A previously healthy 12-year-old girl presented after four days of fever, diarrhea, abdominal pain, mucosal bleeding, jaundice, and acute kidney injury. Initial evaluation confirmed microangiopathic hemolytic anemia and thrombocytopenia. ADAMTS13 activity was preserved, supporting a diagnosis of complement-mediated thrombotic microangiopathy rather than thrombotic thrombocytopenic purpura.
The patient’s presenting features included systemic inflammatory symptoms (fever, abdominal pain, diarrhea), bleeding manifestations (mucosal bleeding, jaundice), and evidence of renal involvement consistent with acute kidney injury. Laboratory testing documented hemolysis with schistocytes consistent with microangiopathic hemolytic anemia and thrombocytopenia. The report states ADAMTS13 activity was preserved; other specific laboratory values and serial measurements were not reported in the abstract.
Nasopharyngeal polymerase chain reaction testing detected influenza A virus subtype H1N1. A multiplex gastrointestinal PCR panel identified enteropathogenic Escherichia coli; testing for Shiga toxin was negative. The authors attribute the clinical picture to aHUS unmasked by infectious triggers, consistent with the known role of infections in precipitating complement-mediated disease in genetically predisposed individuals.
The patient received therapeutic plasma exchange and hemodialysis early in the course. Despite these interventions, there was no hematologic or renal improvement. Multi-organ involvement progressed, including respiratory failure and elevation of pancreatic enzymes. The case report indicates that plasma exchange had limited efficacy in this instance, consistent with membrane-bound complement regulator defects where plasma exchange may not adequately correct the underlying dysregulation.
Given the lack of response to plasma exchange and the clinical evidence for complement-mediated thrombotic microangiopathy, the treating team initiated terminal complement inhibition with ravulizumab. Following initiation of ravulizumab, the patient experienced rapid hematologic normalization. Renal recovery continued over time, with full renal recovery documented by day 106. No additional details about dosing, timing relative to onset, or adverse events were reported in the abstract.
Genetic analysis revealed a homozygous splice-site variant in CD46 (c.286 + 1G > C), consistent with a diagnosis of atypical hemolytic uremic syndrome (aHUS) due to a defect in a membrane-bound complement regulator (membrane cofactor protein). The presence of this pathogenic CD46 variant explains susceptibility to complement-mediated endothelial injury and thrombotic microangiopathy when triggered by infection.
This case highlights several clinically relevant points drawn from the reported course:
Infections such as influenza A(H1N1) can act as triggers that unmask underlying genetic complement abnormalities leading to aHUS.
Preservation of ADAMTS13 activity helps distinguish complement-mediated aHUS from thrombotic thrombocytopenic purpura in the appropriate clinical context.
Therapeutic plasma exchange may have limited utility in aHUS caused by defects in membrane-bound complement regulators (for example, CD46), as illustrated by the lack of hematologic or renal response in this patient.
Early terminal complement inhibition with agents such as ravulizumab can produce rapid hematologic improvement and can be associated with eventual full renal recovery, as observed by day 106 in this case.
The authors used this case to emphasize the importance of recognizing complement-mediated thrombotic microangiopathy, performing appropriate microbiologic and genetic testing, and considering early C5 blockade when membrane regulator defects are suspected or when plasma exchange fails to produce improvement. The abstract did not report certain specifics such as exact laboratory values, ravulizumab dosing regimen, timing of genetic test results relative to therapy initiation, or adverse event details.
The report notes that informed consent was obtained from the patient’s legal guardians. The authors declared no conflicts of interest. Specific institutional review or other ethical approval details were not reported in the abstract.