Complement Mediated Hemolytic Uremic Syndrome associated with Postpartum Hemorrhage: Case Series and Systematic Review of Individual Participants Data

Abstract

BackgroundPostpartum hemorrhage is considered a risk factor for pregnancy-associated Complement-Mediated Hemolytic Uremic Syndrome (CM-HUS) (previously known as atypical Hemolytic Uremic Syndrome[aHUS]), but has not been systematically studied. MethodsA systematic review of individual participant data from case series and reports in addition to a case series from our institution. Search terms were ‘thrombotic microangiopathy (TMA)’, ‘aHUS’, ‘complement mediated’ combined with ‘pregnancy’ ‘postpartum’ and/or post-partum hemorrhage. Cases of TMA other than CM-HUS were excluded. Outcomes were clinical and laboratory characteristics of postpartum hemorrhage-associated CM-HUS, treatment, and outcomes. ResultsThirty-three studies including 48 women with postpartum hemorrhage-associated CM-HUS and three patients from our institution. Most women presented at term (28/45, 62%), delivered by cesarean section (21/41, 51%) and had pregnancy complications, mainly pre-eclampsia (16/51, 31%) or fetal demise (/51; 18%). Hematological and renal abnormalities usually appeared within the first 24 hours post-delivery. Median platelet count was 46x109/L (interquartile range [IQR] 45) and the median maximal lactate dehydrogenase (LDH) was 2638U/L (IQR 1866). Renal function normalized in 20/23 (87%) women treated with C5-inhibitors with or without plasma-exchange; in 7/11 (63%) women treated with plasma-exchange alone; but only in 3/17 (18%) of patients treated with supportive care. Patients treated with C5-inhibitors and/or plasma-exchange achieved significantly better renal outcomes compared with supportive care alone (p<0.001). ConclusionsCM-HUS is a rare complication following postpartum hemorrhage and occurred mainly in women with pre-eclampsia and/or following cesarean section. Patients treated with C5 inhibitors and/or plasma-exchange had a better renal prognosis compared with patients who received supportive treatment alone.