Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects

Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an ant...

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Veröffentlicht in:Circulation (New York, N.Y.) Jg. 124; H. 14; S. 1573
Hauptverfasser: Eerenberg, Elise S, Kamphuisen, Pieter W, Sijpkens, Meertien K, Meijers, Joost C, Buller, Harry R, Levi, Marcel
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 04.10.2011
Schlagworte:
Adult
Anticoagulants - antagonists & inhibitors
Antidotes - pharmacology
Benzimidazoles - antagonists & inhibitors
beta-Alanine - analogs & derivatives
beta-Alanine - antagonists & inhibitors
Blood Coagulation - drug effects
Blood Coagulation Factors - pharmacology
Cross-Over Studies
Dabigatran
Double-Blind Method
Endopeptidases
Factor Xa Inhibitors
Humans
Male
Morpholines - antagonists & inhibitors
Partial Thromboplastin Time
Prothrombin Time
Rivaroxaban
Thiophenes - antagonists & inhibitors
Thrombin - antagonists & inhibitors
Thrombin Time
Young Adult
ISSN:1524-4539, 1524-4539
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Zusammenfassung:Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests. Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2272.
Bibliographie:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
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ISSN:1524-4539
1524-4539
DOI:10.1161/CIRCULATIONAHA.111.029017