Sickle Cell Trait and the Risk of Venous Thromboembolism

Venous thromboembolism is the major cause of maternal mortality in the United States and there are emerging data that the thrombotic risk is higher in peripartum black women as compared to white women. The reasons are unclear: indeed, the few genetic risk factors for venous thrombosis that have been identified are more common in whites than blacks. This raises the possibility of yet undescribed mutations. To bolster this theory, some intriguing studies have noted a similar frequency of 'familial' thrombosis in blacks and whites, supporting the existence of yet unidentified hereditary component(s). Sickle cell anemia is a genetic disease more prevalent in the black population. Whereas sickle cell anemia has been associated with a prothrombotic state, there are limited data to support a prothrombotic state in sickle cell trait. We plan to examine whether sickle cell trait might play a role in increasing the incidence of thrombosis in the black population.

Peripartum women are 4-5 times more likely to develop venous thrombosis. Scant literature exists on the thrombotic risk in women from different races in the peripartum period and there are no studies evaluating venous thrombosis risk in sickle cell trait women during this time of increased thrombogenicity. In a retrospective analysis of deliveries of 12,000 women at Einstein/Montefiore, a higher incidence of venous thrombosis in black peripartum women was observed and, among the black population, a trend for sickle cell trait women to be at higher risk compared to black women with the normal hemoglobin (Hb) AA.

Given the medical importance and financial/sociological impact of venous thrombosis, it is important to determine whether black women, and specifically black women with sickle cell trait, are really at increased risk for thromboembolic disease during the peripartum period and, if so, what intervention(s) might mitigate this risk. We propose to perform a prospective study investigating peripartum white Hb AA, black Hb AA, and black sickle cell trait women by assessing D-Dimer levels. The D-Dimer levels will be assayed at defined times during the peripartum and correlated with pregnancy complications, as well as neonatal and birth data, thrombosis and, in selected cases, lower extremity duplex ultrasonography. If, after analysis, there is evidence confirming an increased thrombotic risk, we will design and institute an interventional trial. The purpose of this application is to fill in the gaps of current knowledge regarding the role of race in venous thromboembolism, to test different methodologies for studying this significant health problem, and to lay the groundwork for clinical trial development to determine whether therapeutic intervention with prophylactic anticoagulation is beneficial during the peripartum period for patients with sickle cell trait.