EFFECT OF LABORATORY VARIATION IN THE PROTHROMBIN-TIME RATIO ON THE RESULTS OF ORAL ANTICOAGULANT-THERAPY

Background. Patients receiving long-term anticoagulant therapy may be subject to unnecessary risks of bleeding or thromboembolism because of variability in the commercial thromboplastins used to determine proth rombin time and consequent uncertainty about the actual intensity of a nticoagulation. Methods. We explored the effect of this uncertainty on the benefits and risks of anticoagulation in patients with prosthetic heart valves, using models of thromboembolic and hemorrhagic complica tions as a function of the intensity of anticoagulation, with quality- adjusted life expectancy and average variable costs used to describe o utcomes. Results. Anticoagulation provides a striking benefit for pati ents whose treatment is conducted within the recommended range of the international normalized ratio (INR) - i.e., 2.5 to 3.5 - but if uncer tainty about the laboratory results causes the intensity of anticoagul ation to fall outside this range, the gain becomes smaller. Uncertaint y about the true intensity of anticoagulation may reduce the potential gain in life expectancy, adjusted for quality of life, by more than h alf and may increase the ratio of costs to effectiveness to almost fiv e times the optimal value. Variability in the intensity of anticoagula tion is even greater if older recommendations advocating a higher leve l of anticoagulation are followed. Conclusions. Uncertainty about the sensitivities of the commercially available thromboplastins used in th e United States can have important clinical and economic effects. This problem could be eliminated if clinical laboratories uniformly report ed the intensity of anticoagulation as the INR, by adjusting prothromb in-time ratios for variability in thromboplastins.