Thromboelastographic Evaluation of Coagulation in Patients with Liver Disease

Background: Patients with acute and chronic liver disease have long been assumed to have a bleeding tendency on the basis of abnormal results for standard tests of hemostasis. The concept that patients with liver disease are at an increased risk of bleeding, based solely on abnormalities of conventional coagulation tests such as prothrombin time (PT) and international normalized ratio (INR), is now recognized to be an overly simplistic interpretation of an extremely complex situation. Thromboelastography (TEG) is a commercially available, rapid, point-of-care whole blood viscoelastic assay that assesses the kinetics of coagulation from initial clot formation to final clot strength in whole blood, including plasmatic and cellular components. The aim of this study was to compare TEG citrated whole blood coagulation parameters and conventional coagulation parameters in liver disease patients and in healthy controls.

 Methods: Between January and July 2015, we investigated citrated blood samples from 35 healthy controls and 171 adult patients with liver disease who were divided into two groups of hepatitis group (including patients with acute and chronic hepatitis) and liver cirrhosis group (including patients with liver cirrhosis with or without hepatocellular carcinoma). The parameters of clot formation, which were R (reaction time, a measure of initial fibrin formation), K (constant, indicative of clot formation time), a (angle, indicative of the rapidity of fibrin cross-linking), MA (maximal amplitude, indicative of overall clot firmness) were measured with activator, kaolin, by using TEG 5000 system (Haemonetics Corporation, USA) and CI (Coagulation Index) was derived from the R, K, α and MA. Hemoglobin, platelet count, creatinine, total bilirubin and PT INR was simultaneously measured. MELD (The Model for End-Stage Liver Disease) score for assessing the severity of liver disease was calculated by creatinine, bilirubin and PT INR. 

Results: A total 206 cases, 53 patients with hepatitis group, 118 patients with liver cirrhosis group, and 35 patients with control group, was enrolled. In the liver cirrhosis group, all of parameters of TEG and hemoglobin showed significant difference with those of control group. In the hepatitis group, only R time and platelet count were significant different from that of the control group. There were significant differences of all parameter, except R time, between hepatitis group and liver cirrhosis group. According to etiology, PT-INR, MELD score, platelet count, K, angle, MA, CI of autoimmune liver disease were different form liver disease of viral and other cause. All parameter of TEG were statistically significantly correlated with the number of platelets and PT INR and MELD score (Table 1).

 Table 1. Correlation coefficients and Pvalue among the parameters of thromboelastography, PT INR, platelets, and MELD score   

	PT INR	Platelets	MELD score
Reaction Time (R)	0.247(<0.001)	-0.286(<0.001)	0.157(<0.01)
Constant (K)	0.296(<0.001)	-0.567(<0.001)	0.219(<0.001)
Angle (α)	-0.293(<0.001)	0.613(<0.001)	-0.206(<0.001)
Maximal Amplitude (MA)	-0.348(<0.001)	0.719(<0.001)	-0.287(<0.001)
Coagulation Index (CI)	-0.364(<0.001)	0.672(<0.001)	-0.275(<0.001)

Conclusion: The patients with liver disease with high MELD score, elevated PT INR, and thrombocytopenia demonstrated the trend to hypocoagulability and hyperfibrinolysis using TEG. TEG is considered as an additional test for investigating liver disease and predicting the prognosis in this category of patients.