Abstract: FR-PO0914
Navigating Diagnostic Complexities in Recurrent Thrombotic Microangiopathy (TMA): A Case Report
Session Information
- Glomerular Case Reports: Lupus, FSGS, Complement, and More
November 07, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Hirschi, Zoe Alaniz, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Wilkinson, Joshua, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Carbo, Alexander R., Brigham and Women's Hospital, Boston, Massachusetts, United States
- McMahon, Gearoid M., Brigham and Women's Hospital, Boston, Massachusetts, United States
Introduction
TMA is a rare but life-threatening condition characterized by microvascular thrombosis and endovascular damage, often targeting the kidneys, with varying underlying etiologies, prognoses, and risk of recurrence.
Case Description
A 69-year-old female with kidney biopsy-proven TMA in the setting of COVID-19, treated with 4 months of hemodialysis and 1 year of eculizumab, had a baseline creatinine 2.02 mg/dL and urine microalbumin to creatinine ratio (UACR) 245.5 mg/g. Two years later, she presented with dyspnea, edema, and hypertension and was found to have creatinine 3.01 mg/dL, UACR 5,548 mg/g, and hemolytic anemia. There was a persistent decline in C3 and an elevation in Soluble C5b-9, concerning for recurrent TMA. A repeat biopsy showed widespread double contour similar to the initial biopsy, and immunofluorescence with newly skewed light chain distribution. However, serum protein electrophoresis, PET CT, and flow cytometry were negative for paraprotein disease. She resumed weekly eculizumab therapy for complement-mediated TMA. Genetic testing during the initial TMA event was negative for predisposing mutations. At discharge, creatinine and hemolysis stabilized, proteinuria improved, and a repeat genetic panel was pending.
Discussion
Recurrent TMA presents a diagnostic challenge due to its diverse etiologies, such as complement dysregulation, drug-induced mechanisms, and infections. This case underscores the difficulty in therapeutic decision-making when advanced diagnostics fail to clarify the etiology. While immunofluorescence and genetic testing are vital, genetic variations alone are insufficient for diagnosis, as many patients may lack detectable mutations or have driver genes not included in current panels. This complicates therapy decisions, as literature supports limited eculizumab use without a genetic driver. If genetic drivers are missed, it could adversely affect outcomes, as timely anti-complement therapy is crucial for stabilizing renal damage in complement-mediated TMA. A comprehensive approach, integrating clinical presentation, lab findings, and advanced testing, is essential. Expanding genetic panels should be prioritized to ensure appropriate candidates for indefinite anti-complement therapy are identified, preventing untreated TMA progression. Clinicians must remain vigilant for atypical TMA presentations.