Introduction. Liver disease patients have complex hemostatic defects leading to a delicate, unstable balance between bleeding and thrombosis. Conventional tests such as PT and APTT are unable to depict these defects completely. Aims. This study aimed at analyzing the abnormal effects of liver disease on sonoclot signature by using sonoclot analyzer (which depicts the entire hemostatic pathway) and 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 to sonoclot analysis and correlated with routine coagulation parameters including platelet count, PT, APTT, fibrinogen, and D-dimer. Results. The sonoclot signatures demonstrated statistically significant abnormalities in patients with liver disease as compared to healthy controls. PT and APTT correlated positively with SONACT ( and <0.0015, resp.) while platelet count and fibrinogen levels depicted significant positive and negative correlations with clot rate and SONACT respectively. Conclusion. Sonoclot analysis may prove to be an efficient tool to assess coagulopathies in liver disease patients. Clot rate could emerge as a potential predictor of hypercoagulability in these patients. 1. Introduction Patients with liver disease show significant changes in the hemostatic system. Consequently, routine diagnostic tests such as platelet count, prothrombin time (PT), and 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, models for end stage liver disease (MELD) score variations up to 12 points have been noted [3]. This could lead to
References
[1]
T. Lisman, S. H. Caldwell, A. K. Burroughs et al., “Hemostasis and thrombosis in patients with liver disease: the ups and downs,” Journal of Hepatology, vol. 53, no. 2, pp. 362–371, 2010.
[2]
P. G. Northup, V. Sundaram, M. B. Fallon et al., “Hypercoagulation and thrombophilia in liver disease,” Journal of Thrombosis and Haemostasis, vol. 6, no. 1, pp. 2–9, 2008.
[3]
T. Lisman, Y. van Leeuwen, J. Adelmeijer et al., “Interlaboratory variability in assessment of the model of end-stage liver disease score,” Liver International, vol. 28, no. 10, pp. 1344–1345, 2008.
[4]
M. A. Mcmichael and S. A. Smith, “Viscoelastic coagulation testing: technology, applications, and limitations,” Veterinary Clinical Pathology, vol. 40, no. 2, pp. 140–153, 2011.
[5]
M. T. Ganter and C. K. Hofer, “Coagulation monitoring: current techniques and clinical use of viscoelastic point-of-care coagulation devices,” Anesthesia and Analgesia, vol. 106, no. 5, pp. 1366–1375, 2008.
[6]
D. A. Hett, D. Walker, S. N. Pilkington, and D. C. Smith, “Sonoclot analysis,” British Journal of Anaesthesia, vol. 75, no. 6, pp. 771–776, 1995.
[7]
R. de Franchis, “Evolving consensus in portal hypertension. Report of the Baveno IV consensus workshop on methodology of diagnosis and therapy in portal hypertension,” Journal of Hepatology, vol. 43, no. 1, pp. 167–176, 2005.
[8]
G. Garcia-Tsao, J. Bosch, and R. J. Groszmann, “Portal hypertension and variceal bleeding—unresolved issues. Summary of an American Association for the study of liver diseases and European Association for the study of the liver single-topic conference,” Hepatology, vol. 47, no. 5, pp. 1764–1772, 2008.
[9]
S. K. Sarin, A. Kumar, J. Almeida, et al., “Acute on chronic liver failure (ACLF): consensus recommendations of the Asia Pacific Association for the Study of the Liver (APASL),” Hepatology International, vol. 3, pp. 269–282, 2009.
[10]
A. Zipprich, G. Garcia-Tsao, S. Rogowski, W. E. Fleig, T. Seufferlein, and M. M. Dollinger, “Prognostic indicators of survival in patients with compensated and decompensated cirrhosis,” Liver International, vol. 39, pp. 1407–1414, 2012.
[11]
R. Jalan, P. Gines, J. C. Olson, et al., “Acute on chronic liver failure,” Journal of Hepatology, vol. 57, pp. 1336–1348, 2012.
[12]
M. Senzolo, P. Burra, E. Cholongitas, and A. K. Burroughs, “New insights into the coagulopathy of liver disease and liver transplantation,” World Journal of Gastroenterology, vol. 12, no. 48, pp. 7725–7736, 2006.
[13]
P. G. Northup, “Hypercoagulation in liver disease,” Clinics in Liver Disease, vol. 13, no. 1, pp. 109–116, 2009.
[14]
P. G. Northup, M. M. McMahon, A. P. Ruhl et al., “Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism,” American Journal of Gastroenterology, vol. 101, no. 7, pp. 1524–1528, 2006.
[15]
J. L. Francis, D. A. Francis, and G. J. Gunathilagan, “Assessment of hypercoagulability in patients with cancer using the Sonoclot analyzer(TM) and thromboelastography,” Thrombosis Research, vol. 74, no. 4, pp. 335–346, 1994.
