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Thrombin Hemostatic

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141. Hemostatic Disorders, Nonplatelet (Diagnosis)

=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMjEwNDY3LW92ZXJ2aWV3 processing > Nonplatelet Hemostatic Disorders Updated: May 12, 2016 Author: Muhammad A Mir, MD, FACP; Chief Editor: Perumal Thiagarajan, MD Share Email Print Feedback Close Sections Sections Nonplatelet Hemostatic Disorders Overview Overview Blood coagulation is triggered by the exposure of tissue factor at injury sites, leading to the generation of minute quantities of thrombin. Thrombin, in turn, activates platelets, as well as factors XI, VIII, and V, and triggers the sequential activation (...) of factors XI, IX, X, and prothrombin on the activated platelet surface, leading to the generation of sufficient thrombin to convert fibrinogen to fibrin and affect hemostasis. Platelets localize coagulation to the hemostatic thrombus and protect coagulation enzymes from inhibition by plasma and platelet inhibitors, thus preventing disseminated intravascular coagulation (DIC). Abnormalities in the coagulation cascade that are independent of the platelet protective mechanisms can affect hemostasis

2014 eMedicine.com

142. A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential. (PubMed)

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential. Thrombin, the major enzyme of the hemostatic system, is involved in biological processes associated with several human diseases. The capacity of a given individual to generate thrombin, called the thrombin generation potential (TGP), can be robustly measured in plasma and was shown to associate with thrombotic disorders. To investigate the genetic architecture underlying (...) the interindividual TGP variability, we conducted a genome-wide association study in 2 discovery samples (N = 1967) phenotyped for 3 TGP biomarkers, the endogenous thrombin potential, the peak height, and the lag time, and replicated the main findings in 2 independent studies (N = 1254). We identified the ORM1 gene, coding for orosomucoid, as a novel locus associated with lag time variability, reflecting the initiation process of thrombin generation with a combined P value of P = 7.1 × 10(-15) for the lead single

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2014 Blood

143. Thrombin Generation Test in Patient With Liver Cirrhosis

Last Verified: August 2017 Keywords provided by RAWI HAZZAN, HaEmek Medical Center, Israel: Coagulation Factor cirrhosis Additional relevant MeSH terms: Layout table for MeSH terms Fibrosis Liver Cirrhosis Pathologic Processes Liver Diseases Digestive System Diseases Thrombin Hemostatics Coagulants (...) Thrombin Generation Test in Patient With Liver Cirrhosis Thrombin Generation Test in Patient With Liver Cirrhosis - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Thrombin Generation Test in Patient

2014 Clinical Trials

144. Redundancy and Interaction of Thrombin- and Collagen-Mediated Platelet Activation in Tail Bleeding and Carotid Thrombosis in Mice. (PubMed)

independent, partially redundant contributions to occlusive thrombus formation in the carotid and to hemostatic clot formation in the tail under the experimental conditions examined. At face value, these results suggest that thrombin- and collagen-induced platelet activation can play partially redundant roles, despite important differences in how these agonists are made available to platelets.© 2014 American Heart Association, Inc. (...) Redundancy and Interaction of Thrombin- and Collagen-Mediated Platelet Activation in Tail Bleeding and Carotid Thrombosis in Mice. Current antiplatelet strategies to prevent myocardial infarction and stroke are limited by bleeding risk. A better understanding of the roles of distinct platelet-activating pathways is needed. We determined whether platelet activation by 2 key primary activators, thrombin and collagen, plays distinct, redundant, or interacting roles in tail bleeding and carotid

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2014 Thrombosis and Vascular Biology

145. Thrombin Generation Mediators and Markers in Sepsis-Associated Coagulopathy and Their Modulation by Recombinant Thrombomodulin.

Thrombin Generation Mediators and Markers in Sepsis-Associated Coagulopathy and Their Modulation by Recombinant Thrombomodulin. Severe sepsis remains the most common cause of death in critically ill patients, and thrombin plays a crucial role in the pathogenesis of sepsis-associated disseminated intravascular coagulation (DIC). The purpose of this study was to profile prothrombin fragment (F1.2), thrombin-antithrombin complex (TAT), and d-dimer (DD) throughout the course of hospital stay (...) a 16% decrease from the baseline to day 7, while the placebo group showed an 8% increase. Both the treatment groups showed a gradual decrease in the TAT and DD, with the group treated with thrombomodulin demonstrating twice the decrease over the 7-day period. Although the data were widely scattered, these results show that DIC represents a hypercoagulable state along with other hemostatic abnormalities and the activation of the inflammatory process. Modulation of these activation processes through

