Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent
Acquired von Willebrand factor deficiency caused by LVAD is ADAMTS-13 and platelet dependent
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DOI：
10.1016/j.thromres.2015.11.002
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发表时间：
2016-01-01
影响因子：
7.5
通讯作者：
Jilma, Bernd
中科院分区：
文献类型：
--
作者：
Jilma-Stohlawetz, Petra;Quehenberger, Peter;Jilma, Bernd
简介：左心室辅助装置引起的高剪切率会导致获得性血管性血友病 (aVWD)。我们假设可以建立离体模型来研究机械剪切应力是否单独导致aVWD，或者该过程是否还依赖于VWF裂解蛋白ADAMTS-13和血小板。 材料和方法：健康志愿者和两名先天性ADAMTS-13缺陷患者捐献血液。使用医学上批准的左心室辅助装置（LVAD）建立体外闭合体外回路。通过凝胶电泳对 VWF 多聚体进行定量；评估了 VWF 抗原、瑞斯托菌素辅因子活性 (VWF: RCo)、ADAMTS-13 水平和血小板功能。结果：体外循环中的高剪切应力迅速降低 VWF: RCo，从而使 VWF: RCo/VWF: Ag 比率降低 47% (p < 0.01) 至病理低值。与此同时，高分子量多聚体 (HMWM) 减少：基线时凝胶上可见多达 14-15 个聚体，最多减少 6-7 个聚体，对应于 HMWM 的密度测定信号平均降低 68% (p < 0.001)。这伴随着各种激动剂的聚集显着减少（p < 0.005）。相比之下，ADAMTS-13 活性几乎完全缺乏的两名先天性血小板减少性紫癜患者的多聚体仅出现极小程度的下降或没有下降（与健康对照相比，p < 0.005）。同样，当正常血浆在没有血小板的情况下循环时，大多聚体不会发生或很少发生消耗。结论：LVAD 相关 aVWD 的体外模型表明 ADAMTS-13 和血小板有助于 VWF 的 HMWM 消耗。 (C) 2015 年作者。由爱思唯尔有限公司出版
Introduction: The high shear rates induced by left ventricular assist devices cause acquired von Willebrand disease (aVWD). We hypothesised that an ex vivo model could be established to study whether mechanical shear stress alone causes aVWD or whether this process depends also on the VWF cleavage protein ADAMTS-13 and on platelets.Materials and methods: Healthy volunteers and two patients with congenital ADAMTS-13 deficiency donated blood. In vitro closed extracorporeal circuits were established using medically approved left ventricular assist devices (LVAD). VWF multimers were quantified by gel electrophoresis; VWF antigen, ristocetin cofactor activity (VWF: RCo), ADAMTS-13 levels and platelet function were assessed.Results: The high shear stress in the extracorporeal circulation rapidly decreased VWF: RCo and thereby the VWF: RCo/VWF: Ag ratio by 47% (p < 0.01) to pathologically low values. Concomitantly, high molecular weight multimers (HMWM) decreased: up to 14-15 mers were visible on the gels at baseline, which were reduced by a maximum of 6-7 mers, corresponding to an average 68% lower densitometry signal of HMWM (p < 0.001). This was accompanied by marked reduction of aggregation by various agonists (p < 0.005). In contrast, the two patients with congenital thrombocytopenic purpura with virtually complete deficiency of ADAMTS-13 activity had only a minimal or no decrease in multimers (p < 0.005 vs. healthy controls). Similarly, no or minimal depletion of large multimers occurred, when normal plasma circulated without platelets.Conclusion: An in vitro model for LVAD associated aVWD demonstrated that ADAMTS-13 and platelets contribute to the depletion of HMWM of VWF. (C) 2015 The Authors. Published by Elsevier Ltd.