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Direct-thrombin inhibitors

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https://www.readbyqxmd.com/read/28737512/thrombin-promotes-diet-induced-obesity-through-fibrin-driven-inflammation
#1
Anna K Kopec, Sara R Abrahams, Sherry Thornton, Joseph S Palumbo, Eric S Mullins, Senad Divanovic, Hartmut Weiler, A Phillip Owens, Nigel Mackman, Ashley Goss, Joanne van Ryn, James P Luyendyk, Matthew J Flick
Obesity promotes a chronic inflammatory and hypercoagulable state that drives cardiovascular disease, type 2 diabetes, fatty liver disease, and several cancers. Elevated thrombin activity underlies obesity-linked thromboembolic events, but the mechanistic links between the thrombin/fibrin(ogen) axis and obesity-associated pathologies are incompletely understood. In this work, immunohistochemical studies identified extravascular fibrin deposits within white adipose tissue and liver as distinct features of mice fed a high-fat diet (HFD) as well as obese patients...
July 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28729433/selective-factor-viii-activation-by-the-tissue-factor-factor-viia-factor-xa-complex
#2
Yuichi Kamikubo, G Loredana Mendolicchio, Antonella Zampolli, Patrizia Marchese, Andrea S Rothmeier, Jennifer Nagrampa Orje, Andrew J Gale, Sriram Krishnaswamy, András Gruber, Henrik Østergaard, Lars C Petersen, Wolfram Ruf, Zaverio M Ruggeri
Safe and effective antithrombotic therapy requires understanding of mechanisms that contribute to pathological thrombosis but have lesser impact on hemostasis. We found that the extrinsic tissue factor (TF) coagulation initiation complex can selectively activate the anti-hemophilic cofactor, FVIII, triggering the hemostatic intrinsic coagulation pathway independently of thrombin feedback loops. In a mouse model with a relatively mild thrombogenic lesion, TF-dependent FVIII activation sets the threshold for thrombus formation through contact phase-generated FIXa...
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28704111/incomplete-dabigatran-reversal-with-idarucizumab
#3
Aaron P Steele, Jin A Lee, William E Dager
CONTEXT: With increasing use of direct oral anticoagulants (DOACs), urgent reversal of these agents becomes a growing concern. Idarucizumab is a humanized monoclonal antibody fragment that specifically binds to dabigatran with higher affinity than thrombin, rapidly neutralizing its anticoagulant effect without increased risk of thrombosis. CASE DETAILS: We describe two cases in which the recommended dose of idarucizumab was unsuccessful in completely reversing the anticoagulant effects of dabigatran...
July 13, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28703014/thrombin-receptor-agonist-peptide-induced-platelet-aggregation-is-reduced-in-patients-receiving-dabigatran
#4
Frantisek Nehaj, Juraj Sokol, Michal Mokan, Jela Ivankova, Maros Mokan
The availability of direct oral anticoagulants has caused a paradigm shift in thrombosis management. The direct thrombin inhibitor dabigatran seems to obstruct tenase complex by inhibiting thrombin generated in the initial phase and feed back to the amplification phase of cell-based coagulation reactions. However, it is still not fully understood if and how dabigatran impact platelet function. This observational study aimed to assess in vitro platelet function in patients with atrial fibrillation receiving dabigatran...
January 1, 2017: Clinical and Applied Thrombosis/hemostasis
https://www.readbyqxmd.com/read/28695302/argatroban-attenuates-diabetic-cardiomyopathy-in-rats-by-reducing-fibrosis-inflammation-apoptosis-and-protease-activated-receptor-expression
#5
Yogesh Bulani, Shyam Sunder Sharma
PURPOSE: Chronic diabetes is associated with cardiovascular dysfunctions. Diabetic cardiomyopathy (DCM) is one of the serious cardiovascular complications associated with diabetes. Despite significant efforts in understanding the pathophysiology of DCM, management of DCM is not adequate due to its complex pathophysiology. Recently, involvement of protease-activated receptors (PARs) has been postulated in cardiovascular diseases. These receptors are activated by thrombin, trypsin, or other serine proteases...
