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Factor Xa inhibitors

Samer Al Said, Christoph Bode, Daniel Duerschmied
The prevention of atherothrombotic events is an essential therapeutic goal in the treatment of patients with arteriosclerotic diseases. After plaque rupture, a rapidly growing thrombus can lead to acute vascular occlusion and thus heart attack, stroke or limb ischaemia. The acute therapy combines anticoagulation and platelet inhibition. However, the only available therapy so far in the primary and secondary prevention of stable patients is the platelet inhibitors aspirin and clopidogrel. Despite the use of antiplatelet therapies, including aspirin and P2Y12 -receptor antagonists, some patients with artery disease continue to experience recurrent cardiovascular ischaemic events due to excessive thrombin generation beyond the acute period...
October 17, 2018: Hämostaseologie
Kang-Ling Wang, Nick van Es, Chris Cameron, Lana A Castellucci, Harry R Büller, Marc Carrier
OBJECTIVE: To evaluate efficacy and safety of oral anticoagulant regimens and aspirin for extended venous thromboembolism (VTE) treatment. METHODS: We searched MEDLINE, Embase, CENTRAL and conference proceedings for randomised controlled trials studying vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or aspirin for secondary prevention of VTE beyond 3 months. ORs (95% credible intervals) between treatments were estimated using random-effects Bayesian network meta-analysis...
October 16, 2018: Heart: Official Journal of the British Cardiac Society
Eran Glikson, Uri Chavkin, Ory Madgar, Doron Sagiv, Gabriel Nakache, Arkadi Yakirevitch, Michael Wolf, Eran E Alon
OBJECTIVES/HYPOTHESIS: To describe the characteristics and severity of epistaxis in patients taking factor Xa inhibitors novel anticoagulants. STUDY DESIGN: Retrospective cohort study. METHODS: A study of adult patients hospitalized due to spontaneous epistaxis under the treatment of warfarin, rivaroxaban, or apixaban between the years 2011 and 2017 was performed. A control group of patients under antiplatelet therapy (acetylsalicylic acid, clopidogrel) was included...
October 16, 2018: Laryngoscope
Beverley J Hunt, Matthew D Neal, Jakob Stensballe
Andexanet alfa, a reversing agent for anticoagulants which inhibit factor Xa, has recently been licensed in the USA. We discuss the impact of this on current practice and review in detail the problems of a neglected and growing clinical area, that of reversing the anticoagulation effect of factor Xa inhibitors in bleeding trauma patients. We identify areas of practice that need research so that care of bleeding trauma patients receiving direct factor Xa inhibitors can be improved.
October 11, 2018: Blood
Dawn Meyer, Frank Chu, Katrina Derry, Lovella Hailey
Intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke (AIS) is contraindicated in patient taking either Factor Xa inhibitors or direct thrombin inhibitors. Idarucizumab completely reverses the biologic effect of dabigatran within minutes. Intravenous rt-PA treatment results in a significant benefit in functional outcome when administered 3-4.5 h after stroke onset or last seen normal time. There is little reported data and no large-scale studies of the reversal of dabigatran with Idarucizumab for the purpose of treating AIS with IV rt-PA...
October 8, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
Claire Pailleret, Georges Jourdi, Virginie Siguret, Isabelle Gouin-Thibault, Sophie Gandrille, Alain Stepanian, Emmanuel Curis, Jean-Louis Golmard, Pascale Gaussem, Bernard Le Bonniec, Charles M Samama
BACKGROUND: Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors...
October 10, 2018: European Journal of Anaesthesiology
Pratima Chowdary
Novel approaches to the treatment of haemophilia are needed due to the limitations of the current standard of care, factor replacement therapy. Aspirations include lessening the treatment burden and effectively preventing joint damage. Treating haemophilia by restoring thrombin generation may be an effective approach. A promising target for restoring thrombin generation is tissue factor pathway inhibitor (TFPI), a multivalent Kunitz-type serine protease inhibitor that regulates tissue factor-induced coagulation via factor Xa-dependent feedback inhibition of the tissue factor-factor VIIa complex...
October 9, 2018: International Journal of Hematology
Xiaomiao Qiu, Junjun Zhou, Weiting Wang, Zhuanyou Zhao, Lida Tang, Shuangyong Sun
In recent years, oral factor Xa inhibitors have become a research focus as anticoagulant drugs. Zifaxaban is the first oral FXa inhibitor to enter clinical trials in China. The aim of this study was to determine the inhibitory effect of zifaxaban on thrombosisthrough a model ofinferior vena cava (IVC) thrombosis in rabbits. IVC thrombosis model was established by electrical injury and stenosis, and zifaxaban was administered (p.o.) for 5 consecutive days, then coagulation indicators and bleeding were observed...
