The number of patients on antithrombotic treatment due to
atrial fibrillation and
venous thromboembolism is increasing fast due to an aging population. A growing proportion will be treated with novel oral
anticoagulants, the first in clinical use was the direct oral
thrombin inhibitor
dabigatran (Pradaxa®). A small percentage of the patients on
dabigatran will experience serious
bleeding or be in need of urgent surgery. The aim of this study was to test the effects of different
hemostatic agents in potentially reversing the
anticoagulant effects in vitro in blood or platelet-rich plasma (PRP) spiked with
dabigatran. Whole blood or PRP was spiked with the active substance
dabigatran, 200 μg/L. We measured clotting time being induced by 1.4 pmol/L
tissue factor using the instrument ReoRox2™ and initial clot growth velocity from a
tissue factor covered surface using the instrument Thrombodynamics Analyzer T-2™.
Dabigatran prolonged clotting time 5-fold but reduced clot growth velocity only slightly. The reversing effects of
prothrombin complex concentrates (PCC), activated PCC (APCC) and recombinant
activated factor VII (
rFVIIa) were then tested. APCC (1.8 U/mL) reduced the prolonged clotting time by 1/3,
rFVIIa (2 μg/L) only slightly (n = 10-20). The reduction was not significant using Mann-Whitney test but significant using t-test with Bonferronis' correction for multiple comparisons, whereas PCC (0.56 U/mL) had no effect on clotting time. APCC doubled initial clot growth velocity, although even more in the absence of
dabigatran. In conclusion, APCC and
rFVIIa, but not PCC, seem to reverse, at least partially, some effects of
dabigatran on coagulation parameters. Systematic evaluation of case reports, registries and, ultimately, randomized clinical trials are needed to elucidate potential benefit for patients.