Prophylaxis use of clotting factor replacement products in people with non-severe haemophilia: A review of the literature

Abstract

Introduction: People with non-severe haemophilia appear to be under-treated in many countries, and this may lead to joint damage and worsen quality of life.

Aim: To review literature for clotting factor replacement prophylaxis in people with non-severe haemophilia A and B (HA/HB) in relation to long-term outcomes to support clinical decision-making.

Methods: A targeted literature search was performed to identify studies published between 2000 and 2021 that included prophylaxis in people with non-severe HA/HB and long-term outcomes, including annualized bleeding rates, joint health and quality of life.

Results: Although eligible articles included 2737 and 2272 people with mild or moderate HA, respectively, only 22% (n = 609) and 29% (n = 668) reported treatment regimens. A total of 549 people with moderate HA were treated with factor replacement prophylaxis and were from high-income countries. On the contrary, nearly all people with mild HA received desmopressin (n = 599). Details of treatment regimens for women with haemophilia and people with HB were sparse. Three studies provided long-term outcomes for people with moderate haemophilia who received prophylaxis with factor concentrate, supporting early prophylaxis in people with a frequent bleeding phenotype regardless of their endogenous clotting factor level to preserve joint health.

Conclusion: There remain large knowledge gaps when considering how to provide optimal treatment for people with non-severe haemophilia. Nonetheless, there is a strong rationale that prophylaxis should be considered early in life according to similar strategies as for severe haemophilia for those with a frequent severe bleeding phenotype.

Keywords: arthropathy; bleeding; episodic/on-demand treatment; non-severe (mild or moderate) haemophilia A or B; prophylactic FVIII or FIX; women with haemophilia (symptomatic carriers).