Detection of decreased response to activated protein C during pregnancy byan endogenous thrombin potential-based assay

Pregnancy has been widely recognized as a predisposing risk factor for deep vein thrombosis (DVT), However, it still remains unclear why pregnant wome n without a history of familial thrombophilia or antiphospholipid syndrome (APS) have a higher incidence of DVT and pulmonary embolism (PE) during pre gnancy and puerperium. We examined the activated protein C (APC) system in healthy pregnant women and in patients with the onset of DVT during puerper ium. Sixty unselected Japanese pregnant women without a past or family hist ory of thrombosis or APS and 3 Japanese women with DVT during puerperium we re evaluated. Endogenous thrombin potential-ratio (ETP-r) was measured by d etermination of thrombin-alpha(2)-macroglobulin complexes in thromboplastin -activated patient plasma. APC sensitivity ratio (APC-sr) was calculated by the determination of ETP-r in patient plasma in the presence and absence o f APC (final concentration [conc,] 5.9 nM) to evaluate the functional APC a nticoagulant activity. Mean APC-sr was significantly increased at 30 weeks' gestation (2.35 +/- 0.72) and remained high during puerperium compared wit h the mean APC-sr in nonpregnant women (1.15 +/- 0.63), Mean APC-sr in pati ents with DVT at the onset was significantly higher (3.57 +/- 0.54) than me an APC-sr during puerperium was, indicating that the sensitivity to APC was reduced in the ETP-based assay. These data suggest a significant reduction in the functional sensitivity to APC associated with an increased risk of venous thrombosis during pregnancy.