Sickle Cell Trait and Exertional Collapse in Athletes: Risk, Mechanisms, and Screening Controversies - a narrative review

Abstract

Background. Sickle cell trait (SCT), the heterozygous carrier state for hemoglobin S, is generally considered benign but has been repeatedly implicated in exercise-related sudden death and exertional rhabdomyolysis in athletes and military recruits. The entity termed exercise collapse associated with sickle cell trait (ECAST) remains incompletely understood, and its recognition, prevention, and screening have generated persistent controversy among hematology and sports medicine organizations.

Aim. To synthesise, from a clinically oriented and critical perspective, the epidemiology, proposed pathophysiology, clinical presentation, screening policies, and prevention strategies relevant to SCT-associated exertional collapse in athletic and military populations.

Materials and Methods. Narrative review of peer-reviewed English-language epidemiological studies, hospital and registry series, case reports, genetic and physiological investigations, and institutional guidance addressing SCT, exertional rhabdomyolysis, and exercise-related collapse.

Results. SCT carriers show a consistently elevated relative risk of exertional rhabdomyolysis and collapse across military and collegiate cohorts, though absolute risk remains low and mortality data are inconsistent. Proposed mechanisms include microvascular sickling under hypoxia/acidosis, altered lactate handling, hydration/thermoregulatory abnormalities, mitochondrial dysfunction, and rare pathogenic variants. NCAA screening coincided with reduced sickling-related deaths in Division I football, but screening remains ethically contested, self-report underestimates true prevalence, and universal precautions are advocated as an alternative.

Conclusions. Current evidence supports individualized risk-stratified precautions, targeted education, and cautious, evidence-based screening rather than blanket policies, with substantial gaps remaining regarding causal mechanisms and optimal prevention.