Registry of 919 patients with thrombotic microangiopathies across Japan: database of Nara Medical University during 1998-2008

Intern Med. 2010;49(1):7-15. doi: 10.2169/internalmedicine.49.2706. Epub 2010 Jan 1.

Abstract

Background: Thrombotic microangiopathies (TMAs) are pathological conditions characterized by generalized microvascular occlusion by platelet thrombi, thrombocytopenia, and microangiopathic hemolytic anemia. Two typical phenotypes of TMAs are hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Severe deficiency of plasma ADAMTS13 activity (ADAMTS13: AC) is more specific for TTP, but not for HUS. Since 1998, our laboratory has functioned as a nationwide referral center for TMAs by analyzing ADAMTS13.

Methods: Of 1,564 patients tested from 426 hospitals, 919 were positive for TMA. Levels of ADAMTS13: AC and the ADAMTS13 neutralizing autoantibody (ADAMTS13: INH) were determined by chromogenic act-ELISA and/or by classic von Willebrand factor multimer assay.

Results: TMA patients consisted of two groups: severe (less than 3% of normal control) and non-severe deficiency of ADAMTS13: AC. Both groups were divided into congenital (n=65) and acquired (n=854) TMA. Of the former, 41 had congenital deficiency of ADAMTS13: AC, while the remaining 24 had disease of unknown etiology. The 854 patients with acquired TMA could be largely grouped into three categories: idiopathic TTP (n=284), idiopathic HUS (n=106), and secondary TMAs (n=464). The secondary TMAs were observed in heterogeneous patient groups and were associated with drugs, connective tissue diseases, malignancies, transplantation, pregnancy, E. coli O157: H7 infection, and other factors. All of the patients with acquired severe ADAMTS13: AC deficiency were positive for ADAMTS13: INH.

Conclusion: Although TMAs are highly heterogeneous pathological conditions, one-third of TMA patients have severe deficiency of ADAMTS13: AC. Platelet transfusions to such patients are contraindicated. Rapid ADAMTS13: AC assays are therefore prerequisite to appropriately treat TMA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / deficiency*
  • ADAMTS13 Protein
  • Algorithms
  • Hemolytic-Uremic Syndrome / blood
  • Hemolytic-Uremic Syndrome / diagnosis*
  • Humans
  • Japan
  • Purpura, Thrombotic Thrombocytopenic / blood
  • Purpura, Thrombotic Thrombocytopenic / diagnosis*
  • Registries*

Substances

  • ADAM Proteins
  • ADAMTS13 Protein
  • ADAMTS13 protein, human