The effect of the plasma levels of proteins C and 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. Clinical Pharmacology and Therapeutics (1992) 52, 42–49; doi: 10.1038/clpt.1992.101