A case report on the effective and safe use of ravulizumab in atypical hemolytic uremic syndrome during pregnancy

Atypical hemolytic uremic Syndrome (aHUS), a form of thrombotic microangiopathy (TMA), had a poor prognosis until the development of complement C5-inhibiting monoclonal antibodies, eculizumab and ravulizumab. While ravulizumab has shown effectiveness in treating postpartum TMA, data about its use during pregnancy remains lacking. A 32-year-old woman with a history of aHUS was initially diagnosed in 2018 at the age of 27 after presenting with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI) requiring hemodialysis and plasma exchange. Kidney biopsy showed evidence of TMA, and genetic testing identified a pathogenic CD46 (MCP) variant, confirming complement-mediated aHUS. She achieved complete hematologic and renal recovery with eculizumab therapy and remained dialysis-independent thereafter. Eculizumab was continued until 2021, with brief interruptions during the COVID-19 pandemic, due to intermittent drug shortages. Treatment was discontinued, and the patient remained clinically stable under close monitoring. In 2022, during routine follow-up, she was found to be pregnant without complications. The pregnancy was unplanned; however, she was closely monitored throughout early gestation with regular assessments of renal function, hematologic parameters, blood pressure, proteinuria, and complement activity. Prophylactic complement inhibition was not initiated during early pregnancy because eculizumab was unavailable, and she remained in remission during the first trimester. At 25 weeks’ gestation, she developed a relapse of aHUS characterized by vomiting, diarrhea, anemia, thrombocytopenia, hypertension, and AKI. Stool testing for Shiga toxin–producing Escherichia coli was negative. Eculizumab was unavailable; thus, after informed consent, ravulizumab was initiated based on her body weight as per the manufacturer’s label: a loading dose of 2,700 mg on Day 1 and a maintenance dose of 3,300 mg on Day 14, and subsequently 3300 mg every eight weeks. The patient achieved rapid hematologic and renal recovery and had a spontaneous full-term vaginal delivery without maternal or neonatal complications. Both mother and child remained well after about four years of follow-up on ravulizumab. This case report highlights the potential role of ravulizumab in managing aHUS during pregnancy. Given the limited safety data, further studies are needed to guide its use in this setting.