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Direct-thrombin inhibitors

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https://www.readbyqxmd.com/read/28525532/the-effects-of-indirect-and-direct-acting-anticoagulants-on-lupus-anticoagulant-assays-a-large-retrospective-study-at-a-coagulation-reference-laboratory
#1
Jansen N Seheult, Michael P Meyer, Franklin A Bontempo, Irina Chibisov
Objectives: To investigate the effects of indirect- and direct-acting anticoagulants on the interpretation of lupus anticoagulant (LAC) assays. Methods: A retrospective database review was performed to identify all LAC panels from November 2012 to November 2015. The positivity rates for three LAC tests were compared among various anticoagulant medications. Results: This analysis included 7,721 LAC panels. Direct oral anticoagulants, warfarin, and unfractionated heparin (UFH) were associated with higher LAC positivity rates compared with patients not receiving documented anticoagulation (83% for argatroban, 58% for dabigatran, 72% for rivaroxaban, 53% for apixaban, 56% for warfarin, and 36% for UFH vs 29% for no anticoagulation, P < ...
May 19, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28509761/dabigatran-in-nonvalvular-atrial-fibrillation-from-clinical-trials-to-real-life-experience
#2
Nicola Mumoli, Daniela Mastroiacovo, Eleonora Tamborini-Permunian, Josè Vitale, Matteo Giorgi-Pierfranceschi, Marco Cei, Francesco Dentali
: Atrial fibrillation is the most common arrhythmia in over-midlife patients. In addition to systolic heart failure, cerebral thromboembolism represents the most dramatic complication of this rhythm disorder, contributing to morbidity and mortality. Traditionally, anticoagulation has been considered the main strategy in preventing stroke and systemic embolism in atrial fibrillation patients and vitamin K-dependent antagonists have been widely used in clinical practice. Recently, the development of direct oral anticoagulants has certainly improved the management of this disease, providing, for the first time, the opportunity to go beyond vitamin K-dependent antagonists limits...
July 2017: Journal of Cardiovascular Medicine
https://www.readbyqxmd.com/read/28509344/cgmp-signalling-inhibits-platelet-shape-change-through-regulation-of-the-rhoa-rho-kinase-mlc-phosphatase-signalling-pathway
#3
Ahmed Aburima, Kochar Walladbegi, Jonathan D Wake, Khalid M Naseem
BACKGROUND: Platelet shape change, spreading and thrombus stability requires activation of the actin cytoskeleton contractile machinery. The mechanisms controlling actin assembly to prevent unwanted platelet activation are unclear. OBJECTIVES: We examined the effects of nitric oxide on the signalling pathways regulating platelet actin-myosin activation. RESULTS: S-nitrosoglutathione (GSNO) inhibited thrombin-induced platelet shape change and myosin phosphorylation of myosin light chain (MLC)...
May 16, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28507269/randomized-multicenter-trial-of-artss-2-argatroban-with-recombinant-tissue-plasminogen-activator-for-acute-stroke
#4
Andrew D Barreto, Gary A Ford, Loren Shen, Claudia Pedroza, Jon Tyson, Chunyan Cai, Mohammad H Rahbar, James C Grotta
BACKGROUND AND PURPOSE: We conducted a randomized exploratory study to assess safety and the probability of a favorable outcome with adjunctive argatroban, a direct thrombin-inhibitor, administered to recombinant tissue-type plasminogen activator (r-tPA)-treated ischemic stroke patients. METHODS: Patients treated with standard-dose r-tPA, not receiving endovascular therapy, were randomized to receive no argatroban or argatroban (100 μg/kg bolus) followed by infusion of either 1 (low dose) or 3 μg/kg per minute (high dose) for 48 hours...
June 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28505011/in-vitro-assessment-of-the-effect-of-dabigatran-on-thrombosis-of-adult-and-neonatal-plasma-comparisons-using-thromboelastography-and-microscopic-visualization-of-fibrin-clot-structure
#5
Fadi F Nossair, Howard H W Chan, Jorell Gantioqui, Helen M Atkinson, Leslie R Berry, Anthony K C Chan
: Thromboelastography (TEG) is a global assay used for evaluating features of clot formation in vitro. Dabigatran is a reversible direct inhibitor of thrombin that has not been studied in neonates using a sophisticated global assay, such as TEG. Neonatal hemostasis differs from adult hemostasis in both quantitative and qualitative characteristics. Our aim was to compare the TEG clotting profile of neonatal and adult platelet-poor plasma when exposed to different concentrations of dabigatran. We used commercially collected adult pooled plasma and neonatal cord blood collected from placentas of healthy full term newborns...
