Rajbeer Singh Sangha, MD
The correlation between sickle cell anemia and stroke has been well established and patients with the condition are considered at risk for ischemic stroke. In contrast, the role of the Sickle cell trait (SCT), the heterozygous carrier state of sickle cell anemia, is still debated as a risk factor for stroke. With a heterozygous allelic frequency of 7 – 9% in African Americans, SCT is estimated to affect over 3 million Americans. Increasing evidence along with numerous case reports suggest the heterozygous carrier state may be associated with thromboembolism as a potential cause for stroke. The authors of the study conducted a prospective epidemiological investigation of SCT and ischemic stroke, by analyzing a cohort of African Americans followed in the Atherosclerosis Risk in Communities (ARIC) Study.
3497 patients were analyzed for the study and of those 223 (6.4%) were identified with SCT. Other than smoking history (lower prevalence) and a higher prevalence of hypercholesterolemia, cerebrovascular risk factors of the study did not differ by SCT classification. In multivariable regression analysis adjusted for traditional risk factors, the stroke rate among those with SCT was significantly higher than those with HbAA, resulting in approximately 2 extra strokes per 1000 person-years (IRD: 1.9, p=0.03). When risk was analyzed as a relative measure, SCT remained associated with incident ischemic stroke, but estimates were more marginal (HR: 1.4, p=0.08).
Even in heterozygous carriers, hemoglobin S is associated with hypercoagulability, which may be an etiologic pathway to stroke. The authors describe numerous conditions such as exertion, dehydration, and high altitude, where SCT erythrocytes are known to sickle and polymerize. The sickling deformation in turn can lead to a cascade of events which may eventually lead to a stroke. Given the increased risk of stroke in patients with SCT, it would be pertinent to consider more aggressive education and testing of patients with a family history of sickle cell disease. Screening measures and appropriate education protocols may help reduce the burden of disease and risk in this patient subpopulation. Further studies should also be conducted into the epidemiology and pathophysiology of stroke mechanisms in the sickle cell trait population going forward.