Acquired thrombotic thrombocytopenic purpura with isolated CFHR3/1 deletion—rapid remission following complement blockade
| Autor: | Arnaud Bonnefoy, Watfa Shahwan Al Dhaheri, Catherine Vezina, Rawan M. Hammad, Martin Bitzan, Georges-Etienne Rivard |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Thrombotic microangiopathy Atypical hemolytic uremic syndrome Thrombotic thrombocytopenic purpura 030204 cardiovascular system & hematology Ultra-large von Willebrand factor multimers Antibodies Monoclonal Humanized 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Complement C3b Inactivator Proteins Humans Complement Activation Acquired Thrombotic Thrombocytopenic Purpura Purpura Thrombotic Thrombocytopenic business.industry Brief Report Microangiopathic hemolytic anemia Blood Proteins Eculizumab medicine.disease ADAMTS13 Morocco Complement Inactivating Agents Treatment Outcome Nephrology Child Preschool Pediatrics Perinatology and Child Health Immunology Alternative complement pathway business Complement factor H-related protein 030215 immunology medicine.drug |
| Zdroj: | Pediatric Nephrology (Berlin, Germany) |
| ISSN: | 1432-198X 0931-041X |
| Popis: | Background Thrombotic thrombocytopenic purpura (TTP) is caused by the abundance of uncleaved ultralarge von Willebrand factor multimers (ULvWF) due to acquired (autoantibody-mediated) or congenital vWF protease ADAMTS13 deficiency. Current treatment recommendations include plasma exchange therapy and immunosuppression for the acquired form and (fresh) frozen plasma for congenital TTP. Case-diagnosis/treatment A previously healthy, 3-year-old boy presented with acute microangiopathic hemolytic anemia, thrombocytopenia, erythrocyturia and mild proteinuria, but normal renal function, and elevated circulating sC5b-9 levels indicating complement activation. He was diagnosed with atypical hemolytic uremic syndrome and treated with a single dose of eculizumab, followed by prompt resolution of all hematological parameters. However, undetectably low plasma ADAMTS13 activity in the pre-treatment sample, associated with inhibitory ADAMTS13 antibodies, subsequently changed the diagnosis to acquired TTP. vWF protease activity normalized within 15 months without further treatment, and the patient remained in long-term clinical and laboratory remission. Extensive laboratory workup revealed a homozygous deletion of CFHR3/1 negative for anti-CFH antibodies, but no mutations of ADAMTS13, (other) alternative pathway of complement regulators or coagulation factors. Conclusions This case, together with a previous report of a boy with congenital TTP (Pecoraro et al. Am J Kidney Dis 66:1067, 2015), strengthens evolving in-vitro and ex-vivo evidence that ULvWF interferes with complement regulation and contributes to the TTP phenotype. Comprehensive, prospective complement studies in patients with TTP may lead to a better pathophysiological understanding and novel treatment approaches for acquired or congenital forms. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |