Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate.

Dabigatran is a direct thrombin inhibitor increasingly used for the prevention and treatment of thromboembolism. Although humanized antibody antidotes for dabigatran are under investigation, no specific antidote is currently available to reverse the anticoagulant effect of dabigatran in case of clinical bleeding. Several ex vivo and animal studies have assessed the efficacy of prothrombin complex concentrate (PCC) and recombinant factor VIIa (rFVIIa) with conflicting results.

In this study, Hoffman et al. used a cell-based model of haemostasis to test the hypothesis that both rFVIIa and a 4-factor PCC may be used to improve thrombin generation in the presence of dabigatran. In addition, this study aimed to correlate the results obtained using this model with haemostatic effects observed in a ‘new’ animal model, more sensitive to the effects of anticoagulants.

PCC reversed the effects of dabigatran on the rate, peak, and total amount of thrombin generated, but did not shorten the lag. In contrast, rFVIIa shortened the lag, increased the rate and the peak, but did not improve total thrombin generation. Interestingly, the effects of PCC were observed with both therapeutic and supratherapeutic concentrations of dabigatran, whereas the effects of rFVIIa decreased when dabigatran concentration increased.

In summary, although this study is interesting, PCC and rFVIIa cannot be considered as ‘optimal’ therapeutic options to reverse the anticoagulant effect of dabigatran in a bleeding context. Specific antidotes are urgently needed and we are waiting for the results of ongoing studies.

– David Faraoni

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