25EPO-15EO composite hemostat showed the steady state releasing in phosphate buffered saline till 10 h immersion at 37.0°C.

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

21 CFR 878.4490 - Absorbable hemostatic agent and dressing.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Absorbable hemostatic agent and dressing. 878.4490 Section 878.4490 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4490 Absorbable...

Safety and usability of hemostats, sealants, and adhesives.

PubMed

Burks, Sandra; Spotnitz, William

2014-08-01

Hemostats, sealants, and adhesives are an integral part of surgical patient care. Nurses who have knowledge about these agents can better help ensure safe, efficient surgical patient care. As a caregiver and patient advocate, the perioperative nurse must understand the most current information about these agents and be prepared to facilitate the transfer of this knowledge to all caregivers. Information about these agents, including the contraindications, warnings, and precautions associated with their use as well as their preparation and application, is provided here. Algorithms designed to clarify the best options for using hemostats, sealants, and adhesives are included as well. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

New generation tissue sealants and hemostatic agents: innovative urologic applications.

PubMed

Traver, Michael A; Assimos, Dean G

2006-01-01

Control of blood loss during urologic surgery is paramount to the success of patient recovery. Hemostatic agents and tissue sealants are used routinely to prevent excess blood loss and in reconstruction during surgical repair. Some of the available products include thrombin sealant, fibrin glue, bovine serum/albumin/glutaraldehyde, and gelatin matrix. Each of these agents differs in mechanism, cost, and application. Complications can include allergic reactions or thromboembolism and the risk of contracting bovine spongiform encephalitis or hepatitis. Many new hemostatic agents are being developed and approved. The benefits and risks of use of these agents versus conventional treatment need to be considered on a case-by-case basis by the surgeon.

Release abilities of adenosine diphosphate from phospholipid vesicles with different membrane properties and their hemostatic effects as a platelet substitute.

PubMed

Okamura, Yosuke; Katsuno, Shunsuke; Suzuki, Hidenori; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji

2010-12-20

We have constructed phospholipid vesicles with hemostatic activity as a platelet substitute. The vesicles were conjugated with a dodecapeptide (HHLGGAKQAGDV, H12), which is a fibrinogen γ-chain carboxy-terminal sequence (γ400-411). We have recently exploited these vesicles as a potential drug delivery system by encapsulation of adenosine 5'-diphosphate (ADP) (H12-(ADP)-vesicles). Here we explore the relationship between the ADP release from H12-(ADP)-vesicles with different membrane properties and their hemostatic effects. In total, we prepared five kinds of H12-(ADP)-vesicles with different lamellarities and membrane flexibilities. By radioisotope-labeling, we directly show that H12-(ADP)-vesicles were capable of augmenting platelet aggregation by releasing ADP in an aggregation-dependent manner. The amount of ADP released from the vesicles was dependent on their membrane properties. Specifically, the amount of ADP released increased with decreasing lamellarity and tended to increase with increasing membrane flexibility. Our in vivo results clearly demonstrated that H12-(ADP)-vesicles with the ability to release ADP exert considerable hemostatic action in terms of correcting prolonged bleeding time in a busulphan-induced thrombocytopenic rat model. We propose a recipe to control the hemostatic abilities of H12-(ADP)-vesicles by modulating ADP release based on membrane properties. We believe that this concept will be invaluable to the development of platelet substitutes and other drug carriers. Copyright © 2010 Elsevier B.V. All rights reserved.

Hemostatic efficacy of EVARREST™, Fibrin Sealant Patch vs. TachoSil® in a heparinized swine spleen incision model.

PubMed

Matonick, John P; Hammond, Jeffrey

2014-12-01

First-generation single-component hemostats such as oxidized regenerated cellulose (ORC), fibrin, collagen, and gelatin have evolved into second and third generations of combination hemostats. This study compares two FDA approved products, EVARREST™, Fibrin Sealant Patch, a hemostat comprised of a matrix of nonwoven polyglactin 910 embedded in ORC coated with human fibrinogen and thrombin to TachoSil® medicated sponge, an equine collagen pad coated with human fibrinogen and thrombin. Swine were anticoagulated with heparin to 3X their baseline activated clotting time and a 15 mm long × 3 mm deep incision was made to create a consistent moderate bleeding pattern. Test material was then applied to the wound site and compressed manually for 3 min with just enough pressure to prevent continued bleeding. Hemostatic effectiveness was evaluated at 3 min and 10 min. At 3 min, the hemostasis success rate was 86% in the EVARREST™ group and 0% in the TachoSil® group, p < .0001. The overall success rate at 10 min was 100% with EVARREST™ and 4% with TachoSil®, p < .0001. Adhesive failure, in which the test material did not stick to the tissue, occurred in 96% of TachoSil® sites. In contrast, 100% of the EVARREST™ applications adhered to the test site. EVARREST™, Fibrin Sealant Patch demonstrated greater wound adhesion and more effective hemostasis than TachoSil®. Adhesive failure was the primary failure mode for TachoSil® in this model.

Preparation of Chitosan-Based Hemostatic Sponges by Supercritical Fluid Technology

PubMed Central

Song, Hu-Fan; Chen, Ai-Zheng; Wang, Shi-Bin; Kang, Yong-Qiang; Ye, Shi-Fu; Liu, Yuan-Gang; Wu, Wen-Guo

2014-01-01

Using ammonium bicarbonate (AB) particles as a porogen, chitosan (CS)-based hemostatic porous sponges were prepared in supercritical carbon dioxide due to its low viscosity, small surface tension, and good compatibility with organic solvent. Fourier transform infrared spectroscopy (FTIR) spectra demonstrated that the chemical compositions of CS and poly-(methyl vinyl ether-co-maleic anhydride) (PVM/MA) were not altered during the phase inversion process. The morphology and structure of the sponge after the supercritical fluid (SCF) process were observed by scanning electron microscopy (SEM). The resulting hemostatic sponges showed a relatively high porosity (about 80%) with a controllable pore size ranging from 0.1 to 200 μm. The concentration of PVM/MA had no significant influence on the porosity of the sponges. Comparative experiments on biological assessment and hemostatic effect between the resulting sponges and Avitene® were also carried out. With the incorporation of PVM/MA into the CS-based sponges, the water absorption rate of the sponges increased significantly, and the CS-PVM/MA sponges showed a similar water absorption rate (about 90%) to that of Avitene®. The results of the whole blood clotting experiment and animal experiment also demonstrated that the clotting ability of the CS-PVM/MA sponges was similar to that of Avitene®. All these results elementarily verified that the sponges prepared in this study were suitable for hemostasis and demonstrated the feasibility of using SCF-assisted phase inversion technology to produce hemostatic porous sponges. PMID:28788577

Acute Management of Hemostasis in Patients With Neurological Injury.

PubMed

Baharoglu, M Irem; Brand, Anneke; Koopman, Maria M; Vermeulen, Marinus; Roos, Yvo B W E M

2017-10-01

Neurological injuries can be divided into those with traumatic and nontraumatic causes. The largest groups are traumatic brain injury (TBI) and nontraumatic stroke. TBI patients may present with intracranial hemorrhages (contusions, or subdural or epidural hematomas). Strokes are ischemic or hemorrhagic. In all these disorders, thrombosis and hemostasis play a major role. Treatment aims to either cease bleeding and/or restore perfusion. We reviewed hemostatic and thrombolytic therapies in patients with neurological injuries by MEDLINE and EMBASE search using various key words for neurological disorders and hemostatic therapies restricted to English language and human adults. Review of articles fulfilling inclusion criteria and relevant references revealed that, in patients with ischemic stroke, intravenous thrombolytic therapy with recombinant tissue plasminogen activator within 4.5-5 hours after onset of symptoms improves clinical outcome. In contrast, there are no hemostatic therapies that are proven to improve clinical outcome of patients with hemorrhagic stroke or TBI. In patients with hemorrhagic stroke who use vitamin K antagonist or direct oral anticoagulants, there is evidence that specific reversal therapies improve hemostatic laboratory parameters but without an effect on clinical recovery. In patients with hemorrhagic stroke or TBI who use concomitant antiplatelet therapy, there is evidence for harm of platelet transfusion. In patients with aneurysmal subarachnoid hemorrhage, tranexamic acid was shown to reduce rebleeding rate without improving clinical outcome. The effects of tranexamic acid in patients with TBI are still under investigation. We conclude that, in patients with ischemic stroke, thrombolytic therapy improves outcome when given within 4.5-5 hours. In hemorrhagic stroke and TBI, most hemostatic therapies improved or corrected laboratory parameters but not clinical outcome. Currently, in several trials, the effects of tranexamic acid are being studied of which the results are eagerly awaited. Because improving clinical outcome should be the goal of new therapies, we encourage to use clinical outcome scales as the primary outcome measure in trials that investigate effects of hemostatic therapies in patients with neurological injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of External Hemorrhage in Tactical Combat Casualty Care: Chitosan-Based Hemostatic Gauze Dressings--TCCC Guidelines-Change 13-05.

PubMed

Bennett, Brad L; Littlejohn, Lanny F; Kheirabadi, Bijan S; Butler, Frank K; Kotwal, Russ S; Dubick, Michael A; Bailey, Jeffrey A

2014-01-01

Hemorrhage remains the leading cause of combat death and a major cause of death from potentially survivable injuries. Great strides have been made in controlling extremity hemorrhage with tourniquets, but not all injuries are amenable to tourniquet application. Topical hemostatic agents and dressings have also contributed to success in controlling extremity and compressible junctional hemorrhage, and their efficacy continues to increase as enhanced products are developed. Since the addition of Combat Gauze™ (Z-Medica Corporation, Wallingford, CT, USA; http://www.z-medica.com/) in April 2008 to the Tactical Combat Casualty Care (TCCC) Guidelines, there are consistent data from animal studies of severe hemorrhage that chitosan-based hemostatic gauze dressings developed for battlefield application are, at least, equally efficacious as Combat Gauze. Successful outcomes are also reported using newer chitosan-based dressings in civilian hospital-based surgical case reports and prehospital (battlefield) case reports and series. Additionally, there have been no noted complications or safety concerns in these cases or across many years of chitosan-based hemostatic dressing use in both the military and civilian prehospital sectors. Consequently, after a decade of clinical use, there is added benefit and a good safety record for using chitosan-based gauze dressings. For these reasons, many specific US military Special Operations Forces, NATO militaries, and emergency medical services (EMS) and law enforcement agencies have already implemented the widespread use of these new recommended chitosan-based hemostatic dressings. Based on the past battlefield success, this report proposes to keep Combat Gauze as the hemostatic dressing of choice along with the new addition of Celox™ Gauze (Medtrade Products Ltd., Crewe, UK; http://www.celoxmedical.com/usa/products /celox-gauze/) and ChitoGauze® (HemCon Medical Technologies, Portland, OR, USA; http://www.hemcon.com/) to the TCCC Guidelines. 2014.

Kaolin-based hemostatic dressing improves hemorrhage control from a penetrating inferior vena cava injury in coagulopathic swine.

PubMed

Koko, Kiavash R; McCauley, Brian M; Gaughan, John P; Nolan, Ryan S; Fromer, Marc W; Hagaman, Ashleigh L R; Choron, Rachel L; Brown, Spencer A; Hazelton, Joshua P

2017-07-01

Retrohepatic inferior vena cava (RIVC) injuries are often lethal due to challenges in obtaining hemorrhage control. We hypothesized that packing with a new kaolin-based hemostatic dressing (Control+; Z-Medica, Wallingford, CT) would improve hemorrhage control from a penetrating RIVC injury compared with packing with standard laparotomy sponges alone. Twelve male Yorkshire pigs received a 25% exchange transfusion of blood for refrigerated normal saline to induce a hypothermic coagulopathy. A laparotomy was performed and a standardized 1.5 cm injury to the RIVC was created which was followed by temporary abdominal closure and a period of uncontrolled hemorrhage. When the mean arterial pressure reached 70% of baseline, demonstrating hemorrhagic shock, the abdomen was re-entered, and the injury was treated with perihepatic packing using standard laparotomy sponges (L; n = 6) or a new kaolin-based hemostatic dressing (K; n = 6). Animals were then resuscitated for 6 hours with crystalloid solution. The two groups were compared using the Wilcoxon rank sum test and Fisher exact test. A p value of 0.05 or less was considered statistically significant. There was no difference in the animal's temperature, heart rate, mean arterial pressure, cardiac output, and blood loss at baseline or before packing was performed (all p > 0.05). In the laparotomy sponge group, five of six pigs survived the entire study period, whereas all six pigs treated with kaolin-based D2 hemostatic dressings survived. Importantly, there was significantly less blood loss after packing with the new hemostatic kaolin-based dressing compared with packing with laparotomy sponge (651 ± 180 mL vs. 1073 ± 342 mL; p ≤ 0.05). These results demonstrate that the use of this new hemostatic kaolin-based dressing improved hemorrhage control and significantly decreased blood loss in this penetrating RIVC model. This is basic science research based on a large animal model, level V.

Combination Effect of Hemostatic and Disinfecting Agents on Micro-leakage of Restorations Bonded with Different Bonding Systems

PubMed Central

H, Farhadpour; F, Sharafeddin; Sc, Akbarian; B, Azarian

2016-01-01

Statement of Problem: Hemostatic agents may affect the micro-leakage of different adhesive systems. Also, chlorhexidine has shown positive effects on micro-leakage. However, their interaction effect has not been reported yet. Objectives: To evaluate the effect of contamination with a hemostatic agent on micro-leakage of total- and self-etching adhesive systems and the effect of chlorhexidine application after the removal of the hemostatic agent. Materials and Methods: Standardized Class V cavity was prepared on each of the sixty caries free premolars at the cemento-enamel junction, with the occlusal margin located in enamel and the gingival margin in dentin. Then, the specimens were randomly divided into 6 groups (n = 10) according to hemostatic agent (H) contamination, chlorhexidine (CHX) application, and the type of adhesive systems (Adper Single Bond and Clearfil SE Bond) used. After filling the cavities with resin composite, the root apices were sealed with utility wax. Furthermore, all the surfaces, except for the restorations and 1mm from the margins, were covered with two layers of nail varnish. The teeth were immersed in a 0.5% basic fuschin dye for 24 hours, rinsed, blot-dried and sectioned longitudinally through the center of the restorations bucco- lingualy. The sections were examined using a stereomicroscope and the extension of dye penetration was analyzed according to a non-parametric scale from 0 to 3. Statistical analysis was performed using Kruskal-Wallis test and Mann-Whitney U-test. Results: While ASB group showed no micro-leakage in enamel, none of the groups showed complete elimination of micro-leakage from the dentin. Regarding micro-leakage at enamel, and dentin margins, there was no significant difference between groups 1 and 2, 1 and 3, and 2 and 3 (p > 0.05). A significantly lower micro-leakage at the enamel and dentin margins was observed in group 3, compared to group 6. No significant difference was observed between groups 4 and 5 in enamel (p = 0.35) and dentin (p = 0.34). Group 6 showed significantly higher micro-leakage, compared to group 4 and 5 (p < 0.05). Conclusions: Hemostatic agent contamination had no significant effect on micro-leakage of total- and self-etching adhesive systems. Application of chlorhexidine after the removal of hemostatic agent increased micro-leakage in self-etching adhesives but did not affect when total-etching was used. PMID:28959756

Epidural spinal cord compression with neurologic deficit associated with intrapedicular application of hemostatic gelatin matrix during pedicle screw insertion.

PubMed

Buchowski, Jacob M; Bridwell, Keith H; Lenke, Lawrence G; Good, Christopher R

2009-06-01

Case report. In order to demonstrate the dangers of intrapedicular application of a hemostatic gelatin matrix to decrease blood loss during pedicle screw insertion, we present 2 patients who--as a result of inadvertent extravasation of the matrix into the spinal canal--developed epidural spinal cord compression (ESCC) requiring emergent decompression. Variety of hemostatic agents can control bleeding during pedicle screw insertion. We have often used a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles by injecting the material into the pedicle after manually palpating the pedicle. Medical records and radiographic studies of 2 patients with AIS who underwent surgical treatment of their deformity and developed a neurologic deficit due to extravasation of FloSeal were reviewed. A 15 year-old male underwent T4 to L2 posterior spinal fusion (PSF). During pedicle screw insertion, a change in NMEPs and SSEPs was noted. A wake-up test confirmed bilateral LE paraplegia. Screws were removed and no perforations were noted on manual palpation. MRI showed T7 to T10 ESCC. He underwent a T5 to T10 laminectomy and hemostatic gelatin matrix noted in the canal and was evacuated. He was ambulatory at 2 weeks and by 3 months he had complete recovery. The second patient was a 15 year-old female who underwent T4 to L1 PSF. Following screw insertion, deterioration in NMEPs and SSEPs was noted. Screws were removed and SCM data returned to baseline. Except for 3 screws that had an inferior breach (Left T7 and Bilateral T8), screws were reinserted and remainder of the surgery was uneventful. Postoperative examination was normal initially but 2 days later, she developed left LE numbness/weakness. Implants were removed and MRI showed T4 to T9 ESCC.She underwent a left (concave) T4 to T9 hemilaminectomy. Hemostatic gelatin matrix was noted and was evacuated. Six weeks following surgery, she had a complete neurologic recovery. The use of a hemostatic gelatin matrix to decrease bleeding from cannulated pedicles during pedicle screw insertion can result in inadvertent extravasation into the spinal canal resulting in ESCC even in the absence of an apparent medial pedicle breach. Given the dangers associated with the technique, we recommend that gelatin matrix products be used judiciously during pedicle screw insertion.

Associations between vitamin K status and hemostatic and inflammatory biomarkers in community-dwelling adults: The multi-ethnic study of atherosclerosis

USDA-ARS?s Scientific Manuscript database

Vitamin K is integral to hemostatic function, and in vitro and animal experiments suggest that vitamin K can suppress production of inflammatory cytokines. To test the hypothesis that higher vitamin K status is associated with lower hemostasic activation and inflammation in community-dwelling adults...

Intentional placental removal on suspicious placenta accreta spectrum: still prohibited?

PubMed

Matsubara, Shigeki; Takahashi, Hironori

2018-01-01

Intentional placental removal for abnormally invasive placenta (AIP) is fundamentally abandoned at planned surgery for it. Whether this holds true even after recent introduction of various hemostatic procedures is unclear. We discussed on this issue based on our own experiences and also on the recent reports on various hemostatic procedures. Studies directly answering this question have been lacking. We must weigh the balance between the massive bleeding and possibility of uterus-preservation when intentional placental removal strategy is employed. An almost forgotten strategy, the "intentional placental removal" for planned AIP surgery may regain its position when appropriate hemostatic procedures are concomitantly used depending on the situation. Even employing this strategy, quick decision to perform hysterectomy under multidisciplinary team may be important.

Effects of Contamination by Hemostatic Agents and Use of Cleaning Agent on Etch-and-Rinse Dentin Bond Strength.

PubMed

Pucci, César Rogério; Araújo, Rodrigo Maximo de; Lacerda, Ana Julia Farias de; Souza, Mirella Anjos de; Huhtala, Maria Filomena Rocha Lima; Feitosa, Fernanda Alves

2016-01-01

The aim of this study was to evaluate the influence of contamination by hemostatic agents and rinsing with chlorhexidine on bond strength between dentin and resin composite. Ninety-six bovine teeth were sectioned to expose a flat dentin surface area. A standardized cavity with 2.0 mm in thickness, superficial diameter of 4.0 mm and bottom diameter of 3.0 mm was prepared with a diamond bur in each dentin specimen. The teeth were divided into four groups according to the hemostatic employed: G1: control; G2: use of ViscoStat, Ultradent; G3: Hemosthasegel, FGM; and G4: Hemostop, Dentsply. The groups were divided into two subgroups according to the cleaning protocol method (n=12): A: without any further cleaning; and B: cleaning with chlorhexidine at 0.2%. All cavities were filled using a dentin adhesive and a resin composite, following the manufacturer's instructions. After 24 h, the specimens were aged by thermal and mechanical cycling. The bond strength was determined by the push out bond test (MPa), Statistical analysis was performed using two-way ANOVA and Tukey test (p<0.05). Statistically significant differences were detected among all groups treated with hemostatic agents and the control group. The post-hoc test showed that cleaning the cavity with chlorhexidine significantly improves the bond strength between dentin and resin composite. Our results suggested that the use of chlorhexidine can reestablish the bond strength between dentin and resin composite when a hemostatic agent was applied.

Managing port-site bleeding during less invasive coronary artery bypass grafting.

PubMed

Kiani, Soroosh; Brecht, Mary-Lynn; Lovinger, Katherine; Poston, Robert S

2012-10-01

Robotic-assisted coronary artery bypass grafting (r-CABG) requires the placement of ports bluntly through the chest wall. When removed, these ports create bleeding sites that can be difficult to detect and treat. This study evaluated whether a topical hemostatic agent placed locally within these sites helps to reduce bleeding and blood product requirements. We retrospectively analyzed outcomes for r-CABG cases where 5 mL of a flowable hemostatic agent was injected locally within all port sites (hemostat group, n = 62) compared with patients whose port sites were untreated (controls, n = 131). Outcomes included chest tube output, red blood cell (RBC) transfusions, length of hospital stay, and the risk of reoperation for bleeding. Analyses were adjusted for risk factors known to influence bleeding and Society of Thoracic Surgeons (STS) risk score as a weighted composite of variables, which controls for patient and clinical variables. The 2 study groups had similar baseline characteristics and underwent the same r-CABG procedure. The hemostat group had significant reductions in RBC transfusion (24.2% versus 40.8% receiving blood; P = .026; 0.44 versus 1.39 U transfused postoperatively, P = .024). After adjustment for bleeding risks (using STS risk score), differences in transfusions remained significant. Reoperation rates for bleeding, length of stay, chest tube drainage, and intraoperative transfusions were not significantly different in the 2 groups. There was significantly reduced postoperative bleeding and less exposure to blood products in the hemostat group. These findings suggest that undetected bleeding from sites used for port access serves as an underappreciated source of morbidity after r-CABG.

Effectiveness of the addition of Lidocaine to a hemostatic, bioresorbable putty in the treatment of iliac crest donor site pain.

PubMed

Müller, Marc Andreas; Mehrkens, Arne; Zürcher, Roman; Vavken, Patrick; Valderrabano, Victor

2014-12-08

The harvest of iliac crest bone grafts (ICBG) is associated with relevant donor site pain, but may be lowered by the application of lidocaine loaded on biodegradable, hemostatic putty for sustained local analgesic release. The goal of this double-blind controlled trial was to assess the efficacy of adding lidocaine to a hemostatic putty (Orthostat ™) to treat donor site pain following harvest of ICBG in foot and ankle procedures. After ICBG harvest during a foot and ankle procedure, the resulting bone defect was either filled with Orthostat™ (n = 7) or with the same hemostatic putty loaded with lidocaine (Orthostat-L™, n = 7). During the first 72 postoperative hours, donor site and surgical site pain were managed by patient controlled morphine delivery and a peripheral nerve block. Donor site pain was periodically quantified on a Visual Analog (VAS) and a Wong Baker FACES scale. Pain scores were plotted over time to calculate the area under the curve (AUC) to quantify the overall pain experienced in specific time intervals. Orthostat-L™ significantly reduced donor site pain over the first 12 hours postoperatively as evidenced by a significant decrease of the AUC in both VAS (p = 0.0366) and Wong Baker FACES pain score plots (p = 0.0024). Cumulated morphine uses were not significantly decreased with Orthostat-L™. The addition of lidocaine to a hemostatic putty offers a significant ICBG donor site pain reduction over the first 12 postoperative hours. ClinicalTrials.gov NCT01504035. Registered January 2nd 2012.

Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching.

PubMed

Park, Jun Chul; Kim, Yeong Jin; Kim, Eun Hye; Lee, Jinae; Yang, Hyun Su; Kim, Eun Hwa; Hahn, Kyu Yeon; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan

2018-02-07

Recently, the application of hemostatic powder to the bleeding site has been used to treat active upper gastrointestinal bleeding (UGIB). We aimed to assess the effectiveness of the polysaccharide hemostatic powder (PHP) in patients with non-variceal UGIB. We reviewed prospectively collected 40 patients with UGIB treated with PHP therapy between April 2016 and January 2017 (PHP group) and 303 patients with UGIB treated with conventional therapy between April 2012 and October 2014 (conventional therapy group). We compared the rate of successful hemostasis and the rebleeding between the two groups after as well as before propensity score matching using the Glasgow-Blatchford score and Forrest classification. Thirty patients treated with the PHP and 60 patients treated with conventional therapy were included in the matched groups. Baseline patient characteristics including comorbidities, vital signs, and bleeding scores were similar in the matched groups. The rate of immediate hemostasis and 7-day and 30-day rebleeding were also similar in the two groups before and after matching. In the subgroup analysis, no significant differences in immediate hemostasis or rebleeding rate were noted between PHP in monotherapy and PHP combined with a conventional hemostatic method. At 30 days after the therapy, there were no significant PHP-related complications or mortality. Given its safety, the PHP proved feasible for endoscopic treatment of UGIB, having similar effectiveness as that of conventional therapy. The PHP may become a promising hemostatic method for non-variceal UGIB. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Normal Hemostatic Profiles and Coagulation Factors in Healthy Free-Living Florida Manatees ( Trichechus manatus latirostris).

PubMed

Barratclough, Ashley; Floyd, Ruth Francis; Conner, Bobbi; Reep, Roger; Ball, Ray; Stacy, Nicole

2016-10-01

Hemostatic disorders presumptively play an important role in the pathophysiology of several important disease conditions in the Florida manatee ( Trichechus manatus latirostris). Prior to pursuing such clinical implications, it is essential to establish normal hemostatic profiles in clinically healthy animals. During annual health assessments of free-living manatees organized by the US Geological Survey, blood samples were collected from 12 healthy animals from the Atlantic coast and 28 from the Gulf of Mexico coast of Florida, with body lengths of 210-324 cm. The following analyses were performed on citrated plasma: prothrombin (PT), partial thromboplastin time (PTT), and concentrations of fibrinogen, D-dimers, and coagulation factors VII, VIII, IX, X, XI, and XII. Compared to other mammalian species, manatees had short PT (9.2±1.5 s) and PTT (10.7±0.5 s), fibrinogen was 369±78.7 mg/dL, antithrombin III was 132±11%, and D-dimer was 142±122 ng/mL. Baseline concentrations for the listed coagulation factors were established. When comparing coagulation factors between locations, Atlantic coast manatees had significantly higher factors VIII, IX, and X than did Gulf Coast manatees. This finding may reflect differences in water salinity, diet, or genetics. There were no differences in coagulation factors when among sexes and sizes. These baselines for hemostatic profiles and coagulation factors in healthy free-living manatees lay the foundation for diagnosis and future research of hemostatic disorders and contribute to understanding their role in the pathophysiology of manatees affected by various diseases.

Hemostatic Agents in Periapical Surgery: A Randomized Study of Gauze Impregnated in Epinephrine versus Aluminum Chloride.

PubMed

Menéndez-Nieto, Isabel; Cervera-Ballester, Juan; Maestre-Ferrín, Laura; Blaya-Tárraga, Juan Antonio; Peñarrocha-Oltra, David; Peñarrocha-Diago, Miguel

2016-11-01

Adequate bleeding control is essential for the success of periapical surgery. The aim of this study was to evaluate the effects of 2 hemostatic agents on the outcome of periapical surgery and their relationship with patient and teeth parameters. A prospective study was designed with 2 randomized parallel groups, depending on the hemostatic agent used: gauze impregnated in epinephrine (epinephrine group) and aluminum chloride (aluminum chloride group). The analysis of the hemorrhage control was judged before and after the application of the hemostatic agents by the surgeon, and 2 examiners independently recorded it as adequate (complete hemorrhage control) or inadequate (incomplete hemorrhage control). Ninety-nine patients with a periradicular lesion were enrolled in this study and divided into 2 groups: gauze impregnated in epinephrine in 48 patients (epinephrine group) or aluminum chloride in 51 (aluminum chloride group). In epinephrine group adequate hemostasis was achieved in 25 cases, and in aluminum chloride group it was achieved in 37 cases (P < .05). The outcome was better in the aluminum chloride group than in the gauze impregnated in epinephrine group. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Osteogenic differentiation of preosteoblasts on a hemostatic gelatin sponge

PubMed Central

Kuo, Zong-Keng; Lai, Po-Liang; Toh, Elsie Khai-Woon; Weng, Cheng-Hsi; Tseng, Hsiang-Wen; Chang, Pei-Zen; Chen, Chih-Chen; Cheng, Chao-Min

2016-01-01

Bone tissue engineering provides many advantages for repairing skeletal defects. Although many different kinds of biomaterials have been used for bone tissue engineering, safety issues must be considered when using them in a clinical setting. In this study, we examined the effects of using a common clinical item, a hemostatic gelatin sponge, as a scaffold for bone tissue engineering. The use of such a clinically acceptable item may hasten the translational lag from laboratory to clinical studies. We performed both degradation and biocompatibility studies on the hemostatic gelatin sponge, and cultured preosteoblasts within the sponge scaffold to demonstrate its osteogenic differentiation potential. In degradation assays, the gelatin sponge demonstrated good stability after being immersed in PBS for 8 weeks (losing only about 10% of its net weight and about 54% decrease of mechanical strength), but pepsin and collagenases readily biodegraded it. The gelatin sponge demonstrated good biocompatibility to preosteoblasts as demonstrated by MTT assay, confocal microscopy, and scanning electron microscopy. Furthermore, osteogenic differentiation and the migration of preosteoblasts, elevated alkaline phosphatase activity, and in vitro mineralization were observed within the scaffold structure. Each of these results indicates that the hemostatic gelatin sponge is a suitable scaffold for bone tissue engineering. PMID:27616161

Hemostatic kaolin-polyurethane foam composites for multifunctional wound dressing applications.

PubMed

Lundin, Jeffrey G; McGann, Christopher L; Daniels, Grant C; Streifel, Benjamin C; Wynne, James H

2017-10-01

There are numerous challenges associated with the acute care of traumatic limb injuries in forward military settings. A lack of immediate medical facilities necessitates that the wound dressing perform multiple tasks including exudate control, infection prevention, and physical protection of the wound for extended periods of time. Here, kaolin was incorporated into recently developed robust polyurethane (PU) hydrogel foams at 1-10wt% in an effort to impart hemostatic character. ATR-IR and gel fraction analysis demonstrated that the facile, one-pot synthesis of the PU hydrogel was unaffected by kaolin loading, as well as the use of a non-toxic catalyst, which significantly improved cytocompatibility of the materials. Kaolin was generally well dispersed throughout the PU matrix, though higher loadings exhibited minor evidence of aggregation. Kaolin-PU composites exhibited burst release of ciprofloxacin over 2h, the initial release rates of which increased with kaolin loading. Kaolin loading imparted excellent hemostatic character to the PU foams at relatively low loading levels (5wt%). This work demonstrates the simple and inexpensive synthesis of robust, hemostatic, and absorptive kaolin-PU foams that have promising potential as multifunctional wound dressing materials. Published by Elsevier B.V.

In vivo degradation of polyurethane foam with 55 wt % polyethylene glycol.

PubMed

Broekema, Ferdinand I; Van Leeuwen, M Barbara M; Van Minnen, Baucke; Bos, Rudolf R M

2015-11-01

Most topical hemostatic agents are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission while adjustments in the production process of these materials are limited. A synthetic hemostatic agent based on polyurethane (PU) and polyethylene glycol (PEG) was developed to overcome these disadvantages. The goal of this study was to compare the degradation process of this biomaterial to collagen and gelatin hemostatic agents. Samples of the test materials were implanted subcutaneously in both rats and rabbits. The animals were sacrificed at certain time intervals up to three years and the explanted samples were microscopically assessed. The histological examination showed a comparable pattern of degradation for the different test materials. Remnants of gelatin and collagen were seen up to 26 and 39 weeks, respectively. For PU, it took up to three years before micro-particles of the material were no longer detected. All biomaterials showed a good biocompatibility and no severe foreign body reactions occurred. The good biocompatibility and predictable pattern of resorption indicate that PU can be used as a topical hemostatic agent. However, a degradation time comparable to collagen and gelatin would be favorable. © 2015 Wiley Periodicals, Inc.

Effects of two combined oral contraceptives containing ethinyl estradiol 20 microg combined with either drospirenone or desogestrel on lipids, hemostatic parameters and carbohydrate metabolism.

PubMed

Klipping, Christine; Marr, Joachim

2005-06-01

To compare the effect of ethinyl estradiol 20 microg/drospirenone 3 mg (EE 20 microg/DRSP 3 mg) administered according to a 24/4 regimen with ethinyl estradiol 20 microg/desogestrel 150 microg (EE 20 microg/DSG 150 microg) administered according to the conventional 21/7 regimen on lipid, carbohydrate and hemostatic parameters. In this open-label study, healthy women were randomized to EE 20 microg/DRSP 3 mg or EE 20 microg/DSG 150 microg for seven cycles. Mean differences in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol levels at cycle 7 compared to baseline were assessed. Secondary variables included changes in other lipid, hemostatic and carbohydrate parameters. Both treatments increased HDL-cholesterol, but decreased LDL-cholesterol by a comparable extent. Although slightly elevated in both groups, blood glucose and C-peptide levels measured during oral glucose tolerance tests were within normal reference ranges at cycle 7. Overall, the differences in lipid, hemostatic or carbohydrate parameters were not significant between the two treatments. EE 20 microg/DRSP 3 mg has a good safety profile comparable with EE 20 microg/DSG 150 microg.

Vaccine Immunotherapy for Prostate Cancer. Addendum

DTIC Science & Technology

2007-07-01

a hemostatic agent. It is a water-insoluble, off-white, non- elastic, porous, pliable product prepared from purified pork skin. The Gelfoam gelatin ...increasing gelatin volume (27). PROTOCOL #1 Lubaroff; final addendum report, page 8 The mechanism of action of surface-mediated hemostatic devices is...and the clinical protocol. 3.2.14 Allergy or religious objection to pork products; Gelfoam is produced from pork. 4. Registration Procedures

Coagulopathy and traumatic shock: Characterizing hemostatic function during the critical period prior to fluid resuscitation

PubMed Central

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

2009-01-01

Aims Identifying early changes in hemostatic clot function as a result of tissue injury and hypoperfusion may provide important information regarding the mechanisms of traumatic coagulopathy. A combat-relevant swine model was used to investigate the development of coagulopathy during trauma by monitoring hemostatic function during increasing severity of shock. Methods Swine were injured (soft tissue + femur fracture) and hemorrhaged while continuously monitoring Oxygen Debt (OD) by indirect calorimetry at the airway. Hemostatic function was assessed by Thrombelastography (TEG), prothrombin time (PT), partial Thromboplastin time (PTT), and fibrinogen concentration and compared before hemorrhage (D0) and during shock when OD= 40 and 80 ml/kg. An instrumented sham group was used for comparison. Results N=23 swine (n=18 hemorrhage, n=5 sham) weighing 45+/−6 Kg were studied after removing an average of 34+/−14% of blood volume during hemorrhage. Hgb, Hct, platelet counts, PT and PTT did not change with increasing OD (p>0.05). Fibrinogen was reduced significantly by OD=40 ml/kg (mean diff =−59.9 mg/dl, 95% CI diff [−95.1, −24.6]). TEG parameters representing clot initiation (R) and polymerization (K and Alpha Angle) did not change with increasing OD during shock (p>0.053). Clot strength (MA) was reduced in the hemorrhage group by OD=80 ml/kg (mean diff = −4.1 mm, 95% CI diff [−7.4, −0.8]). Conclusion In this swine model of traumatic shock, fibrinogen was significantly reduced and an isolated reduction in clot strength (MA) was found with increasing OD. Fibrinogen consumption and altered platelet function may account for the earliest changes in hemostatic function during traumatic shock. PMID:19854556

Interventions for treating acute bleeding episodes in people with acquired hemophilia A.

PubMed

Zeng, Yan; Zhou, Ruiqing; Duan, Xin; Long, Dan; Yang, Songtao

2014-08-28

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation factor VIII (FVIII). In most cases, bleeding episodes are spontaneous and severe at presentation. The optimal hemostatic therapy is controversial. To determine the efficacy of hemostatic therapies for acute bleeds in people with acquired hemophilia A; and to compare different forms of therapy for these bleeds. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2014, Issue 4) and MEDLINE (Ovid) (1948 to 30 April 2014). We searched the conference proceedings of the: American Society of Hematology; European Hematology Association; International Society on Thrombosis and Haemostasis (ISTH); and the European Association for Haemophilia and Allied Disorders (EAHAD) (from 2000 to 30 April 2014). In addition to this we searched clinical trials registers. All randomised controlled trials and quasi-randomised trials of hemostatic therapies for people with acquired hemophilia A, with no restrictions on gender, age or ethnicity. No trials matching the selection criteria were eligible for inclusion. No trials matching the selection criteria were eligible for inclusion. No randomised clinical trials of hemostatic therapies for acquired hemophilia A were found. Thus, we are not able to draw any conclusions or make any recommendations on the optimal hemostatic therapies for acquired hemophilia A based on the highest quality of evidence. GIven that carrying out randomized controlled trials in this field is a complex task, the authors suggest that, while planning randomised controlled trials in which patients can be enrolled, clinicians treating the disease continue to base their choices on alternative, lower quality sources of evidence, which hopefully, in the future, will also be appraised and incorporated in a Cochrane Review.

Which hemostatic markers add to the predictive value of conventional risk factors for coronary heart disease and ischemic stroke? The Caerphilly Study.

PubMed

Smith, Ann; Patterson, Chris; Yarnell, John; Rumley, Ann; Ben-Shlomo, Yoav; Lowe, Gordon

2005-11-15

Few studies have examined whether hemostatic markers contribute to risk of coronary disease and ischemic stroke independently of conventional risk factors. This study examines 11 hemostatic markers that reflect different aspects of the coagulation process to determine which have prognostic value after accounting for conventional risk factors. A total of 2398 men aged 49 to 65 years were examined in 1984 to 1988, and the majority gave a fasting blood sample for assay of lipids and hemostatic markers. Men were followed up for a median of 13 years, and cardiovascular disease (CVD) events were recorded. There were 486 CVD events in total, 353 with prospective coronary disease and 133 with prospective ischemic stroke. On univariable analysis, fibrinogen, low activated protein C ratio, D-dimer, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) were associated significantly with risk of CVD. On multivariable analyses with conventional risk factors forced into the proportional hazards model, fibrinogen, D-dimer, and PAI-1 were significantly associated with risk of CVD, whereas factor VIIc showed an inverse association (P=0.001). In a model that contained the conventional risk factors, the hazard ratio for subsequent CVD in the top third of the distribution of predicted risk relative to the bottom third was 2.7 for subjects without preexisting CVD. This ratio increased to 3.7 for the model that also contained the 4 hemostatic factors. Fibrinogen, D-dimer, PAI-1 activity, and factor VIIc each has potential to increase the prediction of coronary disease/ischemic stroke in middle-aged men, in addition to conventional risk factors.

Stent-Grafts in the Management of Hemorrhagic Complications Related to Hemostatic Closure Devices: Report of Two Cases

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

Giansante Abud, Daniel; Mounayer, Charbel; Saint-Maurice, Jean Pierre

We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved tomore » be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.« less

Evaluation of FloSeal as a Potential Intracavitary Hemostatic Agent

DTIC Science & Technology

2006-02-01

Laws ER Jr. Use of FloSeal hemostatic sealant in transsphenoidal pituitary surgery : technical note. Neurosurgery. 2002;51:513–516. 14. Kheirabadi BS...of death in com- bat and civilian trauma. When surgery is unavailable, one potential solution to such hemorrhage might be the introduction of an agent...situations, including venous and arterial vascular surgery ,7,9 cardiac valve replacement or cardiopulmonary bypass grafting,6 partial nephrectomies,10

Colonoscopic findings and management of patients with outbreak typhoid fever presenting with lower gastrointestinal bleeding.

PubMed

Shaikhani, Mohammad A R; Husein, Hiwa A B; Karbuli, Taha A; Mohamed, Mohamed Abdulrahman

2013-09-01

Lower gastrointestinal bleeding (LGIB) along with intestinal perforation is a well-known complication of typhoid fever. Reports of colonoscopic appearance and intervention of typhoid perforation involve only few cases. This series reports the colonoscopic findings and the role of colonoscopic hemostatic interventions in controlling the bleeding ileocolonic lesions. During the typhoid fever outbreak in Sulaymaniyah City in Iraqi Kurdistan Region, we received 52 patients with LGIB manifesting as fresh bleeding per rectum or melena. We performed total colonoscopy with ileal intubation for all cases. The findings were recorded and endoscopic hemostatic intervention with adrenaline-saline injection and argon plasma coagulation was applied to actively bleeding lesion. These patients were young, 11-30 years of age, with female preponderance. Blood culture was positive in 50 %. Colonoscopic findings were mostly located in the ileocecal region, although other areas of the colon were involved in many cases. Twenty-four percent of the cases required endoscopic hemostatic intervention by adrenaline injection with argon plasma coagulation which was effective in all patients except one who died in spite of surgical intervention in addition of endoscopic hemostasis. Dual endoscopic hemostatic intervention can be a safe and effective management option for patients with LGIB due to typhoid fever.

The Design and Testing of a Dual Fiber Textile Matrix for Accelerating Surface Hemostasis

PubMed Central

Fischer, Thomas H.; Vournakis, John N.; Manning, James E.; McCurdy, Shane L.; Rich, Preston B.; Nichols, Timothy C.; Scull, Christopher M.; McCord, Marian G.; Decorta, Joseph A.; Johnson, Peter C.; Smith, Carr J.

2011-01-01

The standard treatment for severe traumatic injury is frequently compression and application of gauze dressing to the site of hemorrhage. However, while able to rapidly absorb pools of shed blood, gauze fails to provide strong surface (topical) hemostasis. The result can be excess hemorrhage-related morbidity and mortality. We hypothesized that cost-effective materials (based on widespread availability of bulk fibers for other commercial uses) could be designed based on fundamental hemostatic principles to partially emulate the wicking properties of gauze while concurrently stimulating superior hemostasis. A panel of readily available textile fibers was screened for the ability to activate platelets and the intrinsic coagulation cascade in vitro. Type E continuous filament glass and a specialty rayon fiber were identified from the material panel as accelerators of hemostatic reactions and were custom woven to produce a dual fiber textile bandage. The glass component strongly activated platelets while the specialty rayon agglutinated red blood cells. In comparison with gauze in vitro, the dual fiber textile significantly enhanced the rate of thrombin generation, clot generation as measured by thromboelastography, adhesive protein adsorption and cellular attachment and activation. These results indicate that hemostatic textiles can be designed that mimic gauze in form but surpass gauze in ability to accelerate hemostatic reactions. PMID:19489008

Fibrin Sealant: The Only Approved Hemostat, Sealant, and Adhesive—a Laboratory and Clinical Perspective

PubMed Central

Spotnitz, William D.

2014-01-01

Background. Fibrin sealant became the first modern era material approved as a hemostat in the United States in 1998. It is the only agent presently approved as a hemostat, sealant, and adhesive by the Food and Drug Administration (FDA). The product is now supplied as patches in addition to the original liquid formulations. Both laboratory and clinical uses of fibrin sealant continue to grow. The new literature on this material also continues to proliferate rapidly (approximately 200 papers/year). Methods. An overview of current fibrin sealant products and their approved uses and a comprehensive PubMed based review of the recent literature (February 2012, through March 2013) on the laboratory and clinical use of fibrin sealant are provided. Product information is organized into sections based on a classification system for commercially available materials. Publications are presented in sections based on both laboratory research and clinical topics are listed in order of decreasing frequency. Results. Fibrin sealant remains useful hemostat, sealant, and adhesive. New formulations and applications continue to be developed. Conclusions. This agent remains clinically important with the recent introduction of new commercially available products. Fibrin sealant has multiple new uses that should result in further improvements in patient care. PMID:24729902

Radial hemostasis is facilitated with a potassium ferrate hemostatic patch: the Statseal with TR band assessment trial (STAT).

PubMed

Seto, Arnold H; Rollefson, William; Patel, Mitul P; Suh, William M; Tehrani, David M; Nguyen, Jacqueline A; Amador, Daniel G; Behnamfar, Omid; Garg, Vinisha; Cohen, Mauricio G

2018-05-15

Hemostasis is a limiting factor for discharge after uncomplicated transradial procedures. The potassium ferrate hemostatic patch (PFHP) may serve as an adjunct to the air-bladder TR band (TRB) and allow expedited deflation of the TRB. Prospective multicenter randomized controlled trial comparing radial hemostatic protocols. Deflation of the TRB was attempted at 40 minutes with PFHP and at 120 minutes without the PFHP. The primary outcome was time to full deflation of the TRB with hemostasis. At four U.S. sites, 180 patients were enrolled after receiving a minimum of 5,000 units of unfractionated heparin or bivalirudin. Interventions comprised 30% of procedures. Successful TRB deflation occurred at 43 ± 14 minutes with PFHP and 160 ± 43 minutes without PFHP (p<0.001). Minor hematomas occurred in 9 (10.3%) of TRB patients and 16 (17.2%) of PFHP patients (p=0.20). Radial artery occlusion occurred in 2% of patients in the PFHP group (p=NS). Outpatients randomized to PFHP were discharged 51 ± 83.5 minutes earlier than control. The PFHP hemostatic patch facilitated early deflation of the TRB with a nonsignificant increase in forearm hematomas. Use of the PFHP may improve patient throughput and allow for earlier discharge following transradial procedures.

Development of a Standard Swine Hemorrhage Model for Efficacy Assessment of Topical Hemostatic Agents

DTIC Science & Technology

2011-07-01

Blw:kbourne. MD Background: The diverse infomlation of efficacy of hemostatic pmducts. obtained from different military laboratories using ...model was tested with all or some of these modifications in four experimental conditions (n = 5-6 pigs pc:r condition) using Combat Gauze (CG) as...be suitable lf.>r testing every agent and some modifications may be necessary for specific applications. fu•·thermore, laboratory studies using this

Comparison of 10 Hemostatic Dressings in a Groin Puncture Model in Swine

DTIC Science & Technology

2009-09-01

attended or remote surgical theaters as well as for first aid bandaging in extreme sport.Methods to suppress massive external hemorrhage should be provided...Products Newport, O Instaclot (IC) Emergency Medical Devices Loxa WoundStat (WS) TraumaCure, Inc. Bethesda, Md Solid (flexible) agents Alpha Bandage ...referred to throughout are listed in Table I. The hemostatic products and the standard compressed gauze bandage (SD; H&H compressed gauze, H&H

Fibrin glue as a hemostatic agent in hepatic and splenic trauma.

PubMed

Ochsner, M G; Maniscalco-Theberge, M E; Champion, H R

1990-07-01

Fibrin glue is a biologic hemostatic agent that coagulates and seals upon application. It is made by combining human fibrinogen concentrate with standard thrombin solutions containing calcium. Similar to epoxy glue, the two components are applied simultaneously in equal volumes resulting in an almost instantaneous formation of a coagulum. Fibrinogen concentrate is prepared in the blood bank from single donor plasma. Fibrin glue can be applied topically or injected into the parenchyma of solid organs. Twenty-six patients sustained hepatic or splenic trauma from May through August 1989--17 liver and nine splenic injuries. The glue was effective after one application in 21 patients and after a second in five. Hemostasis was achieved despite coagulopathy and thrombocytopenia in eight patients. There were no re-explorations for bleeding, and nine complications occurred in six patients. Our experience suggests fibrin glue is an effective, underutilized adjunctive hemostatic agent in trauma.

[Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

2015-08-01

Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

Robotic surgery and hemostatic agents in partial nephrectomy: a high rate of success without vascular clamping.

PubMed

Morelli, Luca; Morelli, John; Palmeri, Matteo; D'Isidoro, Cristiano; Kauffmann, Emanuele Federico; Tartaglia, Dario; Caprili, Giovanni; Pisano, Roberta; Guadagni, Simone; Di Franco, Gregorio; Di Candio, Giulio; Mosca, Franco

2015-09-01

Robot-assisted partial nephrectomy has been proposed as a technique to overcome technical challenges of laparoscopic partial nephrectomy. We prospectively collected and analyzed data from 31 patients who underwent robotic partial nephrectomy with systematic use of hemostatic agents, between February 2009 and October 2014. Thirty-three renal tumors were treated in 31 patients. There were no conversions to open surgery, intraoperative complications, or blood transfusions. The mean size of the resected tumors was 27 mm (median 20 mm, range 5-40 mm). Twenty-seven of 33 lesions (82%) did not require vascular clamping and therefore were treated in the absence of ischemia. All margins were negative. The high partial nephrectomy success rate without vascular clamping suggests that robotic nephron-sparing surgery with systematic use of hemostatic agents may be a safe, effective method to completely avoid ischemia in the treatment of selected renal masses.

Hemostasis and malignancy.

PubMed

Francis, J L; Biggerstaff, J; Amirkhosravi, A

1998-01-01

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

One amino acid in mouse activated factor VII defines its endothelial protein C receptor (EPCR) binding and modulates its EPCR-dependent hemostatic activity in vivo.

PubMed

Pavani, G; Zintner, S M; Ivanciu, L; Small, J C; Stafford, K A; Szeto, J H; Margaritis, P

2017-03-01

Essentials The lack of factor (F) VIIa-endothelial protein C receptor (EPCR) binding in mice is unresolved. A single substitution of Leu4 to Phe in mouse FVIIa (mFVIIa) enables its interaction with EPCR. mFVIIa with a Phe4 shows EPCR binding-dependent enhanced hemostatic function in vivo vs. mFVIIa. Defining the FVIIa-EPCR interaction in mice allows for further investigating its biology in vivo. Background Human activated factor VII (hFVIIa), which is used in hemophilia treatment, binds to the endothelial protein C (PC) receptor (EPCR) with unclear hemostatic consequences. Interestingly, mice lack the activated FVII (FVIIa)-EPCR interaction. Therefore, to investigate the hemostatic consequences of this interaction in hemophilia, we previously engineered a mouse FVIIa (mFVIIa) molecule that bound mouse EPCR (mEPCR) by using three substitutions from mouse PC (mPC), i.e. Leu4→Phe, Leu8→Met, and Trp9→Arg. The resulting molecule, mFVIIa-FMR, modeled the EPCR-binding properties of hFVIIa and showed enhanced hemostatic capacity in hemophilic mice versus mFVIIa. These data implied a role of EPCR in the action of hFVIIa in hemophilia treatment. However, the substitutions in mFVIIa-FMR only broadly defined the sequence determinants for its mEPCR interaction and enhanced function in vivo. Objectives To determine the individual contributions of mPC Phe4, Met8 and Arg9 to the in vitro/in vivo properties of mFVIIa-FMR. Methods The mEPCR-binding properties of single amino acid variants of mFVIIa or mPC at position 4, 8 or 9 were investigated. Results and conclusions Phe4 in mFVIIa or mPC was solely critical for interaction with mEPCR. In hemophilic mice, administration of mFVIIa harboring a Phe4 resulted in a 1.9-2.5-fold increased hemostatic capacity versus mFVIIa that was EPCR binding-dependent. This recapitulated previous observations made with triple-mutant mFVIIa-FMR. As Leu8 is crucial for hFVIIa-EPCR binding, we describe the sequence divergence of this interaction in mice, now allowing its further characterization in vivo. We also illustrate that modulation of the EPCR-FVIIa interaction may lead to improved FVIIa therapeutics. © 2016 International Society on Thrombosis and Haemostasis.

Comparative Testing of New Hemostatic Agents in a Swine Model of Extremity Arterial and Venous Hemorrhage

DTIC Science & Technology

2010-01-01

by the Institutional Animal Care and Use Committee and all animals received humane care in com- pliance with the Guide for the Care and Use of...diminished markedly in recent military operations, due to sev- eral factors including routine vi-ear of hody armor, judicious use of tourniquets for...extremity hemorrhage, rapid casualty evacuation, and aggressive use of blood products in hemor- rhagic shock.’’ Advanced hemostatic agents further reduce

Self-Expanding, Tough Biodegradable Elastomers for Wound Stasis

DTIC Science & Technology

2015-08-06

results were incon- clusive in mixed (arterial and venous)17 and arterial bleed- ing.18,19 Likewise, QuikClot Zeolite granules were effective in venous...177Y182. 17. Alam HB, Chen Z, Jaskille A, et al. Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin...reactions of hemostatic agents, such as early- generation granular zeolite , have resulted in patient injury.20,21 In this study, the reaction between

Intraoperative anaphylaxis to gelatin in topical hemostatic agents during anterior spinal fusion: a case report.

PubMed

Spencer, Hillard T; Hsu, Joyce T; McDonald, Douglas R; Karlin, Lawrence I

2012-08-01

The use of topical hemostatic agents is widespread and has been shown to reduce bleeding during a wide variety of surgical procedures. Nonetheless, as biologically active agents, there is potential for allergic reactions to these products. This is a report of intraoperative anaphylaxis to gelatin associated with the use of two topical hemostatic agents. Case report. There is no outside funding or potential conflict of interest. A patient with anaphylaxis during anterior spinal fusion. Laboratory assays for tryptase, gelatin-specific immunoglobulin E (IgE), and total IgE. A 14-year-old male with myelomeningocele and scoliosis was treated with anterior spinal fusion from T12 to L3. Gelfoam sponges were applied during the preparation of the disc spaces. Approximately 1 hour later, Floseal hemostatic matrix was applied to a briskly bleeding screw hole in the L3 vertebral body, and the patient experienced an abrupt onset of hypotension and ventilatory difficulty. Epinephrine, dexamethasone, and blood products were administered for hemodynamic support while the surgical site was closed. Removal of the drapes revealed a widespread erythematous rash, and the patient was then transferred to the intensive care unit. When stable 3 days later, he returned to the operating room for completion of the spinal fusion. Postoperative laboratory assays were sent that revealed elevated levels of tryptase, total IgE, porcine, and bovine gelatin-specific IgE. The patient was counseled to avoid gelatin-containing products. At 6-month follow-up, his instrumented spine was radiographically fused and he reported no further allergic issues. Anaphylaxis may occur because of animal gelatin components of topical hemostatic agents. Previous reports have focused on the thrombin components. Care should be taken in the administration of these products, particularly in the atopic individual. Copyright © 2012 Elsevier Inc. All rights reserved.

Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4 Mouse Macrophages

DTIC Science & Technology

2011-09-01

ORIGINAL ARTICLE Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4...not known. Clay minerals are generally considered nontoxic to humans and have been widely used in cosmetics and as excipient in drugs and foods...Bentonite, which has a long history in pharmaceutical formulations,7 along with kaolin are listed in the US Pharmacopeia.8 The sensitivity of some human

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

PubMed

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

2015-02-01

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

[Use of "NovoSeven" (rFVIIa) hemostatic in patients operated with extracorporeal blood circulation].

PubMed

Dement'eva, I I; Sandrikov, V A; Charnaia, M A; Morozov, Iu A; Trekova, N A; Eremenko, A A

2004-01-01

The "NovoSeven" drug was used in 25 patients (male - 18, female - 7) operated on the heart and main vessels including with artificial extracorporeal circulation (AEC). Patients did not have any clinically significant impairment in blood circulation before surgery. Perioperatively, all of them and, immediately after surgery, 4 them had uncontrollable hemorrhages at 10-25 ml/min in spite of extensive hemostatic therapy, including freshly frozen plasma, cryoprecipitate, thromboconcentrate, trasilol and ?-amine acid. Yet in 30 min after "NovoSeven" administration, hemorrhages seized virtually in all patients irrespective of a surgical intervention. It normalized the hemostasis by it differential action on an impairment depending on an activated or suppressed coagulation. Thus, the conclusion is that the "NovoSeven" (rFVIIa) is an effective hemostatic ensuring the correction of massive intra- and postoperative blood losses in cardiosurgery patients. The drug cuts the need in using the donor-blood components, thus, diminishing the risk of multi organ failure that can develop immediately after surgery.

Achieving hemostasis in dermatology – Part 1: Preoperative, intraoperative, and postoperative management

PubMed Central

Kaur, Ravneet Ruby; Glick, Jaimie B.; Siegel, Daniel

2013-01-01

As dermatological procedures continue to become increasingly complex, improved methods and tools to achieve appropriate hemostasis become necessary. The methods for achieving adequate hemostasis are variable and depend greatly on the type of procedure performed and the unique characteristics of the individual patient. In Part 1 of this review, we discuss the preoperative, intraoperative, and postoperative management of patients undergoing dermatologic surgery. We address oral medications and supplements that affect hemostasis, hemostatic anesthesia, and intraoperative interventions such as suture ligation and heat-generating cautery devices. In Part 2 of this review, we will discuss topical hemostats. The authors conducted an extensive literature review using the following keywords: “hemostasis,” “dermatology,” “dermatological surgery,” “dermatologic sutures,” “electrosurgery,” “hemostatic anesthesia,” and “laser surgery.” Sources for this article were identified by searching the English literature in the Pubmed database for the time period from 1940 to March 2012. A thorough bibliography search was also conducted and key references were examined. PMID:23741660

[Hemostatic and analgesic effect of Gonghuan Zhixue Tablet on mice].

PubMed

Fu, Ling-Mei; You, Zhao-Ling; Lei, Lei; Wen, Le-Xi; Chen, Huan-Ming

2004-03-01

To explore the hemostatic and analgesic effect of Gonghuan Zhixue Tablet (GHZXT) on mice and to produce experimental evidence for exploiting new drug for endometrorrhagia caused by Cu-intrauterine contraceptive device (Cu-IUD). Compared with 6-aminocaproic acid and notoginseng, the effects of GHZXT on clotting and bleeding time of mice with capillary method and severed tail were investigated; and compared with aspirin, the analgesic effects of GHZXT on mice were investigated with hot plate and torsive body method. The clotting time of mice was remarkably shortened with a rising of the dosage of GHZXT and the difference between each therapeutic group and distilled water group was remarkable. As compared with distilled water group, the bleeding time of each dosage group of GHZXT was obviously shortened; and each dosage of GHZXT could prolong the time of pain reaction to hot plate and decrease the degree of torsive body of the mice. Pharmacological experiment has proved that GHZXT has evident hemostatic and analgesic function.

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability.

PubMed

Brooks, Marjory B; Turk, James R; Guerrero, Abraham; Narayanan, Padma K; Nolan, John P; Besteman, Elizabeth G; Wilson, Dennis W; Thomas, Roberta A; Fishman, Cindy E; Thompson, Karol L; Ellinger-Ziegelbauer, Heidrun; Pierson, Jennifer B; Paulman, April; Chiang, Alan Y; Schultze, Albert E

2017-01-01

Systemic inflammation co-activates coagulation, which unchecked culminates in a lethal syndrome of multi-organ microvascular thrombosis known as disseminated intravascular coagulation (DIC). We studied an endotoxin-induced inflammatory state in rats to identify biomarkers of hemostatic imbalance favoring hypercoagulability. Intraperitoneal injection of LPS at 15 mg/kg body weight resulted in peripheral leukopenia and widespread neutrophilic sequestration characteristic of an acute systemic inflammatory response. Early indicators of hemostatic pathway activation developed within 4 hours, including increased circulating concentrations of procoagulant extracellular vesicles (EVs), EVs expressing endothelial cell and platelet membrane markers, and high concentration of soluble intercellular adhesion molecule-1 (sICAM-1), plasminogen activator inhibitor-1 (PAI-1), and D-dimers. Inflammation persisted throughout the 48-hour observation period; however, increases were found in a subset of serum microRNA (miRNA) that coincided with gradual resolution of hemostatic protein abnormalities and reduction in EV counts. Dose-adjusted LPS treatment in rats provides a time-course model to develop biomarker profiles reflecting procoagulant imbalance and rebalance under inflammatory conditions.

Hemostatic gauze based on chitosan and hydroquinone: preparation, characterization and blood coagulation evaluation.

PubMed

Cassano, Roberta; Di Gioia, Maria Luisa; Mellace, Silvia; Picci, Nevio; Trombino, Sonia

2017-11-07

This work concerns on the preparation and performance evaluation of a new chitosan hydroquinone based gauze for hemostatic use. Chitosan and hydroquinone were firstly connected by etherification and then linked to the pre-carboxylate gauze. The functionalized material and the chitosan-hydroquinone ether were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy and Differential Scanning Calorimetry (DSC). FT-IR results showed that an esterification occurred on carboxylic group of the gauze. The gauze functionalization degree was also evaluated by volumetric analysis. The ether hydroquinone content was obtained by the Folin test. Moreover, the linkage between hydroquinone and chitosan was confirmed by nuclear magnetic resonance (NMR). The hemostatic activity of functionalized gauze was evaluated by dynamic blood clotting assays. The obtained results showed that the prepared material can shorten the blood clotting time and induce the adhesion and activation of platelets. Finally, swelling characteristic of the new gauze was evaluated to confirm its high capacity to absorb the blood.

Influence of Hemostatic Solution on Bond Strength and Physicochemical Properties of Resin Cement.

PubMed

Araújo, Isabela Sousa de; Prado, Célio Jesus do; Raposo, Luís Henrique Araújo; Soares, Carlos José; Zanatta, Rayssa Ferreira; Torres, Carlos Rocha Gomes; Ruggiero, Reinaldo; Silva, Gisele Rodrigues da

2017-01-01

The aim of this study was to evaluate the degree of conversion, color stability, chemical composition, and bond strength of a light-cured resin cement contaminated with three different hemostatic solutions. Specimens were prepared for the control (uncontaminated resin cement) and experimental groups (resin cement contaminated with one of the hemostatic solutions) according to the tests. For degree of conversion, DC (n = 5) and color analyses (n = 10), specimens (3 mm in diameter and 2 mm thick) were evaluated by Fourier transform infrared spectroscopy (FTIR) and CIELAB spectrophotometry (L*, a*, b*), respectively. For elemental chemical analysis (n = 1), specimens (2 mm thick and 6 mm in diameter) were evaluated by x-ray energy-dispersive spectroscopy (EDS). The bond strengths of the groups were assessed by the microshear test (n = 20) in a leucite-reinforced glass ceramic substrate, followed by failure mode analysis by scanning electron microscopy (SEM). The mean values, except for the elemental chemical evaluation and failure mode, were evaluated by ANOVA and Tukey's HSD test. The color stability was influenced by storage time (p<0.001) and interaction between contamination and storage time (p<0.001). Hemostop and Viscostat Clear contamination did not affect the DC, however Viscostat increased the DC. Bond strength of the resin cement to ceramic was negatively affected by the contaminants (p<0.001). Contamination by hemostatic agents affected the bond strength, degree of conversion, and color stability of the light-cured resin cement tested.

Rapid hemostatic and mild polyurethane-urea foam wound dressing for promoting wound healing.

PubMed

Liu, Xiangyu; Niu, Yuqing; Chen, Kevin C; Chen, Shiguo

2017-02-01

A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50-130μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization. Copyright © 2016 Elsevier B.V. All rights reserved.

The Impact of 10 Years of War on Combat Casualty Care Research: A Citation Analysis

DTIC Science & Technology

2012-01-01

2004 74 14 Alam HB, Chen Z, Jaskille A, et al. Application of a zeolite hemostatic agent achieves 100% survival in a lethal model of complex groin...Among the preclinical studies, the most cited was #14 by Alam et al. (2004), ‘‘Application of a zeolite hemostatic agent achieves 100% survival in a...patients. J Trauma. 2006;60:363Y370. 2006 44 47 Wright JK, Kalns J, Wolf EA, et al. Thermal injury resulting from application of a granular mineral

Role of the Hemostatic System on SCD Pathophysiology and Potential Therapeutics

PubMed Central

Pakbaz, Zahra; Wun, Ted

2014-01-01

Synopsis Recent studies suggest that sickle cell disease is a hypercoagulable state contributing to the vaso-occlusive events in microcirculation resulting in acute and chronic sickle cell related organ damage. In this article, we will review the existing evidence for contribution of hemostatic system perturbation to sickle cell disease pathophysiology. We will also review the data showing increased risk of thromboembolic events, particularly newer information on the incidence of VTE. Finally, the potential role of platelet inhibitors and anticoagulants in SCD will be briefly reviewed. PMID:24589271

Advanced Hemostatic Dressing Development Program: Animal Model Selection Criteria and Results of a Study of Nine Hemostatic Dressings in a Model of Severe Large Venous Hemorrhage and Hepatic Injury in Swine

DTIC Science & Technology

2003-09-01

Pharmaceuticals, Inc. (Westlake, OH), submitted the Hemarrest dressing. This dressing was a thin, sheet-like pad with a mixture of epsilon aminocaproic acid ...chloric acid salt purified bovine corium collagen. It was prepared in a compacted nonwoven web form (7.0 7.0 cm). Ethicon, Inc. (Somerville, NJ...may be related to enhanced platelet procoagulant activity and annexin V binding.46 Another derivative of gallic acid , bis- muth subgallate, appears to

Comparison of New Hemostatic Granules/Powders With Currently Deployed Hemostatic Products in a Lethal Model of Extremity Arterial Hemorrhage in Swine

DTIC Science & Technology

2009-02-01

femoral vein and nerve was avoided. The vessel was then bathed with a few milliliters of 2% lidocaine to relax vasospasm and dilate the artery to its...stop the bleeding resulting in the eventual exsanguination of all tested pigs. Since the army field dress- ing was found to be ineffective in this...efficacy rate was 92% with eight cases of ineffectiveness in morbid patients with possible coagulopathy. The inability to deliver the material to the

Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis

PubMed Central

Cushman, Mary; Jenny, Nancy; Michos, Erin D.; Smith, Nicholas L.; Kestenbaum, Bryan; de Boer, Ian H.

