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Direct thrombin inhibitor

Clemens Feistritzer, Stefan Schmidt
During the 57(th) annual meeting of the American Society of Hematology 2015 in Orlando, Florida, various aspects in the field of hemostaseology were presented. The Choosing Wisely® campaign pointed out the importance of the critical use of diagnostic tools to rule out pulmonary embolism and questioned the relevance of thrombophilia testing in women undergoing routine infertility evaluation. Furthermore, the approval of idarucizumab, a specific antidote for the reversal of the anticoagulant effects of the direct thrombin inhibitor dabigatran, was highlighted...
2016: Memo
William B Hillegass, Gregory S Bradford
No abstract text is available yet for this article.
September 2016: Journal of Thoracic Disease
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
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
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
Aaron C Petrey, Carol A de la Motte
Dynamic alterations of the extracellular matrix in response to injury directly modulate inflammation, and consequently, the promotion and resolution of disease. During inflammation, hyaluronan (HA) is increased at sites of inflammation where it may be covalently modified with the heavy chains (HC) of inter-α-trypsin inhibitor (IαI). Deposition of this unique, pathological form of HA (HC:HA) leads to the formation of cable-like structures that promote adhesion of leukocytes. Naive mononuclear leukocytes bind specifically to inflammation-associated HA matrices but do not adhere to HA constitutively expressed under homeostatic conditions...
September 27, 2016: Journal of Biological Chemistry
Izabela Pawlaczyk-Graja, Sebastian Balicki, Rafał Ziewiecki, Mária Matulová, Peter Capek, Roman Gancarz
A macromolecular complex has been isolated from the dried flowering parts of medicinal plant Sanguisorba officinalis L. (So) by multi-step extraction procedure, including that with extraction by organic solvents to degrease the plant material, then with hot alkali, followed by neutralization, partitioning with organic solvents and dialysis. The complex was purified by size-exclusion chromatography into five fractions labeled as So1-So5. Individual fractions differed in the chemical composition and molecular weight distribution patterns...
September 21, 2016: International Journal of Biological Macromolecules
Karen S Brown, Hamim Zahir, Michael A Grosso, Hans J Lanz, Michele F Mercuri, Jerrold H Levy
BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) are approved for the prevention of stroke in patients with nonvalvular atrial fibrillation and for the treatment of venous thromboembolism. These include the direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. Bleeding is a complication for all anticoagulants and concerns regarding bleeding risk and the suitability of effective reversal strategies may be a barrier to their prescription...
September 23, 2016: Critical Care: the Official Journal of the Critical Care Forum
Marc Maegele, Oliver Grottke, Herbert Schöchl, Oliver A Sakowitz, Michael Spannagl, Jürgen Koscielny
BACKGROUND: Direct (non-vitamin-K-dependent) oral anticoagulants (DOAC) are given as an alternative to vitamin K antagonists (VKA) to prevent stroke and embolic disease in patients with atrial fibrillation that is not due to pathology of the heart valves. Fatal hemorrhage is rarer when DOACs are given (nonvalvular atrial fibrillation: odds ratio [OR] 0.68; 95% confidence interval [95% CI: 0.48; 0.96], and venous thromboembolism: OR 0.54; [0.22; 1.32]). 48% of emergency trauma patients need an emergency operation or early surgery...
September 5, 2016: Deutsches Ärzteblatt International
Jun Cao, Jing-Jing Xu, Xun-Gao Liu, Shu-Ling Wang, Li-Qing Peng
Thrombin was immobilized on dynabeads(®)M-270 epoxy by direct covalent binding method for the first time. The enzyme coated magnetic beads were combined with ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry technique to establish a simple, rapid and reliable approach for screening thrombin inhibitors from Danshen preparation. The conjugation of thrombin to the magnetic beads was characterized using scanning electron microscope, transmission electron microscope and infrared spectroscopy, and the enzyme activity was determined by the analysis of enzyme-bead ratio and peak areas of target compounds...
