THE EFFECT OF THE PLASMA-LEVELS OF PROTEIN-C AND PROTEIN-S ON THE PREDICTION OF WARFARIN MAINTENANCE DOSE REQUIREMENTS

Objective: Determination of the effects of the vitamin K-dependent anticoagulants, proteins C and S, on warfarin dose requirements and on the prediction error of a bayesian warfarin dose predicting program. Methods: Patients in the study were consecutive inpatients (n = 18) starting treatment with warfarin who were monitored as outpatients for 4 weeks. The following measurements were taken: repeated (n = 8) prothrombin times, expressed as the international normalized ratio (INR), plasma protein C and S antigen levels (percentage of pooled normal plasma), demographic, clinical and biochemical variables. Results: Maintenance doses (adjusted to INR 2.5) were 6.7 +/- 3.4 mg/day. Protein C decreased to 56.9% +/- 15.3%, protein S to 63.7% +/- 17.3%, INR increased to 2.46 +/- 0.14. Prediction error decreased from 2.84 +/- 2.0 mg/day to 0.95 +/- 0.78 mg/day. Protein C accounted for only 4.2% of the mean maintenance dose but protein C and S levels accounted for 31% of the mean dose prediction error. Conclusion: Protein C and S levels affect warfarin doses and predictions significantly but not to a clinically meaningful degree.