Pregnancy-related thrombotic microangiopathies: Clues from complement biology

Pregnancy is a high-risk period for various types of thrombotic microangiopathies (TMA). The improvement of our understanding of the pathophysiology of TMAs has translated into better management of pregnancy-related TMAs. The two main types of TMA, TTP (thrombotic thrombocytopenic purpura) and hemolytic uremic syndrome (HUS), can both occur during pregnancy and postpartum. TTP is related in most cases to acquired or congenital deficiency of ADAMTS13; it tends to develop mainly during the second and third trimesters of pregnancy. The treatment of pregnancy-TTP aims to restore a detectable ADAMTS13 activity through plasma therapy, and if needed, to induce or sustain remission, immunosuppressive agents. In contrast, HUS develops mainly in the postpartum period. Accumulating data indicate that pregnancy-HUS is an atypical, i.e., complement-mediated HUS, triggered by pregnancy. Its treatment therefore should include the use of the anti-C5 humanized monoclonal antibody eculizumab. In other TMA-like disorders associated with pregnancy, including HELLP (hemolysis, elevated liver enzymes, low platelets) and pre-eclampsia/eclampsia, complement involvement, and the need for specific anti-complement therapies, is an active area of investigation.