Low-density lipoprotein apheresis describes a variety of technologies used to acutely remove low-density lipoprotein (LDL) from the plasma. The patient initially undergoes an apheresis procedure to isolate the plasma. The low-density lipoproteins are then selectively removed from the plasma by either immunoadsorption, heparin-induced extracorporeal LDL precipitation (also referred to as HELP), or dextran sulfate adsorption. In immunoadsorption, polyclonal antihuman ApoB antibodies from sheep selectively bind and remove LDL. (ApoB is the protein moiety of low-density lipoprotein.) In HELP, LDL and other particles containing ApoB are precipitated by heparin at an acidic pH. Dextran sulfate adsorption removes LDL by binding the positively charged ApoB to dextran sulfate particles bound to cellulose. LDL apheresis must be distinguished from plasma exchange (also referred to as plasmapheresis). In plasma exchange the plasma is collected during apheresis procedure, then discarded and replaced with crystalloids. In contrast, LDL apheresis is a selective procedure in which only pathogenic low-density lipoproteins are removed. The plasma is then returned to the patient. Plasma Exchange is addressed in a separate policy, THE801.006.
LDL apheresis has been investigated as a technique to treat patients with familial hypercholesterolemia (FH). FH is a dominantly inherited disorder involving a mutation of the gene that encodes for the specific cell surface receptor responsible for LDL uptake by the cells. The heterozygous form affects about 1 in 500 people. The number of LDL receptors is halved in this condition, resulting in serum LDL-C levels that are approximately two (2) to three(3) times acceptable levels (i.e., >300 mg/dL). Affected male patients typically develop coronary heart disease in their thirties and forties, while women develop coronary heart disease in their fifties. Heterozygous FH may or may not respond adequately to lipid-lowering drugs.
Homozygous hypercholesterolemia is rare, occurring in only 1 in one million subjects. Serum levels of LDL-C may be elevated six fold (>500 mg/dL), due to the total lack of functioning LDL receptors. Homozygotes develop severe aortic stenosis and coronary heart disease by age 20. These patients typically do not respond adequately to drug or diet modification therapy. In the past, patients with homozygous FH may have been treated with plasma exchange, but the advent of LDL apheresis provides a more targeted approach by permitting selective removal of LDL from the plasma.
Frequency of LDL apheresis varies, but typically averages about once every two (2) weeks to obtain an inter-apheresis level of LDL cholesterol at less than 120 mg/dl. Patients with homozygous FH may be treated more frequently. Patients are simultaneously treated with diet and drug therapy.
Two lipid apheresis systems have received approval from the U.S. Food and Drug Administration (FDA) for marketing. The Liposorber LA 15® System dextran sulfate system was granted FDA approval in 1996. The heparin-induced extracorporeal LDL precipitation (HELP®) system received FDA approval in 1997.