Decreased number of PGD2 binding sites on platelets from patients with type IIa hyperlipoproteinemia.

Platelets from patients with familial hypercholesterolemia (type IIa hyperlipoproteinemia), a condition associated with a high prevalence of atherosclerosis and its ischemic complications, are claimed to be hyperresponsive to aggregating stimuli. We investigated the platelet responsiveness to and the binding of PGD2, a potent endogenous inhibitor of platelet aggregation via stimulation of adenylate cyclase, in a group of 7 patients affected by IIa hyperlipoproteinemia (IIa HLP) and in a control group of 10 healthy subjects. Inhibition by PGD2 of ADP-induced platelet aggregation was significantly lower in IIa HLP patients than in controls. The number of binding sites for PGD2 of platelets from IIa HLP patients was significantly reduced in comparison with that from controls (93 +/- 19 and 232 +/- 23 receptors/platelet, respectively), whereas the affinity for PGD2 was comparable to that of controls (Kd = 68.8 +/- 19.8 nM in patients and 66.1 +/- 15.9 nM in controls). The reduced number of platelet PGD2 binding sites in IIa HLP patients may account for the impaired sensitivity to PGD2 shown in vitro by platelets and may contribute to the increased tendency to thrombotic manifestations observed in IIa HLP.