Background: There have been many improvements in hemophilia treatment over the last 30 years. Complications and resulting causes of death will be impacted by these changes. We aimed to conduct a systematic review and meta-analysis on all cause mortality and causes of death among people with hemophilia.

Methods: Using a predefined search strategy, we systematically searched EMBASE, MEDLINE, Web of Science, CINAHL, Cochrane central register of controlled trials and Google Scholar from inception through November 6, 2019. Studies that reported standardized mortality ratio (SMR) of hemophilia patients 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 further stratified the analysis by the year of cohort entry (before 2000 vs after 2000).

Results: Of the 4072 studies identified , 16 studies from 10 different countries met the eligibility criteria. The pooled SMR for all-cause mortality among people with hemophilia, compared with the general population was 1.93 (95% CI 1.38-2·70; I²=97%) (Figure: 1). The pooled SMR before and after the year 2000 were 2.40 (95% CI 1.92-3·00; I²=87%) and 1.20 (95% CI 1.03-1·40; I²=62%) respectively. Causes of mortality were extracted for 5808 deaths. Before the year 2000, 34% deaths occurred due to AIDS followed by hemorrhage (28%) cardiovascular disease (20%) , liver disease (11%) and cancer (9%) (Table: 1). Fewer (18%) deaths were attributable to AIDS after the year 2000 without any notable difference due to other causes.

Conclusion: : With advancement of treatments, mortality in hemophilia patients have declined over the last few decades. Particularly, effective prevention and treatment of HIV has made an impact. However, hemorrhage and cardiovascular disease still rank as leading causes of death.


Wu:Servier: Other: advisory board; BMS-pfizer: Honoraria, Other: advisory board; leo pharma: Other: advisory board; Pfizer: Honoraria. Sun:Octapharma: Research Funding; Sanofi: Other: Advisory board; Pfizer: Other: Advisory board; Octapharma: Other: Advisory board; Novo Nordisk: Other: Advisory board.

Author notes


Asterisk with author names denotes non-ASH members.