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Abstract: PO1749

An Unusual Case of Complement-Mediated Thrombotic Microangiopathy

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Khan, Sobia N., Stony Brook University, Stony Brook, New York, United States
  • Lieberthal, Wilfred, Stony Brook University, Stony Brook, New York, United States
Introduction

Thrombotic microangiopathy is a specific pathologic lesion in which abnormalities in the vessel wall of arterioles and capillaries lead to microvascular thrombosis. Diagnosis is made by tissue biopsy
Complement mediated TMA is hereditary deficiency of regulatory proteins that restrict activation of alternative pathway or hereditary abnormality of proteins that accelerate activation of this pathway. Deficiency of complement factor H or I can also be acquired

Case Description

19-year-old female with ulcerative colitis presented with bloody diarrhea and decreased oral intake for one week. She endorsed not taking mesalamine and use of naproxen daily for two weeks. Laboratory data, leukocytosis 22k with 84% neutrophils, 5% bands and schistocytosis, hemoglobin 6.1g/dL, thrombocytopenia, BUN 77 mg/dL, creatinine 7.16 mg/dL, Lactate dehydrogenase 1042IU/L and haptoglobin undetectable. Coomb’s test negative
The patient was admitted for presumed Colitis flare given methylprednisolone. Renal biopsy obtained for acute kidney injury showed glomerular basement membrane duplication, multi layering and arterioles showed focal obliterative changes and onion skinning. 5% global sclerosis and 18% of glomeruli showed segmental sclerosis. Electron microscopy showed active endothelial injury, including subendothelial expansion. Microangiopathic anemia, thrombocytopenia and acute kidney injury raised concern for TMA. Shiga toxin negative and ADAMTS13 activity ~ 71%. Complement factors and autoantibodies to H, I, and B and membrane cofactor were sent out
Patient started treatment for TTP, presumably aHUS. She received solumedrol 500mg/day IV x 3 and then prednisone 60mg/day. Plasma exchange was initiated. She was noted to have persistent high LDH and undetectable haptoglobin indicating ongoing MAHA. After 2 weeks of meningococcal vaccine, she was started on Eculizumab. Prednisone, Eculizumab and PEX were continued. In the interim, labs showed CFH level~ 105 mcg/mL (normal range 160-142). A genetic renal panel, which tested for CFH, CFI, CFI, MCP, and several other genes, confirmed she had a heterozygous deletion of a CFH related gene, CFHR1/CFHR3, as well as autoantibodies to CFH

Discussion

In our case, aHUS was likely predisposed by her heterozygous deletion of CFHR1/CFHR3 genes. What makes this case unusual is she did not have a homozygous deletion, but developed autoantibodies to CFH, to our knowledge has not been previously reported.