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https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#1
Sarah Monagle, John W Eikelboom, Kuan H Ng, Vinai C Bhagirath
Direct oral anticoagulants (DOACs) are effective in preventing and treating venous thromboembolism, and preventing stroke in atrial fibrillation. Until recently, there has been no specific reversal agent for DOACs. Now, a specific antidote for the direct thrombin inhibitor, dabigatran has been approved for use, and antidotes for factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) are being developed. We review the evidence for currently used and emerging reversal strategies, and discuss possible clinical implications, including increased prescription of DOACs, use of DOACs in clinical situations previously felt to pose too great a risk of bleeding, and use of reversal agents beyond currently approved indications...
March 2017: Future Cardiology
https://www.readbyqxmd.com/read/28196633/old-and-new-oral-anticoagulants-food-herbal-medicines-and-drug-interactions
#2
REVIEW
Alessandro Di Minno, Beatrice Frigerio, Gaia Spadarella, Alessio Ravani, Daniela Sansaro, Mauro Amato, Joseph P Kitzmiller, Mauro Pepi, Elena Tremoli, Damiano Baldassarre
The most commonly prescribed oral anticoagulants worldwide are the vitamin K antagonists (VKAs) such as warfarin. Factors affecting the pharmacokinetics of VKAs are important because deviations from their narrow therapeutic window can result in bleedings due to over-anticoagulation or thrombosis because of under-anticoagulation. In addition to pharmacodynamic interactions (e.g., augmented bleeding risk for concomitant use of NSAIDs), interactions with drugs, foods, herbs, and over-the-counter medications may affect the risk/benefit ratio of VKAs...
February 5, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28191610/italian-intersociety-consensus-on-doac-use-in-internal-medicine
#3
Domenico Prisco, Walter Ageno, Cecilia Becattini, Armando D'Angelo, Giovanni Davì, Raimondo De Cristofaro, Francesco Dentali, Giovanni Di Minno, Anna Falanga, Gualberto Gussoni, Luca Masotti, Gualtiero Palareti, Pasquale Pignatelli, Roberto M Santi, Francesca Santilli, Mauro Silingardi, Antonella Tufano, Francesco Violi
The direct oral anticoagulants (DOACs) are drugs used in clinical practice since 2009 for the prevention of stroke or systemic embolism in non-valvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism. The four DOACs, including the three factor Xa inhibitors (rivaroxaban, apixaban and edoxaban) and one direct thrombin inhibitor (dabigatran) provide oral anticoagulation therapy alternatives to Vitamin K antagonists (VKAs). Despite their clear advantages, the DOACs require on the part of the internist a thorough knowledge of their pharmacokinetic and pharmacodynamic characteristics to ensure their correct use, laboratory monitoring and the appropriate management of adverse events...
February 13, 2017: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/28185082/dabigatran-etexilate-a-review-in-nonvalvular-atrial-fibrillation
#4
Hannah A Blair, Gillian M Keating
Dabigatran etexilate (Pradaxa(®)) is approved in the EU for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF) and one or more risk factors. Dabigatran etexilate is a prodrug of dabigatran, a direct inhibitor of thrombin. In patients with NVAF in the phase III RE-LY trial, dabigatran etexilate dosages of 110 and 150 mg twice daily were noninferior to warfarin with regard to the risk of stroke or systemic embolism (primary efficacy endpoint). The higher dosage was associated with a significantly lower risk of stroke or systemic embolism than warfarin, with no significant between-group difference in the risk of major bleeding (primary safety endpoint)...
February 9, 2017: Drugs
https://www.readbyqxmd.com/read/28182192/dabigatran-potentiates-gemcitabine-induced-growth-inhibition-of-pancreatic-cancer-in-mice
#5
Kun Shi, Helene Damhofer, Joost Daalhuisen, Marieke Ten Brink, Dick J Richel, C Arnold Spek
Pancreatic cancer is one of the most lethal solid malignancies with little treatment options. We have recently shown that expression of protease activated receptor (PAR)-1 in the tumor microenvironment drives progression and induces chemoresistance of pancreatic cancer. As thrombin is the prototypical PAR-1 agonist, here we addressed the effect of the direct thrombin inhibitor dabigatran on pancreatic cancer growth and drug resistance in an orthotropic pancreatic cancer model. We show that dabigatran treatment did not affect primary tumor growth whereas it significantly increased tumor dissemination throughout the peritoneal cavity...
