A model-based algorithm for the monitoring of long-term anticoagulation therapy

It has been shown that computerized algorithms for the prescription of coumarin derivates can improve the quality of long-term anticoagulation treatment. These algorithms are usually based on an empiric relationship between dosage and International Normalized Ratio and do not quantify the delaying effect of the drug's pharmacokinetics or the effect of alternating doses that are used to approximate a certain average dosage. Our objective was to develop a mathematical model that takes into account these effects and to develop a new algorithm based on this model that can be used to further optimize the quality of long-term anticoagulation treatment. We simplified a general model structure that was proposed by Holford in 1986 so that the parameters can be estimated using data that are available during long-term anticoagulation treatment. The constant parameters in the model were estimated separately for phenprocoumon and acenocoumarol using data from 1279 treatment courses from three different anticoagulation clinics in the Netherlands. The only variable parameter in the model is the sensitivity of the patient, which is estimated during the course of each treatment. A total of 194 dosage and appointment intervals that were proposed by the new algorithm were scored as 'good', 'acceptable', or 'bad' by two dosing experts. One hundred and seventy-eight (91.8%) proposals were considered good by at least one expert and bad by none. In 39 cases the experts disagreed. We believe that this algorithm will allow further improvement of anticoagulation treatments.