Coumarin Anticoagulant Requirement in Relation to Serum Cholesterol and Triglyceride Level

AbstractThe relationship of warfarin requirement to serum cholesterol and triglyceride level was studied in 91 patients, who were on a well stabilized long‐term anticoagulant therapy. In male patients a significant positive correlation was observed between warfarin requirement and serum cholesterol level. A similar trend was observed in female patients, although the correlation did not reach statistical significance. No correlation was present between warfarin requirement and serum triglyceride level. The concentration of warfarin in the plasma 14–15 hours after the preceding warfarin dose was determined in the 91 patients on long‐term warfarin therapy. The plasma warfarin level varied from 0.5 to 6.2 mg per liter with a median value of 2.0 mg per liter. When a serum cholesterol value of 300 mg/100 ml was chosen as a dividing line between normocholesteremia and hypercholesteremia, the median “therapeutic” plasma warfarin level was found to be somewhat higher in hypercholesteremic patients than in normocholesteremic patients. The wide range of individual variation in the “therapeutic” plasma warfarin level indicates that, in addition to the individual variation in the rate of warfarin metabolism, there are considerable individual differences acting at the level of the receptor site for coumarin drugs. The plasma warfarin half‐life was determined in 37 subjects. The mean half‐life of warfarin was 35.6 hours (S.D. 19.1 hours). The range of individual variation was from 10 to 90 hours. There was no correlation between the half‐life of warfarin and serum cholesterol or triglyceride level. The duration of the depression of the prothrombin complex clotting factors after a single warfarin dose was shorter in hypercholesteremic than in normocholesteremic subjects, when related to the half‐life of warfarin in the plasma. A possible explanation of this phenomenon is that a greater amount of vitamin K is available at the receptor site for coumarin drugs in hypercholesteremic subjects. The results support the hypothesis that hypercholesteremia may be associated with increased levels of vitamin K in the plasma and liver.