February 6, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28169097/evaluation-of-the-efficacy-and-safety-of-direct-oral-anticoagulants-in-japanese-patients-analysis-of-pharmaceuticals-and-medical-devices-agency-data
#6
Yasuo Terayama
BACKGROUND: Two forms of direct oral anticoagulant (DOAC) have recently been introduced: direct thrombin inhibitors (DTI; e.g., dabigatran) and factor Xa inhibitors (FXa; e.g., rivaroxaban and apixaban). Despite the advantages of DOACs over warfarin with regard to cerebrovascular complications, those associated with DOACs have been reported with the increasing use of DOACs. Nevertheless, little is known about real-world comparative efficacy and safety of DOACs. METHODS: Cerebrovascular adverse events collected by the Pharmaceutical and Medical Devices Agency (PMDA) during 2014 were analyzed to describe and compare efficacy and safety among patients prescribed DTI and FXa...
February 3, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28150854/imaging-analyses-of-coagulation-dependent-initiation-of-fibrinolysis-on-activated-platelets-and-its-modification-by-thrombin-activatable-fibrinolysis-inhibitor
#7
Tomasz Brzoska, Yuko Suzuki, Hideto Sano, Seiichirou Suzuki, Martyna Tomczyk, Hiroki Tanaka, Tetsumei Urano
Using intravital confocal microscopy, we observed previously that the process of platelet phosphatidylserine (PS) exposure, fibrin formation and lysine binding site-dependent plasminogen (plg) accumulation took place only in the center of thrombi, not at their periphery. These findings prompted us to analyse the spatiotemporal regulatory mechanisms underlying coagulation and fibrinolysis. We analysed the fibrin network formation and the subsequent lysis in an in vitro experiment using diluted platelet-rich plasma supplemented with fluorescently labelled coagulation and fibrinolytic factors, using confocal laser scanning microscopy...
February 2, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28140308/-renal-function-and-plasma-dabigatran-level-measured-at-trough-by-diluted-thrombin-time-assay
#8
Marta E Martinuzzo, Cristina Duboscq, Estela S Viñuales, Beatriz Girardi, Diana Penchasky, José Ceresetto, Germán Stemmelin, Victoria Otero, Luis H Barrera, Marina S López, Juan C Otaso, José Hoyhamburu
Dabigatran etexilate (direct thrombin inhibitor) is effective in preventing embolic stroke in patients with atrial fibrillation. It does not require laboratory control, but given the high renal elimination, its measurement in plasma is important in renal failure. The objectives of the study were to verify the analytical quality of the diluted thrombin time assay for measurement of dabigatran plasma concentration (cc), correlate cc with classic coagulation assays, prothrombin time (PT) and activated partial thromboplastin time (APTT), and evaluate them according to the creatinine clearance (CLCr)...
2017: Medicina
https://www.readbyqxmd.com/read/28105561/the-rise-and-fall-of-anticoagulation-with-bivalirudin-during-percutaneous-coronary-interventions-a-review-article
#9
REVIEW
Constantinos Andreou, Christos Maniotis, Michael Koutouzis
Bivalirudin is a direct thrombin inhibitor used during percutaneous coronary intervention (PCI). Treatment with bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPI) reduced bleeding complications, but resulted in higher rates of ischemic events, including acute stent thrombosis in ST segment elevation myocardial infarction (STEMI) patients. Thus, it may be considered a reasonable alternative antithrombotic agent in patients at high risk of bleeding undergoing PCI. However its superiority over heparin alone is questioned particularly in the era of novel antiplatelet agents and transradial PCI...
January 19, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28057952/direct-thrombin-inhibitor-resistance-and-possible-mechanisms
#10
Maria Cardinale, Michael Ha, Michael H Liu, David P Reardon
Objective: To report 3 cases in which doses of bivalirudin higher than commonly used in clinical practice were required in order to achieve therapeutic anticoagulation as monitored by the activated partial thromboplastin time (aPTT). Case Summary: The medical records of 3 patients who required large doses of bivalirudin to remain therapeutic were thoroughly reviewed. In all 3 patients, bivalirudin was initiated at a rate appropriate for the patients' renal function and titrated using a nurse-driven protocol with recommended dose adjustments based on aPTT...
