Key result
Recombinant factor VIIa, activated prothrombin complex concentrates, and prothrombin complex concentrates variably reversed apixaban-induced alterations in hemostasis in vitro, with rFVIIa significantly reducing prolonged clotting times from 357.9 to 95.1 seconds.
Why the study?
Does the addition of rFVIIa, aPCCs, or PCCs reverse apixaban-induced alterations in hemostasis in human blood in vitro?
Does the addition of rFVIIa, aPCCs, or PCCs reverse apixaban-induced alterations in hemostasis in human blood in vitro?
In vitro, rFVIIa, PCCs, and aPCCs have the potential to variably restore platelet and fibrin components of hemostasis altered by apixaban, suggesting potential reversal strategies.
Answers are grounded in this paper and cite their sources.
Does not support clinical use of these agents for apixaban reversal; leaves open need for human in vivo confirmation.
Apixaban is a new oral anticoagulant with a specific inhibitory action on FXa. No information is available on the reversal of the antihemostatic action of apixaban in experimental or clinical settings. We have evaluated the effectiveness of different factor concentrates at reversing modifications of hemostatic mechanisms induced by moderately elevated concentrations of apixaban (200 ng/ml) added in vitro to blood from healthy donors (n = 10). Effects on thrombin generation (TG) and thromboelastometry (TEM) parameters were assessed. Modifications in platelet adhesive, aggregating and procoagulant activities were evaluated in studies with blood circulating through damaged vascular surfaces, at a shear rate of 600 s(-1). The potential of prothrombin complex concentrates (PCCs; 50 IU/kg), activated prothrombin complex concentrates (aPCCs; 75 IU/kg), or activated recombinant factor VII (rFVIIa; 270 μg/kg), at reversing the antihemostatic actions of apixaban, were investigated. Apixaban interfered with TG kinetics. Delayed lag phase, prolonged time to peak and reduced peak values, were improved by the different concentrates, though modifications in TG patterns were diversely affected depending on the activating reagents. Apixaban significantly prolonged clotting times (CTs) in TEM studies. Prolongations in CTs were corrected by the different concentrates with variable efficacies (rFVIIa≥aPCC>PCC). Apixaban significantly reduced fibrin and platelet interactions with damaged vascular surfaces in perfusion studies (p<0.05 and p<0.01, respectively). Impairments in fibrin formation were normalized by the different concentrates. Only rFVIIa significantly restored levels of platelet deposition. Alterations in hemostasis induced by apixaban were variably compensated by the different factor concentrates investigated. However, effects of these concentrates were not homogeneous in all the tests, with PCCs showing more efficacy in TG, and rFVIIa being more effective on TEM and perfusion studies. Our results indicate that rFVIIa, PCCs and aPCCs have the potential to restore platelet and fibrin components of the hemostasis previously altered by apixaban.
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Escolar et al. (2013) studied Healthy donors (in vitro apixaban reversal) (n=10). Coagulation factor concentrates (rFVIIa, aPCC, PCC) vs. Apixaban 200 ng/mL alone was evaluated on Clotting time (CT) in ROTEM (seconds) (p=<0.01). Recombinant factor VIIa, activated prothrombin complex concentrates, and prothrombin complex concentrates variably reversed apixaban-induced alterations in hemostasis in vitro, with rFVIIa significantly reducing prolonged clotting times from 357.9 to 95.1 seconds.
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