The past and future of haemophilia: A narrative review

Abstract

Haemophilia A and B are genetic bleeding disorders characterized by a lack of or malfunction in coagulation protein factors VIII and IX, respectively, leading to repeated joint and muscle bleeds and progressive damage to the musculoskeletal system. The genes responsible for factors VIII and IX are situated on the X chromosome, resulting in the primary occurrence of symptoms related to congenital haemophilia A and B in males. In the past, individuals with haemophilia received treatments involving whole blood transfusions initially, and later blood plasma. A significant advancement in treatment effectiveness emerged with the introduction of cryoprecipitate, followed by freeze-dried coagulation factor concentrates, derived from plasma. These concentrates had a profound positive impact on patients' overall well-being, enabling them to self-administer prophylactic infusions at home and markedly improving their quality of life. The current treatment approach involves replacing these clotting factors, either when bleeding occurs (on-demand) or on a preventive schedule. However, a significant complication of this treatment is the development of inhibitors, particularly common in haemophilia A. There's potential for substantial treatment enhancement through new modified medications that could address the limitations of current preventive methods by reducing dosing frequency, ultimately making therapy less burdensome for patients. The introduction of subcutaneous administration for some of these new treatments could also simplify preventive care, especially for children with difficult venous access. Gene therapy holds promise as a potential cure, with notable progress seen in treating haemophilia B.