Background/Objectives: Patients with severe hemophilia A on prophylaxis with emicizumab exhibit a mild/moderate bleeding phenotype that requires the use of either recombinant FVIII (rFVIII) or bypassing agents (BPAs) in patients with inhibitors, in the case of breakthrough bleeding or surgery. Since factor IX (FIX) limits the formation of the FIXa–emicizumab–FX complex, exogenously added FIX might enhance complex formation and thrombin generation. This study aimed to compare the procoagulant effects of various FIX concentrates with recombinant activated FVII (rFVIIa), activated prothrombin complex concentrate (aPCC), and rFVIII in SHA patients with and without inhibitors under emicizumab prophylaxis. Methods: Hemostatic changes were monitored using two optimized global coagulation assays: rotational thromboelastometry and calibrated automated thrombin generation. Tubes containing corn trypsin inhibitor (CTI) were used during blood collection to prevent activation. Low concentrations of tissue factor (TF) were used to trigger coagulation in both assays. Results: Ex vivo addition of recombinant FIX concentrates significantly increased the procoagulant activity of emicizumab, achieving levels comparable to therapeutic doses of rFVIIa or rFVIII, and the proportion of active FIXa within the concentrates is a major contributor to their procoagulant function. We assessed the influence of FVIII inhibitors on the hemostatic efficacy of rFIX concentrates and BPAs, finding that rFIX-induced thrombin generation increased in the presence of inhibitors, and no significant differences were observed with BPAs. Conclusions: These findings suggest that FIX concentrates could be an effective alternative to BPAs for emicizumab-treated patients, particularly those with inhibitors. Further studies are needed to confirm their in vivo efficacy and to evaluate thrombotic risk.
Arias-Salgado et al. (Sun,) studied this question.