早期冻干的冷沉淀可提高 ADAMTS13/VWF 比值，减少全身内皮病变，并减轻小鼠多发创伤性出血模型中的肺损伤。
Early lyophilized cryoprecipitate enhances the ADAMTS13/VWF ratio to reduce systemic endotheliopathy and lessen lung injury in a mouse multiple-trauma hemorrhage model.
机构信息
From the Shock Trauma Center and the University of Maryland School of Medicine (A.Z., F.W., R.A.K.), Baltimore, Maryland; Bloodworks Research Institute and Hematology Division, Department of Medicine (J.-F.D.), University of Washington School of Medicine, Seattle, Washington; Shock Trauma Anesthesiology Research (STAR) Center and Department of Epidemiology (R.V.), University of Maryland School of Medicine, Baltimore, Maryland; Trauma and Transfusion Medicine Research Center, Department of Surgery (M.D.N.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Cerus Corporation (L.C.), Concord, California; and Department of Laboratory Medicine (S.P.), University of California San Francisco, San Francisco, California.
出版信息
J Trauma Acute Care Surg. 2023 Aug 1;95(2S Suppl 1):S137-S143. doi: 10.1097/TA.0000000000004065. Epub 2023 May 22.
BACKGROUND
Recent studies in severely injured patients suggest an important role of von Willebrand Factor (VWF) and ADAMTS13 in the endotheliopathy of trauma (EoT). We hypothesized that the early use of cryoprecipitate would be effective as an endothelial protector by supplementing physiologic VWF and ADAMTS13 to reverse the EoT. We tested a pathogen-reduced lyophilized cryoprecipitate (LPRC) that could expedite the early administration of cryoprecipitate in the battlefield.
METHODS
A mouse multiple-trauma model with uncontrolled hemorrhage (UCH) from liver injury was utilized followed by hypotensive resuscitation (mean arterial pressure, 55-60) × 3 hours with lactated Ringer's (LR), fresh frozen plasma (FFP), conventional pathogen-reduced cryoprecipitate (CC), and LPRC. Blood was collected for measurement of syndecan-1, VWF, and ADAMTS13 by ELISA. Lungs were stained for histopathologic injury and syndecan-1 and bronchial alveolar lavage (BAL) fluid harvested for protein as an indicator of permeability. Statistical analysis was by ANOVA followed by Bonferroni correction.
RESULTS
Following multiple trauma and UCH, blood loss was similar across groups. Mean volume of resuscitation was higher in the LR group compared with the other resuscitation groups. Lung histopathologic injury, syndecan-1 immunostaining and BAL protein were higher with LR compared with resuscitation with FFP and CC, while LPRC further reduced BAL compared with FFP and CC. The ADAMTS13/VWF ratio was significantly lower in LR but improved with FFP and CC, comparable to shams while LPRC further increased this ratio.
CONCLUSION
The protective effects of CC and LPRC were comparable to FFP in ameliorating the EoT in our murine multiple trauma and UCH model. Lyophilized cryoprecipitate may also provide additional benefit by enhancing the ADAMTS13/VWF ratio. These data provide evidence of the safety and efficacy of LPRC and warrants further investigation for its potential application in military settings once approved for human administration.
背景
最近对严重受伤患者的研究表明，血管性血友病因子（VWF）和 ADAMTS13 在创伤性内皮病（EoT）中起重要作用。我们假设早期使用冷沉淀作为内皮保护剂通过补充生理性 VWF 和 ADAMTS13 来逆转 EoT 是有效的。我们测试了一种经过病原体减少处理的冻干冷沉淀（LPRC），它可以加快在战场上早期使用冷沉淀。
方法
使用了一种伴有未控制出血（UCH）的小鼠多发伤模型，随后进行低血压复苏（平均动脉压，55-60）×3 小时，使用乳酸林格氏液（LR）、新鲜冷冻血浆（FFP）、常规病原体减少的冷沉淀（CC）和 LPRC。通过 ELISA 测量硫酸乙酰肝素蛋白聚糖-1（syndecan-1）、VWF 和 ADAMTS13。对肺进行染色以评估组织病理学损伤和硫酸乙酰肝素蛋白聚糖-1 免疫染色，并收集支气管肺泡灌洗液（BAL）以获取蛋白作为通透性的指标。通过方差分析（ANOVA）并进行 Bonferroni 校正进行统计分析。
结果
多发伤和 UCH 后，各组的失血量相似。LR 组的复苏平均容量高于其他复苏组。与 FFP 和 CC 相比，LR 组的肺组织病理学损伤、硫酸乙酰肝素蛋白聚糖-1 免疫染色和 BAL 蛋白更高，而 LPRC 与 FFP 和 CC 相比进一步降低了 BAL。LR 组的 ADAMTS13/VWF 比值明显较低，但 FFP 和 CC 可改善该比值，与假手术组相当，而 LPRC 进一步增加了该比值。
结论
CC 和 LPRC 在改善我们的小鼠多发伤和 UCH 模型中的 EoT 方面的保护作用与 FFP 相当。冻干冷沉淀还可以通过增强 ADAMTS13/VWF 比值提供额外的益处。这些数据为 LPRC 的安全性和有效性提供了证据，并在获得人类批准后，为其在军事环境中的潜在应用提供了进一步的研究依据。
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