Risk factors for bleeding in people living with hemophilia A and B treated with regular prophylaxis: A systematic review of the literature
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BACKGROUND: Knowledge about the risk for bleeding in patients with hemophilia (PWH) would be relevant for patients, stakeholders, and policy makers. OBJECTIVES: To perform a systematic review of the literature on risk assessment models (RAMs) and risk factors for bleeding in PWH on regular prophylaxis. METHODS: We searched Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews from inception through August 2019. In duplicate, reviewers screened the articles for inclusion, extracted data, and assessed the risk for bias using the Quality in Prognostic Studies (QUIPS) tool. A qualitative synthesis of the results was not performed due to high heterogeneity in risk factors, outcomes definition and measurement, and statistical analysis of the results. RESULTS: From 1843 search results, 10 studies met the inclusion criteria. No RAM for the risk for bleeding in PWH was found. Most studies included only PWH A or both PWH A and B and were conducted in North America or Europe. Only one study had a low risk for bias in all the domains. Eight categories of risk factors were identified. The risk for bleeding was increased when factor levels were lower and in people with a significant history of bleeding or who engaged in physical activities involving contact. CONCLUSIONS: Our findings suggest that plasma factor levels, history of bleeds, and physical activity should be considered for the derivation analysis when building a RAM for bleeding in PWH, and the role of other risk factors, including antithrombotic treatment and obesity, should be explored.