2016-01-01

Context: Mechanisms explaining documented associations of 25-hydroxyvitamin D [25(OH)D] deficiency with increased risks of cardiovascular disease (CVD) and venous thromboembolism may relate to adverse hemostatic and inflammatory responses. Objective: To evaluate whether 25(OH)D deficiency is associated with a prothrombotic and proinflammatory biological profile. Design: Cross-sectional analyses. Setting: The Multi-Ethnic Study of Atherosclerosis, a multicenter prospective cohort of American adults. Participants: Up to 6554 adults free of CVD. Main Outcome Measures: Ten hemostatic biomarkers (D-dimer, fibrinogen, factor VIII, plasmin-antiplasmin, and homocysteine [n = 6443]; von Willebrand factor, soluble tissue factor, plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin [n = 814]), and three inflammatory biomarkers (IL-6, C-reactive protein [n = 6443], and TNF-α soluble receptor [n = 3802]). Results: Among 6443 subjects (46.6% men; mean age, 62.1 years; mean body mass index, 28.3 kg/m2) of White (37.8%), Black (27.2%), Chinese (12.2%), and Hispanic (21.8%) race/ethnicity, mean 25(OH)D was 25.3 ng/mL. After multiple adjustment, 25(OH)D concentrations were associated with concentrations of IL-6 and homocysteine and also with concentrations of PAI-1 and TFPI: per 10 ng/mL decrement in 25(OH)D, 5.1% higher IL-6 (95% confidence interval [CI], 3.4–6.9; P < .001); 3.7% higher homocysteine (95% CI, 3.0–4.3; P < .001); 7.0% higher PAI-1 (95% CI, 0.9–13.6; P = .025); and 2.1% higher TFPI (95% CI, 0.0–4.2; P = .047), without racial/ethnic heterogeneity. No significant associations were observed for other hemostatic and inflammatory biomarkers. Conclusions: Increased inflammation as reflected by higher circulating IL-6 and increased homocysteine concentrations may represent mechanisms linking 25(OH)D deficiency to greater risks of CVD and perhaps venous thromboembolism. Low concentrations of 25(OH)D were also associated with PAI-1 and TFPI concentrations, but not with other hemostatic biomarkers. PMID:27023449

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

PubMed

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

2017-08-01

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

Randomized clinical trial comparing cold knife conization of the cervix with and without lateral hemostatic sutures.

PubMed

Bueno, Letícia Rossi; Binda, Marcia; Monego, Heleusa; Scherer, Roberta Luísa; Rolim, Karen Machado; Bottini, Alessandra Leal; Fregnani, José H T G; dos Reis, Ricardo

2015-06-01

Compare blood loss during cold knife conization of the cervix with and without lateral hemostatic sutures in the cervical branches of the uterine arteries. Randomized clinical trial. Hospital de Clínicas de Porto Alegre (HCPA). 102 patients that underwent cold knife conization. Women that underwent cold knife conization of the cervix were randomized to undergo the procedure with or without lateral hemostatic sutures. blood loss measured in grams. operative time and postoperative intervention. Only the participants were blinded to group assignment. From March 2009 to August 2012, patients were randomly assigned to one of the study groups. There were no differences in amount of blood loss between patients that underwent the procedure with and without sutures (p = 0.39). Operative time was shorter in the group without suture (p = 0.020). There were no differences in intervention due to bleeding (p = 0.20). Blood loss was greater among menstruating women than for menopausal women (p = 0.011). There were no differences in amount of blood lost between smoking and nonsmoking patients (p = 0.082). Lateral hemostatic sutures do not affect the amount of intraoperative bleeding or the number of postoperative interventions. Their use is not necessary because they result in longer operative time, have a higher cost due to the use of suture material and pose the risk of ureter lesion in case the sutures are not placed at a lower position in the cervix. ClinicalTrials. gov identifier: NCT02184975. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

Hemostatic Effects of Microbubble-Enhanced Low-Intensity Ultrasound in a Liver Avulsion Injury Model

PubMed Central

Feng, Guiying; Liu, Jianhua; Zhao, Xiaochen; Wei, Jinglu; Ou, Wencai; Xiao, Shuyi; Hu, Zhiwen; Wei, Hongqin; Liu, Zheng

2014-01-01

Objectives Microbubble-enhanced therapeutic ultrasound (MEUS) can block the blood flow in the organs. The aim of this study was to evaluate the hemostatic effect of microbubble-enhanced pulsed, low-intensity ultrasound in a New Zealand White rabbit model of avulsion trauma of the liver. The therapeutic ultrasound (TUS) transducer was operated with the frequency of 1.2 MHz and an acoustic pressure of 3.4 MPa. Microbubble-(MB) enhanced ultrasound (MEUS) (n = 6) was delivered to the distal part of the liver where the avulsion was created. Livers were treated by TUS only (n = 4) or MB only (n = 4) which served as controls. Bleeding rates were measured and contrast enhanced ultrasound (CEUS) was performed to assess the hemostatic effect, and liver hemoperfusion before and after treatment. Generally, bleeding rates decreased more than 10-fold after the treatment with MEUS compared with those of the control group (P<0.05). CEUS showed significant declines in perfusion. The peak intensity value and the area under the curve also decreased after insonation compared with those of the control group (P<0.05). Histological examination showed cloudy and swollen hepatocytes, dilated hepatic sinusoids, perisinusoidal spaces with erythrocyte accumulation in small blood vessels, obvious hemorrhage around portal areas and scattered necrosis in liver tissues within the insonation area of MEUS Group. In addition, necrosis was found in liver tissue 48 h after insonation. We conclude that MEUS might provide an effective hemostatic therapy for serious organ trauma such as liver avulsion injury. PMID:24788757

Hemostatic effects of a novel estradiol-based oral contraceptive: an open-label, randomized, crossover study of estradiol valerate/dienogest versus ethinylestradiol/levonorgestrel.

PubMed

Klipping, Christine; Duijkers, Ingrid; Parke, Susanne; Mellinger, Uwe; Serrani, Marco; Junge, Wolfgang

2011-01-01

A novel estradiol-based combined oral contraceptive (COC) is currently available in many countries worldwide, including Europe and the US. Based on previous studies, it is expected that this estradiol-based COC will have a reduced hepatic effect compared with COCs containing ethinylestradiol with regard to proteins controlling the hemostatic balance. The aim of this study was to compare the hemostatic effects of the estradiol valerate/dienogest COC with a monophasic low-estrogen dose COC containing ethinylestradiol/levonorgestrel. Healthy women aged 18-50 years were randomized to receive a COC containing estradiol valerate/dienogest (2 days estradiol valerate 3 mg, 5 days estradiol valerate 2 mg/dienogest 2 mg, 17 days estradiol valerate 2 mg/dienogest 3 mg, 2 days estradiol valerate 1 mg, 2 days placebo) or ethinylestradiol 0.03 mg/levonorgestrel 0.15 mg in a crossover study design. Women received each treatment for three cycles, with two washout cycles between treatments. The primary efficacy variables were the intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three. Data from 29 women were assessed. Intra-individual absolute changes in prothrombin fragment 1 + 2 and D-dimer from baseline to cycle three were less pronounced with estradiol valerate/dienogest than with ethinylestradiol/levonorgestrel. The novel COC containing estradiol valerate/dienogest had similar or less pronounced effects on hemostatic parameters than ethinylestradiol/levonorgestrel.

Antifibrinolytic agents and desmopressin as hemostatic agents in cardiac surgery.

PubMed

Erstad, B L

2001-09-01

To review the use of systemic hemostatic medications for reducing bleeding and transfusion requirements with cardiac surgery. Articles were obtained through computerized searches involving MEDLINE (from 1966 to September 2000). Additionally, several textbooks containing information on the diagnosis and management of bleeding associated with cardiac surgery were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. Due to the large number of randomized investigations involving systemic hemostatic medications for reducing bleeding associated with cardiac surgery, the article selection process focused on recent randomized controlled trials, metaanalyses and pharmacoeconomic evaluations. The primary outcomes extracted from the literature were blood loss and associated transfusion requirements, although other outcome measures such as mortality were extracted when available. Although the majority of investigations for reducing cardiac bleeding and transfusion requirements have involved aprotinin, evidence from recent meta-analyses and randomized trials indicates that the synthetic antifibrinolytic agents, aminocaproic acid and tranexamic acid, have similar clinical efficacy. Additionally, aminocaproic acid (and to a lesser extent tranexamic acid) is much less costly. More comparative information of hemostatic agents is needed retative to other outcomes (eg., reoperation rates, myocardial infarction, stroke). There is insufficient evidence to recommend the use of desmopressin for reducing bleeding and transfusion requirements in cardiac surgery, although certain subsets of patients may benefit from its use. Of the medications that have been used to reduce bleeding and transfusion requirements with cardiac surgery, the antifibrinolytic agents have the best evidence supporting their use. Aminocaproic acid is the least costly therapy based on medication costs and transfusion requirements.

Conservative management of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic suture.

PubMed

Rauf, Melekoglu; Ebru, Celik; Sevil, Eraslan; Selim, Buyukkurt

2017-02-01

The aim of this study was to investigate maternal and neonatal outcomes of conservative management of post-partum hemorrhage due to placenta previa-accreta using hypogastric artery ligation and endo-uterine hemostatic suture to lower uterine segment. The records of 38 patients who were managed conservatively with hypogastric artery ligation and endo-uterine hemostatic suture to control post-partum hemorrhage secondary to placenta previa-accreta between April 2014 and January 2016, were reviewed retrospectively. Placenta previa-accreta was diagnosed according to gray-scale, color and 3-D power Doppler ultrasonography in addition to the intraoperative findings based on fragmentary or difficult separation of the placenta. In the case of conservative treatment protocol failure, cesarean hysterectomy was performed. Of these patients, 55.2% were between 25 and 35 years old; 97.5% were multiparous; 71.2% had two or more previous cesarean section and 68.5% had preterm delivery. Women with placenta accreta had a median estimated blood loss of 450 mL; 57.8% of patients had blood transfusion (mean intraoperative transfusion, 2 units packed red blood cells; range, 0-9 units). Median duration of operation was 112.5 min (range, 45-305 min) and 32 patients (84.3%) with placenta accreta did not undergo cesarean hysterectomy. Conservative treatment of post-partum hemorrhage secondary to placenta previa-accreta with hypogastric artery ligation and endo-uterine hemostatic sutures to the lower segment of the uterus is associated with lower hysterectomy rate compared with the other conservative methods reported in the literature. © 2016 Japan Society of Obstetrics and Gynecology.

Clinical, laboratory, and hemostatic findings in cats with naturally occurring sepsis.

PubMed

Klainbart, Sigal; Agi, Limor; Bdolah-Abram, Tali; Kelmer, Efrat; Aroch, Itamar

2017-11-01

OBJECTIVE To characterize clinical and laboratory findings in cats with naturally occurring sepsis, emphasizing hemostasis-related findings, and evaluate these variables for associations with patient outcomes. DESIGN Prospective, observational, clinical study. ANIMALS 31 cats with sepsis and 33 healthy control cats. PROCEDURES Data collected included history; clinical signs; results of hematologic, serum biochemical, and hemostatic tests; diagnosis; and outcome (survival vs death during hospitalization or ≤ 30 days after hospital discharge). Differences between cats with and without sepsis and associations between variables of interest and death were analyzed statistically. RESULTS The sepsis group included cats with pyothorax (n = 10), septic peritonitis (7), panleukopenia virus infection (5), bite wounds (5), abscesses and diffuse cellulitis (3), and pyometra (1). Common clinical abnormalities included dehydration (21 cats), lethargy (21), anorexia (18), pale mucous membranes (15), and dullness (15). Numerous clinicopathologic abnormalities were identified in cats with sepsis; novel findings included metarubricytosis, hypertriglyceridemia, and high circulating muscle enzyme activities. Median activated partial thromboplastin time and plasma D-dimer concentrations were significantly higher, and total protein C and antithrombin activities were significantly lower, in the sepsis group than in healthy control cats. Disseminated intravascular coagulopathy was uncommon (4/22 [18%] cats with sepsis). None of the clinicopathologic abnormalities were significantly associated with death on multivariate analysis. CONCLUSIONS AND CLINICAL RELEVANCE Cats with sepsis had multiple hematologic, biochemical, and hemostatic abnormalities on hospital admission, including several findings suggestive of hemostatic derangement. Additional research including larger numbers of cats is needed to further investigate these findings and explore associations with outcome.

Hemostatic action of OC-108, a novel agent for hemorrhoids, is associated with regional blood flow arrest induced by acute inflammation.

PubMed

Ono, Takashi; Nakagawa, Haruto; Fukunari, Atsushi; Hashimoto, Toshio; Komatsu, Hirotsugu

2006-11-01

Clinically, hemorrhoidal bleeding and prolapse disappeared immediately after injection of the sclerosing agent OC-108 into submucosa of hemorrhoids. The aim of this study was to elucidate the mechanism of action responsible for the immediate hemostatic effect of OC-108 using anesthetized rats. Subcutaneous injection of OC-108 in rats decreased blood flow at the injection site within 5 min. Aluminum potassium sulfate, one of the main ingredients of OC-108, reduced the skin blood flow. However, tannic acid, another main ingredient, did not. By perfusion of OC-108 on the mesenteric surface, microcirculatory blood flow was arrested without remarkable change in blood vessel diameter, accompanied by increased vascular permeability and venous hematocrit. These results indicate that OC-108 induces regional blood flow arrest with rapid onset, this effect being attributed to the action of aluminum potassium sulfate, and that hemoconcentration due to increased vascular permeability (plasma extravasation), an acute inflammatory reaction, is involved in the mechanisms of the immediate hemostatic action of OC-108.

[Modern biomaterials as hemostatic dressings in kidney nephron sparing surgery (NSS)--murine model. A preliminary report].

PubMed

Nowacki, Maciej; Jundziłł, Arkadiusz; Bieniek, Miłosz; Kowalczyk, Tomasz; Kloskowski, Tomasz; Drewa, Tomasz

2012-01-01

Kidney cancer is now days, one of the main problems in oncological urology. More frequent cases detection of this type of cancer and the implementation of modern methods of treatment, involves the public and good diagnostic radiological imaging methods. Approximately 40% of renal tumors are detected clinically as a changes in T1N0M0 stage. This means that in these patients, surgery can be performed using the method of nephron sparing surgery (NSS), far from consisting the implementation of radical nephrectomy. Unfortunately, despite the saving nature of this type of treatment, NSS methods are associated with local recurrence of tumor formation. Another problem is intra operative bleeding, that's why in order to stop this negative process surgeons currently use hemostatic dressings. Potentially and clinically significant solution could be a combination of this two main problematics points of concern, through the use of modern biomaterials coated on oncostatic substances as a haemostatic dressings, to the prevention of tumor recurrence. The aim of this work, was to present preliminary report of the use of advanced biomaterials, as haemostatic dressings in an experimental technique of nephron sparing surgery on an murine model. In the experiment we use two types of biomaterials and the standard haemostatic dressing used in the nephron sparing surgery (NSS) as a control. We use a polycaprolactone biomaterial obtained by electrospinning. As a second type of biomaterial, we use a homogeneous material with a structure similar to wool, also obtained from medical polycaprolactone by electrospinning. As an murine (in vivo) model in the study, we use 10 C57BL/J mice (with the local ethical committee permission). 8 mice were used in the present study, 2 mice were constituted as a separate control for obtaining the bleeding data. Kidney melanoma cells were implanted under the C57B1/J B16 mouse kidney fibrous capsule, one week before NSS. After 3 weeks the animals were sacrificed for comparison of hemostatic dressings function. Used biomaterials fulfilled their role as a hameostatic dresings. The material (Type I) was convenient and good for suturing. Haemostatic action times were as follows: (Type I) - 30 seconds. (Type III) - 50 seconds. In the control group were also observed, a proper hemostatic function after 30 seconds. In sectional observation was also found in 3 kidneys section preparation samples, a local tumor recurrence and metastasis to the other tissues of the abdomen. The tested biomaterials fulfill their hemostatic effect on kidney after NSS, without any significant difference acording to a standard hemostatic dressing used clinically. This data may be a potential factor for use in further studies to determine their continued relevance in the prevention of local tumor recurrence after nephron sparing surgery.

Visualization of liposomes carrying fibrinogen gamma-chain dodecapeptide accumulated to sites of vascular injury using computed tomography.

PubMed

Okamura, Yosuke; Eto, Kaoruko; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji

2010-04-01

We have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. The liposomes were conjugated with the dodecapeptide (HHLGGAKQAGDV: H12), which is a fibrinogen gamma-chain C-terminal sequence (gamma 400-411). To visualize liposome accumulation at the site of vascular injury by in vivo computed tomography, a water-soluble contrast dye, N,N'-bis[2-hydroxy-1-(hydroxylmethyl)ethyl]-5-[(2S)-2-hydroxylpropanoylamino]-2,4,6-triiodoisophthalamide (iopamidol), was encapsulated into the H12-conjugated liposomes. We achieved direct visualization of specific accumulation of the H12-(iopamidol)liposomes at the jugular vein injured by ferric chloride and succeeded in semiquantitative analyses of the accumulated amount of H12-liposomes in the injured site. We therefore propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol)liposomes would also be clinically useful as diagnostic agents for pathological thrombus detection and as contrast dyes for hepatosplenography. The authors have constructed liposomes with hemostatic activity as a platelet substitute using moderately thrombocytopenic rats. They propose that H12-liposomes that are specifically recruited to, and exert their hemostatic activity at the site of vascular injury, have a significant potential as a carrier and/or as an ideal platelet substitute. Furthermore, the H12-(iopamidol) liposomes would also be clinically useful as diagnostic agents for thrombus detection and as contrast dyes for hepatosplenography. Copyright 2010 Elsevier Inc. All rights reserved.

Neutrophil interaction with the hemostatic system contributes to liver injury in rats cotreated with lipopolysaccharide and ranitidine.

PubMed

Deng, Xiaomin; Luyendyk, James P; Zou, Wei; Lu, Jingtao; Malle, Ernst; Ganey, Patricia E; Roth, Robert A

2007-08-01

Cotreatment of rats with nontoxic doses of ranitidine (RAN) and lipopolysaccharide (LPS) causes liver injury, and this drug-inflammation interaction might be a model for idiosyncratic adverse drug responses in humans. Both polymorphonuclear neutrophils (PMNs) and the hemostatic system have been shown to be important in the injury. We tested the hypothesis that PMNs cause liver injury by interacting with the hemostatic system and producing subsequent hypoxia. In rats cotreated with LPS/RAN, PMN depletion by anti-PMN serum reduced fibrin deposition and hypoxia in the liver. PMN depletion also reduced the plasma concentration of active plasminogen activator inhibitor-1 (PAI-1), a major down-regulator of the fibrinolytic system. This suggests that PMNs promote fibrin deposition by increasing PAI-1 concentration. PMNs were activated in the livers of LPS/RAN-cotreated rats as evidenced by increased staining for hypochlorous acid-modified proteins generated by the myeloperoxidase-hydrogen peroxide-chloride system of activated phagocytes. Antiserum against the PMN adhesion molecule CD18 protected against LPS/RAN-induced liver injury. Because CD18 is important for PMN transmigration and activation, these results suggest that PMN activation is required for the liver injury. Furthermore, anti-CD18 serum reduced biomarkers of hemostasis and hypoxia, suggesting the necessity for PMN activation in the interaction between PMNs and the hemostatic system/hypoxia. Liver injury, liver fibrin, and plasma PAI-1 concentration were also reduced by eglin C, an inhibitor of proteases released by activated PMNs. In summary, PMNs are activated in LPS/RAN-cotreated rats and participate in the liver injury in part by contributing to hemostasis and hypoxia.

Free radical activity and hemostatic factors in NIDDM patients with and without microalbuminuria.

PubMed

Collier, A; Rumley, A; Rumley, A G; Paterson, J R; Leach, J P; Lowe, G D; Small, M

1992-08-01

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA'] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (B beta 15-42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA' was elevated in the microalbuminuric patients compared with control subjects (P less than 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P less than 0.05) and control subjects (P less than 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P less than 0.01). Except for B beta 15-42, all the hemostatic variables were increased (P less than 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P less than 0.03) and t-PA (P less than 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Fibrin, γ’-fibrinogen, and trans-clot pressure gradient control hemostatic clot growth during human blood flow over a collagen/tissue factor wound

PubMed Central

Muthard, Ryan W.; Welsh, John D.; Brass, Lawrence F.; Diamond, Scott L.

2015-01-01

SUMMARY Objective Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (ΔP) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin mediated clot growth. Approach and Results Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and ΔP, we found thrombin to be highly localized in the P-selectin+ core of hemostatic clots. Increasing ΔP from 9 to 29 mm-Hg (wall shear rate = 400 s−1) reduced P-selectin+ core size and total clot size due to enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mM GPRP dysregulated hemostasis by enhancing both P-selectin+ core size and clot size at 400 s−1 (20 mm-Hg). For whole blood flow (no GPRP), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s−1, 20 mm-Hg). Consistent with the antithrombin-1 activity of fibrin implicated with GPRP, anti-γ’-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s−1) but not arterial wall shear rates (2000 s−1). Pathological shear (15,000 s−1) and GPRP synergized to exacerbate clot growth. Conclusions Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the trans-clot ΔP. Also, γ’-fibrinogen had a role in venous but not arterial conditions. PMID:25614284

Antimicrobial activity of chemomechanical gingival retraction products.

PubMed

Hsu, Belinda; Lee, Stephanie; Schwass, Donald; Tompkins, Geoffrey

2017-07-01

Application of astringent hemostatic agents is the most widely used technique for gingival retraction, and a variety of products are offered commercially. However, these products may have additional unintended yet clinically beneficial properties. The authors assessed the antimicrobial activities of marketed retraction products against plaque-associated bacteria in both planktonic and biofilm assays, in vitro. The authors assessed hemostatic solutions, gels, pellets, retraction cords, pastes, and their listed active agents against a collection of microorganisms by means of conventional agar diffusion and minimum bacteriostatic and bactericidal concentration determinations. The authors then tested the most active products against monospecies biofilms grown on hydroxyapatite disks. All of the tested retraction products exhibited some antimicrobial activity. The results of the most active products were comparable with those of a marketed mouthwash. The listed retraction-active agents displayed relatively little activity when tested in pure form. At 10% dilution, some products evidenced inhibitory activity against most tested bacteria within 3 minutes of exposure, whereas others displayed variable effects after 10 minutes. The most active agents reduced, but did not completely prevent, the metabolic activity of a monospecies biofilm. Commercial gingival retraction products exhibit antimicrobial effects to various degrees in vitro. Some products display rapid bactericidal activity. The antimicrobial activity is not owing to the retraction-active agents. Biofilm bacteria are less sensitive to the antimicrobial effects of the agents. The rapidity of killing by some hemostatic agents suggests an antimicrobial effect that may be efficacious during clinical placement. The results of this in vitro study suggest that clinicians should be aware of the potential antimicrobial effects of some hemostatic agents, but more research is needed to confirm these observations in clinical use. Copyright © 2017 American Dental Association. Published by Elsevier Inc. All rights reserved.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

PubMed

Luh, Hui-Tzung; Huang, Abel Po-Hao; Yang, Shih-Hung; Chen, Chien-Ming; Cho, Der-Yang; Chen, Chun-Chung; Kuo, Lu-Ting; Li, Chieh-Hsun; Wang, Kuo-Chuan; Tseng, Wei-Lung; Hsing, Ming-Tai; Yang, Bing-Shiang; Lai, Dar-Ming; Tsai, Jui-Chang

2018-01-01

Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings. Copyright © 2017. Published by Elsevier B.V.

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

PubMed

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

2013-12-01

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

Stability of hemostatic proteins in canine fresh-frozen plasma thawed with a modified commercial microwave warmer or warm water bath.

PubMed

Pashmakova, Medora B; Barr, James W; Bishop, Micah A

2015-05-01

To compare stability of hemostatic proteins in canine fresh-frozen plasma (FFP) thawed with a modified commercial microwave warmer (MCM) or warm water bath (37°C; WWB) or at room temperature (22°C). Fresh-frozen plasma obtained from 8 canine donors of a commercial blood bank. A commercial microwave warmer was modified with a thermocouple to measure surface temperature of bags containing plasma. The MCM and a WWB were each used to concurrently thaw a 60-mL bag of plasma obtained from the same donor. Two 3-mL control aliquots of FFP from each donor were thawed to room temperature without use of a heating device. Concentrations of hemostatic proteins, albumin, and D-dimers; prothrombin time (PT); and activated partial thromboplastin time (aPTT) were determined for all samples. Significant decreases in concentrations of factors II, IX, X, XI, fibrinogen, von Willebrand factor, antithrombin, protein C, and albumin and significant increases in PT and aPTT were detected for plasma thawed with the MCM, compared with results for samples thawed with the WWB. Concentrations of factors VII, VIII, and XII were not significantly different between plasma thawed with the MCM and WWB. Concentrations of D-dimers were above the reference range for all thawed samples regardless of thawing method. No significant differences in factor concentrations were detected between control and WWB-thawed samples. Significant differences in hemostatic protein concentrations and coagulation times were detected for plasma thawed with an MCM but not between control and WWB-thawed samples. Clinical importance of these changes should be investigated.

Splenic injury during percutaneous nephrolithotomy.

PubMed

Thomas, Anil A; Pierce, Gregory; Walsh, R Matthew; Sands, Mark; Noble, Mark

2009-01-01

Injury to the spleen is a recognized complication during percutaneous renal access due to the close anatomical relationship of the spleen and the left kidney. However, transsplenic renal access is a rare complication of percutaneous nephrolithotomy and can also result in considerable morbidity, often requiring emergent splenectomy. We present our experience with splenic injury during percutaneous nephrolithotomy managed conservatively with the use of a collagen-thrombin hemostatic sealant (D-Stat; Vascular Solutions, Inc., Minneapolis, MN) after delayed removal of the nephrostomy tubes. The patient had an uneventful recovery and was discharged home on postoperative day 6. In select hemodynamically stable patients, nonoperative management with the adjunctive use of hemostatic sealants may be considered.

Effects of sulfur-based hemostatic agents and gingival retraction cords handled with latex gloves on the polymerization of polyvinyl siloxane impression materials

PubMed Central

MACHADO, Carlos Eduardo Palhares; GUEDES, Carlos Gramani

2011-01-01

Objectives This study investigated the possible interactions between three addition silicone materials (Express®, Aquasil Ultra® and Adsil®), three hemostatic agents (ferric sulfate, StatGel FS®; aluminum sulfate, GelCord®; and aluminum chloride, Hemostop®) and gingival retraction cords previously handled with latex gloves to determine whether direct contact with medicaments or indirect contamination by latex in conditions similar to those found in clinical practice inhibit or affect the setting of the impression materials. Material and Methods A portable device for the simultaneous test of several specimens was specifically developed for this study. Polymerization inhibition was analyzed by examination of the impressions and the molded surface. Ten trials were performed for each addition silicone material used in the study, at a total of 240 study samples. Results All the samples tested (N=240) were nonreactive regardless of the type of combination used. Conclusions Aluminum sulfate, ferric sulfate and aluminum chloride hemostatic solutions did not show any inhibitory potential on the addition silicone samples under study, and there were no changes in polymerization as a result of contact between addition silicone and retraction cords handled with latex gloves. PMID:22230998

Oral Surgical Procedures Performed Safely in Patients With Head and Neck Arteriovenous Malformations: A Retrospective Case Series of 12 Patients.

PubMed

Karim, Abdul Basit; Lindsey, Sean; Bovino, Brian; Berenstein, Alejandro

2016-02-01

This case series describes patients with head and neck arteriovenous malformations who underwent oral and maxillofacial surgical procedures combined with interventional radiology techniques to minimize blood loss. Twelve patients underwent femoral cerebral angiography to visualize the extent of vascular malformation. Before the surgical procedures, surgical sites were devascularized by direct injection of hemostatic or embolic agents. Direct puncture sclerotherapy at the base of surgical sites was performed using Surgiflo or n-butylcyanoacrylate glue. Surgical procedures were carried out in routine fashion. A hemostatic packing of FloSeal, Gelfoam, and Avitene was adapted to the surgical sites. Direct puncture sclerotherapy with Surgiflo or n-butylcyanoacrylate glue resulted in minimal blood loss intraoperatively. Local application of the FloSeal, Gelfoam, and Avitene packing sustained hemostasis and produced excellent healing postoperatively. Patients with arteriovenous malformations can safely undergo routine oral and maxillofacial surgical procedures with minimal blood loss when appropriate endovascular techniques and local hemostatic measures are used by the interventional radiologist and oral and maxillofacial surgeon. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of sulfur-based hemostatic agents and gingival retraction cords handled with latex gloves on the polymerization of polyvinyl siloxane impression materials.

PubMed

Machado, Carlos Eduardo Palhares; Guedes, Carlos Gramani

2011-01-01

This study investigated the possible interactions between three addition silicone materials (Express®, Aquasil Ultra® and Adsil®), three hemostatic agents (ferric sulfate, StatGel FS®; aluminum sulfate, GelCord®; and aluminum chloride, Hemostop®) and gingival retraction cords previously handled with latex gloves to determine whether direct contact with medicaments or indirect contamination by latex in conditions similar to those found in clinical practice inhibit or affect the setting of the impression materials. A portable device for the simultaneous test of several specimens was specifically developed for this study. Polymerization inhibition was analyzed by examination of the impressions and the molded surface. Ten trials were performed for each addition silicone material used in the study, at a total of 240 study samples. All the samples tested (N=240) were nonreactive regardless of the type of combination used. Aluminum sulfate, ferric sulfate and aluminum chloride hemostatic solutions did not show any inhibitory potential on the addition silicone samples under study, and there were no changes in polymerization as a result of contact between addition silicone and retraction cords handled with latex gloves.

[Hormonal contraception and thromboembolic disease--pathophysiologic findings and practical recommendations].

PubMed

Dulícek, P

2001-09-01

Review the knowledge about changes in hemostatic system in combined oral contraceptives users (focused on studies published between 1997 and 2000). Review of literature. Department of Clinical Hematology, University Hospital Hradec Králové, Czech Republic. Summary of the results of substantial studies published on this topic. Studies were identified by Medline database search. Hemostatic changes were described in all subsystems (in both procoagulant and fibrinolytic systems, in natural inhibitors of coagulation) and could be seen also in molecular marks of coagulation and fibrinolysis activity. Substantial differences were not described for ethinylestradiol doses 20-50 micrograms and up to 1997 also not for different progestins. More expressed acquired resistance to activated protein C at 3rd generation progestins in comparison with levonorgestrel was described recently as well as greater inhibition of fibrinolysis at desogestrel users. The results of recent studies indicate the differences in hemostatic changes between users of 3rd generation progestins, respective desogestrel, and users of levonorgestrel. However, the practical recommendations (aiming at minimalization of VTE risk) are focused on personal and family history and on patient counseling. The choice of progestin could be important but it is not crucial.

The hemostatic effect study of Cirsium setosum on regulating α1-ARs via mediating norepinephrine synthesis by enzyme catalysis.

PubMed

Chang, Nianwei; Li, Yanmei; Zhou, Mengge; Gao, Jie; Hou, Yuanyuan; Jiang, Min; Bai, Gang

2017-03-01

Cirsium setosum (CS) is the aboveground part of Cephalanoplos segetum Kitam. Although it has been used as a hemostatic treatment for thousands of years and is still in use today, the mechanism of CS on regulating ARs is still not clear. In this study, we aimed to clarify the mechanism of CS on regulating ARs. We developed a simple method based on UPLC/Q-TOF MS combined adrenergic receptor dual-luciferase reporter assay systems for the rapid determination of active constituents in CS. The mechanism of tyramine, the main active component for regulating ARs, was further investigated by an in vitro norepinephrine biotransformation test and in vivo vaso activity tests. Two phenethylamine ARs regulators (tyramine and N-methyltyramine) in CS were characterized, and it was found that tyramine could induce vasoconstriction via regulation of α1-ARs by mediating norepinephrine synthesis. The hemostatic effect of CS is associated with tyramine and N-methyltyramine, via regulation of α1-ARs, and the mechanism of tyramine is related to mediating norepinephrine synthesis by enzyme catalysis. Copyright © 2017. Published by Elsevier Masson SAS.

Hemostatic, antibacterial biopolymers from Acacia arabica (Lam.) Willd. and Moringa oleifera (Lam.) as potential wound dressing materials.

PubMed

Bhatnagar, Monica; Parwani, Laxmi; Sharma, Vinay; Ganguli, Jhuma; Bhatnagar, Ashish

2013-10-01

Acacia arabica and Moringa oleifera are credited with a number of medicinal properties. Traditionally gum of Acacia plant is used in the treatment of skin disorders to soothe skin rashes, soreness, inflammation and burns while Moringa seed extracts are known to have antibacterial activity. In the present study the potential of the polymeric component of aqueous extracts of gum acacia (GA) and the seeds of M. oleifera (MSP) in wound management was evaluated. The results revealed that both biopolymers were hemostatic and hasten blood coagulation. They showed shortening of activated partial thromboplastin time and prothrombin time and were non-cytotoxic in nature. Both showed antibacterial activity against organisms known to be involved in wound infections with MIC ranging from 500-600 microg mL(-1) for GA and 300-700 microg mL(-1) for MSP. They were biodegradable and exhibited water absorption capacity in the range of 415 to 935%. The hemostatic character coupled to these properties envisions their potential in preparation of dressings for bleeding and profusely exuding wounds. The biopolymers have been further analysed for their composition by Gas chromatography.

Real-time monitoring of human blood clotting using a lateral excited film bulk acoustic resonator

NASA Astrophysics Data System (ADS)

Chen, Da; Wang, Jingjng; Wang, Peng; Guo, Qiuquan; Zhang, Zhen; Ma, Jilong

2017-04-01

Frequent assay of hemostatic status is an essential issue for the millions of patients using anticoagulant drugs. In this paper, we presented a micro-fabricated film bulk acoustic sensor for the real-time monitoring of blood clotting and the measurement of hemostatic parameters. The device was made of an Au/ZnO/Si3N4 film stack and excited by a lateral electric field. It operated under a shear mode resonance with the frequency of 1.42 GHz and had a quality factor of 342 in human blood. During the clotting process of blood, the resonant frequency decreased along with the change of blood viscosity and showed an apparent step-ladder curve, revealing the sequential clotting stages. An important hemostatic parameter, prothrombin time, was quantitatively determined from the frequency response for different dilutions of the blood samples. The effect of a typical anticoagulant drug (heparin) on the prothrombin time was exemplarily shown. The proposed sensor displayed a good consistency and clinical comparability with the standard coagulometric methods. Thanks to the availability of direct digital signals, excellent potentials of miniaturization and integration, the proposed sensor has promising application for point-of-care coagulation technologies.

Diaminopropionic Acid Reinforced Graphene Sponge and Its Use for Hemostasis.

PubMed

Quan, Kecheng; Li, Guofeng; Tao, Lei; Xie, Qian; Yuan, Qipeng; Wang, Xing

2016-03-01

2,3-Diaminopropionic acid (DapA), a medicinal amino acid, is used for the first time to prepare a DapA cross-linked graphene sponge (DCGS) for hemostasis treatment. In a comparison with the reported ethanediamine (EDA) cross-linked graphene sponge (CGS), this carboxyl-functionalized DCGS can not only quickly absorb plasma, but also stimulate erythrocytes and platelets to change their normal form and structure at the interface, which largely affects a cell's metabolism and biofunction, thus further promoting blood coagulation. Whole blood clotting and rat-tail amputation tests indicated that on the basis of the additional interfacial stimulation, the hemostatic efficiency of the DCGS has been significantly improved in comparison with that of the CGS control (P < 0.05). In-depth insight revealed that the increased oxidation degree and the negative charge density play the crucial rule in the enhanced hemostatic performance. The chiral effect contributes mainly to the selective adhesion of erythrocytes and platelets rather than practical hemostasis. Nevertheless, this presentation demonstrated that, on the premise of keeping the fast absorbability, this is an effective method to improve the hemostatic efficiency by enhancing the cell/graphene interface interaction.

Hemostatic bioactivity of novel Pollen Typhae Carbonisata-derived carbon quantum dots.

PubMed

Yan, Xin; Zhao, Yan; Luo, Juan; Xiong, Wei; Liu, Xiaoman; Cheng, Jinjun; Wang, Yongzhi; Zhang, Meiling; Qu, Huihua

2017-09-05

Pollen Typhae Carbonisata (PTC) is a type of calcined herb drug that has been used as a hemostatic medicine to promote hemostasis for thousands of years. In this study, we discovered and separated novel water-soluble carbon quantum dots (CQDs, named PTC-CQDs) from aqueous extracts of PTC. These PTC-CDs were characterized using transmission electron microscopy (TEM) and high-resolution TEM, as well as Fourier transform infrared, ultraviolet-visible, and fluorescence spectroscopy. Then, we assessed the anti-hemorrhagic effects and related hemostatic mechanisms of the obtained PTC-CQDs. The PTC-CQDs separated from PTC are spherical, monodisperse, and have a narrow size distribution between 2 and 8 nm. In the pharmacology experiment, remarkable anti-hemorrhage effects of PTC-CQDs were revealed. Additionally, the rats showed a profound decrease in activated partial thromboplastin time and increase in fibrinogen and PLT after PTC-CQDs treatment. These results indicated the explicit hemostasis effect of PTC-CQDs, which not only provided a new idea for the material research of PTC, but have also provided new insights into potential biomedical and healthcare applications of CQDs in the field of haemorrhage control and laid a solid foundation for future drug discovery.

Monopolar soft-mode coagulation using hemostatic forceps for peptic ulcer bleeding.

PubMed

Yamasaki, Yasushi; Takenaka, Ryuta; Nunoue, Tomokazu; Kono, Yoshiyasu; Takemoto, Koji; Taira, Akihiko; Tsugeno, Hirofumi; Fujiki, Shigeatsu

2014-01-01

Upper gastrointestinal hemorrhage from bleeding peptic ulcer is sometimes difficult to treat by conventional endoscopic methods. Recently, monopolar electrocoagulation using a soft-coagulation system and hemostatic forceps (soft coagulation) has been used to prevent bleeding during endoscopic submucosal dissection. The aim of this study was to assess the safety and efficacy of soft coagulation in the treatment of bleeding peptic ulcer. A total of 39 patients with peptic ulcers were treated using soft coagulation at our hospital between January 2005 and March 2010. Emergency treatment employed an ERBE soft-mode coagulation system using hemostatic forceps. Second-look endoscopy was performed to evaluate the efficacy of prior therapy. Initial hemostasis was defined as accomplished by soft coagulation, with or without other endoscopic therapy prior to soft coagulation. The rate of initial hemostasis, rebleeding, and ultimate hemostasis were retrospectively analyzed. The study subjects were 31 men and 8 women with a mean age of 68.3±13.7 years, with 29 gastric ulcers and 10 duodenal ulcers. Initial hemostasis was achieved in 37 patients (95%). During follow-up, bleeding recurred in two patients, who were retreated with soft coagulation. The monopolar soft coagulation is feasible and safe for treating bleeding peptic ulcers.

A shape memory foam composite with enhanced fluid uptake and bactericidal properties as a hemostatic agent.

PubMed

Landsman, T L; Touchet, T; Hasan, S M; Smith, C; Russell, B; Rivera, J; Maitland, D J; Cosgriff-Hernandez, E

2017-01-01

Uncontrolled hemorrhage accounts for more than 30% of trauma deaths worldwide. Current hemostatic devices focus primarily on time to hemostasis, but prevention of bacterial infection is also critical for improving survival rates. In this study, we sought to improve on current devices used for hemorrhage control by combining the large volume-filling capabilities and rapid clotting of shape memory polymer (SMP) foams with the swelling capacity of hydrogels. In addition, a hydrogel composition was selected that readily complexes with elemental iodine to impart bactericidal properties to the device. The focus of this work was to verify that the advantages of each respective material (SMP foam and hydrogel) are retained when combined in a composite device. The iodine-doped hydrogel demonstrated an 80% reduction in bacteria viability when cultured with a high bioburden of Staphylococcus aureus. Hydrogel coating of the SMP foam increased fluid uptake by 19× over the uncoated SMP foam. The composite device retained the shape memory behavior of the foam with more than 15× volume expansion after being submerged in 37°C water for 15 min. Finally, the expansion force of the composite was tested to assess potential tissue damage within the wound during device expansion. Expansion forces did not exceed 0.6N, making tissue damage during device expansion unlikely, even when the expanded device diameter is substantially larger than the target wound site. Overall, the enhanced fluid uptake and bactericidal properties of the shape memory foam composite indicate its strong potential as a hemostatic agent to treat non-compressible wounds. No hemostatic device currently used in civilian and combat trauma situations satisfies all the desired criteria for an optimal hemostatic wound dressing. The research presented here sought to improve on current devices by combining the large volume-filling capabilities and rapid clotting of shape memory polymer (SMP) foams with the swelling capacity of hydrogels. In addition, a hydrogel composition was selected that readily complexes with elemental iodine to impart bactericidal properties to the device. The focus of this work was to verify that the advantages of each respective material are retained when combined into a composite device. This research opens the door to generating novel composites with a focus on both hemostasis, as well as wound healing and microbial prevention. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pre-hospital transfusion of plasma in hemorrhaging trauma patients independently improves hemostatic competence and acidosis.

PubMed

Henriksen, Hanne H; Rahbar, Elaheh; Baer, Lisa A; Holcomb, John B; Cotton, Bryan A; Steinmetz, Jacob; Ostrowski, Sisse R; Stensballe, Jakob; Johansson, Pär I; Wade, Charles E

2016-12-09

The early use of blood products has been associated with improved patient outcomes following severe hemorrhage or traumatic injury. We aimed to investigate the influence of pre-hospital blood products (i.e. plasma and/or RBCs) on admission hemostatic properties and patient outcomes. We hypothesized that pre-hospital plasma would improve hemostatic function as evaluated by rapid thrombelastography (rTEG). We conducted a prospective observational study recruiting 257 trauma patients admitted to a Level I trauma center having received either blood products pre-hospital or in-hospital within 6 hours of admission. Clinical data on patient demographics, blood biochemistry, injury severity score and mortality were collected. Admission rTEG was conducted to characterize the coagulation profile and hemostatic function. 75 patients received pre-hospital plasma and/or RBCs (PH group; nearly half received both RBCs and plasma) whereas 182 patients only received in-hospital blood products (RBCs, Plasma and Platelets) within 6 hours of admission (IH group). PH patients had lower Glasgow coma scale (GCS) scores, more penetrating injuries, lower systolic blood pressures, lower hemoglobin levels, lower platelet counts and greater acidosis upon ED admission than the IH group (all p < 0.05). Despite differences in type of injury and admission vitals indicating that the PH group had more signs of bleeding than the IH group, there were no significant differences in in-hospital mortality (PH 26.7% vs. IH 20.9% p = 0.31). When comparing rTEG variables between PH patients transfused with 0, 1 or 2 units of plasma, more pre-hospital plasma transfusion was tendency towards improved rTEG variables. When adjusting for pre-hospital RBC, pre-hospital plasma was associated with significantly higher rTEG MA (p = 0.012) at hospital admission. After adjusting for pre-hospital RBCs, pre-hospital plasma transfusion was independently associated with increased rTEG MA, as well as arrival indices of shock and hemodynamic instability. Besides more severe injury and worse clinical presentation, the group that received pre-hospital transfusion had early and late mortality similar to patients not transfused pre-hospital. These data suggest that early administration of plasma can provide significant hemostatic and potential survival benefit to severely hemorrhaging trauma patients.

Gallium nitrate induces fibrinogen flocculation: an explanation for its hemostatic effect?

PubMed

Bauters, A; Holt, D J; Zerbib, P; Rogosnitzky, M

2013-12-01

A novel hemostatic effect of gallium nitrate has recently been discovered. Our aim was to perform a preliminary investigation into its mode of action. Thromboelastography® showed no effect on coagulation but pointed instead to changes in fibrinogen concentration. We measured functional fibrinogen in whole blood after addition of gallium nitrate and nitric acid. We found that gallium nitrate induces fibrinogen precipitation in whole blood to a significantly higher degree than solutions of nitric acid alone. This precipitate is not primarily pH driven, and appears to occur via flocculation. This behavior is in line with the generally observed ability of metals to induce fibrinogen precipitation. Further investigation is required into this novel phenomenon.

Splenic Injury During Percutaneous Nephrolithotomy

PubMed Central

Thomas, Anil A.; Pierce, Gregory; Walsh, R. Matthew; Sands, Mark

2009-01-01

Background: Injury to the spleen is a recognized complication during percutaneous renal access due to the close anatomical relationship of the spleen and the left kidney. However, transsplenic renal access is a rare complication of percutaneous nephrolithotomy and can also result in considerable morbidity, often requiring emergent splenectomy. Methods: We present our experience with splenic injury during percutaneous nephrolithotomy managed conservatively with the use of a collagen-thrombin hemostatic sealant (D-Stat; Vascular Solutions, Inc., Minneapolis, MN) after delayed removal of the nephrostomy tubes. Results: The patient had an uneventful recovery and was discharged home on postoperative day 6. Conclusion: In select hemodynamically stable patients, nonoperative management with the adjunctive use of hemostatic sealants may be considered. PMID:19660224

Novel keratin (KeraStat™) and polyurethane (Nanosan(R)-Sorb) biomaterials are hemostatic in a porcine lethal extremity hemorrhage model.

PubMed

Burnett, Luke R; Richter, Jillian G; Rahmany, Maria B; Soler, Roberto; Steen, Julie A; Orlando, Giuseppe; Abouswareb, Tamer; Van Dyke, Mark E

2014-02-01

Traumatic injury is the leading cause of death in people aged 44 or less in the US. It is also estimated that 82% of deaths from battlefield hemorrhage may be survivable with better treatment options. In this study, two biomaterial hemostats having disparate mechanisms were evaluated in a large animal lethal hemorrhage model and compared to a commercial product and standard cotton gauze. We hypothesized that the biomaterial with a biologically active mechanism, as opposed to a mechanical mechanism, would be the most effective in this model. Using a published study protocol, the femoral artery in swine was punctured and treated. KeraStat™ (KeraNetics) and Nanosan®-Sorb (SNS Nano) hemostats were compared to a commercial chitosan dressing (second generation Hemcon®) and cotton gauze. Both KeraStat and Nanosan increased survival, significantly increased mean arterial pressure (MAP), and significantly decreased shock index compared to both controls. The Hemcon dressing was no different than gauze. Platelet adhesion assays suggested that the KeraStat mechanism of action involves β1 integrin mediated platelet adhesion while Nanosan-Sorb operates similar to one reported mechanism for Hemcon, absorbing fluid and concentrating clotting components. The Nanosan also swelled considerably and created pressure within the wound site even after direct pressure was removed.

The effective control of a bleeding injury using a medical adhesive containing batroxobin.

PubMed

You, Kyung Eun; Koo, Min-Ah; Lee, Dae-Hyung; Kwon, Byeong-Ju; Lee, Mi Hee; Hyon, Suong-Hyu; Seomun, Young; Kim, Jong-Tak; Park, Jong-Chul

2014-04-01

Many types of hemostatic agents have been studied for the effective control of bleeding. In this study, a powdery medical adhesive composed of aldehyded dextran and ε-poly (L-lysine) was used with the recombinant batroxobin. Batroxobin is a venomous component from the snake Bothrops atrox moojeni and catalyzes fibrinogen conversion to form soluble fibrin clots. This research aims to examine the performance of the batroxobin-containing adhesive for hemostasis, and evaluate its potential as a novel hemostatic adhesive. The fibrinogen conversion ability of batroxobin was evaluated by a fibrinogen clotting assay and a whole blood clotting assay. Both experiments demonstrated the effectiveness of the batroxobin-containing adhesive for blood clot formation. Animal experiments were also conducted. After a pricking wound was made in an ICR (imprinting control region) mouse liver, the adhesive and various concentrations of batroxobin were applied. The total amount of blood loss was reduced with increasing concentrations of batroxobin. For excessive bleeding conditions, the femoral artery wound model of SD (Sprague-Dawley) rats was adopted. With higher concentrations of batroxobin, hemostasis was more rapidly achieved. Histological analysis of the liver model also supports the hemostatic effects through fibrin clot formation. In conclusion, batroxobin and medical adhesive effectively facilitate blood coagulation, and could be developed for clinical use.

Tissue factor-dependent coagulation activation by heme: A thromboelastometry study.

PubMed

de Souza, Gleice Regina; Hounkpe, Bidossessi Wilfried; Fiusa, Maiara Marx Luz; Colella, Marina Pereira; Annichino-Bizzacchi, Joyce M; Traina, Fabiola; Costa, Fernando Ferreira; De Paula, Erich Vinicius

2017-01-01

Heme has been characterized as potent trigger of inflammation. In hemostasis, although heme has been shown to both induce and inhibit different compartments of hemostasis, its net effect on the hemostatic balance, and the biological relevance of these effects remain to be determined. Herein we evaluated the effect of heme on hemostasis using a global assay able to generate clinically relevant data in several other complex hemostatic diseases. Citrated whole blood samples from healthy participants were stimulated by heme or vehicle and incubated for 4h at 37°C. Rotational thromboelastometry was immediately performed. The participation of tissue factor in coagulation activation was evaluated using inhibitory antibody. Heme was able of inducing ex vivo coagulation activation in whole blood, affecting predominantly parameters associated with the initial phases of clot formation. This activation effect was at least partially dependent on hematopoietic tissue factor, since the effects of heme were partially abrogated by the inhibition of human tissue factor. In conclusion, using a global hemostasis assay, our study confirmed that heme is able to activate coagulation in whole blood, in a tissue factor-dependent way. These findings could explain the disturbance in hemostatic balance observed in conditions associated with the release of heme such as sickle cell disease.

Proteomic and transcriptomic analyses to explain the pleiotropic effects of Ankaferd blood stopper

PubMed Central

Simsek, Cem; Selek, Sebnem; Koca, Meltem; Haznedaroglu, Ibrahim Celal

2017-01-01

Ankaferd blood stopper is a standardized mixture of the plants Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica and has been used as a topical hemostatic agent and with its clinical application established in randomized controlled trials and case reports. Ankaferd has been successfully used in gastrointestinal endobronchial mucosal and cutaneous bleedings and also in abdominal, thoracic, dental and oropharyngeal, and pelvic surgeries. Ankaferd’s hemostatic action is thought to form a protein complex with coagulation factors that facilitate adhesion of blood components. Besides its hemostatic action, Ankaferd has demonstrated pleiotropic effects, including anti-neoplastic and anti-microbial activities and tissue-healing properties; the underlying mechanisms for these have not been well studied. Ankaferd’s individual components were determined by proteomic and chemical analyses. Ankaferd also augments transcription of some transcription factors which is shown with transcriptomic analysis. The independent effects of these ingredients and augmented transcription factors are not known precisely. Here, we review what is known of Ankaferd blood stopper components from chemical, proteomic, and transcriptomic analyses and propose that individual components can explain some pleiotropic effects of Ankaferd. Certainly more research is needed focusing on individual ingredients of Ankaferd to elucidate their precise and effects. PMID:28839937

The effects of a low-dose monophasic preparation of levonorgestrel and ethinyl estradiol on coagulation and other hemostatic factors.

PubMed

Archer, D F; Mammen, E F; Grubb, G S

1999-11-01

This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study. Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests. Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P

Hereditary deficiency of the sixth component of complement in man. II. Studies of hemostasis.

PubMed Central

Heusinkveld, R S; Leddy, J P; Klemperer, M R; Breckenridge, R T

1974-01-01

Prompted by previous observations of defective blood clotting in rabbits deficient in the sixth component of complement (C6), an evaluation was made of the hemostatic functions of the homozygous proband of a newly recognized human kindred with hereditary C6 deficiency. This human subject, who had no clinical evidence of a bleeding disorder, exhibited a total lack of C6 by functional and immunoprecipitin assays of serum or plasma. Standard tests of hemostatic function were normal; however, when the whole blood clotting time was measured at 25 degrees C in plastic tubes, it was at the upper range of our normal values. In confirmation of this observation, prothrombin consumption, when performed at 37 degrees C in plastic tubes, was at the lower range of normal. Inulin and endotoxin, in concentrations shown to cause activation of human complement, had little or no effect on clotting times or prothrombin consumption of normal or C6-deficient human blood. These observations indicate that absence of C6 does not have a significant effect on hemostatic function in man. In the light of other investigations, the observed differences in clotting function between C6-deficient human blood and C6-deficient rabbit blood could be due to species differences governing the susceptibility of platelets to complement activation. PMID:11344569

Effects of Chitin and Sepia Ink Hybrid Hemostatic Sponge on the Blood Parameters of Mice

PubMed Central

Zhang, Wei; Sun, Yu-Lin; Chen, Dao-Hai

2014-01-01

Chitin and sepia ink hybrid hemostatic sponge (CTSH sponge), a new biomedical material, was extensively studied for its beneficial biological properties of hemostasis and stimulation of healing. However, studies examining the safety of CTSH sponge in the blood system are lacking. This experiment aimed to examine whether CTSH sponge has negative effect on blood systems of mice, which were treated with a dosage of CTSH sponge (135 mg/kg) through a laparotomy. CTSH sponge was implanted into the abdominal subcutaneous and a laparotomy was used for blood sampling from abdominal aortic. Several kinds of blood parameters were detected at different time points, which were reflected by coagulation parameters including thrombin time (TT), prothrombin time (PT), activated partial thromboplatin time (APTT), fibrinogen (FIB) and platelet factor 4 (PF4); anticoagulation parameter including antithrombin III (AT-III); fibrinolytic parameters including plasminogen (PLG), fibrin degradation product (FDP) and D-dimer; hemorheology parameters including blood viscosity (BV) and plasma viscosity (PV). Results showed that CTSH sponge has no significant effect on the blood parameters of mice. The data suggested that CTSH sponge can be applied in the field of biomedical materials and has potential possibility to be developed into clinical drugs of hemostatic agents. PMID:24727395

Adsorption of tranexamic acid on hydroxyapatite: Toward the development of biomaterials with local hemostatic activity.

PubMed

Sarda, Stéphanie; Errassifi, Farid; Marsan, Olivier; Geffre, Anne; Trumel, Catherine; Drouet, Christophe

2016-09-01

This work proposes to combine tranexamic acid (TAX), a clinically used antifibrinolytic agent, and hydroxyapatite (HA), widely used in bone replacement, to produce a novel bioactive apatitic biomaterial with intrinsic hemostatic properties. The aim of this study was to investigate adsorptive behavior of the TAX molecule onto HA and to point out its release in near physiological conditions. No other phase was observed by X-ray diffraction or transmission electron microscopy, and no apparent change in crystal size was detected. The presence of TAX on the powders was lightly detected on Raman spectra after adsorption. The adsorption data could be fitted with a Langmuir-Freundlich equation, suggesting a strong interaction between adsorbed molecules and the formation of multilayers. The concentration of calcium and phosphate ions in solution remained low and stable during the adsorption process, thus ion exchange during the adsorption process could be ruled out. The release of TAX was fast during the first hours and was governed by a complex process that likely involved both diffusion and dissolution of HA. Preliminary aPTT (activated partial thromboplastin time) hemostasis tests offered promising results for the development of osteoconductive apatitic biomaterials with intrinsic hemostatic properties, whether for dental or orthopedic applications. Copyright © 2016. Published by Elsevier B.V.

Evaluation of thromboelastography in two factor XII-deficient cats.

PubMed

Blois, Shauna L; Holowaychuk, Marie K; Wood, R Darren

2015-01-01

The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine.

PubMed

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)-rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157 μg+L-NAME; BPC 157 μg+L-arginine, BPC 157 μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms.

Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

PubMed Central

Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

2015-01-01

Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

Cost-consequence analysis of different active flowable hemostatic matrices in cardiac surgical procedures.

PubMed

Makhija, D; Rock, M; Xiong, Y; Epstein, J D; Arnold, M R; Lattouf, O M; Calcaterra, D

2017-06-01

A recent retrospective comparative effectiveness study found that use of the FLOSEAL Hemostatic Matrix in cardiac surgery was associated with significantly lower risks of complications, blood transfusions, surgical revisions, and shorter length of surgery than use of SURGIFLO Hemostatic Matrix. These outcome improvements in cardiac surgery procedures may translate to economic savings for hospitals and payers. The objective of this study was to estimate the cost-consequence of two flowable hemostatic matrices (FLOSEAL or SURGIFLO) in cardiac surgeries for US hospitals. A cost-consequence model was constructed using clinical outcomes from a previously published retrospective comparative effectiveness study of FLOSEAL vs SURGIFLO in adult cardiac surgeries. The model accounted for the reported differences between these products in length of surgery, rates of major and minor complications, surgical revisions, and blood product transfusions. Costs were derived from Healthcare Cost and Utilization Project's National Inpatient Sample (NIS) 2012 database and converted to 2015 US dollars. Savings were modeled for a hospital performing 245 cardiac surgeries annually, as identified as the average for hospitals in the NIS dataset. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to test model robustness. The results suggest that if FLOSEAL is utilized in a hospital that performs 245 mixed cardiac surgery procedures annually, 11 major complications, 31 minor complications, nine surgical revisions, 79 blood product transfusions, and 260.3 h of cumulative operating time could be avoided. These improved outcomes correspond to a net annualized saving of $1,532,896. Cost savings remained consistent between $1.3m and $1.8m and between $911k and $2.4m, even after accounting for the uncertainty around clinical and cost inputs, in a one-way and probabilistic sensitivity analysis, respectively. Outcome differences associated with FLOSEAL vs SURGIFLO that were previously reported in a comparative effectiveness study may result in substantial cost savings for US hospitals.

Endothelial effects of hemostatic devices for continuous cardioplegia or minimally invasive operations.

PubMed

Perrault, L P; Menasché, P; Wassef, M; Bidouard, J P; Janiak, P; Villeneuve, N; Jacquemin, C; Bloch, G; Vilaine, J P; Vanhoutte, P M

1996-10-01

Improvements in myocardial protection may include the continuous delivery of normothermic blood cardioplegia. Technical aids are required for optimal visualization of the operative field during the performance of coronary anastomoses if cardioplegia is to be given continuously or during minimally invasive operations. However, the effects of the different hemostatic devices on coronary endothelial function are unknown. We compared the effects on endothelial function of two commonly used hemostatic techniques, coronary clamping and gas jet insufflation, with those of a technique using extravascular balloon occlusion to mimic systolic luminal closure by the surrounding myocardium. The three techniques were applied for 15 minutes on porcine epicardial coronary arteries from explanted hearts. For coronary clamping, standard bulldog clamps were used. Gas jet insufflation was applied by blowing oxygen (12 L/min) tangentially at a 45-degree angle 1 cm away from a 3-mm arteriotomy. Extravascular balloon occlusion was achieved with a needle-tipped silicone loop, the midportion of which, once positioned beneath the coronary artery, was inflated to push a myocardial "cushion" against the back of the vessel until its occlusion. Control rings were taken from the same coronary artery. The endothelial function of control and instrumented arterial rings was then studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution. Contractions to potassium chloride and prostaglandin F2 alpha and endothelium-independent relaxation to sin-1, a nitric oxide donor, were unaffected in all groups. Endothelium-dependent relaxation to serotonin was impaired after clamping and preserved after gas jet insufflation and extravascular balloon occlusion. Maximal endothelium-dependent relaxation to serotonin was as follows: for coronary clamping, 63% +/- 6% versus 87% +/- 3% in controls; for gas jet insufflation, 67% +/- 12% versus 88% +/- 7%; and for extraluminal balloon occlusion, 79% +/- 6% versus 85% +/- 5%. Whereas commonly used hemostatic devices may impair endothelial function, extravascular balloon occlusion appears to achieve effective hemostasis while preserving endothelial integrity.

Hemostatic properties of the free-electron laser

NASA Astrophysics Data System (ADS)

Cram, Gary P., Jr.; Copeland, Michael L.

1998-09-01

We have investigated the hemostatic properties of the free-electron laser (FEL) and compared these properties to the most commonly used commercial lasers in neurosurgery, CO 2 and Nd:YAG, using an acute canine model. Arterial and venous vessels, of varying diameters from 0.1 to 1.0 mm, were divided with all three lasers. Analysis of five wavelengths of the FEL (3.0, 4.5, 6.1, 6.45, and 7.7 microns) resulted in bleeding without evidence of significant coagulation, regardless of whether the vessel was an artery or vein. Hemorrhage from vessels less than 0.4 mm diameter was subsequently easily controlled with Gelfoam® (topical hemostatic agent) alone, whereas larger vessels required bipolar electrocautery. No significant charring, or contraction of the surrounding parenchyma was noted with any of the wavelengths chosen from FEL source. The CO 2 laser, in continuous mode, easily coagulated vessels with diameters of 4 mm and less, while larger vessels displayed significant bleeding requiring bipolar electrocautery for control. Tissue charring was noted with application of the CO 2 laser. In super pulse mode, the CO 2 laser exhibited similar properties, including significant charring of the surrounding parenchyma. The Nd:YAG coagulated all vessels tested up to 1.4 mm, which was the largest diameter cortical artery found, however this laser displayed significant and extensive contraction and retraction of the surrounding parenchyma. In conclusion, the FEL appears to be a poor hemostatic agent. Our results did not show any benefit of the FEL over current conventional means of achieving hemostasis. However, control of hemorrhage was easily achieved with currently used methods of hemostasis, namely Gelfoam® or bipolar electrocuatery. Although only cortical vessels in dogs were tested, we feel this data can be applied to all animals, including humans, and the peripheral, as well as central, vasculature, as our data on the CO 2 and Nd:YAG appear to closely support previous reports of hemostasis of these two lasers obtained in other models.

Levonorgestrel-Releasing Intrauterine Device Use in Female Adolescents with Heavy Menstrual Bleeding and Bleeding Disorders: Single Institution Review.

PubMed

Adeyemi-Fowode, Oluyemisi A; Santos, Xiomara M; Dietrich, Jennifer E; Srivaths, Lakshmi

2017-08-01

To identify complications and efficacy of the levonorgestrel-releasing intrauterine device (LNgIUD) in adolescents with heavy menstrual bleeding (HMB) and bleeding disorders (BD). A retrospective chart review of 13 postmenarchal adolescent girls with HMB/BD who underwent placement of an LNgIUD. Placement of an LNgIUD. Primary outcome was to identify complications from placement of an LNgIUD. Secondary outcome was to evaluate the efficacy of the LNgIUD in adolescents with BD. Thirteen patients met study criteria. The mean age of diagnosis of HMB was 14.08 ± 1.75 years. BD or bleeding risk factor diagnoses included low von Willebrand (VW) activity in 5, type I VW disease in 5, type IIM VW disease in 1, low VW activity and factor 7 deficiency in 1, and acquired VW disease and factor 7 deficiency in 1. Before LNgIUD placement, other hormonal therapy (n = 13) and hemostatic therapy (antifibrinolytic agents, desmopressin acetate; n = 8) yielded poor control of HMB. The LNgIUD was placed using anesthesia with periprocedure hemostatic therapy with no complications. All patients reported significant improvement in HMB after LNgIUD placement and 60% achieved amenorrhea, with mean time to improvement of 94 ± 69 days. Mean hemoglobin and ferritin levels increased after LNgIUD placement compared with before LNgIUD placement values (P = .02, P = .0085, respectively). Use of supplemental hormonal and hemostatic agents decreased (n = 4) after LNgIUD placement. None required LNgIUD removal; 1 spontaneously expelled the LNgIUD with subsequent replacement. Study results indicated the LNgIUD is an effective therapeutic option in postmenarchal adolescents with HMB due to BD/bleeding risk factor with minimal complications, high compliance rate, improvement in HMB and anemia, and no periprocedural bleeding with hemostatic management. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Do fibrin sealants impact negative outcomes after robot-assisted partial nephrectomy?

PubMed

Cohen, Jason; Jayram, Gautam; Mullins, Jeffrey K; Ball, Mark W; Allaf, Mohamad E

2013-10-01

Contemporary rates of postoperative hemorrhage after partial nephrectomy (PN) are low. Commercially available hemostatic agents are commonly used during this surgery to reduce this risk despite a paucity of data supporting the practice. We assessed the impact of fibrin sealant hemostatic agents, a costly addition to surgeries, during robot-assisted partial nephrectomy (RAPN). Between 2007 and 2011, 114 consecutive patients underwent RAPN by a single surgeon (MEA). Evicel fibrin sealant was used in the first 74 patients during renorraphy. The last 40 patients had renorraphy performed without the use of any hemostatic agents. Clinicopathologic, operative, and complication data were compared between groups. Multivariate and univariate logistic regression analysis was performed to test the association between the use of fibrin sealants and operative outcomes. Patient demographic data and clinical tumor characteristics were similar between groups. The use of fibrin sealant did not increase operative time (166.3 vs 176.1 minutes, P=0.28), warm ischemia time (WIT) (14.4 vs 16.1 minutes, P=0.18), or length of hospital stay (2.6 vs 2.4 days, P=0.35). The omission of these agents did not increase estimated blood loss (116.6 vs 176.1 mL, P=0.8) or postoperative blood transfusion (0% vs 2.5%, P=0.17). Univariate analysis demonstrated no association between use of fibrin sealants and increased complications (P>0.05). Multivariable logistic regression showed no statistically significant predictive value of omission of hemostatic agents for perioperative outcomes (P>0.05). Perioperative hemorrhage and other major complications after contemporary RAPN are rare in experienced hands. In our study, the use of fibrin sealants during RAPN does not decrease the rate of complications, blood loss, or hospital stay. Furthermore, no impact is seen on operative time, WIT, or other negative outcomes. Omitting these agents during RAPN could be a safe, effective, cost-saving measure.

Product comparison model in otolaryngology: Equivalency analysis of absorbable hemostatic agents after endoscopic sinus surgery.

PubMed

Antisdel, Jastin L; Meyer, Annika; Comer, Brett; Jang, David; Gurrola, Jose; Khabbaz, Eyad; Christopher, Kara; Kountakis, Stilianos

2016-01-01

Evidence-based medicine in otolaryngology literature continues to be lacking, especially with regard to new products brought to market. The marketing of products often includes statements of benefit that have limited objective support in research or literature. To address this, and to adequately determine product equivalency/superiority, careful evaluation must be made. In order to establish standards for this process in rhinology products, we directly compare three different absorbable hemostatic agents in patients with chronic rhinosinusitis (CRS) after undergoing endoscopic sinus surgery (ESS), using both objective and subjective outcomes. Double-blinded prospective (level 1) comparison and equivalency analysis of three plant-based absorbable hemostatic agents (carboxymethylcellulose [CMC] gel, mucopolysaccharide hemospheres (MPH), and potato starch wafer) in patients undergoing bilateral ESS. Patients with medically refractory CRS who underwent bilateral ESS were recruited and prospectively followed. At the conclusion of ESS, one of three different hemostatic agents was applied to each nasal passage. Subjective patient data was obtained using rated symptoms compared between the two sides (nasal obstruction, bleeding, pain, and nasal discharge) at baseline and on postoperative days 1, 7, and 14. Objective data was obtained by blinded endoscopic scoring to rate mucosal edema, inflammation, granulation, crusting, infection, and synechiae formation on postoperative weeks 1, 3, and 6. Forty-eight patients who underwent ESS for CRS were included. There is no statistical difference in subjective scores for any of the variables measured, although (MPH) nearly reached statistical significance at postoperative day 7 for increased pain (P = 0.06) and obstruction (P = 0.22). Objective measures showed equivalency between all products, except the CMC gel approached significance at week 3 for increased crusting (P = 0.10), granulation (P = 0.24), and debridement (P = 0.07). At 6 weeks, increased debridement (P = 0.14) also approached significance. Careful and deliberate consideration should be taken when choosing products to assist our surgical endeavors. Subjectively, patients treated with MPH showed near-significant increases in pain and obstruction. In objective measures, CMC gel nearly reaches significance for more postoperative debridement, with increased crusting and inflammation. Product choice could consider these factors, although it remains at the discretion of the surgeon. This model of comparison allows careful product comparison and should be applied to other hemostatics, as well as other materials in use in otolaryngology. 1b. Laryngoscope, 126:S5-S13, 2016. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Method of manufacturing fibrous hemostatic bandages

DOEpatents

Larsen, Gustavo; Spretz, Ruben; Velarde-Ortiz, Raffet

2012-09-04

A method of manufacturing a sturdy and pliable fibrous hemostatic dressing by making fibers that maximally expose surface area per unit weight of active ingredients as a means for aiding in the clot forming process and as a means of minimizing waste of active ingredients. The method uses a rotating object to spin off a liquid biocompatible fiber precursor, which is added at its center. Fibers formed then deposit on a collector located at a distance from the rotating object creating a fiber layer on the collector. An electrical potential difference is maintained between the rotating disk and the collector. Then, a liquid procoagulation species is introduced at the center of the rotating disk such that it spins off the rotating disk and coats the fibers.

