Placental Insufficiency Is Characterized by Platelet Activation in the Fetus

Abstract

In Brief OBJECTIVE To investigate whether activation of circulating platelets was present in the fetal and maternal circulation in cases with vascular disease in the fetal–umbilical–placental circulation as identified by umbilical artery Doppler study. METHODS We studied 20 mother–fetus pairs with an abnormal umbilical artery Doppler study indicating umbilical–placental pathology and 9 normal pregnancy pairs. All pregnancies in these two groups had elective cesarean delivery. We also studied 15 healthy nonpregnant women. Blood was collected at delivery, and flow cytometry was used to measure platelet activation. The platelet population was specified by the antiglycoprotein IIIa (CD61) antibody and activated platelets by the anti-P selectin (CD62) antibody. Platelet activation in response to thrombin (0.03 to 0.25 U/mL) was also assessed. RESULTS In the normal, healthy, nonpregnant women, there was no evidence of platelet activation in the fetal circulation (median, 0.63% of platelet population). Platelet activation was present in the fetal circulation in pregnancies with placental insufficiency (median, 4.57%) compared with normal pregnancies (median, 1.19%) (P = .034). The fetal platelets from pregnancies complicated by placental insufficiency also showed resistance to challenge with increasing thrombin concentration compared with normal fetal platelets (at 0.25 U/mL thrombin concentration, placental insufficiency pregnancy 69.82% and normal pregnancy 81.49%, P = .003). In the maternal circulation there were no differences in platelet activation (normal 4.89%, placental insufficiency 5.16%, P = .33) and sensitivity to thrombin challenge. CONCLUSION In the fetal circulation, the presence of Doppler-detected umbilical–placental vascular disease was associated with significantly enhanced fetal platelet activation and resistance to thrombin challenge. These changes were not noted in the maternal circulation. This provides further evidence of a primary vascular pathology in the fetal–placental circulation independent of disease in the uteroplacental circulation when the umbilical Doppler flow velocity waveform reveals a high resistance pattern. Fetal platelet activation is associated with the placental vascular disease that is detected by umbilical artery Doppler study.