Literature review shows no link between sickle cell trait, sudden death
Key takeaways:
- Sickle cell trait has no association with mortality from physical exertion or heat-related injuries without rhabdomyolysis.
- Sickle cell trait does not cause acute pain crises.
Sickle cell trait does not cause individuals to die of physical exertion or heat-related injuries without rhabdomyolysis, according to a findings of a systematic literature review.
Further, sickle cell trait (SCT) has no association with acute vaso-occlusive pain crises.
“To date, this is the most authoritative and definitive systematic review on this subject,” Michael R. DeBaun, MD, MPH, professor of pediatrics and medicine at Vanderbilt University School of Medicine, as well as founder and director of the Vanderbilt-Meharry Sickle Cell Disease Center of Excellence, said in a press release. “This review shows that any primary, secondary or tertiary cause of death attributable to sickle cell trait is not a diagnosis substantiated by the medical evidence.”
Background and methods
Approximately 300 million individuals around the world have SCT, according to study background.
Individuals who have SCT are carriers for sickle cell disease but do not have it.
Median survival for individuals with sickle cell disease is approximately 48 years. People with SCT live as long as those in the general population.
However, case reports from the 1970s and 1980s noted individuals with SCT died or fell ill due to high physical activity. The same happened with military recruits and collegiate athletes.
“In several cases of exertion-related death involving individuals with SCT, ‘sickle cell crisis’ has been documented as the cause of death, and more recently, investigative journalists have uncovered 46 cases in which ‘sickle cell crisis’ has been used as a cause of death for people with SCT who died while in police custody,” the researchers wrote.
ASH convened a group of experts to evaluate the literature and determine if these claims had merit.
They examined two questions in their review:
- “Among individuals with SCT, compared to those with sickle cell disease, do uncomplicated acute pain crises occur?”
- “Among individuals with SCT compared to individuals without SCT, can physical activity above baseline result in sudden death?”
‘Medically impossible’
Researchers found 1,474 citations, seven of which they included in their evaluation.
No studies evaluated acute pain crises for individuals with SCT compared with those with sickle cell disease. No studies showed an association between acute pain crises and SCT, either.
One study reported on the death of an individual with SCT. The study of active soldiers showed SCT to be linked with heat-related-exertional rhabdomyolysis but not mortality.
These findings showed it is “medically impossible” for SCT alone to cause either sudden death or acute pain crises, DeBaun said.
“In the absence of two medical conditions that we are all at risk for — exertional rhabdomyolysis or crush injuries leading to rhabdomyolysis — individuals with SCT are not susceptible to sudden death,” he said in the release. “Even under these extreme environmental conditions, unexplained sudden death cannot be attributed to SCT.”
Researchers acknowledged study limitations, mainly the lack of studies investigating these issues.
“SCT has long been misunderstood, fueling widespread misinformation and medically inaccurate claims that it can lead to sudden death. This misconception has been especially prominent in cases of Black men with SCT,” Belinda Avalos, MD, ASH president and professor of medicine and a senior advisor to the president of Atrium Health Levine Cancer, said in the press release. “In light of the pervasive, widely publicized and harmful nature of this myth, the society aims to further promote accurate information to protect and empower affected communities.”
References:
- ASH. No scientific link found between sickle cell trait and sudden death (press release). Published Jan. 30, 2025. Accessed Jan. 30, 2025.
- Weeks L, et al. Blood. 2025;Published online ahead of print Jan. 30.
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Weeks L, et al. Blood. 2025;Published online ahead of print Jan. 30.