Abstract: PO2229
Pregnancy-Associated Atypical Hemolytic Uremic Syndrome in the Setting of a Rare THBD Mutation and Successful Treatment with Eculizumab
Session Information
- Advances in Women's Health and Kidney Diseases
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Women’s Health and Kidney Diseases
- 2000 Women’s Health and Kidney Diseases
Authors
- Wyatt, Nicole, Brookwood Baptist Health, Birmingham, Alabama, United States
- Vance, Katisha T., Brookwood Baptist Health, Birmingham, Alabama, United States
- Townsley, Erin, Brookwood Baptist Health, Birmingham, Alabama, United States
- Madonia, Phillip, Brookwood Baptist Health, Birmingham, Alabama, United States
Introduction
Pregnancy-associated atypical hemolytic uremic syndrome (PaHUS) is a rare but fatal thrombotic microangiopathy that results from uncontrolled complement activation during the peripartum and postpartum periods. Underlying complement gene mutations are found in a majority of cases. THBD, the gene responsible for encoding thrombomodulin, is a known risk variant associated with PaHUS. We present a case of PaHUS complicated by intrauterine fetal demise and acute renal failure in the setting of a rare THBD gene variance which was successfully treated with the terminal complement inhibitor eculizumab.
Case Description
20-year G1P0 female presented at 30w4d with severe abdominal pain and diffuse vaginal bleeding. An emergent cesarian section revealed a placental abruption with intrauterine fetal demise. Hospital course was complicated by anuria with a maximum serum creatinine 8.43 mg/dL, hemoglobin 5.5 g/dL, platelets 15 x10^3/uL, lactate dehydrogenase 9051 U/L, and schistocytes seen on peripheral smear. She was initiated on renal replacement therapy, daily plasma exchange, and steroids. Despite this, she experienced persistent hemolysis, dialysis dependence, and worsening respiratory failure ultimately requiring intubation. ADAMTS13 activity was normal at 83%. Eculizumab was initiated, and after one week, hematologic parameters normalized with evidence of renal recovery. Outpatient genetic testing revealed a rare variant in THBD. Six months following discharge, the patient remains in remission on maintenance eculizumab.
Discussion
The diagnosis of PaHUS is very challenging; however, prompt recognition and subsequent genetic testing for complement variants are crucial given association with more severe outcomes, progression to ESRD, and increased risk of relapse. Pathologic variances in THBD account for 5% of aHUS cases and have been associated with earlier onset and higher mortality, however, risk of disease relapse with mutations in this gene is unknown. Although eculizumab has been shown effective in PaHUS, there is little data on treatment duration and recurrence rate with therapy in subsequent pregnancies. Further expansion of genetic testing is required to enhance our knowledge of all PaHUS susceptibility factors and improve management of patients similar to the presented case.