Hematologic disorders in pregnancy: the role of the complement system

INTRODUCTION: Complement homeostasis is essential for healthy pregnancy and excessive complement activation can lead to devastating maternal and fetal outcomes by precipitating or worsening complement-mediated disorders. This review summarizes changes in complement regulation during pregnancy, management considerations in paroxysmal nocturnal hemoglobinuria (PNH), thrombotic microangiopathies (TMA), and antiphospholipid syndrome (APS), and emerging evidence regarding the role of complement in the severe hypertensive disorders of pregnancy (preeclampsia with severe features, HELLP syndrome). AREAS COVERED: This is an expert narrative review. Articles were selected based on the authors' subject-matter expertise to highlight key studies, concepts, and areas of active investigation, rather than through a systematic literature search strategy. Relevant articles on the role of complement in pregnancy are summarized and critiqued. We review pregnancy outcomes and management in PNH, TMA, and APS. We prioritize review of clinical trials, registry or systematic review studies, and novel case reports utilizing complement inhibitors during pregnancy. EXPERT OPINION: Complement inhibitors have greatly improved maternal morbidity and mortality in PNH and complement-mediated TMAs. Establishing functional biomarkers of complement activity in pregnancy, defining metrics for prompt use of complement inhibitors in TMAs, and clinical trials of complement inhibition for obstetric APS and hypertensive disorders of pregnancy are urgently needed.