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微流控横断损伤和高剪切力血栓形成表明,在诱导性凝血病模型中,冷储存血小板和复苏的止血效果增强。

Microfluidic transection injury and high-shear thrombus formation demonstrate increased hemostatic efficacy of cold-stored platelets and resuscitation in induced coagulopathy models.

作者信息

Mihalko Emily P, Munitz Refael, Dishong Devin M, Clayton Skye, Shea Susan M

机构信息

Trauma and Transfusion Medicine Research Center, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, United States.

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States.

出版信息

Front Bioeng Biotechnol. 2025 May 12;13:1568113. doi: 10.3389/fbioe.2025.1568113. eCollection 2025.

Abstract

Hemostatic resuscitation is an essential aspect of treating traumatic bleeding. Trauma-induced coagulopathy is a multifactorial disorder that can lead to increased transfusion requirements. However, little is known about the interplay between coagulopathies and stored blood products used for hemostatic resuscitation, which themselves acquire dysfunction in the form of a storage lesion. Physiologically relevant models can aid in the study of trauma and hemostatic resuscitation by incorporating important aspects such as biological surfaces and flow regimes that mimic injury. This study aims to evaluate the contribution of platelet products under varying storage conditions in coagulopathic states. This study utilized microfluidic platforms of high shear, a flow regime relevant to injury, including a stenotic straight channel and a severe transected vessel injury device. Apheresis platelet products were collected from healthy volunteers, stored at room temperature (RT) or cold-stored (CS) (1°C-6°C), and tested for product cell count and intrinsic product function in a high-shear stenotic microfluidic device across storage days (D2, D5, and D7 for RT; D2, D5, D7, D14, and D21 for CS). Hemostatic resuscitation efficacy of products was assessed using induced coagulopathy models of dilution and thrombocytopenia (TP). hemostatic resuscitation was assessed in both the stenotic straight channel for kinetic platelet contributions and the transected-vessel injury device, using blood loss and clot composition as endpoints. CS products conserved inherent function despite decreasing platelet counts through storage D7. When mixed with coagulopathic blood, D2 RT products did not show hemostatic benefit in the dilutional coagulopathy (DC) model. However, both D2 RT and CS showed hemostatic benefits in the thrombocytopenia model. CS products (D5 and D7) also showed an enhanced ability to recruit recipient platelets in the thrombocytopenia model compared to RT. Overall, this study highlights disparate responses associated with product storage duration and temperature, indicating the need to further evaluate hemostatic resuscitation efficacy under flow in pathologically relevant models to guide transfusion practices.

摘要

止血复苏是治疗创伤性出血的一个重要方面。创伤性凝血病是一种多因素疾病,可导致输血需求增加。然而,对于凝血病与用于止血复苏的库存血液制品之间的相互作用知之甚少,而这些血液制品本身会以储存损伤的形式出现功能障碍。生理相关模型可以通过纳入诸如模拟损伤的生物表面和血流状态等重要方面,来辅助创伤和止血复苏的研究。本研究旨在评估不同储存条件下血小板制品在凝血病状态中的作用。本研究利用了高剪切微流控平台,这是一种与损伤相关的血流状态,包括一个狭窄的直通道和一个严重横断血管损伤装置。从健康志愿者采集单采血小板制品,分别在室温(RT)或冷藏(CS)(1°C - 6°C)条件下储存,并在高剪切狭窄微流控装置中,对不同储存天数(RT组为第2、5和7天;CS组为第2、5、7、14和21天)的制品进行细胞计数和内在制品功能测试。使用稀释性和血小板减少症(TP)诱导的凝血病模型评估制品的止血复苏效果。在狭窄直通道中评估血小板的动力学贡献,在横断血管损伤装置中评估止血复苏效果,以失血和血凝块组成为终点指标。尽管CS制品在储存至第7天时血小板计数下降,但其固有功能得以保留。当与凝血病血液混合时,第2天的RT制品在稀释性凝血病(DC)模型中未显示出止血益处。然而,第2天的RT和CS制品在血小板减少症模型中均显示出止血益处。与RT制品相比,CS制品(第5天和第7天)在血小板减少症模型中还表现出更强的募集受者血小板的能力。总体而言,本研究突出了与制品储存持续时间和温度相关的不同反应,表明需要在病理相关模型中进一步评估血流状态下的止血复苏效果,以指导输血实践。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddee/12104287/bf39a94f60f8/fbioe-13-1568113-g001.jpg

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