ADAMTS13 and TTP.
Thrombotic thrombocytopenic purpura (TTP) has been a mysterious and deadly disease that often could be treated effectively by plasma exchange, but without real understanding of the underlying pathophysiology. Recent advances now suggest that deficiency of a specific von Willebrand factor (VWF) cleaving protease promotes tissue injury in TTP. VWF multimers participate in the formation of platelet thrombi. Proteolytic cleavage of VWF multimers normally limits platelet thrombus growth, and failure to cleave VWF appears to encourage microvascular thrombosis. The VWF cleaving protease proves to be a new member of the ADAMTS family of metalloproteases, designated ADAMTS13. Autoantibodies that inhibit ADAMTS13 cause sporadic TTP, and mutations in the ADAMTS13 gene cause an autosomal recessive form of chronic relapsing TTP. Further studies of ADAMTS13 seem likely to change our approach to the diagnosis and treatment of TTP and other thrombotic microangiopathies.
Zheng
Xinglong
X
Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Majerus
Elaine M
EM
Sadler
J Evan
JE
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D006801:Humans; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008833:Microcirculation; D009154:Mutation; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy
D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human