Variability of INR in patients on stable long-term treatment with phenprocoumon and acenocoumarol and implications for analytical quality requirements

Summary

Within each patient treated with vitamin K antagonist (VKA), variation of the international normalised ratio (INR) occurs over the treatment period. The purpose of the present study was to assess INR variation in selected patients on long-term treatment in whom the dose of VKA was not changed.This type of variation is considered as “biological variation” which is caused by many factors but not VKA dose changes or other medication. Four groups of long-term patients were examined: each group with a different VKA (acenocoumarol or phenprocoumon) or a different target intensity (INR 2.0–3.5 or 2.5–4.0). All patients were monitored with the same PT system (Hepato Quick, STA-R Evolution coagulation instrument) by one laboratory.The variation of the INR within each patient was expressed as coefficient of variation (CV, in %).The CV was corrected for the average imprecision of the INR measurement (CV, 2.4%). The mean corrected CV values for the four groups were: 10.9% (acenocoumarol, target INR 2.0–3.5); 10.5% (acenocoumarol, target INR 2.5–4.0); 10.4% (phenprocoumon, target INR 2.0–3.5); 9.1% (phenprocoumon, target INR 2.5–4.0). The analytical performance goal for the INR measurement (imprecision) can be derived from the within-subject biological variation. Desirable INR imprecision goals are <4.9% and <5.3% CV for monitoring of phenprocoumon and acenocoumarol, respectively. These goals were achieved using the aforesaid PT system.

Keywords

Vitamin K antagonist - international normalised ratio - biological variation - analytical performance goal

• References

• 1 Ansell J, Hirsh J, Hylek E. et al. Pharmacology and management of the vitamin K antagonists. American College of Chest Physicians evidence-based clinical practice guidelines (8th Edition). Chest 2008; 133: 160S-198S.
• 2 Fraser CG, Hyltoft Petersen P. et al. Proposals for setting generally applicable quality goals solely based on biology. Ann Clin Biochem 1997; 34: 8-12.
• 3 Van den Besselaar AMHP. Precision and accuracy of the international normalized ratio in oral anticoagulant control. Haemostasis 1996; 26 (Suppl. 04) 248-265.
• 4 Lassen JF, Brandslund I, Antonsen S. International Normalized Ratio for prothrombin times in patients taking oral anticoagulants: critical difference and probability of significant change in consecutive measurements. Clin Chem 1995; 41: 444-447.
• 5 Tripodi A, Chantarangkul V, Akkawat B. et al. A partial factor V deficiency in anticoagulated lyophilized plasmas has been identified as a cause of the international normalized ratio discrepancy in the external quality assessment scheme. Thromb Res 1995; 78: 283-292.
• 6 Costongs GMPJ, Bas BM, Janson PCW. et al. Short-term and long-term intra-individual variations and critical differences of coagulation parameters. J Clin Chem Clin Biochem 1985; 23: 405-410.
• 7 Gadisseur AP, van der Meer FJM, Adriaansen HJ. et al. Therapeutic quality control of oral anticoagulant therapy comparing the short-acting acenocoumarol and the long-acting phenprocoumon. Br J Haematol 2002; 117: 940-946.
• 8 Thijssen HHW, Hamulyák K, Willigers H. 4-Hydroxycoumarin oral anticoagulants: pharmacokinetics-response relationship. Thromb Haemost 1988; 60: 35-38.
• 9 Van Geest-Daalderop JHH, Hutten BA, Péquériaux NCV. et al. The influence on INRs and coagulation factors of the time span between blood sample collection and intake of phenprocoumon or acenocoumarol: consequences for the assessment of the dose. Thromb Haemost 2007; 98: 738-746.
• 10 Tripodi A, Chantarangkul V, Bressi C. et al. International sensitivity index calibration of the near-patient testing prothrombin time monitor, ProTime. Am J Clin Pathol 2003; 119: 241-245.
• 11 Plesch W, Wolf T, Breitenbeck N. et al. Results of the performance verification of the CoaguChek XS system. Thromb Res 2008; 123: 381-389.