NEW YORK – Individuals carrying sickle cell trait (SCT) have a higher risk of developing blood clots across diverse ancestries, regardless of whether those populations are traditionally associated with sickle cell disease, according to a recent study from researchers at Johns Hopkins University, 23andMe, and the National Institutes of Health.
These findings, published Thursday in the journal Blood Advances, challenge race-based associations between SCT and clotting disorders.
Sickle cell disease occurs more frequently among Black populations, and SCT has been traditionally associated with individuals who identify as Black or African American. Because of this, studies investigating the relationship between SCT and blood clots generally only include individuals of African descent and those who self-identify as Black, resulting in a bias that could unintentionally harm others carrying the trait.
To study the prevalence of SCT across diverse ancestries and its correlation with blood clots, researchers examined a cohort of over 4 million consenting participants contained in the 23andMe database.
They compared the risk of clotting between SCT carriers and those of factor V Leiden, a trait that can result in deep vein thrombosis (DVT), a clotting typically associated with European ancestry populations. SCT, on the other hand, is more often associated with pulmonary embolism, a type of blood clot more often found with sickle cell disease.
Because of these associations, healthcare providers rarely test people of African ancestry for factor V Leiden or, conversely, those of other ancestries for SCT.
Venous clots typically form in the lower extremities, with roughly 30 to 40 percent developing into pulmonary embolism, leading the researchers to expect that among individuals with venous thromboembolisms (VTE), 30 to 40 percent would experience pulmonary embolism, while the rest would have isolated DVT.
Although an analysis of the rates of different blood clots did show that result in the full cohort and among factor V Leiden carriers, it showed an opposite pattern among SCT carriers with VTE, with approximately 61 percent of SCT carriers reporting a history of pulmonary embolism.
Additionally, individuals heterozygous for factor V Leiden showed a higher overall risk for clotting than people with SCT.
Although previous studies have suggested that individuals with SCT have a greater risk of blood clots occurring in the lungs than only in the legs, the current study supports the link more definitively with its larger sample size.
This demonstrates, the authors wrote, "clear epidemiologic evidence for a unique mechanism of thrombosis in SCT compared to other thrombophilic states."
Importantly, the study also evaluated the prevalence of individuals with neither SCT nor factor V Leiden and found that the baseline prevalence of pulmonary embolism was higher among people of African descent, particularly those in younger age groups.
"This may suggest that unmeasured confounders, such as socioeconomic factors, may contribute to a higher baseline risk of [pulmonary embolism] in the African population," the authors wrote.
Despite the study's strong statistical associations stemming from its large cohort size, the authors noted that they did not have genotypic data on alpha-thalassemia, another inherited blood disorder, which could modify the SCT phenotype.
"This study provides important insights about patterns of venous blood clots and suggests a unique mechanism of blood clotting in people with sickle cell trait," Rakhi Naik, clinical director for the Division of Hematology at Johns Hopkins University and senior author of the study, said in a statement put out by the NIH. "Knowing the risks of blood clots in people with sickle cell trait is important for situations such as surgeries or hospitalizations, which add to the risk of developing serious blood clots."