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Therapeutic apheresis describes a variety of technologies used to remove select components from the plasma to treat disorders such as familial hypercholesterolemia (FH). Apheresis is a specific form of plasmapheresis that discriminately removes components, such as low-density lipoprotein (LDL) particles, from the plasma while leaving other factors intact, allowing the filtrated plasma to be returned to the patient. LDL apheresis has been investigated as a technique to treat patients with FH and other significant hyperlipidemia. Therapeutic apheresis with selective high-density lipoprotein (HDL) delipidation and plasma reinfusion has been investigated as a technique to reduce atherosclerosis in cardiovascular disease.
Lipid apheresis (also referred to as low-density lipoprotein [LDL] apheresis) involves the extracorporeal removal of apo B‒containing lipoproteins, including LDL, lipoprotein(a), and very low-density lipoprotein.
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 (referred to as HELP), dextran sulfate adsorption, or double-filtration plasma pheresis of lipoprotein. In immunoadsorption, polyclonal antihuman apo B antibodies from sheep selectively bind and remove LDL. (Apo B is the protein moiety of low-density lipoprotein.) In HELP, LDL and other particles containing apo B are precipitated by heparin at an acidic pH. Dextran sulfate adsorption removes LDL by binding the positively charged apo B to dextran sulfate particles bound to cellulose.
Therapeutic apheresis with selective high-density lipoprotein (HDL) delipidation and plasma reinfusion is a procedure in which plasma is removed from the body by apheresis, processed through a delipidation device and then returned to the patient. The delipidation procedure selectively removes cholesterol from HDL, converting the major alpha HDL to pre-beta-like HDL. The plasma with pre-beta-like HDL is then reinfused to the patient. The pre-beta-like HDL is a form of HDL that enhances cholesterol transport to the liver and is thought to reduce atherosclerosis development and burden.
Diseases Treated with Lipid Apheresis
Lipid apheresis is used for disorders with marked hyperlipidemia, primarily 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 2 to 3 times levels that are considered acceptable (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. Depending on the patient, heterozygous FH may or may not respond adequately to lipid-lowering drugs.
Homozygous hypercholesterolemia is rare, occurring in only 1 in 1 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 may 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.
Two lipid apheresis systems have received approval from the U.S. Food and Drug Administration (FDA) for marketing. In February 1996, the dextran sulfate device "Liposorber LA 15® System" (Kaneka Pharma, New York, NY) was approved by FDA through the premarket approval process for use to “acutely remove LDL-C from the plasma of high-risk patient populations for whom diet has been ineffective or not tolerated.”
In October 2013, the Liposorber LA-15 System received approval for additional indications through the humanitarian device exemption process for the treatment of pediatric patients with primary focal segmental glomerulosclerosis, when the following conditions apply:
In September 2007, heparin-induced extracorporeal LDL precipitation HELP® System (B. Braun, Melsungen, Germany) was approved by FDA through the premarket approval process for use in the above indication. FDA product code: MMY.
There are no devices FDA approved specifically for HDL delipidation. The Lipid Sciences Plasma Delipidation System-2 by Lipid Sciences was used in clinical studies. Lipid Sciences ceased business operations in 2012.
Related policies -
POLICYLDL apheresis may be considered medically necessary in patients with homozygous familial hypercholesterolemia as an alternative to plasmapheresis.
LDL apheresis may be considered medically necessary in patients with heterozygous familial hypercholesterolemia who have failed a 6-month trial of diet therapy and maximum tolerated combination drug* therapy AND who meet the following FDA-approved indications: (All LDL levels represent the best achievable LDL level after a program of diet and drug therapy.)
LDL apheresis is considered investigational for all other uses, including use in preeclampsia.
Therapeutic apheresis with selective high-density lipoprotein (HDL) delipidation and plasma reinfusion is considered investigational.
*For definitions of maximum tolerated drug therapy and documented coronary artery disease, please see Policy Guidelines.
POLICY GUIDELINESMaximum tolerated drug therapy is defined as a trial of drugs from at least 2 separate classes of hypolipidemic agents such as bile acid sequestrants, HMG-CoA reductase inhibitors, fibric acid derivatives, or Niacin/Nicotinic acids.
Documented coronary artery disease includes a history of myocardial infarction, coronary artery bypass surgery, percutaneous transluminal coronary angioplasty or alternative revascularization procedure, or progressive angina documented by exercise or non-exercise stress test.
Frequency of LDL apheresis varies, but typically averages about once every 2 weeks to obtain an interapheresis 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.
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
POLICY HISTORY5/1/2008: Policy added
9/18/2008: Annual ICD-9 updates effective 10-1-2008 applied
4/6/2009: Policy reviewed, no changes
09/09/2010: Policy description updated regarding treatment approaches. Policy statement unchanged.
09/28/2011: Policy reviewed; no changes.
09/27/2012: Policy reviewed; no changes.
10/22/2013: Policy reviewed; no changes.
10/21/2014: Policy title changed from "Low-Density Lipid Apheresis" to "Lipid Apheresis." Policy description updated regarding therapeutic apheresis. Added the following policy statement: Therapeutic apheresis with selective high-density lipoprotein (HDL) delipidation and plasma reinfusion is considered investigational. Policy guidelines updated regarding the frequency of LDL apheresis.
08/26/2015: Code Reference section updated for ICD-10. Removed ICD-9 procedure code 99.79.
10/22/2015: Policy description updated regarding devices. Policy statements unchanged. Policy guidelines section updated to add medically necessary and investigative definitions.
05/27/2016: Policy number added.
09/30/2016: Code Reference section updated to add new ICD-10 diagnosis codes E78.00 and E78.01.
SOURCE(S)Blue Cross & Blue Shield Association Policy # 8.02.04
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.