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Thrombin Hemostatic

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281. Activity of Transgene-Produced B-Domain Deleted Factor VIII in Human Plasma Following AAV5 Gene Therapy. (Abstract)

that transgene-produced FVIII-SQ accelerated early factor Xa and thrombin formation, which may explain the higher OS activity based on a kinetic bias between OS and CS assay readout times. Despite the faster onset of coagulation, global thrombin levels were unaffected. A correlation with joint bleeds suggested that both OS and CS assay remained clinically meaningful to distinguish hemophilic from non-hemophilic FVIII activity levels. During clinical development, the CS activity was chosen as a surrogate (...) endpoint to conservatively assess hemostatic efficacy and enable comparison with recombinant FVIII-SQ products. Relevant trials are registered on (NCT02576795 and NCT03370913).Copyright © 2020 American Society of Hematology.

2020 Blood

282. RGS10 and RGS18 differentially limit platelet activation, promote platelet production, and prolong platelet survival. (Abstract)

in platelets. Here, we report that mice missing both proteins show reduced platelet survival and a 40% decrease in platelet count that can be partially reversed with aspirin and a P2Y12 antagonist. Their platelets have increased basal (TREM)-like transcript-1 expression, a leftward shift in the dose/response for a thrombin receptor-activating peptide, an increased maximum response to adenosine 5'-diphosphate and TxA2, and a greatly exaggerated response to penetrating injuries in vivo. Neither (...) -/- mice. Collectively, these results show that RGS10 and RGS18 have complementary roles in platelets. Removing both at the same time discloses the extent to which this regulatory mechanism normally controls platelet reactivity in vivo, modulates the hemostatic response to injury, promotes platelet production, and prolongs platelet survival.© 2020 by The American Society of Hematology.

2020 Blood

283. In Vitro Evaluation of Pro- and Anticoagulant Drugs in Children with End-Stage Liver Disease Undergoing Liver Transplantation. (Abstract)

In Vitro Evaluation of Pro- and Anticoagulant Drugs in Children with End-Stage Liver Disease Undergoing Liver Transplantation.  Pro- and anticoagulant drugs are commonly used in pediatric liver transplantation to prevent and treat thrombotic and bleeding complications. However, the combination of baseline hemostatic changes in children with liver disease and additional changes induced by transplantation makes this very challenging. This study aimed to analyze the efficacy of clinically (...) available pro- and anticoagulant drugs in plasma from children undergoing liver transplantation. In vitro effects of pro- and anticoagulant drugs on thrombin generation capacity were tested in plasma samples of 20 children (≤ 16 years) with end-stage liver disease undergoing liver transplantation, and compared with 30 age-matched healthy controls. Addition of pooled normal plasma had no effect in patients or controls, while 4-factor prothrombin complex concentrate increased thrombin generation in both

2020 Thrombosis and haemostasis

284. A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function. (Abstract)

A Pathological Clarification of Sepsis-Associated Disseminated Intravascular Coagulation Based on Comprehensive Coagulation and Fibrinolysis Function.  The functional dynamics of coagulation and fibrinolysis in patients with disseminated intravascular coagulation (DIC) vary due to the pathology and severity of various underlying diseases. Conventional measurements of hemostasis such as thrombin-antithrombin complex, plasmin-α2-plasmin-inhibitor complex, and fibrinogen-fibrin degradation (...) products may not always reflect critical pathophysiologic mechanisms in DIC. This article aims to clarify the pathology of sepsis-associated DIC using assessment of comprehensive coagulation and fibrinolysis. Plasma samples were obtained from 57 patients with sepsis-associated DIC at the time of initial diagnosis. Hemostasis parameters were quantified by clot-fibrinolysis waveform analysis (CFWA) and thrombin/plasmin generation assays (T/P-GA). The results were expressed as ratios relative to normal

2020 Thrombosis and haemostasis

285. Emicizumab Augments Thrombus Formation in Whole Blood from Patients with Hemophilia A under High Shear Flow Conditions. (Abstract)

enhanced thrombin generation at local sites and improved defective hemostasis in whole blood from PwHAs under high shear conditions. Simple concomitant use of BPAs with emicizumab did not mediate excessive thrombus formation and remains an option for hemostatic management of emicizumab-treated PwHAs with inhibitors.Thieme. All rights reserved. (...) (aPCC) were concomitantly used with emicizumab. Although bypassing agents (BPAs) are vital in the hemostatic treatment for PwHAs with inhibitors, the mechanism of emicizumab-related TMA remains unclear. To assess the risk of excessive thrombus formation associated with BPAs and emicizumab under high shear conditions. Perfusion flow-chamber experiments under high shear conditions were performed using whole blood from PwHAs in the presence of emicizumab without or together with FVIII or BPAs ex vivo

2020 Thrombosis and haemostasis

286. Is placental blood a reliable source for the evaluation of neonatal hemostasis at birth? Full Text available with Trip Pro

