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https://read.qxmd.com/read/30779598/rivaroxaban-for-prevention-and-treatment-of-venous-thromboembolism
#1
Noel C Chan, Jeffrey I Weitz
Until recently, heparins and vitamin K antagonists (VKAs) were the cornerstones for prevention and treatment of venous thromboembolism (VTE). This situation changed with the introduction of the direct oral anticoagulants, which are now replacing low-molecular-weight heparin for thromboprophylaxis after elective hip or knee arthroplasty and VKAs for VTE treatment. Rivaroxaban, an oral factor Xa inhibitor, was the first direct oral anticoagulant licensed for VTE prevention and treatment. This paper provides the rationale for factor Xa as a target for anticoagulants, describes the development of rivaroxaban, reviews its pharmacological profile, discusses the clinical trials with rivaroxaban for VTE prevention and treatment and highlights areas of uncertainty...
February 19, 2019: Future Cardiology
https://read.qxmd.com/read/30772162/deep-venous-thrombosis-with-decreased-cerebral-blood-flow-to-the-thalamus-was-completely-restored-by-factor-xa-inhibitor
#2
Yu Shimizu, Katsuhiro Tsuchiya, Hironori Fujisawa
BACKGROUND: Cerebral venous thrombosis is rare and an uncommon cause of stroke and has diverse etiologies and varied clinical presentations. Here, we report 2 cases of deep cerebral venous thrombosis. CASE DESCRIPTION: A 64-year-old woman presented with cerebral venous thrombosis due to a hypercoagulable state associated with ovarian tumor. On initial fluid-attenuated inversion recovery and diffusion-weighted imaging, there was a diffuse high-intensity lesion in the bilateral thalamus...
February 13, 2019: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://read.qxmd.com/read/30771281/nox2-mediated-platelet-activation-by-glycoprotein-gp-vi-effect-of-rivaroxaban-alone-and-in-combination-with-aspirin
#3
Vittoria Cammisotto, Roberto Carnevale, Cristina Nocella, Lucia Stefanini, Simona Bartimoccia, Antonio Coluccia, Romano Silvestri, Pasquale Pignatelli, Daniele Pastori, Francesco Violi
Factor Xa (FXa) has been reported to activate platelet via interaction with glycoprotein (GP) VI but the underlying mechanism has not been fully elucidated. We investigated if Nox2-derived oxidative stress is implicated in FXa-induced platelet aggregation (PA), and the effect of a FXa inhibitor, namely rivaroxaban, with or without aspirin (ASA), on PA. We performed an in vitro study measuring convulxin-induced PA, thromboxane (Tx) B2 and isoprostanes biosynthesis, soluble Nox2-dp (sNox2-dp), a marker of Nox2 activation, soluble GPVI (sGPVI) and PLA2 activation in platelets from healthy subjects (n=5) added with and without a Nox2 inhibitor...
February 13, 2019: Biochemical Pharmacology
https://read.qxmd.com/read/30756344/potential-role-of-activated-factor-viii-fviiia-in-fviia-tissue-factor-dependent-fxa-generation-in-initiation-phase-of-blood-coagulation
#4
Shoko Furukawa, Keiji Nogami, Kenichi Ogiwara, Midori Shima
Factor VIIa/tissue factor (FVIIa/TF) initiates blood coagulation by promoting FXa generation (extrinsic-Xa). Subsequent generation of intrinsic FXa (intrinsic-Xa) amplifies thrombin formation. Previous studies suggested that FVIIa/TF activates FVIII rapidly in immediate coagulation reactions, and FVIIa/TF/FXa activates FVIII prior to thrombin-dependent feedback. We investigated FVIII/FVIIa/TF/FXa relationships in early coagulation mechanisms. Total FXa generated by FVIIa/TF and FVIIa/TF-activated FVIII (FVIIIaVIIa/TF ) was 22...
February 13, 2019: International Journal of Hematology
https://read.qxmd.com/read/30746012/novel-oral-anticoagulants-as-treatment-for-vertebral-artery-dissection-case-report
#5
Fernando Góngora-Rivera, Héctor R Martínez, Leonel Cantu-Martinez, Carlos R Camara-Lemarroy, Talía Moreno-Andrade
Background and Purpose: Cervical artery dissections, which may be traumatic or spontaneous, account for a significant proportion of strokes in the young. Antithrombotic therapy is the mainstay of treatment, but new oral anticoagulants could be an alternative treatment to the optimal strategy of anticoagulation followed by antiplatelet drugs. Summary of Case: We report the case of a 40-year-old patient with a spontaneous vertebral artery dissection who developed a cerebellar ischemic stroke, who had a favorable outcome and complete vessel recanalization after three months of treatment with the oral factor Xa inhibitor rivaroxaban...