July 10, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28689334/safety-and-interactions-of-direct-oral-anticoagulants-with-antiarrhythmic-drugs
#6
REVIEW
Ipek Celikyurt, Christoph R Meier, Michael Kühne, Beat Schaer
Direct oral anticoagulants (DOACs) are novel direct-acting medications that are selective for either thrombin or activated factor X. Due to their obvious benefits for patients (fewer interactions, broader therapeutic window, etc.), they are increasingly used as an alternative to warfarin, phenprocoumon, or acenocoumarol. One of the major indications for use of DOACs is stroke prevention in patients with atrial fibrillation (AF). However, interactions still exist, especially in combination with antiarrhythmic drugs (AADs), which are frequently given to AF patients for rhythm or rate control...
July 8, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28671072/anticoagulant-activity-of-oral-rivaroxaban-in-healthy-dogs
#7
B Conversy, M C Blais, M Dunn, C Gara-Boivin, J R E Del Castillo
Rivaroxaban is an oral, direct factor Xa inhibitor used in human thrombotic disorders. In view of the in vitro concentration dependent anticoagulant effects of rivaroxaban in dogs, the time course of its anticoagulant effects was characterized in healthy dogs. Twenty-four healthy Beagles were randomized into three groups (n = 8 per group) and received orally either a placebo or 20 mg rivaroxaban once or twice at an 8 h interval. Fifteen blood samples were collected over a 30 h period, and blindly assayed for prothrombin time (PT), activated partial thromboplastin time (aPTT), tissue factor induced thrombin generation (TG) and anti-factor Xa activity...
May 2017: Veterinary Journal
https://www.readbyqxmd.com/read/28662704/thrombocytopenia-induced-by-dabigatran-two-case-reports
#8
Hyun Goo Kang, Seung Jae Lee, Ji Yeon Chung, Jin Sung Cheong
BACKGROUND: Vitamin K inhibitors (e.g. warfarin) and indirect thrombin inhibitors (e.g. heparin) are widely used to prevent thromboembolic disorders (e.g. myocardial infarction, venous thromboembolism, and stroke). These agents have been mainstays of anticoagulation for people older than 60 years. However, their administration is associated with a risk of bleeding and requires careful monitoring of patients. Novel oral anticoagulants (NOACs), such as dabigatran, are significantly safer in preventing thromboembolism than warfarin and heparin (sporadically causes thrombocytopenia) and are more specific for their target protein, thrombin...
June 29, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28652799/direct-oral-anticoagulants-in-patients-with-chronic-kidney-disease-patient-selection-and-special-considerations
#9
REVIEW
Jens Lutz, Kerstin Jurk, Helmut Schinzel
Many patients with chronic kidney disease (CKD) receive 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 (DOAC) inhibiting factor Xa or thrombin represent an alternative for VKAs. In patients with acute and chronic kidney disease, caution is warranted, as DOACs can accumulate as they are partly eliminated by the kidneys...
2017: International Journal of Nephrology and Renovascular Disease
https://www.readbyqxmd.com/read/28639463/adverse-drug-reactions-and-cutaneous-manifestations-associated-with-anticoagulation
#10
Trang T Vu, Melinda Gooderham
Anticoagulants are amongst the most commonly prescribed medications worldwide. Although rare, localised and systemic drug reactions have been reported with anticoagulants that can lead to significant morbidity and mortality. Some of the first signs of drug reactions to anticoagulants are cutaneous changes that, when recognised early, can prevent significant complications. Dermatologists should be aware of these changes to make an early and accurate diagnosis. This is particularly important in instances of skin-induced necrosis caused by systemic toxicity to anticoagulants...
