Use of the Thrombin Generation Test to Evaluate Response to Treatment With Recombinant Activated Factor VII

Abstract

F l i ( ecombinant activated factor VII (rFVIIa; NovoSeven®, Novo Nordisk, Bagsvaerd, Denmark) represents an effecive treatment for hemophilia patients with inhibitors. Howver, there is no consensus on the optimal dosing regimen. sing the recommended dose of 90 g/kg, hemostatic effiacy is obtained in 85% of cases. The efficacy and safety of a ingle high dose of rFVIIa (270 g/kg) also have been demnstrated.1–3 As the final product generated by rFVIIa is hrombin, the thrombin generation test (TGT) could theoretcally be used to monitor individual responses to rFVIIa by ach hemophilia patient with an inhibitor. In this study, we assessed the role of TGT in monitoring he response to rFVIIa in three patients with severe hemohilia A with an inhibitor. Thrombin generation (TG) curves ere obtained in platelet-poor plasma (PPP) and platelet-rich lasma (PRP) samples spiked in vitro with rFVIIa at doses of 5, 90, 120, 160, 200, 240, and 270 g/kg. The ex vivo TG apacity was measured before and 15 minutes, 1 hour, and 2 ours after the infusion of a therapeutic dose of rFVIIa. The in vitro results showed that the addition of rFVIIa ose-dependently increased TG capacity. The comparison of n vitro and ex vivo results suggested that in vitro TG spiking xperiments could be helpful in predicting the individual inimal effective dose of rFVIIa. The ex vivo results showed n important increase in TG capacity following an injection f rFVIIa with a variable rate of correction in the three paients studied. These data are in agreement with clinical nowledge showing an individual response to rFVIIa. In adition, our results clearly demonstrate that the monitoring of FVIIa by TGT using PPP underestimated the hemostatic ef-