THE INFLUENCE OF AGE, LIVER SIZE AND ENANTIOMER CONCENTRATIONS ON WARFARIN REQUIREMENTS

1 We have tested the hypothesis that the fall in hepatic mass with age influences the age related increase in sensitivity to warfarin. In 39 otherwise healthy outpatients, aged 50-87 years, stabilised on warfar in for prophylaxis of thromboembolism, age, mean International Normali sed Ratio (INR), and mean warfarin dosage were recorded. Liver volume was measured by ultrasound, and plasma was assayed for trough concentr ations of (R)- and (S)-warfarin. 2 There was a negative correlation be tween age and liver volume (r = -0.41; P = 0.01) and age and dose (r = -0.53; P = < 0.001) and a positive correlation between liver volume a nd dose (r = 0.49; P = 0.002). There was no significant correlation be tween dosage and (R)- and (S)-warfarin concentrations, nor between dos age and INR. 3 The regression model including both age and liver volum e data showed a better fit for estimation of warfarin dosage requireme nt than regression models based on age and liver volume data alone. Ni nety-five per cent prediction intervals for warfarin dose requirements were wide, whether age alone, or age and liver volume were used in ca lculations. 4 Due to inter-individual variation in warfarin dosage req uirements related to other influences, both explained and unexplained, routine measurement of age and liver volume would not contribute furt her clinically useful information to that obtained by the INR test cur rently used for predicting warfarin dosage requirements.