Sickle cell trait (SCT), defined as heterozygosity for sickle hemoglobin, was positively associated with risk for pulmonary embolism, proteinuria, chronic kidney disease (CKD), and exertional rhabdomyolysis, according to a study published in the Annals of Internal Medicine.

The evidence came from a systematic literature review that sought to evaluate the association between SCT and any of 24 adverse clinical outcomes in children and adults. The outcomes were categorized as renal, vascular, pediatric, and surgery- or trauma-related outcomes, exertion-related injury, and overall mortality.

Of 7083 studies screened from PubMed, CINAHL, the Cochrane Library, Current Contents Connect, Scopus, and Embase between January 1, 1970, and June 30, 2018, and bibliographies of review articles, 41 studies met inclusion criteria. Most of the studies were population-based (16 studies) or case control (16 studies). Adults only, children only, or both were included in 26, 12, and 3 studies, respectively.

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High-strength evidence supported a positive association between SCT and risk for pulmonary embolism, proteinuria, and CKD, while moderate-strength evidence supported an association with risk for exertional rhabdomyolysis.

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A high-quality study showed that individuals with SCT had 5.2% prevalence of pulmonary embolism compared with 2.5% in individuals without SCT (hazard ratio 2.24, CI: 1.28-3.95). Two moderate-quality studies showed similar increased odds for pulmonary embolism. For proteinuria, a high-quality study of 6432 black adults found a 1.86 times greater risk for baseline albuminuria among individuals with SCT compared with those without SCT (31.8% vs 19.6%). Lastly, a high-quality study assessed CKD in 15,969 black patients, and creatinine-based CKD was found in 19.2% of cohort participants with SCT compared with 13.5% of those without SCT. Other studies also found increased risk for CKD among patients with SCT.

A moderate-quality study of 47,944 military personnel found that exertional rhabdomyolysis occurred in 1.2% of soldiers with SCT compared with 0.8% of those without SCT.

Data from other studies showed null associations, contained insufficient data, or had low-strength evidence for the other 20 clinical outcomes.


1. Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical outcomes associated with sickle cell trait [published online October 30, 2018]. Ann Intern Med. doi: 10.7326/M18-1161