PB0535 - How much is the coagulation ability of emicizumab in hemophilia A patients treated with it, when converted to factor VIII activity?

Background: Iorio et al. have shown target plasma factor levels for each scenario in patients with hemophilia (PwH) as a Delphin statement. This scenario should apply to PwH treated with non-factor replacement therapies. The equivalency to coagulation activity in non-factor replacement therapies has not been determined yet, though factor VIII activity equivalent value (FVIIIe) of emicizumab has been guessed about 15%.

Aims: To verify whether emicizumab has the FVIIIe at about 15 % in patients treated with it.

Methods: Plasmas were isolated from blood samples drawn from nine patients treated with emicizumab. Coagulation ability in each plasma was measured by thrombin generation assay (TGA), and its FVIII activity (FVIIIa) was also measured by chromogenic assay (CGA). Patients’ bleeding episodes and their infusion counts of factor concentrates were extracted and determined from their medical records or patients’ handbooks.

Results: All nine patients were not infused with factor concentrate within 6 days before the date of blood collection. There was only one patient at the induction of emicizumab (Case 2). Eight patients except for him had about 15% FVIIIa when measuring with CGA. On the other hand, the median percent peak thrombin levels in the case of comparing with normal plasma was 12.5%. Also, the median percent endogenous thrombin potential (ETP, nM･min) was 21.1%. Case 4 and Case 6 had higher values of those than the others. After starting emicizumb therapy, most patients have had few spontaneous bleeding episodes. However, there was no correlation between the annualized bleeding rate and the percent peak thrombin level and ETP.

Conclusion(s): In many PwH treated with emicizumab, their FVIIIe is suggested at about 12%, when compared to the peak thrombin levels in TGA. However, there are some patients with discrepant values compared to the results measuring CGA.