June 1, 2017: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28635328/dietary-implications-for-patients-receiving-long-term-oral-anticoagulation-therapy-for-treatment-and-prevention-of-thromboembolic-disease
#11
Emmanouela Kampouraki, Farhad Kamali
The effectiveness of oral anticoagulation therapy with warfarin (a vitamin K antagonist) in the treatment of thromboembolic disease, including stroke prophylaxis in patients with atrial fibrillation is well recognised. However, warfarin has a narrow therapeutic window and an unpredictable anticoagulation response, which make it difficult to achieve and maintain optimal anticoagulation. Various dietary factors, including sudden changes in eating patterns, can significantly alter anticoagulation control, thereby potentially exposing patients to the risk of bleeding or thromboembolic complications...
June 26, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28604566/novel-oral-anticoagulants-in-the-peri-endoscopic-period
#12
Michael Genualdi, William H Frishman
Millions of patients in the United States are currently prescribed some form of anticoagulation therapy. Recently, novel oral anticoagulants (NOACs), including direct thrombin inhibitors and direct factor Xa inhibitors, have begun to replace warfarin as the drugs of choice for anticoagulation. As the use of these medications becomes more widespread, it is increasingly important for gastroenterologists to understand the risks associated with performing endoscopic procedures on patients who are taking NOACs. In this review, we provide an overview of the NOACs, as well as current guidelines from international societies regarding the management of patients scheduled to undergo endoscopic procedures who are prescribed these medications...
April 6, 2017: Cardiology in Review
https://www.readbyqxmd.com/read/28600720/comparisons-of-argatroban-to-lepirudin-and-bivalirudin-in-the-treatment-of-heparin-induced-thrombocytopenia-a-systematic-review-and-meta-analysis
#13
REVIEW
Zhengwu Sun, Xiaoyan Lan, Shen Li, Hongling Zhao, Zeyao Tang, Yalin Xi
To prevent thromboembolic events associated with heparin-induced thrombocytopenia (HIT), patients usually are treated with argatroban, lepirudin, and bivalirudin. Here, we conducted a meta-analysis of studies to comparing the treatment of HIT with the following direct thrombin inhibitor: argatroban versus lepirudin and argatroban versus bivalirudin. We systematically searched PubMed, Embase, and Cochrane Library database for relevant studies. The clinical outcomes were thromboembolic complication and bleeding...
June 9, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28598864/advances-in-vascular-thiol-isomerase-function
#14
Robert Flaumenhaft
PURPOSE OF REVIEW: The present review will provide an overview of several recent advances in the field of vascular thiol isomerase function. RECENT FINDINGS: The initial observation that protein disulfide isomerase (PDI) functions in thrombus formation occurred approximately a decade ago. At the time, there was little understanding regarding how PDI or other vascular thiol isomerases contribute to thrombosis. Although this problem is far from solved, the past few years have seen substantial progress in several areas that will be reviewed in this article...
June 8, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28585903/dabigatran-following-acute-transient-ischemic-attack-and-minor-stroke-ii-datas-ii
#15
Kuan H Ng, Mukul Sharma, Oscar Benavente, Laura Gioia, Thalia S Field, Michael D Hill, Shelagh B Coutts, Kenneth Butcher
Rationale Patients with transient ischemic attack or minor stroke are at high risk of early recurrent cerebrovascular events. Anticoagulation with heparin or warfarin acutely after ischemic stroke is at least as efficacious as aspirin for preventing recurrent events but is associated with an increased risk of clinical worsening due to hemorrhagic transformation. Aim and hypothesis We aim to demonstrate the safety of early anticoagulation with dabigatran, an oral direct thrombin inhibitor, in acute cerebrovascular syndrome patients...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/28585189/modulatory-role-of-nurr1-activation-and-thrombin-inhibition-in-the-neuroprotective-effects-of-dabigatran-etexilate-in-rotenone-induced-parkinson-s-disease-in-rats
#16
Esraa A Kandil, Rabab H Sayed, Lamiaa A Ahmed, Mai A Abd El Fattah, Bahia M El-Sayeh
Recently, it has been shown that both decreased nuclear receptor-related 1 (Nurr1) expression and thrombin accumulation are involved in the degeneration of dopaminergic neurons in Parkinson's disease (PD). The new anticoagulant dabigatran etexilate (DE) is a direct thrombin inhibitor that owns benzimidazole group, which has been proposed to activate Nurr1. In the present study, we examined the neuroprotective effects of DE in rotenone model of PD. Rotenone was injected subcutaneously at a dose of 1.5 mg/kg every other day for 21 days...