November 2018: Journal of Vascular and Interventional Neurology
https://read.qxmd.com/read/30745002/real-world-outcomes-of-the-xarelto-post-authorization-safety-effectiveness-study-in-japanese-patients-with-atrial-fibrillation-xapass
#6
Takanori Ikeda, Satoshi Ogawa, Takanari Kitazono, Jyoji Nakagawara, Kazuo Minematsu, Susumu Miyamoto, Yuji Murakawa, Makiko Takeichi, Yohei Ohashi, Yutaka Okayama, Toshiyuki Sunaya, Satoshi Yamanaka
BACKGROUND: Although the efficacy and safety of the factor Xa inhibitor rivaroxaban for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) were shown in global and Japanese phase III clinical trials, safety and effectiveness data from unselected patients in everyday clinical practice are limited. The objective of the XAPASS (Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation) is to investigate the safety and effectiveness of rivaroxaban in Japanese real-world clinical practice...
February 7, 2019: Journal of Cardiology
https://read.qxmd.com/read/30739331/new-guidelines-from-the-thrombosis-and-haemostasis-society-of-australia-and-new-zealand-for-the-diagnosis-and-management-of-venous-thromboembolism
#7
Huyen A Tran, Harry Gibbs, Eileen Merriman, Jennifer L Curnow, Laura Young, Ashwini Bennett, Tan Chee Wee, Sanjeev D Chunilal, Chris M Ward, Ross Baker, Harshal Nandurkar
INTRODUCTION: Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is the third most common cardiovascular disease and, globally, more than an estimated 10 million people have it yearly. It is a chronic and recurrent disease. The symptoms of VTE are non-specific and the diagnosis should actively be sought once considered. The mainstay of VTE treatment is anticoagulation, with few patients requiring additional intervention. A working group of experts in the area recently completed an evidence-based guideline for the diagnosis and management of DVT and PE on behalf of the Thrombosis and Haemostasis Society of Australia and New Zealand (www...
February 10, 2019: Medical Journal of Australia
https://read.qxmd.com/read/30719950/reversal-strategies-in-patients-treated-with-direct-oral-anticoagulants
#8
Paul Gressenberger
Administration of direct oral anticoagulants (DOACs) for the treatment of venous thrombotic events (VTE) or non-valvular atrial fibrillation (AF) is now standard of care and has demonstrated clinical efficacy and safety in numerous clinical studies. Usually these substances have lower overall mortality and less risk of cerebral hemorrhage, but depending on the substance and study, they are more likely to cause gastrointestinal bleeding than vitamin K antagonists (VKA), the medication that used to be standard for VTE and AF...
February 5, 2019: VASA. Zeitschrift Für Gefässkrankheiten
https://read.qxmd.com/read/30719631/betrixaban-for-extended-venous-thromboembolism-prophylaxis-in-high-risk-hospitalized-patients-putting-the-apex-results-into-practice
#9
REVIEW
Kayla M Miller, Michael J Brenner
Acutely ill hospitalized medical patients remain at high thromboembolic risk for several weeks after discharge. Previous trials with extended-duration thromboprophylaxis using enoxaparin, apixaban, and rivaroxaban failed to achieve acceptable net clinical benefit, largely due to excess of major bleeding. Betrixaban is a novel factor Xa inhibitor with unique pharmacokinetic properties, including low renal clearance, long half-life, and low peak-to-trough ratio. The phase III APEX trial (N = 7513) compared a betrixaban 160 mg loading dose followed by 80 mg once daily for 35-42 days, with enoxaparin 40 mg once daily for 6-14 days; the betrixaban dose was reduced for renal impairment or a concomitant strong P-glycoprotein (P-gp) inhibitor...
