Von Willebrand factor–cleaving protease (ADAMTS13) in thrombocytopenic disorders: a severely deficient activity is specific for thrombotic thrombocytopenic purpura

Blood - Tập 100 Số 2 - Trang 710-713 - 2002
Valentina Bianchi1, Rodolfo Robles1, Lorenzo Alberio1, Miha Furlan1, Bernhard Lämmle1
1From the Central Hematology Laboratory, University Hospital, Inselspital, Bern, Switzerland.

Tóm tắt

Abstract A severe deficiency in von Willebrand factor–cleaving protease (ADAMTS13) activity (< 5% that in normal plasma) has been observed in most patients with a diagnosis of thrombotic thrombocytopenic purpura (TTP) but not in those with a diagnosis of hemolytic uremic syndrome. However, ADAMTS13 deficiency has been claimed not to be specific for TTP, since it was observed in various thrombocytopenic and other conditions. We studied 68 patients with thrombocytopenia due to severe sepsis or septic shock (n = 17), heparin-induced thrombocytopenia (n = 16), idiopathic thrombocytopenic purpura (n = 10), or other hematologic (n = 15) or miscellaneous conditions (n = 10). Twelve of the 68 patients had subnormal levels of ADAMTS13 activity (≤ 30%), but none had less than 10%. Thus, the study showed that ADAMTS13 activity is decreased in a substantial proportion of patients with thrombocytopenia of various causes. A severe deficiency of ADAMTS13 (< 5%), identified in more than 120 patients during 1996 to 2001 in our laboratory, is specific for a thrombotic microangiopathy commonly labeled TTP.

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Tài liệu tham khảo

Furlan, 1997, Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura., Blood., 89, 3097, 10.1182/blood.V89.9.3097

Furlan, 1996, Partial purification and characterization of a protease from human plasma cleaving von Willebrand factor to fragments produced by in vivo proteolysis., Blood., 87, 4223, 10.1182/blood.V87.10.4223.bloodjournal87104223

Tsai, 1996, Physiologic cleavage of von Willebrand factor by a plasma protease is dependent on its conformation and requires calcium ion., Blood., 87, 4235, 10.1182/blood.V87.10.4235.bloodjournal87104235

Furlan, 1998, Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome., N Engl J Med., 339, 1578, 10.1056/NEJM199811263392202

Tsai, 1998, Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura., N Engl J Med., 339, 1585, 10.1056/NEJM199811263392203

George, 2000, How I treat patients with thrombotic thrombocytopenic purpura–hemolytic uremic syndrome., Blood., 96, 1223, 10.1182/blood.V96.4.1223

Veyradier, 2001, Specific von Willebrand factor-cleaving protease in thrombotic microangiopathies: a study of 111 cases., Blood., 98, 1765, 10.1182/blood.V98.6.1765

Gerritsen, 2001, Partial amino acid sequence of purified von Willebrand factor-cleaving protease., Blood., 98, 1654, 10.1182/blood.V98.6.1654

Fujikawa, 2001, Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family., Blood., 98, 1662, 10.1182/blood.V98.6.1662

Zheng, 2001, Structure of von Willebrand factor-cleaving protease (ADAMTS13), a metalloprotease involved in thrombotic thrombocytopenic purpura., J Biol Chem., 276, 41059, 10.1074/jbc.C100515200

Soejima, 2001, A novel human metalloprotease synthesized in the liver and secreted into the blood: possibly the von Willebrand factor-cleaving protease?, J Biochem., 130, 475, 10.1093/oxfordjournals.jbchem.a003009

Levy, 2001, Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura., Nature., 413, 488, 10.1038/35097008

Upshaw, 1978, Congenital deficiency of a factor in normal plasma that reverses microangiopathic hemolysis and thrombocytopenia., N Engl J Med., 298, 1350, 10.1056/NEJM197806152982407

Furlan, 2001, Aetiology and pathogenesis of thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome: the role of von Willebrand factor-cleaving protease., Best Pract Res Clin Haematol., 14, 437, 10.1053/beha.2001.0142

Moore, 2001, Decreased von Willebrand factor protease activity associated with thrombocytopenic disorders., Blood., 98, 1842, 10.1182/blood.V98.6.1842

Loof, 2001, Low activity of von Willebrand factor-cleaving protease is not restricted to patients suffering from thrombotic thrombocytopenic purpura., Br J Haematol., 112, 1087, 10.1046/j.1365-2141.2001.02622-5.x

Mannucci, 2001, Changes in health and disease of the metalloproteinase that cleaves von Willebrand factor., Blood., 98, 2730, 10.1182/blood.V98.9.2730

Hunt, 2001, Von Willebrand factor-cleaving protease in childhood diarrhoea-associated haemolytic uraemic syndrome., Thromb Haemost., 85, 975, 10.1055/s-0037-1615949

Oleksowicz, 1999, Deficient activity of von Willebrand's factor-cleaving protease in patients with disseminated malignancies., Cancer Res., 59, 2244

Fontana, 2001, Microangiopathic haemolytic anaemia in metastasizing malignant tumours is not associated with a severe deficiency of the von Willebrand factor-cleaving protease., Br J Haematol., 113, 100, 10.1046/j.1365-2141.2001.02704.x

Barbot, 2001, Ten years of prophylactic treatment with fresh-frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of a congenital deficiency of von Willebrand factor-cleaving protease., Br J Haematol., 113, 649, 10.1046/j.1365-2141.2001.02808.x

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Blood

Tập 100 Số 2

710-713

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