Plasma exchange (PE) is a procedure in which the blood of the patient is extracted and processed through a medical device which separates the plasma from other components of blood. The plasma is discarded and replaced with fluid such as albumin, allogenic plasma or a plasma substitute. PE is a nonspecific therapy, because the entire plasma is discarded. PE has been used in a wide variety of acute and chronic conditions, as well as in the setting of solid organ transplantation.
The terms therapeutic apheresis, plasmapheresis, and plasma exchange are often used interchangeably, but when properly used denote different procedures. The American Society for Apheresis (ASFA) definitions for these other procedures are as follows:
Apheresis: A procedure in which whole blood of the patient or donor is passed through a medical device which separates out any of the particular components of the blood and returns the remainder to circulation, with or without extracorporeal treatment or replacement of the separated component.
Plasmapheresis: A procedure in which whole blood is passed through a medical device that separates the plasma from the other components of the blood. The red and white blood cells are transfused back into the person,the plasma is discarded without a replacement solution.
The proposed therapeutic use of PE is to rapidly remove toxins or autoantibodies which can accumulate in the plasma as a result of a disease process. PE is a non-specific therapy and essentially a symptomatic treatment since it does not remove the source of the pathogenic factors. Although PE can rapidly reduce levels of serum autoantibodies; a feedback mechanism may lead to a rebound overproduction of the same antibodies.
Note: Applications of PE can be broadly subdivided into 2 general categories: (1) acute self-limited diseases, in which PE is used to lower the circulating pathogenic substance; and (2) chronic diseases, in which there is ongoing production of pathogenic autoantibodies. Treatment goals and duration of treatment with PE need to be clearly established before its initiation; without such treatment goals, the use of an acute short-term course of PE may insidiously evolve to a chronic use of PE with uncertain benefit. For example a meaningful clinical response for chronic inflammatory demyelinating polyneuropathy (CIDP) would be an improvement in neurological disability scores (e.g. Hughes GBS Disability Scale, Overall Disability Sum Score). However, studies show progress made will most likely last only for the short term. Another example would be plasma exchange when used to treat myasthenia gravis or Guillain-Barre’ would show measurable improvement in bedside spirometry readings. Additionally neuromyelitis optica and neuromyelitis optica spectrum disorder (NMO/NMOSD), a rare but clinically aggressive demyelinating disease of the central nervous system, that does not respond to initial treatment of steroids may respond to a short course of plasma exchange treatments, especially if previous treatments resulted in improvements in visual acuity or disability scores.
Plasma exchange is considered medically necessary for specified diseases/conditions if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Plasma exchange for the treatment of all other diseases/conditions is considered investigational.
Plasma exchange is considered medically appropriate if ANY ONE of the following are met:
Severe multiple manifestation of mixed cryoglobulinemia (e.g. cryoglobulinemic nephropathy, skin ulcers, sensory motor neuropathy and widespread vasculitis) used in conjunction with immunosuppressive treatment
Catastrophic anti-phospholipid syndrome (CAPS)
Pediatric post-infectious autoimmune neuropsychiatric disorders (e.g., PANDAS, Sydenham’s Chorea; which typically follow Group-A beta-hemolytic streptococcus infection)
Wilson’s Disease, fulminant (autosomal recessive genetic disorder resulting in copper accumulation in the liver, brain, cornea, and kidney)
ABO incompatible hematopoietic progenitor cell transplantation
Hyperviscosity syndrome and ANY ONE of the following:
Thrombotic thrombocytopenia purpura (TTP)
Immune (or idiopathic) thrombocytopenia purpura (ITP) that is refractory
Atypical hemolytic-uremic syndrome (HUS)
Post transfusion purpura
HELLP syndrome of pregnancy (a severe form of preeclampsia, characterized by hemolysis [H], elevated liver enzymes [EL], and low platelet [LP] counts)
Myeloma with acute renal failure
Familial hypercholesterolemia with ALL of the following:
Cholesterol of 650-1000 mg/dL (Homozygotes)
Small blood volume
Solid organ transplantation with ABO incompatibility or positive crossmatch demonstrated by high panel reactive antibody (PRA) screen, when a suitable nonreactive live or cadaveric donor is unavailable in ANY ONE of the following:
Acute allograft cardiac rejection/desensitization
Focal segmental glomerulosclerosis only when following renal transplant
Anti-glomerular basement membrane antibodies (i.e., Goodpasture's syndrome) with progressive renal failure
Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (e.g., Wegner’s granulomatosis) with associated renal failure (serum CR above 5.8 mg/dl)
Dense deposit disease or membranoproliferative glomerulonephritis with renal impairment, neuropathy, arthralgia, and/or ulcerating purpura
Acute fulminant central nervous system demyelination (e.g., Acute Multiple Sclerosis, Acute Transverse Myelitis)
Severe Guillain-Barré syndrome
Acute neuromyelitis optica (NMO) with ALL of the following met:
Failed high-dose intravenous corticosteroids
Chronic neuromyelitis optica (NMO) with ALL of the following met:
Failed high-dose corticosteroids
Failed or not medically appropriate azathioprine with or without low-dose intravenous corticosteroids
Failed or not medically appropriate mycophenolate mofetil with or without low-dose intravenous corticosteroids
Failed or not medically appropriate rituximab
Myasthenia gravis with ANY ONE of the following:
Moderate to severe
Progressive multifocal leukoencephalopathy (all brain white matter diseases) associated with natalizumab
N-methyl D-aspartate receptor antibody encephalitis (autoimmune neurological disorder, NMDAR)
IgM, IgA or IgG chronic acquired paraproteinemia demyelinating polyneuropathy
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
Based on data from published studies and/or clinical support, plasma exchange is considered medically necessary for selected conditions. For all other conditions, there is a lack of data regarding efficacy and clinical support.
