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Direct-thrombin inhibitors

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https://www.readbyqxmd.com/read/28320219/monitoring-of-argatroban-and-lepirudin
#1
Holger Seidel, Hans-Jürgen Kolde
Monitoring of direct thrombin inhibitors (DTIs) in patients with heparin-induced thrombocytopenia (HIT) is primarily performed using the activated partial thromboplastin time (aPTT). This assay is poorly standardized, reagent dependent, and not DTI specific. We compared aPTT, thrombin time (TT), and prothrombin time (PT) to drug levels obtained by the ecarin chromogenic assay (ECA). We analyzed 495 samples of patients with confirmed or suspected HIT on treatment with either argatroban (n = 37) or lepirudin (n = 80)...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28316004/effect-of-the-fxa-inhibitors-rivaroxaban-and-apixaban-on-platelet-activation-in-patients-with-atrial-fibrillation
#2
B Steppich, F Dobler, L C Brendel, G Hessling, S L Braun, A L Steinsiek, I Deisenhofer, A Hyseni, M Roest, I Ott
Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study...
March 18, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28314985/the-role-of-new-oral-anticoagulants-in-orthopaedics-an-update-of-recent-evidence
#3
REVIEW
Dimitrios V Papadopoulos, Ioannis Kostas-Agnantis, Ioannis Gkiatas, Andreas G Tsantes, Panagiota Ziara, Anastasios V Korompilias
Rivaroxaban, dabigatran, apixaban and edoxaban are the four available new oral anticoagulants (NOAC) which are currently approved for venous thromboembolism prophylaxis after total hip and knee replacement. Large phase 3 and phase 4 studies comparing NOAC with low molecular weight heparins have shown similar results regarding the efficacy and safety of these two categories of anticoagulants. Management of bleeding complications is a matter of great significance. Three reversal agents have been developed: idarucizumab, andexanet alfa and ciraparantag...
March 17, 2017: European Journal of Orthopaedic Surgery & Traumatology: Orthopédie Traumatologie
https://www.readbyqxmd.com/read/28314697/demeanor-of-rivaroxaban-in-activated-inactivated-fxa
#4
Kaname Seki, Yosuke Mizuno, Toku Sakashita, Shintaro Nakano, Jun Tanno, Yasushi Okazaki, Toshihiro Muramatsu, Shigeyuki Nishimura, Takaaki Senbonmatsu
Activated factor X (FXa) plays an important role in thrombin generation and inflammation. Factor X is not converted constitutively to FXa, but only after intrinsic clotting factors are activated and/or cellular injury occurs. Although rivaroxaban is one of direct FXa inhibitors, its function in the inactivated coagulation cascade is unclear. In human umbilical vein endothelial cells that natively express protease-activated receptor-1 and -2, high dose rivaroxaban did not alter gene transcripts including pro-inflammatory genes in DNA microarray...
February 24, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28298749/perioperative-considerations-and-management-of-patients-receiving-anticoagulants
#5
REVIEW
Safiya Imtiaz Shaikh, R Vasantha Kumari, Ganapati Hegade, M Marutheesh
Anticoagulants remain the primary strategy for the prevention and treatment of thrombosis. Unfractionated heparin, low molecular weight heparin (LMWH), fondaparinux, and warfarin have been studied and employed extensively with direct thrombin inhibitors typically reserved for patients with complications or those requiring interventions. Novel oral anticoagulants have emerged from clinical development and are expected to replace older agents with their ease to use and more favorable pharmacodynamic profiles...
January 2017: Anesthesia, Essays and Researches
https://www.readbyqxmd.com/read/28290913/-modern-approaches-to-prevention-of-thromboembolic-complications-in-patients-with-nonvalvular-atrial-fibrillation-with-a-direct-thrombin-inhibitor-dabigatran
#6
N M Savina
of recently completed clinical studies and preliminary results of still ongoing studies that support safety and efficacy of dabigatran in patients with nonvalvular atrial fibrillation are under discussion in this article. Currently available data on clinical use of a specific dabigatran antidote idarucizumab are also presented.
