ArticleJournal of thrombosis and haemostasis : JTH2014
Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo.
Article in Journal of thrombosis and haemostasis : JTH, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 66 citations in OpenAlex.
- Anticoagulants beyond coagulation: a narrative review of cardiovascular effects.Cardiovascular research · 2026Review
- Heparin and Direct Oral Anticoagulants have Different Effects on the Phases of Activation and Spatial Spread of Blood Coagulation.Thrombosis and haemostasis · 2026Article
- Fibrinography and thrombography (thrombodynamics-4D) in atrial fibrillation assessment of direct oral anticoagulants in geriatrics patients aged 80 years and older receiving direct oral anticoagulant therapy.Research and practice in thrombosis and haemostasis · 2025Article
- Anticoagulation management for cardiopulmonary bypass using TEG® 6 s in a patient receiving both heparin and dabigatran.JA clinical reports · 2024Article
- Autoimmune Heparin-Induced Thrombocytopenia.Journal of clinical medicine · 2023Review
- Heparin-induced thrombocytopenia (and autoimmune heparin-induced thrombocytopenia): an illustrious review.Research and practice in thrombosis and haemostasis · 2023Article
- Comparison of the efficacy and safety between rivaroxaban and dabigatran in the treatment of acute portal vein thrombosis in cirrhosis.BMC gastroenterology · 2023Article
- Distinct pleiotropic effects of direct oral anticoagulants on cultured endothelial cells: a comprehensive review.Frontiers in pharmacology · 2023Review
- Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits.Open life sciences · 2022Article
- Different DOACs Control Inflammation in Cardiac Ischemia-Reperfusion Differently.Circulation research · 2021Article
- Contradictory to its effects on thrombin, C1-inhibitor reduces plasmin generation in the presence of thrombomodulin.Journal of thrombosis and thrombolysis · 2019Article
- Enoxaparin pretreatment effect on local and systemic inflammation biomarkers in the animal burn model.Inflammopharmacology · 2019Article
- New versus Old Oral Anticoagulants: How Can We Set the Scale Needle? Considerations on a Case Report.Medicina (Kaunas, Lithuania) · 2019Article
- Large Left Ventricular Thrombus as a Cause of Recurrent Cardioembolic Stroke While on Dabigatran.CASE (Philadelphia, Pa.) · 2018Article
- The Effects of Dabigatran and Rivaroxaban on Markers of Polymorphonuclear Leukocyte Activation.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Thrombin Receptor Agonist Peptide-Induced Platelet Aggregation Is Reduced in Patients Receiving Dabigatran.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis · 2018Observational
- Impact of Non-vitamin K Antagonist Oral Anticoagulant Withdrawal on Stroke Outcomes.Frontiers in neurology · 2018Article
- Direct Oral Anticoagulants Form Thrombus Different From Warfarin in a Microchip Flow Chamber System.Scientific reports · 2017Article
- A new measure for in vivo thrombin activity in comparison with in vitro thrombin generation potential in patients with hyper- and hypocoagulability.Clinical and experimental medicine · 2017Article
- Dabigatran and rivaroxaban do not affect AA- and ADP-induced platelet aggregation in patients receiving concomitant platelet inhibitors.Journal of thrombosis and thrombolysis · 2016Observational
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIncreased hypercoagulability has been reported with low doses of direct thrombin inhibitors but not with direct factor Xa inhibitors.
objectivesTo compare the effects of rivaroxaban with those of melagatran and dabigatran on thrombin generation (TG) and tissue factor-induced hypercoagulability and to explore the possible involvement of the thrombin-thrombomodulin/activated protein C system.
methodsIn normal human plasma and in protein C-deficient plasma, TG was investigated in vitro in the presence and absence of recombinant human soluble thrombomodulin (rhs-TM). TG was determined by calibrated automated thrombography and an ELISA for prothrombin fragments 1+2 (F1+2 ). In an in vivo rat model, hypercoagulability was induced by tissue factor; levels of thrombin-antithrombin (TAT) and fibrinogen and the platelet count were determined.
resultsRivaroxaban inhibited TG in a concentration-dependent manner. In the absence of rhs-TM, melagatran and dabigatran also inhibited TG concentration dependently. However, in the presence of rhs-TM, lower concentrations of melagatran (119-474 nmol L(-1) ) and dabigatran (68-545 nmol L(-1) ) enhanced endogenous thrombin potential, peak TG, and F1+2 formation in normal plasma but not in protein C-deficient plasma. In vivo, rivaroxaban dose-dependently inhibited TAT generation, whereas melagatran showed a paradoxical effect, with an increase in TAT and a small decrease in fibrinogen and platelet count at lower doses.
conclusionLow concentrations of the direct thrombin inhibitors melagatran and dabigatran enhanced TG and hypercoagulability, possibly via inhibition of the protein C system. In contrast, rivaroxaban reduced TG and hypercoagulability under all conditions studied, suggesting that it does not suppress this negative-feedback system.
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