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 being pharmacologically treated with HMG-CoA reductase inhibitors and anion exchange resins were investigated. Ex-vivo platelet function was assessed by the aggregation response to ADP before starting apheresis treatment, as well as after 2 and 24 weeks, respectively. In-vivo platelet function was determined by measuring platelet survival after radiolabeling with 111In-oxine before starting LDL-apheresis and after 24 weeks of twice monthly treatment. LDL-apheresis therapy induced a significant (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 platelet aggregation revealed a decreased aggregability of platelets with a decline in the maximal amplitude and the slope of the response curve. Changes in platelet sensitivity to prostaglandins (PG) were significantly for PGI2, but did not reach statistical significance for PGE1. The results revealed a significant (p < 0.001) increase in platelet survival of 111In-oxine-radiolabeled autologous platelets from a mean 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) and recovery (p < 0.001). These data provide evidence for improved hemostatic regulation in vivo as a result of maintainance of lipid-lowering achieved with LDL-apheresis.
Sinzinger
H
H
Wilhelm Auerswald Atherosclerosis Research Group (ASF) Vienna, Austria.
Pirich
C
C
Bednar
J
J
O'Grady
J
J
D000328:Adult; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood* / Q000628:therapy; D066298:In Vitro Techniques; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects
D008077:Lipoproteins, LDL; D000527:Alprostadil