Thromboelastographic Evaluation of Coagulation in Patients with Liver Disease

Abstract

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 P value among the parameters of thromboelastography, PT INR, platelets, and MELD scoreTable 1.PT INRPlateletsMELD scoreReaction 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. Disclosures No relevant conflicts of interest to declare.

Viscoelastic Tests as Point-of-Care Tests in the Assessment and Management of Bleeding and Thrombosis in Liver Disease

“…A prospective observational study comparing cirrhotic and noncirrhotic liver disease patients with healthy controls found strong correlations between the platelet count and two TEG parameters (MA and the coagulation index) in all cohorts. 24 However, only weak correlations were seen between INR/PT and TEG parameters R and K (kinetic time), which reflect time to initial clot formation and speed of clot formation, respectively. Another study examining TEG in 270 patients with cirrhosis found that K, α-angle, and MA correlated well with platelet count and fibrinogen in all subgroups, regardless of cirrhosis etiology.…”

Bleeding Risk with Invasive Procedures in Patients with Cirrhosis and Coagulopathy

“…Misperceptions of the bleeding risk in cirrhosis largely derive from clinicians' interpretation of standard coagulation tests, including prothrombin time (PT), international normalised ratio (INR), and activated partial thromboplastin time (APTT). However, as these conventional coagulation tests only provide a measure of procoagulant factors and are insensitive to the plasma levels of anticoagulant factors, they do not provide an accurate evaluation of the altered in-vivo haemostatic balance [2,12].…”

“…VETs are increasingly being used as point-of-care tests to guide the rapid assessment and management of coagulopathies in trauma, surgery and liver transplantation. VETs provide a dynamic assessment of haemostasis, evaluating the kinetics of the entire coagulation process from initial clot formation to final clot strength, and provide a more comprehensive reflection of the interaction between plasma, blood cells and platelets [12].…”

“…An exception to this was patients with cholestatic liver diseases, who demonstrated hypercoagulability and higher clot firmness [18]. On the contrary, other recent studies have identified a hypocoagulable TEG profile in cirrhosis, indicating slower and less stable clot formation compared to healthy controls [12,19]. In an Italian prospective study of 261 cirrhotic patients undergoing liver transplantation, TEG values were outside the normal reference ranges in 79.3% of patients, with a trend to hypocoagulability [19].…”

Immune thrombocytopenia – in defence of the platelet count. Response to Hill

“…Regarding the use of thromboelastography to predict thrombotic events in patients with ITP, we agree with Dr. Hill that more studies have to be performed to determine its utility in this field. Nevertheless, considering the value of thromboelastography for evaluating haemostasis in trauma patients (Veigas et al , ), major non‐cardiac surgery and liver disease (Shin et al , ) among other situations, we recommend its use to determine haemostasis in ITP patients with a sustained increase in platelet count.…”