February 5, 2019: Drugs
https://read.qxmd.com/read/30706987/routine-measurements-of-factor-viii-activity-and-inhibitor-titer-in-the-presence-of-emicizumab-utilizing-anti-idiotype-monoclonal-antibodies-reply
#10
Keiji Nogami
Emicizumab is a humanized, recombinant bispecific monoclonal antibody to factor IX/IXa and factor X/Xa that mimics the cofactor function of factor VIIIa by positioning factor IXa and factor X suitably to promote the enzymatic activity of factor IXa in the tenase complex. Emicizumab recognizes the epidermal growth factor (EGF)-like domain 1 of factor IX/IXa with one arm, and the EGF-like domain 2 of factor X/Xa with the other arm. This bispecific antibody does not induce antibody-dependent accumulation of factor IX/IXa and/or factor X/Xa in circulation due to much weaker binding than those of other therapeutic monoclonal antibodies...
February 1, 2019: Journal of Thrombosis and Haemostasis: JTH
https://read.qxmd.com/read/30702997/synergy-of-dual-pathway-inhibition-in-chronic-cardiovascular-disease
#11
Michiel Coppens, Jeffrey I Weitz, John W A Eikelboom
Although acetylsalicylic acid is of proven benefit for secondary prevention in patients with cardiovascular disease, the risk of recurrent ischemic events remains high. Intensification of antithrombotic therapy with more potent antiplatelet drugs, dual antiplatelet therapy, or vitamin K antagonists further reduces the risk of major adverse cardiovascular events compared with acetylsalicylic acid alone but increases the risk of bleeding without reducing mortality. In patients with prior coronary artery disease or peripheral arterial disease the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial revealed that compared with acetylsalicylic acid alone, dual pathway inhibition with low-dose rivaroxaban (2...
February 2019: Circulation Research
https://read.qxmd.com/read/30700390/comparison-of-pharmacologic-prophylaxis-in-prevention-of-venous-thromboembolism-following-total-knee-arthroplasty
#12
Shawn S Richardson, William W Schairer, Peter K Sculco, Mathias P Bostrom
BACKGROUND: Anticoagulants are used following total knee arthroplasty (TKA) to prevent venous thromboembolism (VTE). These drugs reduce VTE risk but may lead to bleeding-related complications. Recently, surgeons have advocated using antiplatelet agents including aspirin (ASA). However, there is no consensus regarding which medication has the optimal risk/benefit profile. The purpose of this study was to compare rates of VTE using different anticoagulants in anticoagulation-naïve patients being discharged home after TKA...
January 27, 2019: Knee
https://read.qxmd.com/read/30700116/a-randomized-double-blind-placebo-controlled-trial-on-the-efficacy-of-tranexamic-acid-combined-with-rivaroxaban-thromboprophylaxis-in-reducing-blood-loss-after-primary-cementless-total-hip-arthroplasty
#13
RANDOMIZED CONTROLLED TRIAL
A Clavé, R Gérard, J Lacroix, C Baynat, M Danguy des Déserts, F Gatineau, D Mottier
AIMS: Cementless primary total hip arthroplasty (THA) is associated with risks of bleeding and thromboembolism. Anticoagulants are effective as venous thromboprophylaxis, but with an increased risk of bleeding. Tranexamic acid (TXA) is an efficient antifibrinolytic agent, but the mode and timing of its administration remain controversial. This study aimed to determine whether two intravenous (IV) TXA regimens (a three-hour two-dose (short-TXA) and 11-hour four-dose (long-TXA)) were more effective than placebo in reducing perioperative real blood loss (RBL, between baseline and day 3 postoperatively) in patients undergoing THA who receive rivaroxaban as thromboprophylaxis...
February 2019: Bone & Joint Journal
https://read.qxmd.com/read/30698331/an-in-vitro-study-to-investigate-the-interference-of-enoxaparin-on-plasma-levels-of-direct-oral-factor-xa-inhibitors-measured-by-chromogenic-assays
#14
Michela Cini, Cristina Legnani, Sophie Testa, Armando Tripodi, Benilde Cosmi, Gualtiero Palareti
INTRODUCTION: Co-administration of enoxaparin and a direct oral factor Xa inhibitor (xabans: apixaban, edoxaban, rivaroxaban) could give rise to the problem of overlapping the anti-Xa activity when measuring direct oral anticoagulant (DOAC) levels. We aimed to evaluate in vitro the degree of the interference of increasing enoxaparin concentrations on xaban plasma levels measured by different chromogenic anti-Xa assays with drug-specific calibrators and controls. METHODS: Seven plasma samples were spiked with apixaban, edoxaban, or rivaroxaban at fixed concentration, and enoxaparin at increasing concentrations (0, 0...