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2014 Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis

146. Thrombin Generation Numerical Models Validation in Haemophilic Case

volunteers endogenous thrombin potential Additional relevant MeSH terms: Layout table for MeSH terms Hemophilia A Hemophilia B Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders Hemorrhagic Disorders Genetic Diseases, Inborn Genetic Diseases, X-Linked Thrombin Hemostatics Coagulants (...) Thrombin Generation Numerical Models Validation in Haemophilic Case Thrombin Generation Numerical Models Validation in Haemophilic Case - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove one or more studies before adding more. Thrombin Generation

2014 Clinical Trials

147. Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery

Additional relevant MeSH terms: Layout table for MeSH terms Antithrombin III Deficiency Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Blood Protein Disorders Thrombophilia Genetic Diseases, Inborn Thrombin Antithrombins Antithrombin III Hemostatics Coagulants Serine Proteinase Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anticoagulants (...) Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery Anti-thrombin III (ATIII) vs Placebo in Children (<7mo) Undergoing Open Congenital Cardiac Surgery - Full Text View - ClinicalTrials.gov Hide glossary Glossary Study record managers: refer to the if submitting registration or results information. Search for terms x × Study Record Detail Saved Studies Save this study Warning You have reached the maximum number of saved studies (100). Please remove

2014 Clinical Trials

148. Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis. (PubMed)

Impaired thrombin generation in Reelin-deficient mice: a potential role of plasma Reelin in hemostasis. Reelin is a large extracellular glycoprotein that is present in the peripheral blood. That Reelin interacts with the coagulation components and elicits a functional role in hemostasis has not yet been elucidated.The hemostatic activity of Reelin is investigated and defined in this study.The interplay of Reelin with coagulation components was elucidated by far-Western and liposome/platelet (...) binding assays. In vivo and ex vivo hemostasis-related analyses of Reelin-deficient mice and plasma were also performed.Reelin interacted with the liposomes containing phosphatidylserine (PS) or phosphatidylcholine. Instead of interacting with known Reelin receptors (ApoE receptor 2, very low density lipoprotein receptor and integrin β1), Reelin interacted with PS of the activated platelets. The interaction between Reelin and the coagulation factors of thrombin and FXa was also demonstrated

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2014 Journal of Thrombosis and Haemostasis

149. A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity. (PubMed)

A systems approach to hemostasis: 3. Thrombus consolidation regulates intrathrombus solute transport and local thrombin activity. Hemostatic thrombi formed after a penetrating injury have a distinctive structure in which a core of highly activated, closely packed platelets is covered by a shell of less-activated, loosely packed platelets. We have shown that differences in intrathrombus molecular transport emerge in parallel with regional differences in platelet packing density and predicted (...) by computational modeling, a decrease in thrombin activity and platelet activation in the thrombus core. Collectively, these data (1) demonstrate that in addition to the activation state of individual platelets, the physical properties of the accumulated mass of adherent platelets is critical in determining intrathrombus agonist distribution and platelet activation and (2) define a novel role for integrin signaling in the regulation of intrathrombus transport rates and localization of thrombin activity. © 2014

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2014 Blood

150. Thrombin drives tumorigenesis in colitis-associated colon cancer (PubMed)

Thrombin drives tumorigenesis in colitis-associated colon cancer The established association between inflammatory bowel disease and colorectal cancer underscores the importance of inflammation in colon cancer development. On the basis of evidence that hemostatic proteases are powerful modifiers of both inflammatory pathologies and tumor biology, gene-targeted mice carrying low levels of prothrombin were used to directly test the hypothesis that prothrombin contributes to tumor development (...) in colitis-associated colon cancer (CAC). Remarkably, imposing a modest 50% reduction in circulating prothrombin in fII+/- mice, a level that carries no significant bleeding risk, dramatically decreased adenoma formation following an azoxymethane/dextran sodium sulfate challenge. Similar results were obtained with pharmacologic inhibition of prothrombin expression or inhibition of thrombin proteolytic activity. Detailed longitudinal analyses showed that the role of thrombin in tumor development in CAC

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2014 Cancer research

151. A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting (PubMed)

I. scapularis tick evasion of the host's hemostatic defense as revealed by the ability of rIxscS-1E1 to inhibit adenosine diphosphate- and thrombin-activated platelet aggregation, and delay activated partial prothrombin time and thrombin time plasma clotting in a dose-responsive manner. We conclude that native IxscS-1E1 is part of the tick saliva protein complex that mediates its anti-hemostatic, and potentially inflammatory, functions by inhibiting the actions of thrombin, trypsin and other yet (...) A blood meal-induced Ixodes scapularis tick saliva serpin inhibits trypsin and thrombin, and interferes with platelet aggregation and blood clotting Ixodes scapularis is a medically important tick species that transmits causative agents of important human tick-borne diseases including borreliosis, anaplasmosis and babesiosis. An understanding of how this tick feeds is needed prior to the development of novel methods to protect the human population against tick-borne disease infections

