Nina Haagenrud Schultz‘s PhD thesis contains in vitro-studies of potential reversal agents of the direct-acting oral anticoagulants rivaroxaban and apixaban.

(1/2) Rivaroxaban and apixaban provides anticoagulation by inhibiting activated factor X. Reversal agents of these direct-acting oral anticoagulants could be essential in case of a life-threatening bleeding, but are not yet available in Norway. Haagenrud Schultz and co-workers show that the effects of both apixaban and rivaroxaban are reversed with the activated prothrombin complex concentrate (aPCC) FEIBA® in lower doses than currently recommended.

FEIBA® proved more effective than recombinant factor VIIa and four-factor prothrombin complex concentrate in 50 rivaroxaban-treated and 30 apixaban-treated patients. Their blood samples were spiked with the three inhibitors at 80 %, 100 % and 125 % of suggested therapeutic doses. All doses of FEIBA® were equally effective.

(3) In a case-series of three patients in urgent need of heart surgery, FEIBA® had good hemostatic effect and reversed the effect of apixaban. The treatment reduced clotting time in all patients, and there were no bleeding complications during surgery. However, one of the patient experience bleeding after the operation.

(5/4) Rivaroxaban reduces plasminogen activator inhibitor (PAI-1), thus potentially increasing fibrinolytic activity. No other markers of fibrinolytic activity or endothelial activation were affected by the treatment. Rivaroxaban possibly also causes a reduction in P-selectin but does not influence platelet aggregation or von Willebrand factor.

The studies include twelve patients with venous thrombosis assigned to temporary rivaroxaban treatment, and blood was collected both during and after the treatment period.