Recent research has revealed that having sickle cell trait, which means being a carrier of sickle cell disease, can elevate the risk of blood clots. Notably, this risk remains consistent across various human populations that aren’t typically linked with sickle cell disease. The findings provide valuable estimates for clinical risks associated with sickle cell trait, helping to guide clinical practice recommendations. The research analyzed the largest and most varied group of individuals with sickle cell trait to date, incorporating data from over 19,000 people with different ancestral lineages.
This study, detailed in Blood Advances, was conducted by a team from the National Human Genome Research Institute (NHGRI), part of NIH, as well as The Johns Hopkins University School of Medicine in Baltimore and the company 23andMe based in South San Francisco, California.
Earlier studies looking at the connection between sickle cell trait and blood clots primarily involved participants of African descent and those identifying as Black, stemming from the mistaken belief that this genetic carrier status predominantly affects these groups. Although sickle cell trait is most common among individuals who identify as Black or African American in the U.S., it can be found in people from all ancestral backgrounds, particularly in regions like West and Central Africa, Mediterranean Europe, India, and the Middle East.
Vence Bonham Jr., J.D., co-leader of the study and acting deputy director and associate investigator at NHGRI, emphasized, “Due to the common association of sickle cell trait with Black or African American individuals, it has been under-researched in other populations, leading to biases that can harm those with sickle cell trait. Our findings aim to help clinicians accurately assess the risk of blood clots in all individuals with this trait without the influence of bias.”
The participants in this study were part of the 23andMe research initiative, contributing voluntarily online and providing informed consent for their anonymized data to be analyzed and shared with research partners. From this large cohort comprising more than four million individuals, researchers assessed the risk of venous blood clots, or venous thromboembolism. Statistical evaluations grouped participants based on genetic similarities, revealing that those with sickle cell trait face a 1.45 times greater risk of venous thromboembolism compared to those without the trait, a risk that remains consistent across the diverse genetic backgrounds examined.
To provide a comparison for estimating blood clot risks, the researchers also analyzed individuals who carry Factor V Leiden, a known hereditary blood-clotting disorder primarily seen in those of European descent. The results indicated that carriers of Factor V Leiden exhibited an even higher risk of venous thromboembolism than those with sickle cell trait.
The study also highlighted that individuals with sickle cell trait face a heightened risk of pulmonary embolism, a specific type of blood clot. Pulmonary embolism occurs when a clot dislodges from deep veins, travels to the lungs, and disrupts blood flow. While some patients might not display symptoms, common signs include shortness of breath, chest discomfort, and fainting.
Previous studies have indicated that individuals with sickle cell trait are at a higher risk for clots in the lungs compared to those in the legs, and this latest research strengthens that connection with a larger participant pool.
Rakhi Naik, M.D., clinical director of the Division of Hematology at Johns Hopkins University, which co-led the research, stated, “This study offers crucial insights into the patterns of venous blood clots and proposes a distinctive blood clotting mechanism in those with sickle cell trait. Understanding these risks is vital, particularly in circumstances such as surgeries or hospitalizations that increase the likelihood of severe blood clot development.”
In the United States, over 2 million individuals have sickle cell trait. These individuals carry one copy of the genetic variant responsible for sickle cell disease, a condition that leads to the deformity and stickiness of red blood cells, obstructing blood flow. While those with sickle cell trait generally do not experience health issues, they remain carriers for sickle cell disease. In rare instances, sickle cell trait may contribute to health complications, including muscle breakdown, blood in the urine, and kidney problems.
