A SYSTEMATIC review by the American Society of Hematology (ASH) has found no evidence to support sickle cell trait (SCT) as a cause of acute pain crises or sudden exertion-related death. This finding challenges previous reports that have attributed deaths in athletes, military personnel, and individuals in police custody to SCT.
The ASH convened an expert panel of haematologists and forensic pathologists to conduct a comprehensive review of the literature. The team searched multiple bibliographic databases using controlled vocabulary and keywords such as “sickle cell trait,” “vaso-occlusive pain,” and “death.” From 1,474 citations, 18 studies were selected for analysis. Independent pairs of reviewers extracted data and assessed the evidence. The review found no studies comparing uncomplicated acute pain crises in patients with SCT and sickle cell disease (SCD). Crucially, no evidence was identified to support the occurrence of acute vaso-occlusive pain crises in patients with SCT. Furthermore, the review found no association between SCT and sudden unexplained death in the absence of exertion-related rhabdomyolysis.
These findings have significant implications for clinical practice. The panel concluded that there is no basis for diagnosing acute vaso-occlusive sickle cell crisis as a cause of death in patients with SCT. Additionally, SCT should not be cited as a cause of exertion-related death without evidence of rhabdomyolysis. Future research should focus on understanding the true risks associated with SCT and improving guidelines for managing patients with this condition during extreme physical exertion. Clinicians and forensic pathologists must rely on robust evidence when attributing causes of death, ensuring accurate reporting and reducing stigma associated with SCT.
Katheeja Imani, EMJ
Reference
Weeks LD et al. Sickle cell trait does not cause ‘sickle cell crisis’ leading to exertion-related death: a systematic review. Blood Journal. 2025;blood.2024026899.
