Pregnancy-associated aHUS with a non-complement variant: a case report. Can a coagulation gene variant dictate prognosis?

Postpartum acute kidney injury (AKI) may arise from multiple etiologies, such as amniotic fluid embolism (AFE), renal cortical necrosis (RCN), thrombotic thrombocytopenic purpura (TTP), or atypical hemolytic uremic syndrome (aHUS). Among these, complement system genetic variants are identified in up to 60% of aHUS cases. Here, we describe a rare case of postpartum AKI due to concurrent AFE and pregnancy-associated aHUS (P-aHUS) in a patient with variant in coagulation factor II (F2) genes, suggesting a possible association between F2 variant and aHUS. A 31-year-old woman at 38 weeks of gestation developed sudden cardiovascular collapse, hypoxemia, and coagulopathy immediately following placental delivery, leading to a diagnosis of AFE complicated by disseminated intravascular coagulation (DIC). After successful resuscitation, she was transferred to the intensive care unit. Her clinical course subsequently progressed to acute kidney injury, accompanied by laboratory findings consistent with microangiopathic hemolytic anemia (presence of schistocytes), thrombocytopenia, and evidence of complement activation (markedly decreased C3 and CH50). Renal biopsy confirmed thrombotic microangiopathy (TMA) and genetic testing identified variant in F2 gene. Based on these results, we hypothesized that the variant in F2 gene contributed to complement activation which caused aHUS. Management involved plasma exchange three times per week, combined with anticoagulation therapy (rivaroxaban) and basic life support. Following this regimen, her hemolytic parameters and complement levels normalized, and renal function significantly improved, allowing discontinuation of dialysis. During six years of follow-up after discharge, her renal function remained stable with all key laboratory parameters within normal ranges. We report a pregnancy-associated aHUS case without previously known complement variants but with a positive response to plasma exchange and anticoagulant therapy. The discovery of rare F2 variant hints at a new genetic factor that may induce aHUS.