Sonoclot Signature Analysis In Patients with Liver Disease And Its Correlation With Conventional Coagulation Studies.

 Title: Sonoclot Signature Analysis In Patients with Liver Disease And Its Correlation With Conventional Coagulation Studies.

Running title: Sonoclot analysis in liver disease and correlation with conventional parameters

Priyanka Saxena1, Chhagan Bihari1, Archana Rastogi2, Savita Agarwal 2 , Lovkesh Anand3 and Shiv Kumar Sarin3

Department of Hematology1, Department of Pathology2 Department of Hepatology3

Institute of Liver and Biliary Sciences D-1, Vasant Kunj, New Delhi-110070, India

Word Count: 3498

Number of Figures: 4

Number of Tables: 4

Conflict of Interest: None

Grants and Funds: None Applicable

Address for Correspondence

Dr. Chhagan Bihari

Assistant Professor,

Department of Hematology

Institute of Liver and Biliary Sciences

D-1, Vasant Kunj

New Delhi-110070

Email: drcbsharma@gmail.com

Contact No: +911146300000 (6035)  

Abstract

Introduction: Patients with liver disease have complex hemostatic defects leading to a delicate, unstable balance between bleeding and thrombosis. Conventional coagulation tests such as prothrombin time (PT), activated partial thromboplastin time (APTT) etc. are unable to depict these defects completely. Aims: This study was carried out to analyze the abnormal effects of liver disease on sonoclot signature by using a viscoelastic device (sonoclot analyzer) which provides information on the entire hemostatic pathway. We also aimed at assessing the correlations between sonoclot variables and conventional coagulation tests. Material and methods: Clinical and laboratory data from fifty inpatients of four subgroups of liver disease, including decompensated cirrhosis, chronic hepatitis, cirrhosis with HCC and acute on chronic liver failure were analyzed. All patients and controls were subjected for sonoclot analysis and correlated with routine coagulation parameters including platelets count, PT, APTT, fibrinogen, D-dimer etc. Results: The sonoclot signatures demonstrated statistically significant abnormalities in patients with liver disease as compared to healthy controls. PT and APTT correlated positively with sonoclot activated clotting time (P<0.008 and <0.0015 respectively) while platelet count and fibrinogen levels depicted statistically significant positive and negative correlations with clot rate and sonoclot activated clotting time respectively. Conclusion: Sonoclot analysis may prove to be an efficient tool to assess coagulopathies in patients with liver disease. Clot rate could emerge as a potential predictor of hypercoagulability in these patients.  

Keywords: Sonoclot, Cirrhosis, ACLF, Prothrombin Time, Activated partial thromboplastin time, D-dimer, hypercoagulability, Fibrinolysis.

Introduction

Patients with liver disease show significant changes in the hemostatic system. Consequently, routine diagnostic tests such as platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT) are frequently abnormal. However, interpretation of these tests is much less accurate in patients with complex hemostatic disorders as can be found in patients with liver disease [1]. It is now established that patients with liver disease not only have bleeding tendencies but may develop thrombotic complications as well [2].

The inability of PT-INR and APTT to predict the bleeding risk can be explained by the fact that they incompletely reflect the coagulation process. The parallel decline in the level of natural anticoagulants leading to a prothrombotic tendency is not depicted by these tests. Additionally significant variations in the INR values have been reported in liver disease patients when tested in different laboratories. Due to this poor reproducibility of INR values, model for end stage liver disease(MELD) score variations upto 12 points have been noted[3]. This could lead to significant discrepancies in the management of these patients.

Standard coagulation tests such as PT, APTT etc. do not incorporate cellular elements. They tend to provide data on isolated aspects of coagulation cascade and overlook factors such as rate of clot formation, time taken for maximal clot retraction and maximal clot strength. Instead viscoelastic devices such as Sonoclot provide in vitro assessment of global coagulation.  

Sonoclot may also be useful in diagnosing systemic fibrinolysis, though it may not reflect localized clot breakdown by plasmin. Most conventional coagulation tests end when the first fibrin strands are developing, whereas viscoelastic coagulation tests begin at this point and continue throughout clot development, retraction and lysis [4].

This study was carried out to analyze the abnormalities of sonoclot signature in patients with liver diseases including chronic hepatitis, decompensated cirrhosis, compensated cirrhosis with hepatocellular carcinoma and acute on chronic liver failure. The sonoclot signature parameters studied included sonoclot activated clotting time (SONACT), clot rate (CR), platelet function (PF), time to peak (TP), peak amplitude (PA) and R2 peak character. We also aimed to establish a correlation between the above mentioned sonoclot parameters and conventional coagulation tests like PT, International normalized ratio (INR), APTT, fibrinogen levels, platelet count and D-dimer levels in these patients. 5 Sonoclot Coagulation & Platelet Function Analyzer, Sienco Inc., Arvada, CO, USA The Sonoclot Analyser was introduced by von Kaulla et al in 1975. Sonoclot measurements are based on detection of viscoelastic changes in the whole blood sample. The instrument provides information on the entire hemostatic process in the form of a qualitative graph known as sonoclot signature along with several quantitative measurements [5]. The quantitative measurements include: Sonoclot activated clotting time (SONACT) which is the onset time in seconds until the beginning of fibrin formation. The rate of fibrin formation from fibrinogen is depicted by the gradient of primary slope (R1) and is known as clot rate (CR). It is expressed as units per minute. The secondary slope (R2) reflects fibrin polymerization and platelet-fibrin interaction. The R2 peak indicates completion of fibrin formation and has two variables. The time to peak (in minutes), which is an index of the rate of conversion of fibrinogen to fibrin and peak amplitude (expressed in units) which is an index of fibrinogen concentration. The downward slope (R3) after the peak is produced as platelets induce contraction of the completed clot. In cases of low platelet counts and/or poor platelet function a shallow R3 slope is obtained. Hence the R3 slope gradient determines the number of available platelets and the level of platelet function and is recorded as platelet function (PF) by the analyzer (Fig. 1). In patients with accelerated fibrinolysis the decrease in signal after the R3 slope can be clinically used as a measure of fibrinolysis [6].