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Thrombin Hemostatic

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241. Rivaroxaban

▼) From: Therapeutic area: Risk of serious haemorrhage—clarified contraindications apply to all 3 medicines. Article update September 2016 (...) thrombin, fibrin-bound thrombin and thrombin-induced platelet aggregation. Apixaban (Eliquis ▼) and rivaroxaban (Xarelto ▼) are direct, highly selective, orally active inhibitors of activated factor X (factor Xa). All 3 new oral anticoagulants are licensed for: prevention of venous thromboembolic events in adults who have had elective total hip-replacement (...) and Rivaroxaban in Balance of Anti-Fibrinolysis and Anticoagulation Following Primary Total Knee Replacement: A Pilot Study. 704-711 BACKGROUND This study (...) aimed to assess whether the efficacy of tranexamic acid (TXA) would be altered when rivaroxaban or enoxaparin was used for thromboprophylaxis in primary total knee replacement (TKR). It was hypothesized that the hemostatic effect of TXA would be better with the use of enoxaparin. MATERIAL AND METHODS A randomized clinical trial was conducted on 194

2018 Trip Latest and Greatest

242. Time out: venous thromboembolism in patients with chronic liver disease: is pharmacologic prophylaxis safe?

, and based on this concept it is common [6]. However, literature over the past few years has challenged [7,8]. PT and aPTT might not fully reflect the balance of pro-coagulants and anti-coagulants that is seen in vivo in a condition such as cirrhosis. One postulated explanation for this is that protein C activation relies partially on endothelial receptor thrombomodulin to exert its inhibition of thrombin. However, the plasma and reagents used to test the PT and aPTT do not have significant quantities (...) of thrombomodulin, thus the effect on thrombin is more greatly influenced by the pro-coagulant drive. Therefore, it is proposed that the PT can detect deficiencies in [9]. With data suggesting that patients with CLD are at increased risk for VTE, multiple studies have been performed to evaluate the safety and efficacy of different methods of VTE prophylaxis in this population. One single-center, retrospective cohort study by Barclay and colleagues reviewed medical records for 1581 patients with CLD hospitalized

2019 Clinical Correlations

243. Society of Interventional Radiology Consensus Guidelines for the Periprocedural Management of Thrombotic and Bleeding Risk in Patients Undergoing Percutaneous Image-Guided Interventions—Part I: Review of Anticoagulation Agents and Clinical Considerations Full Text available with Trip Pro

tissue factor ( TF ) exposed on damaged or altered cell surfaces. When tissue factor binds to small amounts of factor VIIa, the complex is called extrinsic tenase, as it will convert factor X to factor Xa. Factors Xa and Va on the cell surface, along with Ca +2 , form prothrombinase complex, which converts prothrombin (factor II) to thrombin (factor IIa). Thrombin has 2 actions. First, it contributes to self-regulation of the tissue factor pathway by activating tissue factor pathway inhibitor ( TFPI (...) ), which will shut down the tissue factor pathway; and second, thrombin will initiate the intrinsic pathway by activating factors XI and IX. Factor XIa will also convert factor IX to factor IXa, which, along with factor VIIIa, forms an intrinsic tenase to convert factor X to factor Xa. This is the main amplification pathway to generate thrombin. The thrombin converts fibrinogen to fibrin monomers. Factor XIIIa cross-links monomers to polymerize and stabilize the clot. Antithrombin ( AT ) inhibits

2019 Society of Interventional Radiology

246. Radiologic Management of Gastric Varices

%) and a relatively high (and sometimes catastrophic) rate of rebleeding (44%-54%) [16,17]. The actuarial 1- and 2-year rebleeding rates of GVs after banding were 63% and 72%, respectively [17]. Cyanoacrylate injection is another endoscopic option resulting in variceal “obturation.” Its use emerged in Germany in the 1980s as a hemostatic agent for gastric variceal bleeding [18]. In the past three decades, cyanoacrylate injection has been established as a primary means of achieving gastric varix obliteration (...) TIPS with a median follow-up of 33 months, Lo et al [24] reported a higher rebleeding rate from GV in the cyanoacrylate group (38%) compared to the TIPS group (11%), with no difference in survival. Additional endoscopic approaches have been reported, including thrombin injection. Intravariceal injection of thrombin has been shown to be effective in controlling active GV bleeding with a relatively good success rate of 75%-100% and a low rebleeding rate of 7%-25% [25- 28]. While cyanoacrylate

