Department of Anesthesiology and Pain Medicine, Laboratory for Cardiovascular Dynamics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Republic of Korea.
Int J Surg. 2020 Dec;84:109-116. doi: 10.1016/j.ijsu.2020.10.030. Epub 2020 Nov 1.
Early allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation.
Of 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed.
The prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28-5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1-4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%.
Pretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation.
早期移植物功能障碍（EAD）已知是移植物衰竭的原型，最终会影响长期移植物衰竭或死亡。我们假设通过促凝和抗凝、血管性血友病因子（vWF）、因子 VIII（FⅧ）、蛋白 C（PC）及其 vWF 与 PC（vWFPCR）和 FVIII 与 PC（FⅧPCR）的不平衡比值来评估移植前的血栓形成与活体相关肝移植（LDLT）后的 EAD 和 90 天移植物失败相关，并在合并全身炎症时导致移植物功能进一步恶化。
在 1199 例前瞻性注册的 LDLT 患者中，分析了 698 例具有每种血栓形成参数测量值的患者。搜索 EAD 发展的危险因素，并根据接收者操作特征曲线分析计算随后的最佳截止值。在比较结果时，进行了多变量回归分析和倾向评分的逆概率处理加权（IPTW）。
LDLT 后 EAD 的患病率为 10.7%（n=75/698）。在参数中，vWFPCR 对 EAD 具有最高的预测能力，最佳截止值为 8.06。vWFPCR≥8.06 与 EAD 发展（OR[95%CI]，2.55[1.28-5.09]，P=0.008）和 90 天移植物失败（HR[95%CI]，2.24[1-4.98]，P=0.043）显著相关。在 IPTW 调整后，vWFPCR 与 C 反应蛋白作为全身炎症的连续指标呈正相关，与血栓形成性较高（即 vWFPCR 较高）的患者呈更陡峭的关系，EAD 的风险增加。将 vWFPCR 添加到 MELD 评分中可将 EAD 风险预测提高 21.9%。
通过促凝和抗凝、血管性血友病因子（vWF）、因子 VIII（FⅧ）、蛋白 C（PC）及其 vWF 与 PC（vWFPCR）和 FVIII 与 PC（FⅧPCR）的不平衡比值评估的移植前血栓形成与 LDLT 后的 EAD 和 90 天移植物失败显著相关，这种关联在合并全身炎症时会恶化。
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