Comparison between Endogenous Thrombin Potential (ETP) and INR To Assess Liver Function in Patients with Liver Cirrhosis.

The decreased hepatic synthesis of coagulation factors is a marker of liver failure and a prognostic indicator of survival in cirrhosis. The aPTT and PT/INR are the conventional coagulation tests to measure the haemostatic capacity of the liver. The INR was developed uniquely for use in patients under oral anticoagulation and may not adequately reflect the coagulation changes in liver cirrhosis. However, prognostic models for liver disease include the INR (MELD). New coagulation assessment tests are obviously needed in liver cirrhosis. Recently a test has become available to routinely measure the endogenous thrombin generation potential (ETP). This more physiological test is currently investigated in several haemostatic disorders but not yet in liver failure.

The aim of the study is to investigate correlations between ETP performed on the BCS® system (both Dade Behring, Marburg, Germany) and liver function tests, and compared with INR. We analysed 112 patients with liver cirrhosis (73 Child A, 21 Child B, 18 Child C) without known pre-existing coagulation abnormalities. In these patients ETP, APTT, PT/INR and S-cholinesterase were measured and an C¹⁴-Aminopyrine breathing test was performed.

Both INR and ETP show good correlation with the Child score (P<0.01) as a whole. Looking at the Child score for bilirubin there is a clear correlation with the normalized ETP with 0.84 (CI₉₅ 0.81 - 0.88) for Child A, 0.74 (CI₉₅ 0.55 - 0.93) for Child B, and 0.67 (CI₉₅ 0.60 - 0.75) for Child C (p<0.01). For the presence of ascites there is a correlation with the ETP with 0.86 (CI₉₅ 0.82 - 0.89) for Child A, 0.71 (CI₉₅ 0.62 - 0.79) for Child B, and 0.69 (CI₉₅ 0.59 - 0.80) for Child C (p<0.01). Looking at the albumin level there is a clear correlation with the normalized ETP with 0.83 (CI₉₅ 0.79 - 0.86) for Child A patients, 0.72 (CI₉₅ 0.57 - 0.88) for Child B, and 0.69 (CI₉₅ 0.60 - 0.78) for Child C (p=0.02). In a linear regression model bilirubin (β= −0.319, p<0.01) and ascites (β= −0.233, p=0.06) are the main predictive factor for decreasing thrombin generation. No such clear relationships can be identified for the INR. Both ETP and INR correlate well with S-cholinesterase levels (p<0.01). ETP correlated better with the breathing test than the INR.

These results indicate that the integrity of the coagulation decreases in line with deterioration of other liver functions in patients with liver cirrhosis. The seriousness of this decrease in haemostatic capacity is better demonstrated by the ETP than by the INR (currently part of MELD). In the future the ETP may supersede the INR in prognostic classification systems for hepatic failure.