(MED-FR-11.4) Unmet treatment needs

While non-factor therapies generally do not require routine laboratory monitoring for patients on prophylaxis, hemostasis assays can be valuable in specific situations such as surgery, breakthrough bleeds, or when used in combination with factor-based treatments. In this context, global hemostasis assays, including the thrombin generation assay (TGA), play a crucial role. These assays have been extensively used in research laboratories during the preclinical and clinical development of non-factor therapies, providing important insights into their hemostatic effects.
Among these tools, TGA is particularly relevant as it assesses overall clotting capacity and correlates with bleeding risk in hemophilia, making it a valuable tool for evaluating therapies and guiding clinical decisions. However, despite its utility in research, the clinical adoption of TGA remains limited due to several challenges. One major issue is the difficulty of working with fresh platelets, leading some to rely on platelet-free plasma (PPP) instead of platelet-rich plasma (PRP). While PPP-based TGA is more convenient, it may underestimate the efficacy of treatments like rFVIIa and emicizumab, which rely on platelet interactions. To address this, modifications such as the addition of factor XIa have been proposed, improving accuracy. However, challenges persist, particularly in evaluating combination treatments like emicizumab with rFVIIa, where misinterpretations of PPP-based TGA could lead to inaccurate safety assessments.
Despite standardization efforts for global hemostasis assays in hemophilia, discrepancies remain between centers. Automated TGA analyzers represent progress, but the main barrier to clinical implementation is the lack of specialized personnel. Without trained hemostasis technicians, standardization alone may not be enough to integrate TGA into routine hospital practice. Consequently, the widespread use of TGA remains constrained by the absence of large-scale standardized studies and practical challenges in hospital settings.