Sci. STKE, 16 October 2001
Pathogenetics ADAMTS13, VWF, and TTP
A hallmark of thrombotic thrombocytopenic purpura (TTP) is destruction of platelets and erythrocytes. It is thought that the greatly reduced proteolytic cleavage of von Willebrand factor [(VWF), a protein that is important for proper blood clotting] seen in TTP patients, provides a clue to the etiology of the disease. In the absence of proteolytic cleavage, VWF multimerizes and leads to pathological platelet aggregation. Levy et al. have identified a mutated gene in TTP patients that may give rise to the serious illness. The gene encodes the long-sought zinc metalloproteinase that cleaves VWF, termed ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type I motif gene 13). ADAMTS13 activity was nearly undetectable in affected TTP patients, reinforcing the suggestion that ADAMTS13 activity is critical for proper VWF enzymatic cleavage and platelet function. See the News & Views by Fosang and Smith for more details.
G. G. Levy, W. C. Nichols, E. C. Lian, T. Foroud, J. N. McClintick, B. M. McGee, A. Y. Yang, D. R. Siemieniak, K. R. Stark, R. Gruppo, R. Sarode, S. B. Shurin, V. Chandrasekaran, S. P. Stabler, H. Sabio, E. E. Bouhassira, J. D. Upshaw Jr., D. Ginsburg, H.-m. Tsai, Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413, 488-494 (2001). [Online Journal]
A. J. Fosang, P. J. Smith, To clot or not to clot. Nature 413, 475-476 (2001). [Online Journal]
Citation: ADAMTS13, VWF, and TTP. Sci. STKE 2001, tw385 (2001).
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