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

Abstract

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 metaanalysis 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 allcause 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.

Prevalence of selected bleeding and thrombotic events in persons with hemophilia versus the general population: A scoping review

“…As described in the following section, the conclusions of this study align with several published reviews examining bleeding, thrombosis, and mortality in persons with hemophilia [ [35] , [36] , [37] , [38] , [39] ].…”

Increased acute care utilisation, comorbidities and mortality in adults with haemophilia: A population‐based cohort study from 2012 to 2019

“…This can be largely attributable to the introduction and widespread adoption of antiretroviral therapy for HIV and hepatitis C virus (HCV), as 54.8% of deaths in Canadian PWH occurred due to HIV during 1982–2003 18 . As a comparison, a recent meta‐analysis reported a pooled SMR after the year 2000 of 1.20 (95% CI 1.03–1.40), with substantial heterogeneity across the studies 19 . Unfortunately, we do not have causes of deaths from administrative data sources to assess whether cause‐specific mortality differs between the haemophilia and control population.…”

Associated comorbidities, healthcare utilization & mortality in hospitalized patients with haemophilia in the United States: Contemporary nationally representative estimates

“…The clinical severity of the disease varies based on the percentage of coagulation factor activity with severe disease in patients who have < 1% factor activity, moderate disease with 1–5%, and mild disease with factor levels > 5–40% of normal activity 4,5 . Haemophilia, once considered a fatal disease, but now with access to haemophilia therapeutics and establishment of comprehensive haemophilia care, the life expectancy in various studies is gradually increasing from 60 years to closer to 70 years 6–16 . As the aging population with haemophilia increases, these individuals are likely to suffer from more chronic diseases and comorbidities associated with aging, increasing the burden on the health care system 17 .…”