Sunday, May 25, 2014

Reversal of Dabigatran-induced Bleeding by Coagulation Factor Concentrates in a Rat-tail Bleeding Model and Lack of Effect on Assays of Coagulation

van Ryn, Joanne Ph.D.; Schurer, Johanna; Kink-Eiband, Monika; Clemens, Andreas M.D.
Dabigatran resulted in an approximately three-fold increase in bleeding time, consistent with supratherapeutic dabigatran plasma levels. Beriplex (35 and 50 IU/kg), Octaplex (40 IU/kg), Profilnine (50 IU/kg), Bebulin (60 IU/kg), Factor Eight Inhibitor Bypassing Activity (100 U/kg), and NovoSeven (500 μg/kg) significantly decreased this prolonged bleeding time over 30 min (P < 0.001). The coagulation assays were prolonged three- to eight-fold over baseline (P = 0.01). None of the CFCs produced a consistent change in these assays that was predictive of reduced bleeding. Thrombin generation reversal was dependent on the concentration of dabigatran and each CFC; normalization occurred at the lower concentration of dabigatran with most CFCs, but not at higher concentrations.
Conclusions: In this animal model, bleeding induced by high doses of dabigatran can be reduced by CFCs. However, routine coagulation assays do not predict this effect.

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