May 12, 2017: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/28503126/in-vitro-and-ex-vivo-measurement-of-prophylactic-dabigatran-concentrations-with-a-new-ecarin-based-thromboelastometry-test
#6
Mareike Kristina Körber, Elisabeth Langer, Martin Köhr, Klaus-Dieter Wernecke, Wolfgang Korte, Christian von Heymann
BACKGROUND: An increasing number of oral anticoagulants has been approved, including dabigatran etexilate (DE). DE is a direct thrombin inhibitor that requires no routine monitoring, but, if necessary (e.g. urgent surgery etc.), the diluted thrombin time measured with Hemoclot® has shown reliable results. So far, no point-of-care (PoC) assay is available to measure DE effects. The EcaTEM assay uses ecarin to initiate the coagulation cascade at the step of thrombin generation and measures the clotting time (CT) by thromboelastometry...
April 2017: Transfusion Medicine and Hemotherapy
https://www.readbyqxmd.com/read/28500254/increased-thromboembolic-events-with-dabigatran-compared-with-vitamin-k-antagonism-in-left-ventricular-assist-device-patients-a-randomized-controlled-pilot-trial
#7
Martin Andreas, Roxana Moayedifar, Georg Wieselthaler, Michael Wolzt, Julia Riebandt, Thomas Haberl, Philipp Angleitner, Thomas Schlöglhofer, Dominik Wiedemann, Heinrich Schima, Guenther Laufer, Daniel Zimpfer
BACKGROUND: Left ventricular assist device-supported patients are usually anticoagulated with a combination of aspirin and vitamin K antagonists. Long-term vitamin K antagonist therapy can be complicated by unstable international normalized ratio values and patient-related compliance problems. Therefore, direct thrombin inhibitors may represent an alternative to vitamin K antagonists. METHODS AND RESULTS: Thirty HeartWare ventricular assist device patients with stable renal function were planned for this prospective, randomized, open-label, single-center study...
May 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28493056/non-vitamin-k-oral-anticoagulants-for-stroke-prevention-in-special-populations-with-atrial-fibrillation
#8
REVIEW
Arnaud Bisson, Denis Angoulvant, Raphael Philippart, Nicolas Clementy, Dominique Babuty, Laurent Fauchier
Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. These strokes may efficiently be prevented in patients with risk factors using oral anticoagulant therapy, with either vitamin K antagonists (VKAs) or non-vitamin K antagonist oral anticoagulants (NOACs) (i.e., direct thrombin inhibitors or direct factor Xa inhibitors). Owing to their specific risk profiles, some AF populations may have increased risks of both thromboembolic and bleeding events...
May 10, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28491164/spinal-subarachnoid-and-subdural-hematoma-presenting-as-a-brown-s%C3%A3-quard-like-myelopathy-following-minor-trauma-in-a-patient-on-dabigatran-etexilate
#9
Allen R Wolfe, Raihan M Faroqui, George A Visvikis, Michael T Mantello, Allan B Perel, Sanjit O Tewari
Dabigatran etexilate is a relatively new anticoagulant from the class of direct thrombin inhibitors which is administered orally and does not require routine blood work monitoring. Dabigatran may be attractive to both clinicians and patients because of both its convenience and efficacy; however, clinical complications are still being elucidated. Here, we present a previously unreported case of spinal subarachnoid and subdural hematoma presenting as a Brown-Séquard-like myelopathy in a patient after minor trauma in the setting of Dabigatran anticoagulation...
