Reversal of apixaban induced alterations in haemostasis by different coagulation factor concentrates in patients after hip or knee replacement surgery.

BACKGROUND: Apixaban is a direct oral anticoagulant (DOAC) with a specific inhibition of activated factor X (FXa). In case of bleeding or need of urgent surgery a direct antidote is not yet available. Off-label application of non-specific haemostatic agents, such as prothrombin complex concentrate (PCC) and recombinant FVIIa (rFVIIa), has been reported to reverse the effects of apixaban in in vitro and animal studies. The aim of this study is to measure the reversal potential of PCC and rFVIIa in patients with prophylactic apixaban concentrations.

MATERIAL AND METHODS: Whole blood from patients under prophylactic therapy with apixaban was spiked with two doses of PCC or rFVIIa. Thromboelastometry (ROTEM® ), prothrombin time (PT), and activated partial prothrombin time (aPTT) were performed.

RESULTS: Prolongations in PT and aPTT were corrected by the different concentrates with variable efficacies (PCC<rFVIIa) for all time points after medication. Compared with baseline, the reversal effects ranged from partial correction (PCC) to overcorrection of the CT-ExTEM, PT and aPTT by rFVIIa.

DISCUSSION: PCC partially reverses the effect of apixaban as measured by point-of-care coagulation testing and standard coagulation tests. Only rFVIIa reliably reverses apixaban anticoagulation.