OBJECTIVES: Advancing treatment option have improved the life expectancy and decreased mortality related to hemophilia. In the past few decades, a shift has been observed in mortality from bleeding related mortality to comorbidity associated mortality among patients with hemophilia (PwH). The current study aimed to report pooled estimate for cause specific mortality among PwH.

METHODS: Using search terms related to Mortality and comorbidities in Hemophilia, we conducted a search in Pubmed, Embase and Cochrane databases up to 31 st March 2021. Studies reporting cause-specific mortality in the form of Standardized mortality ratio (SMR) or Hazard ratio (HR) were included in the analysis. Subgroup analysis based on mid-year of data study period (before 2000 and after 2000) was conducted for published studies.

RESULTS: A total of 3186 studies were identified and screened. A total of 12 studies reported cause-specific mortality among PwH. The pooled Cardiovascular disease specific SMR was 0.49 (95% CI 0.27-0.88) indicating a 51% decrease in mortality in PwH compared to the general population. The decrease in SMR was consistently observed in studies before 2000 (0.67; 95% CI 0.34-1.30) and after 2000 (0.26; 95% CI 0.14-0.49). Almost 13 folds increase in Liver disease specific SMR was observed in PwH (12.67; 95% CI 6.06-26.47), the Liver disease specific SMR declined over the years (before 2000: 19.07; 95% CI 7.87-46.18; after 2000: 6.31; 95% CI 3.39-11.97). Cancer specific SMR among PwH was 0.80 times lower among PwH (95% CI 0.49-1.30), Cancer specific SMR in PwH before 2000 was 1.01 (95% CI 0.55-1.87) and 0.58 after 2000 (95% CI 0.29-1.19).

CONCLUSIONS: Different comorbidities have varying impact on PwH’s mortality.