Journal of Thrombosis and Thrombolysis

, Volume 30, Issue 1, pp 84–89 | Cite as

Assessment of validity of INR system for patients with liver disease associated with viral hepatitis



International Normalized Ratio (INR), which standardizes prothrombin time (PT) during oral anticoagulation, has been extended to standardize PT in liver diseases and is included in all prognostic models of survival, the classification of CHILD-Pugh or Meld. However, the mechanisms of PT prolongation in liver diseases differ from those involved in oral anticoagulation. Our aim was to assess the validity of the INR system for patients with liver disease associated with viral hepatitis. We prospectively collected blood samples from 61 patients with liver disease associated with viral hepatitis; control patients were on warfarin (n = 20). PTs were measured on a STA-R coagulometer with six thromboplastin reagents, and INRs were calculated using instrument-specific ISIs. Simultaneously, we selected 15 pairs of patients in the study population and in the control population such that INR values for each patient pair are almost equal. For these 15 pairs of patients, we performed factor assays and measured the coagulant activities of factors II, V, VI, and X and fibrinogen. Analysis of results for the control population confirms the validity of the INR system for patients on oral anticoagulants in that there was no significant difference between the reported INRs for the six different thromboplastin reagents. Conversely, for the study population, there was a significant difference between the INR results using the different reagents. Results for fibrinogen and factors V, VII, and X showed significant differences between the two groups; however, control and patient results for factor II were not statistically different. The INR system is not valid for comparison of patients with liver disease associated with viral hepatitis because different reagents do not yield the same INR for the same sample.


International normalized ratio (INR) Prothrombin time (PT) Liver disease 


  1. 1.
    Ansell J, Hirsh J, Poller L, Bussey H, Jacobson A, Hylek E (2004) The pharmacology and management of the vitamin K antagonists: seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 26:457S–482SGoogle Scholar
  2. 2.
    Dufour DR, Lott JA, Nolte FS, Gretch DR, Koff RS, Seeff LB (2000) Diagnosis and monitoring of hepatic injury. II. Recommendation for use of laboratory tests in screening, diagnosis, and monitoring. Clin Chem 46:2027–2049PubMedGoogle Scholar
  3. 3.
    Ingram GI, Hills M (1976) Reference method for the one-stage prothrombintime in human blood. International committee for standardization in hematology. Thromb Haemost 36:237–238PubMedGoogle Scholar
  4. 4.
    Loeliger EA (1979) The optimal therapeutic range in oral anticoagulation: history and proposal. Thromb Haemost 42:1141–1152PubMedGoogle Scholar
  5. 5.
    Poller L, Taberner DA (1982) Dosage and control of oral anticoagulants: an international survey. Br J Haematol 51:479–485CrossRefPubMedGoogle Scholar
  6. 6.
    Hull R, Hirsh J, Jay R, Carter C, England C, Gent M et al (1982) Different intensities of oral anticoagulant therapy in the treatment of proximal-vein thrombosis. N Engl J Med 307:1676–1681PubMedGoogle Scholar
  7. 7.
    World Health Organization (1983) World Health Organization Expert Committee on Biological Standardization. 33rd report: Technical Report Series, no. 687. Geneva, SwitzerlandGoogle Scholar
  8. 8.
    Amitrano L, Guardascione MA, Brancaccio V, Balzano A (2002) Coagulation disorders in liver disease. Semin Liver Dis 22:83–96CrossRefPubMedGoogle Scholar
  9. 9.
    Peck-Radosavljevic M (2007) Review article: coagulation disorders in chronic liver disease. Aliment Pharmacol Ther 26:21–28PubMedCrossRefGoogle Scholar
  10. 10.
    Trotter JF (2006) Coagulation abnormalities in patients who have liver disease. Clin Liver Dis 10:665–678CrossRefPubMedGoogle Scholar
  11. 11.
    Stanley TB, Jin DY, Lin PJ, Stafford DW (1999) The propeptides of the vitamin K-dependent proteins possess different affinities for the vitamin K-dependent carboxylase. J Biol Chem 274:16940–16944CrossRefPubMedGoogle Scholar
  12. 12.
    Furie B, Furie BC (1990) Molecular basis of vitamin K-dependent gamma-carboxylation. Blood 75:1753–1762PubMedGoogle Scholar
  13. 13.
    Sallah S, Bobzien W (1999) Bleeding problems in patients with liver disease. Ways to manage the many hepatic effects on coagulation. Postgrad Med 106:187–90, 193–195Google Scholar
  14. 14.
    Paramo JA, Rocha E (1993) Hemostasis in advanced liver disease. Semin Thromb Hemost 19:184–190CrossRefPubMedGoogle Scholar
  15. 15.
    Munoz SJ (1991) Prothrombin time in fulminant hepatic failure. Gastroenterology 100:1480PubMedGoogle Scholar
  16. 16.
    Robert A, Chazouillères O (1996) Prothrombin time in liver failure: Time, ratio, activity percentage, or international ratio? Hepatology 24:1392–1394CrossRefPubMedGoogle Scholar
  17. 17.
    Samada Suarez M, Hernández Perera JC, Ramos Robaina L et al (2008) Factors that predict survival in patients with cirrhosis considered for liver transplantation. Transplant Proc 40:2965–2967CrossRefPubMedGoogle Scholar
  18. 18.
    Cooper GS, Bellamy P, Dawson NV et al (1997) A prognostic model for patients with end-stage liver disease. Gastroenterology 113:1278–1288CrossRefPubMedGoogle Scholar
  19. 19.
    Kamath PS, Wiesner RH, Malinchoc M, Kremers W, Therneau TM, Kosberg CL et al (2001) A model to predict survival in patients with end-stage liver disease. Hepatology 33:464–470CrossRefPubMedGoogle Scholar
  20. 20.
    Carithers RL Jr, Herlong HF, Diehl AM et al (1989) Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial. Ann Intern Med 110:685–690PubMedGoogle Scholar
  21. 21.
    Hirsh J (1991) Oral anticoagulant drugs. N Engl J Med 324(26):1865–1875PubMedGoogle Scholar
  22. 22.
    Bland JM, Altman DG (1986) Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1(8476):307–310Google Scholar
  23. 23.
    Polson J, Lee WM (2005) AASLD Position paper: the management of acute liver failure. Hepatology 41:1179–1197CrossRefPubMedGoogle Scholar
  24. 24.
    Lok AS, Ghany MG, Goodman ZD, Wright EC, Everson GT, Sterling RK et al (2005) Predicting cirrhosis in patients with hepatitis C based on standard laboratory tests: results of the HALT-C cohort. Hepatology 42:282–292CrossRefPubMedGoogle Scholar
  25. 25.
    Sterling RK, Lissen E, Clumeck N, Sola R, Correa MC, Montaner J et al (2006) Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology 43:1317–1325CrossRefPubMedGoogle Scholar
  26. 26.
    Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P et al (2003) United Network for Organ Sharing Liver Disease Severity Score Committee: model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology 124:91–96CrossRefPubMedGoogle Scholar
  27. 27.
    Murray KF, Carithers RL Jr (2005) AASLD practice guidelines: evaluation of the patient for liver transplantation. Hepatology 41:1–26CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Graduate School of the Chinese P.L.A. General HospitalBeijingPeople’s Republic of China
  2. 2.Organ Transplant Center, Second Affiliated Hospital of Chinese P.L.A. General HospitalBeijingPeople’s Republic of China
  3. 3.Department of Clinical LaboratoryChinese P.L.A. General HospitalBeijingPeople’s Republic of China

Personalised recommendations