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Factor Xa inhibitors

Cynthia A Kahlenberg, Shawn S Richardson, William W Schairer, Peter K Sculco
BACKGROUND: The aim of this study was to perform a population-level analysis on the effect of different types of anticoagulation on postoperative stiffness after total knee replacement, requiring manipulation under anesthesia. We hypothesized that patients receiving warfarin would have a higher rate of manipulation under anesthesia compared with patients receiving low-molecular-weight heparin. We also hypothesized that aspirin, direct factor Xa inhibitors, and fondaparinux would have no effect on the rate of manipulation under anesthesia...
August 15, 2018: Journal of Bone and Joint Surgery. American Volume
Uwe Zeymer, Benedikt Schrage, Dirk Westermann
The optimal anti-thrombotic therapy for secondary prevention after an acute coronary syndrome is still a matter of debate. While current guidelines recommend dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months especially in patients with stent implantation, the value of prolonged anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose direct factor Xa inhibition with rivaroxaban compared with placebo reduced the combined primary endpoint of cardiovascular mortality, myocardial infraction and stroke with an increase in major bleeding complications...
August 13, 2018: Thrombosis and Haemostasis
Benjamin F Tillman, Andras Gruber, Owen J T McCarty, David Gailani
Direct oral anticoagulants (DOACs) are small molecule inhibitors of the coagulation proteases thrombin and factor Xa that demonstrate comparable efficacy to warfarin for several common indications, while causing less serious bleeding. However, because their targets are required for the normal host-response to bleeding (hemostasis), DOACs are associated with therapy-induced bleeding that limits their use in certain patient populations and clinical situations. The plasma contact factors (factor XII, factor XI, and prekallikrein) initiate blood coagulation in the activated partial thromboplastin time assay...
April 12, 2018: Blood Reviews
Jiali Xing, Xiangbao Yin, Desheng Chen
BACKGROUND: Although low-molecular-weight heparin (LMWH) is recommended as the first-line treatment in patients with active cancer and venous thromboembolism (VTE), many patients are more willing to choose oral anticoagulants. We collected currently available data to evaluate the efficacy and safety of the oral direct factor Xa inhibitor rivaroxaban compared with enoxaparin in patients with cancer and VTE. METHODS: We retrieved electric databases, including Medline/PubMed and EMBASE, from inception through January, 2018...
August 2018: Medicine (Baltimore)
Katie Lee, Samantha Cham, Sum Lam
Venous thromboembolism (VTE) is a common and preventable cause of morbidity and mortality in hospitalized patients. Low molecular weight heparin, low dose unfractionated heparin, fondaparinux and warfarin have been the mainstay options for the prevention and treatment of VTE before the emergence of non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban and edoxaban. Despite the advantages of NOACs in improving patient adherence, none of them are approved for the prevention of VTE in acutely ill medical patients at high risk of thromboembolism...
July 31, 2018: Cardiology in Review
Hideki Imano, Ryuji Kato, Shota Tanikawa, Fumi Yoshimura, Atsuo Nomura, Yoshio Ijiri, Takehiro Yamaguchi, Yasukatsu Izumi, Minoru Yoshiyama, Tetsuya Hayashi
Patients with obstructive sleep apnea (OSA) have a high prevalence of atrial fibrillation (AF). Rivaroxaban, a coagulation factor Xa inhibitor, has recently been reported to show pleiotropic effects. This study investigated the influence of rivaroxaban on cardiac remodeling caused by intermittent hypoxia (IH). Male C57BL/6J mice were exposed to IH (repeated cycles of 5% oxygen for 1.5 min followed by 21% oxygen for 5 min) for 28 days with/without rivaroxaban (12 mg/kg/day) or FSLLRY, a protease-activated receptor (PAR)-2 antagonist (10 μg/kg/day)...
July 18, 2018: Journal of Pharmacological Sciences
Kelly C Rogers, Shannon W Finks
The use of direct oral anticoagulants over traditional warfarin has increased in the United States over the past 10 years due to advantages such as ease of use, predictable pharmacokinetic response, and safety. In 2015, the FDA approved idarucizumab (Praxbind® ) for the reversal of the direct thrombin inhibitor, dabigatran but no reversal agent was available for oral Factor Xa (FXa) inhibitors until recently. Andexanet alfa was approved in May 2018, under the brand name Andexxa® , for the reversal of two of the FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs...
