Role of Von Willebrand Factor after Injury: It May Do More Than We Think.
Role of Von Willebrand Factor after Injury: It May Do More Than We Think.
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血管性血友病因子在受伤后的作用：它可能比我们想象的要多。
DOI：
10.1097/shk.0000000000001690
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发表时间：
2021-06-01
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急性创伤性凝血病是受伤后的一种复杂现象，也是出血的主要原因。它仍然是创伤患者可预防死亡的主要原因。这种现象是由血管内皮的全身性损伤引起的，血管内皮的全身性损伤因灌注不足、酸中毒和体温过低而加剧，并导致凝血级联的全身性激活和由此产生的凝血病。许多以前的研究集中在内皮病与靶向标志物，如syndecan-1，可溶性血栓调节蛋白，血浆肾上腺素作为潜在的罪魁祸首，这种状态的启动和传播。然而，在最近的研究中，内皮损伤后释放的高粘附性血管性血友病因子（VWF）及其裂解金属蛋白酶ADAMTS 13已成为内皮细胞破坏和凝血失调下游效应的重要靶点。阐明创伤后VWF-ADAMTS 13轴失调导致内皮功能障碍和凝血功能障碍的机制有助于确定新的治疗靶点和干预部位。许多关于VWF的机制性知识来自创伤性脑损伤的研究。在局部脑损伤后，脑源性细胞外囊泡被释放到循环中，在循环中它们诱导高凝状态，该高凝状态迅速转变为消耗性凝血病。从损伤的内皮细胞释放的VWF结合到这些细胞外囊泡，以增强其促进凝血病和增加内皮通透性的活性。然而，我们对受伤后VWF的认识存在许多空白，为进一步研究提供了平台。
Acute traumatic coagulopathy is a complex phenomenon following injury and a main contributor to hemorrhage. It remains a leading cause of preventable death in trauma patients. This phenomenon is initiated by systemic injury to the vascular endothelium that is exacerbated by hypoperfusion, acidosis, and hypothermia and leads to systemic activation of the coagulation cascades and resultant coagulopathy. Many previous studies have focused on endotheliopathy with targeted markers such as syndecan-1, soluble thrombomodulin, and plasma adrenaline as potential culprits for initiation and propagation of this state. However, in more recent studies, hyperadhesive von Willebrand factor (VWF), which is released following endothelial injury, and its cleaving metalloprotease ADAMTS13 have emerged as significant targets of the downstream effect of endothelial breakdown and coagulation dysregulation. Elucidation of the mechanism by which the dysregulated VWF-ADAMTS13 axis leads to endothelial dysfunction and coagulopathy after trauma can help identify new targets for therapy and sites for intervention. Much of what is known mechanistically regarding VWF stems from work done in traumatic brain injury. Following localized brain injury, brain-derived extracellular vesicles are released into circulation where they induce a hypercoagulable state that rapidly turns into consumptive coagulopathy. VWF released from injured endothelial cells binds to these extracellular vesicles to enhance their activity in promoting coagulopathy and increasing endothelial permeability. However, there are numerous gaps in our knowledge of VWF following injury, providing a platform for further investigation.