Tissue factor dependent pathway and the diagnosis of pre-eclampsia

Pre-eclampsia (P-EC) is a major contributor to perinatal and maternal morbidity and mortality worldwide. Its etiology and pathogenesis remains poorly understood, and differential diagnosis is problematic. During a normal pregnancy, coagulation activation is essential for physiological placental hemostasis, but women with P-EC tend to be more hypercoagulable than normal pregnant women. A common proposed mechanism for P-EC is utero-placental thrombosis. Indeed, multiple placental microthrombi are frequently observed in women with P-EC, and these may compromise placental perfusion and fetal development. This suggests that predisposing factors to thrombosis could contribute to the development of P-EC. Thus studying circulating hemostatic proteins may help elucidate some of the pathogenesis of P-EC and may provide a rational basis for its differential diagnosis and effective treatment. Preliminary studies by our group on third-trimester women suggest that raised circulating factor VII (FVII) is a selective marker for P-EC when women with P-EC were compared with healthy nonpregnant or normal pregnant women groups. Plasma FVII levels have shown good sensitivity and specificity for P-EC of 90% and 80%, respectively. However, significant comparable changes in the other tissue factor (TF)-dependent pathway factors (activated FVII), TF, and tissue factor pathway inhibitor were not observed. Thus we propose the use of plasma FVII as a potential marker of P-EC.