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Direct-thrombin inhibitors

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https://www.readbyqxmd.com/read/29758017/the-effects-of-dabigatran-and-rivaroxaban-on-markers-of-polymorphonuclear-leukocyte-activation
#1
Guy A Richards, Annette Theron, Gregory Tintinger, Ronald Anderson
Dabigatran is an oral direct thrombin inhibitor, and rivaroxaban, a factor Xa inhibitor. Dabigatran has been implicated in the etiology of acute coronary syndromes and as these occur following inflammatory changes in the endothelium, we investigated the inflammatory potential of these agents in vitro. In order to do so, polymorphonuclear leukocytes (PMNL) were isolated from heparinized venous blood from non-smoking, healthy adults and exposed to dabigatran or rivaroxaban (0.5⁻10 µM). Generation of reactive oxygen species (ROS), elastase release, cytosolic Ca2+ fluxes, neutrophil extracellular trap (NET) formation and cell viability were measured using chemiluminescence, spectrophotometric and flow cytometric procedures respectively...
May 14, 2018: Pharmaceuticals
https://www.readbyqxmd.com/read/29744595/synthesis-and-biocompatibility-of-an-argatroban-modified-polysulfone-membrane-that-directly-inhibits-thrombosis
#2
Xiao Fu, Jian-Ping Ning
Anticoagulation therapy plays a vital role in the prevention of blood clot formation during hemodialysis and hemofiltration, especially for critical care patients. Here, we synthesized a novel argatroban (Arg)-modified polysulfone (PSf) membrane for anticoagulation. Arg was grafted onto the PSF membrane via chemical modification to increase membrane hydrophilicity. Protein adsorption, coagulation, as well as activation of platelets and complement systems were greatly reduced on the Arg-modified PSf membrane...
May 9, 2018: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/29741099/economic-evaluation-of-prescribing-conventional-and-newer-oral-anticoagulants-in-older-adults
#3
Syed Shahzad Hasan, Chia Siang Kow, Louise E Curley, Darrin L Baines, Zaheer-Ud-Din Babar
Anticoagulants refer to a variety of agents that inhibit one or more steps in the coagulation cascade. Generally, clinical conditions that require the prescribing of an oral anticoagulant increase in frequency with age. However, a major challenge of anticoagulation use among older patients is that this group of patients also experience the highest bleeding risk. To date, economic evaluation of prescribing of anticoagulants that includes the novel or newer oral anticoagulants (NOACs) in older adults has not been conducted and is warranted...
May 9, 2018: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/29735342/dabigatran-reduces-endothelial-permeability-through-inhibition-of-thrombin-induced-cytoskeleton-reorganization
#4
Hyun-Jung Choi, Na-Eun Kim, Jayoung Kim, Sunho An, Seung-Hee Yang, Jimin Ha, Sunghee Cho, Il Kwon, Young Dae Kim, Hyo Suk Nam, Ji Hoe Heo
Dabigatran etexilate (DE), a new oral anti-coagulant, is a direct thrombin inhibitor. Clinical trials showed the favorable benefit-to-risk profile of DE compared to warfarin for the prevention of ischemic stroke in patients with atrial fibrillation. Remarkably, patients treated with dabigatran showed reduced rates of intracerebral hemorrhage compared to warfarin. As the breakdown of endothelial barrier integrity is associated with hemorrhagic events and as thrombin increases endothelial permeability, we hypothesized that dabigatran preserves the endothelial barrier by inhibiting thrombin-induced permeability...
April 25, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29707901/argatroban-is-stable-in-citrated-whole-blood-for-24-hours
#5
S Guy, S Kitchen, J J Van Veen
INTRODUCTION: Argatroban is a direct thrombin inhibitor used as an anticoagulant for patients who have Heparin induced thrombocytopenia. Quantification can be performed using a dilute thrombin time or anti-iia assay. Our preferred method is Hemoclot Thrombin Inhibitor Assay (HTI).To the best of our knowledge, no one has published on the stability of plasma argatroban in whole citrated blood at room temperature. METHODS: Forty matched samples obtained from 4 patients receiving argatroban...