[16]
D. N. Samonakis, I. E. Koutroubakis, A. Sfiridaki et al., “Hypercoagulable states in patients with hepatocellular carcinoma,” Digestive Diseases and Sciences, vol. 49, no. 5, pp. 854–858, 2004.
[17]
B. L. D. Schaer, A. I. Bentz, R. C. Boston, J. E. Palmer, and P. A. Wilkins, “Comparison of viscoelastic coagulation analysis and standard coagulation profiles in critically ill neonatal foals to outcome,” Journal of Veterinary Emergency and Critical Care, vol. 19, no. 1, pp. 88–95, 2009.
[18]
M. Furuhashi, N. Ura, K. Hasegawa et al., “Sonoclot coagulation analysis: new bedside monitoring for determination of the appropriate heparin dose during haemodialysis,” Nephrology Dialysis Transplantation, vol. 17, no. 8, pp. 1457–1462, 2002.
[19]
T. Miyashita and M. Kuro, “Evaluation of platelet function by Sonoclot analysis compared with other hemostatic variables in cardiac surgery,” Anesthesia and Analgesia, vol. 87, no. 6, pp. 1228–1233, 1998.
[20]
J. J. Liszka-Hackzell and G. Ekback, “Analysis of the information content in sonoclot data and reconstruction of coagulation test variables,” Journal of Medical Systems, vol. 26, no. 1, pp. 1–8, 2002.
[21]
S. S. Adam, N. S. Key, and C. S. Greenberg, “D-dimer antigen: current concepts and future prospects,” Blood, vol. 113, no. 13, pp. 2878–2887, 2009.
[22]
N. Bennani-Baiti and H. A. Daw, “Primary hyperfibrinolysis in liver disease: a critical review,” Clinical Advances in Hematology & Oncology, vol. 9, no. 3, pp. 250–252, 2011.
[23]
D. Prisco and E. Grifoni, “The role of D-dimer testing in patients with suspected venous thromboembolism,” Seminars in Thrombosis and Hemostasis, vol. 35, no. 1, pp. 50–59, 2009.
[24]
F. Violi, D. Ferro, S. Basili et al., “Hyperfibrinolysis resulting from clotting activation in patients with different degrees of cirrhosis,” Hepatology, vol. 17, no. 1, pp. 78–83, 1993.
[25]
M. A. Lyew and W. C. Spaulding, “Template for rapid analysis of the Sonoclot signature,” Journal of Clinical Monitoring, vol. 13, no. 4, pp. 273–277, 1997.
[26]
A. Chen and J. Teruya, “Global hemostasis testing thromboelastography: old technology, new applications,” Clinics in Laboratory Medicine, vol. 29, no. 2, pp. 391–407, 2009.
[27]
R. Kaku, M. Matsumi, M. Ichiyama et al., “Massive bleeding due to hyperfibrinolysis during living-related liver transplantation for terminal liver cirrhosis, report of two cases,” Masui, vol. 52, no. 11, pp. 1195–1199, 2003.
[28]
J. B. Segal and W. H. Dzik, “Paucity of studies to support that abnormal coagulation test results predict bleeding in the setting of invasive procedures: an evidence-based review,” Transfusion, vol. 45, no. 9, pp. 1413–1425, 2005.
[29]
K. Ewe, “Bleeding after liver biopsy does not correlate with indices of peripheral coagulation,” Digestive Diseases and Sciences, vol. 26, no. 5, pp. 388–393, 1981.
[30]
R. T. Stravitz, T. Lisman, V. A. Luketic et al., “Minimal effects of acute liver injury/acute liver failure on hemostasis as assessed by thromboelastography,” Journal of Hepatology, vol. 56, no. 1, pp. 129–136, 2012.
[31]
K. A. Tanaka, F. Szlam, H. Y. Sun, T. Taketomi, and J. H. Levy, “Thrombin generation assay and viscoelastic coagulation monitors demonstrate differences in the mode of thrombin inhibition between unfractionated heparin and bivalirudin,” Anesthesia and Analgesia, vol. 105, no. 4, pp. 933–939, 2007.
[32]
P. G. Northup and S. H. Caldwell, “Coagulation in liver disease: a guide for the clinician,” Clinical Gastroenterology and Hepatology, vol. 11, pp. 1064–1074, 2013.
[33]
H. C. Hemker, R. Al Dieri, E. de Smedt, and S. Béguin, “Thrombin generation, a function test of the haemostatic-thrombotic system,” Thrombosis and Haemostasis, vol. 96, no. 5, pp. 553–561, 2006.
[34]
A. Tripodi, F. Salerno, V. Chantarangkul et al., “Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests,” Hepatology, vol. 41, no. 3, pp. 553–558, 2005.
[35]
R. Kar, S. S. Kar, and S. K. Sarin, “Hepatic coagulopathy-intricacies and challenges, a cross sectional descriptive study of 110 patients from a superspeciality institute of North India with review of literature,” Blood Coagulation and Fibrinolysis, vol. 24, pp. 175–180, 2013.
