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Factor xa

P Gueret, S Combe, C Krezel, E Fuseau, P L M van Giersbergen, M Petitou, E Neuhart
INTRODUCTION: EP217609 is a representative of a new class of synthetic parenteral anticoagulants with a dual mechanism of action. It combines in a single molecule a direct thrombin inhibitor and an indirect factor Xa inhibitor. EP217609 can be neutralized by a specific antidote avidin, which binds to the biotin moiety of EP217609. PURPOSE: The primary objective was to assess the neutralization of EP217609 by avidin in healthy subjects. Secondary objectives were to define the optimal avidin monomer/EP217609 molar ratio to achieve an adequate neutralization of EP217609 and to assess the safety and tolerability of EP217609 and avidin...
October 15, 2016: European Journal of Clinical Pharmacology
Ryan Hakimi, Ankur Garg
PURPOSE OF REVIEW: Hemorrhagic stroke comprises approximately 15% to 20% of all strokes. This article provides readers with an understanding of the indications and significance of various neuroimaging techniques available for patients presenting with hemorrhagic strokes of distinct causes. RECENT FINDINGS: The most common initial neuroimaging study is a noncontrast head CT, which allows for the identification of hemorrhage. Once an intracranial hemorrhage has been identified, the pattern of blood and the patient's medical history, neurologic examination, and laboratory studies lead the practitioner to pursue further neuroimaging studies to guide the medical, surgical, and interventional management...
October 2016: Continuum: Lifelong Learning in Neurology
Andreas Hanslik, Erwin Kitzmüller, Ulrich S Tran, Katharina Thom, Hratsch Karapetian, Nicole Prutsch, Jasmin Voitl, Ina Michel-Behnke, Fiona Newall, Christoph Male
BACKGROUND: Unfractionated heparin (UFH) is used for prophylaxis and treatment of thrombosis in children. Laboratory monitoring of UFH is needed to prevent over- or under-anticoagulation. OBJECTIVES: Study objectives were to investigate i) the association between UFH dose and UFH effect as monitored by anti-IIa, ii) the relationship of anti-IIa and anti-Xa effects, and iii) the influence of patients' age and other factors on UFH effect. PATIENTS AND METHODS: Randomized controlled trial in children during cardiac catheterization, comparing high-dose UFH (100 units/kg bolus) versus low-dose UFH (50 units/kg bolus)...
October 13, 2016: Journal of Thrombosis and Haemostasis: JTH
Jamshed J Dalal, Anil Dhall, Abhay Bhave
Oral vitamin K antagonists (VKA) such as warfarin have been the mainstay of therapy for stroke prevention in patients with non valvular atrial fibrillation (NVAF) while low-molecular-weight heparin, fondaparinux and adjusted-dose warfarin or aspirin have been routinely used for thromboembolism (VTE) prophylaxis in patients undergoing total hip or knee replacement. However, VKAs are associated with considerable limitations, including increased risk of bleeding and narrow therapeutic window. Novel oral anticoagulants (NOACs, now referred as Non Vit K dependent oral anticoagulants), including the direct thrombin inhibitor dabigatran and direct Factor Xa inhibitors such as rivaroxaban and apixaban are now approved alternatives to warfarin for prophylaxis of stroke and systemic embolic events (SEE) in patients with NVAF and treatment and prophylaxis of VTE...
April 2016: Journal of the Association of Physicians of India
Jessica W Skelley, C Whitney White, Angela R Thomason
To review the use of the direct oral anticoagulant (DOAC) agents in inherited thrombophilia based on the literature. MEDLINE, International Pharmaceutical Abstracts, and Google Scholar searches (1970-May 2016) were conducted for case reports, case series, retrospective cohorts, or clinical trials using the key words: protein C deficiency, protein S deficiency, antithrombin deficiency, activated protein C resistance, Factor V Leiden, hypercoagulable, NOACs, dabigatran, apixaban, rivaroxaban, betrixaban, edoxaban, Xa inhibitor, direct thrombin inhibitor...
