ADAMTS13 and von Willebrand Factor in Thrombotic Thrombocytopenic Purpura

By X. L. Zheng. 2015

224 citations recorded by the source corpus.

Pathogenesis of thrombotic thrombocytopenic purpura (TTP) was a mystery for over half a century until the discovery of ADAMTS13. ADAMTS13 is primarily synthesized in the liver, and its main function is to cleave von Willebrand factor (VWF) anchored on the endothelial surface, in circulation, and at the sites of vascular injury. Deficiency of plasma ADAMTS13 activity (<10%) resulting from mutations of the ADAMTS13 gene or autoantibodies against ADAMTS13 causes hereditary or acquired (idiopathic) TTP. ADAMTS13 activity is usually normal or modestly reduced (>20%) in other forms of thrombotic microangiopathy secondary to hematopoietic progenitor cell transplantation, infection, and disseminated malignancy or in hemolytic uremic syndrome. Plasma infusion or exchange remains the initial treatment of choice to date, but novel therapeutics such as recombinant ADAMTS13 and gene therapy are under development. Moreover, ADAMTS13 deficiency has been shown to be a risk factor for the development of myocardial infarction, stroke, cerebral malaria, and preeclampsia.

Subfields: Genetics, Immunology, Nephrology

How researchers see this paper

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In Genetics

1. S. Apte
2. S. Zhong
3. R. Khalil
4. T. Mead
5. S. Takeda

In Immunology

1. S. Apte
2. S. Zhong
3. R. Khalil
4. T. Mead
5. S. Takeda

In Nephrology

1. S. Apte
2. S. Zhong
3. R. Khalil
4. T. Mead
5. S. Takeda

Citations in the corpus

• A Disintegrin and Metalloproteinase (ADAM) and ADAM with Thrombospondin Motifs (ADAMTS) Family in Vascular Biology and Disease (2019, background): “ADAMTS-13 cleaves ultra-large vWF multimers, which are prothrombogenic and favor platelet adhesion, into an optimal size required for normal hemostasis [110].”
• ADAM and ADAMTS Family Proteins and Snake Venom Metalloproteinases: A Structural Overview (2016, background): “In addition, fine mapping of epitopes of anti-ADAMTS13 antibodies derived from TTP patients, has provided further insight into the structural elements in ADAMTS13 that are essential for VWF binding.”
• The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family (2015, background): “Autoantibodies to ADAMTS13 also give rise to acquired TTP [55].”
• ADAMTS proteins in human disorders (2018, background): “ADAMTS13 cleavage of ULvWF into smaller fragments mitigates the procoagulative function (reviewed in [89]).”