December 2016: Hospital Pharmacy
https://www.readbyqxmd.com/read/28052306/laboratory-monitoring-of-parenteral-direct-thrombin-inhibitors
#11
Elizabeth M Van Cott, A Joshua Roberts, William E Dager
Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion...
January 4, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28043992/direct-oral-anticoagulants-and-heparins-laboratory-values-and-pitfalls-in-bridging-therapy
#12
Thomas Eller, Tobias Flieder, Vanessa Fox, Tatjana Gripp, Marcus Dittrich, Joachim Kuhn, Susanne Alban, Cornelius Knabbe, Ingvild Birschmann
OBJECTIVES: The three direct oral anticoagulants (DOACs) dabigatran, apixaban and rivaroxaban are now widely used in clinical practice. For patients requiring perioperative interruption of DOACs, heparin bridging is still under discussion. Here we show, for the first time, the influence of concomitantly used DOACs and heparins on laboratory assays. METHODS: For spiking experiments, 10 healthy donors and nine patients treated with DOACs were investigated. The measurement of DOACs and heparins was performed with routine methods on the ACL TOP [HEMOCLOT(®) direct thrombin inhibitor (CoaChrom Diagnostica, Austria), COAMATIC(®) Heparin (Chromogenix, USA) calibrated with rivaroxaban, apixaban, unfractionated heparin (UFH) and low molecular weight heparin (LMWH), additionally PT reagent RecombiPlasTin 2G and aPTT reagent SynthASil (Instrumentation Laboratory, Germany)] and the DOACs were additionally quantified with liquid chromatography-mass spectrometry...
January 2, 2017: European Journal of Cardio-thoracic Surgery
https://www.readbyqxmd.com/read/28042443/differences-between-warfarin-and-new-oral-anticoagulants-in-dental-clinical-practice
#13
REVIEW
M Miranda, L S Martinez, R Franco, V Forte, A Barlattani, P Bollero
The oral anticoagulant therapy is used for the cure and the prevention of thromboembolic diseases. In the last fifty years the warfarin has been considered the oral anticoagulant of choice. However, its use is limited by a narrow therapeutic index and by a complex pharmacodynamics, which requires regular adjustments and monitoring of the dose. Recently, three new oral anticoagulant - dabigatran etexilato (direct thrombin inhibitor), rivaroxaban and apixaban (Xa factor direct inhibitor) - have been approved for use in europe...
July 2016: Oral & Implantology
https://www.readbyqxmd.com/read/28029411/atrial-fibrillation-and-heart-failure-factors-influencing-the-choice-of-oral-anticoagulant
#14
REVIEW
Louise A E Brown, Christopher J Boos
Atrial fibrillation (AF) and heart failure (HF) frequently coexist. AF is identified in approximately one third of patients with HF and is linked to increased morbidity and mortality than from either condition alone. AF is relatively more common in HF with preserved ejection fraction (HFpEF) than with reduced ejection fraction (HFrEF). Nevertheless, the risk of stroke and systemic embolism (SSE) is significantly increased with both HF types and the absolute risk is heavily influenced by the presence and severity of associated additional stroke risk factors...
September 30, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28011314/idarucizumab-praxbind%C3%A2-the-first-reversal-agent-for-a-direct-oral-anticoagulant
#15
EDITORIAL
Shannon W Finks, Kelly C Rogers
Idarucizumab is a humanized monoclonal antibody fragment engineered to specifically neutralize the effects of the oral direct thrombin inhibitor dabigatran in order to restore hemostasis. FDA approval for idarucizumab, under the brand name Praxbind®, was granted in October 2015 for the reversal of dabigatran in settings of emergent life-threatening bleeding episodes or in the case when an emergent surgery or urgent procedure is needed to reverse its anticoagulant effects.(1) This article summarizes pertinent and clinical information regarding idarucizumab and other reversal agents currently under investigation...
