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常温机器灌注的人类供体肝脏可产生功能性止血蛋白。

Normothermic Machine-perfused Human Donor Livers Produce Functional Hemostatic Proteins.

作者信息

Bodewes Silke B, Lascaris Bianca, Adelmeijer Jelle, de Meijer Vincent E, Porte Robert J, Lisman Ton

机构信息

Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

出版信息

Transplantation. 2023 Nov 1;107(11):2377-2383. doi: 10.1097/TP.0000000000004670. Epub 2023 Oct 21.

Abstract

BACKGROUND

Normothermic machine perfusion (NMP) is used for the viability assessment of high-risk donor livers before transplantation. The production of hemostatic proteins is one of the major synthetic functions of the liver. The objective of this study was to measure the concentration and functionality of hemostatic proteins concentration in the NMP perfusate of human donor livers.

METHODS

Thirty-six livers that underwent NMP for viability assessment were included in this study. Perfusate samples taken during NMP (start, 150 min, and 300 min) were used for the measurement of antigen and activity levels of hemostatic proteins (factors II, VII, and X; fibrinogen; plasminogen; antithrombin; tissue plasminogen activator; von Willebrand factor; and proteins induced by vitamin K absence). The antigen levels were correlated with hepatocellular function according to previously proposed individual hepatocellular viability criteria: lactate clearance and perfusate pH.

RESULTS

Antigen levels of hemostatic proteins reached subphysiological levels in the NMP perfusate. Hemostatic proteins that were produced during NMP were at least partially active. All livers produced all hemostatic proteins tested within 150 min of NMP. Hemostatic protein concentrations did not significantly correlate with perfusate lactate and perfusate pH after 150 min of NMP.

CONCLUSIONS

All livers produce functional hemostatic proteins during NMP. The generation of a functional hemostatic system in NMP perfusate confirms the need for adequate anticoagulation of the perfusate to avoid generation of (micro)thrombi that may harm the graft.

摘要

背景

常温机器灌注(NMP)用于移植前高危供肝的活力评估。止血蛋白的产生是肝脏的主要合成功能之一。本研究的目的是测量人供肝NMP灌注液中止血蛋白的浓度和功能。

方法

本研究纳入了36例接受NMP进行活力评估的肝脏。NMP期间(开始、150分钟和300分钟)采集的灌注液样本用于测量止血蛋白(因子II、VII和X;纤维蛋白原;纤溶酶原;抗凝血酶;组织纤溶酶原激活剂;血管性血友病因子;以及维生素K缺乏诱导蛋白)的抗原和活性水平。根据先前提出的个体肝细胞活力标准:乳酸清除率和灌注液pH值,将抗原水平与肝细胞功能相关联。

结果

NMP灌注液中止血蛋白的抗原水平达到亚生理水平。NMP期间产生的止血蛋白至少部分具有活性。所有肝脏在NMP的150分钟内都产生了所有测试的止血蛋白。NMP 150分钟后,止血蛋白浓度与灌注液乳酸和灌注液pH值无显著相关性。

结论

所有肝脏在NMP期间都产生功能性止血蛋白。NMP灌注液中功能性止血系统的产生证实了需要对灌注液进行充分抗凝,以避免产生可能损害移植物的(微)血栓。

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