July 24, 2018: American Journal of Medicine
Joseph R Shaw, Deborah M Siegal
<AbstractText>The direct oral anticoagulants (DOACs) are used for stroke prevention in atrial fibrillation (SPAF) and the prevention and treatment of venous thromboembolic disease (VTE). Although DOAC-associated bleeding events are less frequent as compared to vitamin K antagonists, there is significant concern surrounding physicians' ability to evaluate and manage DOAC-associated bleeding when it does occur. Idarucizumab is a specific reversal agent for dabigatran and is the agent of choice for dabigatran reversal in the setting of major bleeding or urgent surgery/procedures...
April 2018: Research and practice in thrombosis and haemostasis
Ramin Artang, Maren Anderson, Paul Riley, Jorn D Nielsen
<AbstractText Label="Background" NlmCategory="UNASSIGNED">There are clinical situations where monitoring direct oral anticoagulants (DOACs) may be useful. The clinical application of thrombin generation assay (TGA) in monitoring the effect of DOACs has not been well established. An ex vivo study was performed to systematically evaluate the anticoagulant effect of dabigatran, rivaroxaban and apixaban on each individual TGA parameter through serial measurements over time to assess suitability of these parameters for monitoring the anticoagulant effect of DOACs...
October 2017: Research and Practice in Thrombosis and Haemostasis
Paolo Gelosa, Laura Castiglioni, Marco Tenconi, Ludovico Baldessin, Giorgio Racagni, Alberto Corsini, Stefano Bellosta
The use of warfarin, the most commonly prescribed oral anticoagulant, is being questioned by clinicians worldwide due to warfarin several limitations (a limited therapeutic window and significant variability in dose-response among individuals, in addition to a potential for drug-drug interactions). Therefore, the need for non-vitamin K antagonist oral anticoagulants (NOACs) with a rapid onset of antithrombotic effects and a predictable pharmacokinetic (PK) and pharmacodynamic (PD) profile led to the approval of five new drugs: the direct factor Xa (F-Xa) inhibitors rivaroxaban, apixaban, edoxaban and betrixaban (newly approved by FDA) and the direct thrombin (factor-IIa) inhibitor dabigatran etexilate...
July 21, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Thomas A Zelniker, Christian T Ruff, Stephen D Wiviott, Jean-Jacques Blanc, Riccardo Cappato, Francesco Nordio, Michele F Mercuri, Hans Lanz, Elliott M Antman, Eugene Braunwald, Robert P Giugliano
BACKGROUND: The relative efficacy and safety profile of the oral Factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation and established coronary artery disease (CAD) has not been analyzed. MATERIALS AND METHODS: In the ENGAGE AF-TIMI 48 trial, two edoxaban regimens were compared with warfarin in 21,105 patients with atrial fibrillation and CHADS2 ⩾2. We analyzed the primary trial endpoints (efficacy: stroke or systemic embolic event, safety: International Society on Thrombosis and Haemostasis major bleeding) in patients with versus without CAD, and used interaction testing to assess for treatment effect modification...
July 24, 2018: European Heart Journal. Acute Cardiovascular Care
Hartmuth Nowak, Matthias Unterberg
In most patients, oral anticoagulation is performed with vitamin K antagonists (VKA) or non-vitamin K antagonist oral anticoagulants (NOAC). Because of a long half-life, VKA are dosed by measuring INR. In standard cases coagulation tests for NOAC are not necessary; application is performed in a fixed dose. Special coagulation tests like anti-Xa activity (for factor Xa inhibitors: apixaban, edoxaban, rivaroxaban) and diluted thrombin time (for dabigatran) are available. At this time, no cut-off values are validated which show a higher risk of intra- and postoperative bleeding...
July 2018: Anästhesiologie, Intensivmedizin, Notfallmedizin, Schmerztherapie: AINS
Jenan Awesat, Iftach Sagy, Yosef S Haviv, Anat Rabinovich, Alan Jotkowitz, Elena Shleyfer, Leonid Barski
BACKGROUND: Anticoagulant induced renal injury has been previously described with Warfarin treatment. In the last decade direct oral anticoagulants (DOAC) were introduced. They include direct inhibitors of factor Xa (Rivaroxaban, Apixaban, Edoxaban) and a thrombin inhibitor (Dabigatran). There are isolated reports describing acute kidney injury (AKI) due to the use of DOACs. CASE REPORT: We report a clinical case of an 80-year-old patient recently started on Dabigatran for new onset atrial fibrillation...
