Sickle Cell Trait, Oral Contraceptives, and the Risk of Venous Thromboembolism.

We recently reported that sickle-cell trait (SCT) is a risk factor for venous thromboembolism (VTE) among African Americans (1). Since current usage of oral contraceptives (OC’s) is an established risk factor for VTE in women of European descent, we investigated the joint effect of OC’s and SCT on VTE risk in the Genetic Attributes and Thrombosis Epidemiology (GATE) study. This case-control study included 57 African American women with an idiopathic, first deep-vein thrombosis and/or pulmonary embolism and 185 controls between the ages of 18 and 49. Subjects were genotyped at codon 6 (E>V) for the hemoglobin S mutation and were interviewed about OC usage. The distribution of cases and controls according to current OC use and SCT is displayed below: The odds ratio of VTE among OC users versus women not currently using OC’s is 2.7 (95% CI: 1.4, 5.1; P = 0.003). However, among subjects with SCT, the odds ratio for OC use is considerably higher (OR = 7.0; 1.1, 45; P = 0.04) than is the odds ratio for OC use among women without SCT (OR = 2.1; 1.0, 4.3; P = 0.05), although the difference in these two odds ratios is not statistically significant (P > 0.20). Nonetheless, the findings indicate that overall, current OC use is a strong risk factor for VTE among African American women. The observation that there is synergy between current OC use and SCT provides some additional support for the finding that SCT is a risk factor for VTE. However, a limitation of this analysis is small numbers and the resultant imprecision. Replication of these findings is thus required before causation can be established.