Hemophilia A and B are rare, X-linked bleeding disorders characterized by deficiencies in coagulation factor VIII (FVIII) and factor IX (FIX), respectively. Numerous advances have helped to reduce disease burden. However, hemophilia B is not as well studied as hemophilia A, likely reflecting its lower prevalence. Clinical management of hemophilia B has often relied on inference and extrapolation from hemophilia A. Despite being part of the same tenase complex, as enzyme (FIX) and cofactor (FVIII) when activated, with the main task being to activate factor X in the intrinsic pathway, the FIX and FVIII proteins display several molecular differences. These have the potential to impact the clinical phenotype of hemophilia, affect monitoring, and influence treatment options. Consequently, hemophilia B presents several outstanding challenges, requiring a greater degree of understanding and/or attention across a range of areas. Some of these challenges relate to the FIX molecule, with more knowledge needed in relation to: the biological/clinical impact of underlying genetic changes; hemostatic implications of the extravascular distribution of FIX; and FIX clearance. Other challenges relate to clinical management: determining the best ways to monitor the true biological activity of FIX; clarifying the relationship between FIX plasma levels and clinical outcomes when treating patients; inhibitors; affected girls and women; and appreciating the value of novel treatment approaches, while considering possible breakthrough bleeds, thrombosis, and monitoring. In addition, concerted effort is required to address global disparities, which can particularly affect hemophilia B. Identifying such challenges may help to facilitate research that will further existing knowledge, with better understanding being crucial for achieving health equity between hemophilia A and B.
Astermark et al. (Thu,) studied this question.