Resistance of Platelets in Hypercholesterolemia to Inhibition by Activated Coagulation Factor X

Abstract EN

Platelet hyperactivity may be involved in the pathogenesis of both thrombogenesis and hypercholesterolemia.

The cholesterol-enriched states may contribute to accelerated development of atherosclerosis.

The effect of high cholesterol on platelet activation and on inhibition by coagulation factor Xa, was studied in vitro.

Incubation of normal platelets (n=20) with cholesterol-rich dispersion resulted in a small increase of platelet aggregation (PA) and thromboxane A2 (TXA2) synthesis when compared with platelets incubated with cholesterol-normal dispersion.

In hypercholesterolemic patients (n=20), ADP-induced PA and TXA2 synthesis showed only small increases over normal controls.

Addition of factor Xa (1 unit/mL) prevented the ADP-induced PA and markedly inhibited TXA2 synthesis in normal platelets (1.3±0.2 and 8.7±2.0 pmol TXA2/108 platelets, with and without factor Xa, resp.).

However, factor Xa failed to significantly suppress TXA2 synthesis in cholesterol-incubated normal platelets (9.5±1.4 and 11.8±1.3 pmol TXA2/108 platelets, with and without factor Xa; resp., P=NS) as well as in platelets from patients with hypercholesterolemia (8.6±4.0 and 10.9±4.9 pmol TXA2/108 platelets, with and without factor Xa; resp., P=NS).

Exposure of platelets to high cholesterol concentrations, in vitro and in vivo, marginally increased PA and TXA2 synthesis but resulted in loss of responsiveness to factor Xa, which could significantly contribute to platelet activation in hypercholesterolemic states.