Recombinant activated factor VII and prothrombin complex concentrate did not reverse rivaroxaban-induced bleeding in a rabbit model, despite partially improving laboratory parameters.
RCT (n=48)
randomized
Does rFVIIa or PCC reduce blood loss in a rabbit model of rivaroxaban overdose?
In a rabbit model of rivaroxaban overdose, rFVIIa and PCC improved some laboratory coagulation parameters but failed to reverse actual blood loss.
BACKGROUND: As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis. METHODS: First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint. RESULTS: Rivaroxaban increased blood loss (17 g 8-32 vs. 7 g 5-18 for control (median range), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s 65-115 vs. 140 s 75-190, P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions. CONCLUSION: rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.
Godiér et al. (2011) conducted an RCT in rivaroxaban-induced bleeding and thrombosis (n=48). recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) vs. rivaroxaban and saline was evaluated on total amount of blood loss after 15 min following a hepatosplenic section. Recombinant activated factor VII and prothrombin complex concentrate did not reverse rivaroxaban-induced bleeding in a rabbit model, despite partially improving laboratory parameters.