2019 American College of Radiology

247. Is there a role for DOAC level monitoring in clinical practice?

Is there a role for DOAC level monitoring in clinical practice? Is There a Role for DOAC Level Monitoring in Clinical Practice? – Clinical Correlations Search Is There a Role for DOAC Level Monitoring in Clinical Practice? April 9, 2019 11 min read By Thatcher Heumann, MD Peer Reviewed Background Direct Oral Anticoagulants (DOACs) are a class of medications consisting of the thrombin inhibitor, dabigatran (Pradaxa), and the factor Xa inhibitors, rivaroxaban (Xarelto), apixaban (Eliquis (...) to administering thrombolytics or urgent/emergent surgery); 2) a quantification assay for when a clinician is concerned for abnormal absorption/clearance/metabolism (e.g. extremes of weight, renal insufficiency, medication interaction) 14 . Choosing the Appropriate Coagulation Test(s) Routinely Used Coagulation Panel: Prothrombin Time (PT)/Partial Thromboplastin Time (aPTT)/ Thrombin Time (TT) Traditional PT/aPTT cannot be used to draw conclusions on levels of AC in patient on DOACs due to variability

2019 Clinical Correlations

248. Dental Management of Pediatric Patients Receiving Chemotherapy, Hematopoietic Cell Transplantation, and/or Radiation Therapy

support needed; — 40,000 to 75,000/mm 3 : platelet transfusions may be considered pre- and 24 hours post-operatively. Local- ized procedures to manage prolonged bleeding may include sutures, hemostatic agents, pressure packs, and/or gelatin foams; and — <40,000/mm 3 : defer care. In dental emergency cases, contact the patient’s physician to discuss supportive measures (e.g., platelet transfusions, bleeding control, hospital admission and care) before proceeding. In addition, localized procedures (e.g (...) ., microfibrillar col- lagen, topical thrombin) and additional medications as recommended by the hematologist/oncologist (e.g., aminocaproic acid, tranexamic acid) may help control bleeding. 1 • Other coagulation tests may be in order for individual patients. Dental procedures: • Ideally, all dental care should be completed before im- munosuppressive therapy is initiated. When that is not feasible, temporary restorations may be placed and non- acute dental treatment may be delayed until the patient’s

2018 American Academy of Pediatric Dentistry

249. Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab Full Text available with Trip Pro

on Emicizumab remains relatively small and the risk of thrombotic events with these agents cannot be excluded. Based on theoretical considerations, co- administration of FVIII and Emicizumab may be associated with a lower risk of thrombosis than aPCC and rFVIIa 3 but this remains to be confirmed in published clinical studies. It is plausible that the venous thrombotic events are related to in- creased thrombin generation associated with the bispecific antibody interacting with coagulation factors in aPCC. 3 (...) of rFVIIa should not exceed 90 µg/kg. Both Emicizumab and rFVIIa cause thrombin generation and rFVIIa given at doses of 45 µg/kg 4 hourly may be efficacious for some bleeds. It is acknowledged that these dosing schedules are not based on published evidence and may need to be revised as more data become available. The schedule is a pragmatic balance between risk of adverse events and the need to adequately treat bleeds. If lower doses or frequencies of rFVIIa do not result in an adequate haemostasis

2018 United Kingdom Haemophilia Centre Doctors' Organisation

250. The use of viscoelastic haemostatic assays in the management of major bleeding Full Text available with Trip Pro

the performance of coagulation factors through initial thrombin formation and the resulting onset of fibrin formation is reported as the Activated Clotting Time (ACT). The rate of fibrin formation is quantified by the slope of the signature shortly after the ACT and is reported as the Clot Rate. The tracing typically produces a peak that forms during clot retraction and is quantified as a Platelet Function result. Samples with poor clot retraction either lack this peak or have a slowly forming peak (...) between TEG5000 and TEG6s (R time, K time, alpha angle) (Gurbel et al , ) in 157 healthy volunteers and 300 cardiac patients. But, similarly to all VHA devices, theTEG6s remains sensitive to vibration (Gill, ), an important consideration for road‐ or air‐based analysis. TEG6s cartridges to detect anti‐thrombin and anti‐Xa agents are in development and a pilot study (Bliden et al , ) showed high sensitivity and specificity for direct oral anticoagulant (DOAC) therapies. Figure 4 TEG6s technology

