Departments of Surgery, University of Colorado School of Medicine, Aurora, CO, United State of America.
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, United State of America.
Blood Transfus. 2019 Jul;17(4):312-320. doi: 10.2450/2019.0205-18. Epub 2019 Feb 4.
Increased systemic fibrinolytic activity can occur in liver transplant recipients after the donor graft is reperfused. However, it remains unclear whether this is related solely to tissue plasminogen activator (t-PA) levels or whether unique metabolic changes can alter t-PA activity and enhance fibrinolytic activity. We hypothesise that an increase in sensitivity to t-PA-mediated fibrinolysis (StF) following liver reperfusion is associated with specific metabolic abnormalities.
Liver transplant recipients had serial blood samples analysed with a modified thrombelastography assay using exogenous t-PA to measure sensitivity/resistance to fibrinolysis with the lysis 30 min after maximum clot strength (tLY30). Paired plasma samples were analysed with mass spectroscopy-based metabolomics. The tLY30 was correlated to metabolites using Spearman's rho. StF was defined as a tLY30 change of >8.5% from the anhepatic phase to 30 min after reperfusion based on the distribution of tLY30 in a healthy control population.
StF occurred in 53% of patients. Cohorts had similar MELD scores (18 vs 16, p=0.876) and tLY30 at baseline (p=0.867) and anhepatic phase of surgery (p=0.463). Thirty min after reperfusion, the tLY30 was 73% in patient with StF vs 33% in those without StF 33% (p=0.006). StF was associated with increased red blood cell transfusions (p=0.035), during the first 2 hours of reperfusion. Nine metabolites demonstrated a correlation with tLY30 (p<0.05).
StF is a transient event that resolves within 2 hours of graft reperfusion and is associated with increased blood product use. This phenomenon correlates with derangements in citric acid cycle, purine and amino acid metabolism. Future research is needed to determine whether these metabolites are biomarkers or mechanistically linked to increased sensitivity to t-PA-mediated fibrinolytic activity following graft reperfusion.
供体移植物再灌注后，肝移植受者体内的系统性纤维蛋白溶解活性可能会增加。然而，目前尚不清楚这是否仅与组织型纤溶酶原激活物（t-PA）水平有关，或者是否存在独特的代谢变化会改变 t-PA 活性并增强纤维蛋白溶解活性。我们假设，肝再灌注后对 t-PA 介导的纤维蛋白溶解（StF）的敏感性增加与特定的代谢异常有关。
使用改良的血栓弹性图检测对肝移植受者进行连续的血液样本分析，使用外源性 t-PA 测量纤维蛋白溶解的敏感性/抵抗性，以最大凝块强度后 30 分钟的溶解率（tLY30）来表示。用基于质谱的代谢组学分析配对的血浆样本。使用 Spearman's rho 分析 tLY30 与代谢物之间的相关性。StF 定义为再灌注后 30 分钟的 tLY30 与无肝期相比变化>8.5%，基于健康对照组 tLY30 的分布。
53%的患者出现 StF。两组患者的 MELD 评分相似（18 与 16，p=0.876），基线（p=0.867）和无肝期手术（p=0.463）的 tLY30 相似。再灌注后 30 分钟，StF 患者的 tLY30 为 73%，而无 StF 患者的 tLY30 为 33%（p=0.006）。StF 与再灌注后前 2 小时内红细胞输注增加有关（p=0.035）。有 9 种代谢物与 tLY30 相关（p<0.05）。
StF 是一种短暂的事件，在移植物再灌注后 2 小时内得到解决，并与血液制品使用增加有关。这种现象与柠檬酸循环、嘌呤和氨基酸代谢的紊乱有关。需要进一步的研究来确定这些代谢物是标志物还是与移植物再灌注后 t-PA 介导的纤维蛋白溶解活性增加有机制上的联系。
