LDL-apheresis as treatment of severe familial hypercholesterolemia

Abstract

Autosomal dominant hypercholesterolemia is caused by mutations in genes that encode for either the receptor or ligand of Low Density Lipoproteins (LDL). The rare homozygous form of familial hypercholesterolemia (FH) is characterized by severely elevated plasma cholesterol levels (4–5x normal), disfiguring xanthomas in skin and tendons, but more importantly, severe and premature coronary artery disease. Without treatment most of these patients die before adulthood from coronary heart disease. Liver transplantation has been performed to provide LDLreceptors and thereby restore the clearance of LDL from plasma, but this procedure has the obvious disadvantage of immunosuppressive therapy. The preferred way to treat these patients is selective LDL apheresis to remove these cholesterol containing particles from plasma. Several systems have been developed for this purpose: immuno-absorption columns, chemo absorption onto dextran sulphate cellulose beads (Kaneka), heparin precipitation (HELP system) and the Direct Absorption of Lipoproteins (DALI) system. These systems are able to decrease the plasma level of LDL in 2–3 h by more than 60%, and because of the rebound of the plasma