Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura
Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura
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DOI：
10.1056/nejm199811263392203
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发表时间：
1998-11-26
影响因子：
158.5
通讯作者：
Lian, ECY
中科院分区：
文献类型：
--
作者：
Tsai, HM;Lian, ECY
背景血栓性血小板减少性紫癜是一种潜在的致命性疾病，其特征是微循环中广泛存在血小板血栓。在正常循环中，血管性血友病因子被血浆蛋白水解酶切割。方法研究急性血栓性血小板减少性紫癜患者、其他疾病患者和正常对照组血浆中von Willebrand因子裂解酶的活性，并寻找该酶的抑制剂。结果37例急性血栓性血小板减少性紫癜患者的39份血浆标本中均存在严重的von Willebrand因子裂解酶缺陷。16例缓解期血栓性血小板减少性紫癜患者的血浆及74例正常人、随机选择的住院患者或门诊患者、溶血、血小板减少或其他原因引起的血栓形成患者的血浆均未检出缺陷。在疾病急性期获得的39份血浆样本中，有26份(67%)检测到对该蛋白水解酶的抑制活性。抑制物为免疫球蛋白抗体。结论急性血栓性血小板减少性紫癜患者血浆中存在抗von Willebrand因子裂解酶的抑制性抗体，该酶的缺失可能在本病的发病机制中起重要作用。(N Engl J Med 1998；339：1585-94)(C)1998年，马萨诸塞州医学会。
Background Thrombotic thrombocytopenic purpura is a potentially fatal disease characterized by widespread platelet thrombi in the microcirculation. In the normal circulation, von Willebrand factor is cleaved by a plasma protease. We explored the hypothesis that a deficiency of this protease predisposes patients with thrombotic thrombocytopenic purpura to platelet thrombosis.Methods We studied the activity of von Willebrand factor-cleaving protease and sought inhibitors of this protease in plasma from patients with acute thrombotic thrombocytopenic purpura, patients with other diseases, and normal control subjects. We also investigated the effect of shear stress on the ristocetin cofactor activity of purified von Willebrand factor in the cryosupernatant fraction of the plasma samples.Results Thirty-nine samples of plasma from 37 patients with acute thrombotic thrombocytopenic purpura had severe deficiency of von Willebrand factor-cleaving protease. No deficiency was detected in 16 samples of plasma from patients with thrombotic thrombocytopenic purpura in remission or in 74 plasma samples from normal subjects, randomly selected hospitalized patients or outpatients, or patients with hemolysis, thrombocytopenia, or thrombosis from other causes. Inhibitory activity against the protease was detected in 26 of the 39 plasma samples (67 percent) obtained during the acute phase of the disease. The inhibitors were IgG antibodies. Shear stress increased the ristocetin cofactor activity of von Willebrand factor in the cryosupernatant of plasma samples obtained during the acute phase, but decreased the activity in cryosupernatant of plasma from normal subjects.Conclusions Inhibitory antibodies against von Willebrand factor-cleaving protease occur in patients with acute thrombotic thrombocytopenic purpura, A deficiency of this protease is likely to have a critical role in the pathogenesis of platelet thrombosis in this disease. (N Engl J Med 1998;339:1585-94.) (C)1998, Massachusetts Medical Society.