EX-VIVO AND IN-VIVO PLATELET-FUNCTION IN PATIENTS WITH SEVERE HYPERCHOLESTEROLEMIA UNDERGOING LDL-APHERESIS

Patients with severe familial hypercholesterolemia (HC) show abnormal platelet function and shortened platelet survival. Atherosclerosis is associated with platelet hyperactivity. Low-density lipoporotein (LDL) -apheresis eliminates the most atherogenic lipid fraction and inhibits the progression of atherosclerosis inducing even regression. In order to assess the influence of LDL-apheresis on platelet function ex-vivo and in-vivo, 6 patients with severe heterozygous HC, all of them bein g pharmacologically treated with HMG-CoA reductase inhibitors and anio n exchange resins were investigated. Ex-vivo platelet function was ass essed by the aggregation response to ADP before starting apheresis tre atment, as well as after 2 and 24 weeks, respectively. In-vivo platele t function was determined by measuring platelet survival after radiola beling with In-111-oxine before starting LDL-apheresis and after 24 we eks of twice monthly treatment. LDL-apheresis therapy induced a signif icant (p < 0.01) drop in cholesterol by 64 %, LDL-cholesterol by 77 % and in triglycerides by 46 % over a period of 24 weeks. ADP-induced pl atelet aggregation revealed a decreased aggregability of platelets wit h a decline in the maximal amplitude and the slope of the response cur ve. Changes in platelet sensitivity to prostaglandins (PG) were signif icantly for PGI(2), but did not reach statistical significance for PGE (1). The results revealed a significant (p < 0.001) increase in platel et survival of In-111-oxine-radiolabeled autologous platelets from a m ean of 106.50 hours before to 137.50 hours (p < 0.01) after treatment, being accompanied by an increase in labeling efficiency (p < 0.001) a nd recovery (p < 0.001). These data provide evidence for improved hemo static regulation in vivo as a result of maintainance of lipid-lowerin g achieved with LDL-apheresis.