Platelet-dependent thrombin generation in patients with hyperlipidemia.

Abstract

We evaluated coagulability as determined by platelet-dependent thrombin generation in hypercholesterolemic patients before and after treatment with pravastatin and in hypertriglyceridemic patients to investigate the usefulness of coagulability as an index of atherosclerosis and to determine the importance of treating hyperlipidemia. An understanding of the interaction between platelets and the plasma coagulation system is important for clarifying the mechanism of the procoagulant process. We assessed coagulability in 58 patients with hypercholesterolemia (serum total cholesterol level > or = 220 mg/dl, age 56.5 +/- 1.5 years [mean +/- SEM]), 37 patients with hypertriglyceridemia (serum triglyceride level > or = 200 mg/dl, age 59.5 +/- 1.7 years), 13 patients with hypercholesterolemia plus hypertriglyceridemia (age 51.4 +/- 3.1 years) and 75 normal subjects (age 52.2 +/- 1.7 years). We also studied platelet-dependent thrombin generation in patients with hypercholesterolemia before and after treatment with pravastatin. Calcium chloride was added to 0.5 ml of platelet-rich plasma (150 x 10(9)/liter) to initiate coagulation. Ten microliters of the sample was transferred into 90 microliters of 3.8% sodium citrate at 10-min intervals for 30 min. A chromogenic substrate, S-2238, was added to each sample, and absorbance was measured spectrophotometrically at a wavelength of 405 nm to determine thrombin generation. Platelet-dependent thrombin generation was increased in patients with hypercholesterolemia and patients with hypercholesterolemia plus hypertriglyceridemia (p < 0.01) compared with patients with hypertriglyceridemia and control subjects. Treatment with pravastatin normalized thrombin generation. Hypercholesterolemia, but not hypertriglyceridemia, was associated with increased platelet-dependent thrombin generation. Pravastatin normalized the generation of thrombin.