Recurrent Postpartum Atypical Hemolytic Uremic Syndrome Caused by a C3 Pathogenic Variant: A Case Report.

BACKGROUND

Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy (TMA) driven by uncontrolled activation of the complement alternative pathway. Pregnancy and postpartum period are well-recognized triggers for aHUS. In recent years, the prognosis of aHUS has substantially improved with the use of complement-targeted therapies. However, timely recognition, accurate classification, and prompt treatment initiation remain critical. This report describes a case of postpartum aHUS caused by a C3 gene mutation that achieved complete clinical and laboratory remission following a treatment strategy that included early eculizumab, plasma infusion, and renal replacement therapy. Drawing on the literature, we discuss key diagnostic and therapeutic considerations as well as clinical implications to provide guidance for clinical practice.

CASE PRESENTATION: We present a 35-year-old multiparous woman (gravida 3, para 3) who developed acute kidney injury, microangiopathic hemolytic anemia, and severe thrombocytopenia 2 days after cesarean section. She had a history of similar TMA episode 8 years postpartum. Laboratory investigations showed normal ADAMTS13 activity, negative autoimmune antibodies, reduced serum complement C3 and factor I levels, and elevated sC5b-9. Whole-exome sequencing identified a heterozygous pathogenic mutation in the C3 gene: c.1774C>T (p.R592W). Eculizumab was initiated within 24 hours of clinical suspicion, combined with plasma infusion and renal replacement therapy. The patient achieved complete clinical and laboratory remission: renal function, platelet count, hemoglobin, and lactate dehydrogenase returned to normal within 4 weeks. She remained stable during long-term follow-up on maintenance eculizumab. This case is particularly instructive because the patient had a prior TMA episode that was retrospectively suggestive of aHUS following genetic confirmation; however, definitive reclassification could not be established with certainty due to the lack of genetic testing at that time.

CONCLUSION

This case highlights that C3 variant-mediated aHUS can be repeatedly triggered by pregnancy. Early recognition, prompt initiation of C5 inhibition, and multidisciplinary care are critical for renal recovery and favorable outcomes. Clinicians should distinguish postpartum aHUS from preeclampsia, HELLP syndrome, and TTP to prevent treatment delay.