Hemostasis in the Very Young.

PubMed

Kenet, Gili; Barg, Assaf Arie; Nowak-Göttl, Ulrike

2018-06-18

Hemostasis is a dynamic process that starts in utero. The coagulation system evolves with age, as evidenced by marked physiological differences in the concentration of the majority of hemostatic proteins in early life compared with adulthood. This concept, known as "developmental hemostasis," has important biological and clinical implications. Overall, impaired platelet function, along with physiologically reduced levels of vitamin K-dependent and contact coagulation factors, may cause poorer clot firmness even in healthy neonates. However, increased activity of von Willebrand factor and low levels of coagulation inhibitors that promote hemostasis counterbalance the delicate and immature hemostatic system. Since this hemostatic system has little reserve capacity, preterm neonates or sick infants are extremely vulnerable and predisposed to either hemorrhagic or thrombotic complications. This review will address the concept and manifestations of developmental hemostasis with respect to clinical disease phenotypes. It will discuss bleeding diagnosis in neonates, dealing especially with the devastating complications of intracerebral and pulmonary hemorrhage in preterm infants. Neonates, especially the sickest preterm ones, are also extremely susceptible to thrombotic complications; thus, thrombosis in neonates will be reviewed, with special focus on arterial ischemic perinatal stroke. Based on the concept of developmental hemostasis, the phenotypes of clinically relevant bleeding or thrombotic disorders among neonates may differ from those of older infants and children. Treatment options for these conditions will be suggested and reviewed. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential.

PubMed

Zouari Bouassida, Karama; Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Tounsi, Slim; Jlaiel, Lobna; Trigui, Mohamed

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H 2 OE), showing the most potent antibacterial and antioxidant activities in vitro , thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, "CICAFLORA," and U. dioica EtOH-H 2 OE (50  µ L/mm 2 ) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H 2 OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding ( P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H 2 OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H 2 OE in wound healing and supported its traditional use.

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

PubMed

Baudo, Francesco; Collins, Peter; Huth-Kühne, Angela; Lévesque, Hervé; Marco, Pascual; Nemes, László; Pellegrini, Fabio; Tengborn, Lilian; Knoebl, Paul

2012-07-05

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).

Massive oral bleeding after full-mouth extraction in a patient with B-cell lymphocytic leukemia/small lymphocytic lymphoma reversed with recombinant activated factor VII.

PubMed

Sprenker, Collin; Omar, Hesham R; Powless, R Andrew; Mangar, Devanand; Camporesi, Enrico

2016-02-01

Full-mouth extraction can be associated with intraoral bleeding, which usually is controlled with local hemostatic measures. Recombinant activated factor VII (rFVIIa) occasionally is used to stop bleeding in a variety of off-label indications, with the main argument curtailing its use being thrombotic events. The authors describe the use of rFVIIa for bleeding after full-mouth extraction in a patient with undiagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. A 72-year-old man underwent full-mouth extraction (18 teeth). The next day, the patient experienced massive oral bleeding. The authors administered tranexamic acid, aminocaproic acid, and a total of 12 units of packed red blood cells in addition to local hemostatic measures without control of bleeding. On postoperative day 10, the authors administered 5,000 micrograms of rFVIIa, and within 2 hours oral the bleeding ceased. The authors performed flow cytometry and diagnosed B-cell lymphocytic leukemia/small lymphocytic lymphoma. Unexplained massive oral bleeding despite adequate local hemostatic measures should prompt further investigations for underlying bleeding or coagulation disorders. The authors describe the successful use of rFVIIa in massive oral bleeding. Further studies are mandatory to study the effectiveness of this drug for this off-label indication. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Exploring the Urtica dioica Leaves Hemostatic and Wound-Healing Potential

PubMed Central

Bardaa, Sana; Khimiri, Meriem; Rebaii, Tarek; Jlaiel, Lobna

2017-01-01

The present paper investigated the efficiency of Urtica dioica (U. dioica) on hemostatic and wound healing activities. U. dioica leaf extracts were evaluated for their antibacterial and antioxidant effects as well as their flavonoid and polyphenol content. The hydroethanolic extract (EtOH-H2OE), showing the most potent antibacterial and antioxidant activities in vitro, thanks to its flavonoid and polyphenol richness, was selected for hemostatic and wound healing evaluation. Twenty-four rats completing full-thickness wounds were split into four groups. The wounds were topically treated with saline solution, glycerol, “CICAFLORA,” and U. dioica EtOH-H2OE (50 µL/mm2) until day 11. The wound healing effect was assessed by macroscopic, histological, and biochemical parameters. Rats treated with EtOH-H2OE showed fast wound closure (92.39%) compared to the control animals (60.91%) on the 11th day of wounding (P < 0.01). Histopathological and biochemical explorations showed full epidermal regeneration and an improvement of the hydroxyproline content in the U. dioica EtOH-H2OE treated rats. Analysis of fatty acids and sterols by GC-MS showed the presence of unsaturated fatty acids and a high concentration of lupeol known for their involvement in reepithelialization. These results prove the efficiency of U. dioica EtOH-H2OE in wound healing and supported its traditional use. PMID:29201895

Evaluation of thromboelastography in two factor XII-deficient cats

PubMed Central

Holowaychuk, Marie K; Wood, R Darren

2015-01-01

Case summary The current report describes thromboelastography (TEG) findings in two cats with factor XII (FXII) deficiency. The first cat was diagnosed with bilateral perinephric pseudocysts; hemostatic testing was performed prior to performing renal aspirates. The second cat was healthy; hemostatic testing was performed prior to inclusion into a research project. Both cats had markedly prolonged partial thromboplastin times and hypocoagulable TEG tracings when samples were activated with kaolin. However, when tissue factor (TF) was used to activate the sample, both cats had normal-to-hypercoagulable TEG tracings. The cats each had a subnormal FXII level. Relevance and novel information TEG is becoming widely used to investigate hemostasis in veterinary patients, and TEG results in cats with FXII deficiency have not been previously reported. FXII deficiency is the most common hereditary hemostatic defect in cats. While FXII deficiency does not lead to in vivo hemorrhagic tendencies, it can lead to marked prolongation in activated partial thromboplastin and activated clotting times, and cannot be differentiated from true hemorrhagic diatheses without measuring individual factor activity. With the increased use of TEG to evaluate hemostasis in veterinary patients, it is important to recognize the effects of FXII deficiency on this testing modality. The finding of a hypocoagulable kaolin-activated TEG tracing and a concurrent normal TF-activated TEG tracing in samples should prompt clinicians to consider ruling out FXII deficiency. PMID:28491358

Newer Hemostatic Agents Used in the Practice of Dermatologic Surgery

PubMed Central

Brewer, Jerry D.

2013-01-01

Minor postoperative bleeding is the most common complication of cutaneous surgery. Because of the commonality of this complication, hemostasis is an important concept to address when considering dermatologic procedures. Patients that have a bleeding diathesis, an inherited/acquired coagulopathy, or who are on anticoagulant/antiplatelet medications pose a greater risk for bleeding complications during the postoperative period. Knowledge of these conditions preoperatively is of the utmost importance, allowing for proper preparation and prevention. Also, it is important to be aware of the various hemostatic modalities available, including electrocoagulation, which is among the most effective and widely used techniques. Prompt recognition of hematoma formation and knowledge of postoperative wound care can prevent further complications such as wound dehiscence, infection, or skin-graft necrosis, minimizing poor outcomes. PMID:23997764

Proteome analysis of snake venom toxins: pharmacological insights.

PubMed

Georgieva, Dessislava; Arni, Raghuvir K; Betzel, Christian

2008-12-01

Snake venoms are an extremely rich source of pharmacologically active proteins with a considerable clinical and medical potential. To date, this potential has not been fully explored, mainly because of our incomplete knowledge of the venom proteome and the pharmacological properties of its components, in particular those devoid of enzymatic activity. This review summarizes the latest achievements in the determination of snake venom proteome, based primarily on the development of new strategies and techniques. Detailed knowledge of the venom toxin composition and biological properties of the protein constituents should provide the scaffold for the design of new more effective drugs for the treatment of the hemostatic system and heart disorders, inflammation, cancer and consequences of snake bites, as well as new tools for clinical diagnostic and assays of hemostatic parameters.

An update on the use of massive transfusion protocols in obstetrics.

PubMed

Pacheco, Luis D; Saade, George R; Costantine, Maged M; Clark, Steven L; Hankins, Gary D V

2016-03-01

Obstetrical hemorrhage remains a leading cause of maternal mortality worldwide. New concepts involving the pathophysiology of hemorrhage have been described and include early activation of both the protein C and fibrinolytic pathways. New strategies in hemorrhage treatment include the use of hemostatic resuscitation, although the optimal ratio to administer the various blood products is still unknown. Massive transfusion protocols involve the early utilization of blood products and limit the traditional approach of early massive crystalloid-based resuscitation. The evidence behind hemostatic resuscitation has changed in the last few years, and debate is ongoing regarding optimal transfusion strategies. The use of tranexamic acid, fibrinogen concentrates, and prothrombin complex concentrates has emerged as new potential alternative treatment strategies with improved safety profiles. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanistic investigation of a hemostatic keratin biomaterial

NASA Astrophysics Data System (ADS)

Rahmany, Maria Bahawdory

Traumatic injury leads to more productive years lost than heart disease, cancer and stroke combined. Trauma is often accompanied and complicated by uncontrolled bleeding. Human hair keratin biomaterials have demonstrated efficacy in controlling hemorrhage in both small and large animal models; however little is known about the mechanism by which these proteins aid in blood clotting. Inspection of the amino acid sequence of known keratins shows the presence of several cellular binding motifs, suggesting a possible mechanism and potentially eliminating the need to functionalize the material's surface for cellular interaction. In addition to small animal studies, the hemostatic activity of keratin hydrogels was explored through porcine hemorrhage models representing both a high flow and low flow bleed. In both studies, keratin hydrogels appeared to lead to a significant reduction in blood loss. The promising results from these in vivo studies provided the motivation for this project. The objective of this dissertation work was to assess the mechanism of action of a hemostatic keratin biomaterial, and more broadly assess the biomaterial-cellular interaction(s). It is our hypothesis that keratin biomaterials have the capacity to specifically interact with cells and lead to propagation of intracellular signaling pathway, specifically contributing to hemostasis. Through application of biochemical and molecular tools, we demonstrate here that keratin biomaterials contribute to hemostasis through two probable mechanisms; integrin mediated platelet adhesion and increased fibrin polymerization. Platelets are the major cell type involved in coagulation both by acting as a catalytic surface for the clotting cascade and adhering to extracellular matrix (ECM) proteins providing a soft platelet plug. Because keratin biomaterials have structural and biochemical characteristics similar to ECM proteins, we utilized several adhesion assays to investigate platelet adhesion to keratin biomaterial surfaces. While other groups have discussed keratin's capacity to specifically adhere cells, this work was the first to utilize function blocking antibodies to deduce the specific receptors involved in mediating the cell-keratin interaction. To explore keratin's role in the second arm of coagulation, the clotting cascade, we followed the kinetic behavior of fibrin generation in the presence and absence of keratin. Confirmed with samples of plasma and a purified system of fibrinogen and thrombin, we observed an increased rate of fibrin polymerization in the presence of keratin proteins. The final goal of this project was to utilize a Chinese hamster ovary cell line to more specifically explore integrin-mediated cell interactions with keratin biomaterials in a controlled, biologically relevant system. Together, this work provides key details regarding keratin's hemostatic characteristics, providing the foundations for further development and optimizing of the material's unique characteristics for use as a hemostatic agent. More broadly, application of the CHO cell model could provide a useful tool for developing a receptor-ligand profile for keratin biomaterials.

Alteration of Hemostatic Parameters in Patients with Different Levels of Subclinical Hypothyroidism and the Effect of L-thyroxine Treatment.

PubMed

Gao, Fang; Wang, Guangya; Xu, Jinxiu

2017-01-01

Subclinical hypothyroidism (SH) is associated with hypercoagulability and hypofibrinolysis. The objective of this study was to assess the effect of L-thyroxine (L-T4) treatment and to evaluate changes in the hemostatic abnormalities of patients with varying severities of SH. We measured tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), D-dimer (DDI), fibrinogen (FIB), platelet counts (PLT), mean platelet volume (MPV), platelet distribution width (PDW), activated partial thromboplastin time (APTT), and prothrombin time (PT) in 149 female subjects. The prospective study included 54 patients in the control group, 53 patients with 4.2 μIU/mL

Day care PNL using 'Santosh-PGI hemostatic seal' versus standard PNL: A randomized controlled study.

PubMed

Kumar, Santosh; Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission.

Day care PNL using ‘Santosh-PGI hemostatic seal’ versus standard PNL: A randomized controlled study

PubMed Central

Singh, Shivanshu; Singh, Prashant; Singh, Shrawan Kumar

2016-01-01

Introduction To compare the outcomes of tubeless day care PNL using hemostatic seal in the access tract versus standard PNL. Material and methods It was a prospective randomized controlled study. Cases were randomized to either the day care group with hemostatic seal (DCS) or the control group where patients were admitted and a nephrostomy tube was placed at the conclusion of surgery. Results A total of 180 cases were screened and out of these, 113 were included in the final analysis. The stone clearance rates were comparable in both the groups. The mean drop in hemoglobin was significantly lower in DCS group than the control group (1.05 ±0.68 vs. 1.30 ±0.58 gm/dl, p = 0.038).Mean postoperative pain score, analgesic requirement (paracetamol) and duration of hospital stay were also significantly lower in the DCS group (3.79 ±1.23 vs. 6.12 ±0.96, 1.48 ±0.50 vs. 4.09 ±1.11 grams and 0.48 ±0.26 vs. 4.74 ±1.53 days respectively; p <0.05). The incidence of urine leakage through the access tract site was significantly lower in the DCS subgroup when compared to the controls (3.6% vs. 21.1%, p <0.05). Cases in the DCS group resumed their normal activities in a significantly shorter time (8.05 ±3.05 vs.18.42 ±4.42 days; p <0.05). Higher proportion of cases in the DCS group got re-admitted, although it was not a statistically significant number (7.1% vs. 1.8%; p = 0.21). Conclusions Tubeless day care PNL with composite hemostatic tract seal is considered safe. It resulted in a significant reduction of blood loss and analgesic requirement with significantly reduced hospital stay, nephrostomy tube site morbidity and time required to resume normal activity when compared to the standard PNL. However, patients must be compliant with the given instructions and should have access to a health care facility, as few of them may need re-admission. PMID:27551557

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables.

PubMed

Endrikat, Jan; Klipping, C; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

2002-03-01

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers. In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.

Upon admission coagulation and platelet function in patients with thermal and electrical injuries.

PubMed

Wade, Charles E; Baer, Lisa A; Cardenas, Jessica C; Folkerson, Lindley E; Nutall-Aurora, Kisha; Cotton, Bryan A; Matijevic, Nena; Holcomb, John B; Cross, James M; Huzar, Todd

2016-12-01

There has been increased focus on hemostatic potential and function in the initial assessment of the patient with traumatic injuries, that not been extensively studied in patients with burns. We proposed to determine the hemostatic potential of patients with burns upon admission to the emergency department and contrasted their condition with that of healthy controls and patients with other traumatic injuries. In addition we assessed differences due to thermal versus electrical injury and evaluated the effect of burn size. This is a patient based prospective observational study conducted with delayed consented. Subjects at the highest level of trauma activation upon admission to the ED had a blood sample collected for research purposes and were subsequently consented. Hemostatic potential was measured by rapid thromelastography (r-TEG ® ), thrombin generation by calibrated automated thrombogram (CAT) and platelet function by Multiplate ® using five activators. Burn subjects were compared to subjects with other traumatic injuries and controls. Within the burn subjects additional analysis compared mechanism (thermal vs. electrical) and burn size. Values are medians (IQR). Two hundred and eighty two trauma patients (with burns n=40, 14%) and 27 controls were enrolled. Upon admission, compared to controls, subjects with burns or trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot formation and thrombin generation. There were no differences in burns compared to other traumatic injuries. The presence of hyper-coagulation did not appear to be related to the type of burn or the percentage of total body surface area involved. Employing previous defined cut points for R-TEG driven therapeutic interventions burn patients had similar rates of hyper- and hypo-coagulation noted in patients with traumatic injuries. Upon admission patients with burns are in a hyper-coagulable state similar to that of other trauma patients. Employing demonstrated cut points of hemostatic potential in trauma patients associated with increased risk of poor outcomes demonstrated the incidence in burn patients to be similar, suggesting that these values could be used in the early assessment of the patient with burns to guide treatment interventions. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Metastasis: recent discoveries and novel perioperative treatment strategies with particular interest in the hemostatic compound desmopressin.

PubMed

Alonso, D F; Ripoll, G V; Garona, J; Iannucci, N B; Gomez, D E

2011-11-01

Metastatic disease is responsible for most of cancer lethality. A main obstacle for therapy of advanced cancers is that the outcome of metastasis depends on a complex interplay between malignant and host cells. The perioperative period represents an underutilized window of opportunity for cancer treatment where tumor-host interactions can be modulated, reducing the risk of local recurrences and distant metastases. Blood-saving agents are attractive compounds to be administered during tumor surgery. Desmopressin (DDAVP) is a safe and convenient hemostatic peptide with proved antimetastastic properties in experimental models and veterinary clinical trials. The compound seems to induce a dual angiostatic and antimetastatic effect, breaking the cooperative function of cancer cells and endothelial cells during residual tumor progression. DDAVP is therefore an interesting lead compound to develop novel synthetic peptide analogs with enhanced antitumor properties.

Comparison of Floseal(r) and electrocautery in hemostasis after total knee arthroplasty

PubMed Central

Helito, Camilo Partezani; Gobbi, Riccardo Gomes; Castrillon, Lucas Machado; Hinkel, Betina Bremer; Pécora, José Ricardo; Camanho, Gilberto Luis

2013-01-01

Objective To evaluate whether hemostasis with eletrocauterization in comparison with Floseal(r) leads to different bleeding rates during total knee arthroplasty. Methods A comparative study was performed between two groups: group with ten consecutive total knee arthroplasties with Floseal(r) used as hemostatic method and control group with ten consecutive total knee arthroplasties with eletrocauterization as hemostatic method. Bleeding parameters such as debit of the drain, liquid infusion and blood transfusion rate were recorded. Results Floseal(r) group received less blood transfusion, less liquid infusion and lower drainage in absolute numbers compared to the control group. However, no parameter was statistically significant. Conclusion Hemostasis with Floseal(r) is as effective as hemostasis with eletrocauterization, what makes it a viable alternative to patients with contraindication to electric scalpel use. Level of Evidence II, Prospective Comparative Study. PMID:24453689

Hemostatic Changes Associated With Increased Mortality Rates in Hospitalized Patients With HIV-Associated Tuberculosis: A Prospective Cohort Study

PubMed Central

Schutz, Charlotte; Ward, Amy M.; Huson, Mischa A. M.; Wilkinson, Robert J.; Burton, Rosie; Maartens, Gary; Wilkinson, Katalin A.; Meijers, Joost C. M.; Lutter, René; Grobusch, Martin P.; Meintjes, Graeme; van der Poll, Tom

2017-01-01

Background Mortality rates remain high for human immunodeficiency virus (HIV)–associated tuberculosis, and our knowledge of contributing mechanisms is limited. We aimed to determine whether hemostatic changes in HIV-tuberculosis were associated with mortality or decreased survival time and the contribution of mycobacteremia to these effects. Methods We conducted a prospective study in Khayelitsha, South Africa, in hospitalized HIV-infected patients with CD4 cell counts <350/µL and microbiologically proved tuberculosis. HIV-infected outpatients without tuberculosis served as controls. Plasma biomarkers reflecting activation of procoagulation and anticoagulation, fibrinolysis, endothelial cell activation, matricellular protein release, and tissue damage were measured at admission. Cox proportional hazard models were used to assess variables associated with 12-week mortality rates. Results Of 59 patients with HIV-tuberculosis, 16 (27%) died after a median of 12 days (interquartile range, 0–24 days); 29 (64%) of the 45 not receiving anticoagulants fulfilled criteria for disseminated intravascular coagulation. Decreased survival time was associated with higher concentrations of markers of fibrinolysis, endothelial activation, matricellular protein release, and tissue damage and with decreased concentrations for markers of anticoagulation. In patients who died, coagulation factors involved in the common pathway were depleted (factor II, V, X), which corresponded to increased plasma clotting times. Mycobacteremia modestly influenced hemostatic changes without affecting mortality. Conclusions Patients with severe HIV-tuberculosis display a hypercoagulable state and activation of the endothelium, which is associated with mortality. PMID:28363198

Renal, gastrointestinal, and hemostatic effects of oral administration of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis).

PubMed

Dijkstra, Bas; Guzman, David Sanchez-Migallon; Gustavsen, Kate; Owens, Sean D; Hass, Carlyle; Kass, Philip H; Paul-Murphy, Joanne R

2015-04-01

To investigate renal, gastrointestinal, and hemostatic effects associated with oral administration of multiple doses of meloxicam to healthy Hispaniolan Amazon parrots (Amazona ventralis). 12 Hispaniolan Amazon parrots. Birds were assigned to receive meloxicam oral suspension (1.6 mg/kg, PO, q 12 h) and 2.5 mL of tap water inserted into the crop by use of a gavage tube (n = 8) or the equivalent volume of tap water only (control group; 4) for 15 days. Urine and feces were collected 2 hours after treatment administration each day. Feces were evaluated for occult blood. Results of a CBC and serum biochemical analysis and measured N-acetyl-β-d-glucosaminidase (NAG) activity and whole blood clotting time were evaluated before, during, and after completion of treatments. Results of urinalysis and measured urine NAG activity were also evaluated. Birds treated with meloxicam had a significant increase in number of WBCs and decrease in PCV from before to after treatment. The PCV also decreased significantly, compared with results for the control group; however, WBC count and PCV for all birds remained within reference ranges throughout the study. One parrot treated with meloxicam had a single high value for urine NAG activity. Meloxicam administered orally at the dosage used in this study caused no apparent negative changes in several renal, gastrointestinal, or hemostatic variables in healthy Hispaniolan Amazon parrots. Additional studies to evaluate adverse effects of NSAIDs in birds will be needed.

Hemostatic Abnormalities in Multiple Myeloma Patients

PubMed Central

Gogia, Aarti; Sikka, Meera; Sharma, Satender; Rusia, Usha

2018-01-01

Background: Multiple myeloma (MM) is a neoplastic plasma cell disorder characterized by clonal proliferation of plasma cells in the bone marrow. Diverse hemostatic abnormalities have been reported in patients with myeloma which predispose to bleeding and also thrombosis. Methods: Complete blood count, biochemical parameters and parameters of hemostasis i.e. platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), factor VIII assay results, plasma fibrinogen, D-dimer and lupus anticoagulant, were assessed in 29 MM patients and 30 age matched controls. Results: The most frequent abnormal screening parameter was APTT. Of the six indicative of a bleeding tendency i.e. thrombocytopenia, prolonged PT, APTT, TT, reduced plasma fibrinogen and factor VIII, at least one was abnormal in 8 (27.6%) patients. Of the four prothrombotic markers, lupus anticoagulant, D-dimer, elevated factor VIII and plasma fibrinogen, one or more marker was present in 24 (82.7%). D-dimer was the most common prothrombotic marker, being elevated in 22 (75.9%) patients. One or more laboratory parameter of hemostasis was abnormal in all 29 (100%) patients. Though thrombotic complications are reported to be less frequent as compared to hemorrhagic manifestations, one or more marker of thrombosis was present in 24 (82.7%) patients. Conclusion: This study provided laboratory evidence of hemostatic dysfunction which may be associated with thrombotic or bleeding complications at diagnosis in all MM patients. Hence, screening for these abnormalities at the time of diagnosis should help improved prognosis in such cases. PMID:29373903

[Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together to cure epistaxis with blood disease].

PubMed

Liu, Hua; Gao, Zhanmei; Song, Yang; Lu, Mancun

2014-01-01

This study investigated the effects and Numerical Rating Pain Scale (NRS) of using absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together nasal packing in the control of epistaxis with blood disease, and compared it with traditional vaseline gauze. Ninety-six blood disease patient with epistaxis were enrolled between January 2009 and February 2011, they were divided into two groups at random, and differently treated with absorbable shanching satin rb-bFGF prepreg sheet and the vaseline gauze nasal packing for haemostasis. Then haemostasis efficacy,the hemorrhage rate after nasal packing removed and host response, such as nasal pain and headache, which evaluated pain degrees against NRS, were all observed. There was no significant difference between the two groups of the haemostatic effect. But the hemorrhage rate of treatment group was obviously lower than that of the control group after paching,in addition, host responses, such as nasal pain and headache, remarkably better than the control group, the difference had statistical significance. It is indicate that absorbable shanching satin rb-bFGF prepreg sheet presents reliable hemostasis effect, good biocompatibility and compliance; the pain and headache caused by packing are superior to vaseline gauze. Moreover, this method avoids the direct touch of vaseline gauze with nasal mucosal wound, and reduce hemorrhage after packing. Absorbable shanching satin rb-bFGF prepreg sheet and expansion hemostatic sponge together is better to select the nasal packing material for blood disease patient with epistaxis.

Percutaneous suprapubic stone extraction for posterior urethral stones in children: efficacy and safety.

PubMed

Safwat, Ahmed S; Hameed, Diaa A; Elgammal, Mohamed A; Abdelsalam, Yasser M; Abolyosr, Ahmad

2013-08-01

To evaluate the safety and efficacy of percutaneous suprapubic stone extraction (PSPSE) for pediatric posterior urethral stones. Between July 2007 and June 2010, 54 boys presenting with acute urinary retention due to posterior urethral stones underwent PSPSE. Patients were a mean age of 66.4 months (range, 8-180 months). The stone size was 0.7-1.9 cm. Patients were placed under general anesthesia, and a 7F urethroscope was used to pushback the stone to the bladder. A 3-mm suprapubic puncture with a scalpel was performed, followed by insertion of a straight narrow hemostat through the puncture aided with cystoscopic guidance. The stone was grasped with the hemostat in its narrowest diameter and was extracted percutaneously or crushed if friable. The suprapubic puncture was closed with a single 4-0 Vicryl (Ethicon) suture. Intact stone retrieval was achieved in 45 patients, and the stone was crushed into minute fragments in 9 patients. Intraperitoneal extravasation developed in 1 patient that required open surgical intervention. Mean operative time was 22 minutes. Patients were monitored for up to 17 months, with complete resolution of symptoms and stone clearance. PSPSE provides a minimally invasive approach for the extraction of urethral and bladder stones in the pediatric population. The use of a straight hemostat for suprapubic stone extraction or crushing is a good alternative to suprapubic tract dilation, with minimal morbidity. Copyright © 2013 Elsevier Inc. All rights reserved.

Emerging roles for hemostatic dysfunction in malaria pathogenesis.

PubMed

O'Sullivan, Jamie M; Preston, Roger J S; O'Regan, Niamh; O'Donnell, James S

2016-05-12

Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum-infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance. © 2016 by The American Society of Hematology.

COMBAT: Initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock

PubMed Central

Chapman, Michael P.; Moore, Ernest E.; Chin, Theresa L; Ghasabyan, Arsen; Chandler, James; Stringham, John; Gonzalez, Eduardo; Moore, Hunter B.; Banerjee, Anirban; Silliman, Christopher C; Sauaia, Angela

2015-01-01

The existing evidence shows great promise for plasma as the first resuscitation fluid in both civilian and military trauma. We embarked on the Control of Major Bleeding After Trauma (COMBAT) trial with the support of the Department of Defense, in order to determine if plasma-first resuscitation yields hemostatic and survival benefits. The methodology of the COMBAT study represents not only three years of development work, but the integration of nearly two-decades of technical experience with the design and implementation of other clinical trials and studies. Herein, we describe the key features of the study design, critical personnel and infrastructural elements, and key innovations. We will also briefly outline the systems engineering challenges entailed by this study. COMBAT is a randomized, placebo controlled, semi-blinded prospective Phase IIB clinical trial, conducted in a ground ambulance fleet based at a Level I trauma center, and part of a multicenter collaboration. The primary objective of COMBAT is to determine the efficacy of field resuscitation with plasma first, compared to standard of care (normal saline). To date we have enrolled 30 subjects in the COMBAT study. The ability to achieve intervention with a hemostatic resuscitation agent in the closest possible temporal proximity to injury is critical and represents an opportunity to forestall the evolution of the “bloody vicious cycle”. Thus, the COMBAT model for deploying plasma in first response units should serve as a model for RCTs of other hemostatic resuscitative agents. PMID:25784527

Comparative Testing of Hemostatic Dressing in a Large Animal Model (Sus Scorofa) with Severe hepatic Injuries

DTIC Science & Technology

2013-12-02

applicable terms in EACH column) ___ Training: Live Animal ___ Medical Readiness ___ Prolonged Restraint ___ Training: non-Live Animal ... Health Promotion ___ Multiple Survival Surgery ___ Research: Survival (chronic) ___ Prevention ___ Behavioral Study _X__ Research

Clinical experience with fibrin glue in cardiac surgery.

PubMed

Köveker, G; de Vivie, E R; Hellberg, K D

1981-10-01

Cardiac surgery is often associated with hemostatic abnormalities leading to severe bleeding. Special problems are to be expected, if prosthetic material has to be implanted. Preclotting of Dacron prostheses with blood is well established but failures are sometimes encountered. Several years ago a new hemostatic sealing system (fibrin glue) was introduced into therapy. Since 1978 fibrin glue has been applied in 176 patients. The indications were: 1. sealing of woven Dacron prostheses, 2. bleeding from suture-holes (Gore-Tex), 3. diffuse myocardial bleeding and 4. prevention of kinking of coronary artery grafts. In 32 patients with an aortoventriculoplasty operation using Dacron the "blood preclotting" and "fibrin sealing" methods were compared. In the fibrin glue group there was a significant reduction in postoperative blood loss as well as a shortening of the operation time (period of protamin administration to skin closure). No fibrinolytic dissolution of the fibrin layer on the prostheses was observed.

Laser evaporation of the prostate: preliminary findings in canines

NASA Astrophysics Data System (ADS)

Kuntzman, R. S.; Malek, Reza S.; Barrett, David M.; Bostwick, David G.

1996-05-01

Purpose: We evaluated the ability of KTP laser to evaporate prostatic tissue in vivo and compared the results with historical Nd:YAG treated controls. Methods: Five dogs underwent anterograde transurethral evaporation of the prostate (TUEP) with KTP laser at 38 watts and were sacrificed 48 hours after surgery. Results: All procedures were hemostatic and without complications. Laser evaporation produced cavities within the prostate ranging from 2.5 to 3.2 cm in diameter (average equals 2.9 cm) that were free of necrotic tissue. Conclusions: Preliminary findings in this initial canine study of laser evaporation of the prostate, show that KTP laser produces large spherical cavities within the prostate in a hemostatic fashion. These cavities are free of necrotic tissue. In addition, these cavities are comparable in size to those that have been observed 4 to 8 weeks following Nd:YAG VLAP and are significantly larger than the acute cavities produced by Nd:YAG TUEP.

Hemostatic potential of natural/synthetic polymer based hydrogels crosslinked by gamma radiation

NASA Astrophysics Data System (ADS)

Barba, Bin Jeremiah D.; Tranquilan-Aranilla, Charito; Abad, Lucille V.

2016-01-01

Various raw materials and hydrogels prepared from their combination were assessed for hemostatic capability using swine whole blood clotting analysis. Initial screening showed efficient coagulative properties from κ-carrageenan and its carboxymethylated form, and α-chitosan, even compared to commercial products like QuikClot Zeolite Powder. Blending natural and synthetic polymers formed into hydrogels using gamma radiation produced materials with improved properties. KC and CMKC hydrogels were found to have the lowest blood clotting index in granulated form and had the higher capacity for platelet adhesion in foamed form compared to GelFoam. Possible mechanisms involved in the evident thrombogenicity of the materials include adsorption of platelets and related proteins that aid in platelet activation (primary hemostasis), absorption of water to concentrate protein factors that control the coagulation cascade, contact activation by its negatively charged surface and the formation of gel-blood clots.

The use of platelet-rich fibrin as a hemostatic material in oral soft tissues.

PubMed

de Almeida Barros Mourão, Carlos Fernando; Calasans-Maia, Mônica Diuana; de Mello Machado, Rafael Coutinho; de Brito Resende, Rodrigo Figueiredo; Alves, Gutemberg Gomes

2018-06-26

The control of postoperative bleeding represents one of the main intercurrent events associated with soft tissue surgical procedures in the oral cavity. In this context, platelet-rich fibrin (PRF) membranes are materials with great potential for optimizing soft tissue healing and induction of hemostasis. This interventional case series describes the treatment of 10 patients with excisional biopsy of benign oral cavity lesions, following a screening sequence at the surgery clinic of a Brazilian dental school between the years of 2015 and 2017. After treatment with PRF, patients presented mean time for postoperative hemostasis of 10.3 ± 2.5 s, requiring the average use of three membranes to cover the surgical area. The results suggest that the use of platelet-rich fibrin membranes may represent a feasible alternative hemostatic material for the treatment of oral lesions.

Myelofibrosis and acquired hemophilia A: a case report.

PubMed

Wrobel, Marie; Comio, Emilie; Gay, Valerie; Baroudi, Noureddine; Meyer, Pascal; Chuniaud-Louche, Christine; Hacini, Maya; Pica, Gian Matteo

2016-05-07

Myelofibrosis and acquired hemophilia A is a rare association. To the best of our knowledge only one case of myelofibrosis and acquired hemophilia A has been previously described. A 66-year-old Caucasian man diagnosed with myelofibrosis evolving in acute myeloid leukemia was referred to us for postoperative bleeding. Hemostatic studies showed prolonged activated partial thromboplastin time, decreased factor VIII coagulation, and a high factor VIII inhibitor titer; these findings led to a diagnosis of acquired hemophilia A for which he was treated with methylprednisolone and recombinant activated factor VII on admission. Due to a lack of response he was subsequently treated with rituximab combined with activated prothrombin complex concentrates. Furthermore, he received azacytidine to treat the underlying hematological malignancies. Immunosuppressive rituximab therapy resolved acquired hemophilia A with marked efficacy. Rapid and accurate diagnosis, effective hemostatic therapy, and timely treatment for underlying disease are important in the management of acquired hemophilia A secondary to hematological malignancy.

Influence of stearic acid on postprandial lipemia and hemostatic function.

PubMed

Sanders, Thomas A B; Berry, Sarah E E

2005-12-01

It has been suggested that fats rich in stearic acid may result in exaggerated postprandial lipemia and have adverse effects on hemostatic function. The effects of test meals containing different saturated and monounsaturated FA were compared in healthy subjects in a series of studies to investigate this hypothesis. Stearic acid, when present as cocoa butter, resulted in similar postprandial lipemia and factor VII activation compared with a meal containing high-oleic sunflower oil. Stearic acid when presented as shea butter or as randomized stearate-rich TAG resulted in decreased postprandial lipemia and decreased postprandial activation of factor VII. Stearic acid-rich test meals did not result in impaired fibrinolytic activity compared with either a low-fat meal or a meal high in oleate. The difference in responses between the different stearic acid-rich fats appears to be due to varying solid fat contents of the fats at 37 degrees C.

Massive transfusion and nonsurgical hemostatic agents.

PubMed

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

2008-07-01

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

Effects of contamination by either blood or a hemostatic agent on the shear bond strength of orthodontic buttons

PubMed Central

Alkis, Huseyin; Turkkahraman, Hakan

2013-01-01

Objective To evaluate the effects of contamination by either blood or a hemostatic agent on the shear bond strength (SBS) of orthodontic buttons. Methods We used 45 freshly extracted, non-carious, impacted third molars that were divided into 3 groups of 15. Each tooth was etched with 37% phosphoric acid gel for 30 s. Human blood or the blood stopper agent was applied to the tooth surface in groups I and II, respectively. Group III teeth were untreated (controls). Orthodontic buttons were bonded to the teeth using light-curing composite resin. After bonding, the SBS of the button was determined using a Universal testing machine. Any adhesive remaining after debonding was assessed and scored according to the modified adhesive remnant index (ARI). ANOVA with post-hoc Tukey's test was used to determine significant differences in SBS and Fisher's exact test, to determine significant differences in ARI scores among groups. Results ANOVA indicated a significant difference between groups (p < 0.001). The highest SBS values were measured in group III (10.73 ± 0.96 MPa). The SBS values for teeth in groups I and II were significantly lower than that of group III (p < 0.001). The lowest SBS values were observed in group I teeth (4.17 ± 1.11 MPa) (p < 0.001). Conclusions Contamination of tooth surfaces with either blood or hemostatic agent significantly decreased the SBS of orthodontic buttons. When the contamination risk is high, it is recommended to use the blood stopper agent when bonding orthodontic buttons on impacted teeth. PMID:23671834

Pharmacologic Hemostatic Agents in Total Joint Arthroplasty-A Cost-Effectiveness Analysis.

PubMed

Ramkumar, Dipak B; Ramkumar, Niveditta; Tapp, Stephanie J; Moschetti, Wayne E

2018-03-03

Total knee and hip arthroplasties can be associated with substantial blood loss, affecting morbidity and even mortality. Two pharmacological antifibrinolytics, ε-aminocaproic acid (EACA) and tranexamic acid (TXA) have been used to minimize perioperative blood loss, but both have associated morbidity. Given the added cost of these medications and the risks associated with then, a cost-effectiveness analysis was undertaken to ascertain the best strategy. A cost-effectiveness model was constructed using the payoffs of cost (in United States dollars) and effectiveness (quality-adjusted life expectancy, in days). The medical literature was used to ascertain various complications, their probabilities, utility values, and direct medical costs associated with various health states. A time horizon of 10 years and a willingness to pay threshold of $100,000 was used. The total cost and effectiveness (quality-adjusted life expectancy, in days) was $459.77, $951.22, and $1174.87 and 3411.19, 3248.02, and 3342.69 for TXA, no pharmacologic hemostatic agent, and EACA, respectively. Because TXA is less expensive and more effective than the competing alternatives, it was the favored strategy. One-way sensitivity analyses for probability of transfusion and myocardial infarction for all 3 strategies revealed that TXA remains the dominant strategy across all clinically plausible values. TXA, when compared with no pharmacologic hemostatic agent and with EACA, is the most cost-effective strategy to minimize intraoperative blood loss in hip and knee total joint arthroplasties. These findings are robust to sensitivity analyses using clinically plausible probabilities. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term results of laparoscopic treatment of esophageal achalasia in children: a multicentric survey.

PubMed

Esposito, Ciro; Riccipetitoni, Giovanna; Chiarenza, Salvatore Fabio; Roberti, Agnese; Vella, Claudio; Alicchio, Francesca; Fava, Giorgio; Escolino, Maria; De Pascale, Teresa; Settimi, Alessandro

2013-11-01

This report describes three Italian centers' experience in the treatment of children with esophageal achalasia. Between June 2000 and June 2012, 31 children (13 girls and 18 boys, with a median age of 8.4 years) affected by esophageal achalasia were treated in three different institutions with an esophagomyotomy according to Heller's procedure via laparoscopy associated with a Dor antireflux procedure. Between 2000 and 2005 (for 14 patients) we used mono- or bipolar coagulation to perform myotomy; after 2005 (for 17 patients) we used the new hemostatic devices to perform it. Median length of surgery was 120 minutes. Median hospital stay was 4 days. We recorded eight complications in our series: 3 patients (9.6%) had a mucosal perforation, and 5 children (16.1%) presented dysphagia after surgery. When comparing the data before and after 2005, it seems that the new hemostatic devices statistically shortened the length of surgery (P<.01, Student's t test). On the basis of our experience, laparoscopic Heller's myotomy associated with an antireflux procedure is a safe and effective method for the treatment of achalasia in the pediatric population. Intraoperative complications were <10%, and they occurred mostly at the beginning of our experience. Residual dysphagia occurred in about 16% of cases. The use of the new hemostatic devices seems to reduce the length of surgery and intraoperative bleeding. Considering the rarity of this pathology, we believe that patients with achalasia have to be treated only at centers with a strong experience in the treatment of this pathology.

Comparison of clinical and laboratory parameters in patients with end-stage renal failure in the outcome of chronic glomerulonephritis and patients with end-stage renal failure in the outcome of other diseases.

PubMed

Popova, J A; Yadrihinskaya, V N; Krylova, M I; Sleptsovа, S S; Borisovа, N V

frequent complications of hemodialysis treatments are coagulation disorders. This is due to activation of the coagulation of blood flow in the interaction with a dialysis membrane material vascular prostheses and extracorporeal circuit trunks. In addition, in hemodialysis patients receiving heparin for years, there is depletion of stocks in endothelial cells in tissue factor inhibitor, inhibits the activity of an external blood clotting mechanism. the aim of our study was to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure. to evaluate the hemostatic system parameters in patients with end-stage renal failure, depending on the cause of renal failure and hemodialysis treatment duration conducted a study that included 100 patients observed in the department of chronic hemodialysis and nephrology hospital №1 Republican National Medical Center in the period of 2013-2016. in patients with end-stage renal failure in the outcome of chronic glomerulonephritis, a great expression of activation of blood coagulation confirm increased the mean concentration of fibrinogen, whereas in the group, which included patients with end-stage renal failure in the outcome of other diseases, such is not different from the norm, and a higher rate of hyperfibrinogenemia, identified in 2/3 patients in this group. it was revealed that the state of homeostasis in patients with end-stage renal failure in increasingly characterizes the level of fibrinogen and the activation of the hemostatic markers: soluble fibrin monomer complexes, D-dimers.

The role of coagulation/fibrinolysis during Streptococcus pyogenes infection

PubMed Central

Loof, Torsten G.; Deicke, Christin; Medina, Eva

2014-01-01

The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit. PMID:25309880

The role of coagulation/fibrinolysis during Streptococcus pyogenes infection.

PubMed

Loof, Torsten G; Deicke, Christin; Medina, Eva

2014-01-01

The hemostatic system comprises platelet aggregation, coagulation and fibrinolysis and is a host defense mechanism that protects the integrity of the vascular system after tissue injury. During bacterial infections, the coagulation system cooperates with the inflammatory system to eliminate the invading pathogens. However, pathogenic bacteria have frequently evolved mechanisms to exploit the hemostatic system components for their own benefit. Streptococcus pyogenes, also known as Group A Streptococcus, provides a remarkable example of the extraordinary capacity of pathogens to exploit the host hemostatic system to support microbial survival and dissemination. The coagulation cascade comprises the contact system (also known as the intrinsic pathway) and the tissue factor pathway (also known as the extrinsic pathway), both leading to fibrin formation. During the early phase of S. pyogenes infection, the activation of the contact system eventually leads to bacterial entrapment within a fibrin clot, where S. pyogenes is immobilized and killed. However, entrapped S. pyogenes can circumvent the antimicrobial effect of the clot by sequestering host plasminogen on the bacterial cell surface that, after conversion into its active proteolytic form, plasmin, degrades the fibrin network and facilitates the liberation of S. pyogenes from the clot. Furthermore, the surface-localized fibrinolytic activity also cleaves a variety of extracellular matrix proteins, thereby enabling S. pyogenes to migrate across barriers and disseminate within the host. This review summarizes the knowledge gained during the last two decades on the role of coagulation/fibrinolysis in host defense against S. pyogenes as well as the strategies developed by this pathogen to evade and exploit these host mechanisms for its own benefit.

[Comparison on Endoscopic Hemoclip and Hemoclip Combination Therapy in Non-variceal Upper Gastrointestinal Bleeding Patients Based on Clinical Practice Data: Is There Difference between Prospective Cohort Study and Randomized Study?].

PubMed

Lee, Su Hyun; Jung, Jin Tae; Lee, Dong Wook; Ha, Chang Yoon; Park, Kyung Sik; Lee, Si Hyung; Yang, Chang Heon; Park, Youn Sun; Jeon, Seong Woo

2015-08-01

Endoscopic hemoclip application is an effective and safe method of endoscopic hemostasis. We conducted a multicenter retrospective study on hemoclip and hemoclip combination therapy based on prospective cohort database in terms of hemostatic efficacy not in clinical trial but in real clinical practice. Data on endoscopic hemostasis for non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively collected from February 2011 to December 2013. Among 1,584 patients with NVUGIB, 186 patients treated with hemoclip were enrolled in this study. Subjects were divided into three groups: Group 1 (n = 62), hemoclipping only; group 2 (n = 88), hemoclipping plus epinephrine injection; and group 3 (n = 36), hemocliping and epinephrine injection plus other endoscopic hemostatic modalities. Primary outcomes included rebleeding, other therapeutic management, hospitalization period, fasting period and mortality. Secondary outcomes were bleeding associated mortality and overall mortality. Active bleeding and peptic ulcer bleeding were more common in group 3 than in group 1 and in group 2 (p <œ 0.001). However, primary outcomes (rebleeding, other management, morbidity, hospitalization period, fasting period and mortality) and secondary outcomes (bleeding associated mortality and total mortality) were not different among groups. Combination therapy of epinephrine injection and other modalities with hemoclips did not show advantage over hemoclipping alone in this prospective cohort study. However, there is a tendency to perform combination therapy in active bleeding which resulted in equivalent hemostatic success rate, and this reflects the role of combination therapy in clinical practice.

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

PubMed

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

1995-09-01

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

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

PubMed Central

Beer, Sandra; Feihl, François; Ruiz, Juan; Juhan-Vague, Irène; Aillaud, Marie-Françoise; Wetzel, Sandrine Golay; Liaudet, Lucas; Gaillard, Rolf C; Waeber, Bernard

2008-01-01

Aim: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. Methods: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. Results: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. Conclusion: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state. PMID:19337558

The role of hemostatic agents in preventing complications in laparoscopic partial nephrectomy

PubMed Central

y Gregorio, Sergio Alonso; Rivas, Juan Gómez; Bazán, Alfredo Aguilera; Sebastián, Jesús Díez; Martínez-Piñeiro, Luis

2017-01-01

Introduction Nephron-sparing surgery is currently the treatment of choice for renal cell carcinoma stage T1a. During the past years, several hemostatic agents (HA) have been developed in order to reduce surgical complications. We present the results of our series and the impact of the use of HA in the prevention of surgical complications in laparoscopic partial nephrectomies (LPNs). Material and methods We retrospectively analyzed all LPN performed in our center from 2005 to 2012. A total of 77 patients were included for analysis. Patients were divided into two groups: Group A (no use of HA) and Group B (use of HA). HA used included gelatin matrix thrombin (FloSeal) and oxidized regenerated cellulose (Surgicel). Demographics, perioperative variables, and complications were analyzed with a special interest in postoperative bleeding and urinary leakage. Results Median age was 57.17 years old (±12.1), 72.7% were male, most common comorbidities were hypertension (33.8%) and diabetes mellitus (18.2%). All patients had one solitary tumor, and 87% had a tumor ≤4 cm. Renal cell carcinoma was found in 79.2% of cases, and 78.7% were stage pT1a. and were used in 36 cases (46.8%). No differences were found in demographics, perioperative variables, and complications between groups. No conversions to open surgery or perioperative mortality were reported. Conclusions We conclude that in our series the use of a hemostatic agent did not offer benefit in reducing the complication rate over sutures over a bolster. PMID:29410886

Differentiating disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype from coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS).

PubMed

Gando, S; Wada, H; Thachil, J

2013-05-01

Two concepts have been proposed for the hemostatic changes occurring early after trauma. Disseminated intravascular coagulation (DIC) with the fibrinolytic phenotype is characterized by activation of the coagulation pathways, insufficient anticoagulant mechanisms and increased fibrinolysis. Coagulopathy of trauma and acute coagulopathy of trauma-shock (COT/ACOTS) occurs as a result of increased activation of the thrombomodulin and protein C pathways, leading to the suppression of coagulation and activation of fibrinolysis. Despite the differences between these two conditions, independent consideration of COT/ACOTS from DIC with the fibrinolytic phenotype is probably incorrect. Robust diagnostic criteria based on its pathophysiology are required to establish COT/ACOTS as a new independent disease concept. In addition, the independency of its characteristics, laboratory data, time courses and prognosis from DIC should be confirmed. Confusion between two concepts may be based on studies of trauma lacking the following: (i) a clear distinction of the properties of blood between the inside and outside of vessels, (ii) a clear distinction between physiologic and pathologic hemostatic changes, (iii) attention to the time courses of the changes in hemostatic parameters, (iv) unification of the study population, and (v) recognition that massive bleeding is not synonymous with coagulation disorders. More information is needed to elucidate the pathogenesis of these two entities, DIC with the fibrinolytic phenotype and COT/ACOTS after trauma. However, available data suggest that COT/ACOTS is not a new concept but a disease entity similar to or the same as DIC with the fibrinolytic phenotype. © 2013 International Society on Thrombosis and Haemostasis.

Characterizing the O-glycosylation landscape of human plasma, platelets, and endothelial cells

PubMed Central

King, Sarah L.; Joshi, Hiren J.; Schjoldager, Katrine T.; Halim, Adnan; Madsen, Thomas D.; Dziegiel, Morten H.; Woetmann, Anders; Vakhrushev, Sergey Y.

2017-01-01

The hemostatic system comprises platelet aggregation, coagulation, and fibrinolysis, and is critical to the maintenance of vascular integrity. Multiple studies indicate that glycans play important roles in the hemostatic system; however, most investigations have focused on N-glycans because of the complexity of O-glycan analysis. Here we performed the first systematic analysis of native-O-glycosylation using lectin affinity chromatography coupled to liquid chromatography mass spectrometry (LC-MS)/MS to determine the precise location of O-glycans in human plasma, platelets, and endothelial cells, which coordinately regulate hemostasis. We identified the hitherto largest O-glycoproteome from native tissue with a total of 649 glycoproteins and 1123 nonambiguous O-glycosites, demonstrating that O-glycosylation is a ubiquitous modification of extracellular proteins. Investigation of the general properties of O-glycosylation established that it is a heterogeneous modification, frequently occurring at low density within disordered regions in a cell-dependent manner. Using an unbiased screen to identify associations between O-glycosites and protein annotations we found that O-glycans were over-represented close (± 15 amino acids) to tandem repeat regions, protease cleavage sites, within propeptides, and located on a select group of protein domains. The importance of O-glycosites in proximity to proteolytic cleavage sites was further supported by in vitro peptide assays demonstrating that proteolysis of key hemostatic proteins can be inhibited by the presence of O-glycans. Collectively, these data illustrate the global properties of native O-glycosylation and provide the requisite roadmap for future biomarker and structure-function studies. PMID:29296958

Mechanisms of Normal and Abnormal Endometrial Bleeding

PubMed Central

Lockwood, Charles J.

2011-01-01

Expression of tissue factor (TF), the primary initiator of coagulation, is enhanced in decidualized human endometrial stromal cells (HESC) during the progesterone-dominated luteal phase. Progesterone also augments a second HESC hemostatic factor, plasminogen activator inhibitor-1 (PAI-1). In contrast, progestins inhibit HESC matrix metalloproteinase (MMP)-1, 3 and 9 expression to stabilize endometrial stromal and vascular extracellular matrix. Through these mechanisms decidualized endometrium is rendered both hemostatic and resistant to excess trophoblast invasion in the mid-luteal phase and throughout gestation to prevent hemorrhage and accreta. In non-fertile cycles, progesterone withdrawal results in decreased HESC TF and PAI-expression and increased MMP activity and inflammatory cytokine production promoting the controlled hemorrhage of menstruation and related tissue sloughing. In contrast to these well ordered biochemical processes, unpredictable endometrial bleeding associated with anovulation reflects absence of progestational effects on TF, PAI-1 and MMP activity as well as unrestrained angiogenesis rendering the endometrium non-hemostatic, proteolytic and highly vascular. Abnormal bleeding associated with long-term progestin-only contraceptives results not from impaired hemostasis but from unrestrained angiogenesis leading to large fragile endometrial vessels. This abnormal angiogenesis reflects progestational inhibition of endometrial blood flow promoting local hypoxia and generation of reactive oxygen species that increase production of angiogenic factors such as vascular endothelial growth factor (VEGF) in HESCs and Angiopoietin-2 (Ang-2) in endometrial endothelial cells while decreasing HESC expression of angiostatic, Ang-1. The resulting vessel fragility promotes bleeding. Aberrant angiogenesis also underlies abnormal bleeding associated with myomas and endometrial polyps however there are gaps in our understanding of this pathology. PMID:21499503

Microwave coagulation therapy and drug injection to treat splenic injury.

PubMed

Zhang, Guoming; Sun, Yuanyuan; Yu, Jie; Dong, Lei; Mu, Nannan; Liu, Xiaohong; Liu, Lanfen; Zhang, Yan; Wang, Xiaofei; Liang, Ping

2014-01-01

The present study compares the efficacy of 915- and 2450-MHz contrast-enhanced ultrasound (CEUS)-guided percutaneous microwave coagulation with that of CEUS-guided thrombin injection for the treatment of trauma-induced spleen hemorrhage. In a canine splenic artery hemorrhage model with two levels of arterial diameter (A, <1 mm and B, between 1 and 2 mm), hemostatic therapy was performed using 915- and 2450-MHz microwaves and drug injection. Therapy efficacy was measured by comparing bleeding rate, hemostatic time, bleeding index, bleeding volume, and pathology. The most efficient technique was CEUS-guided 915-MHz percutaneous microwave coagulation therapy in terms of action time and total blood loss. The success rate of the 915-MHz microwave group was higher than that of the 2450-MHz microwave and the drug injection groups (except A level, P < 0.05). Hemostatic time, bleeding index, and bleeding volume were significantly less in the 915-MHz microwave group than those in the 2450-MHz microwave and drug injection groups (P < 0.05). Obvious degeneration and necrosis of parenchyma and large intravascular thrombosis were observed in the cavity of larger vessels in the 915-MHz microwave group, but pathologic changes of light injury could be seen in the other groups. The present study provides evidence that microwave coagulation therapy is more efficient than thrombin injection for the treatment of splenic hemorrhage. Furthermore, treatment with 915-MHz microwaves stops bleeding more rapidly and generates a wider cauterization zone than does treatment with 2450-MHz microwaves. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative Study of the Effects of Combined Oral Contraceptives in Hemostatic Variables

PubMed Central

Stocco, Bianca; Fumagalli, Helen F.; Franceschini, Silvio A.; Martinez, Edson Z.; Marzocchi-Machado, Cleni M.; de Sá, Marcos Felipe S.; Toloi, Maria Regina T.

2015-01-01

Abstract Thrombotic risk is associated with the estrogen dose and type of progestin in combined oral contraceptives. Studies published since 1990 showed that third-generation progestins have larger risk to contribute to thrombosis development than the second-generation. However, there are conflicts in the literature regarding the thrombotic risk associated to the drospirenone progestin. So, this study aimed to evaluate the effects of 3 formulations of contraceptives containing ethinylestradiol (EE) (20 and 30 μg) combined with drospirenone versus levonorgestrel combined with EE (30 μg) in hemostatic parameters. This cross-sectional study included 70 healthy women between 18 and 30 years, BMI 19 to 30 kg/m2, not pregnant, non-smokers, and users or non-users (control) of contraceptives for a minimum period of 6 months. The following parameters were assessed: prothrombin time (PT), Factor VII, activated partial thromboplastin time (aPTT), Factor XII, fibrinogen, Factor 1 + 2, Protein C, Protein S, antithrombin, D-dimers, and plasminogen activator inhibitor-1. Significant alterations were found in PT, aPTT, fibrinogen, D-dimers, and protein S, all favoring a state of hypercoagulation for contraceptive containing DRSP/20EE. Both contraceptives containing DRSP/30EE and LNG/30EE promoted changes that favor the hypercoagulability in the coagulant variable PT and in the anticoagulant variables Protein S and Protein C, respectively. We suggest that the progestin drospirenone can contribute to an inadequate balance among procoagulant, anticoagulant, and fibrinolytic factors, since that the contraceptive containing the lowest dose of estrogen and drospirenone (DRSP/20EE) caused a higher number of hemostatic changes. PMID:25634167

Real-world surgical outcomes of a gelatin-hemostatic matrix in women requiring a hysterectomy: a matched case-control study.

PubMed

Obermair, Helena; Janda, Monika; Obermair, Andreas

2016-09-01

The aim of this study was to compare adverse events and surgical outcomes of hysterectomy with or without use of a gelatin-hemostatic matrix (SURGIFLO(®) ). Prospective case-control study (Canadian Task Force classification II2) of total hysterectomy (Piver Type 1) provided by surgeons in Australia between November 2005 and May 2015. Data were collected via SurgicalPerformance, a web-based data project which aims to provide confidential feedback to surgeons about their surgical outcomes. Of 2440 records of women who received a hysterectomy, 1351 were eligible for these analyses; 107 received SURGIFLO(®) hemostatic matrix to prevent postoperative blood loss and 1244 did not. Patients with or without SURGIFLO(®) differed in age, Charlson comorbidity index, and American Society of Anesthesiologists physical status classification system score (ASA), and also differed in clinical outcomes. After matching for patient's age and ASA at surgery, patients with and without SURGIFLO(®) had comparable baseline characteristics. Matched patients with and without SURGIFLO(®) had comparable clinical outcomes including risk of developing vault hematoma, return to the operating room, transfusion of red cells, surgical site infection (pelvis), readmission within 30 days and unplanned ICU admission. In a sample matched by age and ASA, SURGIFLO(®) neither prevented nor caused additional adverse events in women undergoing hysterectomy. Surgeons used SURGIFLO(®) more commonly among women who were older, had more comorbidities and a higher ASA score. This indicates that it may be most useful in complicated surgery or cases. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

PubMed

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients < 12 years of age with severe hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to < 6 years, n = 35; ≥ 6 to < 12 years, n = 49); 81 were assigned to prophylaxis and three to an on-demand regimen. Patients accumulated a total of 5239 exposure days (EDs), with 65 participants reaching > 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children < 12 years of age with severe hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Blood Hemostatic Changes During an Ultraendurance Road Cycling Event in a Hot Environment.

PubMed

Kupchak, Brian R; Kazman, Josh B; Vingren, Jakob L; Levitt, Danielle E; Lee, Elaine C; Williamson, Keith H; Armstrong, Lawrence E; Deuster, Patricia A

2017-09-01

This study aims to examine blood hemostatic responses to completing a 164-km road cycling event in a hot environment. Thirty-seven subjects (28 men and 9 women; 51.8±9.5 [mean±SD] y) completed the ride in 6.6±1.1 hours. Anthropometrics (height, body mass [taken also during morning of the ride], percent body fat [%]) were collected the day before the ride. Blood samples were collected on the morning of the ride (PRE) and immediately after (IP) the subject completed the ride. Concentrations of platelet, platelet activation, coagulation, and fibrinolytic markers (platelet factor 4, β-thromboglobulin, von Willebrand factor antigen, thrombin-antithrombin complex, thrombomodulin, and D-Dimer) were measured. Associations between changes from PRE- to IP-ride were examined as a function of event completion time and subject characteristics (demographics and anthropometrics). All blood hemostatic markers increased significantly (P < .001) from PRE to IP. After controlling for PRE values, finishing time was negatively correlated with platelet factor 4 (r = 0.40; P = .017), while percent body fat (%BF) was negatively correlated with thrombin-antithrombin complex (r = -0.35; P = .038) and to thrombomodulin (r = -0.36; P = .036). In addition, male subjects had greater concentrations of thrombin-antithrombin complex (d = 0.63; P < .05) and natural logarithm thrombomodulin (d = 6.42; P < .05) than female subjects. Completing the 164-km road cycling event in hot conditions resulted in increased concentrations of platelet, platelet activation, coagulation, and fibrinolytic markers in both men and women. Although platelet activation and coagulation occurred, the fibrinolytic system markers also increased, which appears to balance blood hemostasis and may prevent clot formation during exercise in a hot environment. Published by Elsevier Inc.

Effect of Ankaferd Blood Stopper on Skin Superoxide Dismutase and Catalase Activities in Warfarin-Treated Rats.

PubMed

Aktop, Sertaç; Emekli-Alturfan, Ebru; Gönül, Onur; Göçmen, Gökhan; Garip, Hasan; Yarat, Ayşen; Göker, Kamil

2017-03-01

Ankaferd Blood Stopper (ABS) is a new promising local hemostatic agent, and its mechanism on hemostasis has been shown by many studies. However, the effects of ABS on skin superoxide dismutase (SOD) and catalase (CAT) activities have not been investigated before. The aim of this study was to evaluate the effects of this new generation local hemostatic agent on warfarin-treated rats focusing on its the antioxidant potential in short-term soft tissue healing. Twelve systemically warfarin treated (warfarin group) and 12 none treated Wistar Albino rats (control group) were selected for the trial. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were given 1 mL/kg saline 3 days earlier to surgical procedure and continued until killing. All rats had incisions on dorsal dermal tissue, which was applied ABS or no hemostatic agent before suturing. Six of each group were killed on day 4, and the other 6 were killed on day 8. Blood and skin samples were taken. Prothrombin time (PT) in blood samples, CAT, and SOD activities in skin samples were determined. Warfarin treatment dose was found to be convenient and warfarin treatment increased the PT levels as expected. Warfarin treatment decreased CAT activity significantly compared to the control group. The ABS treatment significantly increased SOD activities in the warfarin group at the end of the eighth day. Ankaferd Blood Stopper acted positively in short-term tissue healing by increasing SOD activity in warfarin-treated rats. Therefore, ABS may be suggeted as a promoting factor in tissue healing.

Treatment of Severe Aortic Bleeding Using Hemopatch in Swine on Dual Antiplatelet Therapy.

PubMed

Baumgartner, Bernhard; Draxler, Wolfgang; Lewis, Kevin M

2016-12-01

The perioperative management of patients on antithrombotic therapy is currently an unresolved problem as these therapies pose a considerable risk for perioperative hemorrhagic complications. The presented studies investigated the efficacy of a new collagen technology to achieve hemostasis. A polyethylene glycol-coated collagen pad (PCC) was compared to a marketed fibrinogen-thrombin coated collagen pad (FTC) for the treatment of an aortotomy incision in heparinized swine on dual antiplatelet therapy. Twenty-eight 3-mm aortotomy incisions were created in nine heparinized pigs without antiplatelet therapy and treated with PCC. Sixty-eight aortotomy incisions were created in ten heparinized pigs that received clopidogrel (10-11 mg/kg) and acetylsalicylic acid (8-11 mg/kg) orally for 5 days, and treated with either PCC or FTC (N = 34/group). Dual antiplatelet therapy resulted in significantly reduced platelet function. Aortotomy incisions resulted in life-threatening bleeding of 35-292 ml/min. In animals without antiplatelet treatment, PCC provided 96% immediate hemostatic success. In animals with antiplatelet treatment, FTC provided 18% immediate hemostatic success increasing to 74% after 10 min. Strikingly, PCC provided 94% immediate success increasing to 100% after 10 min. Controlling for differences in pretreatment bleeding rates, statistical model-estimated time to hemostasis was 12 times shorter in PCC-treated lesions (p < .02). The combination of a procoagulant collagen pad with a synthetic sealing component provides excellent hemostatic properties under a worst-case scenario. PCC rapidly and firmly adheres to tissue, thereby controlling severe arterial bleeding, even when platelet function is significantly reduced. Treatment with PCC provided superior time to hemostasis compared to FTC.

Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes.

PubMed

Salazar, Ana M; Vivas, Jeilyn; Sánchez, Elda E; Rodríguez-Acosta, Alexis; Ibarra, Carlos; Gil, Amparo; Carvajal, Zoila; Girón, María E; Estrella, Amalid; Navarrete, Luis F; Guerrero, Belsy

2011-07-01

The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A₂s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecular-weight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD₅₀s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD₅₀ of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD₅₀s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasmin-like activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

Misgav, Mudi; Martinowitz, Uri

2011-02-01

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

New alternatives for laser vaporization of the prostate: experimental evaluation of a 980-, 1,318- and 1,470-nm diode laser device.

PubMed

Wezel, Felix; Wendt-Nordahl, Gunnar; Huck, Nina; Bach, Thorsten; Weiss, Christel; Michel, Maurice Stephan; Häcker, Axel

2010-04-01

Several diode laser systems were introduced in recent years for the minimal-invasive surgical therapy of benign prostate enlargement. We investigated the ablation capacities, hemostatic properties and extend of tissue necrosis of different diode lasers at wavelengths of 980, 1,318 and 1,470 nm and compared the results to the 120 W GreenLight HPS laser. The laser devices were evaluated in an ex vivo model using isolated porcine kidneys. The weight difference of the porcine kidneys after 10 min of laser vaporization defined the amount of ablated tissue. Blood loss was measured in blood-perfused kidneys following laser vaporization. Histological examination was performed to assess the tissue effects. The side-firing 980 and 1,470 nm diode lasers displayed similar ablative capacities compared to the GreenLight HPS laser (n.s.). The 1,318-nm laser, equipped with a bare-ended fiber, reached a higher ablation rate compared to the other laser devices (each P < 0.05). A calculated 'output power efficiency per watt' revealed that the 1,318-nm laser with a bare-ended fiber reached the highest rate compared to the side-firing devices (each P < 0.0001). All three diode lasers showed superior hemostatic properties compared to the GreenLight HPS laser (each P < 0.01). The extend of morphological tissue necrosis was 4.62 mm (1,318 nm), 1.30 mm (1,470 nm), 4.18 mm (980 nm) and 0.84 mm (GreenLight HPS laser), respectively. The diode lasers offered similar ablative capacities and improved hemostatic properties compared to the 120 W GreenLight HPS laser in this experimental ex vivo setting. The higher tissue penetration of the diode lasers compared to the GreenLight HPS laser may explain improved hemostasis.

Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in guinea pigs.

PubMed

Kubrusly, Luiz Fernando; Formighieri, Marina Simões; Lago, José Vitor Martins; Graça, Yorgos Luiz Santos de Salles; Sobral, Ana Cristina Lira; Lago, Marianna Martins

2015-01-01

To evaluate the behavior of castor oil-derived polyurethane as a hemostatic agent and tissue response after abdominal aortic injury and to compare it with 2-octyl-cyanoacrylate. Twenty-four Guinea Pigs were randomly divided into three groups of eight animals (I, II, and III). The infrarenal abdominal aorta was dissected, clamped proximally and distally to the vascular puncture site. In group I (control), hemostasis was achieved with digital pressure; in group II (polyurethane) castor oil-derived polyurethane was applied, and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was subdivided into IIA and IIB according to the time of preparation of the hemostatic agent. Mean blood loss in groups IIA, IIB and III was 0.002 grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and 0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5 seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation: 23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s). Furthermore, polyurethane A had a shorter drying time than polyurethane B (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of the animals had mild/severe fibrosis, while in group II only 12.5% showed this degree of fibrosis (P=0.001). Polyurethane derived from castor oil showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less perivascular tissue response with polyurethane when compared with cyanoacrylate.

Evaluation of the hemostatic and histopathological effects of Ankaferd Blood Stopper in experimental liver injury in rats.

PubMed

Satar, Nihal Y Gul; Akkoc, Ahmet; Oktay, Ayberk; Topal, Ayse; Inan, Kivanc

2013-07-01

We studied the hemostatic and histopathological effects, and intra-abdominal adhesion scores of a new hemostatic agent, Ankaferd Blood Stopper (ABS), in an experimental liver injury model and compared it with regenerated oxidized cellulose. Thirty-six rats were randomly assigned to ABS, oxidized cellulose (Surgicel), and control groups (n=12, each). A wedge resection was performed on the left medial lobe of the liver. In the ABS group the liver surface was sprayed with ABS, whereas in the Surgicel group the liver was covered with double-layered oxidized cellulose. In the control group, saline solution was sprayed on the cut surface. The mean bleeding time was shorter in the ABS (23.08±6.99s) and Surgicel groups (47.91±8.21s) than in the control group (223.42±57.83s). No significant difference was found in the ABS and Surgicel groups in terms of preoperative and postoperative hematocrit (hct) values (P>0.05). Whereas there was no significant difference on day 7 (P>0.05), total adhesion score of ABS group was lower than both Surgicel (P<0.05) and control groups (P<0.01) on day 14. Liver sections from ABS group displayed more favorable histopathological changes when compared with Surgicel group on day 7 and day 14. All livers in the ABS group completed their regeneration process with minimal signs of inflammation. Our findings suggest that ABS is more effective than Surgicel and control groups in achieving hemostasis and in reducing blood loss. Apart from this, ABS causes more encouraging histopathological changes and better intra-abdominal adhesion scores in rat experimental liver trauma model.

Hemostats, sealants, and adhesives: components of the surgical toolbox.

PubMed

Spotnitz, William D; Burks, Sandra

2008-07-01

The surgical toolbox is expanding, and newer products are being developed to improve results. Reducing blood loss so that bloodless surgery can be performed may help minimize morbidity and length of stay. As patients, hospital administrators, and government regulators desire less invasive procedures, the surgical technical challenge is increasing. More operations are being performed through minimally invasive incisions with laparoscopic, endoscopic, and robotic approaches. In this setting, tools that can reduce bleeding by causing blood to clot, sealing vessels, or gluing tissues are gaining an increasing importance. Thus, hemostats, sealants, and adhesives are becoming a more important element of surgical practice. This review is designed to facilitate the reader's basic knowledge of these tools so that informed choices are made for controlling bleeding in specific clinical situations. Such information is useful for all members of the operative team. The team includes surgeons, anesthesiologists, residents, and nurses as well as hematologists and other medical specialists who may be involved in the perioperative care of surgical patients. An understanding of these therapeutic options may also be helpful to the transfusion service. In some cases, these materials may be stored in the blood bank, and their appropriate use may reduce demand for other transfusion components. The product classification used in this review includes hemostats as represented by product categories that include mechanical agents, active agents, flowables, and fibrin sealants; sealants as represented by fibrin sealants and polyethylene glycol hydrogels; and adhesives as represented by cyanoacrylates and albumin cross-linked with glutaraldehyde. Only those agents approved by the Food and Drug Administration (FDA) and presently available (February 2008) for sale in the United States are discussed in this review.

Predicting the severity of systemic inflammatory response syndrome (SIRS)-associated coagulopathy with hemostatic molecular markers and vascular endothelial injury markers.

PubMed

Iba, Toshiaki; Gando, Satoshi; Murata, Atsuo; Kushimoto, Shigeki; Saitoh, Daizoh; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Ikeda, Toshiaki; Ishhikura, Hiroyasu; Ueyama, Masashi; Ogura, Yuji; Endo, Shigeatsu; Shimazaki, Shuji

2007-11-01

The changes in biomarkers of coagulation or fibrinolysis, anticoagulation, inflammation, and endothelial damage occur in patients with systemic inflammatory response syndrome (SIRS). The purpose of this study is to assess the prognostic value of these markers in patients with SIRS-associated hypercoagulopathy. Sixty-six SIRS patients with a platelet count less than 15.0 x 10(4)/mm3 in three university hospital intensive care units were enrolled in this prospective, comparative study. Blood samples were obtained on day 0 and day 2. Twelve hemostatic, inflammatory, and vascular endothelial indices were measured and the data were compared between the severe group (patients with a total maximum Sequential Organ Failure Assessment score of 10 or more and nonsurvivors; n = 25) and the less-severe group (Sequential Organ Failure Assessment score <10; n = 41). Significant changes between the groups were observed in platelet count, fibrin or fibrinogen degradation products, interleukin-6, soluble thrombomodulin, antithrombin (AT) activity, and protein C activity, both on day 0 and on day 2. In contrast, the d-dimer, soluble fibrin, plasmin-[alpha]2-antiplasmin complex, and E-selectin levels were higher in the severe group only on day 2. No significant difference was seen regarding the thrombin-AT complex and total plasminogen activator inhibitor on both days. A comparison of the areas under the receiver operating characteristic curve revealed the AT activity to be the best predictor of a progression of organ dysfunction. The changes in some hemostatic molecular markers and vascular endothelial markers were conspicuous in patients with organ dysfunction. The AT activity is considered to be the most useful predictor of organ dysfunction.

Comparison of polyurethane with cyanoacrylate in hemostasis of vascular injury in guinea pigs

PubMed Central

Kubrusly, Luiz Fernando; Formighieri, Marina Simões; Lago, José Vitor Martins; Graça, Yorgos Luiz Santos de Salles; Sobral, Ana Cristina Lira; Lago, Marianna Martins

2015-01-01

Objective To evaluate the behavior of castor oil-derived polyurethane as a hemostatic agent and tissue response after abdominal aortic injury and to compare it with 2-octyl-cyanoacrylate. Methods Twenty-four Guinea Pigs were randomly divided into three groups of eight animals (I, II, and III). The infrarenal abdominal aorta was dissected, clamped proximally and distally to the vascular puncture site. In group I (control), hemostasis was achieved with digital pressure; in group II (polyurethane) castor oil-derived polyurethane was applied, and in group III (cyanoacrylate), 2-octyl-cyanoacrylate was used. Group II was subdivided into IIA and IIB according to the time of preparation of the hemostatic agent. Results Mean blood loss in groups IIA, IIB and III was 0.002 grams (g), 0.008 g, and 0.170 g, with standard deviation of 0.005 g, 0.005 g, and 0.424 g, respectively (P=0.069). The drying time for cyanoacrylate averaged 81.5 seconds (s) (standard deviation: 51.5 seconds) and 126.1 s (standard deviation: 23.0 s) for polyurethane B (P=0.046). However, there was a trend (P=0.069) for cyanoacrylate to dry more slowly than polyurethane A (mean: 40.5 s; SD: 8.6 s). Furthermore, polyurethane A had a shorter drying time than polyurethane B (P=0.003), mean IIA of 40.5 s (standard deviation: 8.6 s). In group III, 100% of the animals had mild/severe fibrosis, while in group II only 12.5% showed this degree of fibrosis (P=0.001). Conclusion Polyurethane derived from castor oil showed similar hemostatic behavior to octyl-2-cyanoacrylate. There was less perivascular tissue response with polyurethane when compared with cyanoacrylate. PMID:25859876

Absorbable Antimicrobial Battlefield Hemostat

DTIC Science & Technology

2013-04-01

to graphene sheet and carbon nanotubes . Coupled with ABTS, the GQDs can be used for the detection of hydrogen peroxide with the limit of detection......dressing could be made of any material that is compatible to our coating solvent. Examples include gelatin based and cellulose based substrates. The

Ambient particulate matter accelerates coagulation via an IL-6-dependent pathway

EPA Science Inventory

The mechanisms by which exposure to particulate matter increases the risk of cardiovascular events are not known. Recent human and animal data suggest that particulate matter may induce alterations in hemostatic factors. In this study we determined the mechanisms by which particu...

A Synthetic Fibrin-Crosslinking Polymer for Modulating Clot Properties and Inducing Hemostasis

PubMed Central

Chan, Leslie W.-G.; Wang, Xu; Wei, Hua; Pozzo, Lilo D.; White, Nathan J.; Pun, Suzie H.

2015-01-01

Clotting factor replacement is the standard management of acute bleeding in congenital and acquired bleeding disorders. We present a synthetic approach to hemostasis using an engineered hemostatic polymer (PolySTAT) that circulates innocuously in the blood, identifies sites of vascular injury, and promotes clot formation to stop bleeding. PolySTAT induces hemostasis by crosslinking the fibrin matrix within clots, mimicking the function of the transglutaminase Factor XIII. Furthermore, synthetic PolySTAT binds specifically to fibrin monomers and is uniformly integrated into fibrin fibers during fibrin polymerization, resulting in a fortified, hybrid polymer network with enhanced resistance to enzymatic degradation. In vivo hemostatic activity was confirmed in a rat model of trauma and fluid resuscitation in which intravenous administration of PolySTAT improved survival by reducing blood loss and resuscitation fluid requirements. PolySTAT-induced fibrin crosslinking is a novel approach to hemostasis utilizing synthetic polymers for non-invasive modulation of clot architecture with potentially wide-ranging therapeutic applications. PMID:25739763

The effects of BleedArrest on hemorrhage control in a porcine model.

PubMed

Gegel, Brian; Burgert, James; Loughren, Michael; Johnson, Don

2012-01-01

The purpose of this study was to examine the effectiveness of the hemostatic agent BleedArrest compared to control. This was a prospective, experimental design employing an established porcine model of uncontrolled hemorrhage. The minimum number of animals (n=10 per group) was used to obtain a statistically valid result. There were no statistically significant differences between the groups (P>.05) indicating that the groups were equivalent on the following parameters: activating clotting time, the subject weights, core body temperatures, amount of one minute hemorrhage, arterial blood pressures, and the amount and percentage of total blood volume. There were significant differences in the amount of hemorrhage (P=.033) between the BleedArrest (mean=72, SD±72 mL) and control (mean=317.30, SD±112.02 mL). BleedArrest is statistically and clinically superior at controlling hemorrhage compared to the standard pressure dressing control group. In conclusion, BleedArrest is an effective hemostatic agent for use in civilian and military trauma management.

Adhesive and robust multilayered poly(lactic acid) nanosheets for hemostatic dressing in liver injury model.

PubMed

Komachi, Takuya; Sumiyoshi, Hideaki; Inagaki, Yutaka; Takeoka, Shinji; Nagase, Yu; Okamura, Yosuke

2017-10-01

Freestanding biodegradable nanosheets composed of poly(l-lactic acid) (PLLA) have been developed for various biomedical applications. These nanosheets exhibit unique properties such as high adhesiveness and exquisite flexibility; however, they burst easily due to their nanometer thickness. We herein describe a freestanding, multilayered nanosheet composed of PLLA fabricated using a simple combination procedure: (i) multilayering of PLLA and alginate, (ii) gelation of the alginate layers, (iii) fusion-cut sealing, and (iv) elution of the alginate layers. The multilayered nanosheets not only reinforced the bursting strength but also provided a high level of adhesive strength. In fact, they were found to show potential as a hemostatic dressing, and they tended to show reduced tissue adhesion that accompanies liver injury. Therefore, we propose this biomaterial as a candidate for an alternative to conventional therapy in hemorrhage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1747-1757, 2017. © 2016 Wiley Periodicals, Inc.

Comparative Evaluation of Biological Performance, Biosecurity, and Availability of Cellulose-Based Absorbable Hemostats.

PubMed

Wu, Yadong; Wang, Fang; Huang, Yudong

2018-05-01

Hemorrhage remains a leading cause of death after trauma, and developing a hemostat with excellent performance and good biosecurity is an extremely active area of research and commercial product development. Although oxidized regenerated cellulose (ORC) has been developed to address these problems, it is not always efficient and its biosecurity is not perfect. We aimed to refine ORC via a simple and mild neutralization method. The prepared neutralized oxidized regenerated cellulose (NORC) showed a superior gel property due to its chemical structure. The biological performance of both ORC and NORC was systematically evaluated; the results showed that ORC would induce erythema and edema in the irritation test, whereas NORC did not cause any adverse inflammation, indicating NORC had desirable biocompatibility. We further demonstrated that NORC confirmed to the toxicity requirements of International Organization for Standardization (ISO) standards; however, ORC showed an unacceptable cytotoxicity. The rabbit hepatic defect model stated that NORC exhibited better ability of hemostasis, which was attributed to its significant gel performance in physiological environment.

Absorbable Antimicrobial Battlefield Hemostat

DTIC Science & Technology

2012-10-01

image of SiNFs after reation with GA The SiNFs were sonicated for 5mins to achieve homogenous dispersion in water, and then mixed with gentamicin...of coagulation (typical activated clotting times of whole pigs blood using a kaolin clay activator are approximately 90 seconds, in the absence of

Acute Traumatic Coagulopathy

DTIC Science & Technology

2014-12-01

therapeutic approaches are discussed, including viscoelastic coagulation monitoring and the role of tranexamic acid and blood products. Summary...and tranexamic acid in addition to red cell units in order to reduce bleeding and improve clinical outcomes. Keywords acute traumatic coagulopathy...endothelial activation, fibrinolysis, hemostatic resuscitation, hypoperfusion, microparticles, platelet dysfunction, tranexamic acid , viscoelastic

77 FR 8271 - National Heart, Lung, and Blood Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... Institute Special Emphasis Panel; Planning Studies for Rare Thrombotic and Hemostatic Disorders. Date: March... Nos. 93.233, National Center for Sleep Disorders Research; 93.837, Heart and Vascular Diseases Research; 93.838, Lung Diseases Research; 93.839, Blood Diseases and Resources Research, National...

Management of External Hemorrhage in Tactical Combat Casualty Care: Chitosan-Based Hemostatic Gauze Dressings. TCCC Guidelines Change 13-05

DTIC Science & Technology

2014-09-23

dramatically decreased. Coagulation parameters improved significantly over the next 36 hours. Muzzi et al./2012 CEG Acute prosthetic endocarditis ; 4 months...prosthetic endocarditis ; 4 months post aortic dissection surgery Preoperative IV heparin with impaired coagulation state. Yes; discharged

Improving on Army Field Gauze for Lethal Vascular Injuries: Challenges in Dressing Development

USDA-ARS?s Scientific Manuscript database

Accounting for half of all deaths, uncontrolled hemorrhage remains the leading cause of death on the battlefield. Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model compared a...

Electrokinetic and hemostatic profiles of nonwoven cellulosic/ synthetic fiber blends with unbleached cotton

USDA-ARS?s Scientific Manuscript database

Greige cotton contains waxes and pectin on the outer surface of the fiber that are removed from bleached cotton, but present added potential for wound dressing functionality. Innovations to mechanically clean and sterilize greige cotton (or non-bleached cotton) do not remove these exterior componen...

A Novel Swine Model for Evaluation of Potential Intravascular Hemostatic Agents

DTIC Science & Technology

2007-06-01

bovine polymerized hemoglobin on coagulation in controlled hemorrhagic shock in swine. Shock 24:145–152. 2. Bellamy RF. 1984. The causes of death in...WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. 2005. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J

In vitro hemostatic, hydrogen peroxide production and elastase sequestration properties of nonwoven ultra clean greige cotton dressing

USDA-ARS?s Scientific Manuscript database

Nonwoven UltraCleanTM Cotton (highly cleaned and hydroentangled, greige cotton) retains the native wax and pectin content (~2%) of the cotton fiber traditionally removed from scoured and bleached cotton gauze, yet potentially affording wound healing properties. In vitro thromboelastography, hydrog...

Determination of Efficacy of New Hemostatic Dressings in a Model of Extremity Arterial Hemorrhage in Swine

DTIC Science & Technology

2009-09-01

a few milliliters of 2% lidocaine to relax vasospasm and dilate the artery to its normal size. To measure wound temperature, a microelectrode was...clotting function than the untreated samples. The other chitosan product, Celox-D was also found to be ineffective despite successful results with this

Investigating the role of charge on cotton materials designed to intervene in the hemostatic and inflammatory stages of wound healing

USDA-ARS?s Scientific Manuscript database

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and haemostatic phases of wound healing. Hemostasis and inflammation comprise two overlap...

Positively and Negatively Charged Ionic Modifications to Cellulose Assessed as Cotton-Based Protease-Lowering and Haemostatic Wound Agents

USDA-ARS?s Scientific Manuscript database

Recent developments in cellulose wound dressings targeted to different stages of wound healing have been based on structural and charge modifications that function to modulate events in the complex inflammatory and hemostatic phases of wound healing. Hemostasis and inflammation comprise two overlapp...

Bioresponsive Materials for Drug Delivery Based on Carboxymethyl Chitosan/Poly(γ-Glutamic Acid) Composite Microparticles

PubMed Central

Yan, Xiaoting; Tong, Zongrui; Chen, Yu; Mo, Yanghe; Feng, Huaiyu; Li, Peng; Qu, Xiaosai; Jin, Shaohua

2017-01-01

Carboxymethyl chitosan (CMCS) microparticles are a potential candidate for hemostatic wound dressing. However, its low swelling property limits its hemostatic performance. Poly(γ-glutamic acid) (PGA) is a natural polymer with excellent hydrophilicity. In the current study, a novel CMCS/PGA composite microparticles with a dual-network structure was prepared by the emulsification/internal gelation method. The structure and thermal stability of the composite were determined by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), and thermogravimetric analysis (TGA). The effects of preparation conditions on the swelling behavior of the composite were investigated. The results indicate that the swelling property of CMCS/PGA composite microparticles is pH sensitive. Levofloxacin (LFX) was immobilized in the composite microparticles as a model drug to evaluate the drug delivery performance of the composite. The release kinetics of LFX from the composite microparticles with different structures was determined. The results suggest that the CMCS/PGA composite microparticles are an excellent candidate carrier for drug delivery. PMID:28452963

[Topical hemostatic devices in surgery: between science and marketing].

PubMed

González, Héctor Daniel; Figueras Felip, Joan

2009-06-01

Topical hemostatic agents have been used in surgery with varying degrees of success. These agents include oxidized cellulose, absorbable gelatin sponges, microfibrillar collagen and fibrin seals. Fibrin seals have become widely used as they improve perioperative hemostasis, reduce the need for red blood cell transfusions and prevent biliary leaks. Their widespread use, however, contrasts with the scarcity of data from controlled studies to support their clinical effectiveness. Therefore, a prospective, randomized, controlled, single-center study was performed in 300 patients who underwent elective hepatectomy, with and without application of fibrin seal on the raw liver surface. None of the variables evaluated (blood loss, transfusions, biliary fistulas and postoperative results) differed between the two groups. We conclude that the application of fibrin seal does not seem justified and that discontinuing its routine use would substantially reduce costs. The use of a new agent, Tachosil, is supported by a single multicenter, prospective, randomized, controlled trial, which is limited by the small number of patients and by the fact that the variable analyzed--time from application to hemostasis--may not be clinically relevant.

Providing Hemostatic and Blood Conservation Options for Jehovah's Witness Patients in a Large Medical System.

PubMed

Bai, Yu; Castillo, Brian S; Tchakarov, Amanda; Escobar, Miguel A; Cotton, Bryan A; Holcomb, John B; Brown, Robert E

2016-12-01

People of the Jehovah's Witness faith believe that they shall "abstain from blood." Because of this belief, we encounter the challenges from Jehovah's Witness patients who actively seek medical care for themselves and their children, but refuse the transfusion of blood products, which may result in increased morbidity and mortality in this patient population. With the development/availability of new hemostatic/coagulation products and the advances in medical technology, we, in collaboration with our clinical colleagues and our local Jehovah's Witness leadership, have developed a clinical guideline comprising medical protocol and surgical strategy for patients refusing blood products. Included in the medical protocol is an informative handout on related details to help treating physicians and patients make informed decisions about transfusion alternatives. Together, we have entered the medical protocol into the entire Memorial Hermann Hospital's electronic system. We report the detailed development and implementation process in order to share our experience and encourage others to develop their own management plan for this patient population. © 2016 by the Association of Clinical Scientists, Inc.

A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

PubMed

Seo, Junyoung; Al-Hilal, Taslim A; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San

2018-04-01

The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

DIFFERENTIAL EFFECTS OF EPSILON-AMINOCAPROIC ACID AND APROTININ ON MATRIX METALLOPROTEINASE RELEASE IN PATIENTS FOLLOWING CARDIOPULMONARY BYPASS

PubMed Central

Dorman, Bruce H.; Stroud, Robert E.; Wyckoff, Michael M.; Zellner, James L.; Botta, Don; Leonardi, Amy H.; Ikonomidis, John S.; Spinale, Francis G.

2009-01-01

This study examined whether differential effects of two agents commonly used for hemostatic purposes during cardiac surgery, aprotinin or epsilon-aminocaproic acid (EACA), exist with respect to elevations in proinflammatory interleukins (ILs) and matrix metalloproteinases (MMPs) in patients undergoing coronary artery bypass surgery. Sixty patients were prospectively randomized to receive either aprotinin (1×106 KIU;n=30) or EACA (5gIV;n=30) and blood samples were obtained for IL and MMP levels just before induction of anesthesia (Baseline), 10 minutes after separation from cardiopulmonary bypass (Post) and 6 Hours after surgery (6 Hours). IL-6 was increased at Post in the EACA group and increased further at 6 hours. In the aprotinin group, IL-6 was significantly increased only at 6 Hours. MMP subtypes associated with inflammation, MMP-8 and -9 were increased in the EACA group at Post and remained elevated at 6 Hours. Thus, differential effects on IL and MMP release occurred between aprotinin and EACA, indicative of different mechanisms of action independent of hemostatic effects. PMID:18427286

Modulation of Interleukins in Sepsis-Associated Clotting Disorders: Interplay With Hemostatic Derangement.

PubMed

Low, Christopher; Syed, Daneyal; Khan, Daniel; Tetik, Sermin; Walborn, Amanda; Hoppensteadt, Debra; Mosier, Michael; Fareed, Jawed

2017-01-01

Interleukins play a central role in the immune system and are involved in a variety of immunological, inflammatory, and infectious disease states including sepsis syndrome. Levels of interleukins may correlate with overall survival and may directly or indirectly affect some of the regulators of coagulation and fibrinolysis, thereby disrupting hemostasis and thrombosis. Our hypothesis is that in sepsis-associated coagulopathies (SACs), interleukins may be upregulated, leading to hemostatic imbalance by generating thrombogenic mediators. We profiled the levels of interleukins IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10 in addition to d-dimer (DD) in patients with SAC and in normal donors. We observed the highest increase in interleukins IL-6 (322-fold), IL-8 (48-fold), IL-10 (72-fold), and DD (18-fold). This suggests that interleukins such as IL-6 and IL-10 have a close association with coagulopathy and fibrinolytic dysregulation in sepsis and can be considered as candidates for potential therapeutic targets in SAC. © The Author(s) 2016.

Impact of surgery for endometriomas on pregnancy outcomes following in vitro fertilization-intracytoplasmic sperm injection. Who should be the preferred laparoscopists: gynecologists or reproductive surgeons?

PubMed

Cai, He; Guan, Jing; Shen, Huan; Han, Hongjing; Yu, Xiaoming

2017-08-01

To investigate whether laparoscopic excision of ovarian endometriomas pretreated with operation by gynecologists or reproductive surgeons exerts different effects on in vitro fertilization-intracytoplasmic sperm injection results. Retrospective case control study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI from 01/01/2013 to 30/12/2015 in our unit. The study group consisted of 35 women who previously had laparoscopic endometrioma excision by reproductive surgeons in our unit; the control group included 36 patients who underwent surgery for endometriomas by gynecologists in our hospital. There were slightly higher numbers of AFC and higher pregnancy rate in the study group, although differences did not reach statistical significance. For patients over 35 years old, there were more oocyte retrieved, mature oocytes and two pronucei (2PN) in the study group than the control group although observed differences did not reach statistical significance. Electrocautery is more deleterious on ovarian reserve than hemostatic suture. In procedure of patients who wish to conceive, surgeons should use hemostatic suturing technique preferentially.

Novel thrombin and factor Xa inhibitors: challenges to reversal of their anticoagulation effects.

PubMed

Yates, Sean; Sarode, Ravi

2013-11-01

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.

Heart rate variability, hemostatic and acute inflammatory blood parameters in healthy adults after short-term exposure to welding fume.

PubMed

Scharrer, E; Hessel, H; Kronseder, A; Guth, W; Rolinski, B; Jörres, R A; Radon, K; Schierl, R; Angerer, P; Nowak, D

2007-02-01

The present study aimed to investigate, whether short-term experimental exposure to high levels of welding fumes would be capable of exerting acute effects in healthy subjects. Specifically, we assessed cardiovascular function in terms of heart rate variability (HRV) as well as the concentrations of inflammatory mediators and hemostatic proteins in blood as outcome measures. Twenty subjects without a history of airway and cardiovascular diseases were exposed to either control air or welding fume for 1 h on 2 separate days under standardized conditions. The median concentration of the alveolar particle fraction during welding was 3.5 mg/m(3 )(quartiles: 1.4-6.3 mg/m(3); range 1.0-25.3 mg/m(3)). Five hours later a panel of clinical assessments was performed, including HRV measurement and drawing of blood samples. There were no changes in symptom ratings or lung function after welding fume exposure. Exposures did also not differ regarding effects on time- and frequency-domain parameters of HRV. Similarly, blood leukocyte numbers, cell differentials and the blood levels of fibrinogen, C-reactive protein, antithrombin III, factor VIII, von Willebrand factor, ristocetin cofactor, sICAM-1, tumor necrosis factor alpha, interleukin 6, interleukin 8 and epithelial neutrophil activating peptide 78 were not altered by welding fume inhalation. However, there was a significant fall in the level of endothelin-1 (P < 0.01). In conclusion, the data did not indicate effects of clinical significance of a short-term high-level exposure to welding fumes on HRV or a set of blood hemostatic and acute inflammatory parameters in healthy subjects. The small but statistically significant effect on endothelin levels demonstrated that measurable effects could be elicited even in these individuals. Overall, welding fumes are not likely to exert acute cardiovascular effects in healthy individuals.

Multiple electrode aggregometry for the assessment of acquired platelet dysfunctions during extracorporeal circulation.

PubMed

Mutlak, Haitham; Reyher, Christian; Meybohm, Patrick; Papadopoulos, Nestoras; Hanke, Alexander Alfons; Zacharowski, Kai; Weber, Christian Friedrich

2015-02-01

There have been many reports on how the usage of extracorporeal circulation (ECC) is independently associated with the induction of platelet dysfunctions. The aim of the present investigation was to study the capability of the multiple electrode aggregometry (MEA) using the Multiplate (Roche AG, Grenzach, Germany) device to reflect the extent of ECC-associated platelet dysfunctions. The study population consisted of patients who were treated with either hypothermic (cardiopulmonary bypass [CPB]) or normothermic (extracorporeal membrane oxygenation) ECC. Hemostatic analyses included conventional laboratory coagulation tests and aggregometric measures following stimulation with different agonists using MEA. The area under the aggregation curve in the ADPtest (ex vivo adenosine diphosphate induced platelet aggregation) of the MEA was defined as the primary end point. The analyses were performed before the usage of ECC (baseline) and 90 minutes (T1), 120 minutes (T2), 150 minutes (T3), and 180 minutes (T4) after the usage of ECC. In the hypothermic ECC group, additional hemostatic analyses were performed after the patient's postoperative admission to the intensive care unit (T5). Periprocedural data and results of other hemostatic testing were defined as secondary end points. A total of n = 40 patients were assessed for eligibility and n = 25 patients were finally enrolled into the study (hypothermic ECC group: n = 20; normothermic ECC group: n = 5). The extent of ADP-induced platelet aggregation decreased significantly between baseline and consecutive measuring points during hypothermic ECC and remained unchanged between T4 and T5. In the normothermic ECC group, ADP-induced aggregability was significantly lower at T1 compared with baseline and remained unchanged from T1 onward. Data from the present study indicate that ex vivo ADP-induced platelet aggregation in MEA reflects the time-dependent extent of ECC-induced platelet dysfunction. Georg Thieme Verlag KG Stuttgart · New York.

Alveolar fibrin formation caused by enhanced procoagulant and depressed fibrinolytic capacities in severe pneumonia. Comparison with the acute respiratory distress syndrome.

PubMed

Günther, A; Mosavi, P; Heinemann, S; Ruppert, C; Muth, H; Markart, P; Grimminger, F; Walmrath, D; Temmesfeld-Wollbrück, B; Seeger, W

2000-02-01

Changes in the alveolar hemostatic balance in severe pneumonia were compared with those in the acute respiratory distress syndrome (ARDS). Analysis was performed in bronchoalveolar lavage fluids (BALF) of patients with ARDS triggered by nonpulmonary underlying events in the absence of lung infection (ARDS; n = 25), pneumonia demanding mechanical ventilation (PNEU-vent; n = 114), spontaneously breathing patients with pneumonia (PNEU-spon; n = 40), and ARDS in combination with lung infection (ARDS+PNEU; n = 43); comparison with healthy control subjects (n = 35) was performed. In all groups of patients, BALF total procoagulant activity was increased by nearly two orders of magnitude, being largely attributable to the tissue factor pathway of coagulation. Concomitantly, markedly reduced overall fibrinolytic capacity (fibrin plate assay) was noted in the lavage fluids of all patients. BALF levels of urokinase-type plasminogen activator were significantly reduced throughout, whereas the lavage concentrations of tissue-type plasminogen activator did not differ from those in control subjects. In addition, markedly enhanced levels of plasminogen activator- inhibitor I and alpha(2)-antiplasmin were noted in ARDS, ARDS+PNEU, and PNEU-vent, but not in PNEU-spon. In all groups of patients, the changes in the lavage enzymatic activities were paralleled by manifold increased BALF concentrations of fibrinopeptide A and D-dimer, reflecting in vivo coagulation processes. Within the overall number of patients with pneumonia, changes in the alveolar hemostatic balance were more prominent in alveolar and interstitial pneumonia than in bronchopneumonia. Acute inflammatory lung injury, whether triggered by nonpulmonary systemic events or primary lung infection, is thus consistently characterized by both enhanced procoagulant and depressed fibrinolytic activities in the alveolar lining layer, with the appearance of fibrin formation in this compartment. Profile and extent of changes in severe pneumonia demanding respirator therapy are virtually identical to those in ARDS, whereas somewhat less prominent alterations of the alveolar hemostatic balance are noted in spontaneously breathing patients with pneumonia.

A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the "GRAPHE" registry).

PubMed

Haddara, Sami; Jacques, Jeremie; Lecleire, Stéphane; Branche, Julien; Leblanc, Sarah; Le Baleur, Yann; Privat, Jocelyn; Heyries, Laurent; Bichard, Philippe; Granval, Philippe; Chaput, Ulriikka; Koch, Stephane; Levy, Jonathan; Godart, Bruno; Charachon, Antoine; Bourgaux, Jean-François; Metivier-Cesbron, Elodie; Chabrun, Edouard; Quentin, Vincent; Perrot, Bastien; Vanbiervliet, Geoffroy; Coron, Emmanuel

2016-12-01

Background and study aims: The hemostatic powder TC-325 (Hemospray; Cook Medical, Winston-Salem, North Carolina, USA) has shown promising results in the treatment of upper gastrointestinal bleeding (UGIB) in expert centers in pilot studies. The aim of this study was to evaluate the feasibility and efficacy of TC-325 in a large prospective registry of use in routine practice. Patients and methods: The data of all patients treated with TC-325 were prospectively collected through a national registry. Outcomes were the immediate feasibility and efficacy of TC-325 application, as well as the rates of rebleeding at Day 8 and Day 30. Multivariate analysis was performed to determine predictive factors of rebleeding. Results: A total of 202 patients were enrolled and 64 endoscopists participated from 20 centers. TC-325 was used as salvage therapy in 108 patients (53.5 %). The etiology of bleeding was an ulcer in 75 patients (37.1 %), tumor in 61 (30.2 %), postendoscopic therapy in 35 (17.3 %), or other in 31 (15.3 %). Application of the hemostatic powder was found to be very easy or easy in 31.7 % and 55.4 %, respectively. The immediate efficacy rate was 96.5 %. Recurrence of UGIB was noted at Day 8 and Day 30 in 26.7 % and 33.5 %, respectively. Predictive factors of recurrence at Day 8 were melena at initial presentation and use of TC-325 as salvage therapy. Conclusion: These multicenter data confirmed the high rate of immediate hemostasis, excellent feasibility, and good safety profile of TC-325, which could become the treatment of choice in bleeding tumors or postendoscopic bleeding but not in bleeding ulcers where randomized studies are needed. ClinicalTrials.gov (NCT02595853). © Georg Thieme Verlag KG Stuttgart · New York.

Risk of Hemorrhage Attributed to Underlying Chronic Diseases and Uninterrupted Aspirin Therapy of Patients Undergoing Minor Oral Surgical Procedures: A Retrospective Cohort Study.

PubMed

Rojanaworarit, Chanapong; Limsawan, Soontaree

2017-01-01

This study aimed to estimate the risk of bleeding following minor oral surgical procedures and uninterrupted aspirin therapy in high-risk patients or patients with existing chronic diseases compared to patients who did not use aspirin during minor oral surgery at a public hospital. This retrospective cohort study analyzed the data of 2912 patients, aged 20 years or older, who underwent 5251 minor oral surgical procedures at a district hospital in Thailand. The aspirin group was comprised of patients continuing aspirin therapy during oral surgery. The non-aspirin group (reference) included all those who did not use aspirin during surgery. Immediate and late-onset bleeding was evaluated in each procedure. The risk ratio of bleeding was estimated using a multilevel Poisson regression. The overall cumulative incidence of immediate bleeding was 1.3% of total procedures. No late-onset bleeding was found. A significantly greater incidence of bleeding was found in the aspirin group (5.8% of procedures, p<0.001). After adjusting for covariates, a multilevel Poisson regression model estimated that the bleeding risk in the aspirin group was 4.5 times higher than that of the non-aspirin group (95% confidence interval, 2.0 to 10.0; p<0.001). However, all bleeding events were controlled by simple hemostatic measures. High-risk patients or patients with existing chronic diseases who continued aspirin therapy following minor oral surgery were at a higher risk of hemorrhage than general patients who had not used aspirin. Nonetheless, bleeding complications were not life-threatening and could be promptly managed by simple hemostatic measures. The procedures could therefore be provided with an awareness of increased bleeding risk, prepared hemostatic measures, and postoperative monitoring, without the need for discontinuing aspirin, which could lead to more serious complications.

Systemic and Topical Use of Tranexamic Acid in Spinal Surgery: A Systematic Review

PubMed Central

Winter, Sebastian F.; Santaguida, Carlo; Wong, Jean; Fehlings, Michael G.

2015-01-01

Study Design Combination of narrative and systematic literature reviews. Objectives Massive perioperative blood loss in complex spinal surgery often requires blood transfusions and can negatively affect patient outcome. Systemic use of the antifibrinolytic agent tranexamic acid (TXA) has become widely used in the management of surgical bleeding. We review the clinical evidence for the use of intravenous TXA as a hemostatic agent in spinal surgery and discuss the emerging role for its complementary use as a topical agent to reduce perioperative blood loss from the surgical site. Through a systematic review of published and ongoing investigations on topical TXA for spinal surgery, we wish to make spine practitioners aware of this option and to suggest opportunities for further investigation in the field. Methods A narrative review of systemic TXA in spinal surgery and topical TXA in surgery was conducted. Furthermore, a systematic search (using PRISMA guidelines) of PubMed (MEDLINE), EMBASE, and Cochrane CENTRAL databases as well as World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov (National Institutes of Health), and International Standard Randomized Controlled Trial Number registries was conducted to identify both published literature and ongoing clinical trials on topical TXA in spinal surgery. Results Of 1,631 preliminary search results, 2 published studies were included in the systematic review. Out of 285 ongoing clinical trials matching the search criteria, a total of 4 relevant studies were included and reviewed. Conclusion Intravenous TXA is established as an efficacious hemostatic agent in spinal surgery. Use of topical TXA in surgery suggests similar hemostatic efficacy and potentially improved safety as compared with intravenous TXA. For spinal surgery, the literature on topical TXA is sparse but promising, warranting further clinical investigation and consideration as a clinical option in cases with significant anticipated surgical site blood loss. PMID:27099820

A simple technic for repeated collection of blood samples from mice.

PubMed

Stoltz, D R; Bendall, R D

1975-06-01

A device for repeated collection of small blood samples from mice was constructed from a plastic syringe. Blood was collected into a 3.33 lambda capillary tube. Bleeding was stopped by a hemostat made from a rubber stopper. This technic allows easy collection of approximately 20 serial samples within an 8-hr period.

Science, Technology and Requirements - Forum

DTIC Science & Technology

2012-10-18

Visable Absorbing and Electrostatically Adhesive Taggants •2008 Removal of CBRN Materials from Soil & Water using Nanosize Hydroxyapaptite •2009...Ribbon Composite for Optically Transparent Armor Windows •2010 UV Retroreflector Covert Taggants •2013 Proposed Warfighter Bandaging System Company... Bandaging System - Proposed Properties: •Bioactive fiber tissue scaffolding (bonds to both hard and soft tissue) •Hemostatic and Bioresorbable

Application of a Granular Mineral-Based Hemostatic Agent (QuikClot) to Reduce Blood Loss After Grade V Liver Injury in Swine

DTIC Science & Technology

2004-09-01

tion of tiletamine hydrochloride (HCl) and zolazepam HCl (Telazol, Fort Dodge Laboratories, Fort Dodge, IA), anesthe- sia was induced by mask using...Demceva M, Vournakis J, Finkielsztein S, Connolly RJ. Comparison of poly-N-acetyl glucosamine (P-GlcNAc) with absorbable collagen (Actifoam) and fibrin

Platelet aggregating material from equine arterial tissue

DOEpatents

Schneider, Morris D.

1983-02-22

Novel hemostatic agent comprises equine arterial fibrillar collagen in a carrier. The agent is useful for the aggregation of platelets for clinical diagnostic tests and for the clotting of blood, such as for controlling bleeding in warm blooded species. The fibrillar collagen is obtained by extracting homogenized equine arterial tissue with aqueous solutions followed by extensive dialysis.

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

DTIC Science & Technology

1994-10-27

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

Out-of-Hospital Combat Casualty Care in the Current War in Iraq

DTIC Science & Technology

2009-02-01

could not be cleared with available suction equipment (3). There were 10 instances of chitosan hemostatic dressing use (3% of wounded in action). A...Eagle: MAJ David Mathias, MD, CPT Tommy Laird, MPAS, EMPA-C, CPT Scott G. Sullivan, MPAS, PA-C, and CPT Anthony Freiler, PA-C. We also express our

Resuscitation and Transfusion Principles for Traumatic Hemorrhagic Shock

DTIC Science & Technology

2009-11-01

hyperfibrinolysis. We also describe the concept of damage control resuscitation (DCR), an early and aggressive prevention and treatment of hemorrhagic shock... prevention and treatment of acidosis, hypothermia, and hypocalcemia, avoidance of hemodilution, and hemostatic resuscitation with transfusion of red...are potentially preventable and 66–80% of these deaths occur from hemorrhage.3,4 Rural civilian data indicate that approximately 10% of traumatic

Alternative to Blood Replacement in the Critically Ill.

PubMed

Tolich, Deborah J; McCoy, Kelly

2017-09-01

This article reviews treatments and strategies that can be used to reduce, or as adjuncts to, blood transfusion to manage blood volumes in patients who are critically ill. Areas addressed include iatrogenic anemia, fluid management, pharmaceutical agents, hemostatic agents, hemoglobin-based oxygen carriers, and management of patients for whom blood is not an option. Copyright © 2017 Elsevier Inc. All rights reserved.

Disorder of Endothelia Vessels' Functional State with Malignant Tumors in Patients Exposed Anthropogenic Radiation.

PubMed

Pak, Laura; Noso, Yoshihiro; Chaizhunusova, Nailya; Anambaeva, Zukhra; Adylkhanov, Tasbolat; Takeichi, Nobuo; Lzhaev, Sayakhat; Aldyngurov, Daniyar; Tuleutayeva, Raikhan; Argynbekova, Ainur; Tanysheva, Gulyash; Zhazykbayeva, Lashyn; Baissalbayeva, Ainur; Rakhypbekov, Tolebay

2016-01-01

The aim of this research is to determine the characteristics of endothelial factors and the hemostatic system conditions with malignant neoplasms patients, which were exposed to ionizing radiation. Total number of examined people is 223, 153 of them are patients with gastrointestinal tract oncopathology. The article presents the results of the analysis of numerical indicators of endothelial condition and platelet hemostasis of patients, who had cancer. They lived in the regions of Kazakhstan, subjected to contamination of radionuclides as a result of nuclear weapons tests, which took place in this region from 1949 to 1989. These results then were compared to cancer patients and healthy individuals with no radiation risk. The study revealed the presence of higher levels of endothelial dysfunction and following trigger of the hemostatic system in patients with malignant tumors of the gastrointestinal tract. In particular, the defined high degree of endothelial dysfunction include endothelium- dependent vasodilation, content desquamated endothelial cells in peripheral blood and von Willebrand factor. These indicators have a clear correlation with the degree of disorder of studied parameters of the hemostasis, which can cause the development of thrombotic complications.

Comparison of sea turtle thrombocyte aggregation to human platelet aggregation in whole blood.

PubMed

Soslau, Gerald; Prest, Phillip J; Class, Reiner; George, Robert; Paladino, Frank; Violetta, Gary

2005-11-01

The endangered sea turtles are living "fossils" that afford us an opportunity to study the hemostatic process as it likely existed millions of years ago. There are essentially no data about turtle thrombocyte aggregation prior to our studies. Thrombocytes are nucleated cells that serve the same hemostatic functions as the anucleated mammalian platelet. Sea turtle thrombocytes aggregate in response to collagen and beta-thrombin. Ristocetin induces an agglutination/aggregation response indicating the presence of a von Willebrand-like receptor, GPIb, found in all mammalian platelets. Samples treated with alpha-thrombin plus gamma-thrombin followed by ristocetin results in a rapid, stronger response than ristocetin alone. These responses are inhibited by the RGDS peptide that blocks fibrinogen cross-linking of mammalian platelets via the fibrinogen receptor, GPIIb/IIIa. Three platelet-like proteins, GPIb, GPIIb/IIIa and P-selection are detected in sea turtle thrombocytes by fluorescence activated cell sorting. Turtle thrombocytes do not respond to ADP, epinephrine, serotonin, thromboxane A2 mimetic, U46619, trypsin, or alpha-thrombin and gamma-thrombin added alone. Comparison of hemostasis in sea turtles to other vertebrates could provide a framework for understanding the structure/function and evolution of these pathways and their individual components.

Aortic occlusion balloon catheter technique is useful for uncontrollable massive intraabdominal bleeding after hepato-pancreato-biliary surgery.

PubMed

Miura, Fumihiko; Takada, Tadahiro; Ochiai, Takenori; Asano, Takehide; Kenmochi, Takashi; Amano, Hodaka; Yoshida, Masahiro

2006-04-01

Massive intraabdominal hemorrhage sometimes requires urgent hemostatic surgical intervention. In such cases, its rapid stabilization is crucial to reestablish a general hemodynamic status. We used an aortic occlusion balloon catheter in patients with massive intraabdominal hemorrhage occurring after hepato-pancreato-biliary surgery. An 8-French balloon catheter was percutaneously inserted into the aorta from the femoral artery, and the balloon was placed just above the celiac artery. Fifteen minutes inflation and 5 minutes deflation were alternated during surgery until the bleeding was surgically controlled. An aortic occlusion balloon catheter was inserted on 13 occasions in 10 patients undergoing laparotomy for hemostasis of massive hemorrhage. The aorta was successfully occluded on 12 occasions in nine patients. Both systolic pressure and heart rate were normalized during aortic occlusion, and the operative field became clearly visible after adequate suction of leaked blood. Bleeding sites were then easily found and controlled. Hemorrhage was successfully controlled in 7 of 10 patients (70%), and they were discharged in good condition. The aortic occlusion balloon catheter technique was effective for easily controlling massive intraabdominal bleeding by hemostatic procedure after hepato-pancreato-biliary surgery.

Advanced drug delivery systems for antithrombotic agents

PubMed Central

Greineder, Colin F.; Howard, Melissa D.; Carnemolla, Ronald; Cines, Douglas B.

2013-01-01

Despite continued achievements in antithrombotic pharmacotherapy, difficulties remain in managing patients at high risk for both thrombosis and hemorrhage. Utility of antithrombotic agents (ATAs) in these settings is restricted by inadequate pharmacokinetics and narrow therapeutic indices. Use of advanced drug delivery systems (ADDSs) may help to circumvent these problems. Various nanocarriers, affinity ligands, and polymer coatings provide ADDSs that have the potential to help optimize ATA pharmacokinetics, target drug delivery to sites of thrombosis, and sense pathologic changes in the vascular microenvironment, such as altered hemodynamic forces, expression of inflammatory markers, and structural differences between mature hemostatic and growing pathological clots. Delivery of ATAs using biomimetic synthetic carriers, host blood cells, and recombinant fusion proteins that are activated preferentially at sites of thrombus development has shown promising outcomes in preclinical models. Further development and translation of ADDSs that spare hemostatic fibrin clots hold promise for extending the utility of ATAs in the management of acute thrombotic disorders through rapid, transient, and targeted thromboprophylaxis. If the potential benefit of this technology is to be realized, a systematic and concerted effort is required to develop clinical trials and translate the use of ADDSs to the clinical arena. PMID:23798715

Adhesion of Blood Clots Can Be Enhanced When Copolymerized with a Macromer That Is Crosslinked by Coagulation Factor XIIIa.

PubMed

Chan, Karen Y T; Zhao, Chunyi; Siren, Erika M J; Chan, Jeanne C Y; Boschman, Jeffrey; Kastrup, Christian J

2016-06-13

The adhesion of blood clots to blood vessels, such as through the adhesion of fibrin, is essential in hemostasis. While numerous strategies for initiating clot formation and preventing clot lysis are being developed to create improved hemostatic agents, strategies for enhancing clot adhesion have not been widely explored. Here, we show that adhesion of blood clots can be increased by adding a previously characterized synthetic polymer that is crosslinked by coagulation factor XIIIa during clotting. Addition of the polymer to normal plasma increased the adhesive strength of clots by 2-fold. It also recovered the adhesive strength of nonadhesive fibrinogen-deficient whole blood clots from <0.06 kPa to 1.9 ± 0.14 kPa, which is similar to the adhesive strength of a fibrinogen-rich clot (1.8 ± 0.64 kPa). The polymer also enabled plasma clots to remain adhered under fibrinolytic conditions. By demonstrating that the adhesive strength of clots can be increased with a synthetic material, this provides a potential strategy for creating advanced hemostatic materials, such as treatments for fibrinogen deficiency in trauma-induced coagulopathy.

The hemostatic efficacy of chitosan-pads in hemodialysis patients with significant bleeding tendency.

PubMed

Misgav, Mudi; Lubetszki, Ahron; Brutman-Barazani, Tami; Martinowitz, Uri; Kenet, Gili

2017-05-15

Patients on chronic hemodialysis often have acquired coagulopathy that can aggravate bleeding from puncture site after needle extraction. Chitosan-based pads have been reported to accelerate hemostasis even in the presence of coagulopathy. The aim of this study was to evaluate the hemostatic efficacy of the chitosan pads compared to gauze pads, applied for local hemostasis. A crossover study in a cohort of patients on hemodialysis with extended time to hemostasis after needle extraction. At the end of each dialysis, either gauze or chitosan pad was applied on both access points (arterial and venous). The type of pad was changed in the next dialysis all together 5 times in each patient (10 applications per patient for every pad). A total of 288 applications, 144 for each type of pad, were performed in 15 patients. The average time to hemostasis for the entire group was significantly shorter with the chitosan pads compared to the regular gauze pads ("arterial" point 3 vs. 18.5 min, p<0.001 "venous" access 2.8 vs. 13.2 min, p<0.001, respectively). Chitosan pads significantly reduce time to hemostasis and should be considered for the treatment of accessible bleeds in patients with coagulopathy.

Chitosan-based dressing for the treatment of external/accessible bleedings in children with bleeding tendency.

PubMed

Misgav, Mudi; Kenet, Gili; Martinowitz, Uriel

2014-03-01

Bleeding episodes in patients with congenital or acquired bleeding disorders are usually managed with factor concentrates or blood products. However, external and accessible bleeds may effectively be managed with topical hemostasis. After the application of the Hemcon, a Food and Drug Administration-approved chitosan-based hemostatic dressing was used as the "last resort" to successfully control external bleeds in 2 patients with severe bleeding disorders. We describe a single-center experience with this dressing, including its use in pediatric patients as the first mode of therapy. A total of 5 patients (median age 2 y) with severe bleeding disorders were treated with topical chitosan-based dressing for a total of 6 bleeding episodes. The dressing was used either after the failure of extensive systemic therapy or as the first choice of treatment. In 4 of the 6 episodes, bleeding ceased immediately alleviating the need for systemic therapy. There was no rebleeding after the removal of the dressing and no adverse events or local skin reactions were recorded. Hemostatic dressings, such as the chitosan, should be encouraged for the treatment of external/accessible bleeds, especially among the pediatric patients with bleeding tendency.

Liver damage induced in rats by malathion impurities.

PubMed

Keadtisuke, S; Dheranetra, W; Nakatsugawa, T; Fukuto, T R

1990-06-01

Administration of a single oral dose of the malathion impurity, O,O,S-trimethyl phosphorothioate (OOS-Me) or O,S,S-trimethyl phosphorodithioate (OSS-Me), to the rat resulted in hemostatic disorders, e.g. prolongation of blood clotting, prothrombin and thrombin time. Deficiency of coagulation Factors II, V and VII was also observed. OOS-Me and OSS-Me also caused dose-dependent increases of beta-glucuronidase in the blood with a maximum of 15- and 31-fold observed following treatment with 60 mg/kg OOS-Me and 40 mg/kg OSS-Me, respectively. Analysis of serum beta-glucuronidase by isoelectrofocusing electrophoresis showed that the liver endoplasmic reticulum was the source of this enzyme released into the blood. Co-treatment of OOS-Me with 5% O,O,O-trimethyl phosphorothioate (OOO-Me), a potent antagonist of OOS-Me-induced delayed toxicity, prevented hemostatic disorders but had no effect in reducing beta-glucuronidase levels. However, pretreatment of rats with piperonyl butoxide reduced the amount of beta-glucuronidase released into the blood. Of other O,O,S-trialkyl phosphorothioates examined, the O,O-diethyl S-alkyl phosphorothioates showed the highest activity in increasing beta-glucuronidase levels.

Bone wax in Neurosurgery: A Review.

PubMed

Das, Joe M

2018-05-09

In this occasion of 125 years after the so-called "initial" use of bone wax (BW) by Sir Victor Horsley, a review of this age-old hemostatic agent deemed appropriate. The first use of BW for hemostasis is dated back to the 18 th century when modeling or candle wax was used for hemostasis. Though the pioneers in the usage of BW in craniofacial surgeries were Belloq, Professor Khristian Khristianovich Salomon and François Magendie, its first successful use in neurosurgery was demonstrated by Henri Ferdinand Dolbeau in 1864, following the extirpation of a frontal osteoma. This was further popularized by Sir Victor Alexander Haden Horsley, the father of British neurosurgery, who is often incorrectly mentioned as the inventor of BW. Originally derived from bees' wax, the currently available commercial preparation contains paraffin wax and Isopropyl palmitate in addition. The main action being mechanical tamponade, BW has found several other uses in neurosurgery, other than being a hemostatic agent. Though it is cost-effective, the use of BW is associated with several complications also, including ineffective bone healing and infection. So several other alternatives are coming up, but none has yet been able to fully replace "Horsley's wax" till date. Copyright © 2018 Elsevier Inc. All rights reserved.

Characterization of a microbial polysaccharide-based bioflocculant and its anti-inflammatory and pro-coagulant activity.

PubMed

Zhong, Chunying; Cao, Gang; Rong, Kuan; Xia, Zhengwu; Peng, Ting; Chen, Honggao; Zhou, Jiangang

2018-01-01

We describe a novel bioflocculant, MBF-15, which is an exopolysaccharide extracted from the alkaliphilic bacterium Paenibacillus jamilae. The biophysical characteristics of MBF-15 were determined using Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. MBF-15 was also evaluated for its biocompatibility by examining its inflammatory, coagulant, and hemostatic properties in vitro and in vivo. Pretreatment of peripheral blood mononuclear cells with MBF-15 inhibited lipopolysaccharide-stimulated expression of inducible nitric oxide synthase, production of nitric oxide, and secretion of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6. In addition, MBF-15 increased both mRNA and protein levels of the anti-inflammatory cytokines transforming growth factor-β and IL-10. The hemocompatibility of MBF-15 was investigated by measuring the hemolysis ratio and clotting times. MBF-15 had high pro-thrombogenic activity but was not hemolytic. In a rat model, MBF-15 showed superior hemostatic properties compared with chitosan. Thus, MBF-15 offers a promising combination of anti-inflammatory and pro-coagulant properties that may be useful for hemostasis in a variety of clinical settings. Copyright © 2017 Elsevier B.V. All rights reserved.

Residual blood processing by centrifugation, cell salvage or ultrafiltration in cardiac surgery: effects on clinical hemostatic and ex-vivo rheological parameters.

PubMed

Vonk, Alexander B; Muntajit, Warayouth; Bhagirath, Pranav; van Barneveld, Laurentius J; Romijn, Johannes W; de Vroege, Roel; Boer, Christa

2012-10-01

The study compared the effects of three blood concentration techniques after cardiopulmonary bypass on clinical hemostatic and ex-vivo rheological parameters. Residual blood of patients undergoing elective cardiac surgery was processed by centrifugation, cell salvage or ultrafiltration, and retransfused (n = 17 per group). Study parameters included blood loss, (free) hemoglobin, hematocrit, fibrinogen and erythrocyte aggregation, deformability and 2,3-diphosphoglycerate content. Patient characteristics were similar between groups. Ultrafiltration was associated with the highest weight of the transfusion bag [649 ± 261 vs. 320 ± 134 g (centrifugation) and 391 ± 158 g (cell salvage); P < 0.01]. Cell salvage resulted in the lowest hemolysis levels in the transfusion bag. Retransfusion of cell saver blood induced the largest gain in postoperative patient hemoglobin levels when compared to centrifugation and ultrafiltration, and was associated with the largest increase in 2,3-diphosphoglycerate when compared to ultrafiltration (Δ2,3-diphosphoglycerate 1.34 ± 1.92 vs. -0.77 ± 1.56 mmol/l; P = 0.03). Cell salvage is superior with respect to postoperative hemoglobin gain and washout of free hemoglobin when compared to centrifugation or ultrafiltration.

Therapeutic Plasma Transfusion in Bleeding Patients: A Systematic Review.

PubMed

Levy, Jerrold H; Grottke, Oliver; Fries, Dietmar; Kozek-Langenecker, Sibylle

2017-04-01

Plasma products, including fresh frozen plasma, are administered extensively in a variety of settings from massive transfusion to vitamin K antagonist reversal. Despite the widespread use of plasma as a hemostatic agent in bleeding patients, its effect in comparison with other available choices of hemostatic therapies is unclear. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed Central, and databases of ongoing trials for randomized controlled trials that assessed the efficacy and/or safety of therapeutic plasma as an intervention to treat bleeding patients compared with other interventions or placebo. Of 1243 unique publications retrieved in our initial search, no randomized controlled trials were identified. Four nonrandomized studies described the effect of therapeutic plasma in bleeding patients; however, data gathered from these studies did not allow for comparison with other therapeutic interventions primarily as a result of the low number of patients and the use of different (or lack of) comparators. We identified two ongoing trials investigating the efficacy and safety of therapeutic plasma, respectively; however, no data have been released as yet. Although plasma is used extensively in the treatment of bleeding patients, evidence from randomized controlled trials comparing its effect with those of other therapeutic interventions is currently lacking.

[EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

PubMed

Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

2015-01-01

The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

Silica Nanofiber Combat Hemostat (SINCH)

DTIC Science & Technology

2008-10-13

1.5mg 0.6 65 205 High aspect ratio silica fibers (30um x 60nm) 9mg 0.63 58.9 140 Kaolin (TEG control) 0.2mg n/a 59.8 155 TiO2 high aspect ratio...high surface area to volume ratio and thus the material is difficult to handle in an uncontrolled environment. It is easily dispersed and is not easy

The Navy Medical Technology Watch: Hemostatic Dressing Products for the Battlefield

DTIC Science & Technology

2006-09-09

composition and ingredients, external bleeding cessation agents all work to help the rapid formation of a thrombus (clot) or other blockage at the...clotting agent Contraindicated for internal bleeding or deep tissue wounds Collagen. Collagen-like natural substances are created from chemically...2003) Experimental (swine) Complex groin injury, arterial, venous QuikClot produced 0% mortality; RDH had a 66% mortality rate. QuikClot

Assessment of effects of phenolic fractions from leaves and petals of dandelion in selected components of hemostasis.

PubMed

Lis, Bernadetta; Jędrejek, Dariusz; Stochmal, Anna; Olas, Beata

2018-05-01

Aerial parts and roots of Taraxacum officinale (dandelion) have been found to be rich sources of polyphenols, including cinnamic acid derivatives, flavonoids and triterpenoids, which exert different biological activities, such as anti-inflammatory, anticancer and antimicrobial. Additionally, the whole plant is recognized as safe and well tolerated by humans, with no reported adverse effects. Nowadays, dandelion is a commonly available dietary supplement and a component of pharmaceutical preparations used for the treatment of bladder, liver, and spleen. Nevertheless, the effect of dandelion on blood platelets and plasma - components of hemostasis involved in the functioning of a cardiovascular system and linked with various cardiovascular diseases, has not been studied yet. Thus, the main objective of our in vitro experiments was to examine the anti-platelet and antioxidant properties of four standardized dandelion phenolic fractions, i.e. leaves 50% and 85% methanol fractions, and petals 50% and 85% methanol fractions, in blood platelets. Additionally, aforementioned plant preparations were investigated for hemostatic activity in plasma, using three selected hemostatic parameters: the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). None of the studied dandelion fractions, caused the damage of human blood platelets, at the whole tested range. The inhibition of lipid peroxidation in platelets treated with H 2 O 2 /Fe (the donor of OH) was observed for two fractions: leaves and petals 50% fractions, both at the dose 50 μg/mL. Analysis of the effect on the coagulation activity of human plasma demonstrated that three fractions: petals 50% fraction, and leaves and petals 85% fractions, significantly prolonged the thrombin time, at the whole tested range. On the contrary, none of the fractions changed the APTT and the PT. The obtained results demonstrate that dandelion preparations, based on aerial parts, especially rich in hydroxycinnamic acid derivatives (leaves and petals 50% fractions) are promising plant materials exerting both antioxidant and anticoagulant activities of the hemostatic system that is beneficial in the prevention and treatment of cardiovascular diseases. Published by Elsevier Ltd.

Intravenous Esomeprazole for Prevention of Peptic Ulcer Rebleeding: A Randomized Trial in Chinese Patients.

PubMed

Bai, Yu; Chen, Dong-Feng; Wang, Rong-Quan; Chen, You-Xiang; Shi, Rui-Hua; Tian, De-An; Chen, Huifang; Eklund, Stefan; Li, Zhao-Shen

2015-11-01

High-dose intravenous esomeprazole is the only approved pharmacological treatment for the prevention of peptic ulcer rebleeding (currently approved in over 100 countries worldwide), but has not yet been approved in China. This study aimed to evaluate a high-dose esomeprazole intravenous regimen vs. an active control (cimetidine) for the prevention of rebleeding in Chinese patients with a high risk of peptic ulcer rebleeding who had undergone primary endoscopic hemostatic treatment. This was a parallel-group study conducted at 20 centers in China. The study comprised a randomized, double-blind, intravenous treatment phase of 72 h in which 215 patients received either high-dose esomeprazole (80 mg + 8 mg/h) or cimetidine (200 mg + 60 mg/h), followed by an open-label oral treatment phase in which all patients received esomeprazole 40 mg tablets once daily for 27 days. The primary outcome was the rate of clinically significant rebleeding within the first 72 h after initial endoscopic hemostatic therapy. Secondary outcomes included the rates of clinically significant rebleeding within 7 and 30 days; proportions of patients who had endoscopic retreatment and other surgery due to rebleeding; and number of blood units transfused. The rate of clinically significant rebleeding within 72 h was low overall (3.3%) and numerically lower in patients treated with esomeprazole compared with cimetidine (0.9% vs. 5.6%). Overall, the results of the secondary outcomes also showed a numerical trend towards superiority of esomeprazole over cimetidine. All treatments were well tolerated. In this phase 3, multicenter, randomized trial conducted in China, esomeprazole showed a numerical trend towards superior clinical benefit over cimetidine in the prevention of rebleeding in patients who had successfully undergone initial hemostatic therapy of a bleeding peptic ulcer, with a similar safety and tolerability profile. These findings suggest that esomeprazole may be an alternative treatment option to cimetidine for this indication in China. AstraZeneca. ClinicalTrials.gov identifier, NCT01757275.

Gelatin-thrombin hemostatic matrix in neurosurgical procedures: hemostasis effectiveness and economic value of clinical and surgical procedure-related benefits.

PubMed

Esposito, Felice; Cappabianca, Paolo; Angileri, Filippo F; Cavallo, Luigi M; Priola, Stefano M; Crimi, Salvatore; Solari, Domenico; Germanò, Antonino F; Tomasello, Francesco

2016-07-26

Gelatin-thrombin hemostatic matrix (FloSeal®) use is associated with shorter surgical times and less blood loss, parameters that are highly valued in neurosurgical procedures. We aimed to assess the effectiveness of gelatin-thrombin in neurosurgical procedures and estimate its economic value. In a 6-month retrospective evaluation at 2 hospitals, intraoperative and postoperative information were collected from patients undergoing neurosurgical procedures where bleeding was controlled with gelatin-thrombin matrix or according to local bleeding control guidelines (control group). Study endpoints were: length of surgery, estimated blood loss, hospitalization duration, blood units utilized, intensive care unit days, postoperative complications, and time-to-recovery. Statistical methods compared endpoints between the gelatin-thrombin and control groups and resource utilization costs were estimated. Seventy-eight patients (38 gelatin-thrombin; 40 control) were included. Gelatin-thrombin was associated with a shorter surgery duration than control 166±40 versus 185±55, p=0.0839); a lower estimated blood loss (185±80 versus 250±95ml; p=0.0017); a shorter hospital stay (10±3 versus 13±3 days; p<0.001); fewer intensive care unit days (10 days/3 patients and 20 days/4 patients); and shorter time-to-recovery (3±2.2 versus 4±2.8 weeks; p=0861). Fewer gelatin-thrombin patients experienced postoperative complications (3 minor) than the control group (5 minor; 3 major). No gelatin-thrombin patient required blood transfusion; 5 units were administered in the control group. The cost of gelatin-thrombin (€268.40/unit) was offset by the shorter surgery duration (difference of 19 minutes at €858 per hour) and the economic value of improved the other endpoint outcomes (ie, shorter hospital stay, less blood loss/lack of need for transfusion, fewer intensive care unit days, and complications). Gelatin-thrombin hemostatic matrix use in patients undergoing neurosurgical procedures was associated with better intra- and post-operative parameters than conventional hemostasis methods, with these parameters having substantial economic benefits.

A randomized comparative trial of OTSC and Padlock for upper GI hemostasis in a standardized experimental setting.

PubMed

Prosst, Ruediger L; Kratt, Thomas

2017-04-01

Upper gastrointestinal bleeding (UGIB) is the key emergency situation in clinical endoscopy and is traditionally treated with injection, thermal or through the scope clipping therapy. Mortality rates are in the range of 8-10% and demand new treatment approaches. The Over-The-Scope Clip (OTSC ® ) has been described as a very effective hemostatic device in UGIB. We compared OTSC with the Padlock™ device in an established pre-clinical setting. Our test-bed consisted of the biohybrid EASIE model using soft silicone tubes, tunneled into the gastric wall and surfacing at a mucosa defect, representing the bleeding site. After successful deployment of the OTSC and Padlock devices on the spurting ulcer bleed (Forrest Ia) the vessel tubes were pressurized with a manometer to 120 mmHg. Tight closure at this pressure was defined as successful hemostasis (primary endpoint). N = 11 procedures were done with each device. Statistical testing was done using Fisher's exact test. Sample size was adjusted to an assumed α-error of 5% (two-sided test) and a power of 80%. Technically correct placement of the respective hemostatic device was achieved in all procedures. A statistically significant difference was found in the primary endpoint. In OTSC the success proportion was 100%; 11/11 (95% KI 74.1% to 100%); in Padlock it was 0%; 0/11 (95% KI 0%-25.8%). This means that no bleeding was stopped by Padlock. The mean value of perfusion pressure resistance was 300 mmHg (cut-off) for OTSC and 9.2 ± 8.4 mmHg for Padlock. Our data on hemostatic function of OTSC coincide with the clinical literature and earlier pre-clinical studies in the EASIE model, which is widely accepted as a realistic and effective simulation system for clinical conditions. The inability of Padlock to stop hemorrhage may be due to design differences and, thus, its limitation in providing tight sealing of the clipped tissue. Different types of endoscope-tip mounted clips have different performances. OTSC consistently stops simulated spurting bleeding, Padlock fails to do so. These differences are statistically significant.

