Pregnancy induced TMA in severe preeclampsia results from complement-mediated thromboinflammation

Preeclampsia is a multifactorial vascular disease unique to human pregnancy. While genetic and antiangiogenic factors are important contributors to preeclampsia susceptibility, recent studies have shown that dysregulation and/or over-activation of the complement system has an integral role in disease etiology. Furthermore, the role of the coagulation cascade may be underappreciated in the development of the disease. Traditionally, for research purposes, the pool of preeclampsia cases has been divided into non-severe and severe disease depending on the onset and severity of the symptoms. However, of particular interest are a small but important minority of cases that present with symptoms likening to those of hemolysis, elevated liver enzymes and low platelets syndrome, atypical hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura, all thrombotic microangiopathy (TMA) diseases, with the hallmark mechanisms of endothelial dysfunction and aberrant activation of complement and coagulation cascades. We therefore propose a third class, severe TMA-like preeclampsia to be included in the categorization of preeclampsia patients. Identifying these patients would target research, diagnostic differentiation, and novel treatment options to the subclass of patients with life-threatening disease that are most likely to benefit from next-generation drug development.