Intraindividual variability over time of thrombin generation in patients with cirrhosis

Abstract

Background

Patients with cirrhosis are at high risk of thrombotic events, including portal vein thrombosis and venous thromboembolism. In such patients, hypercoagulability is not detected by conventional coagulation tests, but only by the thrombin generation assay (TGA) that integrates the role of pro- and anticoagulant factors. However, TGA use to predict clinical events depends on thrombin generation variability over time.

Objectives

The aim of this study was to compare TGA intraindividual variability over time in patients with cirrhosis and in healthy controls.

Methods

Blood samples were prospectively collected from 34 healthy controls and 52 patients with cirrhosis at week 0 (inclusion), 6, and 12. TGA was performed with the calibrated automated thrombogram method, tissue factor (5 pM), phospholipids, and with and without thrombomodulin (4 nM) or activated protein C (1 nM).

Results

When TGA was performed with thrombomodulin, endogenous thrombin potential in patients with cirrhosis was higher compared with controls and increased with cirrhosis severity. Stability over time of all thrombin generation parameters was excellent in healthy controls, good in Child-Turcotte-Pugh (CTP)-A patients, and poor in CTP-B/C patients (severe cirrhosis). In CTP-B/C patients, the phenotype was more variable because one-third of patients switched to normal or hypercoagulability during the 3-month follow-up.

Conclusion

A study with longer monitoring is needed to correlate the hypercoagulable phenotype of patients with cirrhosis with the occurrence of thrombotic events.