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oral 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/29741099/economic-evaluation-of-prescribing-conventional-and-newer-oral-anticoagulants-in-older-adults
#2
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
#3
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/29704172/a-direct-oral-factor-xa-inhibitor-edoxaban-ameliorates-neointimal-hyperplasia-following-vascular-injury-and-thrombosis-in-apolipoprotein-e-deficient-mice
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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/29566413/rivaroxaban-a-new-treatment-paradigm-in-the-setting-of-vascular-protection
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/29486103/screening-test-for-direct-oral-anticoagulants-with-the-dilute-russell-viper-venom-time
#16
Jackie Pratt, Philip Crispin
OBJECTIVES: To evaluate the dilute Russell viper venom time (DRVVT) for the detection of direct-acting oral anticoagulants (DOACs) and to investigate the effect of DOACS on coagulation assays. METHODS: Patients with DOACs and controls had plasma levels determined by an anti-Xa assay and dilute thrombin clotting time (TCT). Levels were correlated with the DRVVT as well as TCT, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen, protein C, protein S and antithrombin levels...
February 27, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29478266/treatment-for-superficial-thrombophlebitis-of-the-leg
#17
REVIEW
Marcello Di Nisio, Iris M Wichers, Saskia Middeldorp
BACKGROUND: The optimal treatment of superficial thrombophlebitis (ST) of the legs remains poorly defined. While improving or relieving the local painful symptoms, treatment should aim at preventing venous thromboembolism (VTE), which might complicate the natural history of ST. This is the third update of a review first published in 2007. OBJECTIVES: To assess the efficacy and safety of topical, medical, and surgical treatments for ST of the leg in improving local symptoms and decreasing thromboembolic complications...
February 25, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29459207/a-small-group-of-sulfated-benzofurans-induces-steady-state-submaximal-inhibition-of-thrombin
#18
Daniel K Afosah, Stephen Verespy, Rami A Al-Horani, Rio S Boothello, Rajesh Karuturi, Umesh R Desai
Despite the development of promising direct oral anticoagulants, which are all orthosteric inhibitors, a sizable number of patients suffer from bleeding complications. We have hypothesized that allosterism based on the heparin-binding exosites presents a major opportunity to induce sub-maximal inhibition of coagulation proteases, thereby avoiding/reducing bleeding risk. We present the design of a group of sulfated benzofuran dimers that display heparin-binding site-dependent partial allosteric inhibition of thrombin against fibrinogen (ΔY = 55-75%), the first time that a small molecule (MW  < 800) has been found to thwart macromolecular cleavage by a monomeric protease in a controlled manner...
April 1, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29378360/activated-factor-x-based-versus-thrombin-based-antithrombin-testing-in-thrombophilia-workup-in-the-doac-era
#19
Heiko Rühl, Sara Reda, Jens Müller, Johannes Oldenburg, Bernd Pötzsch
Antithrombin (AT) activity tests are used for diagnosing hereditary AT deficiency, a main genetic determinant of thrombophilia. They are either based on inhibition of thrombin (FIIa) or activated factor X (FXa). FXa-based assays have been suggested to be preferable to FIIa-based assays due to their higher sensitivity for certain AT deficiency causing mutations. To assess the performance of these two methods in a real-world scenario, 745 consecutively collected samples from patients referred to our institute during a 3-month period for thrombophilia testing were analysed...
February 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29360845/non-vitamin-k-antagonist-oral-anticoagulants-versus-warfarin-for-the-prevention-of-spontaneous-echo-contrast-and-thrombus-in-patients-with-atrial-fibrillation-or-flutter-undergoing-cardioversion-a-trans-esophageal-echocardiography-study
#20
Yun Gi Kim, Jong-Il Choi, Mi-Na Kim, Dong-Hyuk Cho, Suk-Kyu Oh, Hyungdon Kook, Hee-Soon Park, Kwang No Lee, Yong-Soo Baek, Seung-Young Roh, Jaemin Shim, Seong-Mi Park, Wan Joo Shim, Young-Hoon Kim
Spontaneous echo-contrast (SEC) and thrombus observed in trans-esophageal echocardiography (TEE) is known as a strong surrogate marker for future risk of ischemic stroke in patients with atrial fibrillation (AF) or atrial flutter (AFL). The efficacy of non-vitamin K antagonist oral anticoagulants (NOAC) compared to warfarin to prevent SEC or thrombus in patients with AF or AFL is currently unknown. AF or AFL patients who underwent direct current cardioversion (DCCV) and pre-DCCV TEE evaluation from January 2014 to October 2016 in a single center were analyzed...
2018: PloS One
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