April 29, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29704172/a-direct-oral-factor-xa-inhibitor-edoxaban-ameliorates-neointimal-hyperplasia-following-vascular-injury-and-thrombosis-in-apolipoprotein-e-deficient-mice
#6
Yoshiyuki Morishima, Yuko Honda
Vascular injury activates the coagulation cascade. Some studies report that coagulation factor Xa and thrombin are implicated in proliferation of vascular smooth muscle cells and neointimal hyperplasia after vascular injury. The aim of this study was to determine the effect of an oral direct factor Xa inhibitor, edoxaban, on neointimal hyperplasia following the carotid artery injury in apolipoprotein E (ApoE)-deficient mice. Vascular injury was induced by the application of 10% ferric chloride to the carotid artery for 3 min in ApoE-deficient mice...
April 27, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29703471/the-intersection-of-protein-disulfide-isomerase-and-cancer-associated-thrombosis
#7
Jack D Stopa, Jeffrey I Zwicker
The mechanisms underlying the hypercoagulability of cancer are complex and include the upregulation coagulation factors or procoagulant proteins, shedding of microparticles, and direct activation of vascular cells. Protein disulfide isomerase (PDI) is a thiol isomerase secreted from activated platelets and endothelial cells and plays a critical role in both platelet aggregation and fibrin generation. A number of potential intravascular targets of PDI have been identified including cell surface receptors (e...
April 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29695165/pharmacokinetics-pharmacodynamics-of-dabigatran-75-mg-twice-daily-in-patients-with-nonvalvular-atrial-fibrillation-and-severely-impaired-renal-function
#8
Jack L Martin, Habib Esmaeili, Raymond C Manuel, Michaela Petrini, Sabrina Wiebe, Hugo Maas
INTRODUCTION: Dabigatran etexilate is an oral direct thrombin inhibitor. Dabigatran excretion is 80% renal, so exposure increases with severity of renal failure. The US Food and Drug Administration-approved dabigatran etexilate 75 mg twice daily (BID) for patients with nonvalvular atrial fibrillation (NVAF) having severely impaired renal function (creatinine clearance: 15-30 mL/min), based on post hoc pharmacokinetic modeling. We assessed dabigatran exposure at trough and peak levels in patients with NVAF and severely impaired renal function and compared with model predictions...
January 1, 2018: Journal of Cardiovascular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29692238/advances-in-the-development-of-novel-factor-xa-inhibitors-a-patent-review
#9
Atul N Khadse, Mayank Kumar Sharma, Prashant R Murumkar, Sadhana J Rajput, Mange Ram Yadav
Development of new anticoagulants has been in constant demand throughout the world due to increasing rate of morbidity and mortality caused by thrombotic diseases. Factor Xa (FXa), one of the enzymes and validated target for anticoagulation, regulates the production of thrombin in the coagulation cascade. The importance of oral FXa inhibitors like rivaroxaban, apixaban and edoxaban in thromboembolic conditions is well supported by increasing number of patents and research publications during the recent years...
April 24, 2018: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/29672182/oral-anticoagulant-use-in-cardiovascular-disorders-a-perspective-on-present-and-potential-indications-for-rivaroxaban
#10
A John Camm, Keith A A Fox
BACKGROUND: Four nonvitamin K antagonist oral anticoagulants (NOACs) have been approved for use in various cardiovascular indications. The direct thrombin inhibitor dabigatran and the direct factor Xa inhibitors apixaban, edoxaban, and rivaroxaban are now increasingly used in clinical practice. For some of these agents, available data from real-world studies support the efficacy and safety data in phase III clinical trials. OBJECTIVES: This review aims to summarize the current status of trials and observational studies of oral anticoagulant use over the spectrum of cardiovascular disorders (excluding venous thrombosis), provide a reference source beyond stroke prevention for atrial fibrillation (AF) and examine the potential for novel applications in the cardiovascular field...
