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Thrombin Hemostatic

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261. A decreased and less sustained desmopressin response in hemophilia A carriers contributes to bleeding Full Text available with Trip Pro

Assessment Tool (ISTH-BAT). DDAVP (0.3 μg/kg) was administered either IV or subcutaneously (SC), and blood was drawn at baseline and 1, 2, and 4 hours postadministration. Blood was assessed for factor VIII (FVIII) level, von Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:RCo or VWF:GPIbM), thromboelastography (TEG), and thrombin generation assay (TGA) at all points, and for VWF propeptide (VWFpp):Ag ratio and ABO blood type at baseline. Carriers were older than control patients (median age (...) with those with normal bleeding scores (P = .036). Hemophilia A carriers have a lower and less sustained FVIII response to DDAVP, suggesting an impaired ability to respond to hemostatic stress, which contributes to bleeding.© 2018 by The American Society of Hematology.

2018 Blood advances

262. Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin Full Text available with Trip Pro

, we demonstrate that in APS, the hemostatic balance shifts toward a more prothrombotic phenotype due to elevated prothrombin conversion but unchanged thrombin inactivation rates. Within the group of APS patients, increased TG and prothrombin conversion are associated with a history of thrombosis.© 2018 by The American Society of Hematology. (...) Prothrombin conversion is accelerated in the antiphospholipid syndrome and insensitive to thrombomodulin Antiphospholipid syndrome (APS) is a condition in which the presence of antibodies against phospholipid-binding proteins is associated with thrombophilia and/or pregnancy morbidity. Although antiphospholipid antibodies have anticoagulant characteristics in vitro, they are associated with thromboembolic complications. Thrombin generation (TG) is a sensitive global test of coagulation

2018 Blood advances

263. Factor XIII in plasma, but not in platelets, mediates red blood cell retention in clots and venous thrombus size in mice Full Text available with Trip Pro

imposing deleterious hemostatic consequences are 2 critical unresolved questions. FXIII is present in multiple compartments, including plasma (FXIIIplasma) as a heterotetramer of A2 and B2 subunits and platelets (FXIIIplt) as an A2 homodimer. We determined the role of the FXIII compartment and level in clot contraction, composition, and size in vitro and using in vivo models of hemostasis and venous thrombosis. Reducing overall FXIII levels decreased whole blood clot weight but did not alter thrombin

2018 Blood advances

264. Prognostic value of D-dimer and markers of coagulation for stratification of abdominal aortic aneurysm growth Full Text available with Trip Pro

Prognostic value of D-dimer and markers of coagulation for stratification of abdominal aortic aneurysm growth Abdominal aortic aneurysm (AAA) is associated with high morbidity and mortality and is an established cause of unbalanced hemostasis. A number of hemostatic biomarkers have been associated with AAA; however, the utility of hemostatic biomarkers in AAA diagnosis and prognosis is unclear. The aim of the present study was to characterize the potential prognostic value of D-dimer (...) and markers of altered hemostasis in a large cohort of patients with AAAs characterized by either fast or slow aneurysm growth (frequency matched for baseline diameter) and subaneurysmal dilations. We measured plasma concentrations of thrombin-antithrombin (TAT) complex, platelet factor 4 (PF4), and D-dimer in 352 patients with either fast-growing AAAs (>2 mm/y), slow-growing AAAs (<2 mm/y), subaneurysmal aortic dilations, or nonaneurysmal aortas. Plasma D-dimer and TAT were significantly elevated in both

2018 Blood advances

265. New/Novel Oral Anticoagulants (NOACs): Management of Bleeding

effect 1 ? Not relevant ? Not relevant Thrombin time ? Normal indicates no dabigatran present ? If increased, indicates some anticoagulant effect ? Not relevant ? Not relevant Calibrated anti-Xa ? Not relevant ? 30 ng/mL = likely significant anticoagulant effect 1 ? 30 ng/mL = likely significant anticoagulant effect 1 1 There are no data to establish a hemostatic threshold below which drug levels are unlikely to affect hemostasis. These estimates are extrapolated from observations in clinical trials (...) New/Novel Oral Anticoagulants (NOACs): Management of Bleeding © 2016 Thrombosis Canada Page 1 of 1 NOVEL ORAL ANTICOAGULANTS (NOACS): MANAGEMENT OF BLEEDING OBJECTIVE: To assist clinicians in the management of bleeding in patients receiving direct oral anticoagulants (NOACs). BACKGROUND: Two oral Factor Xa inhibitors (apixaban and rivaroxaban) and an oral thrombin inhibitor (dabigatran) are approved for clinical use in Canada based on findings from large randomized trials. Like all other