Comparison of Hemostatic Efficacy of ChitoGauze and Combat Gauze in a Lethal Femoral Arterial Injury in Swine Model

DTIC Science & Technology

2010-04-01

range of gram positive and gram negative organisms, including methicillin resistant Staphylococcus aureus ATCC33591 (MRSA), Enterococcus faecalis...range of gram positive and gram negative organisms, including methicillin resistant Staphylococcus aureus ATCC33591 (MRSA), Enterococcus faecalis...control with less blood loss than Combat Gauze in this model. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for

Comparison of 10 Different Hemostatic Dressings in an Aortic Injury

DTIC Science & Technology

2003-02-01

lateral peritoneal recesses of the abdomen bilaterally. The rate of bleeding was quantified (grams accumulated every 10 sec- onds) in the suction...used frequently for hemostasis in dental procedures19 D5 TachoComb S Nycomed Amersham, Linz, Austria Collagen -based ( collagen from horse tendons...product with human fibrinogen and thrombin Collagen attracts and activates platelets to achieve hemostasis. D5 also had fibrinogen and thrombin, but at a

Effects of DETANONOate, a nitric oxide donor, on hemostasis in rabbits: an in vitro and in vivo thrombelastographic analysis.

PubMed

Nielsen, V G; Geary, B T; Baird, M S

2000-03-01

The purpose of this study was to determine if whole blood thrombelastographic variables (reaction time, K, alpha, and maximum amplitude) would be adversely effected by exposure to the nitric oxide (NO) donor, DETANONOate, in vitro or after alveolar instillation in vivo. Conscious rabbits (n = 10) had blood sampled from ear arteries anticoagulated with sodium citrate. The blood was then incubated with 0, 1, 5, 10, or 20 mmol/L DETANONOate for 30 minutes. Arterial blood from anesthetized rabbits (n = 4) was obtained and anticoagulated before and 60 minutes after 1 mmol/L DETANONOate (2 mL/kg) was instilled into the right lung. After incubation, all samples were placed in a thrombelastograph and recalcified, with thrombelastographic variables measured for 45 minutes. In vitro, 10 mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha compared with values observed after incubation with 0, 1, and 5 mmol/L DETANONOate. Twenty mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha and maximum amplitude values compared with all other concentrations. In vivo, DETANONOate administration did not significantly affect thrombelastographic variables. DETANONOate significantly decreased hemostatic function in vitro in a dose-dependent fashion but did not significantly affect hemostatic function in vivo.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles

PubMed Central

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-01-01

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly(γ-glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates. PMID:28398222

Hemostatic efficacy of local chitosan linear polymer granule in an experimental sheep model with severe bleeding of arteria and vena femoralis.

PubMed

Ersoy, Gürkan; Rodoplu, Ülkümen; Yılmaz, Osman; Gökmen, Necati; Doğan, Alper; Dikme, Özgür; Aydınoğlu, Aslı; Orhon, Okyanus

2016-05-01

The aim of the present study was to evaluate the hemostatic effect of chitosan linear polymer in a sheep model with femoral bleeding. Following induction of anesthesia and intubation of sheep, groin injury was induced to initiate hemorrhage. Animals were randomly assigned to study and control groups. In the control group, absorbent pads were packed on the wound, and pressure was supplied by a weight placed over the dressing. In the study group, chitosan linear polymer was poured onto the bleeding site; absorbent pads and pressure were applied in the same manner. At 5-min intervals, bleeding was evaluated. Primary endpoint was time to hemostasis. Bleeding had stopped by the 1st interval in 5 members of the study group, and by the 2nd interval in 1 member. One sheep was excluded. The bleeding stopped after the 1st interval in 1 member of the control group and after the 2nd interval in 4 members. Bleeding stopped in 2 cases following ligation of the bleeding vessel. Hemostasis was achieved earlier in the study group, compared to the control group, and the difference was statistically significant. Hemostasis was achieved earlier following application of chitosan linear polymer.

Comparative effectiveness of epsilon-aminocaproic acid and tranexamic acid on postoperative bleeding following cardiac surgery during a national medication shortage.

PubMed

Blaine, Kevin P; Press, Christopher; Lau, Ken; Sliwa, Jan; Rao, Vidya K; Hill, Charles

2016-12-01

The aim of this study was to compare the effectiveness of epsilon-aminocaproic acid (εACA) and tranexamic acid (TXA) in contemporary clinical practice during a national medication shortage. A retrospective cohort study. The study was performed in all consecutive cardiac surgery patients (n=128) admitted to the cardiac-surgical intensive care unit after surgery at a single academic center immediately before and during a national medication shortage. Demographic, clinical, and outcomes data were compared by descriptive statistics using χ 2 and t test. Surgical drainage and transfusions were compared by multivariate linear regression for patients receiving εACA before the shortage and TXA during the shortage. In multivariate analysis, no statistical difference was found for surgical drain output (OR 1.10, CI 0.97-1.26, P=.460) or red blood cell transfusion requirement (OR 1.79, CI 0.79-2.73, P=.176). Patients receiving εACA were more likely to receive rescue hemostatic medications (OR 1.62, CI 1.02-2.55, P=.041). Substitution of εACA with TXA during a national medication shortage produced equivalent postoperative bleeding and red cell transfusions, although patients receiving εACA were more likely to require supplemental hemostatic agents. Published by Elsevier Inc.

Preparation, Characterization and Properties of Alginate/Poly(γ-glutamic acid) Composite Microparticles.

PubMed

Tong, Zongrui; Chen, Yu; Liu, Yang; Tong, Li; Chu, Jiamian; Xiao, Kecen; Zhou, Zhiyu; Dong, Wenbo; Chu, Xingwu

2017-04-11

Alginate (Alg) is a renewable polymer with excellent hemostatic properties and biocapability and is widely used for hemostatic wound dressing. However, the swelling properties of alginate-based wound dressings need to be promoted to meet the requirements of wider application. Poly( γ -glutamic acid) (PGA) is a natural polymer with high hydrophility. In the current study, novel Alg/PGA composite microparticles with double network structure were prepared by the emulsification/internal gelation method. It was found from the structure characterization that a double network structure was formed in the composite microparticles due to the ion chelation interaction between Ca 2+ and the carboxylate groups of Alg and PGA and the electrostatic interaction between the secondary amine group of PGA and the carboxylate groups of Alg and PGA. The swelling behavior of the composite microparticles was significantly improved due to the high hydrophility of PGA. Influences of the preparing conditions on the swelling behavior of the composites were investigated. The porous microparticles could be formed while compositing of PGA. Thermal stability was studied by thermogravimetric analysis method. Moreover, in vitro cytocompatibility test of microparticles exhibited good biocompatibility with L929 cells. All results indicated that such Alg/PGA composite microparticles are a promising candidate in the field of wound dressing for hemostasis or rapid removal of exudates.

Hypertonic saline-epinephrine local injection therapy for post-endoscopic sphincterotomy bleeding: removal of blood clots using pure ethanol local injection.

PubMed

Sakai, Yuji; Tsuyuguchi, Toshio; Sugiyama, Harutoshi; Nishikawa, Takao; Kurosawa, Jo; Saito, Masayoshi; Tawada, Katsunobu; Mikata, Rintaro; Tada, Motohisa; Ishihara, Takeshi; Yokosuka, Osamu

2013-08-01

Bleeding following endoscopic sphincterotomy (EST) is a rare but unavoidable complication of the procedure. We routinely perform local injection of hypertonic saline-epinephrine (HSE) for the treatment of post-EST bleeding. Any blood clot is removed only by irrigation with water after local injection of pure ethanol into the blood clot to cause crusting. We evaluated the usefulness of this treatment method. Subjects were 8 patients (1.2%) with post-EST bleeding requiring hemostatic intervention among 682 patients undergoing EST. After determination of the bleeding point, local injection of HSE was performed. When an adherent blood clot was present, pure ethanol was injected into the blood clot and then irrigation with water was performed to remove the blood clot. Endoscopic hemostasis was successfully achieved in all the 8 patients (100%). In 4 patients (50%), the adherent blood clots were successfully removed only with pure ethanol local injection into the blood clot followed by irrigation with water. No complications of the hemostatic procedure occurred in any patients. This study indicated that hemostasis with HSE local injection can be safe and useful for the treatment of post-EST bleeding, and also that blood clot removal with pure ethanol local injection can be useful.

Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness

PubMed Central

Schaber, Marc; Leichtfried, Veronika; Fries, Dietmar; Wille, Maria; Gatterer, Hannes; Faulhaber, Martin; Würtinger, Philipp; Schobersberger, Wolfgang

2015-01-01

Introduction. The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls. Materials and Methods. 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used. Results. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test). Conclusions. All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected. PMID:26451374

Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness.

PubMed

Schaber, Marc; Leichtfried, Veronika; Fries, Dietmar; Wille, Maria; Gatterer, Hannes; Faulhaber, Martin; Würtinger, Philipp; Schobersberger, Wolfgang

2015-01-01

The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls. 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test). All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected.

Differences in coagulation among Asians and Caucasians and the implication for reconstructive microsurgery.

PubMed

Singhal, Dhruv; Smorodinsky, Emmanuil; Guo, Lifei

2011-01-01

Microvascular reconstructive surgery has seen a revival with the introduction of muscle-sparing perforator flaps. Recognition of potential ethnic differences in coagulation profiles would be important to a microvascular surgeon. Based on clinical observations, we hypothesize that Asian patients have a less thrombogenic coagulation profile than Caucasians. An extensive retrospective review was performed. The annual incidence of venous thromboembolism in the United States is generally accepted to range from 70 to 120 events per 100,000 people versus 16 to 17 events per 100,000 persons in Asia. Autopsy analysis of pulmonary embolism incidence was noted to be 15% in North Americans and less than 1% in Asian populations. Thromboelastography analysis of Asian and Caucasian patients undergoing cholecystectomy revealed different hemostatic mechanisms. Comparison of Asians and Caucasians undergoing the Fontan procedure revealed significantly lower postoperative factor levels in Asians than Caucasians. Baseline comparison of factor and serum levels revealed Asians with the least thrombogenic profiles compared with other ethnic groups. Asians and Caucasians demonstrate different baseline rates of deep vein thrombosis and pulmonary embolism, different hemostatic responses to surgery, and different baseline levels of clotting factors. Further study may lead to better pre-, intra-, and postoperative care of the free flap patient based on their ethnic coagulation profile. © Thieme Medical Publishers.

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.

Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis.

PubMed

Farris, Manuela; Bastianelli, Carlo; Rosato, Elena; Brosens, Ivo; Benagiano, Giuseppe

2017-10-01

The pharmacodynamic effects of various combined oral estrogen-progestin combinations (COC) are examined for their components alone or in the various combined formulations. Special emphasis is given to products containing natural estrogens. Areas covered: Recent information on the effect of androgens, estrogens, progestins, as well as various COC combinations on the coagulation cascade will be reviewed aiming at providing an updated picture. The present article reviews hemostatic changes occurring during use of classic and modern combinations of estrogens (ethinyl estradiol, estradiol, estradiol valerate and estetrol) and new progestins (desogestrel, gestodene, dienogest, drospirenone, nomegestrol acetate), compared to classic compounds, such as levonorgestrel. Both pro- and anti-coagulatory effects of COC in healthy women are detailed and possible links with incidence of thromboembolic events are discussed. Expert commentary: Overall, the picture is reassuring: the use of natural estrogens and of new generation progestins has reduced pro-coagulatory changes in healthy subjects, although the observed differences in the risk of venous thromboembolism between second and third generation progestins is still incompletely understood. At the same time, there still is a need for large comparative and surveillance studies before firm conclusions can be drawn. At any rate, available evidence indicates that hemostatic effects of the newer COC, especially those utilizing natural estrogens, are minimal and often remain with the normal range.

Testing of Intravenous Hemostatic Agents in a Novel Swine Model of Bleeding: Preliminary Results With FXa-PCPs

DTIC Science & Technology

2005-08-01

proceeds through a prothrombinase complex (prothrombin, factor Va, calcium, and phospholipid). Thrombin is the final product in the coagulation cascade...we report preliminary data on the efficacy of mixtures of highly purified blood coagulation factors (FVIIa and FXa) and phospholipids vesicles (PCPS...testing. Further study of these drugs for the use of traumatic hemorrhage is not warranted. 15. SUBJECT TERMS Recombinant Factor VI~a, factor Xa

Extrudable Gel-Forming Bioabsorbable Hemostatic Tissue Adhesives for Traumatic and Burn Wounds

DTIC Science & Technology

1996-12-01

DAMD17-96-1-6241 6. AUTHOR(S) Shalaby W. Shalaby, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) B. PERFORMING ORGANIZATION Poly-Med...Incorporated REPORT NUMBER Anderson, South Carolina 29625 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS( ES ) 10. SPONSORING/MONITORING Commander AGENCY...the wound breaking strength. This was done using a Satec universal testing machine. Details of the animal protocol are given in Appendix A. The

Educating the Educator: Use of Advanced Bleeding Control Mechanisms in Athletic Training: A Shift in the Thought Process of Prehospital Care. Part 2: Hemostatic Agents

ERIC Educational Resources Information Center

Payne, Ellen K.; Berry, David C.; Seitz, S. Robert

2014-01-01

In Part 1 of this series [see: EJ1044392], the concepts of hemorrhaging, shock, and controlling bleeding as they relate to athletic training and prehospital emergency care along with the use of tourniquets were presented for athletic training educators (ATEs) to teach the skill in the classroom. This article, Part 2 of advanced bleeding control,…

Primary Hemostatic Capacity of Whole Blood: A Comprehensive Analysis of Pathogen Reduction and Refrigeration Effects Over Time

DTIC Science & Technology

2013-01-01

reduction and refrigeration is intriguing and suggests that PRT WB may complement the beneficial effects of the antifibrinolytic, tranexamic acid in...and ABBREVIATIONS: aPTT = activated partial thromboplastin time; ASPI = arachidonic acid agonist; COL = collagen; GPIba = glycoprotein Ib alpha; K...riboflavin and ultraviolet (UV) light to damage the nucleic acids of white blood cells (WBCs), parasites, bacteria, and viruses, is being consid- ered

Splash M-knife versus Flush Knife BT in the technical outcomes of endoscopic submucosal dissection for early gastric cancer: a propensity score matching analysis.

PubMed

Esaki, Mitsuru; Suzuki, Sho; Hayashi, Yasuyo; Yokoyama, Azusa; Abe, Shuichi; Hosokawa, Taizo; Ogino, Haruei; Akiho, Hirotada; Ihara, Eikichi; Ogawa, Yoshihiro

2018-02-27

Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer. A new multi-functional ESD device was developed to achieve complete ESD with a single device. A metal plate attached to its distal sheath achieves better hemostasis during the procedure than the other needle-knife device, Flush Knife BT®, that has been conventionally used. The aim of this study was to compare the technical outcomes of ESD for early gastric cancer using the Splash M-Knife® with those using the Flush Knife BT. We conducted a retrospective review of the case records of 149 patients with early gastric cancer treated with ESD using the needle-type ESD knives between January 2012 and August 2016 at Kitakyushu Municipal Medical Center. Lesions treated with ESD using the Splash M-knife (ESD-M) and the Flush Knife BT (ESD-F) were compared. Multivariate analyses and propensity score matching were used to compensate for the differences in age, gender, underlying disease, antithrombotic drug use, lesion location, lesion position, macroscopic type, tumor size, presence of ulceration, operator level and types of electrosurgical unit used. The primary endpoint was the requirement to use hemostatic forceps in the two groups. The secondary endpoints of procedure time, en bloc and complete resection rates, and adverse events rates were evaluated for the two groups. There were 73 patients in the ESD-M group, and 76 patients in the ESD-F group. Propensity score matching analysis created 45 matched pairs. Adjusted comparisons between the two groups showed a significantly lower usage rate of hemostatic forceps in the ESD-M group than in the ESD-F group (6.7% vs 84.4%, p < 0.001). Treatment outcomes showed an en bloc resection rate of 100% in both groups; complete resection rate of 95.6% vs 100%, p = 0.49; median procedure time of 74.0 min vs 71.0 min, p = 0.90; post-procedure bleeding of 2.2% vs 2.2%, p = 1, in the ESD-M and ESD-F groups, respectively. There were no perforations in either group. ESD-M appeared to reduce the usage of hemostatic forceps during ESD for early gastric cancer without increasing the adverse effects. Thus, it may contribute to a reduction in the total ESD cost.

Hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound in the treatment of a rabbit liver trauma model

PubMed Central

Zhao, Da-wei; Tian, Meng; Yang, Jian-zheng; Du, Peng; Bi, Jie; Zhu, Xinjian

2016-01-01

The aim of our study was to investigate the hemostatic mechanism underlying microbubble-enhanced non-focused ultrasound treatment of liver trauma. Thirty rabbits with liver trauma were randomly divided into three groups—the microbubble-enhanced ultrasound (MEUS; further subdivided based on exposure intensity into MEUS1 [0.11 W/cm2], MEUS2 [0.55 W/cm2], and MEUS3 [1.1 W/cm2]), ultrasound without microbubbles (US), and microbubbles without ultrasound (MB) groups. The pre- and post-treatment bleeding weight and visual bleeding scores were evaluated. The serum liver enzyme concentrations as well as the blood perfusion level represented by mean peak contrast intensity (PI) ratio in the treatment area were analyzed. The hemostatic mechanism was evaluated by histological and transmission electron microscopic examination of liver tissue samples. The MEUS subgroups 1–3 (grade 0–1, grade 0–2, and grade 1–2, respectively) exhibited significantly lower post-treatment visual bleeding scores than the US and MB groups (both, grade 3–4; all, P < 0.05). Subgroups MEUS1 (0.346 ± 0.345 g) and MEUS2 (2.232 ± 2.256 g) exhibited significantly lower post-treatment bleeding weight than the US and MB groups (5.698 ± 1.938 and 5.688 ± 2.317 g, respectively; all, P < 0.05). Additionally, MEUS subgroups 1–3 exhibited significantly lower post-treatment blood perfusion levels (PI ratios, 0.64 ± 0.085, 0.73 ± 0.045, and 0.84 ± 0.034, respectively) than the US and MB groups (PI ratios, 1.00 ± 0.005 and 0.99 ± 0.005, respectively; all, P < 0.05). In the MEUS group, hepatic cells became edematous and compressed the hepatic sinus and associated blood vessels. However, the serum liver enzyme levels were not significantly altered. Microbubble-enhanced non-focused ultrasound does not significantly affect blood perfusion and liver function and can be used to induce rapid hemostasis in case of liver trauma. PMID:27633577

A quantitative systems pharmacology model of blood coagulation network describes in vivo biomarker changes in non-bleeding subjects.

PubMed

Lee, D; Nayak, S; Martin, S W; Heatherington, A C; Vicini, P; Hua, F

2016-12-01

Essentials Baseline coagulation activity can be detected in non-bleeding state by in vivo biomarker levels. A detailed mathematical model of coagulation was developed to describe the non-bleeding state. Optimized model described in vivo biomarkers with recombinant activated factor VII treatment. Sensitivity analysis predicted prothrombin fragment 1 + 2 and D-dimer are regulated differently. Background Prothrombin fragment 1 + 2 (F 1 + 2 ), thrombin-antithrombin III complex (TAT) and D-dimer can be detected in plasma from non-bleeding hemostatically normal subjects or hemophilic patients. They are often used as safety or pharmacodynamic biomarkers for hemostatis-modulating therapies in the clinic, and provide insights into in vivo coagulation activity. Objectives To develop a quantitative systems pharmacology (QSP) model of the blood coagulation network to describe in vivo biomarkers, including F 1 + 2 , TAT, and D-dimer, under non-bleeding conditions. Methods The QSP model included intrinsic and extrinsic coagulation pathways, platelet activation state-dependent kinetics, and a two-compartment pharmacokinetics model for recombinant activated factor VII (rFVIIa). Literature data on F 1 + 2 and D-dimer at baseline and changes with rFVIIa treatment were used for parameter optimization. Multiparametric sensitivity analysis (MPSA) was used to understand key proteins that regulate F 1 + 2 , TAT and D-dimer levels. Results The model was able to describe tissue factor (TF)-dependent baseline levels of F 1 + 2 , TAT and D-dimer in a non-bleeding state, and their increases in hemostatically normal subjects and hemophilic patients treated with different doses of rFVIIa. The amount of TF required is predicted to be very low in a non-bleeding state. The model also predicts that these biomarker levels will be similar in hemostatically normal subjects and hemophilic patients. MPSA revealed that F 1 + 2 and TAT levels are highly correlated, and that D-dimer is more sensitive to the perturbation of coagulation protein concentrations. Conclusions A QSP model for non-bleeding baseline coagulation activity was established with data from clinically relevant in vivo biomarkers at baseline and changes in response to rFVIIa treatment. This model will provide future mechanistic insights into this system. © 2016 International Society on Thrombosis and Haemostasis.

Identification of hemostatic genes expressed in human and rat leg muscles and a novel gene (LPP1/PAP2A) suppressed during prolonged physical inactivity (sitting)

PubMed Central

2012-01-01

Background Partly because of functional genomics, there has been a major paradigm shift from solely thinking of skeletal muscle as contractile machinery to an understanding that it can have roles in paracrine and endocrine functions. Physical inactivity is an established risk factor for some blood clotting disorders. The effects of inactivity during sitting are most alarming when a person develops the enigmatic condition in the legs called deep venous thrombosis (DVT) or “coach syndrome,” caused in part by muscular inactivity. The goal of this study was to determine if skeletal muscle expresses genes with roles in hemostasis and if their expression level was responsive to muscular inactivity such as occurs in prolonged sitting. Methods Microarray analyses were performed on skeletal muscle samples from rats and humans to identify genes associated with hemostatic function that were significantly expressed above background based on multiple probe sets with perfect and mismatch sequences. Furthermore, we determined if any of these genes were responsive to models of physical inactivity. Multiple criteria were used to determine differential expression including significant expression above background, fold change, and non-parametric statistical tests. Results These studies demonstrate skeletal muscle tissue expresses at least 17 genes involved in hemostasis. These include the fibrinolytic factors tetranectin, annexin A2, and tPA; the anti-coagulant factors TFPI, protein C receptor, PAF acetylhydrolase; coagulation factors, and genes necessary for the posttranslational modification of these coagulation factors such as vitamin K epoxide reductase. Of special interest, lipid phosphate phosphatase-1 (LPP1/PAP2A), a key gene for degrading prothrombotic and proinflammatory lysophospholipids, was suppressed locally in muscle tissue within hours after sitting in humans; this was also observed after acute and chronic physical inactivity conditions in rats, and exercise was relatively ineffective at counteracting this effect in both species. Conclusions These findings suggest that skeletal muscle may play an important role in hemostasis and that muscular inactivity may contribute to hemostatic disorders not only because of the slowing of blood flow per se, but also potentially because of the contribution from genes expressed locally in muscles, such as LPP1. PMID:23061662

A role for very low-dose recombinant activated factor VII in refractory bleeding after cardiac surgery: Lessons from an observational study.

PubMed

Hoffmann, Till; Assmann, Alexander; Dierksen, Angelika; Roussel, Elisabeth; Ullrich, Sebastian; Lichtenberg, Artur; Albert, Alexander; Sixt, Stephan

2018-04-18

Although off-label use of recombinant activated factor VII against refractory bleeding is incorporated in current guideline recommendations, safety concerns persist predominantly with respect to thromboembolic complications. We analyzed the safety and efficacy of recombinant activated factor VII at a very low dose in cardiosurgical patients with refractory bleeding. This prospective study includes 1180 cardiosurgical patients at risk of bleeding. Goal-directed substitution was based on real-time laboratory testing and clinical scoring of the bleeding intensity. All patients who fulfilled the criteria for enhanced risk of bleeding (n = 281) were consequently included in the present analysis. Patients in whom refractory bleeding developed despite substitution with specific hemostatic compounds (n = 167) received a single shot of very low-dose recombinant activated factor VII (≤20 μg/kg). Mortality and risk of thromboembolic complications, and freedom from stroke and acute myocardial infarction in particular, were analyzed (vs patients without recombinant activated factor VII) by multivariable logistic and Cox regression analyses, as well as Kaplan-Meier estimates. There was no increase in rates of mortality (30-day mortality 4.2% vs 7.0% with P = .418; follow-up survival 85.6% at 13.0 [interquartile range, 8.4-15.7] months vs 80.7% at 10.2 [interquartile range, 7.2-16.1] months with P = .151), thromboembolic complications (6.6% vs 9.6% with P = .637), renal insufficiency, need for percutaneous coronary intervention, duration of ventilation, duration of hospital stay, or rehospitalization in patients receiving very low-dose recombinant activated factor VII compared with patients not receiving recombinant activated factor VII. Complete hemostasis without any need for further hemostatic treatment was achieved after very low-dose recombinant activated factor VII administration in the majority of patients (up to 88.6% vs 0% with P < .001). The key results were confirmed after adjustment by propensity score-based analyses. When combined with early and specific restoration of hemostatic reserves after cardiac surgery, very low-dose recombinant activated factor VII treatment of refractory bleeding is effective and not associated with any apparent increase in adverse events. Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

The Effects of Hemostatic Agents and Hypothermia Control in a Porcine Model

DTIC Science & Technology

2015-07-30

Tacoma, WA 98402 N/A 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S ACRONYM(S) TriService Nursing Research...manipulation of systolic blood pressure, and movement of extremities, QCG was effective in hemorrhage control (p < 0.05). Implications for Military Nursing ...8-98) Prescribed by ANSI Std. Z39.18 Principal Investigator: Johnson, Arthur Don, PhD USU Project Number: N09-C01 TriService Nursing

Comparison of Combat Gauze and TraumaStat in Two Severe Groin Injury Models

DTIC Science & Technology

2011-07-01

especially given their similarity in form to stan· dard gauze currently in use . Recently, two such prod· ucts, Combat Gauze (CBG) and TraumaStat (TMS...if acted upon imme- diately after injury. With proper compression on the wound site, use of adequate hemostatic dressing for bleeding control...be minimized. In an effort for better hemo- static control in noncompressible areas such as the neck or the groin where tourniquets cannot be used

[Hemorrhagic syndrome after transfusion of incompatible blood].

PubMed

Fedorova, Z D; Bsryshev, B A; Khanin, A Z; Chuslov, A G

1979-11-01

The patients were observed by a reanimation-hematological team of the Leningrad emergency service. It has been established that the hemorrhagic syndrome is the main one deterimining the unity of pathogenesis and clinical picture of the hemotransfusional complication. Phase character of the changes in the homeostasis system during the transfusion of incompatible blood was noted. The express diagnosis of the disorders and a scheme of the sequence of administration of hemostatic drugs are proposed. Mortality among such patients was reduced.

Efficacy of FDA-Approved Hemostatic Drugs to Improve Survival and Reduce Bleeding in Rat Models of Uncontrolled Hemorrhage

DTIC Science & Technology

2005-07-01

drugs are used to reduce surgical bleeding. This series of studies tested whether these drugs (aprotinin, desmopressin, tranexamic acid , e- aminocaproic ...desmopressin, tranexamic acid , 8- aminocaproic acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats... acid ) could reduce bleeding due to traumatic injuries in two models of uncontrolled hemorrhage in rats. In the first phase of each study, a lethal

Extrudable Gel-Forming Bioabsorbable Hemostatic Tissue Adhesives for Traumatic and Burn Wounds

DTIC Science & Technology

1997-07-01

and Bum Wounds DAMD17-96-1-6241 6. AUTHOR(S) Shalaby, Shalaby W., Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS( ES ) S. PERFORMING ORGANIZATION...REPORT NUMBER Poly-Med, Incorporated Anderson, South Carolina 29625 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS( ES ) 10.SPONSORING I...five test strips as shown in Figure 1, and the dimensions of each sample was measured. The healed incision strength was measured using a Satec T10000

An Investigation of the Posterior Component of Occlusal Force

DTIC Science & Technology

1994-05-01

of the hemostat allowed subjects to consistently orient the bite force transducer parallel to the occIusal plane , thus allowing the bite force to be...the anterior component of occlusal force was influenced by the steepness of the occlusal plane . Southard et al (1989) was the first to quantify the...young adult males yielded higher mean maximum bite forces at 20 mm opening and at 40 mm opening. The authors suggested that orientation and function of

Experience with the Use of Hemopure in the Care of a Massively Burned Adult

DTIC Science & Technology

2014-03-01

transfusion. They did consent to the use of human albumin and hemostatic adjuncts including tranexamic acid and recombinant fac- tor VII. Adjuncts to...adverse events occurred during the infusion of HBOC- 201 and he remained normotensive. Ascorbic acid was administered intravenously at a dose of 500 mg...obtaining the drug should be initiated as soon as possible. During infusion, ascorbic acid should be given to keep HBOC in a reduced state and to

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus.

PubMed

Arslan, Fatma Demet; Serdar, Muhittin; Merve Ari, Elif; Onur Oztan, Mustafa; Hikmet Kozcu, Sureyya; Tarhan, Huseyin; Cakmak, Ozgur; Zeytinli, Merve; Yasar Ellidag, Hamit

2016-06-01

In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges.

Potentially life-threatening coagulopathy associated with simultaneous reduction in coagulation and fibrinolytic function in pediatric acute leukemia after hematopoietic stem-cell transplantation.

PubMed

Ishihara, Takashi; Nogami, Keiji; Matsumoto, Tomoko; Nomura, Akitaka; Takeshita, Yasufumi; Ochi, Satoshi; Shima, Midori

2017-07-01

The pathogenesis of sinusoidal obstruction syndrome (SOS) and thrombotic microangiopathy (TMA) after hematopoietic stem cell transplantation (HSCT) is poorly understood, and limited information is available on global hemostatic function in HSCT. We assessed changes in coagulation and fibrinolysis using a simultaneous thrombin and plasmin generation assay (T/P-GA) during HSCT. Measurements of endogenous thrombin potential (T-EP) and plasmin peak height (P-Peak) using T/P-GA in six pediatric acute leukemia patients treated with HSCT were compared to normal plasma. In the SOS case, the ratios of T-EP and P-Peak to normal were simultaneously decreased at four weeks post-HSCT (Pre; ~1.1/1.1-1.4, Week+4; 0.14/0.0084, respectively). Similarly, in the TMA patient, both ratios were decreased at 3 weeks and recovered after 8 weeks (Pre; 1.2/~0.95, Week+3; 0.59/0.22, Week+8; 1.2/0.64-0.85). In the other patients, when SOS/TMA was not evident, the T/P-GA data remained within normal limits. These findings suggest that the simultaneous reduction of coagulation and fibrinolytic function in patients developing SOS/TMA can lead to a life-threatening coagulopathy. Further research is warranted to clarify global hemostatic function after HSCT to establish optimal supportive therapy for these critical clinical disorders of hemostasis.

CLONING, EXPRESSION, AND HEMOSTATIC ACTIVITIES OF A DISINTEGRIN, r-MOJASTIN 1, FROM THE MOHAVE RATTLESNAKE (Crotalus scutulatus scutulatus)

PubMed Central

Sánchez, Elda E.; Lucena, Sara E.; Reyes, Steven; Soto, Julio G.; Cantu, Esteban; Lopez-Johnston, Juan Carlos; Guerrero, Belsy; Salazar, Ana Maria; Rodríguez-Acosta, Alexis; Galán, Jacob A.; Tao, W. Andy; Pérez, John C.

2012-01-01

Interactions with exposed subendothelial extracellular proteins and cellular integrins (endothelial cells, platelets and lymphocytes) can cause alterations in the hemostatic system associated with atherothrombotic processes. Many molecules found in snake venoms induce pathophysiological changes in humans, cause edema, hemorrhage, and necrosis. Disintegrins are low molecular weight, non-enzymatic proteins found in snake venom that mediate changes by binding to integrins of platelets or other cells and prevent binding of the natural ligands such as fibrinogen, fibronectin or vitronectin. Disintegrins are of great biomedical importance due to their binding affinities resulting in the inhibition of platelet aggregation, adhesion of cancer cells, and induction of signal transduction pathways. RT-PCR was used to obtain a 216 bp disintegrin cDNA from a C. s. scutulatus snake venom gland. The cloned recombinant disintegrin called r-mojastin 1 codes for 71 amino acids, including 12 cysteines, and an RGD binding motif. r-Mojastin 1 inhibited platelet adhesion to fibronectin with an IC50 of 58.3 nM and ADP-induced platelet aggregation in whole blood with an IC50 of 46 nM. r-Mojastin 1 was also tested for its ability to inhibit platelet ATP release using PRP resulting with an IC50 of 95.6 nM. MALDI-TOF mass spectrum analysis showed that r-mojastin has a mass of 7.9509 kDa. PMID:20598348

Pharmacokinetic and hemostatic properties of the recombinant plasminogen activator bm 06.022 in healthy volunteers.

PubMed

Martin, U; von Möllendorff, E; Akpan, W; Kientsch-Engel, R; Kaufmann, B; Neugebauer, G

1991-11-01

In a randomized, single-blind, placebo-controlled, cross-over Phase-I study pharmacokinetic and hemostatic properties of BM 06.022 were investigated in seven healthy, male human volunteers. The novel recombinant plasminogen activator BM 06.022 consists of the kringle 2 domain and the protease domain of human t-PA and is unglycosylated due to its expression in Escherichia coli cells. Vehicle or 6 MU (= 10.4 mg) BM 06.022 was administered as a single i.v. bolus injection of 10 ml over 2 min. BM 06.022 was well tolerated. Fibrinogen levels and clotting times remained unchanged at baseline levels after 6 MU BM 06.022; plasminogen and alpha 2-antiplasmin (collected on chloromethylketone) decreased maximally to 83 +/- 1% and 64 +/- 3%, respectively, of baseline. D-dimers and fibrinogen degradation products increased to 1,006 +/- 234 ng/ml and 555 +/- 155 ng/ml, respectively, after BM 06.022. Half-life of BM 06.022-activity was 11.2 +/- 0.4 min and of antigen was 13.9 +/- 0.7 min, followed by a terminal half-life only for antigen of 173 +/- 33 min. Plasma clearance of BM 06.022 was 371 +/- 13 ml/min for activity and 183 +/- 15 ml/min for antigen. Thus, BM 06.022 is not fibrinogenolytic at 6 MU and is a fibrinolytic agent with a longer half-life than t-PA.

Polycystic ovary syndrome: cardiovascular risk factors according to specific phenotypes.

PubMed

Aziz, Mubeena; Sidelmann, Johannes J; Faber, Jens; Wissing, Marie-Louise M; Naver, Klara V; Mikkelsen, Anne-Lis; Nilas, Lisbeth; Skouby, Sven O

2015-10-01

Polycystic ovary syndrome (PCOS) is associated with obesity and insulin resistance. The objective of this cross-sectional study was to investigate the impact of insulin resistance and body mass index (BMI) on inflammatory and hemostatic variables associated with long-term risk of cardiovascular disease in women with PCOS. 149 premenopausal women with PCOS were recruited consecutively from April 2010 to February 2012 at three Danish University Hospitals. The study was conducted at the Department of Gynecology and Obstetrics, Herlev University Hospital, Denmark. PCOS was diagnosed in accordance with the Rotterdam criteria and the women were classified into four phenotypes according to BMI and insulin resistance measured by the homeostasis model assessment of insulin resistance index. Body composition was determined by dual-energy X-ray absorptiometry. Main outcome measures were the biomarkers C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor antigen. Normal weight insulin-resistant PCOS women were characterized by abdominal obesity and elevated levels of plasma PAI-1. Overweight/obese insulin-resistant PCOS women had increased levels of both PAI-1 and CRP. Of the three Rotterdam criteria, only hyperandrogenemia was significantly associated with the hemostatic risk marker of long-term cardiovascular disease risk. Surrogate risk markers for cardiovascular disease are elevated in women with PCOS, especially insulin-resistant and overweight/obese women. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

First In Vivo Results of a Novel Pediatric Oxygenator with an Integrated Pulsatile Pump.

PubMed

Stang, Katharina; Borchardt, Ralf; Neumann, Bernd; Kurz, Julia; Stoppelkamp, Sandra; Greiner, Tim O; Fahrner, Christine; Schenk, Martin; Schlensak, Christian; Schubert, Maria; Lausberg, Henning; Herold, Sabine; Schlanstein, Peter C; Steinseifer, Ulrich; Arens, Jutta; Wendel, Hans-Peter

2015-01-01

Extracorporeal membrane oxygenation (ECMO) is a pivotal bridge to recovery for cardiopulmonary failure in children. Besides its life-saving quality, it is often associated with severe system-related complications, such as hemolysis, inflammation, and thromboembolism. Novel oxygenator and pump systems may reduce such ECMO-related complications. The ExMeTrA oxygenator is a newly designed pediatric oxygenator with an integrated pulsatile pump minimizing the priming volume and reducing the surface area of blood contact. The aim of our study was to investigate the feasibility and safety of this new ExMeTrA (expansion mediated transport and accumulation) oxygenator in an animal model. During 6 h of extracorporeal circulation (ECC) in pigs, parameters of the hemostatic system including coagulation, platelets and complement activation, and flow rates were investigated. A nonsignificant trend in C3 consumption, thrombin-antithrombin-III (TAT) complex formation and a slight trend in hemolysis were detected. During the ECC, the blood flow was constantly at 500 ml/min using only flexible silicone tubes inside the oxygenator as pulsatile pump. Our data clearly indicate that the hemostatic markers were only slightly influenced by the ExMeTrA oxygenator. Additionally, the oxygenator showed a constant quality of blood flow. Therefore, this novel pediatric oxygenator shows the potential to be used in pediatric and neonatal support with ECMO.

von Willebrand factor, Jedi knight of the bloodstream.

PubMed

Springer, Timothy A

2014-08-28

When blood vessels are cut, the forces in the bloodstream increase and change character. The dark side of these forces causes hemorrhage and death. However, von Willebrand factor (VWF), with help from our circulatory system and platelets, harnesses the same forces to form a hemostatic plug. Force and VWF function are so closely intertwined that, like members of the Jedi Order in the movie Star Wars who learn to use "the Force" to do good, VWF may be considered the Jedi knight of the bloodstream. The long length of VWF enables responsiveness to flow. The shape of VWF is predicted to alter from irregularly coiled to extended thread-like in the transition from shear to elongational flow at sites of hemostasis and thrombosis. Elongational force propagated through the length of VWF in its thread-like shape exposes its monomers for multimeric binding to platelets and subendothelium and likely also increases affinity of the A1 domain for platelets. Specialized domains concatenate and compact VWF during biosynthesis. A2 domain unfolding by hydrodynamic force enables postsecretion regulation of VWF length. Mutations in VWF in von Willebrand disease contribute to and are illuminated by VWF biology. I attempt to integrate classic studies on the physiology of hemostatic plug formation into modern molecular understanding, and point out what remains to be learned. © 2014 by The American Society of Hematology.

Plasma markers of inflammation and hemostatic and endothelial activity in naturally overweight and obese dogs.

PubMed

Barić Rafaj, R; Kuleš, J; Marinculić, A; Tvarijonaviciute, A; Ceron, J; Mihaljević, Ž; Tumpa, A; Mrljak, V

2017-01-06

Obesity is one of the most prevalent health problems in the canine population. While haemostatic parameters and markers of endothelial function have been evaluated in various disease conditions in dogs, there are no studies of these markers in canine obesity. This study was designed to evaluate the effect of naturally gained weight excess and obesity on inflammatory, hemostatic and endothelial biomarkers in dogs. A total of 37 overweight and obese dogs were compared with 28 normal weight dogs. Overweight and obese dogs had significantly elevated concentrations of serum interleukin-6 (IL-6) and C-reactive protein (hsCRP). Number of platelets, activity of factor X and factor VII were significantly higher, while activated partial thromboplastine time (aPTT) and soluble plasminogen activator receptor (suPAR) were significantly decreased. Statistical analysis of high mobility group box - 1 protein (HMGB-1), soluble intercellular adhesive molecule -1 (sICAM-1) and plasminogen activator inhibitor type 1 (PAI-1) concentrations did not show significant differences between the total overweight and obese group and the normal weight group of dogs. Analytical changes in the dogs in our study reflects that weight excess in dogs can be associated with a chronic low degree of inflammation and a hypercoagulable state, where primary and secondary hemostasis are both affected. However obesity is not associated with impairment of endothelial function in dogs.

Identifying novel genetic determinants of hemostatic balance.

PubMed

Ginsburg, D

2005-08-01

Incomplete penetrance and variable expressivity confound the diagnosis and therapy of most inherited thrombotic and hemorrhagic disorders. For many of these diseases, some or most of this variability is determined by genetic modifiers distinct from the primary disease gene itself. Clues toward identifying such modifier genes may come from studying rare Mendelian disorders of hemostasis. Examples include identification of the cause of combined factor V and VIII deficiency as mutations in the ER Golgi intermediate compartment proteins LMAN1 and MCFD2. These proteins form a cargo receptor that facilitates the transport of factors V and VIII, and presumably other proteins, from the ER to the Golgi. A similar positional cloning approach identified ADAMTS-13 as the gene responsible for familial TTP. Along with the work of many other groups, these findings identified VWF proteolysis by ADAMTS-13 as a key regulatory pathway for hemostasis. Recent advances in mouse genetics also provide powerful tools for the identification of novel genes contributing to hemostatic balance. Genetic studies of inbred mouse lines with unusually high and unusually low plasma VWF levels identified polymorphic variation in the expression of a glycosyltransferase gene, Galgt2, as an important determinant of plasma VWF levels in the mouse. Ongoing studies in mice genetically engineered to carry the factor V Leiden mutation may similarly identify novel genes contributing to thrombosis risk in humans.

Comparing the Effect of 3 Kinds of Different Materials on the Hemostasis of the Central Venous Catheter

NASA Astrophysics Data System (ADS)

Li, Yan-Ming; Liang, Zhen-Zhen; Song, Chun-Lei

2016-05-01

To compare the effect of 3 kinds of different materials on the hemostasis of puncture site after central venous catheterization. Method: A selection of 120 patients with peripheral central venous catheter chemotherapy in the Affiliated Hospital of our university from January 2014 to April 2015, Randomly divided into 3 groups, using the same specification (3.5cm × 2cm) alginate gelatin sponge and gauze dressing, 3 kinds of material compression puncture point, 3 groups of patients after puncture 24 h within the puncture point of local blood and the catheter after the catheter 72 h within the catheter maintenance costs. Result: (1) The local infiltration of the puncture point in the 24 h tube: The use of alginate dressing and gelatin sponge hemostatic effect is better than that of compression gauze. The difference was statistically significant (P <0.05). Compared with gelatin sponge and alginate dressing hemostatic effect, The difference was not statistically significant. (2) Tube maintenance cost: Puncture point using gelatin sponge, The local maintenance costs of the catheter within 72 h after insertion of the tube are lowest, compared with alginate dressing and gauze was significant (P<0.05). Conclusion: The choice of compression hemostasis material for the puncture site after PICC implantation, using gelatin sponge and gauze dressing is more effective and economic.

Splenic artery embolization with Ankaferd blood stopper in a sheep model

PubMed Central

Koç, Osman; Acar, Kadir; Özbek, Orhan; Güler, İbrahim; Sarıtaş, Kadir; Erdem, Tuba Bera; Solak, Yalçın; Toy, Hatice; Küçükapan, Ahmet; Özbek, Seda; Gaipov, Abduzhappar; Haznedaroğlu, İbrahim C.

2016-01-01

PURPOSE Splenic artery embolization is a minimally invasive therapeutic procedure utilized in a number of disorders. Ankaferd blood stopper (ABS) is a novel hemostatic agent with a new mechanism of action independent of clotting factors. We aimed to investigate the safety and efficiency of ABS for splenic artery embolization in a sheep model. METHODS Seven adult female sheep were included in the study. Selective celiac angiography was performed using a 5F diagnostic catheter and then a 2.7F hydrophilic coating microcatheter was advanced coaxially to the distal part of the main splenic artery. Under fluoroscopic guidance, 6 mL mixture composed of half-and-half ABS and contrast agent was slowly injected. Fluoroscopy was used to observe the deceleration and stagnation of the flow. Control celiac angiograms were obtained immediately after the embolization. After the procedure, the animals were observed for one day and then sacrificed with intravenous sodium thiopental. RESULTS Technical success rate was 100%. None of the animals died or experienced a major systemic adverse event during the procedure. All of the spleens appeared dark on macroscopic examination due to excessive thrombosis. Microscopically, the majority of the splenic sinusoids (90%–95%) were necrotic. CONCLUSION In our study, splenic artery embolization by ABS was found to be safe and effective in the shortterm. Further studies are needed to better understand the embolizing potential of this novel hemostatic agent. PMID:27306661

Hemostatic powder TC-325 in the management of upper and lower gastrointestinal bleeding: a two-year experience at a single institution.

PubMed

Chen, Yen-I; Barkun, Alan; Nolan, Sabrina

2015-02-01

TC-325 is a novel endoscopic hemostatic powder. Our aim was to describe a single-center experience with the use of TC-325 in the upper and lower gastrointestinal tract, while for the first time attempting to determine how long the powder remains on a lesion. The charts of consecutive patients receiving TC-325 therapy between July 2011 and July 2013 were reviewed retrospectively. Primary endpoints included immediate hemostasis and early rebleeding (≤ 72 hours). Overall, 60 patients received 67 treatments with TC-325: 21 for nonmalignant nonvariceal upper gastrointestinal bleeding, 19 for malignant upper gastrointestinal bleeding, 11 for lower gastrointestinal bleeding, and 16 for intra-procedural bleeding. Immediate hemostasis was achieved in 66 cases (98.5 %), with 6 cases (9.5 %) of early rebleeding. No serious adverse events were noted. No TC-325 powder was identified in the 11 patients who underwent second-look endoscopy, performed within 24 hours in 4 patients. TC-325 appears safe and effective for managing bleeding in the upper and lower gastrointestinal tract with a variety of causes. The time during which the powder remains in the gastrointestinal tract is short, with complete elimination from the gastrointestinal tract as early as within 24 hours after use. © Georg Thieme Verlag KG Stuttgart · New York.

Use of Gelatin Sponge Affects Postoperative Morbidity In Cesarean Section Patients.

PubMed

Özer, Alev; Köstü, Bülent

2017-03-04

BACKGROUND This study aimed to determine the effects of use of a local hemostatic gelatin sponge (GS) on postoperative morbidity in patients undergoing cesarean section (CS). MATERIAL AND METHODS The records of 318 patients who underwent CS surgery were retrospectively evaluated. Group 1 consisted of 59 patients with gelatin sponge (GS) applied, and Group 2 consisted of 259 patients with no GS applied. The groups were compared for time to the first flatus, nausea and vomiting, requirement for anti-emetic drugs, development of postoperative ileus, and the length of hospitalization. RESULTS The patients in Group 1 and Group 2 were statistically similar in mean age, gravida, parity, and body mass index (BMI) (p=0.352, p=0.275, p=0.458, and p=0.814, respectively). No significant difference was determined in the number of patients with nausea, vomiting, anti-emetic drug use, febrile morbidity, and postoperative ileus (p=0.063, p=0.436, p=328, p=0.632, and p=0.179, respectively). Time to the first flatus and length of hospitalization were significantly longer in Group 2 (p<0.001 and p<0.001, respectively). CONCLUSIONS Delay in recovery of bowel motility may be due to the local hypersensitivity reaction caused by GS and/or dislocation of this local hemostat. Women who receive gelatin sponge treatment during CS should be monitored closely for the recovery of postoperative intestinal motility.

Comparison between self-assembling peptide nanofiber scaffold (SAPNS) and fibrin sealant in neurosurgical hemostasis.

PubMed

Xu, Fei-Fan; Wang, Yue-Chun; Sun, Stella; Ho, Amy S W; Lee, Derek; Kiang, Karrie M Y; Zhang, Xiao-Qin; Lui, Wai-Man; Liu, Bai-Yun; Wu, Wu-Tian; Leung, Gilberto K K

2015-10-01

RADA16-I is a synthetic type I self-assembling peptide nanofiber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16-I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke inflammation in the surgically injured brain. We conducted an animal study to compare RADA16-I with fibrin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague-Dawley rats were randomized into three treatment groups: RADA16-I, fibrin sealant or gelatin sponge (control). Animals were sacrificed on day 3 and 42. Astrocytic and microglial infiltrations within the cerebral parenchyma adjacent to the operative site were significantly lower in the RADA16-I and fibrin sealant groups than control. RADA16-I did not cause more cellular inflammatory response despite its acidity when compared with fibrin sealant. Immunohistochemical studies showed infiltration by astrocytes and microglia into the fibrin sealant and RADA16-I grafts, suggesting their potential uses as tissue scaffolds. RADA16-I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofiber scaffold as well as drug and cell carrier. © 2015 Wiley Periodicals, Inc.

Blood conservation strategies to reduce the need for red blood cell transfusion in critically ill patients

PubMed Central

Tinmouth, Alan T.; McIntyre, Lauralynn A.; Fowler, Robert A.

2008-01-01

Anemia commonly affects critically ill patients. The causes are multifactorial and include acute blood loss, blood loss from diagnostic testing and blunted red blood cell production. Blood transfusions are frequently given to patients in intensive care units to treat low hemoglobin levels due to either acute blood loss or subacute anemia associated with critical illness. Although blood transfusion is a life-saving therapy, evidence suggests that it may be associated with an increased risk of morbidity and mortality. A number of blood conservation strategies exist that may mitigate anemia in hospital patients and limit the need for transfusion. These strategies include the use of hemostatic agents, hemoglobin substitutes and blood salvage techniques, the reduction of blood loss associated with diagnostic testing, the use of erythropoietin and the use of restrictive blood transfusion triggers. Strategies to reduce blood loss associated with diagnostic testing and the use of hemostatic agents and erythropoietin result in higher hemoglobin levels, but they have not been shown to reduce the need for blood transfusions or to improve clinical outcomes. Lowering the hemoglobin threshold at which blood is transfused will reduce the need for transfusions and is not associated with increased morbidity or mortality among most critically ill patients without active cardiac disease. Further research is needed to determine the potential roles for other blood conservation strategies. PMID:18166731

Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

DTIC Science & Technology

2012-12-15

and its correction (or normalization of pH) has been suggested before clinical use of rFVIIa [21, 22]. FVII is one of the many coagulation factors ...A or B (deficient in Factor VIII and Factor IX). Mice lacking FVII die in-utero or soon after birth due to vascular and hemostatic defects [23...the activity of recombinant activated Factor VII (rFVIIa) in vitro. However, it is not known if acidosis induced by hemorrhagic shock or infusion of

Clot-Inducing Minerals Versus Plasma Protein Dressing for Topical Treatment of External Bleeding in the Presence of Coagulopathy

DTIC Science & Technology

2010-11-01

results using human blood samples.14–16 Therefore, this study was performed to analyze the hemostatic efficacy of WS in coagulopathic subjects and to... zeolite ). Smectite is used in industries as filler in paints and rubber products and as a sealer and plasticizer in civil engineering for tunnel...180 minutes or until death. Angiography using the computed tomography method was performed on survivors, and local tissues were collected for

Effect of android fat distribution on thrombin-activatable fibrinolysis inhibitor levels in women with polycystic ovary syndrome.

PubMed

Mendonça-Louzeiro, Maria R M F; Andrade, Kleber C; Yela, Daniela A; Benetti-Pinto, Cristina L

2018-06-21

Women with polycystic ovary syndrome (PCOS) often present with thromboembolic risk factors, such as obesity, hyperandrogenism, and insulin resistance [1]. Furthermore, some PCOS-related metabolic abnormalities represent cardiovascular risk factors. We aimed to assess the association between hemostatic parameters and clinical and dual-energy X-ray absorptiometry (DXA) measurements of fat distribution in these women. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The Effect of a Third Generation Hemostatic Dressing in a Subclavian Artery and Vein Transection Porcine Model

DTIC Science & Technology

2014-04-01

The MSD is comprised of a syringe applicator filled with compressed chitosan coated sponges which are delivered into the wound at the site of the...transmitted effectively to the deep subclavian vessels to stop hemorrhage. As a result of their non-compressible nature and paucity of effective field...followed by three minutes of compression to the packed dressing. The mini- sponge dressing (MSD) is a novel product that utilizes compressed, chitosan

Is Limited Prehospital Resuscitation with Plasma More Beneficial than Using a Synthetic Colloid? An Experimental Study in Rabbits with Parenchymal Bleeding

DTIC Science & Technology

2015-04-01

pediatric TBI patients.36,37 The albumin solution used in this rabbit study was a 5% human albumin (Albminar) in an isotonic solution ( normal saline ... reconstituted easily at the point of injury and injected . Hemostatic properties and bene- fits of FDP or sprayed-dried plasma have been demonstrated...rabbit albumin solution appro- priate for intravenous injection is not commercially available. Rabbit albumin is sold by chemical companies as

The Use of Fresh Whole Blood Transfusions by the SOF Medic for Hemostatic Resuscitation in the Austere Environment

DTIC Science & Technology

2010-11-24

training and safety measures, WFWB transfu- sions can be that tool. Shipment of whole blood collected from rear echelon troops in the ETO , December 1944...Operations. ( ETO ) WWII. (U.S. AMEDD Office of Medical History) Journal of Special Operations Medicine Volume 10, Edition 3 / Summer 1030 Whole blood...27. 5. Brohi, K ., Singh, J., et al. (2003). Acute traumatic coagulo- pathy. Journal of Trauma; 54:1127-1130. 6. Borgman, M. A., Spinella

Povidone-iodine and hydrogen peroxide mixture soaked gauze pack: a novel hemostatic technique.

PubMed

Arakeri, Gururaj; Brennan, Peter A

2013-11-01

Persistent oozing of blood is a common occurrence in maxillofacial surgery, and occasionally it hampers visibility and delays or even prevents continuation of the procedure. This report describes a novel method of controlling blood ooze using swabs soaked with povidone-iodine and hydrogen peroxide (PI-HP pack) that is particularly useful in relatively inaccessible areas of the maxillofacial region. Copyright © 2013 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Thromboelastography as a Better Indicator of Postinjury Hypercoagulable State Than Prothrombin Time or Activated Partial Thromboplastin Time

DTIC Science & Technology

2009-08-01

trauma 53 Yes 9 Acute desaturation and lung consolidation Abbreviation: DVT, deep venous thrombosis. a All patients were men. All had pulmonary embolism. J Trauma. Author manuscript; available in PMC 2012 August 09. ...pulmonary embolism indicated that our current prophylaxis regimen could be improved. Keywords deep vein thrombosis; pulmonary embolism...important to accurately evaluate an injured patient’s hemostatic status to assess the need for and efficacy of deep vein thrombosis (DVT) prophylaxis

Neutralization of Lethality and Proteolytic Activities of Malayan Pit Viper (Calloselasma rhodostoma) Venom with North American Virginia Opossum (Didelphis virginiana) Serum

PubMed Central

Pornmanee, Piboon; Sánchez, Elda E.; López, Gonzalo; Petsom, Amorn; Khow, Orawan; Pakmanee, Narumol; Chanhome, Lawan; Sangvanich, Polkit; Pérez, John C.

2012-01-01

Malayan pit viper (Calloselasma rhodostoma) envenomation is a major health problem in South East Asia. During envenomation, venom components mainly affect the hemostatic system. The sera from the North American Virginia opossums (Didelphis virginiana) were able to neutralize the venom of the Malayan pit viper. These natural inhibitors could be explored as potential therapeutics against envenomations of a variety of venomous snake species in different geographical habitats. PMID:18617212

Technologies for Hemostasis and Stabilization of the Acute Traumatic Wound

DTIC Science & Technology

2012-10-01

Fibrinogen Produced in the Milk of Transgenic Cows ” (see abstract in Appendix A10). 4. A poster presentation “Development of Novel Hemostatic Devices in...biosynthesis and material characterization of rFI made in the milk of cloned, transgenic dairy cows . To our knowledge, rFI is one of the most challenging...rFI was purified from 32 liters of milk collected on eight lactation days from two transgenic cows (Foxy and Fantasy) of the BFI2n8c83-EGFIneo

Hemostatic Function of Apheresis Platelets Stored at 4 deg C and 22 deg C

DTIC Science & Technology

2014-05-01

utilized. Thromboxane B2 (TxB2) enzyme immunoassay kits were purchased from Cayman Chemicals (Ann Arbor, MI), and human soluble CD40L (sCD40L) extra...sensitive platinum enzyme linked immunosorbent assay kits were pur chased from eBioscience (Vienna, Austria). CG4+ and CHEM8+ cartridges were purchased from...TruCount tubes (BD Biosciences). Enzyme linked immunosorbent assay Commercially available kits were used to assess sCD40L and TxB2 levels released into

Percutaneous BioOrganic Sealing of Duodenal Fistulas: Case Report and Review of Biological Sealants with Potential Use in Interventional Radiology

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

Wadhwa, Vibhor, E-mail: vwadhwa1@jhmi.edu; Leeper, William R., E-mail: rob.leeper@jhmi.edu; Tamrazi, Anobel, E-mail: atamraz1@jhmi.edu

2015-08-15

Biological sealants are being increasingly used in a variety of surgical specialties for their hemostatic and sealing capabilities. However, their use in interventional radiology has not been widely reported. The authors describe a case of duodenal perforation occurring after 15 years of gastric bypass surgery, in whom surgical diversion was unsuccessfully attempted and the leakage was successfully controlled using percutaneous administration of a combination of biological and organic sealants.

Determination of Age-Dependent Reference Ranges for Coagulation Tests Performed Using Destiny Plus

PubMed Central

Arslan, Fatma Demet; Serdar, Muhittin; Merve Ari, Elif; Onur Oztan, Mustafa; Hikmet Kozcu, Sureyya; Tarhan, Huseyin; Cakmak, Ozgur; Zeytinli, Merve; Yasar Ellidag, Hamit

2016-01-01

Background In order to apply the right treatment for hemostatic disorders in pediatric patients, laboratory data should be interpreted with age-appropriate reference ranges. Objectives The purpose of this study was to determining age-dependent reference range values for prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen tests, and D-dimer tests. Materials and Methods A total of 320 volunteers were included in the study with the following ages: 1 month - 1 year (n = 52), 2 - 5 years (n = 50), 6 - 10 years (n = 48), 11 - 17 years (n = 38), and 18 - 65 years (n = 132). Each volunteer completed a survey to exclude hemostatic system disorder. Using a nonparametric method, the lower and upper limits, including 95% distribution and 90% confidence intervals, were calculated. Results No statistically significant differences were found between PT and aPTT values in the groups consisting of children. Thus, the reference ranges were separated into child and adult age groups. PT and aPTT values were significantly higher in the children than in the adults. Fibrinogen values in the 6 - 10 age group and the adult age group were significantly higher than in the other groups. D-dimer levels were significantly lower in those aged 2 - 17; thus, a separate reference range was established. Conclusions These results support other findings related to developmental hemostasis, confirming that adult and pediatric age groups should be evaluated using different reference ranges. PMID:27617078

Hepatic arterial embolization in the management of blunt hepatic trauma: indications and complications.

PubMed

Letoublon, Christian; Morra, Irene; Chen, Yao; Monnin, Valerie; Voirin, David; Arvieux, Catherine

2011-05-01

The objective was to clarify the role of hepatic arterial embolization (AE) in the management of blunt hepatic trauma. Retrospective observational study of 183 patients with blunt hepatic trauma admitted to a trauma referral center over a 9-year period. The charts of 29 patients (16%) who underwent hepatic angiography were reviewed for demographics, injury specific data, management strategy, angiographic indication, efficacy and complications of embolization, and outcome. AE was performed in 23 (79%) of the patients requiring angiography. Thirteen patients managed conservatively underwent emergency embolization after preliminary computed tomography scan. Six had postoperative embolization after damage control laparotomy and four had delayed embolization. Arterial bleeding was controlled in all the cases. Sixteen patients (70%) had one or more liver-related complications; temporary biliary leak (n=11), intra-abdominal hypertension (n=14), inflammatory peritonitis (n=3), hepatic necrosis (n=3), gallbladder infarction (n=2), and compressive subcapsular hematoma (n=1). Unrecognized hepatic necrosis could have contributed to the late posttraumatic death of one patient. AE is a key element in modern management of high-grade liver injuries. Two principal indications exist in the acute postinjury phase: primary hemostatic control in hemodynamically stable or stabilized patients with radiologic computed tomography evidence of active arterial bleeding and adjunctive hemostatic control in patients with uncontrolled suspected arterial bleeding despite emergency laparotomy. Successful management of injuries of grade III upward often entails a combined angiographic and surgical approach. Awareness of the ischemic complications due to angioembolization is important.

Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption.

PubMed

Lockwood, C J; Paidas, M; Murk, W K; Kayisli, U A; Gopinath, A; Huang, S J; Krikun, G; Schatz, F

2009-11-01

Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Among the cell types at the maternal fetal interface at term, TF expression is highest in decidual cells indicating that this TF meets the hemostatic demands of labor and delivery. TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggesting that the maintenance of elevated circulating progesterone provides hemostatic protection and that abruption-generated thrombin acts in an autocrine/paracrine fashion on decidual cells to promote hemostasis via enhanced TF expression.

Laboratory hemostasis: from biology to the bench.

PubMed

Lippi, Giuseppe; Favaloro, Emmanuel J

2018-06-27

Physiological hemostasis is an intricate biological system, where procoagulant and anticoagulant forces interplay and preserves blood fluidity when blood vessels are intact, or trigger clot formation to prevent excessive bleeding when blood vessels are injured. The modern model of hemostasis is divided into two principal phases. The first, defined as primary hemostasis, involves the platelet-vessel interplay, whilst the second, defined as secondary hemostasis, mainly involves coagulation factors, damaged cells and platelet surfaces, where the so-called coagulation cascade rapidly develops. The activation and amplification of the coagulation cascade is finely modulated by the activity of several physiological inhibitors. Once bleeding has been efficiently stopped by blood clot formation, dissolution of the thrombus is essential to restore vessel permeability. This process, known as fibrinolysis, also develops through coordinate action of a vast array of proteins and enzymes. An accurate diagnosis of hemostasis disturbance entails a multifaceted approach, encompassing family and personal history of hemostatic disorders, accurate collection of clinical signs and symptoms, integrated with laboratory hemostasis testing. Regarding laboratory testing, a reasonable approach entails classifying hemostasis testing according to cost, complexity and available clinical information. Laboratory workout may hence initiate with some rapid and inexpensive "screening" tests, characterized by high negative predictive value, then followed by second- or third-line analyses, specifically aimed to clarify the nature and severity of bleeding or thrombotic phenotype. This article aims to provide a general overview of the hemostatic process, and to provide some general suggestions to optimally facilitate laboratory hemostasis testing.

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.

Preliminary study of the effects of smectite granules (WoundStat) on vascular repair and wound healing in a swine survival model.

PubMed

Gerlach, Travis; Grayson, J Kevin; Pichakron, Kullada O; Sena, Matthew J; DeMartini, Steven D; Clark, Beth Z; Estep, J Scot; Zierold, Dustin

2010-11-01

WoundStat (WS) (TraumaCure, Bethesda, MD) is a topical hemostatic agent that effectively stops severe hemorrhage in animal models. To the best of our knowledge, no survival study has been conducted to ensure long-term product safety. We evaluated vascular patency and tissue responses to WS in a swine femoral artery injury model with survival up to 5 weeks. Anesthetized swine received a standardized femoral artery injury with free hemorrhage for 45 seconds followed by WS application. One hour after application, the WS was removed, the wound copiously irrigated, and the artery repaired using a vein patch. Six groups of three animals received WS and were killed either immediately after surgery or at weekly intervals up to 5 weeks. Three control animals were treated with gauze packing and direct pressure followed by identical vascular repair and survival for 1 week. At the time of killing, angiograms were performed, and tissue was collected for histopathology. Hemostasis was complete in all WS animals. All animals survived the procedure, and there were no clinically evident postoperative complications. Vascular repairs were angiographically patent in 15 of 18 animals (83%) receiving WS. Histopathologic examination of WS animals revealed severe diffuse fibrogranulomatous inflammation, early endothelial degeneration with subsequent intimal hyperplasia, moderate myocyte necrosis, and fibrogranulomatous nerve entrapment with axonal degeneration. Although an effective hemostatic agent, WS use was associated with a substantial local inflammatory response and neurovascular changes up to 5 weeks postinjury.

Safety Evaluation of New Hemostatic Agents, Smectite Granules, and Kaolin-Coated Gauze in a Vascular Injury Wound Model in Swine

DTIC Science & Technology

2010-02-01

risk of using WS when compared with kaolin-coated gauze, Combat Gauze (CG); or regular gauze, Kerlix (KX) to treat an external wound with vascular...communication with combat medics implied limited use or avoidance of these agents in the field because of either painful side effects (thermal injury with QC...potential thrombogenicity of WS and CG when they are used to control external bleeding due to major vascular injury. For this purpose, a new wound model was

[Peculiarities of laparoscopic diagnosis of the closed hepatic traumatic damage].

PubMed

Kapshitar', A A; Kapshitar', A V; Syrbu, I F

2008-01-01

Diagnostic possibilities of laparoscopy were studied in 24 injured persons, suffering closed hepatic damage in noninformity of results of clinical, laboratory-biochemical, roentgenologic, ultrasound investigations and diagnostic peritoneal lavage as well, were studied. Isolated trauma was revealed in 8 injured persons, the multiple one in 7 and the combined--in 9. Open operation was performed in 21 patients, relaparotomy--in 3, laparoscopic intervention with curative intent--in 3 hepatic wound tamponade, using hemostatic sponge with ambene, lubricated by dicinon. Three patients died due to severe combined trauma.

Endoscopic Management of Vascular Sinonasal Tumors, Including Angiofibroma.

PubMed

Snyderman, Carl H; Pant, Harshita

2016-06-01

The greatest challenge in the surgical treatment of angiofibromas is dealing with the hypervascularity of these tumors. Staging systems that take into account the vascularity of the tumor may be more prognostic. A variety of treatment strategies are used to deal with the vascularity of angiofibromas, including preoperative embolization, segmentation of the tumor into vascular territories, use of hemostatic tools, and staging of surgery. Even large angiofibromas with intracranial extension and residual vascularity can be successfully managed by a skull base team using endoscopic techniques. Copyright © 2016 Elsevier Inc. All rights reserved.

[The set of wearable medical equipment for medical and nursing teams].