January 30, 2019: International Journal of Laboratory Hematology
https://read.qxmd.com/read/30685261/factor-xa-inhibitors-and-direct-thrombin-inhibitors-versus-low-molecular-weight-heparin-for-thromboprophylaxis-after-total-hip-or-total-knee-arthroplasty-a-systematic-review-and-meta-analysis
#15
Guangwei Sun, Jingjing Wu, Qian Wang, Qiang Liang, Jian Jia, Kai Cheng, Guoliang Sun, Zili Wang
BACKGROUND: The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA). METHODS: MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017 for eligible randomized controlled studies. RESULTS: Thirty-two randomized controlled studies were included...
December 1, 2018: Journal of Arthroplasty
https://read.qxmd.com/read/30680652/rivaroxaban-with-or-without-aspirin-for-the-secondary-prevention-of-cardiovascular-disease-clinical-implications-of-the-compass-trial
#16
REVIEW
Stephen J Nicholls, Adam J Nelson
The COMPASS trial compared the impact of the selective direct factor Xa inhibitor, rivaroxaban, as monotherapy or in combination with aspirin on major adverse cardiovascular events (MACE) in patients with stable atherosclerotic disease. Patients treated with rivaroxaban 2.5 mg twice daily in combination with aspirin experienced fewer cardiovascular events but more bleeding complications than those who received aspirin monotherapy. In contrast, a higher dose of rivaroxaban (5 mg twice daily) and aspirin produced no clinical benefit and continued to be associated with greater bleeding rates than aspirin...
January 25, 2019: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://read.qxmd.com/read/30658963/management-of-direct-factor-xa-inhibitor-related-major-bleeding-with-prothrombin-complex-concentrate-a-meta-analysis
#17
REVIEW
Siavash Piran, Rasha Khatib, Sam Schulman, Ammar Majeed, Anne Holbrook, Daniel M Witt, Wojtek Wiercioch, Holger J Schünemann, Robby Nieuwlaat
A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor-related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found...
January 22, 2019: Blood Advances
https://read.qxmd.com/read/30658513/pharmacogenomics-of-novel-direct-oral-anticoagulants-newly-identified-genes-and-genetic-variants
#18
REVIEW
Sri H Kanuri, Rolf P Kreutz
Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a relatively new area of research. There is a need to understand the role of pharmacogenomics in the interpatient variability of the four most commonly prescribed DOACs, namely dabigatran, rivaroxaban, apixaban, and edoxaban...
January 17, 2019: Journal of Personalized Medicine
https://read.qxmd.com/read/30651183/four-factor-prothrombin-complex-concentrate-for-the-reversal-of-factor-xa-inhibitors-for-traumatic-intracranial-hemorrhage
#19
Daniel Dybdahl, Grant Walliser, M Chance Spalding, Michelle Pershing, Michelle Kincaid
OBJECTIVE: The objective of this study was to determine the effectiveness and safety of four-factor prothrombin complex concentrate (4F-PCC) for the reversal of factor Xa inhibitors in patients with traumatic intracranial hemorrhage (ICH). METHODS: This was a retrospective cohort study of patients taking factor Xa inhibitors with traumatic ICH between March 1, 2015 and August 31, 2017 at two trauma centers. The primary outcome was in-hospital mortality in patients who received 4F-PCC (4F-PCC group) compared to those who did not (no reversal group)...
January 9, 2019: American Journal of Emergency Medicine
https://read.qxmd.com/read/30630206/how-to-optimize-activated-partial-thromboplastin-time-aptt-testing-solutions-to-establishing-and-verifying-normal-reference-intervals-and-assessing-aptt-reagents-for-sensitivity-to-heparin-lupus-anticoagulant-and-clotting-factors
#20
Emmanuel J Favaloro, Geoffrey Kershaw, Soma Mohammed, Giuseppe Lippi
The activated partial thromboplastin time (APTT) assay is a very common coagulation test, used for several reasons. The test is conventionally used for assessing the contact factor (intrinsic) pathway of blood coagulation, and thus for screening deficiencies in this pathway, most typically factors VIII, IX, and XI. The APTT is also sensitive to contact factor deficiencies, including factor XII, prekallikrein, and high-molecular-weight kininogen. The APTT may also be elevated in a variety of conditions, including liver disease, vitamin K deficiency, and disseminated intravascular coagulation...
February 2019: Seminars in Thrombosis and Hemostasis
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