Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura
Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura
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DOI：
10.1182/blood.v89.9.3097
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发表时间：
1997-05-01
期刊：
影响因子：
20.3
通讯作者：
Lammle, B
中科院分区：
文献类型：
--
作者：
Furlan, M;Robles, R;Lammle, B
在血栓性血小板减少性紫癜（TTP）患者中，过度的血管内血小板聚集与血浆中异常大的血管性血友病因子（VWF）多聚体的出现有关。这些粘附性极强的vWF多聚体可能是由于缺乏一种通过减少二聚体间二硫键或蛋白水解降解将vWF切割成更小分子形式的“解聚酶”而产生的。我们研究了最近描述的一种切割vWF的蛋白酶在四名慢性复发性TIP患者中的活性。TTP患者的稀释血浆样品与纯化的正常人vWF在丝氨酸蛋白酶抑制剂的存在下，在低离子强度下，以及在尿素和钡离子的存在下孵育。vWF降解的程度通过十二烷基硫酸钠-琼脂糖凝胶电泳和免疫印迹法测定。四名患者，其中包括两名兄弟，与慢性复发TTP表现出的vWF切割蛋白酶活性的水平大幅降低或完全缺乏，在这些患者的血浆中没有一个是一种抑制剂或抗体对vWF切割蛋白酶建立。我们的数据表明，TTP患者中发现的异常大的vWF多聚体可能是由vWF切割蛋白酶活性不足引起的。这种蛋白酶的缺乏可能以常染色体隐性方式遗传，似乎易患慢性复发性TTP。vWF切割蛋白酶活性的测定可用作鉴定具有潜伏TTP倾向的受试者的灵敏诊断工具。(C)1997年，美国血液学会。
In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (VWF) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a ''depolymerase'' cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by proteolytic degradation, We studied the activity of a recently described vWF-cleaving protease in four patients with chronic relapsing TIP. Diluted plasma samples of TTP patients were incubated with purified normal human vWF in the presence of a serine protease inhibitor, at low ionic strength, and in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. Four patients, that included two brothers, with chronic relapsing TTP displayed either substantially reduced levels or a complete absence of vWF-cleaving protease activity, In none of these patient plasmas was an inhibitor of or an antibody against the vWF-cleaving protease established. Our data suggest that the unusually large vWF multimers found in TTP patients may be caused by deficient vWF-cleaving protease activity. Deficiency of this protease may be inherited in an autosomal recessive manner and seems to predispose to chronic relapsing TTP. The assay of the vWF-cleaving protease activity may be used as a sensitive diagnostic tool for identification of subjects with a latent TTP tendency. (C) 1997 by The American Society of Hematology.