April 19, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29657252/periprocedural-complications-in-patients-undergoing-catheter-ablation-of-atrial-fibrillation-without-discontinuation-of-a-vitamin-k-antagonist-and-direct-oral-anticoagulants
#11
Toshiya Kojima, Katsuhito Fujiu, Nobuaki Fukuma, Hiroshi Matsunaga, Tsukasa Oshima, Jun Matsuda, Takumi Matsubara, Yu Shimizu, Gaku Oguri, Eriko Hasumi, Hiroyuki Morita, Issei Komuro
BACKGROUND: Periprocedural anticoagulation is important in catheter ablation (CA) of atrial fibrillation (AF) and there is increasing evidence that uninterrupted vitamin K antagonist (VKA) therapy is superior to interrupted anticoagulation strategies. Since the emergence of direct oral anticoagulants (DOACs), numerous studies have shown promising results for their use in uninterrupted strategies. However, further studies are needed to further define the efficacy and safety of performing AF ablation with uninterrupted factor XA inhibitors or direct thrombin inhibitors...
April 13, 2018: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/29622761/simultaneous-pancreas-kidney-transplantation-in-a-patient-with-heparin-induced-thrombocytopenia-on-dabigatran-therapy
#12
Agnieszka Jóźwik, Wojciech Lisik, Jarosław Czerwiński, Maciej Kosieradzki
BACKGROUND New oral anticoagulants like direct thrombin inhibitors are an attractive alternative to vitamin K antagonists as anticoagulation therapy and can be used in heparin-induced thrombocytopenia. They are convenient in low-risk surgery, as there is no need for bridging with heparins. Patients who need urgent major surgery are at similar risk as on warfarin therapy, which, however, is much higher than in elective procedures. Due to their elimination profiles, these drugs are generally contraindicated in patients with severe renal insufficiency...
April 6, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
https://www.readbyqxmd.com/read/29614521/targeting-coagulase-activity-in-staphylococcus-aureus-bacteraemia-a-randomized-controlled-single-centre-trial-of-staphylothrombin-inhibition
#13
Marijke Peetermans, Laurens Liesenborghs, Kathelijne Peerlinck, Eric Van Wijngaerden, Olivier Gheysens, Karolien E Goffin, Marc F Hoylaerts, Marc Jacquemin, Jan Verhaegen, Willy E Peetermans, Peter Verhamme, Thomas Vanassche
BACKGROUND:   Staphylococcus aureus ( S. aureus ) bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by S. aureus initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs). DTIs inhibit the coagulase-prothrombin complex, or staphylothrombin, and improve outcome in preclinical models of S. aureus infection...
April 3, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29611444/combination-oral-antithrombotic-therapy-for-the-treatment-of-myocardial-infarction-recent-developments
#14
Udaya S Tantry, Eliano P Navarese, Aung Myat, Rahul Chaudhary, Paul A Gurbel
There have been significant new developments in the treatment of patients with myocardial infarction with respect to oral antithrombotic agents over the past decade. Recent studies have explored the potential utility of targeting the dual pathway inhibition of platelet function with single or dual antiplatelet agents and the thrombin pathway with direct thrombin inhibitors or factor Xa inhibitors. Areas covered: In this review, the authors focus on the recent developments of oral antithrombotic agents including antiplatelet and antithrombin agents...
April 3, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29605959/heparin-induced-thrombocytopenia-in-infants-after-heart-surgery
#15
Juma N Abdillah, Qinghua Hu, Xuliang Chen, Xing Chen, Wu Zhou, Wanjun Luo, Lingjin Huang
BACKGROUND:  Heparin-induced thrombocytopenia (HIT) in infants is a rare disorder, and the diagnosis and management of HIT still remains challenging. Argatroban is a synthetic direct thrombin inhibitor (DTI) that is widely used for treating HIT. However, little is known about the efficacy of the activated clotting time (ACT) test in monitoring DTI treatment as an alternative to the routinely used activated partial thromboplastin time (aPTT). METHODS:  Between July 2013 and January 2015, four infants were diagnosed with HIT after surgical correction of congenital anomalies...
April 1, 2018: Thoracic and Cardiovascular Surgeon
https://www.readbyqxmd.com/read/29574610/platelet-response-to-direct-thrombin-inhibitor-or-fondaparinux-treatment-in-patients-with-suspected-heparin-induced-thrombocytopenia
#16
Tiffany K Pon, Anjlee Mahajan, Aaron Rosenberg, Alpesh Amin, Digish Shah, Ian Jenkins, Vineet Gupta, Heather Hofmann, Anthony Bejjani, Richard White
Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT...
March 24, 2018: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/29573340/the-adsorption-of-dabigatran-is-as-efficient-as-addition-of-idarucizumab-to-neutralize-the-drug-in-routine-coagulation-assays
#17
M Jacquemin, J Toelen, L Feyen, J Schoeters, I Van Horenbeeck, I Vanlinthout, M Debasse, T Vanassche, K Peerlinck, P Verhamme
INTRODUCTION: The direct thrombin inhibitor dabigatran interferes with thrombophilia screening and with the diagnosis of hemostasis disorders that develop during treatment with the anticoagulant. In vitro addition of idarucizumab, a humanized antibody fragment that binds dabigatran, to plasma samples containing dabigatran fully neutralizes the drug. This study was carried out to determine whether binding of dabigatran on selected insoluble commercial adsorbent material, DOAC-STOPR , was as efficient as idarucizumab to neutralize the anticoagulant activity of the drug in vitro...
March 24, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29566413/rivaroxaban-a-new-treatment-paradigm-in-the-setting-of-vascular-protection
#18
Rupert Bauersachs, Faiez Zannad
The pathophysiology of atherosclerosis involves a diseased endothelium, lipid accumulation and low-grade inflammation. In later stages of coronary artery disease (CAD) and peripheral arterial disease (PAD), plaque rupture may induce atherothrombosis caused by fibrin formation and platelet activation, leading to vessel occlusion with subsequent organ damage such as myocardial infarction, stroke or limb ischaemia. Because of the high disease burden associated with CAD and PAD, there is a need for continuous vascular protection beyond currently available treatments including antiplatelet agents...
March 22, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29514375/venous-thromboembolism-prophylaxis-after-total-knee-arthroplasty
#19
Hayden N Box, Sean Shahrestani, Michael H Huo
Venous thromboembolic disease (VTED) is a major cause of morbidity and mortality after total knee arthroplasty (TKA). Current VTED prophylaxis protocols consist of early mobilization, mechanical compression devices, and pharmacologic agents. Venous phasic flow-regulated below-knee devices are generally favored, but the optimal duration and method of mechanical prophylaxis is unknown. Risk stratification models have been developed to guide pharmacologic prophylaxis. For patients with standard VTED risk profile, aspirin has become increasingly popular...
March 7, 2018: Journal of Knee Surgery
https://www.readbyqxmd.com/read/29488150/stroke-prevention-with-oral-anticoagulants-summary-of-the-evidence-and-efficacy-measures-as-an-aid-to-treatment-choices
#20
REVIEW
José Francisco Kerr Saraiva
Atrial fibrillation (AF) is an established risk factor for a first or recurrent stroke. Despite proven efficacy in preventing stroke in patients with AF, warfarin is underused, partly due to safety concerns. Recent randomized trials have shown that non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) and apixaban, edoxaban, and rivaroxaban (factor Xa inhibitors) are not only non-inferior or superior to warfarin but also demonstrate a decreased risk of cerebrovascular bleeding among patients with AF and moderate to high risk of stroke...
February 27, 2018: Cardiology and Therapy
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