Zanetto Alberto, Campello Elena, Bulato Cristiana, Willems Ruth, Konings Joke, Roest Mark, Gavasso Sabrina, Nuozzi Giorgia, Toffanin Serena, Zanaga Paola, Burra Patrizia, Russo Francesco Paolo, Senzolo Marco, de Laat Bas, Simioni Paolo
Gastroenterology and Multivisceral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padova University Hospital, Padova, Italy. Electronic address: https://twitter.com/azanetto.
General Internal Medicine Unit, Azienda Ospedale - Università Padova, Padova, Italy; Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center, Department of Medicine, University of Padova, Italy.
J Thromb Haemost. 2024 Feb;22(2):480-492. doi: 10.1016/j.jtha.2023.10.008. Epub 2023 Oct 21.
Patients with cirrhosis have a normal to increased thrombin generation (TG) capacity in platelet-poor plasma (PPP). By reflecting the contribution of all circulating blood cells, whole blood (WB) TG may allow a more physiological assessment of coagulation.
We compared WB-TG vs PPP-TG in patients with cirrhosis.
Assessment of coagulation included routine tests, factor VIII, natural anticoagulants, PPP-TG, and WB-TG. TG assays were performed with and without thrombomodulin. Twenty-five healthy subjects were included as controls.
We included 108 patients (Child-Pugh A/B/C, 44/24/40). Compared with controls, patients had significantly lower platelet count, longer international normalized ratio, higher FVIII, and lower levels of protein C/S and antithrombin. Regarding thrombomodulin-modified TG assays, in compensated cirrhosis, both PPP-TG and WB-TG indicated an increased TG capacity, as reflected by an endogenous thrombin potential (ETP) significantly higher than controls. In contrast, in decompensated cirrhosis, PPP-TG indicated a hypercoagulable state with increased ETP, higher peak height, and shorter time-to-peak than controls, whereas WB-TG revealed a progressive impairment of TG kinetics and total capacity, ultimately resulting in a profound hypocoagulable state in patients with Child-Pugh C cirrhosis (ie, significant prolongation of lag time and time-to-peak with reduction of both ETP and peak height). In decompensated patients, bacterial infections and severity of anemia were associated with a further reduction of both ETP and peak height.
Compensated cirrhosis is associated with an increased TG capacity. In decompensated cirrhosis, contrary to PPP-TG, which indicates hypercoagulability, WB-TG shows a significant hypocoagulable state. The clinical value of these findings deserves further investigation.
肝硬化患者在乏血小板血浆（PPP）中的凝血酶生成（TG）能力正常或增强。全血（WB）TG通过反映所有循环血细胞的作用，可能对凝血进行更符合生理的评估。
我们比较了肝硬化患者的WB-TG与PPP-TG。
凝血评估包括常规检测、因子VIII、天然抗凝剂、PPP-TG和WB-TG。在有和没有血栓调节蛋白的情况下进行TG检测。纳入25名健康受试者作为对照。
我们纳入了108例患者（Child-Pugh A/B/C级，分别为44/24/40例）。与对照组相比，患者的血小板计数显著降低，国际标准化比值延长，因子VIII水平升高，蛋白C/S和抗凝血酶水平降低。关于血栓调节蛋白修饰的TG检测，在代偿期肝硬化中，PPP-TG和WB-TG均显示TG能力增强，内源性凝血酶潜力（ETP）显著高于对照组即反映了这一点。相比之下，在失代偿期肝硬化中，PPP-TG显示高凝状态，ETP增加、峰值高度更高且达到峰值的时间比对照组更短，而WB-TG显示TG动力学和总能力逐渐受损，最终导致Child-Pugh C级肝硬化患者出现严重的低凝状态（即滞后时间和达到峰值的时间显著延长，同时ETP和峰值高度降低）。在失代偿期患者中，细菌感染和贫血严重程度与ETP和峰值高度的进一步降低相关。
代偿期肝硬化与TG能力增强有关。在失代偿期肝硬化中，与显示高凝性的PPP-TG相反，WB-TG显示出显著的低凝状态。这些发现的临床价值值得进一步研究。
