Acquired thrombotic thrombocytopenic purpura with isolated CFHR3/1 deletion-rapid remission following complement blockade.
Pediatr Nephrol
; 33(8): 1437-1442, 2018 08.
Article
in En
| MEDLINE
| ID: mdl-29728803
ABSTRACT
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 661067, 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Purpura, Thrombotic Thrombocytopenic
/
Complement C3b Inactivator Proteins
/
Blood Proteins
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Complement Inactivating Agents
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Antibodies, Monoclonal, Humanized
Type of study:
Diagnostic_studies
/
Guideline
Limits:
Child, preschool
/
Humans
/
Male
Country/Region as subject:
Africa
Language:
En
Journal:
Pediatr Nephrol
Journal subject:
NEFROLOGIA
/
PEDIATRIA
Year:
2018
Type:
Article
Affiliation country:
Canada