December 20, 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/28003564/anticoagulation-increases-alveolar-hemorrhage-in-mice-infected-with-influenza-a
#16
Kohei Tatsumi, Silvio Antoniak, Saravanan Subramaniam, Bertrand Gondouin, Scott D Neidich, Melinda A Beck, Jacqueline Mickelson, Dougald M Monroe, Julie A Bastarache, Nigel Mackman
Influenza A virus infection is a common respiratory tract infection. Alveolar hemorrhage has been reported in patients with influenza pneumonia and in mice infected with influenza A. In this study, we investigated the effect of two anticoagulants on alveolar hemorrhage after influenza A virus (IAV) infection of wild-type mice. Wild-type mice were anticoagulated with either warfarin or the direct thrombin inhibitor dabigatran etexilate and then infected with a mouse-adapted influenza virus (A/Puerto Rico/8/34 H1N1)...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28000559/in-models-of-intracerebral-hemorrhage-rivaroxaban-is-superior-to-warfarin-to-limit-blood-brain-barrier-disruption-and-hematoma-expansion
#17
Shigenobu Sawada, Yoko Ono, Yusuke Egashira, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Intracerebral hemorrhage (ICH) during oral anticoagulation therapy with an oral vitamin K epoxidase reductase such as warfarin is a life-threatening complication. However, whether direct oral anticoagulants (DOACs) are associated with larger hematoma volume and higher mortality rates remains controversial. We evaluated the hematoma volume and pathophysiology of ICH during anticoagulation with warfarin or rivaroxaban, an orally active direct factor Xa inhibitor. Mice were orally pretreated with rivaroxaban (10 or 30 mg/kg), warfarin (4 mg/kg), or vehicle...
December 16, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27993122/in-models-of-intracerebral-hemorrhage-rivaroxaban-is-superior-to-warfarin-to-limit-blood-brain-barrier-disruption-and-hematoma-expansion
#18
Shigenobu Sawada, Yoko Ono, Yusuke Egashira, Toshinori Takagi, Kazuhiro Tsuruma, Masamitsu Shimazawa, Toru Iwama, Hideaki Hara
Intracerebral hemorrhage (ICH) during oral anticoagulation therapy with an oral vitamin K epoxidase reductase such as warfarin is a life-threatening complication. However, whether direct oral anticoagulants (DOACs) are associated with larger hematoma volume and higher mortality rates remains controversial. We evaluated the hematoma volume and pathophysiology of ICH during anticoagulation with warfarin or rivaroxaban, an orally active direct factor Xa inhibitor. Mice were orally pretreated with rivaroxaban (10 or 30 mg/kg), warfarin (4 mg/kg), or vehicle...
December 16, 2016: Current Neurovascular Research
https://www.readbyqxmd.com/read/27992120/dabigatran-enhances-platelet-reactivity-and-platelet-thrombin-receptor-expression-in-patients-with-atrial-fibrillation
#19
A Achilles, A Mohring, L Dannenberg, M Grandoch, T Hohlfeld, J W Fischer, B Levkau, M Kelm, T Zeus, A Polzin
: Essentials Whether or not dabigatran enhances the risk of myocardial infarction is under discussion. We measured platelet reactivity and thrombin receptor expression in dabigatran patients. Platelet reactivity and thrombin receptor expression is enhanced during dabigatran treatment. This should be considered when choosing the optimal direct oral anticoagulant for individuals. SUMMARY: Background The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor...
December 19, 2016: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/27935888/-effect-of-angioprotective-therapy-with-bioflavonoids-on-endothelial-dysfunction-in-patients-with-acute-venous-thromboses
#20
A Yu Bryushkov, P V Ershov, N A Sergeeva, V Yu Bogachev
The study was aimed at evaluating a possibility of correcting endothelial dysfunction by means of angioprotective therapy with natural-origin bioflavonoids in patients presenting with acute venous thromboses. Ours was an open comparative prospective study including a total of thirty 34-to-60-year-old patients suffering from lower limb deep vein thrombosis. The patients were subdivided into two groups. The Study Group was composed of 15 patients receiving on the background of anticoagulant therapy with direct thrombin inhibitors (dabigatran etexilate at a daily dose of 300 mg) natural-origin angioprotectors (red grape leaf extract)...
2016: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
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