TREATMENT OF CHILDREN WITH HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA - SAFETY AND EFFICACY OF LOW-DENSITY-LIPOPROTEIN APHERESIS

We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p < 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p < 0.01) and preapheresis LDL-cholesterol values (r 0.61; p < 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL-apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death.