Sickle Cell Trait (SCT) is defined as the heterozygous inheritance of sickle hemoglobin. This represents the carrier state for Sickle Cell Disease (SCD). In the United States, 6 to 9% of African Americans and 0.01 to 0.07% of others have SCT. Elsewhere, the prevalence is 2 to 30%. In general, individuals who carry SCT have a normal lifespan.1 Given ongoing public and medical discussions about SCT and mortality, we are sharing this update to highlight current evidence and facilitate appropriate clinical understanding.
In a recent publication,2 the authors discussed the continuing confusion regarding the role of SCT and morbidity. There are known rare events that can occur at higher rates in individuals with SCT including renal medullary carcinoma, hematuria, pulmonary embolism, chronic kidney disease, and exertional rhabdomyolysis.1,2
For decades, it has been recognized that sickled red blood cells (RBCs) are a postmortem artifact related to hypoxemia and acidosis in the decedent. These physiological conditions can lead to hemoglobin polymerization and the presence of sickled cells. The presence of this artifact has led to medical examiners and other officials to cite sickle cell trait as a cause of or a major factor in the deaths of Black individuals while in custody.2,3 To evaluate the medical validity of listing SCT, acute sickle cell crises, or both on the autopsy report as a cause of death in individuals with SCT, the American Society of Hematology (ASH) convened an expert panel of hematologists and forensic pathologists to review the literature to determine the validity of sickle cell crises and exertion-related mortality in individuals with SCT. After systematically reviewing 1474 citations, the panel found no studies comparing uncomplicated acute sickle cell pain crises in individuals with SCT to those with SCD. Additionally, no study was identified to support the occurrence of vaso-occlusive pain crises in individuals with SCT. Given that sickle cell crisis is not identified as a clinical entity in individuals with SCT, there can be no evidence that sickle cell crisis is responsible for death in individuals with SCT.2,4
Lastly, to further elucidate the natural history of SCT, the Achieving Understanding of the Natural History of Sickle Cell Trait (AUNT) study was initiated in 2023.5 The purpose of the study is to create a longitudinal cohort of individuals with SCT to better understand the hematologic phenotype of SCT carriers, assess for differences in those with varying quantities of hemoglobin S (HbS), and assess for potential clinical complications of SCT. The primary outcome measures are hemoglobin variant quantification as determined by the range of variability in baseline percentage of HbS and the relationship of that percentage to markers of hemolysis (lactate dehydrogenase [LDH], reticulocytes, haptoglobin), coagulopathy (D-dimer), and renal disease (urine albumin/creatinine ratio). The secondary outcome measures include evaluating RBC rheology by identifying the range of variation in baseline RBC rheological parameters in the study subjects and their relationship to the percentage of HbS and other baseline clinical parameters. Additionally, in studying the natural history of SCT, the frequency of hemolysis, the potential for and progression of chronic kidney disease and albuminuria, the relative risk of thrombosis based on medical history, and the prevalence of episodes of pain or exercise-related symptoms will be evaluated.
References:
- Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical outcomes associated with sickle cell trait: a systematic review. Ann Intern Med. 2018;169(9):619–627. doi: 10.7326/M18-1161
- DeBaun MR, Hebert CJ, Miller YM. Debunking myths: sickle cell trait, crises, and sudden death. Blood Adv. 2025 Nov 25;9(22):5787-5789. doi: 10.1182/bloodadvances.2025016736. PMID: 41021313; PMCID: PMC12661294.
- Mack AK, Bercovitz RS, Lust H. Some medical examiners say sickle cell trait causes sudden death—they’re wrong [Internet]. New York: Scientific American; 2021 Jun 20 [cited 2026 Feb 3]. Available from: https://www.scientificamerican.com/article/some-medical-examiners-say-sickle-cell-trait-causes-sudden-death-theyre-wrong/.
- Weeks LD, Wilson AM, Naik RP, et al. Sickle cell trait does not cause “sickle cell crisis” leading to exertion-related death: a systematic review. Blood. 2025;145(13):1345-1352.
- National Alliance for Sickle Cell Centers. Achieving understanding of the natural history of sickle cell trait (AUNT) [Internet]. Bethesda (MD): National Library of Medicine; 2025 Nov 6 [cited 2026 Feb 6]. Available from: https://clinicaltrials.gov/study/NCT06071377?tab=study#study-plan
