Potential utility of a multi-component coagulation factor panel to assess the risk of portal vein thrombosis in chronic liver disease

Abstract Background: Portal vein thrombosis (PVT) pre-liver transplant (LT) is a major contributor to morbidity in chronic liver disease (CLD); the means of detecting and/or predicting PVT are limited. Objectives: Explore whether plasma coagulation factor activity levels can help detect PVT and/or serve as a substitute for prothrombin time / international normalized ratio (PT/INR) in the Model for End-stage Liver Disease (MELD). Methods: Factor V (FV), Factor VIII (FVIII), Protein C (PC), and Protein S (PS) activity levels and the concentrations of D-dimer, sP-selectin, and asTF were assessed in two cohorts of CLD patients (ambulatory, n=42; LT, n=43). Results: A significant inverse correlation between FVIII activity levels and PVT was found in the LT cohort (p=0.010); FV and PS activity levels were in-trend (p=0.069, p=0.064). We developed a logistic regression-based compensation score to identify patients at risk of PVT. FV and PC activity levels strongly correlated with MELD scores, which enabled the development of a novel scoring system based on multiple linear regressions of the correlations of FV and PC activity with MELD-Na that substitutes PT/INR. 6-month follow-up revealed that our novel formula was non-inferior to MELD-Na at predicting 6-month mortality (c-statistic of 0.627 and 0.615, respectively). Conclusions: We demonstrate for the first time the potential of using the combination of FV, FVIII, and PS activity levels to assess the risk of PVT in CLD. We also show that FV and PC activity levels may be used to replace PT/INR in MELD scoring.