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ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13)—also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted in blood and degrades large vWf multimers, decreasing their activity.[1]


The ADAMTS13 gene maps to the ninth chromosome (9q34).[1]


Since 1982 it had been known that thrombotic thrombocytopenic purpura (TTP), one of the microangiopathic hemolytic anemias (see below), was characterized in its familial form by the presence in plasma of unusually large von Willebrand factor multimers (ULVWF).[1]

In 1994, vWF was shown to be cleaved between a tyrosine at position 1605 and a methionine at 1606 by a plasma metalloprotease enzyme when it was exposed to high levels of shear stress. In 1996, two research groups independently further characterized this enzyme. In the next two years, the same two groups showed that the congenital deficiency of a vWF-cleaving protease was associated with formation of platelet microthrombi in the small blood vessels. In addition, they reported that IgG antibodies directed against this same enzyme caused TTP in a majority of non-familial cases.[1]


Genomically, ADAMTS13 shares many properties with the 19 member ADAMTS family, all of which are characterised by a protease domain (the part that performs the protein hydrolysis), an adjacent disintegrin domain and one or more thrombospondin domains. ADAMTS13 in fact has eight thrombospondin domains. It has no hydrophobic transmembrane domain, and hence it is not anchored in the cell membrane.[1]

Role in disease

Deficiency of ADAMTS13 was originally discovered in Upshaw Schulman Syndrome, the recurring familial form of thrombotic thrombocytopenic purpura. By that time it was already suspected that TTP occurred in the autoimmune form as well, owing to its response to plasmapheresis and characterisation of IgG inhibitors. Since the discovery of ADAMTS13, specific epitopes on its surface have been shown to be the target of inhibitory antibodies.[1][2][3]

Low levels of ADAMTS13 are also associated with an increased risk of arterial thrombosis,[4] including myocardial infarction[5] and cerebrovascular disease.[6][7]

Finally, since the link between aortic valve stenosis and angiodysplasia was proven to be due to high shear stress (Heyde's syndrome), it has been accepted that increased exposure of vWf to ADAMTS13 due to various reasons would predispose to bleeding by causing increased degradation of vWf. This phenomenon is characterised by a form of von Willebrand disease (type 2a).[1]

See also


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Levy GG, Motto DG, Ginsburg D (July 2005). "ADAMTS13 turns 3". Blood. 106 (1): 11–7. doi:10.1182/blood-2004-10-4097. PMID 15774620.
  2. Tsai HM (April 2003). "Advances in the pathogenesis, diagnosis, and treatment of thrombotic thrombocytopenic purpura". Journal of the American Society of Nephrology. 14 (4): 1072–81. doi:10.1097/01.ASN.0000060805.04118.4C. PMID 12660343.
  3. Furlan M, Lämmle B (June 2001). "Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease". Best Practice & Research. Clinical Haematology. 14 (2): 437–54. doi:10.1053/beha.2001.0142. PMID 11686108.
  4. Sonneveld MA, de Maat MP, Leebeek FW (July 2014). "Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis". Blood Reviews. 28 (4): 167–78. doi:10.1016/j.blre.2014.04.003. PMID 24825749.
  5. Maino A, Siegerink B, Lotta LA, Crawley JT, le Cessie S, Leebeek FW, Lane DA, Lowe GD, Peyvandi F, Rosendaal FR (August 2015). "Plasma ADAMTS-13 levels and the risk of myocardial infarction: an individual patient data meta-analysis". Journal of Thrombosis and Haemostasis. 13 (8): 1396–404. doi:10.1111/jth.13032. PMID 26073931.
  6. Sonneveld MA, de Maat MP, Portegies ML, Kavousi M, Hofman A, Turecek PL, Rottensteiner H, Scheiflinger F, Koudstaal PJ, Ikram MA, Leebeek FW (December 2015). "Low ADAMTS13 activity is associated with an increased risk of ischemic stroke". Blood. 126 (25): 2739–46. doi:10.1182/blood-2015-05-643338. PMID 26511134.
  7. Denorme F, Kraft P, Pareyn I, Drechsler C, Deckmyn H, Vanhoorelbeke K, Kleinschnitz C, De Meyer SF (2017). "Reduced ADAMTS13 levels in patients with acute and chronic cerebrovascular disease". PLOS One. 12 (6): e0179258. doi:10.1371/journal.pone.0179258. PMC 5462472. PMID 28591212.

Further reading

External links