October 14, 2016: Journal of Chromatography. A
Céline Jumeau, Alain Rupin, Pauline Chieng-Yane, Nathalie Mougenot, Noël Zahr, Monique David-Dufilho, Stéphane N Hatem
The present study tested the hypothesis that thrombin participates in formation of left atrial remodeling and that direct oral anticoagulants, such as direct thrombin inhibitors (DTIs), can prevent its progression. In a rat model of heart failure associated with left atrial dilation, we found that chronic treatment with DTIs reduces the atrial remodeling and the duration of atrial fibrillation (AF) episodes induced by burst pacing by inhibiting myocardial hypertrophy and fibrosis. In addition to the prevention of thromboembolism complicating AF, DTIs may be of interest to slow down the progression of the arrhythmogenic substrate...
August 2016: JACC. Basic to Translational Science
Bethany T Samuelson, Adam Cuker, Deborah M Siegal, Mark Crowther, David A Garcia
BACKGROUND: The direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or non-cancer associated venous thromboembolic disease. While routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this study was to systematically review and summarize current evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban and edoxaban...
September 13, 2016: Chest
N G Khorev, A P Momot, V O Kon'kova
During the last 10 years, several novel direct oral anticoagulants (NOACs) have entered the clinical arena and were registered in the Russian Federation for use in patients presenting with atrial fibrillation, venous thrombosis, and pulmonary artery thromboembolism. NOACs are classified into two groups: direct thrombin inhibitor (notably dabigatran) and factor Xa inhibitors (including rivaroxaban, apixaban, and edoxaban). Their disadvantage is lack of specific antidotes in case of an emergency situation (injury, infarction, stroke requiring thrombolysis, urgent operation)...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
Bethany T Samuelson, Adam Cuker
Direct oral anticoagulants (DOACs) offer noninferior efficacy and improved safety compared to vitamin K antagonists (VKAs) for the prevention and treatment of venous thromboembolism and for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Unlike VKAs, DOACs do not require routine laboratory monitoring of anticoagulant effect and dose adjustment. In certain situations, however, laboratory assessment of anticoagulant effect may be desirable. Here we review the utility of currently available assays for assessment of DOAC effect and recommend an optimal assessment strategy for each drug, including calibrated dilute thrombin time or ecarin-based assays for dabigatran and calibrated anti-Xa activity assays for the factor Xa inhibitors...
September 2, 2016: Blood Reviews
Mark R Gillrie, Bernard Renaux, Eleanor Russell-Goldman, Marion Avril, Andrew J Brazier, Koichiro Mihara, Enrico Di Cera, Danny A Milner, Morley D Hollenberg, Joseph D Smith, May Ho
UNLABELLED: Plasmodium falciparum malaria remains one of the most deadly infections worldwide. The pathogenesis of the infection results from the sequestration of infected erythrocytes (IRBC) in vital organs, including the brain, with resulting impairment of blood flow, hypoxia, and lactic acidosis. Sequestration occurs through the adhesion of IRBC to host receptors on microvascular endothelium by Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large family of variant surface antigens, each with up to seven extracellular domains that can bind to multiple host receptors...
2016: MBio
Walter Ageno, Alexander G G Turpie
Venous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs)...
September 14, 2016: Thrombosis and Haemostasis
Reece A Davies, Nisal K Perera, Yishay Orr
A best evidence topic was written according to a structured protocol. The question addressed was 'In patients requiring an implanted cardiac rhythm device, do novel oral anticoagulant agents lead to increased rates of peri-procedural complications?' Altogether 1228 papers were found using the reported search, of which 5 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated...
September 5, 2016: Interactive Cardiovascular and Thoracic Surgery
Fabrizio Vianello, Luisa Sambado, Ashley Goss, Fabrizio Fabris, Paolo Prandoni
Thrombin activates its G-coupled seven transmembrane protease-activated receptor (PAR-1) by cleaving the receptor's N-terminal end. In several human cancers, PAR1 expression and activation correlates with tumor progression and metastatization. This provides compelling evidence for the effectiveness of an appropriate antithrombin agent for the adjuvant treatment of patients with cancer. Dabigatran is a selective direct thrombin inhibitor that reversibly binds to thrombin. In this study, we aimed to explore if dabigatran may affect mechanisms favoring tumor growth by interfering with thrombin-induced PAR-1 activation...
September 7, 2016: Cancer Medicine
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