Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development.

Pregnancy and postpartum are high-risk periods for different forms of thrombotic microangiopathy (TMA). However, the management of pregnancy-associated TMA remains ill-defined. This report by an international multidisciplinary (obstetricians, nephrologists, hematologists, intensivists, neonatologists and complement biologists) working group summarizes the current knowledge of these potentially severe disorders and proposes a practical clinical approach to diagnose and manage an episode of pregnancy-associated TMA. This approach takes into account the timing of TMA in pregnancy or postpartum, co-existing symptoms, first-line laboratory work-up and probability-based assessment of possible causes of pregnancy-associated TMA. Its aims are to urgently rule in or out thrombotic thrombocytopenic purpura (TTP) with ADAMTS13 activity testing, to consider alternative disorders with features of TMA (preeclampsia/eclampsia, Hemolysis Elevated Liver enzymes Low Platelets (HELLP) syndrome, antiphospholipid syndrome (APS)) or ultimately to diagnose complement-mediated atypical hemolytic uremic syndrome (aHUS) as a diagnosis of exclusion. Even though rare, it is paramount to diagnose TTP and aHUS associated with pregnancy and postpartum, as both require urgent specific treatment.