Athletes with sickle cell trait (SCT) have up to a 37-fold increased risk of exercise-related death. Exertional collapse associated with sickle cell trait (ECAST) is uncommon but can lead to exercise-related death due to exertional sickling. We present a case series of fatal ECAST in high school athletes aged 14 to 16 years. All 3 athletes experienced collapse during practice sessions with muscle pain or weakness. Upon evaluation at the hospital, the athletes had a significant metabolic acidosis that did not respond as expected to fluid resuscitation. Admitting diagnoses for the athletes included exertional heat stroke or dehydration. All 3 athletes had profound rhabdomyolysis leading to acute renal failure, worsening metabolic acidosis, and hyperkalemia. They rapidly progressed to disseminated intravascular coagulation, multiorgan system failure, and death. The autopsies of all 3 athletes showed extensive sickle cell vaso-occlusion involving the spleen liver, and muscles. Final clinical and pathologic diagnosis supported ECAST with fatal exertional rhabdomyolysis. Exertional collapse associated with sickle cell trait is an uncommon but potentially deadly condition that is often underrecognized or misdiagnosed as exertional heat stroke. The development of ECAST is thought to be multifactorial with exercise intensity, recent illness, and exercising conditions (ie, heat and altitude). Prevention should be the primary goal for athletes with SCT through exercise modification, education of precipitation factors, and cessation of exercise with recent illness. Athletes with suspected ECAST should undergo aggressive resuscitation with a low threshold for early transfer to a tertiary care facility for further management and potential hemodialysis.
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