Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate: A Sonoclot in vitro study

Abstract

Objective. Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring the coagulation process in whole blood. The aim of this study was to investigate the effect of dabigatran and reversal with PCC and rFVIIa, as monitored by the Sonoclot. Methods. Citrated whole blood was drawn and mixed in vitro with dabigatran, dabigatran + PCC or dabigatran + rFVIIa and analyzed with three different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated. Results. The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC we used. There was no certain reversing effect of rFVIIa. Conclusions. The Sonoclot can detect the anticoagulant effect of dabigatran. Our results do not support efficient reversal of dabigatran with PCC and rFVIIa, or alternatively do not support the ability of Sonoclot to detect a reversing effect of the PCC and rFVIIa in our study. Clinical studies of dabigatran-treated patients with severe bleeding are called for, as well as the continued development of specific antidotes and monitoring techniques.

Key Words::

• Antithrombins
• blood coagulation factors
• blood coagulation tests
• factor VII
• hemorrhage
• thrombelastography

Acknowledgements

Dabigatran was kindly provided by Boehringer Ingelheim Pharma GmbH & Co. This research was partly funded by Gross. L. F. Foghts Fond, Broedrene Hartmann Fonden and Aase and Ejner Danielsens Fond.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.