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Abstract: TH-PO674

A Rare Presentation of Genetic Complement-Mediated Thrombotic Microangiopathy

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Almoushref, Allaa, Cleveland Clinic, Cleveland, Ohio, United States
  • Sokola, Maria, Cleveland Clinic, Cleveland, Ohio, United States
  • Toljan, Karlo, Cleveland Clinic, Cleveland, Ohio, United States
  • Khawaja, Zeshaun, Cleveland Clinic, Cleveland, Ohio, United States
  • Ashour, Tarek, Cleveland Clinic, Cleveland, Ohio, United States
Introduction

Complement genetics has recently gained prominence in understanding the pathogenesis of complement mediated thrombotic microangiopathy (CM-TMA) and the development of a specific therapy that is potentially lifesaving.
We present a rare case of ischemic cortical infarcts concurrently with CM-TMA, successfully treated with eculizumab.

Case Description

A 46-year-old male with a history of hypertension and chronic type B aortic dissection presented to the hospital for evaluation of presyncope and paraparesis.
Labs showed profound renal failure with serum creatinine (sCr) of 14 mg/dl (baseline 1.14 mg/dl about 4 years before his presentation). A urinalysis showed > 300 mg of proteins, urine Pr/Cr of 8.0, and > 25 non dysmorphic RBCs/HPF.
The patient was started on hemodialysis for worsening uremia, and shortly he developed ischemic stroke symptoms. MRI of the brain showed acute multifocal ischemic infarcts.
Additional testing showed anemia, thrombocytopenia, elevated lactate dehydrogenase, low haptoglobin, and schistocytes in the peripheral smear. ADAMTS13 was normal. Further workup and serologies for possible infectious or autoimmune diseases were negative. SPEP was normal.
A kidney biopsy showed thrombotic microangiopathy with negative immunofluorescence. Additional testing of complement factors showed elevated factor H, C3a, and C5a, with a normal CH50, and factor B, supporting CM-TMA diagnosis.
The patient was started on an induction dose of eculizumab and remained on a maintenance dose every two weeks. Genetic testing showed homozygous deletion of CFHR1, supporting the long-term use of a C5 inhibitor.
The patient started to show signs of renal recovery. Hemodialysis was discontinued 6 weeks after initiation, and sCr improved and remained stable around 2.4 mg/dl while on eculizumab.
Over a 2-year follow-up, hemoglobin and platelets normalized, and neurologic recovery was full.

Discussion

CM-TMA is caused by dysregulation of the alternative pathway. Eculizumab, a humanized anti-C5 monoclonal antibody, is effective in terminating the microangiopathic hemolytic activity in patients with CM-TMA. Early identification and treatment of this disease can be life-saving. We also highlight the importance of genetic testing as it can guide long-term treatment plans. Patients with high-risk variants and severe disease manifestations may need a prolonged treatment period.