July 19, 2018: Thrombosis Research
Yuya Horinouchi, Yasumasa Ikeda, Keijo Fukushima, Masaki Imanishi, Hirofumi Hamano, Yuki Izawa-Ishizawa, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Hiromichi Fujino, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Renal tubulointerstitial injury, an inflammation-associated condition, is a major cause of chronic kidney disease (CKD). Levels of activated factor X (FXa), a blood coagulation factor, are increased in various inflammatory diseases. Therefore, we investigated the protective effects of an FXa inhibitor against renal tubulointerstitial injury using unilateral ureteral obstruction (UUO) mice (a renal tubulointerstitial fibrosis model) and the Food and Drug Administration Adverse Events Reporting System (FAERS) database...
July 18, 2018: Scientific Reports
Chien-Jung Chang, Chen-Chuan Cheng, Yao-Chang Chen, Satoshi Higa, Jen-Hung Huang, Shih-Ann Chen, Yi-Jen Chen
Factor Xa inhibitors reduce stroke in patients with atrial fibrillation. Pulmonary veins (PVs) and the sinoatrial node (SAN) are crucial for genesis of atrial fibrillation. However, the electrophysiological effects of factor Xa inhibitors (edoxaban and rivaroxaban) on PVs and the SAN remain unclear. Conventional microelectrodes were used to record the action potential in isolated rabbit PVs and SAN preparations before and after administration of edoxaban (0.1, 0.3, and 1 μM) or rivaroxaban (0.01, 0.03, 0...
August 15, 2018: European Journal of Pharmacology
Cheng-Ta Wu, Bradley Chen, Jun-Wen Wang, Shih-Hsiang Yen, Chung-Cheng Huang
BACKGROUND: Venous thromboembolism (VTE) is a serious complication following total joint replacement. The use of rivaroxaban, a highly selective and direct factor Xa inhibitor, has been used widely as a safe and efficacious way to prevent VTE after total joint replacements. However, little is known about the diagnostic efficacy of plasma D-dimer test on deep vein thrombosis (DVT) in patients using rivaroxaban for thromboprophylaxis. The study is aimed to investigate the trend and the diagnostic efficacy of D-dimer test on DVT in patients with primary total knee arthroplasty (TKA) using rivaroxaban for thromboprophylaxis...
July 11, 2018: Journal of Orthopaedic Surgery and Research
Daishi Nonaka, Hiroyuki Takase, Masashi Machii, Kazuto Ohno
RATIONALE: Inferior vena cava (IVC) thrombosis is an under-recognized entity that is associated with a mortality rate approaching twice that of lower extremity deep venous thrombosis (DVT). Thrombolytic therapy not only results in greater lysis, but also results in higher complication rates than anticoagulation alone. Catheter-directed thrombolysis (CDT), which is effective in accomplishing local resolution whilst reducing bleeding complications, has been established as an alternative treatment for patients with extensive DVT...
July 2018: Medicine (Baltimore)
Jan Beyer-Westendorf, Peter Verhamme, Rupert Bauersachs
Venous thromboembolism (VTE) is a common, potentially preventable cause of morbidity and mortality among acute medically ill patients. More than half of VTE events in this population occur after hospital discharge. Thus, providing extended-duration VTE prophylaxis from in-hospital through the post-discharge continuum may improve the quality of care in patients at risk of VTE. Betrixaban is a new oral, once-daily factor Xa inhibitor approved by the United States (US) Food and Drug Administration (FDA) for extended-duration prophylaxis of VTE in acute medically ill patients...
May 2018: European Heart Journal Supplements: Journal of the European Society of Cardiology
Dimitrios Farmakis, Periklis Davlouros, Gregory Giamouzis, George Giannakoulas, Athanasios Pipilis, Georgios Tsivgoulis, John Parissis
Direct or new oral anticoagulants (NOACs), including the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have recently revolutionized the field of antithrombotic therapy for stroke and systemic embolism prevention in nonvalvular atrial fibrillation (NVAF). Randomized controlled trials have shown that these agents have at least comparable efficacy with vitamin K antagonists along with superior safety, at least in what concerns intracranial hemorrhage...
2018: Cardiology
Menno V Huisman, Melanie Ferrreira, Martin Feuring, Mandy Fraessdorf, Frederikus A Klok
INTRODUCTION: While Direct Oral Anticoagulants (DOACs) are associated with a better safety profile than warfarin in patients with acute venous thromboembolism (VTE), direct factor Xa-inhibitors involve a higher risk of abnormal uterine bleeding (AUB). We aimed to determine the risk of AUB during anticoagulation with dabigatran compared to warfarin. METHODS: Post-hoc analysis of the pooled RE-COVER studies and the RE-MEDY trial. Incidences of AUB, based on a defined preferred terms search in adverse events, in female patients aged 18-50 years treated with dabigatran were compared with those treated with warfarin...
July 5, 2018: Journal of Thrombosis and Haemostasis: JTH
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