American Academy of Neurology. (2016). Continuum. Multiple sclerosis and other demyelinating diseases. Retrieved June 30, 2016 from www.ContinuumJournal.com.
American Society for Apheresis (2016) Guidelines on the use of therapeutic apheresis in clinical practice - evidence-based approach from the writing committee of the American society for apheresis: the seventh special issue. Journal of Clinical Apheresis, 31, 149-162.
Bambauer, R., Latza, R., Bambauer, C., Burgard, D., and Schiel, R. (2013, November) Therapeutic apheresis in autoimmune diseases. Rheumatology: Research and Reviews, 5, 93–103. (Level 2 evidence)
Bonnan, M., & Cabre, P. (2012). Plasma exchange in severe attacks of neuromyelitis optica. Multiple Sclerosis International, 2012, Article ID 787630. (Level 1 evidence)
Centers for Medicare & Medicaid Services. CMS.gov. NCD for apheresis (110.14). Retrieved January 8, 2016 from https://www.cms.gov.
Codron, P., Cousin, M., Subra, J., Pautot, V., Letournel, F., Verny, C., et. al., (2017, March) Therapeutic plasma exchange in chronic dysimmune peripheral neuropathies: A 10-year retrospective study. Journal of Clinical Apheresis, [e-published ahead of print] Abstract retrieved July 18, 2017 from PubMed database.
Deschamps, R., Gueguen, A., Parquet, N., Saheb, S., Driss, F., Mesnil, M., et. al. (2016, May) Plasma exchange response in 34 patients with severe optic neuritis. Journal of Neurology, 263 (5) 883-887. Abstract retrieved July 18, 2017 from PubMed database.
Gorson, L. (2012) An update on the management of chronic inflammatory demyelinating polyneuropathy. Therapeutic Advances in Neurological Disorders, 5 (6), 359-373. (Level 5 evidence)
Kobayashim, M., Nanri, K., Taguchi, T., Ishiko, T., Yoshida, M., Yoshikawa, N. et. al., (2015, February) Immunoadsorption therapy for neuromyelitis optica spectrum disorders long after the acute phase. Journal of Apheresis, 30 (1), 43-5. Abstract retrieved July 18, 2017 from PubMed database.
Mehndiratta, M,, Hughes, R., and Pritchard. J. (2015) Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database of Systematic Reviews, Issue 8. Art. No.: CD003906. (Level 2 evidence)
National Comprehensive Cancer Network. (2017, January). NCCN clinical practice guidelines in oncology®. Waldenstrom’s macroglobulinemia/lymphoplasmacytic lymphoma - V.2.2017. Retrieved April 27, 2017 from http://www.nccn.org.
National Comprehensive Cancer Network. (2018, February). NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Multiple myeloma - V.4.2018. Retrieved July 20, 2018 from http://www.nccn.org.
Nickerson, M and Marrie, R. (2013) The multiple sclerosis relapse experience: patient-reported outcomes from the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry. BMC Neurology, 13 (119). (Level 4 evidence)
Oaklander, A., Lunn, M., Hughes, R., van Schaik, I., Frost, C., Chalk, C., et. al (2017, January) Treatments for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP): an overview of systematic reviews. Cochrane Database Systems Review. January, 13; 1:CD010369. Abstract retrieved April 27, 2017 from PubMed database.
Sherman, E. and Han, M. (2015) Acute and chronic management of neuromyelitis optica spectrum disorder. Current Treatment Options in Neurology, 17 (48). (Level 2 evidence)
U. S. Food and Drug Administration. (2004, July). Center for Devices and Radiological Health. 510(k) Pre-market Notification Database. K040041 (Apheresis System). Retrieved November 15, 2010 from http://www.fda.gov.
Walsh, M., Catapano, F., Szpirt, W., Thorlund, K., Bruchfeld, A., Guillevin, L. (2011). Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. American Journal of Kidney Disease, 57 (4), 566-574. (Level 1 evidence - Independent)
ORIGINAL EFFECTIVE DATE: 5/1981
MOST RECENT REVIEW DATE: 12/30/2018
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