2016 Thrombosis Interest Group of Canada

266. New/Novel Oral Anicoagulants (NOACs): Coagulation Tests

effect 1 ? Not relevant ? Not relevant Thrombin time ? Normal indicates no dabigatran present ? If increased, indicates some anticoagulant effect ? Not relevant ? Not relevant Calibrated anti-Xa ? Not relevant ? 30 ng/mL = likely significant anticoagulant effect 1 ? 30 ng/mL = likely significant anticoagulant effect 1 1 There are no data to establish a hemostatic threshold below which drug levels are unlikely to affect hemostasis. These estimates are extrapolated from observations in clinical trials (...) New/Novel Oral Anicoagulants (NOACs): Coagulation Tests © 2016 Thrombosis Canada Page 1 of 1 NOVEL ORAL ANTICOAGULANTS (NOACS): MANAGEMENT OF BLEEDING OBJECTIVE: To assist clinicians in the management of bleeding in patients receiving direct oral anticoagulants (NOACs). BACKGROUND: Two oral Factor Xa inhibitors (apixaban and rivaroxaban) and an oral thrombin inhibitor (dabigatran) are approved for clinical use in Canada based on findings from large randomized trials. Like all other

2016 Thrombosis Interest Group of Canada

267. New/Novel Oral Anticoagulants (NOACS): Comparison and Frequently-Asked Questions

of the procedure; consideration can also be given to the use of the pro-hemostatic tranexamic acid mouthwash before and after the procedure. Alternatively, the patient can skip one day’s dose of the NOAC before the procedure and resume the NOAC on the evening after the procedure. For the management of patients who require other procedures or surgery, see the Clinical Guide: New/Novel Oral Anticoagulants (NOACs): Peri-Operative Management. What if the patient has a prosthetic heart valve? In patients (...) of action Direct factor IIa (thrombin) inhibitor Direct factor Xa inhibitor Direct factor Xa inhibitor Renal clearance 80% 33% (active drug) 25% Half-life: Normal to mild impairment (CrCl >50 mL/min) 7-17 hours 7-11 hours 8-12 hours Moderate renal impairment (CrCl 30-49 mL/min) 17-20 hours 7-11hours 8-12 hours Severe renal impairment (CrCl 50 110 or 150 mg twice daily Consider 110 mg dose in patients at increased risk for bleeding or in the elderly (e.g. age = 80 years) Measure CrCl every 12 months 30

2015 Thrombosis Interest Group of Canada

268. Detection of A and B Subunits of Factor XIII and Detection of an Anti-Factor XIII by ELISA

precursor cells. On average, 50% of FXIII-B is found in its free form, and helps stabilize FXIII-A by preventing it from being rapidly eliminated from circulation. Plasma thrombin, with its fibrin cofactors (fibrinogen) and Ca 2+ ions, initiates the activation of FXIII during the final stage of the coagulation cascade. Thrombin cleaves the FXIII-A activation peptide and, in the presence of Ca 2+ , A and B subunits dissociate, and the FXIII-A 2 dimer transforms into an active transglutaminase, activated (...) deficiency have been reported worldwide [Wada et al., 2013]. Clinically, FXIII-B deficiency is characterized by mild bleeding caused by the presence of small quantities of plasma FXIII-A (< 10%) and normal concentrations of intracellular FXIII-A (Table 1). For this reason, the diagnosis of congenital FXIII-B deficiency may easily be missed. However, when there are other concurrent hemostatic disorders, severe or deadly hemorrhagic episodes may be observed [Schroeder and Kohler, 2013]. Treatment

2015 Canadian Agency for Drugs and Technologies in Health - Rapid Review

269. Reducing the Risk - Thrombosis and Embolism during Pregnancy and the Puerperium

be avoided antenatally and intrapartum because of the risk of anaphylactoid reaction. Oral thrombin and Xa inhibitors Non-vitamin K antagonist oral anticoagulants (NOACs) should be avoided in pregnant women. [New 2015] Use of NOACs is not currently recommended in women who are breastfeeding. [New 2015] Anti-embolism stockings The use of properly applied anti-embolism stockings (AES) of appropriate size and providing graduated compression with a calf pressure of 14–15 mmHg is recommended in pregnancy

