Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura
Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura
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DOI：
10.1182/blood.v91.8.2839.2839_2839_2846
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发表时间：
1998-04-15
期刊：
影响因子：
20.3
通讯作者：
Lämmle, B
中科院分区：
文献类型：
--
作者：
Furlan, M;Robles, R;Lämmle, B
血栓性血小板减少性紫癜（TTP）患者的血浆中含有异常大的血管性血友病因子（VWF）多聚体，可引起体内血小板凝集，新鲜冷冻血浆输注和血浆置换代表了急性TTP的最有效疗法。最近从正常人血浆中分离出了一种负责切割vWF多聚体的特异性蛋白酶，并发现在四名TTP患者中存在缺陷。慢性复发性TTP我们检测了在400天的时间内从另一个患有TTP复发发作的患者收集的血浆样品中vWF裂解蛋白酶的活性，该患者通过血浆交换、血浆输注、长春新碱、皮质类固醇治疗和脾切除术进行治疗。在TTP的第一次发作期间建立了vWF裂解蛋白酶的完全缺陷。随后血小板计数的正常化与蛋白酶活性的出现有关。在从初始TTP事件缓解后3个月，vWF裂解蛋白酶再次消失，血小板计数逐渐降低。在TTP首次急性发作后7个月和11个月发生重度血小板减少症复发。蛋白酶活性缺陷与患者血浆中存在抑制剂（发现为IgG）相关。血浆置换/输注后抗体滴度暂时升高，而长春新碱治疗导致血小板计数恢复，而不影响抑制剂浓度，脾切除术和皮质类固醇治疗导致自身抗体消失，蛋白酶活性和血小板计数正常化，我们的数据表明，该TTP患者的血小板减少症与自身免疫机制导致的vWF切割蛋白酶活性缺失有关。使我们得出结论，获得性以及体质缺陷的vWF切割蛋白酶可能易患TTP。(C)1998年，美国血液学会。
Plasma of patients with thrombotic thrombocytopenic purpura (TTP) has been shown to contain unusually large von Willebrand factor (VWF) multimers that may cause platelet agglutination in vivo, Fresh frozen plasma infusions and plasma exchange represent the most efficient therapy of acute TTP A specific protease responsible for cleavage of vWF multimers has been recently isolated from normal human plasma and was found to be deficient in four patients with chronic relapsing TTP We examined the activity of the vWF-cleaving protease in plasma samples collected over a period of 400 days from a further patient with recurrent episodes of TTP who was treated by plasma exchange, plasma infusion, vincristine, corticosteroid therapy, and splenectomy. Complete deficiency of the vWF-cleaving protease was established during the first episode of TTP. The ensuing normalization of the platelet count was associated with the appearance of the protease activity. Three months after remission from the initial TTP event, the vWF-cleaving protease again disappeared and the platelet count gradually decreased, Relapses of severe thrombocytopenia occurred 7 and 11 months after the first acute episode of TTP Deficient protease activity was associated with the presence in the patient plasma of an inhibitor that was found to be an IgG. Plasma exchange/infusion was followed by a temporary increase in the antibody titer, whereas treatment with vincristine led to a recovery of the platelet count without affecting the inhibitor concentration, Splenectomy and corticosteroid treatment resulted in disappearance of the autoantibody and normalization of the protease activity and of the platelet count, Our data suggest that the thrombocytopenia in this patient with TTP was associated with a lack of the vWF-cleaving protease activity depleted by an autoimmune mechanism, This case, together with our previously reported patients, leads us to conclude that acquired as well as constitutional deficiency of the vWF-cleaving protease may predispose to TTP. (C) 1998 by The American Society of Hematology.