October 12, 2016: Journal of Thrombosis and Thrombolysis
Christopher M McLaughlin, Steven L Marks, David C Dorman, Alison Motsinger-Reif, Rita M Hanel
OBJECTIVE: To characterize the correlation between thromboelastography (TEG) variables using strong activators and anti-Xa (AXa) activity in healthy dogs administered subcutaneous unfractionated heparin (UFH). DESIGN: Prospective experimental study. SETTING: University research facility. ANIMALS: Eight adult random-source male dogs. INTERVENTION: Dogs were randomized to receive subcutaneous UFH at 200, 250, or 300 IU/kg every 8 hours for a total of 10 injections...
October 12, 2016: Journal of Veterinary Emergency and Critical Care
Brady S Moffett, Kimberly Dinh, Jennifer Placencia, Gregory Pelkey, Shiu-Ki Rocky Hui, Jun Teruya
BACKGROUND: Enoxaparin is often diluted to accurately deliver doses to neonatal and infant patients. Current recommendations for dilutions may not be adequate for the smallest patients. METHODS: Review of dosing at our institution occurred, and an 8 mg/mL concentration of enoxaparin was chosen. A concentration of 8 mg/mL was compounded by diluting 0.4 mL of enoxaparin (100 mg/mL) into 4.6 mL of sterile water for injection into an empty sterile vial. Four syringes of the 8 mg/mL concentration were prepared by 5 technicians (20 total syringes)...
July 2016: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
Christopher J Pannucci, Matthew T Rondina
No abstract text is available yet for this article.
October 3, 2016: Surgery
Maria L Rodríguez-Pozo, Lara Armengou, Luis Monreal, Judit Viu, Carla Cesarini, Eduard Jose-Cunilleras
OBJECTIVE: To assess whether an oral direct factor Xa inhibitor (DiXaI) anticoagulant drug used at the low end of the recommended dose in people achieves presumed prophylactic plasma concentrations and does not induce bleeding in horses. DESIGN: Experimental study. SETTING: Field study. ANIMALS: Ten healthy adult horses. INTERVENTIONS: A DiXaI was administered at a dose of 0.125 mg/kg every 24 h orally for 4 days...
October 6, 2016: Journal of Veterinary Emergency and Critical Care
Truman J Milling, Scott Kaatz
Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development...
September 28, 2016: American Journal of Emergency Medicine
Jerrold H Levy
Patients taking direct oral anticoagulants (DOACs) who then need an emergency invasive procedure require specialized management strategies. Appropriate patient evaluation includes assessment of the current anticoagulation state, including timing of the last dose. DOACs require particular coagulation assays to measure anticoagulation levels accurately, although standard coagulation screening tests may provide qualitative guidance. Specialty societies have endorsed general recommendations for patient management to promote hemostasis in anticoagulated patients requiring surgery or other invasive procedures...
September 29, 2016: American Journal of Emergency Medicine
Truman J Milling, Alex C Spyropoulos
Direct oral anticoagulants (DOACs) are a relatively recent addition to the oral anticoagulant armamentarium, and provide an alternative to the use of vitamin K antagonists such as warfarin. Regardless of the type of agent used, bleeding is the major complication of anticoagulant therapy. The decision to restart oral anticoagulation following a major hemorrhage in a previously anticoagulated patient is supported largely by retrospective studies rather than randomized clinical trials (mostly with vitamin K antagonists), and remains an issue of individualized clinical assessment: the patient's risk of thromboembolism must be balanced with the risk of recurrent major bleeding...
September 28, 2016: American Journal of Emergency Medicine
Menno V Huisman, John Fanikos
As expected with all antithrombotic agents, there is a risk of bleeding complications in patients receiving direct oral anticoagulants (DOACs) because of the DOAC itself, acute trauma, invasive procedures, or underlying comorbidities. For many bleeding events, a prudent course of action will be to withdraw the DOAC, then "wait and support" the patient, with the expectation that the bleeding event should resolve with time. Likewise, DOAC therapy may be interrupted ahead of a planned procedure, the stopping time being dependent on the agent involved and the patient's renal function...
