Department of Surgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
National Institute for Health and Care Research Cambridge Biomedical Research Centre, Cambridge, United kingdom.
Transplantation. 2023 Jun 1;107(6):1311-1321. doi: 10.1097/TP.0000000000004475. Epub 2023 May 23.
Deceased donor livers are prone to biliary complications, which may necessitate retransplantation, and we, and others, have suggested that these complications are because of peribiliary vascular fibrin microthrombi. We sought to determine the prevalence and consequence of occult fibrin within deceased donor livers undergoing normothermic ex situ perfusion (NESLiP) and evaluate a role for fibrinolysis.
D-dimer concentrations, products of fibrin degradation, were assayed in the perfusate of 163 livers taken after 2 h of NESLiP, including 91 that were transplanted. These were related to posttransplant outcomes. Five different fibrinolytic protocols during NESLiP using alteplase were evaluated, and the transplant outcomes of these alteplase-treated livers were reviewed.
Perfusate D-dimer concentrations were lowest in livers recovered using in situ normothermic regional perfusion and highest in alteplase-treated livers. D-dimer release from donation after brain death livers was significantly correlated with the duration of cold ischemia. In non-alteplase-treated livers, Cox proportional hazards regression analysis showed that D-dimer levels were associated with transplant survival ( P = 0.005). Treatment with alteplase and fresh frozen plasma during NESLiP was associated with significantly more D-dimer release into the perfusate and was not associated with excess bleeding postimplantation; 8 of the 9 treated livers were free of cholangiopathy, whereas the ninth had a proximal duct stricture.
Fibrin is present in many livers during cold storage and is associated with poor posttransplant outcomes. The amount of D-dimer released after fibrinolytic treatment indicates a significant occult fibrin burden and suggests that fibrinolytic therapy during NESLiP may be a promising therapeutic intervention.
已故供体肝脏容易发生胆道并发症，可能需要再次移植，我们和其他人认为这些并发症是由于胆管周围血管纤维蛋白微血栓形成。我们试图确定在进行常温离体灌注（NESLiP）的已故供体肝脏中隐匿性纤维蛋白的流行程度和后果，并评估纤维蛋白溶解的作用。
测定了 163 例 NESLiP 后 2 小时采集的肝脏灌流液中的 D-二聚体浓度，这些肝脏包括 91 例已移植的肝脏。这些与移植后的结果有关。评估了 NESLiP 中使用阿替普酶的 5 种不同纤维蛋白溶解方案，并回顾了这些阿替普酶处理肝脏的移植结果。
原位常温区域性灌注回收的肝脏灌流液中的 D-二聚体浓度最低，阿替普酶处理的肝脏中最高。脑死亡后供体肝脏 D-二聚体的释放与冷缺血时间明显相关。在未用阿替普酶治疗的肝脏中，Cox 比例风险回归分析显示 D-二聚体水平与移植存活率相关（ P = 0.005）。在 NESLiP 期间用阿替普酶和新鲜冷冻血浆治疗与灌流液中更多的 D-二聚体释放相关，与植入后过度出血无关；9 例治疗的肝脏中有 8 例无胆管病，而第 9 例有近端胆管狭窄。
在冷储存过程中，许多肝脏中存在纤维蛋白，与移植后不良结果有关。纤维蛋白溶解治疗后释放的 D-二聚体量表明存在大量隐匿性纤维蛋白负担，表明 NESLiP 期间的纤维蛋白溶解治疗可能是一种有前途的治疗干预措施。
