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Dabigatran but not rivaroxaban or apixaban treatment decreases fibrinolytic resistance in patients with atrial fibrillation.
- Source :
-
Thrombosis research [Thromb Res] 2016 Feb; Vol. 138, pp. 22-29. Date of Electronic Publication: 2015 Dec 24. - Publication Year :
- 2016
-
Abstract
- Introduction: Most anticoagulants stimulate fibrinolysis in vitro through mechanisms dependent on and independent of thrombin activatable fibrinolysis inhibitor (TAFI). We evaluated the effect of dabigatran, rivaroxaban and apixaban treatment on plasma fibrinolysis in patients with non-valvular atrial fibrillation.<br />Methods and Results: Patients treated with dabigatran etexilate (n=22), rivaroxaban (n=24) or apixaban (n=22) were studied. Plasma was obtained before (trough) and 2h after drug intake (peak). Fibrinolytic resistance of clots exposed to exogenous tissue plasminogen activator was significantly lower in peak than in trough samples and correlated with drug concentration only in dabigatran group. Moreover, fibrinolytic resistance at peak was lower in dabigatran than in rivaroxaban and apixaban groups. This difference disappeared if the TAFI pathway was inhibited. Thrombin generation and TAFI activation were markedly lower in peak than in trough samples in all three groups. However, TAFIa levels in trough and peak samples were significantly lower in dabigatran group than in rivaroxaban and apixaban groups. Circulating levels of prothrombin fragment F1+2 (reflecting in vivo thrombin generation) and plasmin-antiplasmin complex (reflecting plasmin generation) were not or barely influenced by drug levels in all groups.<br />Conclusions: Our data suggest that dabigatran, contrary to rivaroxaban and apixaban, reduces fibrinolytic resistance by virtue of its greater impact on TAFI activation. The profibrinolytic effect of dabigatran may play a role locally, at sites of fibrin formation, by making the nascent thrombus more susceptible to plasminogen-dependent degradation.<br /> (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Subjects :
- Aged
Aged, 80 and over
Antithrombins therapeutic use
Atrial Fibrillation blood
Atrial Fibrillation metabolism
Carboxypeptidase B2 blood
Carboxypeptidase B2 metabolism
Factor Xa Inhibitors therapeutic use
Female
Humans
Male
Thrombin metabolism
Anticoagulants therapeutic use
Atrial Fibrillation drug therapy
Dabigatran therapeutic use
Fibrinolysis drug effects
Pyrazoles therapeutic use
Pyridones therapeutic use
Rivaroxaban therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1879-2472
- Volume :
- 138
- Database :
- MEDLINE
- Journal :
- Thrombosis research
- Publication Type :
- Academic Journal
- Accession number :
- 26826504
- Full Text :
- https://doi.org/10.1016/j.thromres.2015.12.023