Thrombotic thrombocytopenic purpura

Nat Rev Dis Primers. 2017 Apr 6:3:17020. doi: 10.1038/nrdp.2017.20.


Thrombotic thrombocytopenic purpura (TTP; also known as Moschcowitz disease) is characterized by the concomitant occurrence of often severe thrombocytopenia, microangiopathic haemolytic anaemia and a variable degree of ischaemic organ damage, particularly affecting the brain, heart and kidneys. Acute TTP was almost universally fatal until the introduction of plasma therapy, which improved survival from <10% to 80-90%. However, patients who survive an acute episode are at high risk of relapse and of long-term morbidity. A timely diagnosis is vital but challenging, as TTP shares symptoms and clinical presentation with numerous conditions, including, for example, haemolytic uraemic syndrome and other thrombotic microangiopathies. The underlying pathophysiology is a severe deficiency of the activity of a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13), the protease that cleaves von Willebrand factor (vWF) multimeric strings. Ultra-large vWF strings remain uncleaved after endothelial cell secretion and anchorage, bind to platelets and form microthrombi, leading to the clinical manifestations of TTP. Congenital TTP (Upshaw-Schulman syndrome) is the result of homozygous or compound heterozygous mutations in ADAMTS13, whereas acquired TTP is an autoimmune disorder caused by circulating anti-ADAMTS13 autoantibodies, which inhibit the enzyme or increase its clearance. Consequently, immunosuppressive drugs, such as corticosteroids and often rituximab, supplement plasma exchange therapy in patients with acquired TTP.

Publication types

  • Review

MeSH terms

  • ADAMTS13 Protein / analysis
  • ADAMTS13 Protein / blood
  • Acetylcysteine / pharmacology
  • Acetylcysteine / therapeutic use
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Female
  • Glucocorticoids / pharmacology
  • Glucocorticoids / therapeutic use
  • HIV Infections / etiology
  • Humans
  • Immunologic Factors / pharmacology
  • Immunologic Factors / therapeutic use
  • Immunomodulation
  • Pregnancy
  • Pregnancy Complications / etiology
  • Purpura, Thrombotic Thrombocytopenic / complications*
  • Purpura, Thrombotic Thrombocytopenic / diagnosis*
  • Purpura, Thrombotic Thrombocytopenic / physiopathology
  • Rituximab / pharmacology
  • Rituximab / therapeutic use
  • Shiga Toxins / adverse effects
  • Splenectomy / methods


  • Antiviral Agents
  • Glucocorticoids
  • Immunologic Factors
  • Shiga Toxins
  • Rituximab
  • ADAMTS13 Protein
  • ADAMTS13 protein, human
  • Acetylcysteine