June 2017: Radiology case reports
https://www.readbyqxmd.com/read/28488882/development-of-bioanalytical-assays-for-variegin-a-peptide-based-bivalent-direct-thrombin-inhibitor
#10
Norrapat Shih, Leonardo Pinto de Carvalho, Yie Hou Lee, Mauricio Macario Rocha, Adriano Henrique Pereira Barbosa, José Marconi A de Sousa, Antonio Carlos de C Carvalho, R Manjunatha Kini, Mark Y Chan
AIM: Variegin is an anticoagulant peptide that will be tested in porcine models of percutaneous coronary intervention. We developed three bioanalytical assays for variegin quantitation and utilized these methods to evaluate pharmacokinetics of variegin in pigs. Results & methodology: The LC-MS/MS, thrombin amidolytic and modified thrombin time assays had a quantitation range of 21.6-5541.7, 10.8-5541.7 and 5.4-5541.7 nM in human plasma, respectively. The elimination half-lives obtained using the LC-MS/MS, modified thrombin time and thrombin amidolytic assays were 52...
May 10, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28487393/potent-thrombolytic-effect-of-n-acetylcysteine-on-arterial-thrombi
#11
Sara Martinez de Lizarrondo, Clément Gakuba, Bradley A Herbig, Yohann Repessé, Carine Ali, Cécile V Denis, Peter Lenting, Emmanuel Touzé, Scott L Diamond, Denis Vivien, Maxime Gauberti
Background -Platelet crosslinking during arterial thrombosis involves von Willebrand Factor (VWF) multimers. Therefore, proteolysis of VWF appears promising to disaggregate platelet-rich thrombi and restore vessel patency in acute thrombotic disorders such as ischemic stroke, acute coronary syndrome or acute limb ischemia. N-Acetylcysteine (NAC, a clinically approved mucolytic drug) can reduce intrachain disulfide bonds in large polymeric proteins. In the present study, we postulated that NAC might cleave the VWF multimers inside occlusive thrombi, thereby leading to their dissolution and arterial recanalization...
May 9, 2017: Circulation
https://www.readbyqxmd.com/read/28479844/american-college-of-cardiology
#12
Walter Alexander
We report on selected research presented at the ACC 66th Annual Scientific Session and Expo, including sessions on proprotein convertase subtilisin/kexin type 9 inhibitors, anti-Xa anticoagulants, and a direct thrombin inhibitor.
May 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28479184/systemic-thrombolysis-in-acute-ischemic-stroke-after-dabigatran-etexilate-reversal-with-idarucizumab-a-case-report
#13
Derya Tireli, Jun He, Mette Maria Nordling, Troels Wienecke
INTRODUCTION: Idarucizumab is a reversal agent for dabigatran etexilate. By reversing the anticoagulating effect of dabigatran etexilate with idarucizumab (Praxbind), patients presenting with an acute ischemic stroke can now be eligible for thrombolysis. PATIENT: We describe our experience with idarucizumab in a 71-year-old male patient pretreated with dabigatran etexilate. The patient arrived with a hemiparesis, central facial palsy, and dysarthria. METHOD: Dabigatran etexilate was antagonized with idarucizumab, approximately 2...
May 4, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28471371/the-reversal-of-direct-oral-anticoagulants-in-animal-models
#14
Markus Honickel, Necib Akman, Oliver Grottke
Several direct oral anticoagulants (DOACs), including direct thrombin and factor Xa inhibitors, have been approved as alternatives to vitamin K antagonist (VKA) anticoagulants. As with any anticoagulant, DOAC use carries a risk of bleeding. In patients with major bleeding or needing urgent surgery, reversal of DOAC anticoagulation may be required, presenting a clinical challenge. The optimal strategy for DOAC reversal is being refined, and may include use of hemostatic agents such as prothrombin complex concentrates (PCCs; a source of concentrated clotting factors), or DOAC-specific antidotes (which bind their target DOAC to abrogate its activity)...
April 4, 2017: Shock
https://www.readbyqxmd.com/read/28469072/uncoupling-of-the-profibrotic-and-hemostatic-effects-of-thrombin-in-lung-fibrosis
#15
Barry S Shea, Clemens K Probst, Patricia L Brazee, Nicholas J Rotile, Francesco Blasi, Paul H Weinreb, Katharine E Black, David E Sosnovik, Elizabeth M Van Cott, Shelia M Violette, Peter Caravan, Andrew M Tager
Fibrotic lung disease, most notably idiopathic pulmonary fibrosis (IPF), is thought to result from aberrant wound-healing responses to repetitive lung injury. Increased vascular permeability is a cardinal response to tissue injury, but whether it is mechanistically linked to lung fibrosis is unknown. We previously described a model in which exaggeration of vascular leak after lung injury shifts the outcome of wound-healing responses from normal repair to pathological fibrosis. Here we report that the fibrosis produced in this model is highly dependent on thrombin activity and its downstream signaling pathways...