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2014 International Journal for Parasitology

152. Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study (PubMed)

Combination of thrombin-antithrombin complex, plasminogen activator inhibitor-1, and protein C activity for early identification of severe coagulopathy in initial phase of sepsis: a prospective observational study Current criteria for early diagnosis of coagulopathy in sepsis are limited. We postulated that coagulopathy is already complicated with sepsis in the initial phase, and severe coagulopathy or disseminated intravascular coagulation (DIC) becomes overt after progressive consumption (...) , fibrinogen and fibrin degradation product (FDP)); markers of thrombin generation (thrombin-antithrombin complex (TAT) and soluble fibrin); markers of anticoagulants (protein C (PC) and antithrombin); markers of fibrinolysis (plasminogen, α2-plasmin inhibitor (PI), plasmin-α2-PI complex, and plasminogen activator inhibitor (PAI)-1); and a marker of endothelial activation (soluble E-selectin) were assayed. Patients who had overt DIC at baseline were excluded, and the remaining patients were followed

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2014 Critical Care

153. Thrombin generation mediators and markers in sepsis-associated coagulopathy and their modulation by recombinant thrombomodulin. (PubMed)

Thrombin generation mediators and markers in sepsis-associated coagulopathy and their modulation by recombinant thrombomodulin. Severe sepsis remains the most common cause of death in critically ill patients, and thrombin plays a crucial role in the pathogenesis of sepsis-associated disseminated intravascular coagulation (DIC). The purpose of this study was to profile prothrombin fragment (F1.2), thrombin-antithrombin complex (TAT), and d-dimer (DD) throughout the course of hospital stay (...) a 16% decrease from the baseline to day 7, while the placebo group showed an 8% increase. Both the treatment groups showed a gradual decrease in the TAT and DD, with the group treated with thrombomodulin demonstrating twice the decrease over the 7-day period. Although the data were widely scattered, these results show that DIC represents a hypercoagulable state along with other hemostatic abnormalities and the activation of the inflammatory process. Modulation of these activation processes through

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2014 Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis Controlled trial quality: uncertain

154. Evarrest - human fibrinogen / human thrombin

Evarrest - human fibrinogen / human thrombin 7 Westferry Circus ? Canary Wharf ? London E14 4HB ? United Kingdom An agency of the European Union Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7523 7455 E-mail info@ema.europa.eu Website www.ema.europa.eu 27 June 2013 EMA/464286/2013 Committee for Medicinal Products for Human Use (CHMP) Assessment report EVARREST Common name: Human Fibrinogen / Human Thrombin Procedure No. EMEA/H/C/002515 Note Assessment report as adopted by the CHMP with all (...) Haemostasis is an essential and often challenging part of surgical procedures. As first line, surgeons need to apply conventional haemostatic methods i.e. meticulous surgical techniques such as sutures, ligatures, or cautery. Topical haemostatic agents (gelatine, collagen, or oxidized regenerated cellulose) are widely used as an adjunct to these methods. Fibrin sealants consisting of the biological components human fibrinogen and human thrombin directly apply a fibrin layer on the tissue, either

2013 European Medicines Agency - EPARs

155. The use of Tachosil® as hemostatic sealant in nephron sparing surgery for Wilms tumor: Preliminary observations. (PubMed)

The use of Tachosil® as hemostatic sealant in nephron sparing surgery for Wilms tumor: Preliminary observations. TachoSil, which is an absorbable collagen sponge coated with human fibrinogen and thrombin, has proven to enhance hemostasis and promote optimal wound healing in adults undergoing nephron sparing surgery (NSS). We report our preliminary experience using this hemostatic agent during NSS in children.Prospective analysis of 3 patients with Wilms tumor (synchronous bilateral in one

2013 Journal of Pediatric Surgery

156. Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage. (PubMed)