September 28, 2016: American Journal of Emergency Medicine
David J Seiffge, Christopher Traenka, Alexandros Polymeris, Lisa Hert, Urs Fisch, Nils Peters, Gian Marco De Marchis, Raphael Guzman, Christian H Nickel, Philipp A Lyrer, Leo H Bonati, Dimitrios Tsakiris, Stefan Engelter
Plasma levels of Rivaroxaban (RivLev) might be useful to guide therapeutic decisions in patients with acute stroke under Rivaroxaban. A prerequisite for the potential clinical usefulness is their rapid availability in emergency situations. Single-center explorative analysis from the Novel-Oral-Anticoagulants-in-Stroke-Patients-registry (NOACISP, We included consecutive patients with acute ischemic or hemorrhagic stroke under Rivaroxaban (last intake <48 h) in which RivLev determined by an automated anti-factor Xa-based chromogenic assay (Hyphen-Biomed, France) are available...
October 1, 2016: Journal of Thrombosis and Thrombolysis
Denisse Menendez, Jeffrey Michel
Novel oral anticoagulants including the factor Xa inhibitor rivaroxaban are important alternatives to warfarin for the prevention of thromboembolic stroke in patients with nonvalvular atrial fibrillation. The pharmacology and metabolism of these agents differ from those of the vitamin K antagonists used over the decades preceding their introduction. We present a case of spontaneous hemopericardium and cardiac tamponade following administration of rivaroxaban. A review of the patient's medications revealed a total of seven agents known to be metabolized through cytochrome P450 3A4 (CYP3A4), the major pathway for rivaroxaban metabolism...
October 2016: Proceedings of the Baylor University Medical Center
Christopher J Pannucci, Thomas K Varghese, Kencee K Graves, Ann Marie Prazak
INTRODUCTION: Enoxaparin prophylaxis prevents venous thromboembolism in surgical patients. Real time anti-Factor Xa monitoring for surgical patients on enoxaparin prophylaxis is increasingly common. PRESENTATION OF CASES: We report on three cancer patients with therapeutic or supratherapeutic anti-Factor Xa levels while on prophylactic doses of enoxaparin after surgical procedures. In all cases, elevated anti-Factor Xa levels were the result of blood specimens being removed from a heparinized chemoport...
September 25, 2016: International Journal of Surgery Case Reports
Pasquale Pignatelli, Daniele Pastori, Simona Bartimoccia, Danilo Menichelli, Tommasa Vicario, Cristina Nocella, Roberto Carnevale, Francesco Violi
Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40)...
September 28, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jean Amiral, Claire Dunois, Cédric Amiral, Jerard Seghatchian
In the past decade Direct Oral Anti-Coagulants (DOACs), targeting Thrombin or Factor Xa, have enormously facilitated the daily treatment of all relevant patients, including those requiring lifelong therapy. These DOACs have considerable advantages over the use of oral Vitamin K Antagonist (VKA) treatments, in view of having little interferences with food and other medications and also not requiring adjustment for age, gender or weight, with some well-defined exceptions. In this current What's Happening Section we focus on measurements of DiXaIs in plasma using anti-Xa assays, with the objective of providing a tribute to Professor Michel Meyer Samama, who was not only a real leader in this field but, in the past, both authors benefited from his wisdom, as a teacher who dedicated his scientific and professional life (among many other interests in hemostasis, thrombosis and fibrinolysis) to develop and promote methods and strategies for laboratory monitoring of anticoagulants...
October 2016: Transfusion and Apheresis Science
Christopher J Pannucci, Ann Marie Prazak, Melody Scheefer
BACKGROUND: Between 2% and 10% of the highest risk surgery, patients have a "breakthrough" venous thromboembolism (VTE) event despite receipt of chemoprophylaxis. The goals of this review are to summarize how patient-level factors may predict enoxaparin metabolism and how alterations in enoxaparin dose magnitude and frequency affect both anti-factor Xa (aFXa) levels and downstream VTE events. DATA SOURCES: Relevant articles were identified on PubMed. Fixed-dose prophylaxis provides inadequate enoxaparin prophylaxis for most surgical patients based on anti-factor Xa levels...
September 2, 2016: American Journal of Surgery
Jan Beyer-Westendorf, Franziska Michalski, Luise Tittl, Susann Hauswald-Dörschel, Sandra Marten
BACKGROUND: Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age. METHODS: To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden...
October 2016: Lancet Haematology
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