Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
J Thromb Haemost. 2024 Nov;22(11):3097-3106. doi: 10.1016/j.jtha.2024.08.004. Epub 2024 Aug 22.
Normothermic machine perfusion (NMP) is used for preservation and assessment of human donor livers prior to transplantation. During NMP, the liver is metabolically active, which allows detailed studies on the physiology of human livers.
To study the production of hemostatic proteins in human donor livers during NMP for up to 7 days.
In this observational study, 9 livers underwent NMP for up to 7 days with a heparinized perfusate based on red blood cells and colloids using a modified Liver Assist device (XVIVO). Perfusate samples were collected before NMP and daily thereafter for measurement of antigen and activity levels of a comprehensive panel of hemostatic proteins after heparin neutralization.
Within 1 day, perfusate samples displayed the potential for coagulation activation as evidenced by international normalized ratio and activated partial thromboplastin assays. This was accompanied by detection of substantial quantities of functionally active coagulation proteins and inhibitors, although the specific activity of many proteins was decreased, compared with that in normal plasma. Perfusate levels of hemostatic proteins increased in the first days, reaching a stable level after 3 to 4 days of perfusion.
During long-term NMP of human livers, functionally active hemostatic proteins are released into the perfusate in substantial quantities, but some proteins appear to have decreased functional properties compared with proteins in normal human plasma. We propose that NMP may be used as a platform to test efficacy of drugs that stimulate or inhibit the production of coagulation factors or to test liver-mediated clearance of prohemostatic protein therapeutics.
常温机器灌注（NMP）用于在移植前保存和评估人类供体肝脏。在 NMP 期间，肝脏具有代谢活性，这允许对人类肝脏的生理学进行详细研究。
研究人类供体肝脏在长达 7 天的 NMP 期间止血蛋白的产生情况。
在这项观察性研究中，9 个肝脏使用基于红细胞和胶体的肝素化灌注液在改良的 LiverAssist 设备（XVIVO）中进行 NMP，时间长达 7 天。在 NMP 之前和之后的每天收集灌注液样本，用于在肝素中和后测量全面止血蛋白组的抗原和活性水平。
在 1 天内，灌注液样本显示出凝血激活的潜力，这可以通过国际标准化比值和激活部分凝血活酶时间测定来证明。这伴随着大量功能活性凝血蛋白和抑制剂的检测，尽管与正常血浆中的蛋白质相比，许多蛋白质的特定活性降低。止血蛋白的灌注液水平在最初几天增加，在灌注 3 到 4 天后达到稳定水平。
在人类肝脏的长期 NMP 期间，大量功能活性的止血蛋白被释放到灌注液中，但与正常人类血浆中的蛋白质相比，一些蛋白质的功能特性似乎有所降低。我们提出，NMP 可作为一种平台，用于测试刺激或抑制凝血因子产生的药物的疗效，或测试肝脏介导的前止血蛋白治疗药物清除的疗效。
