phenprocoumon and Hyperlipidemias

When testing the effect of a new clofibrate analogue (BM 15.075) on oral anticoagulation and blood clotting in 15 patients for over four weeks it was demonstrated that, depending on the dose of the drug, there was an increase in anticoagulation. The dose of phenprocoumon had to be reduced by 20.6 or 28.7%, respectively, when BM 15.075 was given at a dose of 450 or 600 mg. There was an inhibition of collagen-induced platelet-aggregation. In parallel there was an increase in bleeding time. Fibrinogen concentration was slightly but statistically not significantly decreased. Euglobulin lysis was shortened, especially if previously abnormally long. There was no direct influence on other plasmatic clotting factors.

Topics: Aged; Blood Coagulation; Blood Platelets; Clofibrate; Drug Synergism; Female; Fibrinogen; Humans; Hyperlipidemias; Male; Middle Aged; Phenprocoumon; Platelet Aggregation

The influence of a new hypolipidaemic agent, bezafibrate, on anticoagulant requirements and fibrinolysis was studied in 15 patients with hyperlipidaemia on long-term treatment with racemic phenprocoumon. Our results suggest a dose-dependent augmentation of the anticoagulant response to the coumarin drug. Treatment with bezafibrate at 450 and 600 mg daily required a reduction of the phenprocoumon dose by 18.5 and 33.5%, respectively. Correspondingly, the serum level of phenprocoumon decreased by 11.6 and 35.3%. No evidence for an altered drug elimination of racemic phenprocoumon could be found during treatment with bezafibrate. The results support the hypothesis that bezafibrate and analogous hypolipidaemic drugs enhance the response to oral anticoagulant drugs by increasing the affinity of the receptor site for coumarins or the rate of degradation of the vitamin-K-dependent clotting factors. The investigation of the fibrinolytic enzyme system demonstrated an increase of the fibrinolytic activity by enhancing the activity of the plasminogen activator. The lysis time for euglobulin clot was reduced significantly, plasma fibrinogen only moderately. The antiplasmin activity could not be altered substantially by a decrease of alpha1-antitrypsin and a slight increase of alpha2-macroglobulin. In contrast with the inhibition of platelet function the effect of bezafibrate on the fibrinolytic enzyme system showed no dose dependence.

Topics: 4-Hydroxycoumarins; Blood Coagulation; Blood Coagulation Factors; Drug Synergism; Drug Therapy, Combination; Female; Fibrinolysis; Humans; Hyperlipidemias; Hypolipidemic Agents; Male; Phenprocoumon; Plasminogen Activators