2018 British Committee for Standards in Haematology

251. NOACs/DOACs: Management of Bleeding

bleed ? Continue anticoagulant ? Confirm the patient is receiving the appropriate drug and dose based on indication, age, weight, and creatinine clearance. ? Consider checking hemoglobin, platelet count and renal function to see if they are stable. Moderate Bleeding e.g. hemodynamically stable GI bleed, major epistaxis, hematuria ? Hold anticoagulant therapy ? Assess the patient to determine the cause of bleeding ? Apply local hemostatic measures (e.g. compression, packing) if applicable ? Obtain (...) of 6 Severe/Life-threatening bleeding e.g. intracranial hemorrhage, severe GI bleed Initial management ? Hold anticoagulant therapy ? Initiate resuscitation in a monitored setting ? Assess the patient to determine the cause of bleeding ? Apply local hemostatic measures (e.g. compression, packing, splinting) if applicable ? Consult an expert urgently (hematologist, internist, ER physician, pharmacist) for advice ? Refer for procedural/surgical intervention if appropriate ? Obtain CBC, PT/INR, PTT

2017 Thrombosis Interest Group of Canada

252. NOACs/DOACs: Comparison And Frequently-asked Questions

, during the first week after VTE. In this case, if a morning dose is missed, the morning dose should be taken as soon as possible so that 2 of the 10 mg tablets are taken that day. What if the patient needs dental work? For patients who need minor dental work such as teeth cleaning or a tooth extraction, it is probably safe to continue the DOACs around the time of the procedure; consideration can also be given to the using tranexamic acid mouthwash (a pro- hemostatic, antifibrinolytic agent) before (...) mg daily 10 mg daily 2.5 mg twice daily Not applicable Key Pharmacologic Properties Mechanism of action Direct factor IIa (thrombin) inhibitor Direct factor Xa inhibitor Direct factor Xa inhibitor Direct factor Xa inhibitor Renal clearance 80% 33% (active drug) 25% 50% Half-life: Normal to mild impairment (CrCl >50 mL/min) 7-17 hours 7-11 hours 8-12 hours 10-14 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

2017 Thrombosis Interest Group of Canada

253. Regional Anesthesia in the Patient Receiving Antithrombotic or Thrombolytic Therapy

through 1994, Vandermeulen et al reported 61 cases of spinal hematoma associated with epidural or spinal anesthesia; 60% of cases occurred in the last decade of the study period. In 42 (68%) of the 61 patients, the spinal hematomas associated with central neural blockade occurred in patients with evidence of hemostatic abnormality. Twenty-five of the patients had received intravenous (IV) or subcutaneous (SC) (unfractionated or low molecular weight) heparin, whereas an additional 5 patients were (...) to inactivate thrombin (factor IIa), factor Xa, and factor IXa. Anticoagulant activities of UFH depend on both the number of heparin molecules with the pentasaccharide chain and the size of the molecules containing the pentasaccharide sequence. Larger-molecular-weight heparins will catalyze inhibition of both factors IIa and Xa. Smaller-molecular-weight heparins will catalyze inhibition of only factor Xa. Intravenous injection results in immediate anticoagulant activity, whereas SC injection results in a 1

2018 American Society of Regional Anesthesia and Pain Medicine

254. Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications

enhancement of fibrinolysis. Aspirin, unlike non-ASA NSAIDs, decreases thrombin formation in clotting blood. Aspirin at higher doses prevents endothelial cell prostacyclin production by inhibiting COX-2. Prostacyclin inhibits platelet coagulation and stimulates vasodilation. | Phosphodiesterase Inhibitors Phosphodiesterase (PDE) inhibitors are also used as antiplatelet therapies. Platelets express 3 PDE isoenzymes: PDE-2, PDE-3, and PDE-5. Two commonly encountered PDE inhibitors are dipyridamole, which

2018 American Society of Regional Anesthesia and Pain Medicine

255. The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines - Anticoagulation During Cardiopulmonary Bypass

heparin dosing during CPB [15]. Another study found reduced platelet activation and evidence of reduced thrombin generation with heparin concentration monitoring compared with routine ACT monitoring [16]. Together, these studies suggest that whole blood heparin concen- tration monitoring results in larger doses of unfractio- nated heparin during CPB and improved hemostatic suppression compared with ACT monitoring alone. However, these results did not translate into improved clinical outcomes and have (...) the heparin dose required to achieve an adequate ACT for initiation of CPB. (Level of Evidence B) Use ofheparin concentrationmonitoring inaddition to ACT might be considered for the maintenance of CPB, as this strategy has been associated with a signi?cant reduction in thrombin generation, ?bri- nolysis, and neutrophil activation. However, its ef- fects on postoperative bleeding and blood transfusion are inconsistent. (Level of Evidence B) During CPB, routine administration of unfractio- nated heparin