May 4, 2017: JCI Insight
https://www.readbyqxmd.com/read/28467656/direct-oral-anticoagulants-vs-enoxaparin-for-prevention-of-venous-thromboembolism-following-orthopedic-surgery-a-dose-response-meta-analysis
#16
R A Boyd, L DiCarlo, J W Mandema
We carried out a dose-response model-based meta-analysis to assess venous thromboembolism (VTE) and bleeding with factor Xa (FXa) inhibitors (apixaban, edoxaban, rivaroxaban) and a thrombin inhibitor (dabigatran) compared with European (EU) (40 mg q.d.) and North American (NA) (30 mg Q12H) dose regimens of a low molecular weight heparin (enoxaparin) following orthopedic surgery. Statistically significant differences in both VTE and bleeding outcomes were found between the NA and EU doses of enoxaparin, with odds ratios (95% confidence interval) for the NA vs...
May 3, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28447415/the-danger-of-relying-on-the-aptt-and-pt-in-patients-on-doac-therapy-a-potential-patient-safety-issue
#17
REVIEW
D M Adcock, R C Gosselin
Prolongation of the activated partial thromboplastin time (APTT) and prothrombin time/international normalized ratio (PT/INR) correlates poorly with plasma concentrations of direct oral anticoagulant agents (DOACS) including direct thrombin and direct Xa inhibitors. It has been repeatedly demonstrated that patients can have normal APTT and PT/INR with a therapeutic plasma concentration of a DOAC. Clinicians can no longer rely on a normal APTT and PT to determine that an anticoagulated patient is safe to undergo an invasive procedure...
May 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28440204/apixaban-metabolism-pharmacologic-properties-and-drug-interaction
#18
Peter Kubisz, Lucia Stanciakova, Miroslava Dobrotova, Matej Samos, Marian Mokan, Jan Stasko
BACKGROUND: Apixaban is an oral, potent, highly selective, reversible and direct inhibitor of activated coagulation factor X, that is the end point of the intrinsic and extrinsic coagulation pathway. Additionally, apixaban has the capacity to indirectly inhibit thrombin-induced platelet aggregation. This new oral anticoagulant represents an immediate-release form of peroral drug with quick dissolution, linear pharmacokinetics, good bioavailability and rapid onset and offset of action...
April 24, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28439778/dabigatran-etexilate-appropriate-use-in-patients-with-chronic-kidney-disease-and-in-the-elderly-patients
#19
REVIEW
Mauro Molteni, Mario Bo, Giovanni Di Minno, Giuseppe Di Pasquale, Simonetta Genovesi, Danilo Toni, Paolo Verdecchia
Dabigatran etexilate (DE) is a direct thrombin inhibitor, which has been approved for the treatment of non-valvular atrial fibrillation (AF), and for the prevention and treatment of venous thromboembolism (VTE). Despite large randomized clinical trials and independent observational studies providing robust data concerning DE safety and efficacy, some physicians still perceive mild-to-moderate renal impairment and old age as a relative contraindication to its use. In this article, we review the available scientific evidence supporting the use of DE in these clinical situations...
April 24, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28439702/a-comparison-of-apixaban-and-dabigatran-etexilate-for-thromboprophylaxis-following-hip-and-knee-replacement-surgery
#20
Adriane Mayer, Philipp Schuster, Bernd Fink
INTRODUCTION: Patients who have undergone hip or knee replacement surgery are exposed to a high risk of developing a post-operative venous thromboembolus and so have a need for an effective, medication-based, thrombosis prophylaxis. New orally active anticoagulants have been available for a few years now. These specific substances directly block either thrombin (e.g., dabigatran etexilate) or Factor Xa (e.g., apixaban). It is not clear whether there are any efficacy differences between these two substances because there have never been any head-to-head studies carried out...
April 24, 2017: Archives of Orthopaedic and Trauma Surgery
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