Congenital and acquired ADAMTS13 deficiency: Two mechanisms, one patient

J Clin Apher. 2015 Aug;30(4):252-6. doi: 10.1002/jca.21366. Epub 2014 Nov 4.

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microangiopathy with a heterogeneous and largely unpredictable course. It is caused by ADAMTS13 deficiency, that can be either congenital or due to anti-ADAMTS13 autoantibodies development. ADAMTS13 deficiency is necessary but not always sufficient to cause acute clinical manifestations and trigger factors may be needed. We report the case of a woman diagnosed with congenital TTP in her adulthood, presenting with anti-ADAMTS13 autoantibodies in acute phase during ticlopidine consumption. Noteworthy, the two ADAMTS13 mutations identified in this patient are novel: one is a splice-site mutation located in intron 11 (c.1308+2_5delTAGG) and the other is a point missense mutation in exon 29 (c.4184T>C leading to p.Leu1395Pro substitution). Since congenital TTP is an extremely rare disease and drug-induced TTP is an uncommon side effect of treatment with ticlopidine, the simultaneous occurrence of both mechanisms of disease in one patient is exceptional. This case represents TTP as a multifactorial disease, with ADAMTS13 genetic abnormality and environmental exposures acting together in determining individual clinical phenotype.

Keywords: ADAMTS13; congenital; mutation; thrombotic thrombocytopenic purpura; ticlopidine.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / blood
  • ADAM Proteins / deficiency*
  • ADAM Proteins / genetics*
  • ADAMTS13 Protein
  • Adult
  • Autoantibodies / chemistry
  • Environmental Exposure
  • Family Health
  • Female
  • Humans
  • Infant, Newborn
  • Male
  • Mutation, Missense
  • Pedigree
  • Phenotype
  • Point Mutation
  • Purpura, Thrombotic Thrombocytopenic / blood
  • Purpura, Thrombotic Thrombocytopenic / congenital
  • Purpura, Thrombotic Thrombocytopenic / genetics*
  • Ticlopidine / chemistry

Substances

  • Autoantibodies
  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human
  • Ticlopidine

Supplementary concepts

  • Thrombotic thrombocytopenic purpura, acquired