June 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28581998/controversies-in-the-management-of-st-elevation-myocardial-infarction-thrombin-inhibition
#17
REVIEW
Neeraj Shah, David Cox
Anticoagulation is essential in patients with ST elevation myocardial infarction (STEMI) to prevent further thrombosis and to maintain patency of the infarct-related artery after reperfusion. The various anticoagulant medications available for use in patients with STEMI include unfractionated heparin (UFH), low-molecular-weight heparin, fondaparinux, and bivalirudin, a direct thrombin inhibitor. The authors review the current anticoagulation strategies for patients with STEMI undergoing primary percutaneous coronary intervention (PCI), fibrinolysis, or no reperfusion...
October 2016: Interventional cardiology clinics
https://www.readbyqxmd.com/read/28581331/exploring-indications-for-the-use-of-direct-oral-anticoagulants-and-the-associated-risks-of-major-bleeding
#18
Truman J Milling, Jennifer Frontera
Thrombosis is a leading cause of morbidity and mortality in the United States. Arterial and venous thromboses are implicated in the pathogenesis of major disorders, including myocardial infarction, ischemic stroke, and venous thromboembolism. Over the past decade, direct oral anticoagulants (DOACs) (eg, direct thrombin inhibitor and factor Xa [FXa] inhibitors) have been adopted as alternatives to warfarin due to their clinical advantages and efficacy for the treatment of thrombosis. As with all anticoagulants, treatment with DOACs is associated with a risk of major bleeding, including life-threatening gastrointestinal bleeds and intracranial hemorrhages (ICHs)...
April 2017: American Journal of Managed Care
https://www.readbyqxmd.com/read/28580515/dabigatran-reduces-thrombin-induced-platelet-aggregation-and-activation-in-a-dose-dependent-manner
#19
Pernille Just Vinholt, Christian Nielsen, Anna Cecilia Söderström, Axel Brandes, Mads Nybo
Dabigatran is an oral anticoagulant and a reversible inhibitor of thrombin. Further, dabigatran might affect platelet function through a direct effect on platelet thrombin receptors. The aim was to investigate the effect of dabigatran on platelet activation and platelet aggregation. Healthy donor blood was incubated with dabigatran 0, 50, 500 ng/mL, corresponding to the therapeutic range of dabigatran peak plasma concentrations, and 10,000 ng/mL comprising a supra-therapeutic dabigatran plasma level. Platelet aggregation was tested with 96-well aggregometry...
August 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28565918/role-for-thrombin-receptor-antagonism-with-vorapaxar-in-secondary-prevention-of-atherothrombotic-events-from-bench-to-bedside
#20
Jae Youn Moon, Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo
In spite of treatment with the current standard of care antiplatelet regimens including dual antiplatelet therapy, recurrence rates of ischemic events remain elevated for high-risk patients with atherosclerotic disease. This may be in part attributed to the fact that other key platelet activation pathways remain uninhibited and can thus continue to trigger platelet activation and lead to thrombotic complications. Thrombin is a powerful inducer of platelet activation and mediates its effects directly on platelets through protease activator receptors (PARs), particularly the PAR-1 subtype, making PAR-1 inhibition an attractive approach for reducing atherothrombotic events...
January 1, 2017: Journal of Cardiovascular Pharmacology and Therapeutics
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