July 2016: Kardiologiia
https://www.readbyqxmd.com/read/28287382/effect-of-dabigatran-on-a-prothrombinase-based-assay-for-detecting-activated-protein-c-resistance-an-ex-vivo-and-in-vitro-study-in-normal-subjects-and-factor-v-leiden-carriers
#7
Gianluca Gessoni, Sara Valverde, Letizia Valle, Pierpaolo Caruso, Francesca Gessoni, Roberto Valle
BACKGROUND: The aim of this study was to evaluate ex vivo and in vitro interference of a direct factor IIa inhibitor, dabigatran, on a prothrombinase-based assay to detect activated protein C resistance. MATERIALS AND METHODS: An ex vivo study was performed in six heterozygous factor V Leiden carriers and 12 normal subjects without the factor V Leiden mutation who were treated with dabigatran. An in vitro study was also performed considering 12 plasma samples (six from normal subjects and six from heterozygous factor V Leiden carriers) spiked with dabigatran...
March 7, 2017: Blood Transfusion, Trasfusione del Sangue
https://www.readbyqxmd.com/read/28276481/identification-of-berberine-as-a-direct-thrombin-inhibitor-from-traditional-chinese-medicine-through-structural-functional-and-binding-studies
#8
Xing Wang, Yuxin Zhang, Ying Yang, Xia Wu, Hantian Fan, Yanjiang Qiao
Thrombin acts as a key enzyme in the blood coagulation cascade and represents a potential drug target for the treatment of several cardiovascular diseases. The aim of this study was to identify small-molecule direct thrombin inhibitors from herbs used in traditional Chinese medicine (TCM). A pharmacophore model and molecular docking were utilized to virtually screen a library of chemicals contained in compositions of traditional Chinese herbs, and these analyses were followed by in vitro bioassay validation and binding studies...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275614/considerations-for-analgosedation-and-antithrombotic-management-during-extracorporeal-life-support
#9
REVIEW
Pamela K Burcham, Alan J Rozycki, Erik E Abel
Despite the immense growth in extracorporeal life support (ECLS) technology and experience, opportunity remains to better characterize the pharmacotherapeutic considerations during ECLS. Analgosedation can be particularly challenging in the ECLS population due to in drug-circuit interactions that may lead to decreased systemic concentrations and pharmacodynamic effect. ECLS also requires the use of antithrombotic agents to mitigate the prothrombotic state created by the artificial surface in the ECLS circuit...
February 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28270004/-the-first-use-of-iv-idarucizumab-for-dabigatran-reversal-in-hungary
#10
Lajos Driesz, Éva Barabás, Ildikó Bodócs, Zoltán Szántó, György Herr, Gábor Bencsik, László Pál, József Borbola
At present, the direct thrombin inhibitor dabigatran is the only one amongst the new direct anticoagulants which has an effective, specific reversal agent. The novel agent idarucizumab is a humanized, monoclonal antibody fragment binds to dabigatran within minutes thereby offers an opportunity to induce a safe, long-lasting reverse of the anticoagulant effects of dabigatran. The authors describe the first use of idarucizumab in Hungary (23. 05. 2016) in an old female patient with non-valvular paroxysmal atrial fibrillation of high stroke risk-score and renal dysfunction who was taking dabigatran (2 x 110 mg/day) when an acute abdomen developed requiring emergency cholecystectomy...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28263937/identifying-drug-drug-interactions-by-data-mining-a-pilot-study-of-warfarin-associated-drug-interactions
#11
Peter Wæde Hansen, Line Clemmensen, Thomas S G Sehested, Emil Loldrup Fosbøl, Christian Torp-Pedersen, Lars Køber, Gunnar H Gislason, Charlotte Andersson
BACKGROUND: Knowledge about drug-drug interactions commonly arises from preclinical trials, from adverse drug reports, or based on knowledge of mechanisms of action. Our aim was to investigate whether drug-drug interactions were discoverable without prior hypotheses using data mining. We focused on warfarin-drug interactions as the prototype. METHODS AND RESULTS: We analyzed altered prothrombin time (measured as international normalized ratio [INR]) after initiation of a novel prescription in previously INR-stable warfarin-treated patients with nonvalvular atrial fibrillation...
