Pathophysiology of Placenta in Antiphospholipid Syndrome

Abstract

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by clinical manifestations caused by arterial or venous thrombosis and pregnancy conditions such as recurrent miscarriage, fetal death, or premature birth in the presence of antiphospholipid antibodies. The obstetrical manifestations are strongly related to the placental alterations. The aim of this review is to summarize the latest data on pathophysiology of obstetrical APS, emphasizing the disturbance of the placentation process. Due to a lack of extravillous trophoblasts to properly reconstruct the spiral arteries, APS causes hypoxic or ischemic injury or high-speed blood flow that damages the placenta. This results in decreased or interrupted maternal blood flow to the placenta and a lack of nutrients for the fetus. Antiphospholipid antibodies can lower the proliferation and infiltration of the extravillous trophoblasts. The placental mal-perfusion causes the release of antiangiogenic substances such as soluble fms-like tyrosine kinase-1 and soluble endoglin. Placental growth factor and vascular endothelial growth factor (VEGF) may be sequestered by sFlt1 and blocked from binding to trophoblast and endothelial cell VEGF receptors, inhibiting their proangiogenic effects. Preeclampsia is the clinical result from a lack of angiogenic factors needed for endothelial vascular homeostasis due to an excess of sFlt1 in the maternal circulation.