PubMed

Efimenko, N a; Valevskii, V V; Lyutov, V V; Makhnovskii, A I; Sorokin, S I; Blinda, I V

2015-06-01

The kit is designed in accordance with the list of the first medical aid procedures and syndromic standards of emergency medical care providing. The kit contains modern local hemostatic agents, vent tubes, cricothyrotomy, needles to eliminate pneumothorax, portable oxygen machine, sets for intravenous and intraosseous infusion therapy, collapsible plastic tires, anti-shock pelvic girdle, and other medical products and pharmaceuticals. As containers used backpack and trolley bag on wheels camouflage colours. For the convenience and safety of the personnel of the vest is designed discharge to be converted in the body armour.

Comparison of Topical Hemostatic Agents in a Swine Model of Extremity Arterial Hemorrhage: BloodSTOP iX Battle Matrix vs. QuikClot Combat Gauze

DTIC Science & Technology

2016-04-12

sponge was immediately placed over the product, pressing against the wound with sufficient and equal pressure to try to stop blood loss. Resuscitation...intervals. Any shed blood and blood absorbed by the dressing or laparotomy sponge during this period was collected and measured as post-treatment blood...the hemostasis provided by Int. J. Mol. Sci. 2016, 17, 545 10 of 12 the test products. At the conclusion of these tests, the laparotomy sponge and

The TachoSil-Pledget stitch: towards eradication of suture hole bleeding.

PubMed

Shimamoto, Takeshi; Marui, Akira; Nishina, Takeshi; Saji, Yoshiaki; Komeda, Masashi

2008-12-01

We describe a novel suture consisting of a small piece of TachoSil (Nycomed, Copenhagen, Denmark) and a felt pledget-the TachoSil-pledget stitch-which was used to facilitate mechanical and biologic hemostasis in 5 patients undergoing aortic arch aneurysm repair. The TachoSil-pledget stitch achieved good or very good hemostasis at all 56 bleeding points to which it was applied, while 5 of 12 points to which a conventional felt-pledget stitch was applied required additional stitching or an additional hemostatic method.

Needleless Electrospinning of Pure and Blended Chitosan

NASA Astrophysics Data System (ADS)

Grimmelsmann, Nils; Homburg, Sarah Vanessa; Ehrmann, Andrea

2017-08-01

Chitosan is a biopolymer with bactericidal, fungicidal, hemostatic and other interesting properties. It can be used, e.g., in medical products, as a filter medium, in biotechnological purposes etc. For these possible applications, nanofiber mats with a large inner surface will be most efficient. This is why in a recent project, the electrospinning properties of pure chitosan as well as chitosan blended with poly(ethylene oxide) were investigated. Using a needleless nanospinning process, the technology under examination can be upscaled from lab to industrial scale, enabling direct transfer of the gained experiences to the intended application.

Evolving Complexity in Hemophilia Management.

PubMed

Croteau, Stacy E

2018-06-01

Rapid expansion of therapeutic options have increased the complexity of hemophilia care. Previously, on-demand therapy aimed to reduce morbidity and early mortality; however, now aggressive prophylaxis, particularly in children, encourages an active lifestyle. Accurate diagnosis, recognition of early threats to musculoskeletal health, and optimization of therapy are critical for both males and females affected by hemophilia. The diversity of emerging hemophilia therapies, from modified factor protein concentrates, to gene therapy, to nonfactor hemostatic strategies, provide an exciting opportunity to target unmet needs in the bleeding disorder community. Copyright © 2018 Elsevier Inc. All rights reserved.

Multicenter accuracy and interobserver agreement of spot sign identification in acute intracerebral hemorrhage.

PubMed

Huynh, Thien J; Flaherty, Matthew L; Gladstone, David J; Broderick, Joseph P; Demchuk, Andrew M; Dowlatshahi, Dar; Meretoja, Atte; Davis, Stephen M; Mitchell, Peter J; Tomlinson, George A; Chenkin, Jordan; Chia, Tze L; Symons, Sean P; Aviv, Richard I

2014-01-01

Rapid, accurate, and reliable identification of the computed tomography angiography spot sign is required to identify patients with intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to assess the accuracy and interobserver agreement for spot sign identification. A total of 131 neurology, emergency medicine, and neuroradiology staff and fellows underwent imaging certification for spot sign identification before enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for evaluation of spot sign presence, number, and mimics. True spot positivity was determined by consensus of 2 experienced neuroradiologists. Diagnostic performance, agreement, and differences by training level were analyzed. Mean accuracy, sensitivity, and specificity for spot sign identification were 87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity (P<0.001) because of true spot signs incorrectly perceived as spot mimics. Interobserver agreement for spot sign presence was moderate (k=0.60). When true spots were correctly identified, 81% correctly identified the presence of single or multiple spots. Median time needed to evaluate the presence of a spot sign was 1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance, interobserver agreement, and time needed for spot sign evaluation were similar among staff physicians and fellows. Accuracy for spot identification is high with opportunity for improvement in spot interpretation sensitivity and interobserver agreement particularly through greater reliance on computed tomography angiography source data and awareness of limitations of multiplanar images. Further prospective study is needed.

Involvement of human decidual cell-expressed tissue factor in uterine hemostasis and abruption

PubMed Central

Lockwood, C.J.; Paidas, M.; Murk, W.K.; Kayisli, U.A.; Gopinath, A.; Krikun, G.; Huang, S.J.; Schatz, F.

2009-01-01

Vascular injury increases access and binding of plasma-derived factor VII to perivascular cell membrane-bound tissue factor (TF). The resulting TF/VIIa complex promotes hemostasis by cleaving pro-thrombin to thrombin leading to the fibrin clot. In human pregnancy, decidual cell-expressed TF prevents decidual hemorrhage (abruption). During placentation, trophoblasts remodel decidual spiral arteries into high conductance vessels. Shallow trophoblast invasion impedes decidual vascular conversion, producing an inadequate uteroplacental blood flow that elicits abruption-related placental ischemia. Thrombin induces several biological effects via cell surface protease activated receptors. In first trimester human DCs thrombin increases synthesis of sFlt-1, which elicits placental ischemia by impeding angiogenesis-related decidual vascular remodeling. During pregnacy, the fibrillar collagen-rich amnion and choriodecidua extracellular matrix (ECM) provides greater than additive tensile strength and structural integrity. Thrombin acts as an autocrine/paracrine mediator that degrades these ECMs by augmenting decidual cell expression of: 1) matrix metalloproteinases and 2) interleukin-8, a key mediator of abruption-associated decidual infiltration of neutrophils, which express several ECM degrading proteases. Our recent observations that: 1) among the cell types at the maternal fetal interface at term TF expression is highest in decidual cells indicates that this TF meets the hemostatic demands of labor and delivery; 2) TF expression in cultured term decidual cells is enhanced by progestin and thrombin suggest that maintenance of elevated circulating progesterone at term provides hemostatic protection, whereas abruption-generated thrombin can act in autocrine/paracrine fashion on DCs to promote hemostasis via enhanced TF expression. PMID:19720393

Effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing surgery for fracture repair.

PubMed

Bergmann, Hannes M L; Nolte, Ingo J A; Kramer, Sabine

2005-08-01

To evaluate effects of preoperative administration of carprofen on renal function and hemostasis in dogs undergoing general anesthesia for fracture repair. 26 client-owned dogs. Anesthesia was induced with levomethadone, diazepam, and propofol and maintained by administration of isoflurane in oxygen-nitrous oxide. Carprofen (4 mg/kg, SC) was administered 1 hour before induction to 13 dogs (group 1) and after extubation to the other 13 dogs (group 2). All dogs also received carprofen (4 mg/kg, SC, q 24 h) for the first 4 days after surgery. Renal function (glomerular filtration rate [GFR], urinary protein-to-urinary creatinine ratio [UP:UC], and results of urinalysis and biochemical analysis of plasma), hemostatic variables (bleeding time, platelet aggregation, prothrombin time [PT], activated partial thromboplastin time [APTT], and platelet count), and Hct were assessed before and at various time points after surgery. Analysis of results for renal function tests, most of the hemostatic and plasma biochemical variables, and Hct did not reveal significant differences between treatment groups. Values for GFR, UP:UC, PT, APTT, and platelet aggregation were outside reference ranges in many dogs before surgery and during the first 6 hours after surgery. In most dogs, these trauma-induced pathologic changes returned to within reference ranges during the 4-day period after surgery. Carprofen did not cause clinically relevant adverse effects in dogs anesthetized for fracture repair after 5 days of treatment, even when it was administered before surgery or given to patients with trauma-induced alterations in renal function or hemostasis.

Tubeless percutaneous nephrolithotomy with non-absorbable hemostatic sealant (Quikclot®) versus nephrostomy tube placement: a propensity score-matched analysis.

PubMed

Koo, Kyo Chul; Park, Sang Un; Jang, Ho Sung; Hong, Chang-Hee

2015-11-01

The purpose of this study was to determine the efficacy and safety of tubeless percutaneous nephrolithotomy (PNL) using a non-absorbable hemostatic sealant (Quikclot(®)) as an adjunct compared to nephrostomy tube placement in patients exhibiting significant parenchymal bleeding following PNL. We identified 113 PNL cases performed between May 2011 and October 2014. For patients with insignificant parenchymal bleeding following stone removal, defined as a clear visualization of the surgical field at full irrigation of the nephroscope, tubeless PNL was performed. For patients with significant parenchymal bleeding, we introduced the tubeless Quikclot(®) technique as of September 2013 and have performed it ever since. Formerly, nephrostomy placement PNL was performed. In this study, 40 Quikclot(®) applied PNL cases were matched with an equal number of nephrostomy placement cases by propensity scoring based on body mass index, stone size, and Guy's stone score. The mean postoperative drop in hematocrit was comparative between the Quikclot(®) group and the nephrostomy group on both postoperative days 1 (p = 0.459) and 2 (p = 0.325). Quikclot(®) application was associated with lower VAS scores throughout the postoperative period, lower cumulative analgesic requirement (p = 0.025), and with shorter hospitalization (p = 0.002). Complication rates were comparable with no need for blood transfusions in any patients. Tubeless Quikclot(®) PNL was safe and provided effective hemostasis of significant parenchymal bleeding. By avoiding nephrostomy placement, we were able to reduce postoperative pain, analgesic requirements, and hospitalization. Application of Quikclot(®) may be considered prior to nephrostomy placement in patients with significant parenchymal bleeding.

Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation.

PubMed

Hollis, Allison L; Lowery, Ashleigh V; Pajoumand, Mehrnaz; Pham, Si M; Slejko, Julia F; Tanaka, Kenichi A; Mazzeffi, Michael

2016-01-01

Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.

Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia.

PubMed

Giordano, Paola; Molinari, Angelo Claudio; Del Vecchio, Giovanni Carlo; Saracco, Paola; Russo, Giovanna; Altomare, Maria; Perutelli, Paolo; Crescenzio, Nicoletta; Santoro, Nicola; Marchetti, Marina; De Mattia, Domenico; Falanga, Anna

2010-05-01

In a group of newly diagnosed acute lymphocytic leukemia (ALL) children we evaluated a number of hemostatic and inflammatory markers at diagnosis and at different time points during chemotherapy for the remission induction to identify alterations in the plasma levels of prothrombotic markers before and during the course of chemotherapy. The following plasma markers were evaluated: thrombin-antithrombin complex (TAT), D-Dimer, plasminogen activator inhibitor 1 (PAI-1), antithrombin, fibrinogen, von Willebrand factor (VWF) antigen and high molecular weight VWF (HMW-VWF) multimers, P-selectin, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6). Plasma samples were collected at the following time points: at T0 (baseline) and T1 (+24 days of therapy), T2 (+36 days therapy), and T3 (+64 days therapy). The results show that, at diagnosis, ALL children presented with laboratory signs of increased thrombin generation and fibrin formation (i.e. high TAT and D-dimer levels), fibrinolysis inhibition (i.e. high PAI-1 level), endothelial activation (i.e., high HMW-VWF and soluble P-selectin levels) and inflammation (i.e. high TNF-alpha and IL-6 levels). After starting induction therapy, the thrombin generation markers and inflammatory cytokines significantly decreased. To the opposite, PAI-1 and P-selectin significantly increased, suggesting an insult by chemotherapy on the vascular endothelium. These effects were more evident during steroid administration. Symptomatic venous thromboembolism (VTE) episodes developed in two cases during induction therapy, which did not allow the evaluation of the predictive value for VTE of laboratory markers. (c) 2010 Wiley-Liss, Inc.

[Risk and crisis management by anesthesiologists regarding 'Guidelines for Actions Against Intraoperative Critical Hemorrhage' published by the Japanese Society of Anesthesiologists and the Japan Society of Transfusion Medicine and Cell Therapy].

PubMed

Irita, Kazuo; Yoshimura, Hayashi; Sakaguchi, Yoshiro; Takamatsu, Chihiro; Tokuda, Kentaro

2008-09-01

According to a survey of anesthesia-related critical incidents by the Japanese Society of Anesthesiologists, hemorrhage was the major cause of cardiac arrest developing in the operating room. To deal with critical hemorrhage swiftly, not only cooperation between anesthesiologists and surgeons but also the linkage of operating rooms with transfusion management divisions and the blood center is important. It is desirable for the hospital transfusion committee to prepare hospital regulations on 'actions to be taken to manage critical hemorrhage', and practice the implementation of these guidelines by simulated drills. When critical hemorrhage occurs, a person in charge is appointed, and an emergency is declared (call for manpower and notification of the emergency to the transfusion management divisions). A person in charge comprehensively assesses the hemostatic condition, hemodynamics, laboratory data, and blood product supply system, and consults the operator regarding the continuation of surgery or changing surgical procedures. When time is short, the cross-matching test is omitted, and the ABO-identical blood is used. When a supply of the identical ABO-type blood is not available, compatible blood type is used. The evolving concept of hemostatic resuscitation seems to be important to prevent coagulopathy, which easily develops during massive hemorrhage. Anesthesiologists should be aware of the risk of such an emergency transfusion and procedures to be taken to switch to transfusion of the ABO-identical blood. Establishment of a hospital emergency transfusion system depends on the overall capability of the critical and crisis management systems of the hospital.

Changes in blood aggregation with differences in molecular weight and degree of deacetylation of chitosan.

PubMed

Hattori, Hidemi; Ishihara, Masayuki

2015-01-22

Because the molecular weight (Mw) and degree of deacetylation (DDA) of chitosan can vary depending on the purification method, the identification of appropriate chitosan structures is important for developing more effective hemostatic agents. In this study, the influence of varying Mw and DDA of chitosan on blood aggregation was characterized by 10 types of chitosan with different Mw and DDA, including oligomers. The highest aggregation of whole blood, washed erythrocytes and platelets in platelet-rich plasma (PRP) were observed in chitosan with Mw of 8.6 kDa or more and with DDA of 75 to 88%. However, chitosan with too high Mw (247 kDa) inhibited the aggregation of whole blood, washed erythrocytes and PRP at high chitosan concentration. At certain concentrations, chitosan with 75-85% DDA and 50-190 kDa and chitosan with 87.6% DDA and 247 kDa both aggregated proteins in PRP. Chitosan oligomer did not affect blood aggregation. The results suggested that the aggregation by chitosan depended on the interaction of positively charged chitosan with negatively charged erythrocytes, platelets and plasma protein. It seemed that a suitable balance of positive charge in chitosan and negative charge in hemocytes and some kinds of proteins was important. To develop a hemostatic with effective blood aggregation, the chitosan should not be limited to a single Mw and a single DDA but may be a mixed chitosan with wide range of Mw (8.6-247 kDa) and DDA of 75 to 88%.

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials.

PubMed

Baracat, Felipe; Moura, Eduardo; Bernardo, Wanderley; Pu, Leonardo Zorron; Mendonça, Ernesto; Moura, Diogo; Baracat, Renato; Ide, Edson

2016-06-01

Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy. Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials. Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone. Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

Effects of recombinant human prothrombin on thrombin generation in plasma from patients with hemophilia A and B.

PubMed

Hansson, K M; Gustafsson, D; Skärby, T; Frison, L; Berntorp, E

2015-07-01

The present study was carried out to investigate the impact of FII levels, and their increase, on the hemostatic potential in plasma from hemophilia A and B patients with and without inhibitors. Recombinant human factor (F) II (rhFII) was added ex vivo to plasma from 68 patients with hemophilia A and B, with or without inhibitors. The hemostatic potential as measured by thrombin generation (calibrated automated thrombogram [CAT]) was focused on the endogenous thrombin potential (ETP) as it has been shown to correlate with the clinical phenotype of bleeding in hemophilia patients and has also been used to guide bypassing therapy in hemophilia patients with inhibitors before elective surgery. The factor eight inhibitor bypassing agent (FEIBA(®) ) was used as a reference to the clinical situation. The study shows that rhFII concentration-dependently increased ETP by a similar magnitude in hemophilia A and B, both with and without inhibitors. Compared with FEIBA, rhFII showed a shallower concentration-response curve. In both types of hemophilia 100 mg L(-1) of rhFII roughly doubled the ETP. A corresponding response was obtained by 0.5 U mL(-1) of FEIBA. These data support the theory that FII is one of the major components responsible for the efficacy of FEIBA. The data also indicate that rhFII may be useful, alone or in combination with other coagulation factors, in some of the conditions for which FEIBA is used today, although more data are needed to substantiate this. © 2015 International Society on Thrombosis and Haemostasis.

Inner Mitochondrial Membrane Disruption Links Apoptotic and Agonist-Initiated Phosphatidylserine Externalization in Platelets.

PubMed

Choo, Hyo-Jung; Kholmukhamedov, Andaleb; Zhou, ChengZing; Jobe, Shawn

2017-08-01

Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus. Platelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus. © 2017 American Heart Association, Inc.

Predictive variables for mortality after acute ischemic stroke.

PubMed

Carter, Angela M; Catto, Andrew J; Mansfield, Michael W; Bamford, John M; Grant, Peter J

2007-06-01

Stroke is a major healthcare issue worldwide with an incidence comparable to coronary events, highlighting the importance of understanding risk factors for stroke and subsequent mortality. In the present study, we determined long-term (all-cause) mortality in 545 patients with ischemic stroke compared with a cohort of 330 age-matched healthy control subjects followed up for a median of 7.4 years. We assessed the effect of selected demographic, clinical, biochemical, hematologic, and hemostatic factors on mortality in patients with ischemic stroke. Stroke subtype was classified according to the Oxfordshire Community Stroke Project criteria. Patients who died 30 days or less after the acute event (n=32) were excluded from analyses because this outcome is considered to be directly attributable to the acute event. Patients with ischemic stroke were at more than 3-fold increased risk of death compared with the age-matched control cohort. In multivariate analyses, age, stroke subtype, atrial fibrillation, and previous stroke/transient ischemic attack were predictive of mortality in patients with ischemic stroke. Albumin and creatinine and the hemostatic factors von Willebrand factor and beta-thromboglobulin were also predictive of mortality in patients with ischemic stroke after accounting for demographic and clinical variables. The results indicate that subjects with acute ischemic stroke are at increased risk of all-cause mortality. Advancing age, large-vessel stroke, atrial fibrillation, and previous stroke/transient ischemic attack predict mortality; and analysis of albumin, creatinine, von Willebrand factor, and beta-thromboglobulin will aid in the identification of patients at increased risk of death after stroke.

Arachidonic acid depletion extends survival of cold-stored platelets by interfering with the [glycoprotein Ibα – 14-3-3ζ] association

PubMed Central

van der Wal, Dianne E.; Gitz, Eelo; Du, Vivian X.; Lo, Kimberly S.L.; Koekman, Cornelis A.; Versteeg, Sabine; Akkerman, Jan Willem N.

2012-01-01

Background Cold storage of platelets reduces bacterial growth and preserves their hemostatic properties better than current procedures do. However, storage at 0°C induces [14-3-3ζ-glycoprotein Ibα] association, 14-3-3ζ release from phospho-Bad, Bad activation and apoptosis. Design and Methods We investigated whether arachidonic acid, which also binds 14-3-3ζ, contributes to coldinduced apoptosis. Results Cold storage activated P38-mitogen-activated protein kinase and released arachidonic acid, which accumulated due to cold inactivation of cyclooxygenase-1/thromboxane synthase. Accumulated arachidonic acid released 14-3-3ζ from phospho-Bad and decreased the mitochondrial membrane potential, which are steps in the induction of apoptosis. Addition of arachidonic acid did the same and its depletion made platelets resistant to cold-induced apoptosis. Incubation with biotin-arachidonic acid revealed formation of an [arachidonic acid-14-3-3ζ-glycoprotein Ibα] complex. Indomethacin promoted complex formation by accumulating arachidonic acid and released 14-3-3ζ from cyclo-oxygenase-1. Arachidonic acid depletion prevented the cold-induced reduction of platelet survival in mice. Conclusions We conclude that cold storage induced apoptosis through an [arachidonic acid-14-3-3ζ-glycoprotein Ibα] complex, which released 14-3-3ζ from Bad in an arachidonic acid-dependent manner. Although arachidonic acid depletion reduced agonist-induced thromboxane A2 formation and aggregation, arachidonic acid repletion restored these functions, opening ways to reduce apoptosis during storage without compromising hemostatic functions post-transfusion. PMID:22371179

Effect of routine rapid insertion of Bakri balloon tamponade on reducing hemorrhage from placenta previa during and after cesarean section.

PubMed

Soyama, Hiroaki; Miyamoto, Morikazu; Sasa, Hidenori; Ishibashi, Hiroki; Yoshida, Masashi; Nakatsuka, Masaya; Takano, Masashi; Furuya, Kenichi

2017-09-01

To evaluate the effectiveness of routine rapid insertion of a Bakri balloon during cesarean section for placenta previa based on a retrospective control study. Women with singleton pregnancies who underwent cesarean section for placenta previa at our institution between 2003 and 2016 were enrolled. Between 2015 and 2016, women who routinely underwent balloon tamponade during cesarean section were defined as the balloon group. Between 2003 and 2014, women who underwent no hemostatic procedures except balloon tamponade were defined as the non-balloon group. The clinical outcomes of the two groups were retrospectively analyzed. Of the 266 women with placenta previa, 50 were in the balloon group and 216 were in the non-balloon group. The bleeding amounts were significantly smaller in the balloon group than in the non-balloon group: intraoperative bleeding (991 vs. 1250 g, p < 0.01), postoperative bleeding (62 vs. 150 g, p < 0.01), and total bleeding (1066 vs. 1451 g, p < 0.01). Furthermore, the mean surgical duration was shorter in the balloon group than the non-balloon group (30 vs. 50 min, p < 0.01). In the balloon group, five patients suffered from increasing hemorrhage due to prolapse of the balloon from the uterus after the operation, but the hemorrhage was controlled by balloon re-insertion without additional hemostatic procedures. This study demonstrated that the routine rapid insertion of Bakri balloon tamponade during cesarean section significantly decreased intra- and postoperative hemorrhage and shortened the surgical duration in women with placenta previa.

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Influence of stearic acid on hemostatic risk factors in humans.

PubMed

Tholstrup, Tine

2005-12-01

Stearic acid has been claimed to be prothrombotic. Elevated plasma factor VII coagulant activity (FVIIc) may raise the risk of coronary thrombosis in the event of plaque rupture. Fibrinogen, an acute-phase protein, is necessary for normal blood clotting; however, elevated levels of fibrinogen increase the risk of coronary heart disease (CHD). Here I report the results of three controlled, human dietary intervention studies, which used a randomized crossover design to investigate the hemostatic effects of stearic acid-rich test diets in healthy young men. A diet high in stearic acid (shea butter) resulted in a 13% lower fasting plasma FVIIc than a high palmitic acid diet, and was 18% lower than a diet high in myristic and lauric acids (P = 0.001) after 3 wk of intervention. The stearic acid-rich test fat increased plasma fibrinogen concentrations slightly compared with the myristic-lauric acid diet (P < 0.01). When investigating the acute effects of fatty meals, those high in stearic acid (synthesized test fat) resulted in a smaller postprandial increase in FVII than those high in trans and oleic FA, indicating a smaller increase in activated FVII after ingesting stearic acid compared with fats high in monounsaturated FA, probably caused by lower postprandial lipemia. Thus, the present investigations did not find dietary stearic acid to be more thrombogenic, in either fasting effects compared with other long-chain FA, or in acute effects compared with dietary unsaturated FA, including trans monounsaturated FA. The slightly increased effect on fasting plasma fibrinogen may be biologically insignificant, but it should be investigated further.

The effects of the decaffeination of coffee samples on platelet aggregation in hyperlipidemic rats.

PubMed

Silvério, Alessandra dos Santos Danziger; Pereira, Rosemary Gualberto Fonseca Alvarenga; Lima, Adriene Ribeiro; Paula, Fernanda Borges de Araújo; Rodrigues, Maria Rita; Baldissera, Lineu; Duarte, Stella Maris da Silveira

2013-09-01

The effect of coffee on cardiovascular diseases is still controversial. It is known that the process of decaffeination may influence the chemical constitution and, therefore, the biological effects of coffee. This study thus evaluated the effects of decaffeination on the levels of total phenols and chlorogenic acids in Coffea arabica L. samples, as well as the effects of ingesting both integral and decaffeinated coffee on the lipid profile and hemostatic and hematological parameters in normal and hyperlipidemic rats. Samples of integral and decaffeinated lyophilized coffee (Coffea arabica L., planted in Brazil) were used for chemical analysis (total phenols, chlorogenic acid and caffeine contents). For the bioassays, coffee beverages were prepared with non-lyophilized samples (10% w/v) and were filtered and administered to animals by gavage (7.2 mL/kg/day) over 30 days. On the 31st day after beginning the treatment with coffee beverages, hyperlipidemia was induced to the animals by administering Triton WR-1339 (300 mg/kg body weight). On day 32, blood was taken to determine the lipid profile, platelet aggregation, prothrombin time, partially activated thromboplastin time and hemogram. The contents of both phenolic compounds and chlorogenic acid in the integral coffee beverage were significantly lower than those in the decaffeinated coffee beverage. The animals treated with Triton WR-1339 presented a mixed hyperlipidemia. Although the decaffeination process caused a relative increase in total phenols and chlorogenic acids, the coffee drinks were unable to change the lipid profile or the hemostatic and hematological parameters in the studied animals.

Compare Complication of Classic versus Patent Hemostasis in Transradial Coronary Angiography.

PubMed

Roghani, Farshad; Tajik, Mohammad Nasim; Khosravi, Alireza

2017-01-01

Coronary artery disease (CAD) is multifactorial disease, in which thrombotic occlusion and calcification occur usually. New strategies have been made for diagnosis and treatment of CAD, such as transradial catheterization. Hemostasis could be done in two approaches: traditional and patent. Our aim is to find the best approach with lowest complication. In a comparative study, 120 patients were recruited and divided randomly into two subgroups, including traditional group (60 patients; 24 females, 36 males; mean age: 64.35 ± 10.56 years) and patent group (60 patients; 28 females, 32 males; mean age: 60.15 ± 8.92 years). All demographic data including age, gender, body mass index, and CAD-related risk factors (smoking, diabetes, hypertension) and technical data including the number of catheters, procedure duration, and hemostatic compression time and clinical outcomes (radial artery occlusion [RAO], hematoma, bleeding) were collected. Data were analyzed by SPSS version 16. Our findings revealed that the incidence of RAO was significantly lower in patent groups compared with traditional group ( P = 0.041). Furthermore, the difference incidence of RAO was higher in early occlusion compare with late one ( P = 0.041). Moreover, there were significant relationship between some factors in patients of traditional group with occlusion (gender [ P = 0.038], age [ P = 0.031], diabetes mellitus [ P = 0.043], hemostatic compression time [ P = 0.036]) as well as in patent group (age [ P = 0.009], hypertension [ P = 0.035]). Our findings showed that RAO, especially type early is significantly lower in patent method compared classic method; and patent hemostasis is the safest method and good alternative for classical method.

The story of a unique molecule in hemophilia A: recombinant single-chain factor VIII.

PubMed

Pabinger-Fasching, Ingrid

2016-05-01

For patients with hemophilia A, replacement of deficient factor VIII (FVIII) using plasma-derived or recombinant FVIII (rFVIII) products to restore hemostatic control can reduce bleeding complications and preserve musculoskeletal function. Despite the clinical availability of several of these products, challenges remain in the treatment of hemophilia A, the most notable of which are the risk of inhibitor development and the limited half-life of existing FVIII concentrates, which can make prophylaxis burdensome for patients. The use of recombinant protein technology may lead to novel FVIII products with improved properties. This article describes the story of a unique recombinant FVIII protein, rVIII-SingleChain, which is currently in development. In contrast to native FVIII and other commercially available rFVIII preparations, rVIII-SingleChain uses a strong, covalent bond to connect the light and heavy chains, thereby creating a stable, single-chain rFVIII. It has enhanced intrinsic stability, better integrity after reconstitution, and a higher binding affinity to von Willebrand factor. The physicochemical profile of rVIII-SingleChain and preclinical data on its activity and phamacokinetics strengthened the rationale for its clinical investigation. Available data from the AFFINITY clinical trial program are promising; indicating that it has good hemostatic efficacy when used on demand, for prophylaxis, and in the surgical setting, and is also very well tolerated. A pediatric study and an extension study are ongoing as part of the AFFINITY program. © 2016 Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

[A 50-year history of new drugs in Japan-the development and trends of hemostatics and antithrombotic drugs].

PubMed

Ozawa, Hikaru; Abiko, Yasushi; Akimoto, Takeshi

2003-01-01

The developments and trends of hemostatic and antithrombotic drugs in Japan were investigated chronologically for the last 50 years after the 2nd World War. 1. Hemostatic drugs are classified into three groups ; capillary stabilizers, blood coagulants and antifibrinolytics. l) As to capillary stabilizers, flavonoid (rutin, 1949), adrenochrome derivative (carbazochrome, 1954) and conjugated estrogen (Premarin, 1964) were introduced therapeutically. Especially, the soluble types of adrenochrome compounds (Adona 1956, S-Adchnon, 1962) were devised and used widely in Japan. 2) Drugs concerning blood coagulation, thrombin, introduced in 1953, and hemocoagulase, a snake venom introduced in 1966, were used clinically. V.K. groups producing various coagulation factors were introduced as V.K1 (Phytonadione, 1962) and V.K2 (rnenatetrenone,1972), and they were admitted in "The Japanese Pharmacopoeia"editions 8 and 14, respectively). 3) Regarding antifibrinolytic drugs, Japanese researchers have made remarkable contributions. e-Aminocapronic acid (Ipsilon, 1962) and tranexamic acid (Transamin, 1965) were developed and used for various abnormal bleedings or hemorrhage associated with plasmin over-activation. tranexamic acid also proved to suppress inflammations of the throat such as tonsillitis, pharyngitis or laryngitis. 2. Antithrombotic drugs are also divided into three groups; anticoagulants, antiplatelet drugs and fibrinolytics.1) The anticoagulants used therapeutically by injection are heparins (Na-salt, 1951; Ca-salt, 1962) and low-molecular-weight heparins such as dalteparin (1992), parnaparin (1994) and reviparin (1999). The low molecule compounds are superior to the original heparins in reducing the risk of bleeding. As oral anticoagulants, coumarin derivatives, dicumarol (1950), ethylbiscoumacetate (1954), phenylindandione (1956) and warfarin (1962) are known. Warfarin potassium is the main drug for oral therapy of thromboembolism lately. Gabexate mesilate (1989) and nafamostat mesilate (1989) were developed in Japan and used for DIC and acute pancreatitis to inhibit protease enzymes. Argatroban is a unique antithrombin product developed by Japanese researchers in 1990, and is used for vascular or cerebral thrombosis. After noticing in 1968 that aspirin inhibits platelet aggregation and prevents myocardial infraction, projects for developing antiplatelet drugs were initiated worldwide. Ticlopidine, originally developed in France, was introduced in 1981 and prevailed widely in Japan for reducing the risk of thrombotic stroke. Aspirin itself was recognized by the FDA (USA) as an antithrombotic drug in 1988, and was also approved by Japanese authorities in 2000. PGE1 clathrate compounds have also been developed as antiplatelet drugs; alprostadil alfadex for injection (1979), and limaprost alfadex for oral use (1988). The PGI2 product, beraprost sodium, for oral use followed them in 1992. Other antiplatelet drugs with unique mechanisms explored in Japan: Ozagrel (1988), which inhibits TXA2 synthetase, cilostazol (1988), which inhibits cAMP phosphodiesterase, and sarpogrelate (1993), which blocks 5HT in platelets, are the notable drugs in this field. Ethyl icosapentate, from fish oil, is available for antiplatelet therapy. Concerning the fibrinolytic system, plasminogen activators are useful for thromboembolism. The streptokinase from bacterial origin developed in the USA and Europe was not introduced, and urokinase (1965) was the first plasminogen activator developed in Japan. Then tissue plasminogen activators (t-PA) tisokinase (cell culture, 1991), alteplase (genetical recombination, 1991), nateplase (genetical recombination, 1996), monteplase (1998) and pamiteplase (1998) were developed and approved for acute myocardial infarction. Nasaruplase (prourokinase, cell culture,1991) was also approved for the same indication. While the development of the hemostatic drugs ceased in the 1960s, avid project studies for antithrombotic drugs including fibrinolytics began in the 1980s and are progressing now towards new molecular targets. This may be due to the increasing tendency of cardiovascular thromboembolic diathesis in Japan. (The figures in parentheses are the years approved by the Japanese Ministry of Health, Labor and Welfare.)

Aluminum Potassium Sulfate and Tannic Acid Injection for Hemorrhoids

PubMed Central

2012-01-01

A quick hemostatic effect, as well as sclerosing and shrinkage of hemorrhoids, can be attained when internal hemorrhoids are treated by using injection therapy with aluminum potassium sulfate and tannic acid (ALTA), the outcomes of treatment may be similar to those of a hemorrhoidectomy. However, if the type of hemorrhoid or the method of injection is not appropriate for ALTA treatment, complications peculiar to ALTA or recurrence may develop. Accordingly, sufficient understanding of the treatment mechanism of ALTA injection and repeated training for injection are required for effective use of the ALTA treatment. PMID:22606645

Chemical Burns Following Massage With Chopped Pulsatilla koreana.

PubMed

Song, Jinkyung; Tae, Sangpil; Joo, Hongsil; Lee, Sang-Yeul; Sung, Kun-Yong

2017-11-01

Herbal massage is commonly used for cosmetic and antirheumatic purposes in the Republic of Korea. Cutaneous burns can complicate herbal massages, but this is a very rare occurrence. Pulsatilla koreana, the Korean pasque flower, is a species of the genus Pulsatilla from the Ranunculaceae family. It is a perennial plant native to Korea, where it is used in herbal and folk medicine for its antipyretic, analgesic, anti-inflammatory, astringent, and hemostatic effects. Three cases of burns as a result of herbal massages with Pulsatilla koreana are presented herein to increase public awareness about the adverse effects of products used incorrectly for herbal massage.

A noninvasive method of examination of the hemostasis system.

PubMed

Kuznik, B I; Fine, I W; Kaminsky, A V

2011-09-01

We propose a noninvasive method of in vivo examination the hemostasis system based on speckle pattern analysis of coherent light scattering from the skin. We compared the results of measuring basic blood coagulation parameters by conventional invasive and noninvasive methods. A strict correlation was found between the results of measurement of soluble fibrin monomer complexes, international normalized ratio (INR), prothrombin index, and protein C content. The noninvasive method of examination of the hemostatic system enable rough evaluation of the intensity of the intravascular coagulation and correction of the dose of indirect anticoagulants maintaining desired values of INR or prothrombin index.

Recombinant activated factor VII in cardiac surgery: a systematic review.

PubMed

Warren, Oliver; Mandal, Kaushik; Hadjianastassiou, Vassilis; Knowlton, Lisa; Panesar, Sukhmeet; John, Kokotsakis; Darzi, Ara; Athanasiou, Thanos

2007-02-01

Postoperative hemorrhage is a common complication in cardiac surgery, and it is associated with a considerable increase in morbidity, mortality, and cost. Recombinant activated factor VII (rFVIIa) is an emerging hemostatic agent, increasingly used in cardiac surgery. This article systematically reviews the evidence regarding the efficacy, safety, and cost of rFVIIa in this setting. Although definitive evidence from randomized controlled trials is lacking, the use of rFVIIa in patients experiencing refractory postoperative hemorrhage seems promising and relatively safe. However further research is required to definitively establish its clinical utility in the postoperative cardiac patient.

Negative-Pressure Wound Therapy: A Hemostatic Adjunct for Control of Coagulopathic Hemorrhage in Large Soft Tissue Wounds

DTIC Science & Technology

2012-01-01

65.6 (2.05) 64.6 (1.7) 69.4 (2.6) 63.8 (0.8) 0.20 Hemoglobin level , g/dL 10.4 (0.12) 4.6 (0.23) 4.3 (0.18) 4.5 (0.17) 4.4 (0.13) 0.50 Hematocrit ...and level of negative pressure, wound filter, and wound contact layer. This modality creates a wound environment of subat- mospheric pressure (j50 to...inhibitory factors such as collagenases and inflammatory cytokines, (2) decreasing the level of bacteria, (3) improving blood flow in the wound bed and

Platelets as autonomous drones for hemostatic and immune surveillance.

PubMed

Li, Jackson LiangYao; Zarbock, Alexander; Hidalgo, Andrés

2017-07-18

Platelets participate in many important physiological processes, including hemostasis and immunity. However, despite their broad participation in these evolutionarily critical roles, the anucleate platelet is uniquely mammalian. In contrast with the large nucleated equivalents in lower vertebrates, we find that the design template for the evolutionary specialization of platelets shares remarkable similarities with human-engineered unmanned aerial vehicles in terms of overall autonomy, maneuverability, and expendability. Here, we review evidence illustrating how platelets are uniquely suited for surveillance and the manner in which they consequently provide various types of support to other cell types. © 2017 Li et al.

Pure Small Cell Carcinoma of the Bladder: A Case Report

PubMed Central

Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

2010-01-01

Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases. PMID:29147197

Pure Small Cell Carcinoma of the Bladder: A Case Report.

PubMed

Trabelsi, Amel; Abdelkrim, Soumaya Ben; Tebra, Samah; Gharbi, Olfa; Jaidane, Lilia; Bouaouina, Noureddine; Abbassi, Dajla Bakir; Mokni, Moncef

2010-06-01

Small cell carcinoma of the urinary bladder is an uncommon tumor that has been described in case reports or small series. We report a new case in a 67-year-old male who presented with gross hematuria and irritative symptoms. Cystoscopy revealed an extensive mass of the bladder and computed tomography scan showed an important thickening of the bladder wall. Diagnosis of small cell carcinoma was established after radical cystectomy and microscopic examination. The patient received pelvic hemostatic radiotherapy and platinium-based chemotherapy. Three months after the diagnosis, he developed bone, renal and adrenal metastases.

Platelets: versatile effector cells in hemostasis, inflammation, and the immune continuum

PubMed Central

Vieira-de-Abreu, Adriana; Campbell, Robert A.; Weyrich, Andrew S.

2015-01-01

Platelets are chief effector cells in hemostasis. In addition, however, their specializations include activities and intercellular interactions that make them key effectors in inflammation and in the continuum of innate and adaptive immunity. This review focuses on the immune features of human platelets and platelets from experimental animals and on interactions between inflammatory, immune, and hemostatic activities of these anucleate but complex and versatile cells. The experimental findings and evidence for physiologic immune functions include previously unrecognized biologic characteristics of platelets and are paralleled by new evidence for unique roles of platelets in inflammatory, immune, and thrombotic diseases. PMID:21818701

Analysis of the hemostatic potential of modern topical sealants on arterial and venous anastomoses: an experimental porcine study.

PubMed

Fonouni, Hamidreza; Kashfi, Arash; Majlesara, Ali; Stahlheber, Oliver; Konstantinidis, Lukas; Kraus, Thomas W; Mehrabi, Arianeb; Oweira, Hani

2017-09-01

One of the widely accepted adjunctive agents in the variety of surgical modalities are sealants. Our study aim was to compare four commonly used modern sealants in a standardized experimental setting to assess their feasibility, and hemostatic efficacy in vascular anastomosis. Forty landrace pigs (weight: 24.7 ± 3.8 kg) were randomized into the control (n = 8) and four sealant groups; TachoSil® (n = 8), Tissucol Duo® (n = 8), Coseal® (n = 8), and FloSeal® (n = 8). After doing a portal vein end-to-end anastomosis as well as stitches of aortic incision, the sealants were applied on anastomotic site. The control group was left intact. In portal vein anastomosis, the sealants led to a complete hemostasis significantly better than control group. The mean of blood loss was also significantly reduced. In successful subgroups, there was a difference in the mean-time to reach complete hemostasis ranging from 15 s in Coseal® to 76 s in FloSeal® group (p  < 0.05). In aortotomy experiments, except Tissucol Due®, which had insufficient hemostasis, other sealants led to a complete hemostasis. The mean blood loss was significantly reduced in sealants groups as well. The four sealants are effective in reducing the suture-hole bleeding in portal vein anastomosis. However, the hemostatic potential is heterogeneous among sealants. This means that "one-size-fits-all" approach is not appropriate for application of sealants in diversity of vascular surgery and it should be based on the type and the severity of injury and the structure of tissue. Comparison of hemostasis efficacy of four modern sealants (TachoSil®, Tissucol Duo®, Coseal®, and FloSeal®) in vascular anastomosis in porcine model. The figures below show the total blood loss (g) in the control and sealant groups after aortotomy (left) and portal vein anastomosis (right). The mean of blood loss decreased significantly by the usage of sealants in both experiment groups as compared to control group (*: p < 0.05; sealant groups vs. control group). 1. The right column shows the mean of blood loss (g) in all experiments in each group. 2. The middle column presents the subgroup with unsuccessful hemostasis at the end of observation time (Tmax = 20 sec. for aortotmy and 300 sec. for portal vein anastomosis). 3. The left column shows mean of total blood loss in subgroups with successful hemostasis during observation time (20 sec for aortotomy and 300 sec for portal vein).

Hemostatic effects of the ticagrelor antidote MEDI2452 in pigs treated with ticagrelor on a background of aspirin.

PubMed

Pehrsson, S; Johansson, K J; Janefeldt, A; Sandinge, A-S; Maqbool, S; Goodman, J; Sanchez, J; Almquist, J; Gennemark, P; Nylander, S

2017-06-01

Essentials MEDI2452 is a specific antidote of the platelet P2Y 12 receptor antagonist ticagrelor. Hemostatic effects of MEDI2452 were evaluated in pigs treated with ticagrelor and aspirin. MEDI2452 eliminated free ticagrelor within 5 min and gradually normalized platelet aggregation. Improvements in blood pressure (significant) and in blood-loss and survival (non-significant) were observed. Background Ticagrelor, a P2Y 12 antagonist, is approved for the prevention of thromboembolic events. However, antiplatelet therapies carry a risk of bleeding. Objective To explore the hemostatic effects of MEDI2452, an antidote for ticagrelor. Methods Pigs, pre-treated with aspirin, were given an intravenous infusion of ticagrelor or vehicle. At the end of the infusion, a piece of a liver lobe was cut off and a bolus of MEDI2452 or vehicle was administered intravenously. Blood was collected to monitor blood loss, mean arterial blood pressure (MAP) was recorded and survival time was observed over 4 h. Blood samples for drug plasma exposures and platelet aggregation were collected. Results MEDI2452 eliminated the free concentrations of ticagrelor and its active metabolite AR-C124910XX within 5 min. ADP-induced platelet aggregation was close to normal at 60 min, which was not significantly different from aspirin alone. MEDI2452 numerically reduced ticagrelor-mediated effects: body-weight-adjusted blood loss in the 15- to 90-min interval, 12 (confidence interval [CI] 95% 7-28] vs. 17 (CI 95% 5-31) (ticagrelor and aspirin) vs. 5 (CI 95% 3-9) mL kg -1 (aspirin alone), survival 70% (CI 95% 47-100) vs. 45% (CI 95% 21-92) (ticagrelor and aspirin) vs. 100% (CI 95% 100-100) (aspirin alone), and median survival time, 240 (CI 95% 180-240) vs. 169 (CI 95% 64-240) (ticagrelor and aspirin) vs. 240 (CI 95% 240-240) min (aspirin alone). Finally, MEDI2452 significantly attenuated the decline in MAP, 0.08 (CI 95% 0.07-0.09) vs. 0.141 (CI 95% 0.135-0.148) (ticagrelor and aspirin) vs. 0.04 (CI 95% 0.03-0.05) mmHg per min (aspirin alone) and maintained MAP at a significantly higher level, 73 (CI 95% 51-95) vs. 48 (CI 95% 25-70) (ticagrelor and aspirin) vs. 115 (CI 95% 94-136) mmHg (aspirin alone). Conclusion MEDI2452 eliminated free ticagrelor and AR-C124910XX within 5 min. This translated into a gradual normalization of ADP-induced platelet aggregation and significant improvement in blood pressure and numerical but non-significant improvements in blood-loss and survival. © 2017 International Society on Thrombosis and Haemostasis.

Effects of P2Y12 receptor inhibition with or without aspirin on hemostatic system activation: a randomized trial in healthy subjects.

PubMed

Traby, L; Kollars, M; Kaider, A; Eichinger, S; Wolzt, M; Kyrle, P A

2016-02-01

ESSENTIALS: In acute coronary syndromes, dual antiplatelet therapy inhibits platelets but confers a bleeding risk. Healthy male volunteers received clopidogrel or ticagrelor plus aspirin or clopidogrel or ticagrelor alone. The decrease in β-thromboglobulin in shed blood was comparable after single and dual antiplatelet therapy. We hypothesize that patients with acute coronary syndromes may not require dual antiplatelet therapy. Dual antiplatelet therapy with a P2Y12 inhibitor and aspirin is standard in acute coronary syndromes. Dual antiplatelet therapy causes more bleeding than single antiplatelet therapy with a P2Y12 inhibitor. To compare the effects of dual and single antiplatelet therapies on hemostatic system activation. In a randomized, parallel-group, double-blind, placebo-controlled study, 44 healthy volunteers received clopidogrel (600 mg, then 150 mg d(-1) ) and aspirin (100 mg d(-1) ) or placebo for 7 days; An additional 44 volunteers received single-dose ticagrelor (180 mg) and aspirin (300 mg) or placebo. β-Thromboglobulin (β-TG [IU L(-1) ]) and prothrombin fragment 1.2 (f1.2 [nmol L(-1) ]) were measured in blood obtained from bleeding time incisions. Data are given as geometric mean ratio (GMR [95% confidence interval]) to describe the differences in the first 2 h and as mean differences (Δ [95% confidence interval]) in area under the curve (AUC) to discriminate differences in effects over the total observation time. Clopidogrel plus aspirin and clopidogrel plus placebo reduced β-TG by a GMR of 0.51 (0.42-0.63) and 0.54 (0.46-0.64) at 2 h. Ticagrelor plus aspirin and ticagrelor plus placebo decreased β-TG by a GMR of 0.38 (0.26-0.57) and 0.47 (0.31-0.72). Ticagrelor plus aspirin and ticagrelor plus placebo reduced f1.2 by a GMR of 0.58 (0.45-0.75) and 0.55 (0.38-0.80); clopidogrel did not. Over 24 h, no difference in β-TG occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -2.9 [-9.9 to 4.1]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.5 [-11.8 to 4.7]). No difference in f1.2 occurred between clopidogrel plus aspirin and clopidogrel plus placebo (ΔAUC = -4.2 [-10.2 to 1.8]) or between ticagrelor plus aspirin and ticagrelor plus placebo (ΔAUC = -3.6 [-10.9 to 3.7]). P2Y12 inhibitor monotherapy and dual antiplatelet therapy inhibit hemostatic system activation to a comparable extent. © 2015 International Society on Thrombosis and Haemostasis.

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

PubMed

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

2017-05-01

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

Increased Coagulation and Decreased Fibrinolysis as Measured with Overall Hemostatic Potential Are Dependent on BMI and Not Associated with PCOS.

PubMed

Rakusa, Matej; Jensterle, Mojca; Božič-Mijovski, Mojca; Janez, Andrej

2017-05-01

Overall hemostatic potential (OHP) captures all factors that affect coagulation and fibrinolysis cascade. It has not yet been assessed in polycystic ovary syndrome (PCOS). The aim of the study was to identify the relationship of OHP with a syndrome per se and body mass index (BMI). In 90 women with PCOS aged 30.9 ± 8.1 years (50 obese, 13 overweight, and 27 lean) and 21 healthy age-matched controls (11 obese and 10 lean), OHP with overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) was determined spectrophotometrically. OFP was calculated. OHP increased with BMI in PCOS (9.6 ± 2.3 in lean, 12.5 ± 5.1 in overweight, and 15.5 ± 3.8 Abs-sum in obese) and in controls (9.1 ± 1.0 in lean and 17.3 ± 4.6 Abs-sum in obese). There was significant difference between lean and obese PCOS (P < 0.001) and between lean and obese controls (P < 0.001). OCP also increased with BMI in PCOS (P < 0.001 for lean vs. obese) and in controls (P < 0.001 for lean vs. obese). OFP decreased with BMI in PCOS (P < 0.001 for obese vs. overweight vs. lean) and in controls (P < 0.001 for obese vs. lean). OHP in healthy obese and obese PCOS did not differ significantly, while OHP for healthy obese was increased in comparison to overweight and lean PCOS (P < 0.001). PCOS was not associated with increased OHP compared with BMI and age-matched controls. However, increase in OHP was positively associated with BMI in PCOS and healthy women.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro

PubMed Central

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-01-01

Aim: To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Methods: Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Results: Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration, while Na+ and K+ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations. Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Conclusion: Zeolite releases Ca2+ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time. PMID:23334236

First Safety and Performance Evaluation of T45K, a Self-Assembling Peptide Barrier Hemostatic Device, After Skin Lesion Excision.

PubMed

Rahmani, George; Prats, Jayne; Norchi, Terrence; Kates, Steven; McInerney, Veronica; Woods, Jack; Kelly, Jack

2018-01-29

The self-assembling peptide barrier T45K (SAPB-T45K) is an oligopeptide that rapidly forms a biocompatible hemostatic barrier when applied to wounds. Evaluate safety and performance of SAPB-T45K in cutaneous surgery. In this single-blind study, after sequential shave excision of 2 lesions, wounds were randomized (intrapatient) to SAPB-T45K or control treatment. Safety was assessed at treatment, Day 7, and Day 30. Performance was evaluated using time to hemostasis (TTH) and ASEPSIS wound scores, with a subgroup analysis for patients with or without antiplatelet therapy. Each of 46 patients (10 [22%] with antiplatelet therapy) received randomized SAPB-T45K or control treatment for 2 wounds. Safety assessments were similar, and ASEPSIS scores reflected normal healing in both wound groups. SAPB-T45K demonstrated significantly faster median TTH (24.5 [range, 7-165] seconds) compared with control (44 [10-387] seconds), for a 41% median TTH reduction (18 [95% confidence interval, 7-35] seconds, p < .001). SAPB-T45K provided an identical median TTH of 24 seconds, regardless of antiplatelet therapy. Control median TTH was 90 and 40 seconds for patients taking or not taking antiplatelet therapy, respectively. SAPB-T45K provided significantly faster median TTH versus control, especially with antiplatelet therapy, and safety profiles were similar.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

Large-Vessel Sealing in Laparoscopic Colectomy with an Ultrasonic Device

PubMed Central

Plasencia, Gustavo; Van der Speeten, Kurt; Hinoul, Piet; Batiller, Jonathan; Severin, Kimberley S.; Schwiers, Michael L.; Rockall, Tim

2016-01-01

Background and Objective: The Harmonic ACE+7 Shears with Advanced Hemostasis Mode (Ethicon, Somerville, NJ, USA) is an ultrasonic device designed to transect and seal vessels up to 7 mm in diameter. The device applies an algorithm that optimizes ultrasonic energy delivery combined with a longer sealing cycle. The purpose of this study was to assess the initial clinical experience with the Harmonic device by evaluating large-vessel sealing during laparoscopic colectomy in consecutive cases. Methods: This prospective, multicenter, observational series involved 40 adult patients who were to undergo elective laparoscopic colectomy where dissection and transection of the inferior mesenteric artery was indicated. The primary study endpoint was first-pass hemostasis, defined as a single activation of the Advanced Hemostasis Mode to transect and seal the inferior mesenteric artery. The use of any additional energy device or hemostatic product to establish or maintain hemostasis was noted. Patients were observed after surgery for ∼4 weeks for adverse events that were considered to be related to the study procedure or study device. Descriptive statistical analyses were performed for study endpoints. Results: Forty patients underwent the laparoscopic colectomy procedure. First-pass hemostasis of the inferior mesenteric artery was achieved and maintained in all 40 patients, with no required additional hemostatic measures. Exposure of the vessel was reported as skeletonized in 22 of 40 (55%) patients. Mean transection time was 21.9 ± 7.4 s. One adverse event (postoperative anemia) was considered possibly related to the study device. Conclusion: In this initial clinical consecutive series, the device demonstrated successful transection and sealing of the large mesenteric vessels during laparoscopic colorectal surgery. PMID:27186065

Compare Complication of Classic versus Patent Hemostasis in Transradial Coronary Angiography

PubMed Central

Roghani, Farshad; Tajik, Mohammad Nasim; Khosravi, Alireza

2017-01-01

Background: Coronary artery disease (CAD) is multifactorial disease, in which thrombotic occlusion and calcification occur usually. New strategies have been made for diagnosis and treatment of CAD, such as transradial catheterization. Hemostasis could be done in two approaches: traditional and patent. Our aim is to find the best approach with lowest complication. Materials and Methods: In a comparative study, 120 patients were recruited and divided randomly into two subgroups, including traditional group (60 patients; 24 females, 36 males; mean age: 64.35 ± 10.56 years) and patent group (60 patients; 28 females, 32 males; mean age: 60.15 ± 8.92 years). All demographic data including age, gender, body mass index, and CAD-related risk factors (smoking, diabetes, hypertension) and technical data including the number of catheters, procedure duration, and hemostatic compression time and clinical outcomes (radial artery occlusion [RAO], hematoma, bleeding) were collected. Data were analyzed by SPSS version 16. Results: Our findings revealed that the incidence of RAO was significantly lower in patent groups compared with traditional group (P = 0.041). Furthermore, the difference incidence of RAO was higher in early occlusion compare with late one (P = 0.041). Moreover, there were significant relationship between some factors in patients of traditional group with occlusion (gender [P = 0.038], age [P = 0.031], diabetes mellitus [P = 0.043], hemostatic compression time [P = 0.036]) as well as in patent group (age [P = 0.009], hypertension [P = 0.035]). Conclusion: Our findings showed that RAO, especially type early is significantly lower in patent method compared classic method; and patent hemostasis is the safest method and good alternative for classical method. PMID:29387670

Bothrops jararaca envenomation: Pathogenesis of hemostatic disturbances and intravascular hemolysis.

PubMed

Senise, Luana V; Yamashita, Karine M; Santoro, Marcelo L

2015-11-01

To attain fully functional biological activity, vitamin-K dependent coagulation factors (VKDCF) are γ-carboxylated prior to secretion from liver. Warfarin impairs the γ-carboxylation, and consequently their physiological function. Bothrops jararaca snake venom (BjV) contains several activators of blood coagulation, especially procoagulant enzymes (prothrombin and factor X activators) and thrombin-like enzymes. In order to clarify the relative contribution of prothrombin and factor X activators to the hemostatic disturbances occurring during experimental B. jararaca envenomation, warfarin was used to deplete VKDCF, prior to BjV administration. Male Wistar rats were pretreated with saline (Sal) or warfarin (War) and inoculated subsequently with BjV or saline, thus forming four groups: Sal + Sal (negative control), Sal + BjV (positive control), War + Sal (warfarinization control), and War + BjV. Three hours after inoculation, prothrombin and factor X levels fell 40% and 50%, respectively; levels of both factors decreased more than 97% in the War + Sal and War + BjV groups. Platelet counts dropped 93% and 76% in Sal + BjV and War + BjV, respectively, and plasma fibrinogen levels decreased 86% exclusively in Sal + BjV. After 6 and 24 h, platelet counts and fibrinogen levels increased progressively. A dramatic augmentation in plasma hemoglobin levels and the presence of schizocytes and microcytes in the Sal + BjV group indicated the development of intravascular hemolysis, which was prevented by warfarin pretreatment. Our findings show that intravascular thrombin generation has the foremost role in the pathogenesis of coagulopathy and intravascular hemolysis, but not in the development of thrombocytopenia, in B. jararaca envenomation in rats; in addition, fibrinogenases (metalloproteinases) may contribute to coagulopathy more than thrombin-like enzymes. © 2015 by the Society for Experimental Biology and Medicine.

In vitro efficacy of pro- and anticoagulant strategies in compensated and acutely ill patients with cirrhosis.

PubMed

Lisman, Ton; Kleiss, Simone; Patel, Vishal C; Fisher, Caleb; Adelmeijer, Jelle; Bos, Sarah; Singanayagam, Arjuna; Stoy, Sidsel Hyldgaard; Shawcross, Debbie L; Bernal, William

2018-05-16

A simultaneous decline in pro- and anticoagulant drivers in patients with liver diseases results in a 'rebalanced' hemostatic system, even in acutely ill patients. Nevertheless, both bleeding and thrombotic events are common. Here, we explored efficacy of pro- and antihemostatic strategies in compensated and acutely ill cirrhotics which may be unpredictable given the profound hemostatic changes. We tested the effects in vitro of the addition of clinically relevant doses of commonly used pro- and antihemostatic strategies in plasma from healthy individuals (n=30) and patients with compensated (n=18) and acutely decompensated cirrhosis (n=18), and acute-on-chronic liver failure (n=10). We used thrombin generation tests and fibrin clot permeability assays to assess potency of various approaches. Fresh frozen plasma and recombinant factor VIIa modestly increased thrombin generation (10-20%). Prothrombin complex concentrate increased thrombin generation 2-fold in controls and 2-4-fold in patients. Clot permeability decreased after addition of fibrinogen concentrate by 51% in controls and by 50-60% in patients. Low molecular weight heparin decreased thrombin generation by 18% in controls and by 23-54% in patients. Similarly, dabigatran decreased thrombin generation by 33% in controls and by 47-100% in patients. In contrast, rivaroxaban decreased thrombin generation by 55% in controls, but only by 11-38% in patients. These in vitro data suggest little prohemostatic effect of fresh frozen plasma and recombinant factor VIIa in acutely ill cirrhotics, whereas prothrombin complex concentrate and fibrinogen concentrate clearly improved hemostasis. Furthermore, our data suggest the requirement for dose-adjustments of commonly used anticoagulants in these patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A French National Survey on Clotting Disorders in Mastocytosis.

PubMed

Carvalhosa, Ana B; Aouba, Achille; Damaj, Gandhi; Canioni, Danielle; Brouzes, Chantal; Gyan, Emmanuel; Durupt, Stéphane; Durieu, Isabelle; Cathebras, Pascal; Costédoat-Chalumeau, Nathalie; Launay, David; Pilmis, Benoit; Barete, Stephane; Frenzel, Laurent; Lortholary, Olivier; Hermine, Olivier; Hermans, Cedric; Chandesris, Marie-Olivia

2015-10-01

Mastocytosis is characterized by a clonal mast cell proliferation with organ infiltration and uncontrolled degranulation. Although not characteristic and poorly explained, some patients develop clotting abnormalities. We retrospectively identified patients with established diagnosis of mastocytosis and related clotting abnormalities (clinical and/or biological) using the national French Reference Centre for Mastocytosis database. From our cohort of 14 adult patients with clotting abnormalities (median age 46 years [range 26-75]), 4 had a presentation suggestive of a primary hemostasis disorder alone (by their symptoms and/or abnormal clotting tests [PFA, von Willebrand's disease [vWD] screening]) and 10 had a laboratory impairment of secondary hemostasis. Among these, 7 had bleeds characteristic of a coagulation cascade disorder (severe/life-threatening in 5 and mild in 2 patients). Clotting abnormalities were of variable severity, typically related to intense crisis of degranulation, such as anaphylactic reactions, and/or to severe organ infiltration by mast cells. Importantly, classical hemostatic management with platelet transfusion, fresh frozen plasma, or vitamin K infusions was unsuccessful, as opposed to the use of agents inhibiting mast cell activity, particularly steroids. This illustrates the crucial role of mast cell mediators such as tryptase and heparin, which interfere both with primary (mainly via inhibition of von Willebrand factor) and secondary hemostasis. There was interestingly an unusually high number of aggressive mastocytosis (particularly mast cell leukemia) and increased mortality in the group with secondary hemostasis disorders (n = 5, 36% of the whole cohort). Mast cell degranulation and/or high tumoral burden induce both specific biologic antiaggregant and anticoagulant states with a wide clinical spectrum ranging from asymptomatic to life-threatening bleeds. Hemostatic control is achieved by mast cell inhibitors such as steroids.

Damage control: Concept and implementation.

PubMed

Malgras, B; Prunet, B; Lesaffre, X; Boddaert, G; Travers, S; Cungi, P-J; Hornez, E; Barbier, O; Lefort, H; Beaume, S; Bignand, M; Cotte, J; Esnault, P; Daban, J-L; Bordes, J; Meaudre, E; Tourtier, J-P; Gaujoux, S; Bonnet, S

2017-12-01

The concept of damage control (DC) is based on a sequential therapeutic strategy that favors physiological restoration over anatomical repair in patients presenting acutely with hemorrhagic trauma. Initially described as damage control surgery (DCS) for war-wounded patients with abdominal penetrating hemorrhagic trauma, this concept is articulated in three steps: surgical control of lesions (hemostasis, sealing of intestinal spillage), physiological restoration, then surgery for definitive repair. This concept was quickly adapted for intensive care management under the name damage control resuscitation (DCR), which refers to the modalities of hospital resuscitation carried out in patients suffering from traumatic hemorrhagic shock within the context of DCS. It is based mainly on specific hemodynamic resuscitation targets associated with early and aggressive hemostasis aimed at prevention or correction of the lethal triad of hypothermia, acidosis and coagulation disorders. Concomitant integration of resuscitation and surgery from the moment of admission has led to the concept of an integrated DCR-DCS approach, which enables initiation of hemostatic resuscitation upon arrival of the injured person, improving the patient's physiological status during surgery without delaying surgery. This concept of DC is constantly evolving; it stresses management of the injured person as early as possible, in order to initiate hemorrhage control and hemostatic resuscitation as soon as possible, evolving into a concept of remote DCR (RDCR), and also extended to diagnostic and therapeutic radiological management under the name of radiological DC (DCRad). DCS is applied only to the most seriously traumatized patients, or in situations of massive influx of injured persons, as its universal application could lead to a significant and unnecessary excess-morbidity to injured patients who could and should undergo definitive treatment from the outset. DCS, when correctly applied, significantly improves the survival rate of war-wounded. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Serum bilirubin levels are inversely associated with PAI-1 and fibrinogen in Korean subjects.

PubMed

Cho, Hyun Sun; Lee, Sung Won; Kim, Eun Sook; Shin, Juyoung; Moon, Sung Dae; Han, Je Ho; Cha, Bong Yun

2016-01-01

Oxidative stress may contribute to atherosclerosis and increased activation of the coagulation pathway. Bilirubin may reduce activation of the hemostatic system to inhibit oxidative stress, which would explain its cardioprotective properties shown in many epidemiological studies. This study investigated the association of serum bilirubin with fibrinogen and plasminogen activator inhibitor-1 (PAI-1), respectively. A cross-sectional analysis was performed on 968 subjects (mean age, 56.0 ± 11.2 years; 61.1% men) undergoing a general health checkup. Serum biochemistry was analyzed including bilirubin subtypes, insulin resistance (using homeostasis model of assessment [HOMA]), C-reactive protein (CRP), fibrinogen, and PAI-1. Compared with subjects with a total bilirubin (TB) concentration of <10.0 μmol/L, those with a TB concentration of >17.1 μmol/L had a smaller waist circumference, a lower triglyceride level, a lower prevalence of metabolic syndrome, and decreased HOMA-IR and CRP levels. Correlation analysis revealed linear relationships of fibrinogen with TB and direct bilirubin (DB), whereas PAI-1 was correlated with DB. After adjustment for confounding factors, bilirubin levels were inversely associated with fibrinogen and PAI-1 levels, respectively. Multivariate regression models showed a negative linear relationship between all types of bilirubin and fibrinogen, whereas there was a significant linear relationship between PAI-1 and DB. High bilirubin concentrations were independently associated with low levels of fibrinogen and PAI-1, respectively. The association between TB and PAI-1 was confined to the highest TB concentration category whereas DB showed a linear association with PAI-1. Bilirubin may protect against the development of atherothrombosis by reducing the hemostatic response. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Clinical use of virally inactived plasma. The experience of Blood Transfusion Unit in Mantova, Italy].

PubMed

Lepri, Debora; Capuzzo, Enrico; Mattioli, Anna Vittoria; Dall'Oglio, Daniela; Sgarioto, Vincenzo; Terenziani, Isabella; Caramaschi, Giacomo; Manzato, Franco; Franchini, Massimo

2013-03-01

Fresh Frozen Plasma (FFP) is a blood component whose clinical use is widespread worldwide. Transfusion safety of this product is ensured by legally obligatory tests. Although these tests are carried out on each plasma donation, safety levels can be further improved by using some technical procedures, such as, among others, methylene blue (MB) and solvent-detergent (SD) viral inactivation methods. The DMTE (Blood Transfusion Unit) in Mantova has used the pharmaceutical-like SD virally inactivated plasma since 2007 (Plasmasafe, Kedrion) as replacement of the PFC by each single donor. Guidelines for the usage of both products are the same. With the main aim of assessing the therapeutic effectiveness and safety of Plasmasafe, we decided to clinically monitor transfusions performed with this product on patients of the Intensive Care Unit at the city hospital in Mantova. In addition, we controlled some coagulation parameters (PT, aPTT, ATIII, Fibrinogen, PC, PS, FV, FVII, FVIII) before and 24 hours after the Plasmasafe infusion. From a clinical point of view, the use of Plasmasafe always led to a significant reduction, or complete stop, of the bleeding. No transfusion-related adverse events were recorded. As regards, the most relevant laboratory results, a marked increase in the above mentioned hemostatic parameters was detected. Furthermore, patients transfused with this product received a mean volume significantly lower than an historical cohort of patients treated with FFP (503 mL with Plasmasafe versus 1549 mL with FFP, P<0.001). The results of our study clearly document that Plasmasafe, a virally inactivated pharmaceutical-like product with a standardized content of coagulation factors, is a safe and cost-effective treatment, able to rapidly correct hemostatic abnormalities, for critical patients.

Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives.

