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Direct thrombin inhibitor

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https://www.readbyqxmd.com/read/28057952/direct-thrombin-inhibitor-resistance-and-possible-mechanisms
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
Alina Achilles, Annemarie Mohring, Lisa Dannenberg, Maria Grandoch, Thomas Hohlfeld, Jens Fischer, Bodo Levkau, Malte Kelm, Tobias Zeus, Amin Polzin
BACKGROUND: The direct oral anticoagulant (DOAC) dabigatran is a direct thrombin inhibitor. Its landmark trial, the RE-LY study, observed a trend towards a higher incidence of myocardial infarctions (MI) in dabigatran treated patients. Since then, it has been discussed whether dabigatran increases the risk of MI. OBJECTIVE: In this study, we aimed to assess platelet reactivity and platelet thrombin receptor expression in dabigatran-treated patients. METHODS: We conducted a cross-sectional study in 13 hospitalized patients with planned initiation of dabigatran medication...
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
#11
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
https://www.readbyqxmd.com/read/27933406/differential-roles-for-the-coagulation-factors-xi-and-xii-in-regulating-the-physical-biology-of-fibrin
#12
Joanna L Sylman, Uranbileg Daalkhaijav, Ying Zhang, Elliot M Gray, Parsa A Farhang, Tiffany T Chu, Jevgenia Zilberman-Rudenko, Cristina Puy, Erik I Tucker, Stephanie A Smith, James H Morrissey, Travis W Walker, Xiaolin L Nan, András Gruber, Owen J T McCarty
In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation...
December 8, 2016: Annals of Biomedical Engineering
https://www.readbyqxmd.com/read/27929577/a-practical-approach-to-the-new-oral-anticoagulants-used-for-stroke-prevention-in-patients-with-atrial-fibrillation
#13
S Bashir, A Al-Mohammed, S Gupta
This review evaluates the research undertaken in the last six years on the use of new oral anticoagulants for stroke prevention in atrial fibrillation and provides evidence-based answers to common clinical questions. Two types of new oral anticoagulants - direct thrombin (IIa) inhibitors, and Xa inhibitors - are currently available. These drugs have similar pharmacokinetics and pharmacodynamics. They are more predictable than, though in many respects comparable to, warfarin. They do not require frequent laboratory tests, nor do they have a narrow therapeutic window...
June 2016: Journal of the Royal College of Physicians of Edinburgh
https://www.readbyqxmd.com/read/27928886/f376a-m388a-solulin-a-new-promising-antifibrinolytic-for-severe-haemophilia-a
#14
J Parcq, K U Petersen, A Borel-Derlon, P Gautier, M Ebel, D Vivien, Y Repessé
INTRODUCTION: Haemophilia is a major bleeding disorder due to a deficiency of procoagulant factor VIII (type A) or IX (type B). The treatment is substitutive and based on infusion of factor concentrates. Main limitations of this therapy are cost, short factor half-life and the development of inhibitors (up to 30% of severe HA patients). An important aggravating factor of haemophilia is due to a premature fibrinolysis, directing attention to the therapeutic potential of suitable antifibrinolytics...
December 8, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27917715/antiplatelet-agents-and-anticoagulants-in-patients-with-chronic-kidney-disease-from-pathophysiology-to-clinical-practice
#15
Jens Lutz, Kerstin Jurk
Progressive impairment of renal function can lead to uremia, which is associated with thus increasing the risk of bleeding as well as thrombosis. Furthermore, many patients with chronic kidney disease (CKD) have an indication for an anticoagulation or antiplatelet therapy due to atrial fibrillation, coronary artery disease, thromboembolic disease, or peripheral artery disease. The treatment usually includes vitamin-K antagonists (VKAs) and/or platelet aggregation inhibitors. The direct oral anticoagulants (DOACs) inhibiting factor Xa or thrombin activity represent an alternative for heparins and VKAs...
December 5, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27913536/reversal-of-direct-oral-anticoagulants-a-practical-approach
#16
Andrew W Shih, Mark A Crowther
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27910004/dabigatran-overdose-a-case-report-of-acute-hepatitis-extracorporeal-treatment
#17
Mariagrazia Porru, Antonella Mameli, Maria E Cianchetti, Mario Musu, Paola Schirru, Maria F Ruberto, Doris Barcellona, Francesco Marongiu
Dabigatran is an oral, direct thrombin inhibitor approved by international regulatory agencies for stroke prevention in patients with paroxysmal or persistent non-rheumatic atrial fibrillation (AF). The benefits of dabigatran are widely described, but its use in the geriatric population is not without risk. Chronic kidney disease is a common comorbidity with AF, and thus frequent checks of renal function in elderly patients are recommended. We report a case of dabigatran intoxication in an elderly man affected by heart failure and worsening renal function, who developed acute hepatitis and coma, which was successfully treated with continuous veno-venous hemodiafiltration...
December 1, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27909544/reducing-the-risk-of-stroke-in-patients-with-nonvalvular-atrial-fibrillation-with-direct-oral-anticoagulants-is-one-of-these-not-like-the-others
#18
REVIEW
Paul P Dobesh Pharm D, John Fanikos Mba R Ph
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and increases risk of stroke by nearly 5-fold. While warfarin has been employed successfully to reduce the risk of stroke in these patients, there are a number of challenges with therapy. These include the need for therapeutic monitoring due to variability in patient response, frequent dose adjustments, numerous drug-drug, drug-food, and drug-disease interactions, and a heightened risk of thrombosis and bleeding due to these issues. Current guidelines recommend that the vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs) should be used for thromboprophylaxis in patients with nonvalvular AF at risk for stroke or systemic embolic events...
August 2016: Journal of Atrial Fibrillation
https://www.readbyqxmd.com/read/27904902/a-novel-hirudin-derivative-inhibiting-thrombin-without-bleeding-for-subcutaneous-injection
#19
Bing Zhao, Yanling Zhang, Yinong Huang, Jinchao Yu, Yaran Li, Qi Wang, Yixin Ma, Hou-Yan Song, Min Yu, Wei Mo
Currently, anticoagulants would be used to prevent thrombosis. Thrombin is an effector enzyme for haemostasis and thrombosis. We designed a direct thrombin inhibitor peptide (DTIP) using molecular simulation and homology modelling and demonstrated that the C-terminus of DTIP interacts with exosite I, and N-terminus with the activity site of thrombin, respectively. DTIP interfered with thrombin-mediated coagulation in human, rat and mouse plasma (n=10 per group) and blocked clotting in human whole blood in vitro...
December 1, 2016: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/27904901/effect-of-ticagrelor-on-endothelial-calcium-signalling-and-barrier-function
#20
Dursun Gündüz, Christian Tanislav, Klaus-Dieter Schlüter, Rainer Schulz, Christian Hamm, Muhammad Aslam
The P2Y12 receptor is a Gi-coupled receptor whose activation inhibits adenylyl cyclase and thereby reduces the concentration of intracellular cAMP. Here the hypothesis was tested whether AR-C 66096 or ticagrelor, two direct-acting and reversibly binding P2Y12 receptor antagonists, protect endothelial cell (EC) barrier function by raising intracellular cAMP in ECs. The study was carried out on primary human umbilical vein ECs (HUVECs) and human pulmonary microvascular ECs (hPMECs). AR-C66096 (10 µM) induced a 50 % increase in cAMP in ECs whereas ticagrelor (2-10 µM) had no effect...
December 1, 2016: Thrombosis and Haemostasis
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