Excellent Response to Eculizumab in a Patient With Complement-Mediated Thrombotic Microangiopathy and a Novel Plasminogen Gene Variant.

Abstract

A middle-aged man presented with myalgia, fever, hematemesis, and melena. He was found to have acute kidney injury, acute coronary syndrome, thrombocytopenia, and Coombs-negative hemolytic anemia, raising concern for thrombotic microangiopathy (TMA). While awaiting confirmatory testing, empirical plasma exchange was initiated. Initially, minimal red blood cell fragmentation was observed, which later progressed to florid fragmentation. Despite supportive care, his clinical status deteriorated requiring hemodialysis. The presence of TMA, along with ADAMTS13 metalloprotease activity above the diagnostic threshold, worsening kidney function, and negative stool Shiga toxin testing suggested complement-mediated TMA (C-TMA). Stool PCR testing revealed rotavirus. Eculizumab was initiated, resulting in rapid normalization of hematological parameters and eventual renal recovery. Genetic testing identified a heterozygous PLG c.1735G > A (p.Gly579Arg) variant classified as a variant of uncertain significance (VUS). The importance of serial review of peripheral blood smears and the diagnostic challenge of differentiating TTP, STEC-HUS, and C-TMA are the key learning points.