2015 Royal College of Obstetricians and Gynaecologists

270. Evaluation of hemostasis in patients with end-stage renal disease. Full Text available with Trip Pro

PFA-ADP-test (p<0.05), while no patient on peritoneal dialysis and no HC offered this modification. Thrombin generating potential was significantly lower in patients on hemodialysis, while clot lysis time revealed a hypofibrinolytic state in patients on hemo- and peritoneal dialysis compared to HC (p<0.001). In conclusion, patients with end-stage renal disease have complex hemostatic changes with both hyper- and hypocoagulable features, which are dependent on use and type of dialysis (...) . Hypercoagulable features include elevated fibrinogen levels and a hypofibrinolytic state, whereas hypocoagulable features include decreased thrombin generating capacity and platelet dysfunction. Our results may contribute to a more rational approach to hemostatic management in these patients.

2019 PLoS ONE

271. Novel Insights and New Developments Regarding Coagulation Revealed by Studies of the Anti-Factor IXa (Activated Factor IX)/Factor X Bispecific Antibody, Emicizumab. (Abstract)

Novel Insights and New Developments Regarding Coagulation Revealed by Studies of the Anti-Factor IXa (Activated Factor IX)/Factor X Bispecific Antibody, Emicizumab. Emicizumab is a humanized anti-FIXa/FX (factor IXa/X) bispecific monoclonal antibody that mimics FVIIIa (activated factor VIII) cofactor function. The hemostatic efficacy of emicizumab has been confirmed in clinical studies of patients with hemophilia A, irrespective of the presence of FVIII inhibitors. Emicizumab differs in some (...) properties from FVIIIa molecule. Emicizumab requires no activation by thrombin and is not inactivated by activated protein C, but emicizumab-mediated coagulation is regulatable and maintains hemostasis. A small amount of FIXa (activated factor IX) is required to initiate emicizumab-mediated hemostasis, whereas tissue factor/FVIIa (activated factor VII)-mediated FXa (activated factor X) and thrombin activation initiates FVIIIa-mediated hemostasis. Fibrin formation, followed by fibrinolysis, appears

2020 Thrombosis and Vascular Biology

273. A local and global sensitivity analysis of a mathematical model of coagulation and platelet deposition under flow. Full Text available with Trip Pro

A local and global sensitivity analysis of a mathematical model of coagulation and platelet deposition under flow. The hemostatic response involves blood coagulation and platelet aggregation to stop blood loss from an injured blood vessel. The complexity of these processes make it difficult to intuit the overall hemostatic response without quantitative methods. Mathematical models aim to address this challenge but are often accompanied by numerous parameters choices and thus need to be analyzed (...) for sensitivity to such choices. Here we use local and global sensitivity analyses to study a model of coagulation and platelet deposition under flow. To relate with clinical assays, we measured the sensitivity of three specific thrombin metrics: lag time, maximum relative rate of generation, and final concentration after 20 minutes. In addition, we varied parameters of three different classes: plasma protein levels, kinetic rate constants, and platelet characteristics. In terms of an overall ranking

2018 PLoS ONE

274. Thrombodynamics-A new global hemostasis assay for heparin monitoring in patients under the anticoagulant treatment. Full Text available with Trip Pro

tests available to date.A total of 296 patients with high risk of venous thromboembolism (deep vein thrombosis (DVT), early postoperative period, hemoblastosis) were enrolled in the study. We used a case-crossover design to evaluate the sensitivity of new thrombodynamics assay (TD) to the hemostatic state before and after unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) therapy/prophylaxis and to compare it with the activated partial thromboplastin time (APTT), anti-Xa activity (...) test, thrombin generation test (TGT) and thromboelastography (TEG). A receiver operating characteristic (ROC) curve analysis was used to evaluate changes before and after heparin prophylaxis and therapy. Blood was sampled before heparin injection, at the time of maximal blood heparin concentration and before the next injection.Hypercoagulation before the start of heparin treatment was detected by TD, TGT and TEG but not by APTT. The area under the ROC curve (AUC) was maximal for TD and anti-Xa