October 8, 2018: Journal of Thrombosis and Thrombolysis
Andrea Cervi, Mark Crowther
While associated life-threatening and fatal bleeding events are less frequent with the direct factor Xa inhibitors compared to vitamin K antagonists, significant concern surrounding management of major bleeds and urgent periprocedural interruption of these agents exists among clinicians. Andexanet alfa is a recombinant human factor Xa decoy protein developed in response to this clinical gap in the care of patients receiving anticoagulation with factor Xa inhibitors. Areas covered: This paper reviews results from preclinical and healthy-volunteer studies demonstrating the ability of andexanet to rapidly and reliably normalize coagulation indices in patients treated with both direct and indirect factor Xa inhibitors...
October 9, 2018: Expert Review of Hematology
Tarek Nafee, C Michael Gibson, Megan K Yee, Fahad Alkhalfan, Gerald Chi, Ryan Travis, Mahshid Mir, Arzu Kalayci, Mehrian Jafarizade, Aditya Ganti, Syed Hassan Kazmi, Eiman Ghaffarpasand, Anmol Pitliya, Sudarshana Datta, Sadaf Sharfaei, Mahda Alihashemi, Ahmed Elsaiey, Iqra Qamar, Mohamadmostafa Jahansouz, Usama Talib, Farima Kahe, Shaghayegh Habibi, Mohammed Abdelwahed, Feham Tariq, Manpreet Kaur, Ahmed Younes, Sargun S Walia, Amandeep Singh, Syed Muhammad Dildar, M Khurram Afzal, Mathieu Kerneis
Compared to other direct oral anticoagulants, betrixaban has a longer half-life, smaller peak-trough variance, minimal renal clearance, and minimal hepatic Cytochrome P (CYP) metabolism. The Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial evaluated the efficacy and safety of extended duration betrixaban compared to standard duration enoxaparin in acutely ill hospitalized patients. Areas covered: This article describes the role of betrixaban in the prevention of venous thromboembolism (VTE) in acutely ill medical patients...
October 8, 2018: Expert Review of Cardiovascular Therapy
Jennifer Lagoutte-Renosi, Julien Le Poupon, Alexandra Girard, Damien Montange, Siamak Davani
Direct Oral Anticoagulants (DOACs) available for the treatment and prevention of thromboembolic diseases include dabigatran, a direct thrombin (IIa) inhibitor, and apixaban, edoxaban and rivaroxaban, which are direct inhibitors of Stuart factor (Xa). DOACs have a different pharmacokinetic and pharmacodynamics profiles, with less probable drug-drug interactions than vitamin K antagonists. They do not require systematic therapeutic monitoring except in specific clinical situations such as emergency procedures or drug non-compliance...
September 27, 2018: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Junji Yamaguchi, Nobuhiro Hara, Tetsuo Yamaguchi, Yasutoshi Nagata, Toshihiro Nozato, Takamichi Miyamoto
We report a case of acute massive pulmonary embolism in a patient with antithrombin III deficiency. The patient was treated with rivaroxaban. The patient responded well to the therapy, and contrast-enhanced computed tomography showed nearly complete disappearance of the pulmonary embolism. Patients with low antithrombin III activity may have resistance to heparin therapy, leading to insufficient anticoagulation during the acute phase of thromboembolism. This case suggests that direct oral anticoagulants, such as rivaroxaban, may be effective first-line agents for treating venous thromboembolism in patients with antithrombin III deficiency...
November 2017: Journal of Cardiology Cases
Andreas Hillarp, Karin Strandberg, Fariba Baghaei, Inger Fagerberg Blixter, Kerstin M Gustafsson, Tomas L Lindahl
Edoxaban is an oral direct factor Xa inhibitor for prophylaxis and treatment of thromboembolic disorders. The effects on common coagulation assays are clinically valuable information and in certain clinical situations a quick assessment of the anticoagulant is wanted. Our aim was to investigate the effect of edoxaban on routine coagulation methods and evaluate anti-Xa assays, commonly used for other direct factor Xa inhibitors, for estimation of the drug concentration. Edoxaban was spiked to plasma samples from healthy subjects in the concentration range 0-742 µg/L and analyzed using different reagents for activated partial thromboplastin time (APTT) and prothrombin time (PT)...
