Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity

Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity
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DOI:
10.1111/trf.15856
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发表时间:
2020-05-22
期刊:
影响因子:
2.9
通讯作者:
Neal, Matthew D.
Neal, Matthew D.
中科院分区:
医学3区
文献类型:
--
作者:
Dyer, Mitchell R.;Plautz, William E.;Neal, Matthew D.

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血浆血管性血友病因子(VWF)水平的增加,伴随着金属蛋白酶ADAMTS 13,研究设计和方法来自随机对照试验的37名创伤患者的队列研究了院前血浆输注的使用,分析了0和10分钟时ADAMTS 13和VWF的活性和抗原水平。入院后24小时。从病历中提取相关临床资料。通过琼脂糖凝胶电泳分析创伤患者血浆,以评估与健康对照相比,创伤对VWF多聚体组成的影响。(189% [110%-263%] vs. 95% [74%-120%]),持续24小时(213% [146%-257%] vs. 132% [57%-160%])。与合并的正常血浆相比,创伤患者在0和24小时的超大VWF(UL-VWF)形式均升高(分别为10.0% [8.9%-14.3%]和11.3% [9.1%-21.2%],vs. 0.6%)。在创伤患者中,循环血浆ADAMTS 13活性在0小时(66% [47%-86%] vs. 100% [98%-100%])和24小时(72.5% [56%-87.3%] vs. 103% [103%-103%])降低。ADAMTS 13活性独立预测凝血功能障碍的发展,并与国际标准化比率,血栓弹力图值,损伤严重程度,和血液制品transmitting.CONCLUSION创伤性损伤与急性凝血功能障碍,其特征是增加UL-VWF多聚体和减少ADAMTS 13,这与失血量,输血需求,和损伤严重程度。这些发现表明,未来的试验可能靶向ADAMTS 13的补充,以提高清除VWF多聚体。
BACKGROUND Increases in plasma von Willebrand Factor (VWF) levels, accompanied by decreases in the metalloprotease ADAMTS13, have been demonstrated soon after traumatic injury while downstream effects remain unclear.STUDY DESIGN AND METHODS A cohort of 37 injured trauma patients from a randomized control trial investigating the use of prehospital plasma transfusion were analyzed for activity and antigen levels of ADAMTS13 and VWF at 0 and 24 hours after admission. Relevant clinical data were abstracted from the medical records. Trauma patient plasma was analyzed via agarose gel electrophoresis to evaluate the effects of injury on VWF multimer composition compared to healthy controls.RESULTS von Willebrand factor levels were elevated at presentation (189% [110%-263%] vs. 95% [74%-120%]), persisting through 24 hours (213% [146%-257%] vs. 132% [57%-160%]), compared to healthy controls. Ultralarge VWF (UL-VWF) forms were elevated in trauma patients at both 0 and 24 hours, when compared to pooled normal plasma (10.0% [8.9%-14.3%] and 11.3% [9.1%-21.2%], respectively, vs. 0.6%). Circulating plasma ADAMTS13 activity was decreased at 0 hours (66% [47%-86%] vs. 100% [98%-100%]) and at 24 hours (72.5% [56%-87.3%] vs. 103% [103%-103%]) in trauma patients. ADAMTS13 activity independently predicted the development of coagulopathy and correlated with international normalized ratio, thromboelastography values, injury severity, and blood product transfusion.CONCLUSION Traumatic injury is associated with acute coagulopathy that is characterized by increased UL-VWF multimers and reduction in ADAMTS13, which correlates with blood loss, transfusion requirement, and injury severity. These findings suggest the potential for future trials targeting ADAMTS13 repletion to enhance clearance of VWF multimers.