2018 Society of Thoracic Surgeons

256. Antithrombotic Therapy for Atrial Fibrillation: CHEST Guideline and Expert Panel Report

Effects of Idar- ucizumab on Active Dabigatran; ROCKET AF = Rivaroxaban Once daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation; RR = risk ratio; SPAF-I = Stroke Prevention in AF; TEE = transesophageal echocardiography; TIA = transient ischemic attack; t.i.d. = ter in die (three times daily); TT = thrombin time; TTE = transthoracic echocardiography; TTR = time in therapeutic range; UFH = unfractionated heparin

2018 American College of Chest Physicians

257. Stroke Prevention in Patients With Atrial Fibrillation: A Systematic Review Update

—dabigatran 150mg and 110mg vs. warfarin 122 Table 52. Observational studies: myocardial infarction—dabigatran 150mg or 110mg vs. warfarin 123 viii Table 53. Strength of evidence—thrombin inhibitor (dabigatran) vs. warfarin 126 Table 54. Outcomes of interest within rct studies evaluating factor Xa inhibitors: apixaban, rivaroxaban, or edoxaban vs. warfarin 132 Table 55. Observational studies: stroke or systemic embolism—apixaban, rivaroxaban, or edoxaban vs. warfarin 137 Table 56. Observational studies (...) (moderate SOE) and also shows a trend toward increased ischemic stroke (low SOE) compared with warfarin alone. These findings are based on 1 good-quality observational study involving 52,180 patients • Thrombin inhibitors (dabigatran) versus warfarin: Based on 1 large good-quality RCT involving 18,113 patients and 35 observational studies involving 1,737,961 patients we found: o Dabigatran at a 150mg dose is superior to warfarin in reducing the incidence of the composite outcome of stroke (including

2018 Effective Health Care Program (AHRQ)

258. Spectrum of fresh frozen plasma and cryoprecipitate products Full Text available with Trip Pro

thromboelastometry (ROTEM ® ) and thrombin generation] (Green et al , ). However, the potential risk of bacterial contamination arising from storing cryoprecipitate at ambient temperature will need to be assessed before the shelf life of thawed cryoprecipitate can be extended beyond 4 h. Recommendations Once thawed, standard fresh frozen plasma (FFP) or methylene blue treated FFP (MBFFP) may be stored at +4 ± 2°C in an approved temperature‐controlled blood storage refrigerator before administration (...) randomised control trial (stopped early for futility) recruited non‐bleeding critically ill patients with an INR of 1·5–3·0 who were about to undergo an invasive procedure, and randomised patients to receive either FFP 12 ml/kg or no FFP (Muller & Juffermans, ). The authors reported a post hoc analysis where coagulation factors, anticoagulant levels, thrombin generation and thromboelastometry assays (ROTEM ® ) were measured before and after FFP transfusion at the protocol‐defined doses. FFP transfusion

2018 British Committee for Standards in Haematology

259. The Diagnosis and Acute Management of Childhood Stroke, Clinical Guideline

to investigate the role of circulating endothelial cells and microparticles, as markers of endothelial injury, cellular activation, and microparticle-mediated thrombin generation, in a cross-sectional convenience population of 46 children with arteriopathies (128). Circulating endothelial cells and microparticles of endothelial or platelet origin were raised in children with recurrent arterial ischaemic stroke at diagnosis, and remained high over time in a subgroup with follow up data, compared to those (...) with no recurrence and controls. Microparticle-mediated thrombin generation was enhanced in children with recurrent stroke compared to those with no recurrence, suggesting that a state of chronic endothelial activation and injury, platelet activation and increased MP- mediated thrombin generation, may be determinants of arterial ischaemic stroke recurrence (128). An analysis of the same cohort using flow cytometry, investigated the relationship between the number and function of circulating endothelial

2017 Stroke Foundation - Australia

260. CRACKCast E122 – Disorders of Hemostasis

CRACKCast E122 – Disorders of Hemostasis CRACKCast E122 - Disorders of Hemostasis - CanadiEM CRACKCast E122 – Disorders of Hemostasis In by Chris Lipp October 30, 2017 This 122nd episode of CRACKCast covers Rosen’s 9th edition, Chapter 114, Disorders of Hemostasis. These blood disorders are numerous and this episode attempts to break their classification and approach down in a systematic manner. Shownotes – Key Concepts Although hemostatic disorders are confirmed by specific patterns (...) of laboratory test results, a careful history and focused physical examination are often the key to the diagnosis of hematologic diseases. All patients with bleeding disorders of unknown cause or of a significant degree should be admitted to the hospital for further evaluation. The frequency of hemostatic disorders seen in the ED is unknown; however, they are likely to be more common than thought. Although classic diseases such as hemophilia and DIC are uncommon, the use of antiplatelet and anticoagulation

2017 CandiEM

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