Diagnostic and Therapeutic Challenge: A Case Report of Thrombotic Thrombocytopenic Purpura vs. Atypical Hemolytic Uremic Syndrome in a Postpartum Patient

Introduction: Thrombotic microangiopathies (TMAs) in pregnancy, such as thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome (aHUS), present with overlapping features. Accurate diagnosis is essential due to significant differences in treatment and prognosis. Case Description: An 18-year-old G1P1 at 38.2 weeks presented 1 day postpartum with mild preeclampsia but postoperatively developed anemia, thrombocytopenia, and acute kidney injury (AKI) (serum creatine 2.0 mg/dl from baseline of 0.9 mg/dl). Initial labs showed 1–2 schistocytes/HPF, thrombocytopenia without clumping, mildly elevated AST, and normal ALT. A PLASMIC score of 7 indicated a high risk for TTP. ADAMTS13 activity was <2% from LabCorp and Machaon, suggesting TTP. Treatment with high-dose steroids, eculizumab, and plasmapheresis (PLEX) (9 sessions) was started. Due to thrombocytopenia and worsening AKI (serum creatinine 10 mg/dl), eculizumab was changed to caplacizumab after 9 days. She received three doses of rituximab (1 g each) and was started on hemodialysis. Repeat ADAMTS13 was 109% and inhibitor-negative, essentially ruling out congenital TTP. Genetic testing showed a pathogenic variant in the C3 gene (Arg1303Cys) affecting the TED domain—the cleavage site for Factor H. The mutation likely led to impaired regulation of complement activation, favoring a diagnosis of aHUS. The patient was transitioned to ravulizumab. caplacizumab was discontinued after 6 days due to a transient drop in platelets, prompting a brief resumption of PLEX (3 sessions). Platelet counts later stabilized, and hemoglobin remained stable following transfusion of 4 units of RBCs. Although the initial picture suggested TTP, but the final diagnosis was aHUS. Kidney biopsy was deferred, as it would not distinguish TTP from aHUS or impact management. She was discharged on a prednisone taper, prophylactic antibiotics, and hemodialysis. Outpatient care includes scheduled eculizumab infusions and close hematology follow-ups. Her follow-up platelet count was 272000, and her serum creatinine level was 1.64 mg/dl. Discussion: Pregnancy-associated TMAs require a high index of suspicion, early ADAMTS13 testing, and genetic analysis to distinguish between overlapping syndromes. Treatment must be tailored dynamically based on evolving clinical and diagnostic findings.