Complement-mediated hemolytic uremic syndrome associated with postpartum hemorrhage: case series and systematic review of individual participant data

Background: Postpartum hemorrhage is considered a risk factor for pregnancy-associated complement-mediated hemolytic uremic syndrome (CM-HUS; previously known as atypical hemolytic uremic syndrome) but has not been systematically studied. Objectives: To systematically examine the role of postpartum hemorrhage in precipitating CM-HUS and to describe the characteristics of postpartum hemorrhage-associated CM-HUS, its prognosis and recommended management. Methods: A 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,” “atypical hemolytic uremic syndrome,” and “complement mediated” combined with “pregnancy,” “postpartum,” and/or “postpartum hemorrhage”. Cases of thrombotic microangiopathy other than CM-HUS were excluded. Outcomes were clinical and laboratory characteristics of postpartum hemorrhage-associated CM-HUS, treatment, and outcomes. Results: Thirty-three studies comprising 48 women with postpartum hemorrhage-associated CM-HUS and 3 patients from our institution were included in the study. Most women presented at term (28/45; 62%), delivered by cesarean section (21/41; 51%), and had pregnancy complications, mainly preeclampsia (16/51; 31%) or fetal demise (9/51; 18%). Hematological and renal abnormalities usually appeared within the first 24 hours postdelivery. The median platelet count was 46 × 10⁹/L (IQR, 26-72), and the median maximal lactate dehydrogenase was 2638 U/L (IQR, 1620-3588). 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%) 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 < .001). Conclusion: CM-HUS is a rare complication following postpartum hemorrhage and occurs mainly in women with preeclampsia 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.