Comparison of Three Methods to Assess Therapeutic Quality Control of Treatment with Vitamin K Antagonists

Summary

During treatment with vitamin K antagonists, International Normalized Ratios (INR) are determined periodically to maintain a therapeutic level of anticoagulation. We evaluated two existing methods for therapeutic quality control (linear interpolation and equidivision), with regard to their validity and reproducibility. In addition, we proposed and evaluated a (hybrid) method that takes into account potential effects of dosage modifications when INRs are far out of the target range. Validity was assessed by deleting intermediary INR results and estimating this INR based on the two surrounding INRs with each of the three methods. The estimated INRs were then compared with the observed INR.

Reproducibility of time spent in an INR range was evaluated for each of the three methods by deleting at random increasing proportions of INRs and comparing these estimates with the situation without deletions. We found that estimates of time spent in INR categories obtained with equidivision were most reproducible, but least valid. The hybrid method showed slightly higher validity and reproducibility in comparison with linear interpolation. Since these differences were small, linear interpolation is preferable to the hybrid method, since the calculations involved are easier.

Keywords

Factor IX - translational initiation - CHO cells - factor IX production - factor IX intron I

• References

• 1 Hirsh J. Oral anticoagulant drugs. N Engl J Med 1991; 324: 1865-75.
• 2 The European Atrial Fibrillation Trial Study Group. Optimal oral anticoagulant therapy in patients with non-rheumatic atrial fibrillation and recent cerebral ischemia. N Engl J Med 1995; 333: 5-9.
• 3 Cannegieter SC, Rosendaal FR, Wintzen AR, Van der Meer FJM, Vandenbroucke JP, Briët E. Optimal oral anticoagulant therapy in patients with mechanical heart valves. N Engl J Med 1995; 333: 11-7.
• 4 Loelinger EA. Laboratory control, optimal therapeutic ranges and therapeutic quality control in oral anticoagulation. Acta Haematol 1985; 74: 125-31.
• 5 Duxbury BmcD. Therapeutic control of anticoagulant treatment. Br Med J 1982; 284: 702-4.
• 6 Rosendaal FR, Cannegieter SC, Van der Meer FJM, Briët E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost 1993; 69: 236-9.
• 7 Van den Besselaar AMHP, van der Meer FJM, Gerrits-Drabbe CW. Therapeutic control of oral anticoagulant treatment in the Netherlands. Am J Clin Pathol 1988; 90 (06) 685-90.
• 8 Azar A, Deckers JW, Rosendaal FR, Van Bergen PFMM, Van der Meer FJM, Jonker JJC, Briët E. Assessment of therapeutic quality control in a long-term anticoagulant trial in post-myocardial infarction patients. Thromb Haemost 1994; 72 (03) 347-51.
• 9 Koopman MMW, Prandoni P, Piovella F, Ockelford PA, Brandjes DPM, Van der Meer J, Gallus AS, Simonneau G, Chesterman CH, Prins MH, Bossuyt PMM, De Haes H, Van den Belt AGM, Sagnard L, d’Azemar P, Büller HR. for the Tasman Study Group. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared to subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334: 682-7.
• 10 Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337 (10) 657-62.
• 11 Gallus AS, Hirsh J. Antithrombotic drugs. In: Cardiovascular Drugs Vol. 3: Antithrombotic Drugs. Avery GS. ed. ADIS press Australasia Pty Ltd; 1978: 85-142.
• 12 Van der Meer FJM, Rosendaal FR, Vandenbroucke JP, Briët E. Bleeding complications in oral anticoagulant therapy. An analysis of risk factors. Arch Intern Med 1993; 153: 1557-62.
• 13 Besselaar van den AM, Breddin K, Lutze G, Parker-Williams J, Taborski U, Vogel G, Tritschler W, Zerback R, Leinberger R. Multicenter evaluation of a new capillary blood prothrombin time monitoring system. Blood Coagul Fibrinolysis 1995; 6 (08) 726-32.