PubMed

Salzano, Andrea; Arcopinto, Michele; Marra, Alberto M; Bobbio, Emanuele; Esposito, Daniela; Accardo, Giacomo; Giallauria, Francesco; Bossone, Eduardo; Vigorito, Carlo; Lenzi, Andrea; Pasquali, Daniela; Isidori, Andrea M; Cittadini, Antonio

2016-07-01

Klinefelter syndrome (KS) is the most frequently occurring sex chromosomal aberration in males, with an incidence of about 1 in 500-700 newborns. Data acquired from large registry-based studies revealed an increase in mortality rates among KS patients when compared with mortality rates among the general population. Among all causes of death, metabolic, cardiovascular, and hemostatic complication seem to play a pivotal role. KS is associated, as are other chromosomal pathologies and genetic diseases, with cardiac congenital anomalies that contribute to the increase in mortality. The aim of the current study was to systematically review the relationships between KS and the cardiovascular system and hemostatic balance. In summary, patients with KS display an increased cardiovascular risk profile, characterized by increased prevalence of metabolic abnormalities including Diabetes mellitus (DM), dyslipidemia, and alterations in biomarkers of cardiovascular disease. KS does not, however, appear to be associated with arterial hypertension. Moreover, KS patients are characterized by subclinical abnormalities in left ventricular (LV) systolic and diastolic function and endothelial function, which, when associated with chronotropic incompetence may led to reduced cardiopulmonary performance. KS patients appear to be at a higher risk for cardiovascular disease, attributing to an increased risk of thromboembolic events with a high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism with higher risk of deep venous thrombosis or pulmonary embolism. It appears that cardiovascular involvement in KS is mainly due to chromosomal abnormalities rather than solely on low serum testosterone levels. On the basis of evidence acquisition and authors' own experience, a flowchart addressing the management of cardiovascular function and prognosis of KS patients has been developed for clinical use. © 2016 European Society of Endocrinology.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

PubMed

Li, Jing; Cao, Wei; Lv, Xiao-xing; Jiang, Li; Li, Yue-jun; Li, Wang-zhou; Chen, Shao-zong; Li, Xue-yong

2013-03-01

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca(2+) concentration, while Na(+) and K(+) concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca(2+) and Na(+) concentrations. Si(4+) (0.2434 g/L) and Al(3+) (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca(2+) concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca(2+) into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

The management of vertebral artery injury in anterior cervical spine operation: a systematic review of published cases.

PubMed

Park, Hyung-Ki; Jho, Hae-Dong

2012-12-01

Anterior cervical spine operations (ACSO) are generally considered to be safe and effective, but the vertebral artery (VA) is at risk during the procedure. Because the consequences of VA injury can be catastrophic, properly managing a VA injury is very important. However, due to the rarity of these injuries, there is no agreed upon treatment strategy. Studies were identified for inclusion in the review via sensitive searches of electronic databases through 31 December 2011. All cases included in the review were qualitatively analyzed to explore the relationship between type of VA injury management and neurological complications. Seventeen articles describing 39 cases of VA injury during ACSO were included in this study. Seven patients (17.9 %) had neurological complications followed by VA insufficiency. Two patients (5.1 %) had root damage due to ligation. One case (2.6 %) resulted in intraoperative death due to fatal bleeding. Delayed vascular complications were identified in nine (45.0 %) of the 20 patients that underwent only tamponade or hemostatic agent during the operation. Four patients underwent intraoperative endovascular treatment, and three of these patients had a cerebral infarction. All three patients who underwent clipping also had neurological complications. The five patients treated by direct repair did not have any complications. Our review suggests the management of VA injury should be considered in order listed: (1) performing tamponade with a hemostatic agent, (2) direct repair, (3) postoperative endovascular procedures to prevent delayed complications. If tamponade fails to achieve proper hemostasis, additional procedures as endovascular embolization, clipping and ligation should be considered but carry the risk of neurological complications. Because of the limitations of this review, further studies are recommended with larger sample sizes.

Refrigerated storage of platelets initiates changes in platelet surface marker expression and localization of intracellular proteins.

PubMed

Wood, Ben; Padula, Matthew P; Marks, Denese C; Johnson, Lacey

2016-10-01

Platelets (PLTs) are currently stored at room temperature (22°C), which limits their shelf life, primarily due to the risk of bacterial growth. Alternatives to room temperature storage include PLT refrigeration (2-6°C), which inhibits bacterial growth, thus potentially allowing an extension of shelf life. Additionally, refrigerated PLTs appear more hemostatically active than conventional PLTs, which may be beneficial in certain clinical situations. However, the mechanisms responsible for this hemostatic function are not well characterized. The aim of this study was to assess the protein profile of refrigerated PLTs in an effort to understand these functional consequences. Buffy coat PLTs were pooled, split, and stored either at room temperature (20-24°C) or under refrigerated (2-6°C) conditions (n = 8 in each group). PLTs were assessed for changes in external receptor expression and actin filamentation using flow cytometry. Intracellular proteomic changes were assessed using two-dimensional gel electrophoresis and Western blotting. PLT refrigeration significantly reduced the abundance of glycoproteins (GPIb, GPIX, GPIIb, and GPIV) on the external membrane. However, refrigeration resulted in the increased expression of high-affinity integrins (αIIbβ3 and β1) and activation and apoptosis markers (CD62P, CD63, and phosphatidylserine). PLT refrigeration substantially altered the abundance and localization of several cytoskeletal proteins and resulted in an increase in actin filamentation, as measured by phalloidin staining. Refrigerated storage of PLTs induces significant changes in the expression and localization of both surface-expressed and intracellular proteins. Understanding these proteomic changes may help to identify the mechanisms resulting in the refrigeration-associated alterations in PLT function and clearance. © 2016 AABB.

Is prophylaxis required for delivery in women with factor VII deficiency?

PubMed Central

Baumann Kreuziger, Lisa M.; Morton, Colleen T.; Reding, Mark T.

2013-01-01

Introduction Factor VII (fVII) deficiency is a rare congenital bleeding disorder in which fVII activity level and bleeding tendency do not completely correlate. Pregnancy and delivery present a significant hemostatic challenge to women with fVII deficiency. Treatment with recombinant factor VIIa (rfVIIa) carries a thrombotic risk and the literature is unclear whether prophylaxis is necessary prior to delivery. Aim To define management, hemorrhagic and thrombotic complications of pregnant women with fVII deficiency through a systematic review. Methods Medical databases (PubMed, MEDLINE, CINAHL, Academic Search Premier, Cochrane Library, Web of Science and Scopus) were searched using “factor VII deficiency” and “pregnancy” or “surgery.” Overall 34 articles, 4 abstracts, and 3 institutional cases were reviewed. Results Literature from 1953–2011 reported 94 live births from 62 women with fVII deficiency. The median fVII activity was 5.5%. Hemostatic prophylaxis was used in 32% of deliveries. Without prophylaxis, 40 vaginal deliveries and 16 cesarean sections were completed. The odds of receiving prophylaxis were 2.9 times higher in women undergoing cesarean section compared to vaginal delivery. Post-partum hemorrhage occurred in 10% of deliveries with prophylaxis and 13% of deliveries without prophylaxis. The fVII level did not significantly differ between women who did and did not receive prophylaxis. Conclusion We present the only systematic review of the management of pregnancy in fVII deficient women. No difference in post-partum hemorrhage was seen in deliveries with and without prophylaxis. Therefore we recommend that rfVIIa be available in the case of hemorrhage or surgical intervention, but not as mandatory prophylaxis. PMID:23607277

Recombinant factor VIIa (eptacog alfa): a review of its use in congenital hemophilia with inhibitors, acquired hemophilia, and other congenital bleeding disorders.

PubMed

Croom, Katherine F; McCormack, Paul L

2008-01-01

Recombinant factor VIIa (NovoSeven; also known as recombinant activated factor VII or eptacog alfa) is structurally similar to human plasma-derived coagulation factor VIIa, but is manufactured using DNA biotechnology. Recombinant factor VIIa interacts with thrombin-activated platelets to produce a thrombin burst leading to accelerated fibrin clot formation localized to the site of vascular injury. It is approved in many countries for use as an intravenous hemostatic agent in patients with congenital hemophilia with inhibitors, and also for acquired hemophilia, factor VII deficiency, and Glanzmann thrombasthenia in some countries. Studies have shown it to be effective and generally well tolerated when used intravenously to treat bleeding episodes or provide hemostatic cover during surgery in patients with congenital hemophilia with inhibitors, acquired hemophilia, factor VII deficiency or Glanzmann thrombasthenia. Based on available data, its efficacy in terms of patient-assessed response may be similar to that of activated prothrombin complex concentrate (aPCC), but treatment with a single 270 microg/kg dose of recombinant factor VIIa might reduce the need for rescue therapy compared with aPCC. Recombinant factor VIIa is not immunogenic in patients with hemophilia, does not produce an anamnestic response in hemophilia patients with inhibitors, and has very low thrombogenicity. It is recommended in guidelines as the treatment of choice for bleeds in patients with hemophilia B with high-responding inhibitors and for patients with factor VII deficiency, and is also a first-line therapeutic option for high-responder hemophilia A patients with inhibitors and those with acquired hemophilia. Cost data from pharmacoeconomic analyses support its use in hemophilia patients with inhibitors. Thus, recombinant factor VIIa is a valuable treatment option for patients with these rare, but potentially serious, bleeding disorders.

Long- and Short-Term Exposure To Air Pollution and Inflammatory/Hemostatic Markers in Midlife Women

PubMed Central

Green, Rochelle; Broadwin, Rachel; Malig, Brian; Basu, Rupa; Gold, Ellen B.; Qi, Lihong; Sternfeld, Barbara; Bromberger, Joyce T.; Greendale, Gail A.; Kravitz, Howard M.; Tomey, Kristin; Matthews, Karen; Derby, Carol; Jackson, Elizabeth A.; Green, Robin; Ostro, Bart

2016-01-01

Background Studies have reported associations between long-term air pollution exposures and cardiovascular mortality. The biological mechanisms connecting them remain uncertain. Methods We examined associations of fine particles (PM2.5) and ozone with serum markers of cardiovascular disease risk in a cohort of midlife women. We obtained information from women enrolled at six sites in the multi-ethnic, longitudinal Study of Women's Health Across the Nation, including repeated measurements of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor Type 1 (PAI-1), and Factor VIIc (Factor VII coagulant activity). We obtained residence-proximate PM2.5 and ozone monitoring data for a maximum five annual visits, calculating prior year, six-month, one-month, and one-day exposures and their relations to serum markers using longitudinal mixed models. Results For the 2,086 women studied from 1999 through 2004, PM2.5 exposures were associated with all blood markers except Factor VIIc after adjusting for age, race/ethnicity, education, site, body mass index, smoking, and recent alcohol use. Adjusted associations were of the strongest for prior year exposures for hs-CRP (21% increase per 10 μg/m3 PM2.5, 95% CI: 6.6, 37), tPA-ag (8.6%, 95% CI: 1.8, 16), and PAI-1 (35%, 95% CI: 19, 53). An association was also observed between year prior ozone exposure and Factor VIIc (5.7% increase per 10 ppb ozone, 95% CI: 2.9, 8.5). Conclusions Our findings suggest that prior year exposures to PM2.5 and ozone are associated with adverse effects on inflammatory and hemostatic pathways for cardiovascular outcomes in midlife women. PMID:26600256

Moderate-intensity exercise improves the thromboelastography coagulation index in children with severe hemophilia A.

PubMed

Li, Kui-Xing; Xiao, Juan; Zhao, Yong-Qiang; Shou, Wei-Ling; Chen, Meng; Li, Zhuo; Poon, Man-Chiu; Han, Hui-Jun

2016-10-01

This pilot study explored the effect of moderate-intensity exercise on factor VIII (FVIII) activity and global hemostatic status of the children with severe hemophilia A. Eleven children aged 6 to 15 years with severe hemophilia A participated in a moderate-intensity exercise test by using Recumbent Cross Trainer (NuStep, T5XR) for at least 10 min after reaching the target heart rate or until volitional exhaustion within a safety framework. Blood samples were collected pre and postexercise for plasma FVIII: C and thromboelastography (TEG) parameters and coagulation index. The average duration of exercise was 11.8 min (10-13 min). There was no report on bleeding events or adverse symptoms requiring termination of the exercise test. The average FVIII activity of the 11 children was 0.66 (0.5-0.8) IU/dl before and 0.93 (0.5-2.3) IU/dl after exercise. The increase of FVIII in the 11 children as a group was not statistically significant (P = 0.052). There were significant changes of TEG measurements, with shortening of R (P < 0.05), and increase in K decrease (P < 0.05), alpha angle (P < 0.05), maximum amplitude (P < 0.05), and coagulation index (P < 0.01). Among the 11 children, the relative coagulation index increase after exercise was greater than 50% in seven (63.6%), less than 20% in three (27.3%), and less than 10% in one (9.1%). TEG analysis showed that the global hemostatic function for the children with severe hemophilia A can be enhanced after moderate-intensity exercise.

A prospective observational study evaluating the efficacy of prophylactic internal iliac artery balloon catheterization in the management of placenta previa–accreta

PubMed Central

Fan, Yao; Gong, Xun; Wang, Nan; Mu, Ketao; Feng, Ling; Qiao, Fuyuan; Chen, Suhua; Zeng, Wanjiang; Liu, Haiyi; Wu, Yuanyuan; Zhou, Qiong; Tian, Yuan; Li, Qiang; Yang, Meitao; Li, Fanfan; He, Mengzhou; Beejadhursing, Rajluxmee; Deng, Dongrui

2017-01-01

Abstract We studied the efficacy of prophylactic internal iliac artery balloon catheterization for managing severe hemorrhage caused by pernicious placenta previa. This prospective observational study was conducted in Tongji Hospital, Wuhan, China. One hundred sixty-three women past 32-week's gestation with placenta previa–accreta were recruited and managed. Women in the balloon group accepted prophylactic internal iliac artery balloon catheterization before scheduled caesarean delivery and controls had a conventional caesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications, and neonatal outcomes were discussed. Significant differences were detected in estimated blood loss (1236.0 mL vs 1694.0 mL, P = .01), calculated blood loss (CBL) (813.8 mL vs 1395.0 mL, P < .001), CBL of placenta located anteriorly (650.5 mL vs 1196.0 mL, P = .03), and anterioposteriorly (928.3 mL vs 1680.0 mL, P = .02). Prophylactic balloon catheterization could reduce intraoperative red blood cell transfusion (728.0 mL vs 1205.0 mL, P = .01) and lessen usage of perioperative hemostatic methods. The incidence of hysterectomy was lower in balloon group. Mean radiation dose was 29.2 mGy and mean exposure time was 92.2 seconds. Neonatal outcomes and follow-up data did not have significant difference. Prophylactic internal iliac artery balloon catheterization is an effective method for managing severe hemorrhage caused by placenta previa–accreta as it reduced intraoperative blood loss, lessened perioperative hemostatic measures and intraoperative red cell transfusions, and reduce hysterectomies. PMID:29137011

Platelet gene therapy improves hemostatic function for integrin αIIbβ3-deficient dogs

PubMed Central

Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

2011-01-01

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects. PMID:21606353

A systems approach to hemostasis: 4. How hemostatic thrombi limit the loss of plasma-borne molecules from the microvasculature

PubMed Central

Welsh, John D.; Muthard, Ryan W.; Stalker, Timothy J.; Taliaferro, Joshua P.; Diamond, Scott L.

2016-01-01

Previous studies have shown that hemostatic thrombi formed in response to penetrating injuries have a core of densely packed, fibrin-associated platelets overlaid by a shell of less-activated, loosely packed platelets. Here we asked, first, how the diverse elements of this structure combine to stem the loss of plasma-borne molecules and, second, whether antiplatelet agents and anticoagulants that perturb thrombus structure affect the re-establishment of a tight vascular seal. The studies combined high-resolution intravital microscopy with a photo-activatable fluorescent albumin marker to simultaneously track thrombus formation and protein transport following injuries to mouse cremaster muscle venules. The results show that protein loss persists after red cell loss has ceased. Blocking platelet deposition with an αIIbβ3 antagonist delays vessel sealing and increases extravascular protein accumulation, as does either inhibiting adenosine 5′-diphosphate (ADP) P2Y12 receptors or reducing integrin-dependent signaling and retraction. In contrast, sealing was unaffected by introducing hirudin to block fibrin accumulation or a Gi2α gain-of-function mutation to expand the thrombus shell. Collectively, these observations describe a novel approach for studying vessel sealing after injury in real time in vivo and show that (1) the core/shell architecture previously observed in arterioles also occurs in venules, (2) plasma leakage persists well beyond red cell escape and mature thrombus formation, (3) the most critical events for limiting plasma extravasation are the stable accumulation of platelets, ADP-dependent signaling, and the emergence of a densely packed core, not the accumulation of fibrin, and (4) drugs that affect platelet accumulation and packing can delay vessel sealing, permitting protein escape to continue. PMID:26738537

Clotting Factor Changes during the First Cycle of Oral Contraceptive Use

PubMed Central

Westhoff, Carolyn L.; Eisenberger, Andrew; Tang, Rosalind; Cremers, Serge; Grossman, Lisa V.; Pike, Malcolm C.

2016-01-01

Objectives The risk of venous thromboembolism (VTE) is highest during the initial months of oral contraceptive (OC) use. We sought to evaluate the extent of hemostatic variable changes during the initial OC cycle and if such changes are related to systemic ethinyl estradiol (EE2) exposure. Study Design Participants provided multiple blood samples during a 21-day OC cycle (30 mcg EE2; 150 mcg levonorgestrel) and after a single dose following a wash-out period. Analytes included D-dimer, factor VIII activity, protein C total antigen and the hepatic proteins corticosteroid- and sex-hormone-binding globulins (CBG and SHBG). EE2 pharmacokinetic analyses related to the 24 hours after the first OC tablet (OC1) and at steady state (OC21). Results Seventeen women completed the study. D-dimer more than doubled by OC6 (p = 0.013) and remained elevated at OC21 (p=0.012). D-dimer levels within women varied widely from day-to-day. Factor VIII increased 27% by OC2 (p < 0.001), but declined to a 9% increase by OC21. Protein C increased only 6%. EE2 steady-state area-under-the-curve ranged from 488 to 1103 pg·h/mL; higher levels were not correlated with greater increases in clotting variables. CBG and SHBG increased significantly, but were not significantly correlated with levels of EE2 or with the hemostatic variables. Conclusions D-dimer increases during the first OC cycle were at least as great as increases seen with longer OC use. These results provide support for the increased VTE risk during initial OC use. The extreme variability in D-dimer levels may be an important component of this risk. PMID:26452328

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

PubMed Central

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.

PubMed

Fang, Juan; Jensen, Eric S; Boudreaux, Mary K; Du, Lily M; Hawkins, Troy B; Koukouritaki, Sevasti B; Cornetta, Kenneth; Wilcox, David A

2011-06-07

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

Development of Novel Criteria of the "Lethal Triad" as an Indicator of Decision Making in Current Trauma Care: A Retrospective Multicenter Observational Study in Japan.

PubMed

Endo, Akira; Shiraishi, Atsushi; Otomo, Yasuhiro; Kushimoto, Shigeki; Saitoh, Daizoh; Hayakawa, Mineji; Ogura, Hiroshi; Murata, Kiyoshi; Hagiwara, Akiyoshi; Sasaki, Junichi; Matsuoka, Tetsuya; Uejima, Toshifumi; Morimura, Naoto; Ishikura, Hiroyasu; Takeda, Munekazu; Kaneko, Naoyuki; Kato, Hiroshi; Kudo, Daisuke; Kanemura, Takashi; Shibusawa, Takayuki; Hagiwara, Yasushi; Furugori, Shintaro; Nakamura, Yoshihiko; Maekawa, Kunihiko; Mayama, Gou; Yaguchi, Arino; Kim, Shiei; Takasu, Osamu; Nishiyama, Kazutaka

2016-09-01

To evaluate the utility of the conventional lethal triad in current trauma care practice and to develop novel criteria as indicators of treatment strategy. Retrospective observational study. Fifteen acute critical care medical centers in Japan. In total, 796 consecutive trauma patients who were admitted to emergency departments with an injury severity score of greater than or equal to 16 from January 2012 to December 2012. None. All data were retrospectively collected, including laboratory data on arrival. Sensitivities to predict trauma death within 28 days of prothrombin time international normalized ratio greater than 1.50, pH less than 7.2, and body temperature less than 35°C were 15.7%, 17.5%, and 15.9%, respectively, and corresponding specificities of these were 96.4%, 96.6%, and 93.6%, respectively. The best predictors associated with hemostatic disorder and acidosis were fibrin/fibrinogen degradation product and base excess (the cutoff values were 88.8 µg/mL and -3.05 mmol/L). The optimal cutoff value of hypothermia was 36.0°C. The impact of the fibrin/fibrinogen degradation product and base excess abnormality on the outcome were approximately three- and two-folds compared with those of hypothermia. Using these variables, if the patient had a hemostatic disorder alone or a combined disorder with acidosis and hypothermia, the sensitivity and specificity were 80.7% and 66.8%. Because of the low sensitivity and high specificity, conventional criteria were unsuitable as prognostic indicators. Our revised criteria are assumed to be useful for predicting trauma death and have the potential to be the objective indicators for activating the damage control strategy in early trauma care.

Chronic dietary fat intake modifies the postprandial response of hemostatic markers to a single fatty test meal.

PubMed

Delgado-Lista, Javier; Lopez-Miranda, Jose; Cortés, Begoña; Perez-Martinez, Pablo; Lozano, Aquiles; Gomez-Luna, Rafael; Gomez, Purificacion; Gomez, Maria Jose; Criado, Juan; Fuentes, Francisco; Perez-Jimenez, Francisco

2008-02-01

Hemostasis is the result of a complex equilibrium between coagulation and fibrinolysis, and the influence of different dietary models on this equilibrium is not entirely known. The objective was to compare the effects of the chronic intake of different dietary models on postprandial hemostasis. In a randomized crossover design, 20 healthy men consumed for 28 d each diets rich in monounsaturated fatty acids (MUFAs), saturated fatty acids (SFAs), and carbohydrates plus n-3 fatty acids (CHO/N3). Fasting and postprandial hemostatic factors (factor VII coagulant activity, plasminogen activator inhibitor-1, tissue-type plasminogen activator, d-dimer, and thromboxane B(2)) were measured; meal tests for the postprandial measures were based on butter, virgin olive oil, and walnuts for the SFA, MUFA, and CHO/N3 diets, respectively. There were no differences in the fasting variables after the dietary periods. After the 3 fatty meals were consumed, we observed an increase in thromboxane B(2) and d-dimer and a reduction in tissue plasminogen activator, irrespective of the dietary model. The MUFA or CHO/N3 meals lowered postprandial concentrations of factor VII coagulant activity, although the reduction was greater after the MUFA-enriched meal. The concentration of plasminogen activator inhibitor-1 was greater after the SFA meal than after the other 2 meals. The administration of a fatty meal induces a postprandial procoagulant tendency, irrespective of the type of fat consumed. However, the use of a dietary model rich in SFA creates a more procoagulant environment than does a model that includes MUFA or CHO/N3 as the source of fatty acids.

The hemostatic profile of recombinant activated factor VII. Can low concentrations stop bleeding in off-label indications?

PubMed Central

2010-01-01

Background High concentrations of recombinant activated factor VII (rFVIIa) can stop bleeding in hemophilic patients. However the rFVIIa dose needed for stopping haemhorrage in off-label indications is unknown. Since thrombin is the main hemostatic agent, this study investigated the effect of rFVIIa and tissue factor (TF) on thrombin generation (TG) in vitro. Methods Lag time (LT), time to peak (TTP), peak TG (PTG), and area under the curve after 35 min (AUCo-35 min) with the calibrated automated thrombography was used to evaluate TG. TG was assayed in platelet-rich plasma (PRP) samples from 29 healthy volunteers under basal conditions and after platelet stimulation with 5.0 μg/ml, 2.6 μg/ml, 0.5 μg/ml, 0.25 μg/ml, and 0.125 μg/ml rFVIIa alone and in normal platelet-poor plasma (PPP) samples from 22 healthy volunteers, rFVIIa in combination with various concentrations of TF (5.0, 2.5, 1.25 and 0.5 pM). Results In PRP activated by rFVIIa, there was a statistically significant increase in TG compared to basal values. A significant TF dose-dependent shortening of LT and increased PTG and AUCo→35 min were obtained in PPP. The addition of rFVIIa increased the effect of TF in shorting the LT and increasing the AUCo→35 min with no effect on PTG but were independent of rFVIIa concentration. Conclusion Low concentrations of rFVIIa were sufficient to form enough thrombin in normal PRP or in PPP when combined with TF, and suggest low concentrations for normalizing hemostasis in off-label indications. PMID:20444280

Dental management of patients receiving anticoagulant and/or antiplatelet treatment

PubMed Central

Chaveli-López, Begonya; Gavaldá-Esteve, Carmen

2014-01-01

Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can give rise to complications associated with important morbidity-mortality. The dental treatment of patients who tend to an increased risk of bleeding due to the use of anticoagulant and/or antiplatelet drugs raises a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis, and the optimized management of such patients, are therefore very important issues. Objectives: A study is made of the anticoagulant / antiplatelet drugs currently available on the market, with evaluation of the risks and benefits of suspending such drugs prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and Methods: A literature search was made in the PubMed, Cochrane Library and Scopus databases, covering all studies published in the last 5 years in English and Spanish. Studies conducted in humans and with scientific evidence levels 1 and 2 (metaanalyses, systematic reviews, randomized phase 1 and 2 trials, cohort studies and case-control studies) were considered. The keywords used for the search were: tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol. Results and Conclusions: Many management protocols have been developed, though in all cases a full clinical history is required, together with complementary hemostatic tests to minimize any risks derived from dental treatment. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from dental treatment. Key words:Tooth extraction, oral surgery, hemostasis, platelet aggregation inhibitors, antiplatelet drugs, anticoagulants, warfarin, acenocoumarol. PMID:24790716

Comparison of analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair.

PubMed

Bergmann, Hannes M; Nolte, Ingo; Kramer, Sabine

2007-10-01

To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. Blind, randomized clinical study. Dogs with femoral (n=18) or pelvic (27) fractures. Dogs were grouped by restricted randomization into 4 groups: group 1 = carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2 = carprofen immediately after extubation, no epidural anesthesia; group 3 = carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4 = mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.

Extraterrestrial Hemorrhage Control: Terrestrial Developments in Technique, Technology, and Philosophy with Applicability to Traumatic Hemorrhage in Space

NASA Technical Reports Server (NTRS)

Kirkpatrick, Andrew; Dawson, David; Campbell, Mark; Jones, Jeff; Ball, Chad G.; Hamilton, Douglas R.; Dulchavsky, Scott; McBeth, Paul; Holcomb, John

2004-01-01

Managing injury and illness during long duration space flight limits efforts to explore beyond low earths orbit. Traumatic injury may be expected to occur in space and is a frequent cause of preventable deaths, often related to uncontrolled or ongoing hemorrhage (H). Such bleeding causes 40% of terrestrial injury mortality. Current guidelines emphasize early control of H compared to intravenous infusions. Recent advances in surgical and critical care may be applicable to trauma care in space, with appropriate considerations of the extreme logistical and personnel limitations. Methods: Recent developments in technique, resuscitation fluids, hemoglobin (Hb) substitutes, hemostatic agents, interventional angiography, damage control principles, and concepts related to suspended animation were reviewed. Results: H associated with instability frequently requires definitive intervention. Direct pressure should be applied to all compressible bleeding, but novel approaches are required for intracavitary noncompressible bleeding. Intravenous hemostatic agents such as recombinant Factor VII may facilitate hemostasis especially when combined with a controlled hypotension approach. Both open and laparoscopic techniques could be used in weightlessness, but require technical expertise not likely to be available. Specific rehearsed invasive techniques such as laparotomy with packing, or arterial catherterization with with robotic intravascular embolization might be considered . Hemodynamic support, thermal manipulation, or pharmacologic induction of a state of metabolic down regulation for whole body preservation may be appropriate. Hypertonic saline, with or without dextran, may temporize vascular support and decrease reperfusion injury, with less mass than other solutions. Hb substitutes have other theoretical advantages. Conclusions: Terrestrial developments suggest potential novel strategies to control H in space, but will required a coordinated program of evaluation and training to evaluate.

Identifying the bleeding trauma patient: predictive factors for massive transfusion in an Australasian trauma population.

PubMed

Hsu, Jeremy Ming; Hitos, Kerry; Fletcher, John P

2013-09-01

Military and civilian data would suggest that hemostatic resuscitation results in improved outcomes for exsanguinating patients. However, identification of those patients who are at risk of significant hemorrhage is not clearly defined. We attempted to identify factors that would predict the need for massive transfusion (MT) in an Australasian trauma population, by comparing those trauma patients who did receive massive transfusion with those who did not. Between 1985 and 2010, 1,686 trauma patients receiving at least 1 U of packed red blood cells were identified from our prospectively maintained trauma registry. Demographic, physiologic, laboratory, injury, and outcome variables were reviewed. Univariate analysis determined significant factors between those who received MT and those who did not. A predictive multivariate logistic regression model with backward conditional stepwise elimination was used for MT risk. Statistical analysis was performed using SPSS PASW. MT patients had a higher pulse rate, lower Glasgow Coma Scale (GCS) score, lower systolic blood pressure, lower hemoglobin level, higher Injury Severity Score (ISS), higher international normalized ratio (INR), and longer stay. Initial logistic regression identified base deficit (BD), INR, and hemoperitoneum at laparotomy as independent predictive variables. After assigning cutoff points of BD being greater than 5 and an INR of 1.5 or greater, a further model was created. A BD greater than 5 and either INR of 1.5 or greater or hemoperitoneum was associated with 51 times increase in MT risk (odds ratio, 51.6; 95% confidence interval, 24.9-95.8). The area under the receiver operating characteristic curve for the model was 0.859. From this study, a combination of BD, INR, and hemoperitoneum has demonstrated good predictability for MT. This tool may assist in the determination of those patients who might benefit from hemostatic resuscitation. Prognostic study, level III.

Topical hemostatic powder promotes reepithelialization and reduces scar formation after extensive esophageal mucosal resection.

PubMed

Beye, B; Barret, M; Alatawi, A; Beuvon, F; Nicco, C; Pratico, C A; Chereau, C; Chaussade, S; Batteux, F; Prat, F

2016-08-01

The development of techniques for endoscopic resection has provided new strategies for radical conservative treatment of superficial esophageal neoplasms, even those that are circumferential, such as Barrett's neoplasia. However, it is necessary to prevent the formation of scar tissue that can be responsible for esophageal strictures following circumferential resection. Preliminary data have suggested the possible efficacy of a hemostatic powder in the promotion of wound healing. The study aims to assess the effectiveness of Hemospray (Cook Medical) in a swine model of post-endoscopic esophageal stricture. Our prospective controlled study included 21 pigs. A 6-cm circumferential submucosal dissection of the esophagus (CESD) was performed in each pig. Group 1 (n = 11) only underwent CESD and Group 2 (n = 10) had repeated Hemospray applications after CESD. Clinical, endoscopic, and radiological monitoring were performed, blood levels of four inflammatory or pro-fibrotic cytokines were assessed, and histological analysis was performed. Median esophageal diameter was greater in the group treated with Hemospray (2 mm [1-3] vs. 3 mm [2-4], P = 0.01), and the rate of symptomatic esophageal stricture was 100% and 60% in Groups 1 and 2, respectively (P = 0.09). The thicknesses of esophageal fibrosis and inflammatory cell infiltrate were significantly lower in Group 2 than in Group 1 (P = 0.002 and 0.0003, respectively). The length of the neoepithelium was greater in Group 2 than in Group 1 (P = 0.0004). Transforming growth factor-β levels were significantly lower in Group 2 than in Group 1 (P = 0.01). The application of Hemospray after esophageal CESD reduces scar tissue formation and promotes reepithelialization, and therefore is a promising therapeutic approach in the prevention of post-endoscopic esophageal stricture. © 2015 International Society for Diseases of the Esophagus.

Efficacy, Reliability, and Safety of Completely Autologous Fibrin Glue in Neurosurgical Procedures: Single-Center Retrospective Large-Number Case Study.

PubMed

Nakayama, Noriyuki; Yano, Hirohito; Egashira, Yusuke; Enomoto, Yukiko; Ohe, Naoyuki; Kanemura, Nobuhiro; Kitagawa, Junichi; Iwama, Toru

2018-01-01

Commercially available fibrin glue (Com-FG), which is used commonly worldwide, is produced with pooled human plasma from multiple donors. However, it has added bovine aprotinin, which involves the risk of infection, allogenic immunity, and allergic reactions. We evaluate the efficacy, reliability, and safety of completely autologous fibrin glue (CAFG). From August 2014 to February 2016, prospective data were collected and analyzed from 153 patients. CAFG was prepared with the CryoSeal System using autologous blood and was applied during neurosurgical procedures. Using CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets, we performed a pinpoint hemostasis, transposed the offending vessels in a microvascular decompression, and covered the dural incision to prevent cerebrospinal fluid leakage. The CryoSeal System had generated up to a mean of 4.51 mL (range, 3.0-8.4 mL) of CAFG from 400 mL autologous blood. Com-FG products were not used in our procedures. Only 6 patients required an additional allogeneic blood transfusion. The hemostatic effective rate was 96.1% (147 of 153 patients). Only 1 patient who received transsphenoidal surgery for a pituitary adenoma presented with the complication of delayed postoperative cerebrospinal fluid leakage (0.65%). No patient developed allergic reactions or systemic complications associated with the use of CAFG. CAFG effectively provides hemostatic, adhesive, and safety performance. The timing and three-dimensional shape of CAFG-soaked oxidized regenerated cellulose and/or polyglycolic acid sheets solidification can be controlled with slow fibrin formation. The cost to prepare CAFG is similar compared with Com-FG products, and it can therefore be easily used at most institutions. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of aliskiren and valsartan combination versus aliskiren monotherapy on hemostatic biomarkers in hypertensive diabetics: Aliskiren and Valsartan Impact in Diabetics pilot trial.

PubMed

Serebruany, Victor L; Pokov, Alex N; Aradi, Daniel; Can, Mehmet; DiNicolantonio, James; Kipshidze, Nodar; Atar, Dan

2014-01-01

Valsartan is known to inhibit platelet activity in both in vitro and ex vivo clinical setting, whereas aliskiren in vitro modulates antithrombin-III in plasma. The authors tested how aliskiren and valsartan combination versus aliskiren monotherapy will affect hemostatic biomarkers in mild-to-moderate hypertensive diabetics in the frame of the Aliskiren and Valsartan Impact in Diabetics (AVID) trial. A total of 52 patients with type 2 diabetes and mild-to-moderate hypertension were equally randomized to aliskiren (150-300 mg/d) and valsartan (160 mg/d) versus aliskiren (150-300 mg/d) alone for 4 weeks. A total of 25 biomarkers were serially measured, of which 16 are related to platelet function, 6 to coagulation, and 3 to fibrinolysis. Aliskiren monotherapy has no significant impact on any of the assessed biomarkers. In contrast, valsartan on top of aliskiren provided significant inhibition of ADP-induced platelet aggregation (P=0.032), decreased shear-induced activation measured with PFA-100 analyzer (P=0.041), and diminished expression of GP IIb/IIIa activity (P=0.027) measured by PAC-1 antibody, GP Ib (CD42b, P=0.033), vitronectin receptor (CD51/61, P=0.046), P-selectin (CD62p, P=0.026), lysosome-associated membrane protein (CD107a, P=0.042), and CD40-ligand (CD154, P=0.048). In AVID trial, valsartan in combination with aliskiren mildly but significantly inhibited platelets, confirming previous observations. In contrast, aliskiren monotherapy does not enhance antithrombin activity, suggesting that previous data probably represent a laboratory artifact. Importantly, these randomized data were generated on top of low-dose daily aspirin, supporting extra benefit for combination use of angiotensin receptor blockers and renin inhibitors in high-risk diabetic population.

Facilitating Hemostasis After Proximal Aortic Surgery: Results of The PROTECT Trial.

PubMed

Khoynezhad, Ali; DelaRosa, Jacob; Moon, Marc R; Brinkman, William T; Thompson, Richard B; Desai, Nimesh D; Malaisrie, S Chris; Girardi, Leonard N; Bavaria, Joseph E; Reece, T Brett

2018-05-01

This study intended to evaluate the safety and hemostatic efficacy of a novel vascular sealant (Tridyne; Neomend, Inc, Irvine, CA) compared with an accepted adjunctive hemostatic agent applied to aortotomy and sutures lines in cardiovascular operations. Patients undergoing aortic valve replacement, ascending aortic replacement, or aortic root replacement were randomly assigned 2:1 to Tridyne (n = 107) or Gelfoam Plus (Baxter Healthcare Corp, Hayward, CA) (n = 51). These groups were similar with regard to age, sex, race, medical history, duration of bypass and cross-clamping, and number of suture lines treated. Suture lines were treated after confirmation of some leakage but before formal removal of the clamp. The median bleeding time was significantly lower for Tridyne versus Gelfoam Plus (0 versus 10.0 minutes, p < 0.0001). Immediate hemostasis was achieved in 59.4% of the Tridyne group versus 16.0% of Gelfoam Plus group (p < 0.0001). A significantly greater proportion of patients in the Tridyne group achieved successful hemostasis at the aortic suture line than patients in the Gelfoam Plus group (85.7% versus 40.0%, p < 0.0001). The Clinical Events Committee adjudicated 7 patients with possible device-related serious adverse events: 3 patients (2.9%) in the Tridyne group and 4 patients (8.2%) in the Gelfoam Plus group (p = 0.2097). Tridyne was safe and effective when used as an adjunct to conventional hemostasis to treat high-pressure vessels in patients who receive anticoagulation agents, in reducing time to hemostasis, and in promoting both immediate and persistent hemostasis. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Tissue factor levels and the fibrinolytic system in thin and thick intraluminal thrombus and underlying walls of abdominal aortic aneurysms.

PubMed

Siennicka, Aldona; Zuchowski, Marta; Kaczmarczyk, Mariusz; Cnotliwy, Miłosław; Clark, Jeremy Simon; Jastrzębska, Maria

2018-03-20

The hemostatic system cooperates with proteolytic degradation in processes allowing abdominal aortic aneurysm (AAA) formation. In previous studies, it has been suggested that aneurysm rupture depends on intraluminal thrombus (ILT) thickness, which varies across each individual aneurysm. We hypothesized that hemostatic components differentially accumulate in AAA tissue in relation to ILT thickness. Thick (A1) and thin (B1) segments of ILTs and aneurysm wall sections A (adjacent to A1) and B (adjacent to B1) from one aneurysm sac were taken from 35 patients undergoing elective repair. Factor levels were measured using enzyme-linked immunosorbent assay of protein extract. Tissue factor (TF) activities were significantly higher in thinner segments of AAA (B1 vs A1, P = .003; B vs A, P < .001; B vs A1, P < .001; B vs B1, P = .001). Significantly higher tissue plasminogen activator was found in thick thrombus-covered wall segments (A) than in B, A1, and B1 (P = .015, P < .001, and P < .001, respectively). Plasminogen concentrations were highest in ILT. Concentrations of α 2 -antiplasmin in thin ILT adjacent walls (B) were higher compared with wall (A) adjacent to thick ILT (P = .021) and thick ILT (A1; P < .001). Significant correlations between levels of different factors were mostly found in thick ILT (A1). However, no correlations were found at B sites, except for a correlation between plasmin and TF activities (r = 0.55; P = .004). These results suggest that higher TF activities are present in thinner AAA regions. These parameters and local fibrinolysis may be part of the processes leading to destruction of the aneurysm wall. Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Life-threatening gastrointestinal system bleeding in Hodgkin disease: multidetector CT findings and review of the literature.

PubMed

Akpinar, Erhan; Türkbey, Bariş; Cil, Barbaros Erhan; Canyiğit, Murat; Dündar, Ziya; Balkanci, Ferhun

2007-06-01

Acute lower gastrointestinal system (GIS) bleeding is a life-threatening condition. Immediate determination of the origin of the bleeding is crucial, since hemostatic management must be initiated as rapidly as possible. Colonoscopy, radionuclide studies, and conventional angiography are considered the most important methods for assessing the origin of the bleeding. There are few published reports about the feasibility of computed tomography (CT) in acute GIS bleeding. We present multidetector CT (MDCT) findings in a case of Hodgkin disease status one month post-chemotherapy (CHOP protocol; cyclophosphamide, doxorubicin, vincristine, prednisone) that presented with acute lower GIS bleeding.

Foreign Body Reaction with High Standard Uptake Value Level in 18-FDG PET/CT Mimicking Relapse in an 8-Year-Old Patient Diagnosed with Hodgkin Lymphoma: A Case Report

PubMed Central

Erdoğan, Derya; Bozkurt, Ceyhun; Özmen, Özlem; Boduroglu, Esin; Sahin, Gürses

2013-01-01

Combined positron emission tomography and computed tomography (PET/CT) using 18-fluorodeoxyglucose (18-FDG) is one of the most effective methods to identify pathological lymph node involvement. We report the case of a child who underwent cervical lymph node biopsy and chemotherapy for Hodgkin disease. Three years after surgery, PET/CT identified an intense localization of 18-FDG in the inferior cervical region. This finding led to a reexcision of the mass. The only finding was a granuloma arising in reaction to a hemostatic sponge. PMID:25755956

Coronary artery bypass grafting in a patient with hemophilia B: continuous recombinant factor IX infusion as per the Japanese guidelines for replacement therapy.

PubMed

Suzuki, Tomoyuki; Kawamoto, Shunsuke; Kumagai, Kiichiro; Adachi, Osamu; Kanda, Keisuke; Ishikawa, Masaaki; Okitsu, Yoko; Harigae, Hideo; Kurosawa, Shin; Saiki, Yoshikatsu

2016-08-01

We herein report our experience of successfully managing the hemostatic system by controlling serum factor IX levels throughout the perioperative period in a patient with hemophilia B. Coronary artery bypass grafting with cardiopulmonary bypass was planned for a 52-year-old man with moderate severity of hemophilia B. During surgery, recombinant factor IX (rFIX; BeneFIX(®) Pfizer Japan inc., Tokyo, Japan) was administered by bolus infusion followed by continuous infusion as per the guidelines of the Japanese Society on Thrombosis and Hemostasis. The operative course was uneventful without any considerable bleeding or complications.

Cranial surgery in ancient Peru.

PubMed

Rifkinson-Mann, S

1988-10-01

Trephination is the oldest known surgical technique. Peru has been recognized as a major source of ancient trephined skulls, many of which date back 2300 years. This presentation reviews from a neurosurgical perspective many of the archaeological studies performed on these skulls. Comparative osteology has shown that almost 70% of patients survived the procedure. The various instruments, hemostatic agents, anesthetics, surgical techniques, and cranioplasties used are reconstructed from the anthropological literature. The possible reasons for the use of trephination are discussed. Analysis of the data leads to the conclusion that, despite their rudimentary knowledge of disease, the ancient Incas must have had some knowledge of anatomy and proper surgical procedure.

Damage Control for Vascular Trauma from the Prehospital to the Operating Room Setting.

PubMed

Pikoulis, Emmanouil; Salem, Karim M; Avgerinos, Efthymios D; Pikouli, Anastasia; Angelou, Anastasios; Pikoulis, Antreas; Georgopoulos, Sotirios; Karavokyros, Ioannis

2017-01-01

Early management of vascular injury, starting at the field, is imperative for survival no less than any operative maneuver. Contemporary prehospital management of vascular trauma, including appropriate fluid and volume infusion, tourniquets, and hemostatic agents, has reversed the historically known limb hemorrhage as a leading cause of death. In this context, damage control (DC) surgery has evolved to DC resuscitation (DCR) as an overarching concept that draws together preoperative and operative interventions aiming at rapidly reducing bleeding from vascular disruption, optimizing oxygenation, and clinical outcomes. This review addresses contemporary DCR techniques from the prehospital to the surgical setting, focusing on civilian vascular injuries.

Numerical simulations of a reduced model for blood coagulation

NASA Astrophysics Data System (ADS)

Pavlova, Jevgenija; Fasano, Antonio; Sequeira, Adélia

2016-04-01

In this work, the three-dimensional numerical resolution of a complex mathematical model for the blood coagulation process is presented. The model was illustrated in Fasano et al. (Clin Hemorheol Microcirc 51:1-14, 2012), Pavlova et al. (Theor Biol 380:367-379, 2015). It incorporates the action of the biochemical and cellular components of blood as well as the effects of the flow. The model is characterized by a reduction in the biochemical network and considers the impact of the blood slip at the vessel wall. Numerical results showing the capacity of the model to predict different perturbations in the hemostatic system are discussed.

Uterine atony: definition, prevention, nonsurgical management, and uterine tamponade.

PubMed

Breathnach, Fionnuala; Geary, Michael

2009-04-01

Uterine atony, or failure of the uterus to contract following delivery, is the most common cause of postpartum hemorrhage. This review serves to examine the prevention and treatment of uterine atony, including risk-factor recognition and active management of the third stage of labor. A range of uterotonic agents will be compared for efficacy, safety, and ease of administration. Oxytocin and ergot alkaloids represent the cornerstone of uterotonic therapy, while prostaglandin therapy has been studied more recently as an attractive alternative, particularly for resource-poor settings. Newer supplementary medical therapies, such as recombinant factor VII and hemostatic agents, and adjunctive nonsurgical methods aimed at achieving uterine tamponade will be evaluated.

Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac arrest syndrome patients: study protocol for a randomized controlled trial.

PubMed

Meyer, Anna Sina P; Ostrowski, Sisse R; Kjaergaard, Jesper; Johansson, Pär I; Hassager, Christian

2016-08-02

Morbidity and mortality following initial survival of cardiac arrest remain high despite great efforts to improve resuscitation techniques and post-resuscitation care, in part due to the ischemia-reperfusion injury secondary to the restoration of the blood circulation. Patients resuscitated from cardiac arrest display evidence of endothelial injury and coagulopathy (hypocoagulability, hyperfibrinolysis), which in associated with poor outcome. Recent randomized controlled trials have revealed that treatment with infusion of prostacyclin reduces endothelial damage after major surgery and AMI. Thus, a study is pertinent to investigate if prostacyclin infusion as a therapeutic intervention reduces endothelial damage without compromising, or even improving, the hemostatic competence in resuscitated cardiac arrest patients. Post-cardiac arrest patients frequently have a need for vasopressor therapy (catecholamines) to achieve the guideline-supported blood pressure goals. To evaluate a possible catecholamine interaction with the primary endpoints of this study, included patients will be randomized into two different blood pressure goals within guideline-recommended targets. A randomized, placebo-controlled, double-blind investigator-initiated pilot trial in 40 out-of-hospital-cardiac-arrest (OHCA) patients will be conducted. Patients will be randomly assigned to either the active treatment group (48 hours of active study drug (iloprost, 1 ng/kg/min) or to the control group [placebo (saline) infusion]. Target mean blood pressure levels will be allocated 1:1 to 65 mmHg or approximately 75 mmHg, which gives four different permutations, namely: (i) iloprost/65 mHg, (ii) iloprost/75 mmHg, (iii) placebo/65 mmHg, and (iv) placebo/75 mmHg. All randomized patients will be treated in accordance with state-of-the art therapy including targeted temperature management. The primary endpoint of this study is change in biomarkers indicative of endothelial activation and damage, [soluble thrombomodulin (sTM), sE-selectin, syndecan-1, soluble vascular endothelial growth factor (sVEGF), nucleosomes] and sympathoadrenal over activation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization. The secondary endpoints of this trial will include: (1) the hemostatic profile [change in functional hemostatic blood test (thrombelastography (TEG) and whole blood platelet aggregometry (multiplate)) blood cell and endothelial cell-derived microparticles]; (2) feasibility of blood pressure target intervention (target 90 %); (3) interaction of primary endpoints and blood pressure target; (4) levels of neuron-specific enolase at 48 hours post-inclusion according to blood pressure targets. The ENDO-RCA study is a pilot study trial that investigates safety and efficacy of low-dose infusion of prostacyclin administration as compared to standard therapy in post-cardiac arrest syndrome patients. Trial registration at ClinicalTrials.gov (identifier NCT02685618 ) on 18 February 2016.

Hemostatic agents and instruments in laparoscopic renal surgery.

PubMed

Msezane, Lambda P; Katz, Mark H; Gofrit, Ofer N; Shalhav, Arieh L; Zorn, Kevin C

2008-03-01

Control of bleeding is one of the most technically challenging steps in laparoscopic renal surgery, especially partial nephrectomy. Although there is no consensus on how best to approach hemostasis, the options continue to expand. The original method of sutured renorrhaphy is, perhaps, the most effective; however, great skill is needed to avoid prolonged warm ischemia. Tissue sealants and adhesives serve as a barrier to leakage and as a hemostat. The four classes are fibrin sealants, collagen-based adhesives, hydrogel, and glutaraldehyde-based adhesive. Additionally, oxidized cellulose can be applied to the surface of kidney or used as a bolster. Fibrin sealants are self-activating and work best on a dry field. The gelatin matrix agent consists of human-derived thrombin with a calcium chloride solution and bovine-derived gelatin matrix. The fibrinogen required to form a clot comes from autologous blood. Another product is polyethylene glycol-based hydrogel, which acts as a mechanical sealant. The tissue glue consists of bovine serum albumin and glutaraldehyde, which cross-link to each other, as well as to other tissue proteins. Excessive use or spillage around the renal pelvis and ureter may compromise urinary flow. The methylcellulose products, consisting of oxidized cellulose sheets, usually are positioned within a sutured bolster and act in part by providing direct pressure. A number of energy-based technologies also have been utilized. Monopolar cautery consists of a high-frequency electrical current delivered from a single electrode. Care must be taken to avoid injurious current transfer to surrounding structures. With bipolar cautery, hemostasis occurs only between the electrodes. In the argonbeam coagulator, argon, an inert non-flammable gas that clears from the body rapidly, is coupled with an electrosurgical generator. The gas creates a more even distribution of the energy and better sealing of the tissues. There have been a few reports of serious complications, including gas embolism and tension pneumothorax. The holmium:YAG laser simultaneously dissects and coagulates tissue. However, its use may be limited by smoke and by blood splashing onto the camera lens, and the tissue vaporization and liquid could promote tumor-cell spillage. The potassium-titanyl-phosphate (KTP) and diode lasers have shown promise in animal studies. The saline-coupled radiofrequency tool uses a standard electrosurgical generator to deliver energy through the conductive fluid. The fluid keeps the surface temperature much lower, increases the contact area, and reduces char and eschar formation. One caveat for the use of instruments that coagulate and ablate tissue is that they can damage the collecting system. Furthermore, the char can make it difficult to assess margin status. In practice, a combination of instruments, sealants, or both generally is utilized to obtain hemostasis. These multimodality efforts may be especially useful in the patient with compromised renal function. On the other hand, the cost can rise quickly when multiple agents are employed. Combining suturing and hemostatic technology may be the best strategy.

Hypothermia as a cause of coagulopathy during hepatectomy.

PubMed

Lau, Albert Wai-Cheung; Chen, Chia-Chen; Wu, Rick Sai-Chuen; Poon, Kin-Shing

2010-06-01

We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8 degrees C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed. 2010 Taiwan Society of Anesthesiologists. Published by Elsevier B.V. All rights reserved.

[Effects of hypophyseal Lys-Glu-Asp-Gly and Ala-Glu-Asp-Gly synthetic peptides on immunity, hemostasis, morphology and functions of the thyroid gland in neonatally hypophysectomized chicken and one-year-old birds].

PubMed

Kuznik, B I; Pateiuk, A V; Rusaeva, N S; Baranchugova, L M; Obydenko, V I

2010-01-01

Neonatal hypophysectomy in chicken produces enlarged follicles of the thyroid gland, accumulation of colloids, impressed follicular epithelium, increased nucleus-cytoplasm ratio in thyrocytes, atrophied inter-follicular epithelium, depressed immunity, development of hypercoagulation and depressed fibrinolysis. When hypophysectomy is performed in one-year-old birds the impairments developing in thyroid morphology, immunity and hemostasis are less pronounced. Peptides of the anterior (Lys-Glu-Asp-Gly) and posterior (Ala-Glu-Asp-Gly) thyroid lobes injected to hypophysectomized birds prevent atrophic changes of the thyroid gland, normalize immune and hemostatic parameters.

Blood-loss Management in Spine Surgery.

PubMed

Bible, Jesse E; Mirza, Muhammad; Knaub, Mark A

2018-01-15

Substantial blood loss during spine surgery can result in increased patient morbidity and mortality. Proper preoperative planning and communication with the patient, anesthesia team, and operating room staff can lessen perioperative blood loss. Advances in intraoperative antifibrinolytic agents and modified anesthesia techniques have shown promising results in safely reducing blood loss. The surgeon's attention to intraoperative hemostasis and the concurrent use of local hemostatic agents also can lessen intraoperative bleeding. Conversely, the use of intraoperative blood salvage has come into question, both for its potential inability to reduce the need for allogeneic transfusions as well as its cost-effectiveness. Allogeneic blood transfusion is associated with elevated risks, including surgical site infection. Thus, desirable transfusion thresholds should remain restrictive.

Principles and safety measures of electrosurgery in laparoscopy.

PubMed

Alkatout, Ibrahim; Schollmeyer, Thoralf; Hawaldar, Nusrat A; Sharma, Nidhi; Mettler, Liselotte

2012-01-01

Electrosurgical units are the most common type of electrical equipment in the operating room. A basic understanding of electricity is needed to safely apply electrosurgical technology for patient care. We reviewed the literature concerning the essential biophysics, the incidence of electrosurgical injuries, and the possible mechanisms for injury. Various safety guidelines pertaining to avoidance of injuries were also reviewed. Electrothermal injury may result from direct application, insulation failure, direct coupling, capacitive coupling, and so forth. A thorough knowledge of the fundamentals of electrosurgery by the entire team in the operating room is essential for patient safety and for recognizing potential complications. Newer hemostatic technologies can be used to decrease the incidence of complications.

Principles and Safety Measures of Electrosurgery in Laparoscopy

PubMed Central

Alkatout, Ibrahim; Schollmeyer, Thoralf; Hawaldar, Nusrat A.; Sharma, Nidhi

2012-01-01

Background: Electrosurgical units are the most common type of electrical equipment in the operating room. A basic understanding of electricity is needed to safely apply electrosurgical technology for patient care. Methods: We reviewed the literature concerning the essential biophysics, the incidence of electrosurgical injuries, and the possible mechanisms for injury. Various safety guidelines pertaining to avoidance of injuries were also reviewed. Results: Electrothermal injury may result from direct application, insulation failure, direct coupling, capacitive coupling, and so forth. Conclusion: A thorough knowledge of the fundamentals of electrosurgery by the entire team in the operating room is essential for patient safety and for recognizing potential complications. Newer hemostatic technologies can be used to decrease the incidence of complications. PMID:22906341

[Bites of venomous snakes in Switzerland].

PubMed

Plate, Andreas; Kupferschmidt, Hugo; Schneemann, Markus

2016-06-08

Although snake bites are rare in Europe, there are a constant number of snake bites in Switzerland. There are two domestic venomous snakes in Switzerland: the aspic viper (Vipera aspis) and the common European adder (Vipera berus). Bites from venomous snakes are caused either by one of the two domestic venomous snakes or by an exotic venomous snake kept in a terrarium. Snake- bites can cause both a local and/or a systemic envenoming. Potentially fatal systemic complications are related to disturbances of the hemostatic- and cardiovascular system as well as the central or peripheral nervous system. Beside a symptomatic therapy the administration of antivenom is the only causal therapy to neutralize the venomous toxins.

The effects of QuikClot Combat Gauze on hemorrhage control in the presence of hemodilution.

PubMed

Johnson, Don; Agee, Samantha; Reed, Amanda; Gegel, Brian; Burgert, James; Gasko, John; Loughren, Michael

2012-01-01

Although hemostatic agents may be effective at stopping hemorrhage, they may fail because of hemodilution from intravenous fluids. The purpose of this study was to investigate the effects of QuikClot Combat Gauze (QCG) on rebleeding in a class II hemorrhage in the presence of hemodilution in a lethal femoral injury. This was a prospective experimental, between swine subjects design. Pigs were assigned to one of two groups: QCG (n=15) or control (n=15). Thirty percent of the pig's blood was exsanguinated and then a 3:1 ratio of ringers lactate was administered. A groin injury was created by transecting the femoral artery and vein to simulate a battlefield injury and allowed to bleed for one minute. After one minute of hemorrhage, proximal pressure was applied to the injury, and QCG was placed into the wound followed by standard wound packing. The control group underwent the same procedures with the exception of the hemostatic agent. For both groups, 5 minutes of direct pressure was applied to the wound followed by a standard pressure dressing. Dressings were removed after 30 minutes, and the amount of hemorrhage was calculated in milliliters for each group for a period of 5 minutes. An activated clotting time was used to exclude any pigs with coagulation pathology. A multivariate analysis of variance indicated that there were no significant differences in the groups relative to weight, amount of one minute hemorrhage, fluid deficit replacement, blood volume, and the activated clotting time (P>.05) indicating that the groups were equivalent on these parameters. A t test indicated that there was significantly less bleeding (P=.002) in the QCG group (36 mL±112 mL) compared to the control group (340 mL±297 ml). QCG produces a robust clot that can more effectively tolerate hemodilution compared to a control group.

[The morphology, typical combinations of polymorphic genes of hemostasis, and specific features of the pathogenesis of retrochorial hematoma in missed abortion].

PubMed

Milovanov, A P; Kuznetsova, N B; Bushtyreva, I O

to identify mutations and hemostatic gene polymorphisms typical for retrochorial hematoma (RCH) and to study its pathogenesis in missed abortion. A PCR assay was used to detect the genetic forms of thrombophilia in 270 patients with ultrasonographically verified RCH. Logistic regression analysis revealed that with the F7 (proconvertin, coagulation factor (CF) VII G10976A polymorphism or with the F13 (fibrinase, CF XIII) G>T, or FGB (fibrinogen β-chain) G455A polymorphism, the risk of RCH was 2.72, 2.16, and 1.92 times higher, respectively. First trimester missed abortion was found in 42 (15.5%) cases; among them there were 24 (8.8%) women with different polymorphism combinations: F7 (G10976A), F13 (fibrinase, G>T), FGB (G455A). A total of 18 cases of missed abortion due to morphologically verified endometritis, endocrinopathies, and antiphospholipid syndrome were excluded from the sample. Compared to the morphology of medical abortions of the same period (16 women), patients with polymorphic genes of hemostasis were found to have statistically significant incomplete endometrial decidualization, thinning or absence of a Rohr's fibrinoid layer, a smaller number and shortening of syncytiotrophoblast microvilli, and the maximum amount of dissecting hemorrhage and RCH in the utero-chorionic region. The stages of RCH pathogenesis were determined; these included penetration of maternal erythrocytes deep into the decidua ~ dissociation of a layer of decidual cells with impairment of a «hemostatic envelope» ~ formation of RCH with a dense network of fibrin threads ~ final necrosis of surrounding cells and tissues. The investigators identified for the first time the typical combinations of polymorphic genes of predisposition to a high risk for RCH; its complete formation requires additional changes in maternal and placental components that provide local hemostasis.

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.

Differential roles of fibrinogen and von Willebrand factor on clot formation and platelet adhesion in reconstituted and immune thrombocytopenia.

PubMed

Misgav, Mudi; Shenkman, Boris; Budnik, Ivan; Einav, Yulia; Martinowitz, Uri

2011-05-01

Bleeding tendencies in immune thrombocytopenia (ITP) do not always correlate with the number of platelets, suggesting platelet function variation. We used a model of normal whole blood thrombocytopenia to compare platelet function and other hemostatic variables with ITP patients. We further investigated the effect of in vitro spiking with von Willebrand factor (vWF) and fibrinogen on platelet function and hemostatic variables. The Cone and Plate(let) Analyzer was used to measure platelet adhesion (surface coverage [SC], %) and aggregation (average size, μm(2)) under defined shear rate (1200 s(-1)). Rotational thromboelastometry was used to determine variables of clot formation triggered by CaCl(2) and tissue factor. In both the model of thrombocytopenia as well as in ITP, the SC and to some extent the average size were correlated to the platelet number over a range of 5 to 80 × 10(6)/mL. The results obtained for most ITP samples were within the boundaries of the lower and upper limits set by the whole blood model of thrombocytopenia. The addition of 2 U/mL vWF (Haemate-P) to whole blood (calculated to plasma volume) results in an increase in the SC and average size without affecting clot formation. Spiking with fibrinogen (100 and 300 mg/dL) did not affect platelet deposition but improved clot formation. Using a model of whole blood thrombocytopenia enables us to establish reference variables for the Cone and Plate(let) Analyzer and rotational thromboelastometry and to assess platelet function and clot formation in the presence of severe thrombocytopenia. We demonstrated that in most cases of ITP, platelet function is comparable to normal platelets. This work also suggests that vWF and fibrinogen differentially affect primary and secondary hemostasis and therefore both may perform a function in the bleeding phenotype and possibly may be considered for treatment in patients with ITP. © 2011 International Anesthesia Research Society

Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

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

Beyerle, Andrea, E-mail: andrea.beyerle@cslbehring.com; Nolte, Marc W.; Solomon, Cristina

Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii)more » the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated, with no adverse events. • Overall, human fibrinogen concentrate demonstrated a good safety profile. • This data adds to the safety information available to date on this hemostatic agent.« less

Primary hemostatic capacity of whole blood: a comprehensive analysis of pathogen reduction and refrigeration effects over time

PubMed Central

Pidcoke, Heather F.; McFaul, Steve J.; Ramasubramanian, Anand K.; Parida, Bijaya K.; Mora, Alex G.; Fedyk, Chriselda G.; Valdez-Delgado, Krystal K.; Montgomery, Robbie K.; Reddoch, Kristin M.; Rodriguez, Armando C.; Aden, James K.; Jones, John A.; Bryant, Ron S.; Scherer, Michael R.; Reddy, Heather L.; Goodrich, Raymond P.; Cap, Andrew P.

2014-01-01

BACKGROUND Whole blood (WB) has been used in combat since World War I as it is readily available and replaces every element of shed blood. Component therapy has become standard; however, recent military successes with WB resuscitation have revived the debate regarding wider WB use. Characterization of optimal WB storage is needed. We hypothesized that refrigeration preserves WB function and that a pathogen reduction technology (PRT) based on riboflavin and ultraviolet light has no deleterious effect over 21 days of storage. STUDY DESIGN AND METHODS WB units were stored for 21 days either at 4°C or 22°C. Half of each temperature group underwent PRT, yielding four final treatment groups (n = 8 each): CON 4 (WB at 4°C); CON 22 (WB at 22°C); PRT 4 (PRT WB at 4°C); and PRT 22 (PRT WB at 22°C). Testing was at baseline, Days 1–7, 10, 14, and 21. Assays included coagulation factors; platelet activation, aggregation, and adhesion; and thromboelastography (TEG). RESULTS Prothrombin time (PT) and partial thromboplastin time increased over time; refrigeration attenuated the effects on PT (p ≤ 0.009). Aggregation decreased over time (p ≤ 0.001); losses were attenuated by refrigeration (p ≤ 0.001). Refrigeration preserved TEG parameters (p ≤ 0.001) and PRT 4 samples remained within normal limits throughout the study. Refrigeration in combination with PRT inhibited fibrinolysis (p ≤ 0.001) and microparticle formation (p ≤ 0.031). Cold storage increased shear-induced platelet aggregation and ristocetin-induced platelet agglutination (p ≥ 0.032), as well as GPIb-expressing platelets (p ≤ 0.009). CONCLUSION The in vitro hemostatic function of WB is largely unaffected by PRT treatment and better preserved by cold storage over 21 days. Refrigerated PRT WB may be suitable for trauma resuscitation. Clinical studies are warranted. PMID:23301966

Investigation of the hemostatic effect of a transdermal patch containing 0.55 mg ethinyl estradiol and 2.1 mg gestodene compared with a monophasic oral contraceptive containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel: an open-label, randomized, crossover study.

PubMed

Junge, Wolfgang; Heger-Mahn, Doris; Trummer, Dietmar; Merz, Martin

2013-09-01

Transdermal delivery of contraceptives offers several advantages over combined oral contraceptives (COCs), including effective absorption and the provision of relatively constant serum concentrations. Ethinyl estradiol (EE) and the progestin gestodene are well-absorbed through the skin and, therefore, well-suited for use in a transdermal contraceptive patch. The objective of this study was to investigate the impact of a once-weekly transparent, transdermal patch delivering low doses of EE and gestodene equivalent to a COC containing 0.02 mg EE and 0.06 mg gestodene on hemostasis parameters compared with a monophasic COC containing 0.03 mg EE and 0.15 mg levonorgestrel. In this single-center, open-label, randomized, crossover study, 30 women (aged 18-35 years) received three cycles of each treatment, separated by a two-cycle washout period. The primary outcome measure was the absolute change from baseline in prothrombin fragments 1 + 2 and D-dimer. For both treatments, prothrombin fragments 1 + 2 remained stable during the first treatment period, and increased only slightly in the second period (mean absolute change 0.025 and 0.028 nmol/L in the novel Bayer patch and COC groups, respectively). Increases in D-dimer were observed in both periods (mean absolute change 107.0 ± 147.2 ng/L for the novel Bayer patch and 113.7 ± 159.0 ng/L for the COC). There were no statistically significant treatment differences in prothrombin 1 + 2 or D-dimer (p = 0.667 and p = 0.884, respectively) and no statistically significant treatment sequence or period effects. A COC containing 0.03 mg EE and 0.15 mg levonorgestrel and the novel Bayer patch have comparable influence on hemostatic endpoints. Both treatments were well-tolerated by subjects.

Hemostatic interference of Indian king cobra (Ophiophagus hannah) Venom. Comparison with three other snake venoms of the subcontinent.