October 2, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
Scott E Kasner, Balakumar Swaminathan, Pablo Lavados, Mukul Sharma, Keith Muir, Roland Veltkamp, Sebastian F Ameriso, Matthias Endres, Helmi Lutsep, Steven R Messé, J David Spence, Krassen Nedeltechev, Kanjana Perera, Gustavo Santo, Veronica Olavarria, Arne Lindgren, Shrikant Bangdiwala, Ashkan Shoamanesh, Scott D Berkowitz, Hardi Mundl, Stuart J Connolly, Robert G Hart
BACKGROUND: Patent foramen ovale (PFO) is a contributor to embolic stroke of undetermined source (ESUS). Subgroup analyses from previous studies suggest that anticoagulation could reduce recurrent stroke compared with antiplatelet therapy. We hypothesised that anticoagulant treatment with rivaroxaban, an oral factor Xa inhibitor, would reduce the risk of recurrent ischaemic stroke compared with aspirin among patients with PFO enrolled in the NAVIGATE ESUS trial. METHODS: NAVIGATE ESUS was a double-blinded, randomised, phase 3 trial done at 459 centres in 31 countries that assessed the efficacy and safety of rivaroxaban versus aspirin for secondary stroke prevention in patients with ESUS...
September 28, 2018: Lancet Neurology
Arthur Bracey, Wassim Shatila, James Wilson
In optimizing anticoagulation therapy, it is essential to balance treatment efficacy with the major adverse effect of anticoagulant treatment, bleeding risk. This narrative review examines the efficacy and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban compared with standard anticoagulation or placebo. NOAC therapies provide equivalent to superior protection versus standard therapy, with similar or superior safety, and potential benefits in convenience...
September 30, 2018: Therapeutic Advances in Cardiovascular Disease
Juraj Sokol, Frantisek Nehaj, Jela Ivankova, Michal Mokan
No abstract text is available yet for this article.
September 24, 2018: American Journal of Therapeutics
Teresa A Allison, Pei Jen Lin, Jennifer A Gass, Kenneth Chong, Samuel J Prater, Miguel A Escobar, Heather D Hartman
OBJECTIVE: This study investigated the percentage of patients who achieved hemostasis with 4-factor prothrombin complex concentrate (4-factor PCC) 35 U/kg. The primary end point was to determine the effect of 4-factor PCC 35 U/kg on bleeding progression, assessed using computed tomography. METHODS: This was a retrospective, observational, single-center study conducted in patients with a major bleed admitted to a level 1 trauma center from May 1, 2013, to June 15, 2015, who received 4-factor PCC 35 U/kg for reversal of a direct factor Xa inhibitor taken prior to admission...
September 24, 2018: Journal of Intensive Care Medicine
Jen-Hung Huang, Yung-Kuo Lin, Cheng-Chih Chung, Ming-Hsiung Hsieh, Wan-Chun Chiu, Yi-Jen Chen
Rivaroxaban, a direct factor Xa inhibitor, is widely used to reduce the chance of stroke in patients with atrial fibrillation (AF). It is not clear why the prothrombin time (PT) of the international normalized ratio (INR) fails to correlate with treatment using rivaroxaban in patients with AF. In this study, patient characteristics, the rivaroxaban dosage, AF type, drug history, biochemical properties, and hematological profiles were assessed in patients treated with rivaroxaban. In 69 patients with AF receiving rivaroxaban, 27 (39...
September 24, 2018: Clinical and Applied Thrombosis/hemostasis
Monica Sacco, Stefano Lancellotti, Federico Berruti, Alessandro Arcovito, Andrea Bellelli, Tiziana Ricciardelli, Ida Autiero, Luigi Cavallo, Romina Oliva, Raimondo De Cristofaro
The direct oral anticoagulant apixaban (APX), a strong factor Xa inhibitor, binds also to plasma proteins, especially albumin, and minimally to α1 -acid glycoprotein. Although APX can cross the red cell membrane, due to its chemical structure, and could bind to haemoglobin (Hb), no investigation was performed on this possible phenomenon that could affect the APX plasma concentration and thus its pharmacokinetics and pharmacodynamics. We addressed this issue by (1) measuring the levels of APX and haematological/biochemical parameters in 90 patients on APX therapy; (2) assessing the effect of APX on oxygen saturation curves of Hb; (3) testing the direct APX binding to Hb by fluorescence spectroscopy and a zinc-induced precipitation of Hb coupled to a reversed-phase high-performance liquid chromatography (HPLC)-based method; and (4) simulating in silico by molecular docking the APX interaction with human Hb...
October 2018: Thrombosis and Haemostasis
Kassandra Marsh, Tania Ahuja, Veronica Raco, David Green, Akhilesh K Sista, John Papadopoulos
Limited evidence is available to guide periprocedural management of oral anticoagulants in the setting of interventional radiology (IR) procedures. For direct oral anticoagulants, therapy interruption (TI) is based on medication half-life and procedural bleeding risk. Periprocedural management of warfarin includes INR monitoring, and possible bridging with parenteral anticoagulants. It is unknown if these recommendations apply to IR procedures. To evaluate bleeding complications and thromboembolic events following periprocedural management of the factor Xa (FXa) inhibitors or warfarin in patients undergoing IR procedures...
November 2018: Journal of Thrombosis and Thrombolysis
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