Is placental blood a reliable source for the evaluation of neonatal hemostasis at birth? Phlebotomy is among the main determinants of anemia of prematurity. Blood sparing policies endorsed umbilical cord blood (here called placental) as an alternative source for laboratory testing. Little is known on the suitability of placental blood to evaluate neonatal hemostasis of newborn infants. We aimed to compare the hemostatic profile of paired placental and infant venous blood, by means (...) of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, antithrombin, protein C, thromboelastography (TEG) and thrombin generation assay (TGA).This was an observational single-center study.We collected at birth venous citrated blood from both placental and infant venous source and performed PT, APTT, fibrinogen, antithrombin, protein C, TEG (reaction time-R; kinetics-K alpha angle-α, maximum amplitude-MA and lysis at 30 minutes-LY30), and TGA (endogenous thrombin potential-ETP).We

2020 Transfusion

287. A prospective observational study of acute traumatic coagulopathy in traumatic bleeding from the battlefield. Full Text available with Trip Pro

coagulopathy. This study aimed to characterize military ATC on admission to a military hospital in Afghanistan and to explore any differences due to the mechanism of injury.Severely injured military casualties were enrolled in the study. Blood samples were taken on admission and after routine testing, waste plasma was prepared, frozen, and transported to the United Kingdom for in-depth hemostatic analysis.Seventy-seven percent of casualties had ATC defined by a PTr greater than 1.2 and 19% when defined (...) by rotational thromboelastometry (ROTEM) A5 less than 36 mm. Coagulation factor depletion correlated with degree of shock, particularly factor V (p < 0.01), factor X (p < 0.01), and fibrinogen levels (p < 0.01). Thrombin generation was well preserved. Fibrinolytic biomarkers were raised correlating with the degree of shock (p < 0.01), and 8% of casualties had hyperfibrinolysis on ROTEM analysis. Plasmin-antiplasmin complexes (p < 0.01) and d-dimer levels (p = 0.01) were higher and clot firmness lower (p

2020 Transfusion

288. Field-expedient thawing of fresh-frozen plasma. Full Text available with Trip Pro

water; affixing flameless ration heaters from meals ready-to-eat (MREs) to FFP and submerging in water; exposing FFP to electric kettle-boiled water; incubating with a sous vide immersion circulator; or using a clinical thawer (control). Hemostatic function, thrombin generation, factor activities, and essential chemistry were measured after thawing.Even at the highest temperatures, without preheated water the slow cooker doubled thawing time (62.5 min vs. control, 32.5 min; p < 0.0001

2020 Transfusion

289. Anabolic-Androgenic Steroid Abuse Impairs Fibrin Clot Lysis. (Abstract)

Anabolic-Androgenic Steroid Abuse Impairs Fibrin Clot Lysis. Abuse of anabolic-androgenic steroids (AASs) is suspected to increase the risk of cardiovascular disease (CVD) and cardiovascular mortality in otherwise healthy individuals. AAS abuse may increase the incidence of CVD by altering the hemostatic balance toward a procoagulant state. Studies on the effect of AAS abuse on the fibrinolytic system, however, have either demonstrated a profibrinolytic effect or no effect of AAS abuse (...) , but the overall effect of AAS on fibrinolysis has not been addressed so far. This cross-sectional study investigated the effect of AAS on fibrin clot lysis, fibrin structure, and the hemostatic proteins, potentially affecting these measures in current and former AAS abusers and healthy age-matched controls. The study population consisted of 37 current and 33 former AAS abusers, along with 30 healthy age-matched controls. Fibrin clot lysis, fibrin structure properties, fibrinogen, coagulation factor XIII

2020 Seminars In Thrombosis And Hemostasis

290. 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

292. 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

293. 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

294. 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

295. 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

298. 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

299. 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

300. Scientific rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic stroke

or PT >15 s Current use of direct thrombin inhibitors or direct factor Xa inhibitors with elevated sensitive laboratory tests (eg, aPTT, INR, platelet count, ECT, TT, or appropriate factor Xa activity assays) Blood glucose concentration <50 mg/dL (2.7 mmol/L) CT demonstrates multilobar infarction (hypodensity >1/3 cerebral hemisphere) Relative exclusion criteria Recent experience suggests that under some circumstances, with careful consideration and weighting of risk to benefit, patients may receive (...) clotting time; FDA, US Food and Drug Administration; INR, international normalized ratio; OAC, oral anticoagulant; PT, partial thromboplastin time; rtPA, recombinant tissue-type plasminogen activator; SAH, subarachnoid hemorrhage; and TT, thrombin time. Reprinted from Jauch et al. Copyright © 2013, American Heart Association, Inc. Some of these exclusions are much more common than others, and some are potentially treatable, modifiable, or reversible before alteplase administration. The prevalence rates

2015 American Academy of Neurology

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