2018 PLoS ONE

275. Management of antithrombotic agents for patients undergoing GI endoscopy

, Princeton, NJ, USA], edoxaban [Savaysa, Daiichi Sankyo Co, LTD, Tokyo, Japan]), and direct thrombin inhibitors (eg, dabigatran [Pradaxa, Boehringer Ingelheim Pharmaceu- ticals Inc, Ridge?eld, Conn, USA], hirudins, argatraban [Acova, Abbott Laboratories, North Chicago, Ill, USA]). APAs decrease platelet aggregation, thus preventing thrombus formation. APAs include the thienopyridines (eg, clopidogrel, [Plavix, Bristol-Myers Squibb/Sano? Pharmaceu- ticals Partnership, Bridgewater, NJ, USA], prasugrel [Ef (...) Charcoal (if last intake within 2-3 hours); nonactivated PCC or activated PCC Direct thrombin inhibitor, oral: dabigatran (Pradaxa) IV: Desirudin (Iprivask, Aventis Pharmaceuticals Inc., Bridgewater, NJ, USA) See Table 9 Hold Charcoal (if last intake within 2-3 hours); nonactivated PCC or activated PCC; HD NSAIDs, Nonsteroidal anti-inflammatory drugs; NA, not applicable; HD, hemodialysis; PCC, prothrombin complex concentrate; rVIIa, recombinant factor VIIa. *Caution: Can cause severe hypotension

2016 American Society for Gastrointestinal Endoscopy

276. Rixubis - nonacog gamma

factor and it is synthesised in the liver. Factor IX is activated by factor XIa in the intrinsic coagulation pathway and by factor VII/tissue factor complex in the extrinsic pathway. Activated factor IX, in combination with activated factor VIII, activates factor X. Activated factor X converts prothrombin into thrombin. Thrombin then converts fibrinogen into fibrin and a clot is formed. The Applicant applied for the following indication which was finally approved: Rixubis is indicated (...) such as the thrombin generation assay, as well as the efficiency of activation by FXIa and FVIIa in the presence of tissue factor and the capacity to bind to phospholipid vesicles sufficiently support primary PD of nonacog gamma as discussed under Quality aspects Secondary pharmacodynamic studies Secondary pharmacodynamic studies have not been submitted. Safety pharmacology programme Three in vivo safety pharmacology studies were conducted in rabbits and monkeys to assess the thrombogenic potential of nonacog

2014 European Medicines Agency - EPARs

279. Practice Guidelines for Perioperative Blood Management

acid), (3) topical hemostatics ( i.e. , fibrin glue, thrombin gel), (4) PCCs, (5) coagulation factor concentrates (recombinant factor VIIa), and (6) treatments for hypofibrinogenemia (cryoprecipitate, fibrinogen concentrate). Desmopressin: Literature Findings: Meta-analysis of placebo-controlled RCTs indicate that desmopressin is effective in reducing the volume of postoperative blood loss (Category A1-B evidence). Survey Findings: Both the consultants and ASA members agree that, in patients (...) : The consultants and ASA members both agree that, in patients with excessive bleeding, consider the use of antifibrinolytics ( i.e. , ε-aminocaproic acid, tranexamic acid), if not already being used. Topical Hemostatics: Literature Findings: Meta-analysis of RCTs indicates that fibrin glue is effective in reducing the volume of perioperative blood loss and the number of patients transfused when compared with no fibrin glue (Category A1-B evidence ). RCTs indicate that thrombin gel is effective in reducing

2015 American Society of Anesthesiologists

280. Guidelines for the management of spontaneous intracerebral hemorrhage Full Text available with Trip Pro

). (Unchanged from the previous guideline) Medical Treatment for ICH Hemostasis and Coagulopathy, Antiplatelets, and Deep Vein Thrombosis Prophylaxis Underlying hemostatic abnormalities can contribute to ICH. Patients at risk include those taking oral anticoagulant drugs (OACs), antiplatelet agents, those with acquired or congenital coagulation factor deficiencies, and those with inherited or acquired qualitative or quantitative platelet abnormalities. Patients taking OACs constitute 12% to 20% of patients (...) to <1.5. rFVIIa, licensed to treat hemophilia patients with high titer inhibitors or congenital factor VII deficiency, has garnered attention as a potential treatment for spontaneous and OAC-associated ICH. Although rFVIIa can rapidly normalize INR in the setting of VKA-associated ICH, it does not replenish all of the vitamin K–dependent factors and may not restore thrombin generation as effectively as PCCs. Thus, rFVIIa is not currently recommended for routine use in warfarin reversal. New

2015 American Academy of Neurology

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