Evaluating the individual risk of venous thrombo-embolism in patients with liver cirrhosis: Usefulness of in vivo and ex vivo thrombin generation parameters

Introduction Venous thrombo-embolic events (VTE) and especially splanchnic vein thromboses (SVT) are common complications in patients with liver cirrhosis. SVT can worsen portal hypertension and cause ascitic decompensation. Identification of high-risk patients and consecutive targeted primary prophylactic anticoagulation could prevent these complications, preserving favorable conditions for liver transplantation and improving patient quality of life and prognosis. In this study, we aimed to investigate the role of in vivo and ex vivo thrombin generation (TG) parameters in the prediction of VTE in patients with liver cirrhosis.

Method We performed a prospective single-centre study at Lausanne University Hospital (CHUV) including patients with liver cirrhosis. The main outcome was VTE including deep venous thrombosis, pulmonary embolism and SVT. We analysed in vivo TG parameters (prothrombin fragments 1 and 2 [F1+2], thrombin-antithrombin complexes [TAT], D-dimers) and ex vivo TG. Ex vivo parameters were measured using the ST Genesia Thrombin Generation System (Stago, Asnières-sur-Seine, France). The analyses were performed with an intermediate concentration of tissue factor, as well as without and with thrombomodulin (TM) as protein C/S system activator. We focused on the velocity index without TM (representing the thrombin generation velocity), peak height (representing the maximal thrombin concentration), and TM-mediated inhibition (which is the degree of diminution of TG after TM addition, reflecting the activity of the protein C/S system). We also analysed routine hemostatic tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], fibrinogen, factor V activity). Comparisons between groups were assessed by Mann-Whitney test ([Tab. 1]).

Tab. 1  Comparisons between groups with and without venous thrombo-embolic events; Data are number (%), respectively median (standard deviation) and results of Mann-Whitney tests. VTE, venous thrombo-embolic events; ETP, endogenous thrombin potential; TM, thrombomodulin; aPTT, activated partial thromboplastin time.

Results We included 294 non-anticoagulated patients. Median age was 59 years (range, 18-81 years) and 68 patients (23%) were female. Regarding cirrhosis severity, 235 (79.9%) had a Child-Pugh score A, 49 (16.7%) B and 10 (3.4%) C. Comparisons of the parameters between groups with and without VTE are presented in Table 1. The velocity index, TM-mediated inhibition, TAT, F1+2 and D-dimers as well as aPTT and PT were significantly associated with the risk of VTE.

Conclusion In vivo and ex vivo TG parameters are associated with the risk of VTE in patients with liver cirrhosis. The integration of these parameters with clinical (e.g. etiology of liver cirrhosis, history of VTE, or presence of cancer) and paraclinical variables (in particular, parameters of portal hemodynamics such as portal vein flow) is a promising approach to identify high-risk patients who could benefit from primary prophylactic anticoagulation. Analyses are ongoing to develop a VTE risk prediction score in patients with liver cirrhosis.

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Artikel online veröffentlicht:
20. Februar 2023