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.

Inclusion Criteria:

- Peripartum women (White, Black) with Hemoglobin AA or AS

Exclusion Criteria:

- Hispanic ethnicity