An International Sensitivity Index (ISI) derived from patients with abnormal liver function improves agreement between INRs determined with different reagents

Anne M. Sermon; Julie M. Smith; Rhona Maclean; Steve Kitchen

doi:10.1160/TH09-08-0535

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(04): 757-768
DOI: 10.1160/TH09-08-0535

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

An International Sensitivity Index (ISI) derived from patients with abnormal liver function improves agreement between INRs determined with different reagents

Anne M. Sermon

¹Department of Coagulation, Northern General Hospital, Sheffield, UK

,

Julie M. Smith

¹Department of Coagulation, Northern General Hospital, Sheffield, UK

,

Rhona Maclean

²Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK

,

Steve Kitchen

²Haemophilia and Thrombosis Centre, Royal Hallamshire Hospital, Sheffield, UK

› Author Affiliations

Abstract

Summary

The International Normalised Ratio (INR)/International Sensitivity Index (ISI) system was developed as a way to standardise the prothrombin time during the monitoring of patients undergoing oral anti-coagulant therapy with vitamin K antagonists. The wide acceptance of the INR has led to its use as one of three parameters used in the Model for End stage Liver disease (MELD) scoring system to aid the prioritisation of patients for liver transplant. Literature published recently has highlighted the potential inadequacy of the INR system in this context. Our aim was to investigate the degree of difference between INR values calculated using an ISI derived from warfarinised patients and those calculated using an ISI derived from patients with liver disease. Prothrombin times from 60 patients with liver disease were determined using three working thromboplastin reagents; Innovin^®, Thromborel S^® and Thromboplastin C^® and two reference thromboplastins; rTF/95 and RBT/05. All thromboplastin reagents tested had standard international sensitivity indices (ISIs) assigned following calibration with patients on oral anticoagulant therapy (ISI_vka). As a result of the new calibration each of the working thromboplastin reagents was assigned a specific “liver patient” ISI. Two INR values were calculated for each thromboplastin patient involved in the calibration. A comparison of the mean INRliver with INR_vka showed a statistically significant difference between the two values (p<0.0001). A similar relationship existed for INRs on a further 20 patients with liver disease whose plasmas were not used to derive the ISIliver. This difference led to a change in the final MELD score and could therefore affect the prioritisation and management of these patients.

Keywords

Liver disease - international normalised ratio - standardisation

Full Text

References

References
1 World Health Organisation.. WHO Technical Report Series No 889 (1999) Guidelines for Thromboplastins and Plasma Used To Control Oral Anticoagulant Therapy. http://www.who.int/bloodproducts/publications/WHO_TRS_889_A3.pdf.
2 Kovacs MJ, Wong A, MacKinnon K. et al. Assessment of the validity of the INR system for patients with liver impairment. Thromb Haemost 1994; 71: 727-730.
3 Denson KWE, Reed SV, Haddon ME. Validity of the INR system for patients with liver impairment. Thromb Haemost 1995; 73: 162-166.
4 Trotter JF, Brimhall B, Arjal R. et al. Specific laboratory methodologies achieve higher Model for End Stage Liver Disease (MELD) scores for patients listed for liver transplantation. Liver Transpl 2004; 10: 995-1000.
5 Trotter JF, Olson J, Lefkowitz J. et al. Changes in International Normalised Ratio (INR) and Model for Endstage Liver Disease (MELD) based on selection of clinical laboratory. Am J Transpl 2007; 07: 1624-1628.
6 Bellest L, Eschwège V, Poupon R. et al. A modified International Normalised Ratio as an effective way of prothrombin time standardisation. Hepatol 2007; 46: 528-534.
7 Tripodi A, Chantarangkul V, Primignani M. et al. The International Normalised Ratio calibrated for cirrhosis (INR_lver) normalises prothrombin time results for Model for End-Stage Liver Disease calculation. Hepatol 2007; 46: 520-527.
8 Kamath PS, Wiesner RH, Malinchoc M. et al. A model to predict survival in patients with end-stage liver disease. Hepatol 2001; 33: 464-470.
9 Wiesner RH, McDiarmid SV, Kamath PS. et al. MELD and PELD: Application of survival models to liver allocation. Liver Transpl 2001; 07: 567-580.
10 Freeman RB, Weisner RH, Harper A. et al. The New Liver Allocation System: moving towards evidence-based transplantation policy. Liver Transpl 2002; 08: 851-858.
11 Tripodi A, Chantarangkul V, Negri B. et al. International Collaborative Study for the Calibration of a Proposed Reference Preparation for Thromboplastin, Human Recombinant Plain. Thromb Haemost 1998; 79: 439-443.
12 Chantarangkul V, Van Den Besselaar AMHP, Witteveen E. et al. International Collaborative Study for the Calibration of a Proposed International Standard for Thromboplastin, Rabbit, Plain. J Thromb Haemost 2006; 04: 1339-1345.
13 United Network for Organ Sharing: Organ Donation and transplantation MELD/ PELD Calculator http://www.unos.org/resources.
14 Denson KWE, Reed SV, Haddon ME. et al. Comparative studies of rabbit and human recombinant tissue factor reagents. Thromb Res 1999; 94: 255-261.
15 Deitcher SR. Interpretation of the International Normalised Ratio in patients with liver disease. Lancet 2002; 359: 47-48.
16 Tripodi A, Chantarangkul V, Primignani M. et al. Point-of-care coagulation monitors calibrated for the international normalised ratio for cirrhosis (INRliver) can help to implement the INRliver for the calculation of the MELD score. J Hepatol 2009; 51: 288-295.
17 Malinchoc M, Kamath PS, Gordon FD. et al. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatol 2000; 31: 864-871.