November 2016: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28247290/determination-of-non-vitamin-k-oral-anticoagulant-noac-effects-using-a-new-generation-thrombelastography-teg-6s-system
#12
Kevin P Bliden, Rahul Chaudhary, Nafees Mohammed, Adina A Muresan, Carlos G Lopez-Espina, Eli Cohen, Gabriel Raviv, Marc Doubleday, Fowzia Zaman, Blessy Mathew, Udaya S Tantry, Paul A Gurbel
Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs...
February 28, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28243155/perioperative-care-in-an-adolescent-patient-with-heparin-induced-thrombocytopenia-for-placement-of-a-cardiac-assist-device-and-heart-transplantation-case-report-and-literature-review
#13
Mineto Kamata, Roby Sebastian, Patrick I McConnell, Daniel Gomez, Aymen Naguib, Joseph D Tobias
Heparin-induced thrombocytopenia (HIT) can cause life-threatening complications following the administration of heparin. Discontinuation of all sources of heparin exposure and the use of alternative agents for anticoagulation are necessary when HIT is suspected or diagnosed. We present the successful use of bivalirudin anticoagulation in an adolescent patient during cardiopulmonary bypass who underwent both placement of a left ventricular assist device and subsequent heart transplantation within a 36-hour period...
2017: International Medical Case Reports Journal
https://www.readbyqxmd.com/read/28239301/the-reversal-effect-of-prothrombin-complex-concentrate-pcc-activated-pcc-and-recombinant-activated-factor-vii-against-anticoagulation-of-xa-inhibitor
#14
Nina Haagenrud Schultz, Hoa Thi Tuyet Tran, Stine Bjørnsen, Carola Elisabeth Henriksson, Per Morten Sandset, Pål Andre Holme
BACKGROUND: An increasing number of patients are treated with direct-acting oral anticoagulants (DOACs), but the optimal way to reverse the anticoagulant effect is not known. Specific antidotes are not available and prothrombin complex concentrate (PCC), activated PCC (aPCC) and recombinant factor VIIa (rFVIIa) are variously used as reversal agents in case of a major bleeding. We aimed to determine the most effective haemostatic agent and dose to reverse the effect of rivaroxaban in blood samples from patients taking rivaroxaban for therapeutic reasons...
2017: Thrombosis Journal
https://www.readbyqxmd.com/read/28230176/antithrombotic-therapy-for-patients-with-stemi-undergoing-primary-pci
#15
REVIEW
Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
Antithrombotic therapy, including antiplatelet and anticoagulant agents, is the cornerstone of pharmacological treatment to optimize clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Intravenous anticoagulant drugs available for PPCI include the indirect thrombin inhibitors unfractionated heparin and low-molecular-weight heparin, and the direct thrombin inhibitor bivalirudin. Intravenous antiplatelet drugs mainly include glycoprotein IIb/IIIa inhibitors and the P2Y12-receptor inhibitor cangrelor...
February 23, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28229819/dabigatran-aggravates-topoisomerase-i-peptide-loaded-dendritic-cells-induced-lung-and-skin-fibrosis
#16
Heena Mehta, Shunya Mashiko, Philippe-Olivier Goulet, Jade Desjardins, Gemma Pérez, Martial Koenig, Jean-Luc Senécal, Marika Sarfati
OBJECTIVES: Dysregulated coagulation cascade has been implicated in development of fibrosis in systemic sclerosis (SSc). Thrombin, a key mediator of the coagulation pathway, has both proinflammatory and procoagulant properties. Here, we evaluated the efficacy of oral dabigatran, a direct thrombin inhibitor, on topoisomerase I dendritic cells (TOPOIA DCs)-induced lung and skin fibrosis, an experimental model of SSc. METHODS: Mice were repeatedly immunized with TOPOIA DCs...
February 8, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28198201/clinical-implications-of-reversal-agents-for-direct-oral-anticoagulants
#17
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
#18
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
#19
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
#20
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
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