All-cause mortality and causes of death in persons with haemophilia: A systematic review and meta-analysis

Introduction Improvements in haemophilia treatment over the last decades resulted in increased life expectancy in persons with haemophilia (PWH). Aim We conducted a systematic review and meta-analysis to examine all-cause mortality and causes of death among PWH. Methods We systematically searched EMBASE, MEDLINE, Web of Science, CINAHL and Cochrane central register of controlled trials from inception through March 15, 2021. Studies that reported a mortality estimate of PWH compared with the general population and/or reported causes of death were included. Random-effects meta-analysis with inverse variance method was used to obtain pooled estimates. We stratified the analysis by the year of cohort entry (before 2000 vs after 2000). Result Of the 4769 studies identified, 52 met the eligibility criteria. The pooled all-cause standardized mortality ratio (SMR) from 9 studies in PWH was 1.93 (95% CI 1.38-2.70; I-2 = 97%). The pooled SMRs before and after the year 2000 were 2.40 (95% CI 1.92-3.00; I-2 = 87%) and 1.20 (95% CI 1.03-1.40; I-2 = 62%), respectively. Before the year 2000, 31.2% deaths occurred due to HIV followed by haemorrhage (26.0%), cardiovascular disease (18.2%), liver disease (9.0%), and cancer (8.9%). Fewer (13.9%) deaths were attributable to HIV after the year 2000 with the proportion of deaths due to haemorrhage remaining unchanged. Conclusion With treatment advances, mortality in PWH has declined over the last few decades approaching that of the general population. However, haemorrhage remains a leading cause of death requiring further attention.