Tsai H M, Lian E C
Division of Hematology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY 10467, USA.
N Engl J Med. 1998 Nov 26;339(22):1585-94. doi: 10.1056/NEJM199811263392203.
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.
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.
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.
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.
血栓性血小板减少性紫癜是一种潜在的致命性疾病，其特征为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一种血浆蛋白酶裂解。我们探讨了这种蛋白酶缺乏使血栓性血小板减少性紫癜患者易发生血小板血栓形成的假说。
我们研究了血管性血友病因子裂解蛋白酶的活性，并在急性血栓性血小板减少性紫癜患者、其他疾病患者及正常对照者的血浆中寻找该蛋白酶的抑制剂。我们还研究了剪切应力对血浆样本冷上清液部分中纯化的血管性血友病因子瑞斯托霉素辅因子活性的影响。
37例急性血栓性血小板减少性紫癜患者的39份血浆样本严重缺乏血管性血友病因子裂解蛋白酶。处于缓解期的血栓性血小板减少性紫癜患者的16份血浆样本、随机选取的住院患者或门诊患者的74份血浆样本、或因其他原因出现溶血、血小板减少或血栓形成的患者的血浆样本中均未检测到缺乏。在疾病急性期获得的39份血浆样本中的26份（67%）检测到了针对该蛋白酶的抑制活性。这些抑制剂为IgG抗体。剪切应力增加了急性期获得的血浆样本冷上清液中血管性血友病因子的瑞斯托霉素辅因子活性，但降低了正常受试者血浆冷上清液中的活性。
急性血栓性血小板减少性紫癜患者存在针对血管性血友病因子裂解蛋白酶的抑制性抗体。这种蛋白酶的缺乏可能在该疾病血小板血栓形成的发病机制中起关键作用。
