Pathophysiology of thrombotic thrombocytopenic purpura

Blood. 2017 Sep 7;130(10):1181-1188. doi: 10.1182/blood-2017-04-636431. Epub 2017 Aug 2.

Abstract

The discovery of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) revolutionized our approach to thrombotic thrombocytopenic purpura (TTP). Inherited or acquired ADAMTS13 deficiency allows the unrestrained growth of microthrombi that are composed of von Willebrand factor and platelets, which account for the thrombocytopenia, hemolytic anemia, schistocytes, and tissue injury that characterize TTP. Most patients with acquired TTP respond to a combination of plasma exchange and rituximab, but some die or acquire irreversible neurological deficits before they can respond, and relapses can occur unpredictably. However, knowledge of the pathophysiology of TTP has inspired new ways to prevent early deaths by targeting autoantibody production, replenishing ADAMTS13, and blocking microvascular thrombosis despite persistent ADAMTS13 deficiency. In addition, monitoring ADAMTS13 has the potential to identify patients who are at risk of relapse in time for preventive therapy.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / deficiency
  • Humans
  • Platelet Adhesiveness
  • Purpura, Thrombotic Thrombocytopenic / pathology
  • Purpura, Thrombotic Thrombocytopenic / physiopathology*
  • Purpura, Thrombotic Thrombocytopenic / therapy
  • Recurrence
  • Risk Factors
  • von Willebrand Factor / metabolism

Substances

  • von Willebrand Factor
  • ADAM Proteins