PubMed

Gowtham, Yashonandana J; Kumar, M S; Girish, K S; Kemparaju, K

2012-06-01

Unlike Naja naja, Bungarus caeruleus, Echis carinatus, and Daboia/Vipera russellii venoms, Ophiophagus hannah venom is medically ignored in the Indian subcontinent. Being the biggest poisonous snake, O. hannah has been presumed to inject several lethal doses of venom in a single bite. Lack of therapeutic antivenom to O. hannah bite in India makes any attempt to save the victim a difficult exercise. This study was initiated to compare O. hannah venom with the above said venoms for possible interference in hemostasis. Ophiophagus hannah venom was found to actively interfere in hemostatic stages such as fibrin clot formation, platelet activation/aggregation, and fibrin clot dissolution. It decreased partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin clotting time (TCT). These activities are similar to that shown by E. carinatus and D. russellii venoms, and thus O. hannah venom was found to exert procoagulant activity through the common pathway of blood coagulation, while N. naja venom increased aPTT and TCT but not PT, and hence it was found to exert anticoagulant activity through the intrinsic pathway. Venoms of O. hannah, E. carinatus, and D. russellii lack plasminogen activation property as they do not hydrolyze azocasein, while they all show plasmin-like activity by degrading the fibrin clot. Although N. naja venom did not degrade azocasein, unlike other venoms, it showed feeble plasmin-like activity on fibrin clot. Venom of E. carinatus induced clotting of human platelet rich plasma (PRP), while the other three venoms interfered in agonist-induced platelet aggregation in PRP. Venom of O. hannah least inhibited the ADP induced platelet aggregation as compared to D. russellii and N. naja venoms. All these three venoms showed complete inhibition of epinephrine-induced aggregation at varied doses. However, O. hannah venom was unique in inhibiting thrombin induced aggregation.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A.

PubMed

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I; Fischer, Kathelijn; Gill, Joan C; P'Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St Ledger, Katie; Pabinger, Ingrid

2016-08-04

Recombinant VIII (rVIII)-SingleChain is a novel B-domain-truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. © 2016 by The American Society of Hematology.

Challenges with Navigating the Precarious Hemostatic Balance during Extracorporeal Life Support: Implications for Coagulation and Transfusion Management.

PubMed

Andrews, Jennifer; Winkler, Anne M

2016-10-01

For the past four decades, extracorporeal life support (ECLS) has been used to treat critically ill adult and pediatric patients with cardiac and/or respiratory failure, and there are increasingly numbers of centers worldwide performing ECLS for numerous indications. Despite the progress with advancing the technology, hemorrhagic and thrombotic complications are frequently reported and associated with worse outcomes, but the exact cause is often elusive or multifactorial. As a result of the interaction between blood and an artificial circuit, anticoagulation is necessary and there is resultant activation of coagulation, fibrinolysis, as well as, an increased inflammatory response. While unfractionated heparin (UFH) remains the mainstay anticoagulant used during ECLS, there is a paucity of published data to develop a universal anticoagulation guideline and centers are forced to create individualized protocols to guide anticoagulation management while lacking expertise. From an international survey, centers often use a combination of tests, which in turn result in discordant results and confused management. Studies are urgently needed to investigate optimization of current anticoagulation strategies with UFH, as well as, use of alternative anticoagulants and non-thrombogenic biomaterials. Blood transfusion during extracorporeal support typically occurs for several reasons, which includes circuit priming, restoration of oxygen carrying capacity, maintenance of a hemostatic balance, and treatment of hemorrhagic complications. As a result, the majority of patients will have been exposed to at least one blood product during extracorporeal support and transfusion utilization is high. ECLS Centers have adopted transfusion thresholds based upon practice rather than evidence as there have been no prospective studies investigating the efficacy of red cell (RBC) transfusion in patients receiving extracorporeal support. In addition, RBC transfusion has been associated with increased mortality in ECLS in several retrospective studies. Additional studies are needed to establish evidence based thresholds for transfusion support and diagnostics to guide transfusion therapy to assess efficacy of transfusion in this population, as well as, exploration of alternatives to transfusion. Copyright © 2016 Elsevier Inc. All rights reserved.

Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease. The Caerphilly and Speedwell collaborative heart disease studies.

PubMed

Yarnell, J W; Baker, I A; Sweetnam, P M; Bainton, D; O'Brien, J R; Whitehead, P J; Elwood, P C

1991-03-01

Recent studies have suggested that hemostatic factors and white blood cell count are predictive of ischemic heart disease (IHD). The relations of fibrinogen, viscosity, and white blood cell count to the incidence of IHD in the Caerphilly and Speedwell prospective studies are described. The two studies have a common core protocol and are based on a combined cohort of 4,860 middle-aged men from the general population. The first follow-up was at a nearly constant interval of 5.1 years in Caerphilly and 3.2 years in Speedwell; 251 major IHD events had occurred. Age-adjusted relative odds of IHD for men in the top 20% of the distribution compared with the bottom 20% were 4.1 (95% confidence interval, 2.6-6.5) for fibrinogen, 4.5 (95% confidence interval, 2.8-7.4) for viscosity, and 3.2 (95% confidence interval, 2.0-4.9) for white blood cell count. Associations with IHD were similar in men who had never smoked, exsmokers, and current smokers, and the results suggest that at least part of the effect of smoking on IHD is mediated through fibrinogen, viscosity, and white blood cell count. Multivariate analysis shows that white blood cell count is an independent risk factor for IHD as is either fibrinogen or viscosity, or possibly both. Jointly, these three variables significantly improve the fit of a logistic regression model containing all the main conventional risk factors. Further, a model including age, smoking habits, fibrinogen, viscosity, and white blood cell count predicts IHD as well as one in which the three hemostatic/rheological variables are replaced by total cholesterol, diastolic pressure, and body mass index. Jointly, fibrinogen, viscosity, and white blood cell count are important risk factors for IHD.

RNA-Seq Analysis of Abdominal Fat in Genetically Fat and Lean Chickens Highlights a Divergence in Expression of Genes Controlling Adiposity, Hemostasis, and Lipid Metabolism

PubMed Central

Resnyk, Christopher W.; Chen, Chuming; Huang, Hongzhan; Wu, Cathy H.; Simon, Jean; Le Bihan-Duval, Elisabeth; Duclos, Michel J.; Cogburn, Larry A.

2015-01-01

Genetic selection for enhanced growth rate in meat-type chickens (Gallus domesticus) is usually accompanied by excessive adiposity, which has negative impacts on both feed efficiency and carcass quality. Enhanced visceral fatness and several unique features of avian metabolism (i.e., fasting hyperglycemia and insulin insensitivity) mimic overt symptoms of obesity and related metabolic disorders in humans. Elucidation of the genetic and endocrine factors that contribute to excessive visceral fatness in chickens could also advance our understanding of human metabolic diseases. Here, RNA sequencing was used to examine differential gene expression in abdominal fat of genetically fat and lean chickens, which exhibit a 2.8-fold divergence in visceral fatness at 7 wk. Ingenuity Pathway Analysis revealed that many of 1687 differentially expressed genes are associated with hemostasis, endocrine function and metabolic syndrome in mammals. Among the highest expressed genes in abdominal fat, across both genotypes, were 25 differentially expressed genes associated with de novo synthesis and metabolism of lipids. Over-expression of numerous adipogenic and lipogenic genes in the FL chickens suggests that in situ lipogenesis in chickens could make a more substantial contribution to expansion of visceral fat mass than previously recognized. Distinguishing features of the abdominal fat transcriptome in lean chickens were high abundance of multiple hemostatic and vasoactive factors, transporters, and ectopic expression of several hormones/receptors, which could control local vasomotor tone and proteolytic processing of adipokines, hemostatic factors and novel endocrine factors. Over-expression of several thrombogenic genes in abdominal fat of lean chickens is quite opposite to the pro-thrombotic state found in obese humans. Clearly, divergent genetic selection for an extreme (2.5–2.8-fold) difference in visceral fatness provokes a number of novel regulatory responses that govern growth and metabolism of visceral fat in this unique avian model of juvenile-onset obesity and glucose-insulin imbalance. PMID:26445145

Significance of a soft-coagulation system with monopolar electrode for hepatectomy: A retrospective two-institution study by propensity analysis.

PubMed

Hamada, Takeomi; Nanashima, Atsushi; Yano, Koichi; Sumida, Yorihisa; Hiyoshi, Masahide; Imamura, Naoya; Tobinaga, Shuichi; Tsuchimochi, Yuki; Takeno, Shinsuke; Fujii, Yoshiro; Nagayasu, Takeshi

2017-09-01

The VIO soft-coagulation system (VIO) with a monopolar electrode is a novel hemostatic device that provides hemostasis by superficial contact at the bleeding site without carbonization. Because heat injury remains a concern, surgical records and postoperative liver dysfunction were retrospectively evaluated in a cohort study. Between September 2010 and March 2016, 322 patients underwent hepatectomy in which hemostatic devices were used at two institutions. Surgical results with use of VIO at one institute (VIO group) were compared with those without use of VIO at a second institute (control group), and propensity analysis was performed. In limited resection and segmentectomy or sectionectomy performed in the VIO group, the prevalence of liver cirrhosis was significantly higher and the operation time was significantly longer in comparison with the control group (p < 0.05). In all hepatectomies, postoperative levels of total bilirubin and aspartate or alanine transaminase tended to be increased and prothrombin activity tended to be lower in the VIO group in comparison with the control group (p < 0.05). The prevalence of hepatic failure in the VIO group was significantly higher in comparison with that in the control group (p < 0.05). In cases of segmentectomy or sectionectomy, blood loss was significantly increased in the VIO group in comparison with that in the control group (p < 0.05) Propensity score matching showed that although the surgical records and outcomes were not significantly different between the groups, postoperative liver dysfunction was significant in the VIO group in comparison with the control group (p < 0.05). Mild postoperative hepatic thermal injury with VIO was confirmed, and therefore, surgeons should take care when using the VIO system to make frequent wide resected cuts on the surface of the liver. Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Laser wound: (two) mixed-beam (cw Nd:YAG-PW XeCl) lasing results in mixed injuries

NASA Astrophysics Data System (ADS)

Kull, Mart M.; Kruuv, H.; Zeltzer, Gregory L.; Nevorotin, Alexey J.

1992-08-01

The POLYCON system has been developed for simultaneous passage of different laser beams to a target. In this study, CW Nd:YAG (9 W/cm2) and XeCl excimer (30 mJ/pulse, 80 nsec, 10 Hz) laser beams were directed via individual fibers to a cone-shaped optical mixer continuously connected at the site of its outlet aperture with a common flexible cable destined for surgery. Contact mode cuts were made on rat liver and biopsy samples taken for electron microscopy. Injuries of mixed type have been found within the same cells, e.g., mitochondrial ballooning detected recently after Nd:YAG and vesiculation of the endoplasmic reticulum which is a feature characteristic of XeCl excimer laser. Taking into consideration satisfactory cutting properties, good hemostatic effect and favorable prognosis for recovery as evidenced by active phagocytosis along with proteolytic digestibility of debris in the wound, mixed beam lasing with the parameters tested can be approved as a perspective kind of surgery. In one study, a low potential for healing after CW mode Nd:YAG lasing has been revealed by specially devised tests. Contrary to that, the PW mode XeCl laser has been shown to provide better conditions for local recovery not incompatible with the impression of other workers. The excimers are also believed to be good cutters but they are mainly utilized in the experiments on tissues with low blood supply, due presumably to inherent poor hemostatic capacity of these tools. The lasers of that kind would undoubtedly be tried for tissues with high levels of blood supply provided hemostasis could be secured at the site of surgery by some means. In this paper, such a means is offered, and it is a mixed beam system in which XeCl excimer laser is used in the capacity of a cutter while Nd:YAG one is operating to stop bleeding with minimal side effects on healing in the post-operation period.

Secure hemostasis in transhiatal esophagectomy for esophageal cancer with gauze packing.

PubMed

Hirahara, Noriyuki; Matsubara, Takeshi; Hari, Yoko; Fujii, Yusuke; Wake, Hitomi; Tajima, Yoshitsugu

2012-12-19

Transhiatal esophagectomy for esophageal cancer implies blind manipulation of the intrathoracic esophagus. We report a secure hemostatic method with gauze packing in transhiatal esophagectomy. The gauze-packing technique is utilized for hemostasis just after removal of the thoracic esophagus during transhiatal esophagectomy. After confirming cancer-free margins, the abdominal esophagus and cervical esophagus are transected. A vein stripper is inserted into the oral-side stump of the esophagus and led to exit from the abdominal-side stump of the esophagus. The vein stripper and the oral stump of the esophagus are affixed by silk thread. A polyester tape is then affixed to the vein stripper, as the polyester tape is left in the posterior mediastinum after removal of the esophagus toward the abdominal side. The polyester tape on the cervical side is ligated with gauze and the polyester tape is removed toward the abdominal side. The oral stump of gauze and new additional gauze are affixed. As the first gauze is pulled out from the abdominal side, the second gauze gets drawn from the cervical wound into the mediastinum. The posterior mediastinum is finally packed with gauze and possible bleeding at this site undergoes a complete astriction. The status of hemostasis with the gauze packing is checked by an observation of color and bloodstain on the gauze. Between January 2005 and February 2012, 13 consecutive patients with esophageal cancer underwent a transhiatal esophagectomy with the gauze-packing hemostatic technique. Hemostasis at the posterior mediastinum was performed successfully and quickly in all cases with this method, requiring up to four pieces of gauze for a complete hemostasis. Median required time for hemostasis was 1219 (range 1896 to 1293) seconds and estimated blood loss was 20.4 (range 15 to 25) ml during gauze packing. Our technique could minimize bleeding after the removal of the thoracic esophagus. The gauze-packing method is a simple and easy technique for secure hemostasis when performing a transhiatal esophagectomy.

Secure hemostasis in transhiatal esophagectomy for esophageal cancer with gauze packing

PubMed Central

2012-01-01

Background Transhiatal esophagectomy for esophageal cancer implies blind manipulation of the intrathoracic esophagus. We report a secure hemostatic method with gauze packing in transhiatal esophagectomy. Methods The gauze-packing technique is utilized for hemostasis just after removal of the thoracic esophagus during transhiatal esophagectomy. After confirming cancer-free margins, the abdominal esophagus and cervical esophagus are transected. A vein stripper is inserted into the oral-side stump of the esophagus and led to exit from the abdominal-side stump of the esophagus. The vein stripper and the oral stump of the esophagus are affixed by silk thread. A polyester tape is then affixed to the vein stripper, as the polyester tape is left in the posterior mediastinum after removal of the esophagus toward the abdominal side. The polyester tape on the cervical side is ligated with gauze and the polyester tape is removed toward the abdominal side. The oral stump of gauze and new additional gauze are affixed. As the first gauze is pulled out from the abdominal side, the second gauze gets drawn from the cervical wound into the mediastinum. The posterior mediastinum is finally packed with gauze and possible bleeding at this site undergoes a complete astriction. The status of hemostasis with the gauze packing is checked by an observation of color and bloodstain on the gauze. Results Between January 2005 and February 2012, 13 consecutive patients with esophageal cancer underwent a transhiatal esophagectomy with the gauze-packing hemostatic technique. Hemostasis at the posterior mediastinum was performed successfully and quickly in all cases with this method, requiring up to four pieces of gauze for a complete hemostasis. Median required time for hemostasis was 1219 (range 1896 to 1293) seconds and estimated blood loss was 20.4 (range 15 to 25) ml during gauze packing. Conclusions Our technique could minimize bleeding after the removal of the thoracic esophagus. The gauze-packing method is a simple and easy technique for secure hemostasis when performing a transhiatal esophagectomy. PMID:23253358

A prospective study on the effects on hemostasis of two oral contraceptives containing drospirenone in combination with either 30 or 20 microg ethinyl estradiol and a reference containing desogestrel and 30 microg ethinyl estradiol.

PubMed

Kluft, Cornelis; Endrikat, Jan; Mulder, Simone M; Gerlinger, Christoph; Heithecker, Renate

2006-04-01

In this open-label, randomized study, we assessed the effects on hemostasis of two combined oral contraceptives containing drospirenone (DRSP) as progestogen component. Three milligrams of DRSP, a progestogen with antimineralocorticoid activity, was combined with either 30 or 20 microg ethinyl estradiol (EE) (DRSP/30EE; DRSP/20EE) and compared with a preparation containing 150 microg desogestrel (DSG) and 30 microg ethinyl estradiol (DSG/30EE). A total of 75 healthy female volunteers aged 18-35 years were enrolled. The hemostasis variables were measured in the medication-free precycle (baseline); in the first, third and sixth treatment cycle; and in the follow-up phase. The target variables for comparison were the relative changes from baseline to Cycle 6. Data of 25 volunteers in each group were valid for the per-protocol evaluation. Most changes in hemostasis variables were similar in the three treatment groups. All procoagulatory variables and the anticoagulatory variable protein C antigen increased slightly, while protein S antigen and activity decreased. For fibrinogen and protein S activity, the changes were statistically significant: less pronounced with DRSP/20EE compared to DSG/30EE at Cycle 6. There were no statistically significant differences in the changes of antifibrinolytic variables, the global clotting tests and D-dimer. All pairwise comparisons of DRSP/30EE vs. DSG/30EE yielded nonsignificant results; however, there was a trend of a lower impact of DRSP/20EE on nearly all hemostatic parameters compared to the 30EE products. All three study treatments were safe and well tolerated by the volunteers and provided adequate contraceptive reliability. The changes in the hemostatic variables for DRSP/20EE were less pronounced compared to DSG/30EE and DRSP/30EE. The results were in accordance with previous reports on effects of similar OCs.

PubMed Central

Toth, Bettina; Würfel, Wolfgang; Bohlmann, Michael; Zschocke, Johannes; Rudnik-Schöneborn, Sabine; Nawroth, Frank; Schleußner, Ekkehard; Rogenhofer, Nina; Wischmann, Tewes; von Wolff, Michael; Hancke, Katharina; von Otte, Sören; Kuon, Ruben; Feil, Katharina; Tempfer, Clemens

2018-01-01

Purpose Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members. Methods Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting. Recommendations Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration. PMID:29720743

Nasal packing and stenting

PubMed Central

Weber, Rainer K.

2011-01-01

Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

THE PROTECTIVE EFFECT OF LOCAL BONE MARROW ASPHYXIA IN ACUTE RADIATION SICKNESS IN ANIMALS (in Russian)

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

Zherebchenko, P.G.; Krasnykh, I.G.; Lebkova, N.P.

1960-10-01

In experiments on mice, rats, and dogs, a study was made of the effect of local bone marrow asphyxia on the course and outcome of radiation sickness. Asphyxia was induced by applying a hemostatic tourniquet on the extremity of animals during irradiation. It was established that local asphyxia of the bone marrow alleviates the severity of acute radiation sickness and increases the survival of animals. It is shown that at the basis of the radioprotective action lies the reduced degeneration of the bone marrow, subsequently facilitating the regeneration of hematopeiesis. Data are obtained relative to the intensification of the effectmore » of local asphyxia with the aid of prophylactic (mercamine) and curative (streptomycin) agents. (auth)« less

Carbon dioxide laser microsurgery of the uterine tube.

PubMed

Baggish, M S; Chong, A P

1981-07-01

The carbon dioxide (CO2) laser was used to perform microsurgical excision of obstructed tubal segments in rabbit and human subjects. Approximation of the freshly severed tubes by means of laser "welding" was evaluated in both groups investigated. More important, the laser beam cuts accurately and atraumatically while sealing small vascular channels. Scanning electron microscopic studies of the human fallopian tube following laser surgery were done to determine the extent of tissue injury. At a distance of 1 mm distal to the vaporization and necrotic impact zone, normal tubal anatomy was observed. Follow-up data are presented for 7 women who underwent laser beam tuboplasty between 1979 and 1980. The principle advantages of the CO2 laser are its precise control, minimal tissue injury, and hemostatic properties.

Protective effects of panax notoginseng saponins on cardiovascular diseases: a comprehensive overview of experimental studies.

PubMed

Yang, Xiaochen; Xiong, Xingjiang; Wang, Heran; Wang, Jie

2014-01-01

Panax notoginseng saponins (PNS) are one of the most important compounds derived from roots of the herb Panax notoginseng which are traditionally used as a hemostatic medicine to control internal and external bleeding in China for thousands of years. To date, at least twenty saponins were identified and some of them including notoginsenoside R1, ginsenoside Rb1, and ginsenoside Rg1 were researched frequently in the area of cardiovascular protection. However, the protective effects of PNS on cardiovascular diseases based on experimental studies and its underlying mechanisms have not been reviewed systematically. This paper reviewed the pharmacology of PNS and its monomers Rb1, Rg1, and R1 in the treatment for cardiovascular diseases.

[Spontaneous liver rupture in a patient with choledocholithiasis resolved by ERCP].

PubMed

Bahena-Aponte, Jesús A; Ramírez de Aguilar, Guillermo; Torres Carrillo, Juan Carlos; Espino Urbina, Luis; Sánchez González, Jesús A

2016-01-01

We present the case of a 34 years old female patient who presents with abdominal pain and elevated total and direct bilirrubins, so she underwent ERCP Reporting: a) successful sphincterotomy without complications, b) choledocholithias is endoscopically resolved, c) secondary cholangitis. She developed significant abdominal pain at 72 h, with hypovolemic shock and peritoneal irritation. She was taken to the surgery, finding a grade III liver laceration. This one was resolved with liver raffia and packing, during the same operative time cholecystectomy was performed. A second look was performed at 24 h, achieving adequate control of bleeding after placing hemostatic (Nexstat®). The patient developed a subdiaphragmatic abscess which needed drainage by another laparotomy. After which the patient had a satisfactory evolution, so she was discharged.

[History and development of carbonization of Chinese materia medica and exploration on its mechanism of hemostatic action].

PubMed

He, R J; Diao, T M; DU, D

2017-03-28

The first material recorded about hair charcoal is seen in Nei jing ( Inner Canon ). It has a history of over 2 000 years for the carbonization of Chinese materia medica. There were controversies on this matter and its clinical application was seldom seen and underdeveloped. After the Yuan Dynasty, the main theory of carbonic herbs for hemostasis, and keeping the nature of the medicines after carbonization was gradually formed, and physicians of generations began to conduct in-depth research. Through repeated practice and verification, people summed up the suitable species of Chinese materia medica and its principle for carbonization. The methods and degree of carbonization of Chinese materia medica are reasonably discussed, with its principle and basis for application primarily interpreted.

A Deep Insight Into the Sialotranscriptome of the Chagas Disease Vector, Panstrongylus megistus (Hemiptera: Heteroptera)

PubMed Central

Ribeiro, José M. C.; Schwarz, Alexandra; Francischetti, Ivo M. B.

2015-01-01

Saliva of blood-sucking arthropods contains a complex cocktail of pharmacologically active compounds that assists feeding by counteracting their hosts’ hemostatic and inflammatory reactions. Panstrongylus megistus (Burmeister) is an important vector of Chagas disease in South America, but despite its importance there is only one salivary protein sequence publicly deposited in GenBank. In the present work, we used Illumina technology to disclose and publicly deposit 3,703 coding sequences obtained from the assembly of >70 million reads. These sequences should assist proteomic experiments aimed at identifying pharmacologically active proteins and immunological markers of vector exposure. A supplemental file of the transcriptome and deducted protein sequences can be obtained from http://exon.niaid.nih.gov/transcriptome/P_megistus/Pmeg-web.xlsx. PMID:26334808

Port closure techniques.

PubMed

Shaher, Z

2007-08-01

Laparoscopic trocars do create wounds. This article aims to review and list different techniques used for closure of the fascia incision at trocar sites. A literature search was performed for articles dealing with closure techniques. The author searched this subject in English on Medline by combining the words "trocar" and "hernia," as well as "Deschamps" and "Reverdin." All articles reporting techniques with their references were reviewed. The articles described many techniques in addition to classical closure using curved needles, including Grice needle, Maciol needles, Endoclose device, Carter-Thomason device, Tahoe ligature device, Endo-Judge device, eXit puncture closure device, Lowsley retractor, spinal cord needles, dual hemostat, suture carrier, Riverdin and Deschamps needles, and Gore-Tex closure device. Three main groups of techniques were found with favor of extracorporeal manipulations under direct visualization. Old methods are sufficient and cost-effective.

Mechanism of action of recombinant activated factor VII: an update.

PubMed

Hedner, Ulla

2006-01-01

Bleeding episodes in patients with hemophilia and inhibitors must be managed using agents that are hemostatically active in the absence of factor VIII or IX. Activated prothrombin complex concentrates have long been used in this context. However, the search for safer and more effective agents has led to the development of recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark). This paper presents an update on the mechanism of action of rFVIIa, and describes how pharmacologic doses of this agent enhance thrombin production and thus contribute to the development of a stable, lysis-resistant fibrin plug at the site of vessel damage. This mechanism explains the reported efficacy of rFVIIa in a range of clinical situations characterized by impaired thrombin generation.

[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.

[Experimental liver and kidney surgery with CO2, CO, holmium, and neodym lasers. Cutting effect, hemostasis, histopathology, and healing (author's transl)].

PubMed

Karbe, E; Königsmann, G; Beck, R

1980-01-01

Various laser devices (CO2, CO, Nd: YAG, and holmium: YAG lasers) have been used on pig livers and on dog kidneys for comparison with conventional surgical instruments (electroscalpel, cryoscalpel, and scalpel). CO2 and CO lasers caused the least tissue damage, followed by the holmium laser; severe damage was caused by the Nd: YAG laser. The order was reverse for coagulative effect. The conventional reference instruments showed a weaker hemostatic effect. Surfaces cut by laser healed in four to eight weeks without complications. Remnants of charred tissue in various quantities could still be detected after eight weeks in all cases where CO2, CO, and Nd: YAG lasers had been used. This obviously did not affect scar formation.

Hemostatic, inflammatory, and oxidative markers in pesticide user farmers.

PubMed

Madani, Fatima Zohra; Hafida, Merzouk; Merzouk, Sid Ahmed; Loukidi, Bouchra; Taouli, Katia; Narce, Michel

2016-01-01

The aim of this work was to investigate inflammatory, oxidative, and thrombotic parameters as biomarkers in farmers exposed to pesticides. Fifty farmers using chemical pesticides and 60 unexposed control men participated in this study. The Mediterranean diet compliance, the duration of pesticide use, and personal protection for pesticides handling were recorded using self-administered questionnaires. Serum biochemical parameters, oxidant/antioxidant, inflammatory, and thrombosis markers were determined. Our findings showed oxidative stress reflected by an increase in malondialdehyde, carbonyl proteins and superoxide anion levels and a decrease in vitamins C and E, glutathione, catalase, and superoxide dismutase activities in farmers. Serum C-reactive protein, prothrombin, and fibrinogen levels were enhanced in these farmers. In conclusion, inflammation, oxidative stress, and metabolic perturbations reflected the possibility of the effects of pesticides to farmers.

Gene Variations in the Protein C and Fibrinolytic Pathway: Relevance for Severity and Outcome in Pediatric Sepsis.

PubMed

Boeddha, Navin P; Emonts, Marieke; Cnossen, Marjon H; de Maat, Moniek P; Leebeek, Frank W; Driessen, Gertjan J; Hazelzet, Jan A

2017-02-01

The host response to infection involves complex interplays between inflammation, coagulation, and fibrinolysis. Deregulation of hemostasis and fibrinolysis are major causes of critical illness and important determinants of outcome in severe sepsis. The hemostatic responses to infection vary widely between individuals, and are in part explained by polymorphisms in genes responsible for the protein C and fibrinolytic pathway. This review gives an overview of genetic polymorphisms in the protein C and fibrinolytic pathway associated with susceptibility and severity of pediatric sepsis. In addition, genetic polymorphisms associated with adult sepsis and other pediatric thromboembolic disorders are discussed, as these polymorphisms might be candidates for future molecular genetic research in pediatric sepsis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Fibrin sealants: surgical hemostat, sealant and adhesive.

PubMed

Mandell, Samuel P; Gibran, Nicole S

2014-06-01

Fibrin sealants (FS) have been approved for use in the United States since 1998. Since approval, they have been used in a wide variety of clinical settings and new products continue to be introduced. This review covers the literature supporting the USA FDA-approved indications for FS products produced by Baxter Corp. Literature review of PubMed, the Cochrane Library, FDA approval documents and product websites yielded information contained in this article. Mechanism of action, efficacy and safety of these products are covered. FS are generally safe, popular and are used for a wide variety of off-label indications. Their use appears to be expanding rapidly. For many uses, including approved ones, large well-controlled trials are still needed. Additionally, cost-effectiveness data for these products would be a great benefit in guiding their future use.

Hemostatic findings of pleural fluid in dogs and the association between pleural effusions and primary hyperfibrino(geno)lysis: A cohort study of 99 dogs

PubMed Central

Drigo, Michele; Piek, Christine J.; Simioni, Paolo; Caldin, Marco

2018-01-01

The primary objective of this study was to determine if activation of coagulation and fibrinolysis occurs in canine pleural effusions. Thirty-three dogs with pleural effusions of different origin were studied. Pleural effusion fibrinogen concentrations were significantly lower, while pleural fibrin-fibrinogen degradation products (FDPs) and D-dimer concentrations were significantly higher than those in plasma (P < 0.001 for all comparisons). These results show that, in canine pleural fluids, there is evidence of coagulation activation and fibrinolysis. The secondary aims of the current study were to determine if primary hyperfibrinolysis ([PHF] i.e., elevated plasma FDPs with a normal D-dimer concentrations), occurs in dogs with pleural effusion, and whether the presence of a concurrent inflammatory process may have activated the hemostatic cascade, with its intrinsically linked secondary hyperfibrinolysis, masking the concurrent PHF. The previously 33 selected dogs with pleural effusion (group 1) were compared to two control groups of 33 healthy (group 2) and 33 sick dogs without pleural effusion (group 3). Serum fibrinogen, FDPs, D-dimer, C-reactive protein (CRP), fibrinogen/CRP ratio, and frequency of PHF were determined. Fibrinogen, FDPs, D-dimer and CRP concentrations in group 1 were significantly increased compared to group 2 (P < 0.001 for all comparisons). FDPs and CRP concentrations in group 1 were also significantly increased compared to group 3 (P = 0.001 and P < 0.001, respectively). The fibrinogen/CRP ratio was significantly decreased in group 1 compared to groups 2 and 3 (P < 0.001 for both comparison). The frequency of PHF was significantly higher in group 1 compared to groups 2 (P = 0.004), but not compared to group 3. These results support the hypothesis that PHF occurs significantly more often in dogs with pleural effusion compared to healthy dogs. Nevertheless, the decrease in the fibrinogen/CRP ratio in group 1 compared to group 3, considering the higher FDPs and similar D-dimer concentrations, would suggest that PHF is also more frequent in dogs with pleural effusion compared to sick control dogs, and that this phenomenon is hidden due to concurrent secondary hyperfibrinolysis. PMID:29462172

Hemostatic findings of pleural fluid in dogs and the association between pleural effusions and primary hyperfibrino(geno)lysis: A cohort study of 99 dogs.

PubMed

Zoia, Andrea; Drigo, Michele; Piek, Christine J; Simioni, Paolo; Caldin, Marco

2018-01-01

The primary objective of this study was to determine if activation of coagulation and fibrinolysis occurs in canine pleural effusions. Thirty-three dogs with pleural effusions of different origin were studied. Pleural effusion fibrinogen concentrations were significantly lower, while pleural fibrin-fibrinogen degradation products (FDPs) and D-dimer concentrations were significantly higher than those in plasma (P < 0.001 for all comparisons). These results show that, in canine pleural fluids, there is evidence of coagulation activation and fibrinolysis. The secondary aims of the current study were to determine if primary hyperfibrinolysis ([PHF] i.e., elevated plasma FDPs with a normal D-dimer concentrations), occurs in dogs with pleural effusion, and whether the presence of a concurrent inflammatory process may have activated the hemostatic cascade, with its intrinsically linked secondary hyperfibrinolysis, masking the concurrent PHF. The previously 33 selected dogs with pleural effusion (group 1) were compared to two control groups of 33 healthy (group 2) and 33 sick dogs without pleural effusion (group 3). Serum fibrinogen, FDPs, D-dimer, C-reactive protein (CRP), fibrinogen/CRP ratio, and frequency of PHF were determined. Fibrinogen, FDPs, D-dimer and CRP concentrations in group 1 were significantly increased compared to group 2 (P < 0.001 for all comparisons). FDPs and CRP concentrations in group 1 were also significantly increased compared to group 3 (P = 0.001 and P < 0.001, respectively). The fibrinogen/CRP ratio was significantly decreased in group 1 compared to groups 2 and 3 (P < 0.001 for both comparison). The frequency of PHF was significantly higher in group 1 compared to groups 2 (P = 0.004), but not compared to group 3. These results support the hypothesis that PHF occurs significantly more often in dogs with pleural effusion compared to healthy dogs. Nevertheless, the decrease in the fibrinogen/CRP ratio in group 1 compared to group 3, considering the higher FDPs and similar D-dimer concentrations, would suggest that PHF is also more frequent in dogs with pleural effusion compared to sick control dogs, and that this phenomenon is hidden due to concurrent secondary hyperfibrinolysis.

Radiofrequency bipolar hemostatic sealer reduces blood loss, transfusion requirements, and cost for patients undergoing multilevel spinal fusion surgery: a case control study.

PubMed

Frank, Steven M; Wasey, Jack O; Dwyer, Ian M; Gokaslan, Ziya L; Ness, Paul M; Kebaish, Khaled M

2014-07-05

A relatively new method of electrocautery, the radiofrequency bipolar hemostatic sealer (RBHS), uses saline-cooled delivery of energy, which seals blood vessels rather than burning them. We assessed the benefits of RBHS as a blood conservation strategy in adult patients undergoing multilevel spinal fusion surgery. In a retrospective cohort study, we compared blood utilization in 36 patients undergoing multilevel spinal fusion surgery with RBHS (Aquamantys, Medtronic, Minneapolis, MN, USA) to that of a historical control group (n = 38) matched for variables related to blood loss. Transfusion-related costs were calculated by two methods. Patient characteristics in the two groups were similar. Intraoperatively, blood loss was 55% less in the RBHS group than in the control group (810 ± 530 vs. 1,800 ± 1,600 mL; p = 0.002), and over the entire hospital stay, red cell utilization was 51% less (2.4 ± 3.4 vs. 4.9 ± 4.5 units/patient; p = 0.01) and plasma use was 56% less (1.1 ± 2.4 vs. 2.5 ± 3.4 units/patient; p = 0.03) in the RBHS group. Platelet use was 0.1 ± 0.5 and 0.3 ± 0.6 units/patient in the RBHS and control groups, respectively (p = 0.07). The perioperative decrease in hemoglobin was less in the RBHS group than in the control group (-2.0 ± 2.2 vs. -3.2 ± 2.1 g/dL; p = 0.04), and hemoglobin at discharge was higher in the RBHS group (10.5 ± 1.4 vs. 9.7 ± 0.9 g/dL; p = 0.01). The estimated transfusion-related cost savings were $745/case by acquisition cost and approximately 3- to 5-fold this amount by activity-based cost. The use of RBHS in patients undergoing multilevel spine fusion surgery can conserve blood, promote higher hemoglobin levels, and reduce transfusion-related costs.

Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force.

PubMed

Martinowitz, U; Michaelson, M

2005-04-01

Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%-57%). As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses.

Acquired Hemophilia A in an advanced age patient of hispanic origin: a case report.

PubMed

Rivera Cora, Nalyssa I; Irizarry Delgado, Freddie; Merle Ramírez, Santa M; Vera Quiñones, Jorge

2017-09-04

Acquired Hemophilia A (AHA) is a rare hematological disorder that exhibits an incidence of approximately 1.5 cases per million patients a year. It is characterized by the development of autoantibodies against circulating Factor VIII coagulation proteins which, in turn, which in turn lead to potentially life-threatening hemorrhagic episodes. The incidence of AHA increases with age; with 80% of the affected patient population encompassing men and women that are 65 years or older. Some of the challenges that are highlighted in managing this disorder relate to the delayed diagnosis of this condition due to the rarity of the latter, the difficulty in establishing reliable hemostasis, and the secondary complications that are found when using immunosuppressive and hemostatic treatments in tandem with the elderly population afflicted with this disease. A 90-year-old female of Hispanic origin presented with a 2-week history of generalized weakness, dizziness, shortness of breath and extensive purpuric formations that involved the left arm towards the lateral aspect of the thorax with the inclusion of a small right lateral neck hematoma formation. Upon initial laboratory screening, a hemoglobin level of 7.9, a hematocrit level of 21.9 and a PTT value of 70.9 were discovered. Despite conventional hemostatic treatment approaches, the patient did not show marked improvement of the laboratory values. Ongoing specialized laboratory reports, combined with the clinical presentation of the patient, led to the diagnosis of Acquired Hemophilia A. Treatment with recombinant porcine Factor VIII was initiated, which led to rapid improvement of clinical symptoms and laboratory values. The patient was discharged with current treatment plan and emergent follow/up with a hematologist was scheduled. Acquired Hemophilia A is an elusive bleeding disorder that has been seldom encountered in the demographics of Puerto Rico. The prompt detection of this diagnosis based on the clinical presentation alone is paramount to prevent the occurrence of grave hemorrhagic episodes. General knowledge and awareness of the treatment options available is key to ameliorate the prognosis of this ailment.

Effect of hypobaric hypoxia, simulating conditions during long-haul air travel, on coagulation, fibrinolysis, platelet function, and endothelial activation.

PubMed

Toff, William D; Jones, Chris I; Ford, Isobel; Pearse, Robert J; Watson, Henry G; Watt, Stephen J; Ross, John A S; Gradwell, David P; Batchelor, Anthony J; Abrams, Keith R; Meijers, Joost C M; Goodall, Alison H; Greaves, Michael

2006-05-17

The link between long-haul air travel and venous thromboembolism is the subject of continuing debate. It remains unclear whether the reduced cabin pressure and oxygen tension in the airplane cabin create an increased risk compared with seated immobility at ground level. To determine whether hypobaric hypoxia, which may be encountered during air travel, activates hemostasis. A single-blind, crossover study, performed in a hypobaric chamber, to assess the effect of an 8-hour seated exposure to hypobaric hypoxia on hemostasis in 73 healthy volunteers, which was conducted in the United Kingdom from September 2003 to November 2005. Participants were screened for factor V Leiden G1691A and prothrombin G20210A mutation and were excluded if they tested positive. Blood was drawn before and after exposure to assess activation of hemostasis. Individuals were exposed alternately (> or =1 week apart) to hypobaric hypoxia, similar to the conditions of reduced cabin pressure during commercial air travel (equivalent to atmospheric pressure at an altitude of 2438 m), and normobaric normoxia (control condition; equivalent to atmospheric conditions at ground level, circa 70 m above sea level). Comparative changes in markers of coagulation activation, fibrinolysis, platelet activation, and endothelial cell activation. Changes were observed in some hemostatic markers during the normobaric exposure, attributed to prolonged sitting and circadian variation. However, there were no significant differences between the changes in the hypobaric and the normobaric exposures. For example, the median difference in change between the hypobaric and normobaric exposure was 0 ng/mL for thrombin-antithrombin complex (95% CI, -0.30 to 0.30 ng/mL); -0.02 [corrected] nmol/L for prothrombin fragment 1 + 2 (95% CI, -0.03 to 0.01 nmol/L); 1.38 ng/mL for D-dimer (95% CI, -3.63 to 9.72 ng/mL); and -2.00% for endogenous thrombin potential (95% CI, -4.00% to 1.00%). Our findings do not support the hypothesis that hypobaric hypoxia, of the degree that might be encountered during long-haul air travel, is associated with prothrombotic alterations in the hemostatic system in healthy individuals at low risk of venous thromboembolism.

Safety evaluation of new hemostatic agents, smectite granules, and kaolin-coated gauze in a vascular injury wound model in swine.

PubMed

Kheirabadi, Bijan S; Mace, James E; Terrazas, Irasema B; Fedyk, Chriselda G; Estep, J Scot; Dubick, Michael A; Blackbourne, Lorne H

2010-02-01

In 2007, a potent procoagulant mineral called WoundStat (WS), consisting of smectite granules, received clearance from the Food and Drug Administration for marketing in the United States for temporary treatment of external hemorrhage. Previously, we found that microscopic WS particles remained in the injured vessels that were treated, despite seemingly adequate wound debridement. Thus, we investigated the thromboembolic risk of using WS when compared with kaolin-coated gauze, Combat Gauze (CG); or regular gauze, Kerlix (KX) to treat an external wound with vascular injuries in pigs. The right common carotid artery and external jugular vein of pigs were isolated and sharply transected (50%). After 30 seconds of free bleeding, the neck wounds were packed with WS, CG, or KX and compressed until hemostasis was achieved (n = 8 per group). Wounds were debrided after 2 hours, and vascular injuries were primarily repaired with suture. Blood flow was restored after infusing 1 L of crystalloid (no heparin or aspirin) and the wounds were closed. Two hours later, computed tomographic angiography was performed, and the wounds were reopened to harvest the vessels. The brains and lungs were recovered for gross and microscopic examination after euthanasia. No differences were found in baseline measurements. Thrombelastography showed similar hypercoagulability of the final blood samples when compared with baselines in all groups. All vessels treated with KX or CG were patent and had no thrombus or blood clot in their lumen. In contrast, seven of eight carotid arteries and six of eight jugular veins treated with WS developed large occlusive red thrombi and had no flow. Small clots and WS residues were also found in the lungs of two pigs. Histologically, significant endothelial and transmural damage was seen in WS-treated vessels with luminal thrombi and embedded WS residues. WS granules caused endothelial injury and significant transmural damage to the vessels that render them nonviable for primary surgical repair. The granules can enter systemic circulation and cause distal thrombosis in vital organs. More relevant in vitro and in vivo safety tests should be required for clearance of new hemostatic agents.

Effects of two combined oral contraceptives containing ethinyl estradiol 30 microg combined with either gestodene or drospirenone on hemostatic parameters, lipid profiles and blood pressure.

PubMed

Yildizhan, Recep; Yildizhan, Begum; Adali, Ertan; Yoruk, Pinar; Birol, Fatih; Suer, Necdet

2009-08-01

The aim of this study is to compare the effect of ethinyl estradiol 0.03 mg/gestodene 0.075 mg (EE/GSD) with ethinylestradiol 0.03 mg/drospirenone 3 mg (EE/DRSP) administered according to conventional 21/7 regimen on body mass index (BMI), blood pressure (BP), lipid metabolism and hemostatic parameters. In this study, 160 healthy women were randomized to EE/GSD mg or EE/DRSP for 12 months. Mean differences in BMI, high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), total cholesterol (TC) levels and BP compared to baseline were assessed. One hundred and forty-five (89%) of the women completed all 12 treatment cycles. The subjects randomly assigned into two treatment groups. Group EE/GSD (n = 71) and group EE/DRSP (n = 72). In group B, BMI values were significantly lower than baseline at the sixth cycle. DRSP/EE had more favorable effects on BP than GSD/EE with the mean systolic and diastolic BPs remaining lower in the DRSP/EE group. The difference between the two preparations was not statistically significant at the end of the study. TC levels remained similar in both groups throughout the study period. In both groups LDL-C levels decreased, triglyceride and HDL-C levels significantly increased from baseline levels. These changes result in increasing HDL-C/LDL-C ratio, demonstrating anti-atherogenic effect. Menstrual cycle patterns and the incidence of adverse events were similar between groups. The duration of withdrawal bleeding decreased during the study for both groups and was similar. The EE/DRSP regimen provides good cycle control with reliable contraceptive efficacy and low incidence of adverse events. Compared with the EE/GSD preparation, the EE/DRSP preparation demonstrated a more favorable effect on BMI and BP with the mean BMI and mean BP remaining lower than baseline mean. The new formulation may be especially beneficial for women susceptible to body weight gain and rise in BP.

Compression Socks Worn During Flight and Hemostatic Balance in Boston Marathon Runners on Oral Contraceptives.

PubMed

Taylor, Beth A; Zaleski, Amanda L; Ballard, Kevin D; Panza, Gregory A; Fernandez, Antonio B; Corso, Lauren; Pescatello, Linda S; Baggish, Aaron L; Troyanos, Christopher; Thompson, Paul D

2018-05-01

To investigate the effect of oral contraceptive (OC) use and compression socks on hemostatic activation in women flying cross-country to and from a marathon. Prospective study. 2015 Boston Marathon. Women were divided into non-OC using (CONTROL; n = 12), OC-using (OC; n = 15), and OC-using plus compression sock (OC + SOCK; n = 14) groups. Women in OC + SOCK wore compression socks during flights to and from the marathon. Venous blood samples were collected within 24 hours of arriving in Boston (EXPO), immediately after the marathon (RUN), and within 24 hours after a return flight home (Post-Flight) for analysis of thrombin-antithrombin complex (TAT), d-dimer, and tissue plasminogen activator (t-PA). TAT did not increase with exercise (P = 0.48) and was not affected by group (P = 0.08) or the interaction between these 2 factors (P = 0.80). Group, time, and their interaction were significant for d-dimer (all P < 0.05) such that d-dimer increased with acute exercise to a greater extent (Δ d-dimer from expo to postrace = 909.5 ± 1021.9 ng/mL) in the OC + SOCK group relative to OC (Δ d-dimer = 240.0 ± 178.5 ng/mL; P = 0.02) and CONTROL (Δ d-dimer = 230.3 ± 120.3 ng/mL; P = 0.02). There was a significant effect of time, group, and the interaction on t-PA (all P < 0.01) such that t-PA increased with acute exercise to a greater extent (Δ t-PA from expo to postrace = 19.6 ± 10.0 ng/mL) in the CONTROL group relative to OC (Δ t-PA = 4.0 ± 1.8 ng/mL; P < 0.01) and OC + SOCK (Δ t-PA = 3.3 ± 1.2 ng/mL; P < 0.01). Female runners using OCs did not exhibit disproportionately increased coagulation. The use of compression socks in women on OCs, surprisingly, resulted in a greater increase in d-dimer after exercise.

Aronia melanocarpa extract suppresses the biotoxicity of homocysteine and its metabolite on the hemostatic activity of fibrinogen and plasma.

PubMed

Malinowska, Joanna; Babicz, Karolina; Olas, Beata; Stochmal, Anna; Oleszek, Wieslaw

2012-07-01

Aronia melanocarpa fruits (Rosaceae) are one of the richest plant sources of phenolic substances, and it has been shown to have various biological activities. Berries of A. melanocarpa (chokeberry) have been supposed to be beneficial for the prevention of cardiovascular events. In this study the influence of aronia extract on the clot formation (using human plasma and purified fibrinogen) and the fibrin lysis during the model of hyperhomocysteinemia was investigated. Hyperhomocysteinemia was induced using a reduced form of Hcys (at final dose of 0.1mM) and the most reactive form of Hcys - its cyclic thioester, homocysteine thiolactone (HTL, 1 μM). The aim of our study in vitro was also to investigate the modifications of human plasma total proteins and the oxidative stress (by measuring the total antioxidant level - TAS) in plasma after incubation with Hcys, HTL and/or aronia extract. The biological properties of aronia extract were compared with the action of a well characterized antioxidative commercial polyphenol - resveratrol (3,4',5- trihydroxystilbene). The HTL, like its precursor, Hcys stimulated polymerization of fibrinogen. The results also demonstrated that Hcys (0.1mM) and HLT at lower doses than Hcys (1 μM) reduced the fibrin lysis in human plasma. Moreover, Hcys and HTL change the level of thiol and amino groups in plasma total proteins and induce the oxidative stress in plasma. Our results indicate that aronia extract reduced the biotoxicity action of Hcys and HTL on hemostatic properties of fibrinogen or plasma, suggesting its possible protective properties in hyperhomocysteinemia - induced cardiovascular diseases. Moreover, our results showed that the extract from berries of A. melanocarpa due to antioxidant action, significantly reduced the oxidative stress (measured by TAS) in plasma during the model of hyperhomocysteinemia. In the comparative studies, the extract from berries of A. melanocarpa and reseveratrol had similar protective properties. It gives hopes for development of diet supplements, which may be preventing thrombosis in pathological states where plasma procoagulant activity and oxidative stress are observed e.g. in hyperhomocysteinemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Toward correlating structure and mechanics of platelets.

PubMed

Sorrentino, Simona; Studt, Jan-Dirk; Horev, Melanie Bokstad; Medalia, Ohad; Sapra, K Tanuj

2016-09-02

The primary physiological function of blood platelets is to seal vascular lesions after injury and form hemostatic thrombi in order to prevent blood loss. This task relies on the formation of strong cellular-extracellular matrix interactions in the subendothelial lesions. The cytoskeleton of a platelet is key to all of its functions: its ability to spread, adhere and contract. Despite the medical significance of platelets, there is still no high-resolution structural information of their cytoskeleton. Here, we discuss and present 3-dimensional (3D) structural analysis of intact platelets by using cryo-electron tomography (cryo-ET) and atomic force microscopy (AFM). Cryo-ET provides in situ structural analysis and AFM gives stiffness maps of the platelets. In the future, combining high-resolution structural and mechanical techniques will bring new understanding of how structural changes modulate platelet stiffness during activation and adhesion.

Overview on platelet preservation: better controls over storage lesion.

PubMed

Ohto, Hitoshi; Nollet, Kenneth E

2011-06-01

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

[Use of thrombelastography to guide posttraumatic hemostatic therapy: More coagulation factor concentrates and less allogenic blood transfusion?

PubMed

David, J S; Imhoff, E; Parat, S; Augey, L; Geay-Baillat, M-O; Incagnoli, P; Tazarourte, K

2016-11-01

Viscoelastic technics are used for 10 years and include the ROTEM ® and the TEG ® . These devices that exploit the viscoelastic properties of the clotting blood, allow a rapid and global analysis of the haemostatic process taking into account all the process interfering with haemostasis such as inflammation. It has been shown that the use of these technics in clinical situations such as trauma, postpartum haemorrhage, gastrointestinal bleeding or cardiac surgery may reduce the need for blood product, the cost and perhaps may improve the outcome of the patients. Thanks to a rapid identification of the underlying coagulation deficit, these technics facilitate decision-making during acute care and help to guide the treatment, particularly with coagulation factor's concentrate. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Contemporary review of the 532 nm laser for treatment of benign prostatic hyperplasia.

PubMed

Chughtai, Bilal; Laor, Leanna; Dunphy, Claire; Te, Alexis

2015-04-01

Benign prostatic hyperplasia (BPH) is a condition that occurs increasingly with age. The established gold standard treatment for BPH has been the electrocautery-based transurethral resection of the prostate (TURP). TURP, however, is associated with several complications and side effects. Therefore, there is an increasing interest in a number of emerging minimally invasive therapies as alterative treatment options. Laser therapy using the Greenlight laser is a promising alternative to the traditional TURP. Selective absorption by hemoglobin allows rapid, hemostatic vaporization of prostate tissue. Additional advantages include avoidance or minimization of complications such as intraoperative fluid absorption, and bleeding, retrograde ejaculation, impotence, and incontinence, as well as its use in treating high volume BPH. We review the use of the Greenlight laser in the treatment of BPH, when comparing complications and advantages in relation to TURP.

Superhydrophobic/Superhydrophilic Janus Fabrics Reducing Blood Loss.

PubMed

Zhu, Tang; Wu, Junrong; Zhao, Ning; Cai, Chao; Qian, Zhenchao; Si, Fangfang; Luo, Heng; Guo, Jing; Lai, Xuan; Shao, Longquan; Xu, Jian

2018-04-01

Hemostatic fabrics are most commonly used in baseline emergency treatment; however, the unnecessary blood loss due to the excessive blood absorption by traditional superhydrophilic fabrics is overlooked. Herein, for the first time, superhydrophobic/superhydrophilic Janus fabrics (superhydrophobic on one side and superhydrophilic on the other) are proposed: the superhydrophilic part absorbs water in the blood to expedite the clotting while the superhydrophobic part prevents blood from further permeating. Compared with the common counterparts, effective bleeding control with reducing blood loss more than 50% can be achieved while the breathability largely remain by using Janus fabrics. The proposed prototypes can even prolong the survival time in the rat model with serious bleeding. This strategy for reducing blood loss via simply tuning wettability is promising for the practical applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microsurgical resection of skull base meningioma-expanding the operative corridor.

PubMed

Raheja, Amol; Couldwell, William T

2016-11-01

A better understanding of surgical anatomy, marked improvement in illumination devices, provision of improved hemostatic agents, greater availability of more precise surgical instruments, and better modalities for skull base reconstruction have led to an inevitable evolution of skull base neurosurgery. For the past few decades, many skull base neurosurgeons have worked relentlessly to improve the surgical approach and trajectory for the expansion of operative corridor. With the advent of newer techniques and their rapid adaptation, it is foundational, especially for young neurosurgeons, to understand the basics and nuances of modifications of traditional neurosurgical approaches. The goal of this topic review is to discuss the evolution of, concepts in, and technical nuances regarding the operative corridor expansion in the field of skull base surgery for intracranial meningioma as they pertain to achieving optimal functional outcome.

Point-of-Care Coagulation Tests Monitoring of Direct Oral Anticoagulants and Their Reversal Therapy: State of the Art.

PubMed

Iapichino, Giacomo E; Bianchi, Paolo; Ranucci, Marco; Baryshnikova, Ekaterina

2017-06-01

Direct oral anticoagulants (DOACs) exert similar anticoagulant effects to vitamin K antagonists and are increasingly used worldwide. Nevertheless, an evidence-based approach to patients receiving DOACs when any unplanned urgent surgery or bleeding (either spontaneous or traumatic) occurs is still missing. In this review, we investigate the role of point-of-care coagulation tests when other, more specific tests are not available. Indeed, thromboelastography and activated clotting time can detect dabigatran-induced coagulopathy, while their accuracy is limited for apixaban and rivaroxaban, mostly in cases of low drug plasma concentrations. These tests can also be used to guide the reversal of DOAC-induced coagulopathy providing a quick, before-and-after picture in case of therapeutic use of hemostatic compounds. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effects of Nd:YAG and CO2 lasers on cerebral microvasculature. Study in normal rabbit brain.

PubMed

Kuroiwa, T; Tsuyumu, M; Takei, H; Inaba, Y

1986-01-01

The effect of Nd:YAG and CO2 laser beams on cerebral microvasculature was examined in experimental animals. Soft x-ray microangiography and histological examination of the brain after Nd:YAG laser exposure revealed broad avascular or oligovascular zones in the irradiated and the surrounding edematous tissue, in which the surviving vessels were narrowed and tapered without significant leakage of blood. After CO2 laser exposure, a wedge-shaped tissue defect surrounded by layers of charring, coagulation, and edema was observed. The main finding in the surrounding coagulation and edematous layers was dilatation of the vessels. Hemorrhage was sometimes observed, mainly in the edematous layer. These findings seem to explain the effective hemostatic capability of the Nd:YAG laser and the occasional hemorrhage following CO2 laser exposure, especially at high energy output.

Modeling thrombin generation: plasma composition based approach.

PubMed

Brummel-Ziedins, Kathleen E; Everse, Stephen J; Mann, Kenneth G; Orfeo, Thomas

2014-01-01

Thrombin has multiple functions in blood coagulation and its regulation is central to maintaining the balance between hemorrhage and thrombosis. Empirical and computational methods that capture thrombin generation can provide advancements to current clinical screening of the hemostatic balance at the level of the individual. In any individual, procoagulant and anticoagulant factor levels together act to generate a unique coagulation phenotype (net balance) that is reflective of the sum of its developmental, environmental, genetic, nutritional and pharmacological influences. Defining such thrombin phenotypes may provide a means to track disease progression pre-crisis. In this review we briefly describe thrombin function, methods for assessing thrombin dynamics as a phenotypic marker, computationally derived thrombin phenotypes versus determined clinical phenotypes, the boundaries of normal range thrombin generation using plasma composition based approaches and the feasibility of these approaches for predicting risk.

Mechanobiology of Platelets: Techniques to Study the Role of Fluid Flow and Platelet Retraction Forces at the Micro- and Nano-Scale

PubMed Central

Feghhi, Shirin; Sniadecki, Nathan J.

2011-01-01

Coagulation involves a complex set of events that are important in maintaining hemostasis. Biochemical interactions are classically known to regulate the hemostatic process, but recent evidence has revealed that mechanical interactions between platelets and their surroundings can also play a substantial role. Investigations into platelet mechanobiology have been challenging however, due to the small dimensions of platelets and their glycoprotein receptors. Platelet researchers have recently turned to microfabricated devices to control these physical, nanometer-scale interactions with a higher degree of precision. These approaches have enabled exciting, new insights into the molecular and biomechanical factors that affect platelets in clot formation. In this review, we highlight the new tools used to understand platelet mechanobiology and the roles of adhesion, shear flow, and retraction forces in clot formation. PMID:22272117

Percutaneous Portal Vein Access and Transhepatic Tract Hemostasis

PubMed Central

Saad, Wael E. A.; Madoff, David C.

2012-01-01

Percutaneous portal vein interventions require minimally invasive access to the portal venous system. Common approaches to the portal vein include transjugular hepatic vein to portal vein access and direct transhepatic portal vein access. A major concern of the transhepatic route is the risk of postprocedural bleeding, which is increased when patients are anticoagulated or receiving pharmaceutical thrombolytic therapy. Thus percutaneous portal vein access and subsequent closure are important technical parts of percutaneous portal vein procedures. At present, various techniques have been used for either portal access or subsequent transhepatic tract closure and hemostasis. Regardless of the method used, meticulous technique is required to achieve the overall safety and effectiveness of portal venous procedures. This article reviews the various techniques of percutaneous transhepatic portal vein access and the various closure and hemostatic methods used to reduce the risk of postprocedural bleeding. PMID:23729976

Poland's syndrome: report of a variant.

PubMed

Legbo, Jacob Ndas

2006-01-01

Poland's syndrome is a rare congenital anomaly consisting of unilateral partial or total absence of a breast and/or pectoralis major muscle, and ipsilateral symbrachydactyly. Many structural and functional abnormalities have been described in association with the syndrome. However, only a few hemostatic disorders have been reported. The case of a 12-year-old secondary school girl with unilateral hypoplasia of the breast, absence of anterior axillary fold and absence of the pectoralis major muscle is hereby presented. She also had thrombocytopenia and several episodes of spontaneous bleeding from the ipsilateral anterior chest wall. She did well on medical treatment, with no recurrence of bleeding 10 months after treatment. The author is not aware of any previously reported case of Poland's syndrome associated with bleeding disorder in Africa. This case is presented to alert clinicians of its existence and possible association with hematological disorders.

Repeated General Anesthesia in a Patient With Noonan Syndrome.

PubMed

Asahi, Yoshinao; Fujii, Ryosuke; Usui, Naoko; Kagamiuchi, Hajime; Omichi, Shiro; Kotani, Junichiro

2015-01-01

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial anomalies, short stature, chest deformity, congenital heart diseases, and other comorbidities. The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies. Here we describe dental treatment under general anesthesia performed for a 28-year-old man with NS. He had characteristic features of NS along with mild pulmonary valve stenosis. Dental treatment under general anesthesia was performed successfully on 13 occasions with nasotracheal intubation under curve-tipped suction catheter guidance or insertion of a reinforced laryngeal mask airway. This case suggests that for patients with NS, who might present several challenges, dental anesthesiologists should consider the extent of the patient's disorders to enable them to perform dental treatment safely under general anesthesia.

Repeated General Anesthesia in a Patient With Noonan Syndrome

PubMed Central

Asahi, Yoshinao; Fujii, Ryosuke; Usui, Naoko; Kagamiuchi, Hajime; Omichi, Shiro; Kotani, Junichiro

2015-01-01

Noonan syndrome (NS) is an autosomal dominant disorder characterized by facial anomalies, short stature, chest deformity, congenital heart diseases, and other comorbidities. The challenges faced during anesthetic management of patients with NS could be due to congenital heart diseases, hemostatic disorders, and airway anomalies. Here we describe dental treatment under general anesthesia performed for a 28-year-old man with NS. He had characteristic features of NS along with mild pulmonary valve stenosis. Dental treatment under general anesthesia was performed successfully on 13 occasions with nasotracheal intubation under curve-tipped suction catheter guidance or insertion of a reinforced laryngeal mask airway. This case suggests that for patients with NS, who might present several challenges, dental anesthesiologists should consider the extent of the patient's disorders to enable them to perform dental treatment safely under general anesthesia. PMID:26061577

Fibrin glue in ophthalmology

PubMed Central

Panda, Anita; Kumar, Sandeep; Kumar, Abhiyan; Bansal, Raseena; Bhartiya, Shibal

2009-01-01

Suturing is a time consuming task in ophthalmology and suture induced irritation and redness are frequent problems. Postoperative wound infection and corneal graft rejection are examples of possible suture related complications. To prevent these complications, ophthalmic surgeons are switching to sutureless surgery. A number of recent developments have established tissue adhesives like cyanoacrylate glue and fibrin glue as attractive alternatives to sutures. A possible and promising new application for tissue adhesives is to provide a platform for tissue engineering. Currently, tissue glue is being used for conjunctival closure following pterygium and strabismus surgery, forniceal reconstruction surgery, amniotic membrane transplantation, lamellar corneal grafting, closure of corneal perforations and descematoceles, management of conjunctival wound leaks after trabeculectomy, lid surgery, adnexal surgery and as a hemostat to minimise bleeding. The purpose of this review is to discuss the currently available information on fibrin glue. PMID:19700876

GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.

PubMed

Law, Luke A; Graham, Douglas K; Di Paola, Jorge; Branchford, Brian R

2018-01-01

The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.

[Clinical epidemiological characteristics and change trend of upper gastrointestinal bleeding over the past 15 years].

PubMed

Wang, Jinping; Cui, Yi; Wang, Jinhui; Chen, Baili; He, Yao; Chen, Minhu

2017-04-25

To investigate the clinical epidemiology change trend of upper gastrointestinal bleeding (UGIB) over the past 15 years. Consecutive patients who was diagnosed as continuous UGIB in the endoscopy center of The First Affiliated Hospital of Sun-Yat University during the period from 1 January 1997 to 31 December 1998 and the period from 1 January 2012 to 31 December 2013 were enrolled in this study. Their gender, age, etiology, ulcer classification, endoscopic treatment and hospitalization mortality were compared between two periods. In periods from 1997 to 1998 and 2012 to 2013, the detection rate of UGIB was 9.99%(928/9 287) and 4.49%(1 092/24 318)(χ 2 =360.089, P=0.000); the percentage of male patients was 73.28%(680/928) and 72.44% (791/1 092) (χ 2 =0.179, P=0.672), and the onset age was (47.3±16.4) years and (51.4±18.2) years (t=9.214, P=0.002) respectively. From 1997 to 1998, the first etiology of UGIB was peptic ulcer bleeding, accounting for 65.2%(605/928)[duodenal ulcer 47.8%(444/928), gastric ulcer 8.3%(77/928), stomal ulcer 2.3%(21/928), compound ulcer 6.8%(63/928)],the second was cancer bleeding(7.0%,65/928), and the third was esophageal and gastric varices bleeding (6.4%,59/928). From 2012 to 2013, peptic ulcer still was the first cause of UGIB, but the ratio obviously decreased to 52.7%(575/1092)(χ 2 =32.467, P=0.000)[duodenal ulcer 31.9%(348/1092), gastric ulcer 9.4%(103/1092), stomal ulcer 2.8%(30/1092), compound ulcer 8.6%(94/1092)]. The decreased ratio of duodenal ulcer bleeding was the main reason (χ 2 =53.724, P=0.000). Esophageal and gastric varices bleeding became the second cause (15.1%,165/1 092, χ 2 =38.976, P=0.000), and cancer was the third cause (9.2%,101/1 092, χ 2 =3.352, P=0.067). The largest increasing amplitude of the onset age was peptic ulcer bleeding [(46.2±16.7) years vs. (51.9±18.9) years, t=-5.548, P=0.000), and the greatest contribution to the amplitude was duodenal ulcer bleeding [(43.4±15.9) years vs. (48.4±19.4) years, t=-3.935, P=0.000], while the onset age of esophageal and gastric varices bleeding [(49.8±14.1) years vs. (48.8±13.9) years, t=0.458, P=0.648] and cancer [(58.4±13.4) years vs. (58.9±16.7) years, t=-0.196, P=0.845] did not change significantly. Compared with the period from 1997 to 1998, the detection rate of high risk peptic ulcer rebleeding (Forrest stage I(a, I(b, II(a and II(b) increased (χ 2 =39.958, P=0.000) in the period from 2012 to 2013. From 1997 to 1998, 54 patients underwent endoscopic treatment, and the achievement ratio of hemostasis was 79.6% (43/54). From 2012 to 2013, 261 patients underwent endoscopic treatment and the achievement ratio of hemostasis was 96.9%(253/261), which was significantly higher (χ 2 =23.287, P=0.000). Compared to the period from 1997 to 1998, more patients with variceal bleeding or non-variceal bleeding received endoscopic treatment in time (39.0% vs. 70.3%, χ 2 =51.930, P=0.000; 3.6% vs. 15.6%, χ 2 =62.292, P=0.000, respectively), and higher ratio of patients staging Forrest stage I(a to II(b also received endoscopic treatment in the period from 2012 to 2013 [27.4%(26/95) vs. 68.5%(111/162), χ 2 =40.739, P=0.000]. More qualified endoscopic hemostatic techniques were used, containing thermocoagulation (0 vs. 15.2%, χ 2 =79.518, P=0.000), hemostatic clip (0 vs. 55.9%, χ 2 =20.879, P=0.000), hemostatic clip combined with thermocoagulation (4.3% vs. 16.4%, χ 2 =5.154, P=0.023), while less single injection was used (87.1% vs. 6.2%, χ 2 =10.420, P=0.001), and single spraying for hemostasis was completely abandoned in the period from 2012 to 2013. The ratio of inpatients undergoing reoperation decreased obviously in the period from 2012 to 2013 [9.3%(86/928) vs. 6.0%(65/1092), χ 2 =7.970, P=0.005], while no significant difference was found in mortality during hospitalization between two periods. Compared with the period from 1997 to1998, the mean onset age of UGIB increased, and the ratio of peptic ulcer bleeding decreased due to the reduction of duodenal ulcer bleeding, the detection rate of high risk peptic ulcer rebleeding increased, the cure rate of endoscopic treatment for UGIB increased, more reasonable and immediate hemostatic methods were used, but overall mortality did not change obviously in the period from 2012 to 2013.

Linear Hand Burn Contracture Release under Local Anesthesia without Tourniquet.

PubMed

Prasetyono, Theddeus O H; Koswara, Astrid F

2015-10-01

The objective of this report is to present a case of hand burn linear contracture release performed under local anesthesia. It also introduces the one-per-mil tumescent solution consisted of 0.2% lidocaine and 1:1.000.000 epinephrine as a local anesthesia formula, which has the potential of providing adequate anesthesia as well as hemostatic effect during surgery of the hand without tourniquet. The surgery was performed on a 19 year-old male patient with multiple thumb and fingers flexion linear contracture for 105 minutes without any obstacle. The patient did not complain any pain and discomfort during the procedure; while bloodless operative field was successfully achieved. At four-month follow up, the patient could fully extend his thumb, middle and ring finger, while the index was limited by 10° at the DIP joint. Overall, the patient was satisfied with the outcome.