ADAMTS13 and microvascular thrombosis.
Interaction between platelet and von Willebrand factor, a circulating adhesive glycoprotein, is essential for hemostasis under the high shear environments of arterioles and capillaries. If unregulated, this interaction may lead to unwarranted platelet thrombosis. ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motif, number 13), a plasma zinc metalloprotease synthesized primarily in the stellate cells of the liver, cleaves shear stress-activated von Willebrand factor, thereby preventing the occurrence of von Willebrand factor-platelet interaction in the circulation. A profound deficiency of ADAMTS13, due to genetic mutations or autoimmune inhibition, results in intravascular von Willebrand factor platelet aggregation and widespread microvascular thrombosis characteristic of thrombotic thrombocytopenic purpura. Cloning of ADAMTS13 and structure-function analyses of the enzyme are leading to exciting advances in the diagnosis and therapy of this hitherto mysterious disease.
Tsai
Han-Mou
HM
Montefiore Medical Center and Albert Einstein College of Medicine, Unified Division of Hematology, Bronx, New York, NY, USA. htsai@montefiore.org
D051722:ADAM Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000071120:ADAMTS13 Protein; D001792:Blood Platelets / Q000502:physiology; D003001:Cloning, Molecular; D006801:Humans; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology* / Q000628:therapy; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000378:metabolism / Q000502:physiology
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human