Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies.
Abnormalities of von Willebrand factor multimers in drug-associated thrombotic microangiopathies.
复制标题
药物相关血栓性微血管病中冯维勒布兰德因子多聚体的异常。
DOI：
10.1002/ajh.2830420306
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发表时间：
1993
影响因子：
12.8
通讯作者：
Hester,JP
中科院分区：
文献类型：
--
作者：
Charba,D;Moake,JL;Harris,MA;Hester,JP
6例血栓性微血管病与药物治疗的血管性血友病因子（vWF）的多聚体模式在他们的EDTA-血浆样本的十二烷基硫酸钠-1%琼脂糖凝胶电泳和放射自显影进行了系列分析。在血浆中的5名患者（慢性粒细胞白血病，前列腺癌，淋巴瘤和两个），vWF异常的血栓性微血管病的演变过程中观察到。这些异常是存在异常大（UL）的vWF多聚体，其类型与内皮细胞内发现的并由内皮细胞释放或分泌的类型相似（3例患者），或可诱导附着于血小板的最大血浆vWF多聚体类型相对减少（1例患者），或不同系列样本中的vWF异常（1例患者）。在一个心脏移植患者谁没有发展与血栓性微血管病相关的vWF多聚体异常，vWF抗原水平升高超过三倍。这位后来的个体接受了单独使用环孢菌素A的治疗。其他5名血栓性微血管病患者接受环孢菌素A与其他化疗药物联合治疗（2名患者）;丝裂霉素-C，沿着其他化疗（2名患者）;或多种化疗药物，但不接受环孢菌素A或丝裂霉素C（1名患者）。在对6名药物相关血栓性微血管病患者中的5名患者的血浆样本进行系列分析期间发现vWF多聚体异常，这表明来源于受损或刺激的内皮细胞的ULvWF形式与最大的血浆vWF多聚体一起沿着可能参与血管内血小板凝集，这是这种疾病的病理生理学的重要部分。
Six patients with thrombotic microangiopathy associated with drug therapy had serial analyses of von Willebrand factor (vWF) multimeric patterns in their EDTA-plasma samples by sodium dodecyl sulfate-1% agarose gel electrophoresis and autoradiography. In the plasma of five patients (one with chronic myelogenous leukemia, two with prostatic cancer, and two with lymphoma), vWF abnormalities were observed during evolution of the thrombotic microangiopathy. These abnormalities were either the presence of unusually large (UL) vWF multimers of the type similar to those found within, and released or secreted by, endothelial cells (three patients) or a relative decrease in the largest plasma vWF multimers of the type that can be induced to attach to platelets (one patient) or both vWF abnormalities in different serial samples (one patient). In the one cardiac transplant patient who did not develop vWF multimeric abnormalities associated with thrombotic microangiopathy, vWF antigen levels were elevated more than threefold. This later individual received therapy with cyclosporin A alone. The other five thrombotic microangiopathy patients received cyclosporin A in combination with other chemotherapeutic agents (two patients); mitomycin-C, along with other chemotherapy (two patients); or multiple chemotherapeutic drugs, but not cyclosporin A or mitomycin C (one patient). The finding of vWF multimeric abnormalities during serial analysis of plasma samples from five of six patients with drug-associated thrombotic microangiopathy suggests the possibility that ULvWF forms derived from damaged or stimulated endothelial cells, along with the largest plasma vWF multimers, may be involved in the intravascular platelet clumping that is an essential part of the pathophysiology of this disorder.© 1993 Wiley-Liss, Inc.