Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review

Patients with severe hemophilia A (HA) have an increased risk of spontaneous and trauma‐related bleeding because of a congenital absence of factor VIII (FVIII). Most severe HA patients use prophylactic FVIII concentrate, the effect of which can be monitored with FVIII activity level measurement. However, FVIII activity level is less valuable in predicting the potential clinical bleeding risk. Some patients still experience breakthrough bleeds despite adequate FVIII trough levels, whereas others do not bleed with trough levels below threshold. This difference may be caused by inter‐individual differences in pro‐ and anticoagulant factors, the so‐called hemostatic balance. Thrombin generation assays (TGAs) measure the hemostatic balance as a whole. Thereby, the TGAs may be a better tool in the guidance and monitoring of treatment in HA patients. In addition, TGAs offer the opportunity to determine the response to bypassing agents and treatment with non‐factor replacement therapy, in which FVIII activity assays are not suitable for monitoring. This review summarizes the current knowledge about monitoring different HA treatment modalities by TGA, as a single treatment option and when used in a concomitant fashion.