Abstract: PO1668
Drug-Induced Thrombotic Microangiopathy as a "Second-Hit" Phenomenon
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - 2
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Liaqat, Aimen, Cleveland Clinic, Cleveland, Ohio, United States
- Mehdi, Ali, Cleveland Clinic, Cleveland, Ohio, United States
- Hassanein, Mohamed, Cleveland Clinic, Cleveland, Ohio, United States
- Vachharajani, Tushar J., Cleveland Clinic, Cleveland, Ohio, United States
Introduction
Thrombotic Microangiopathy (TMA) syndrome is a diverse group of inherited or acquired diseases characterized by microvascular thrombosis and endothelial damage. Etiologies include drugs, thrombotic thrombocytopenic purpura, shiga toxin mediated hemolytic uremic syndrome (HUS), and complement mediated HUS. Environmental triggers are proposed as a second hit precipitating the disease process in some cases of atypical HUS (aHUS). We hereby present a case of drug induced TMA in a patient with an underlying pathogenic mutation for aHUS.
Case Description
41-year-old male with presented to an outside hospital with AKI requiring dialysis and uncontrolled hypertension. He had a positive urine toxicology and admitted to marijuana, amphetamines (crystal meth), and heroin use. Labs revealed severe anemia and thrombocytopenia along with low haptoglobin, elevated LDH, and schistocytes on blood smear. Shiga toxin assay was negative with normal ADAMS-TS 13 and coagulation profile. C3 was notably low at 63 mg/dL. As such, he was diagnosed with presumed aHUS and treated with steroids, eculizumab, and plasmapheresis. He was then transferred to our facility where a kidney biopsy confirmed TMA. The etiology was presumed to be drug induced, however genetic evaluation showed heterozygosity for a pathogenic variant in the Complement Factor H (CFH) gene region. Notably, his sister also carried the diagnosis of aHUS. The patient was restarted on eculizumab and remained dialysis dependent on discharge. Unfortunately, he was then lost to follow up.
Discussion
Atypical HUS is associated with a myriad of genetic mutations involving the alternate complement pathway. Pathogenic variants of CFH gene have been implicated in autosomal dominant and recessive forms of the disease. While drug use might have triggered the TMA in our patient, it is likely that his underlying mutation was the first hit creating a disease predisposition. It remains unclear how frequently a culprit mutation is present in patients with presumed drug induced TMA. However, in patients with persistent TMA and a suggestive family history, clinical suspicion for aHUS should be maintained. This distinction is important as drug discontinuation alone would be ineffective for aHUS whereas complement-blocking therapies could be potentially curative.