Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity
Elevated levels of von Willebrand factor in cirrhosis support platelet adhesion despite reduced functional capacity
复制标题
DOI：
10.1002/hep.21231
复制
发表时间：
2006-07-01
期刊：
影响因子：
13.5
通讯作者：
Leebeek, FWG
中科院分区：
文献类型：
--
作者：
Lisman, T;Bongers, TN;Leebeek, FWG
肝硬变常伴有复杂的止血系统改变，导致出血倾向。虽然肝病中的许多止血变化会促进出血，但也发现了代偿机制，包括高水平的血小板黏附蛋白von Willebrand因子(VWF)。然而，在文献中出现了关于VWF在肝硬变中的功能特性的相互矛盾的报道。我们测量了不同严重程度和病因的肝硬变患者血浆中的一组VWF参数。此外，我们通过测量肝硬变患者血浆在流动条件下支持正常或患者血小板黏附的能力，评估了VWF对血小板黏附的贡献。肝硬变患者VWF抗原水平明显升高。相反，与对照组相比，患者组的相对胶原结合活性和瑞索西汀辅因子的相对活性显著降低，表明功能丧失。因此，患者的高分子量VWF多聚体比例减少。在个别患者中，VWF裂解酶ADAMTS13的活性和抗原水平均显著升高和降低。与对照血浆相比，当正常或患者的血小板重新悬浮在肝硬变患者的血浆中时，这些血小板与胶原表面的粘附性显著增加。总之，尽管VWF分子的功能特性降低，但在肝硬变患者中，VWF水平的高度升高有助于诱导初级止血。这种现象可能弥补了肝硬变患者在血小板数量和功能方面的缺陷。
Cirrhosis of the liver is frequently accompanied by complex alterations in the hemostatic system, resulting in a bleeding tendency. Although many hemostatic changes in liver disease promote bleeding, compensatory mechanisms also are found, including high levels of the platelet adhesive protein von Willebrand Factor (VWF). However, conflicting reports on the functional properties of VWF in cirrhosis have appeared in literature. We have measured a panel of VWF parameters in plasma from patients with cirrhosis of varying severity and causes. Furthermore, we assessed the contribution of VWF to platelet adhesion, by measuring the ability of plasma from patients with cirrhosis to support adhesion of normal or patient platelets under flow conditions. VWF antigen levels were strongly increased in patients with cirrhosis. In contrast, the relative collagen binding activity, as well as the relative ristocetin cofactor activity, was significantly lower in patients as compared with controls, indicating loss of function. Accordingly, patients had a reduced fraction of high-molecular-weight VWF multimers. Both strongly elevated and reduced activity and antigen levels of the VWF cleaving protease ADAMTS13 were found in individual patients. Adhesion of either normal or patient platelets to a collagen surface was substantially increased when these platelets were resuspended in plasma of patients with cirrhosis, as compared with control plasma. In conclusion, highly elevated levels of VWF in patients with cirrhosis contribute to the induction of primary hemostasis despite reduced functional properties of the molecule. This phenomenon might compensate for defects in platelet number and function in patients with cirrhosis.