Background: Evidence on the prevalence of a family history of sudden death in hemoglobinopathies is limited. This study synthesizes evidence concerning first-degree relatives of affected individuals and carriers and identifies gaps in understanding its clinical relevance.
Materials and Methods: We searched PubMed/MEDLINE, Scopus, Web of Science, the Cochrane Library, SID, Magiran, and CIVILICA for English- and Persian-language publications through June 2026. Two reviewers independently screened titles and abstracts. Evidence was classified as direct, comparative, or contextual and synthesized narratively. The primary outcome was the proportion of individuals with hemoglobinopathies or carriers with at least one first-degree relative with a history of sudden death.
Results: No extractable prevalence estimate was identified in the included literature for individuals with hemoglobinopathies or carriers. The absence of adequate numerators, denominators, and verified family-history data precluded prevalence estimation and comparisons across hemoglobinopathy types, carrier status, and categories of first-degree relatives. Studies of hemoglobinopathies primarily focused on patient mortality, arrhythmias, and cardiopulmonary complications rather than sudden death among relatives. Comparative cardiac literature reported a family history of sudden cardiac death in 34.2% of ischemic sudden-death victims, 13.4% of nonischemic victims, and 17.6% of controls without heart disease; this history was significantly more common in the ischemic group. Although these findings provide contextual information, they do not establish prevalence among individuals with hemoglobinopathies or carriers.
Conclusion: Evidence is insufficient to estimate the prevalence of a family history of sudden death among individuals with hemoglobinopathies, including carriers. Studies using standardized definitions, appropriate denominators, and validated family-history ascertainment are needed to establish prevalence and assess associations with patient outcomes. Its predictive value and screening utility remain uncertain.