Burden of mild haemophilia A: Systematic literature review

Introduction Although the clinical manifestations of severe haemophilia A (HA) are well studied, the challenges, if any, of living with mild HA are not clearly delineated to date. Aim To assess available evidence of clinical risks and societal/economic impacts of disease in adult patients with mild HA using a systematic literature review. Methods Prespecified study selection criteria were applied in a comprehensive literature search. Included studies varied in design and reported outcomes of interest for adults (>= 13 years of age) with mild HA. Results Seventeen studies with a total of 3213 patients met eligibility criteria (published or presented in English, 1966-2017). Most studies were observational, and the outcomes reported were too sparse and dissimilar to support a formal meta-analysis. Mean annual bleeding rates ranged from 0.44 to 4.5 episodes per patient per year. Quality of life (QoL; SF-36 General Health) was impacted compared to healthy controls. Health care costs and productivity were seldom assessed and no robust comparisons to healthy controls were available. Conclusion Quantifying outcomes for adult patients with mild HA remains challenging, with estimates of key QoL and cost data often based on small data sets and without comparison to population norms. Therefore, the clinical impact of mild haemophilia may be under-represented and unmet needs may remain unaddressed. As paradigm-changing therapies for HA emerge, stronger knowledge of mild HA can guide the development of care options that minimize burden and enhance the QoL for this segment of the haemophilia community, and for the haemophilia community in totality.