van der Plas R M, Schiphorst M E, Huizinga E G, Hené R J, Verdonck L F, Sixma J J, Fijnheer R
Thrombosis and Haemostasis Laboratory, Department of Haematology, Institute of Biomembranes, University Medical Centre Utrecht, Utrecht, The Netherlands.
Blood. 1999 Jun 1;93(11):3798-802.
Thrombotic thrombocytopenic purpura (TTP) after bone marrow transplantation (BMT) differs from classic TTP in its clinical course and therapy. A characteristic of classic TTP is the inhibition of a plasma protease that specifically cleaves von Willebrand factor (vWF), thus reducing its multimeric size. We investigated whether this protease was also inhibited in BMT-associated TTP. Plasma from patients with classic or BMT-associated TTP was incubated with recombinant vWF R834Q, a vWF mutant with enhanced sensitivity to the protease. The proteolysis of vWF multimers was analyzed and quantified on Western blot. Metalloprotease activity was strongly inhibited in the classic TTP patient group. However, metalloprotease activity was normal in the BMT-associated TTP patient group. The difference in activity between the two patient groups was highly significant (P =.0016). The results indicate that the etiologies of classic and BMT-associated TTP are indeed different and provide an explanation for the lack of success of plasma exchange in BMT-associated TTP.
骨髓移植（BMT）后发生的血栓性血小板减少性紫癜（TTP）在临床病程和治疗方面与经典TTP有所不同。经典TTP的一个特征是一种血浆蛋白酶受到抑制，该蛋白酶可特异性切割血管性血友病因子（vWF），从而减小其多聚体大小。我们研究了这种蛋白酶在BMT相关TTP中是否也受到抑制。将经典TTP或BMT相关TTP患者的血浆与重组vWF R834Q（一种对该蛋白酶敏感性增强的vWF突变体）一起孵育。在蛋白质印迹上分析并定量vWF多聚体的蛋白水解情况。经典TTP患者组中的金属蛋白酶活性受到强烈抑制。然而，BMT相关TTP患者组中的金属蛋白酶活性正常。两组患者之间的活性差异非常显著（P = 0.0016）。结果表明，经典TTP和BMT相关TTP的病因确实不同，并为血浆置换在BMT相关TTP中未取得成功提供了解释。
