Clofibrate Reversal of Platelet Hypersensitivity in Hyperbetalipoproteinemia

Abstract

Platelet function was evaluated in 29 patients with familial hyperbetalipoproteinemia; 17 were untreated and 12 were receiving clofibrate (Atromid-S). In comparison with 26 normal subjects, the untreated patients aggregated in response to 1/3 the concentration of adenosine diphosphate (ADP), 1/25 the concentration of epinephrine, and 1/4 the concentration of collagen. Treatment with clofibrate, 2 g daily, returned the ADP sensitivity of the platelets to normal and returned epinephrine and collagen sensitivity towards normal, even though it did not alter total cholesterol, low-density-lipoprotein (LDL) cholesterol, or triglyceride concentrations significantly. Platelet nucleotide release was also 3-to-5 fold increased in untreated type II patients. Clofibrate treatment failed to diminish the elevated platelet nucleotide release. Incubation of clofibrate at therapeutic concentrations (100-200 µu/ml) with normal platelets in vitro decreased their sensitivity to ADP and epinephrine and reduced ¹⁴C-serotonin release by these agents. The effect on the release was probably mediated through decreased platelet sensitivity since higher doses of epinephrine could reverse the inhibitory effect of clofibrate. Clofibrate may decrease the incidence of thrombotic complications of atherosclerosis by altering platelet sensitivity to aggregation.