Thrombosomes: a platelet-derived hemostatic agent for control of noncompressible hemorrhage. Uncontrolled hemorrhage is responsible for ∼80% of the potentially survivable deaths in combat and over 40% of early mortality in the under 65 age group in the United States. Providing an easily used infusible hemostatic agent to first responders could significantly reduce these fatalities. We report on an infusible lyophilized platelet-derived hemostatic agent stabilized with trehalose and polysucrose (...) prior to and during lyophilization.Characterization included determining the particle population size range, surface marker expression GPIb, GPIIbIIIa, and Annexin V binding. Function was assessed by aggregation, thromboelastography, and thrombin generation. Pharmacokinetics, biodistribution, and immunogenicity established using Indium(111) labeled Thrombosomes in healthy New Zealand white rabbits (NZWRs), efficacy in thrombocytopenic NZWR, and safety in NZWRs, canines, and nonhuman

2013 Transfusion

157. Hemostatic abnormalities in sickle cell disease. (PubMed)

Hemostatic abnormalities in sickle cell disease. Although it has long been recognized that sickle cell disease (SCD) and other hemoglobinopathies are associated with a state of chronic hyperactivation of coagulation, the study of the epidemiology of venous thromboembolic (VTE) complications in SCD is only now beginning to evolve. In parallel, mechanistic studies of the hypercoagulable state in humans and mouse models implicate an increasingly important causative role of hemolysis.The case (...) for SCD as a thrombophilic state has been strengthened by the recent literature. In an attempt to better understand the underlying mechanism(s), global assays of coagulation (thromboelastography and thrombin generation assays) have been utilized by several groups, but thus far, the results have been inconsistent, probably because of the technical differences. However, global assays continue to support the case for an important role of peripheral blood cells and their derived microparticles

2013 Current Opinion in Hematology

158. Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness. (PubMed)

Activated prothrombin complex concentrate (APCC)-mediated activation of factor (F)VIII in mixtures of FVIII and APCC enhances hemostatic effectiveness. Activated prothrombin complex concentrates (APCCs), utilized in bypassing therapy for hemophiliacs with inhibitor, contain factors (Fs) VII, FII, FIX and FX, and their active forms. A recent report has demonstrated that mixtures of APCC and FVIII potentiated thrombin generation, in vitro, in plasma from patients with severe hemophilia (...) A, but the mechanism(s) involved remains unknown.APCC (0.05 U mL(-1) ) increased FVIII activity ~ 4-fold within 1 min in one-stage clotting assays, followed by a return to initial levels within 10 min. This reaction was dependent on the presence of tissue factor and phospholipid. Thrombin generation produced from APCC was ~ 3.5-fold greater in the presence of FVIII than that in its absence. SDS-PAGE analysis revealed that APCC sequentially proteolyzed the heavy chain of FVIII at Arg(372) and Arg(740) , followed

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2013 Journal of Thrombosis and Haemostasis

159. In vivo hemostatic efficacy of polyurethane foam compared to collagen and gelatin. (PubMed)

In vivo hemostatic efficacy of polyurethane foam compared to collagen and gelatin. Topical hemostatic agents are used in all surgical disciplines. Most of these hemostats are based on animal-derived products like collagen and gelatin. They carry the potential risk of pathogen transmission. A newly developed biodegradable, fully synthetic hemostatic agent based on polyurethane foam (PU) with 55 % polyethylene glycol (PEG) would prevent these potential risks.The hemostatic efficacy of this new (...) agent was compared to gelatin and collagen in humans who underwent extraction of an upper and lower molar (split-mouth model). After extraction of a molar in the maxilla and mandible, a PU foam and collagen or gelatin were inserted in the extraction socket for 2 min. Hereafter, the agents were removed and stored in ethylenediaminetetraacetic acid to stop coagulation. Then, the concentration of coagulation parameters thrombin-antithrombin III (TAT) complexes, fibrinogen, and thromboxane B2 (TxB2

2013 Clinical oral investigations Controlled trial quality: uncertain

160. Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy. (PubMed)

Immediate effects of individualized heparin and protamine management on hemostatic activation and platelet function in adult patients undergoing cardiac surgery with tranexamic acid antifibrinolytic therapy. This randomized prospective study was initiated to clarify whether individualized heparin and protamine dosing has immediate effects on hemostatic activation and platelet function in adult cardiac surgery.Sixty adults undergoing elective coronary artery bypass grafting (CABG) were assigned (...) to receive individualized heparin and protamine (HMS group, n= 29) or a standard dose (ACT group, n=24). Measures of thrombin generation and Multiplate (Verum Diagnostica, Munich, Germany) platelet function tests were performed before and after cardiopulmonary bypass (CPB).HMS patients received higher heparin (p = 0.006) and lower protamine (p<0.001) doses. Post-CPB, HMS managed patients showed significantly lower thrombin generation (thrombin-antithrombin (TAT) p<0.02) than the ACT group. Moreover, HMS

2013 Perfusion Controlled trial quality: uncertain

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