BlueCross BlueShield of Tennessee Medical Policy Manual

Plasma Exchange


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:

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 acutely 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.  


    • ABO incompatible solid organ transplant; liver

    • Acute disseminated encephalopathy

    • Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome) in children younger than 10 with mild or moderate forms

    • Acute liver failure

    • Amyotrophic lateral sclerosis

    • Aplastic anemia

    • Asthma

    • Autoimmune hemolytic anemia; warm hemolytic anemia; cold agglutinin disease

    • Bullous pemphigoid

    • Cardiomyopathy, post-transplant

    • Central pontine myelinolysis

    • Chronic fatigue syndrome

    • Coagulation factor inhibitors

    • Cryoglobulinemia; (except for severe mixed cryoglobulinemia, as noted below)

    • Heart transplant antibody mediated rejection

    • Hemolytic uremic syndrome (HUS) with typical presentation (diarrhea related)

    • Idiopathic thrombocytopenic purpura (ITP); refractory or non-refractory

    • Inclusion body myositis

    • Lambert-Eaton myasthenic syndrome

    • Mild Guillain-Barré syndrome

    • Multiple sclerosis; chronic progressive or relapsing remitting

    • Mushroom poisoning

    • Myasthenia gravis with anti-MUSK antibodies

    • Obsessive-compulsive disorder and tic disorder of childhood

    • Overdose and poisoning (other than mushroom)

    • Paraneoplastic syndromes

    • Paraproteinemic polyneuropathy, (IgM)

    • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)

    • Pemphigus vulgaris

    • Phytanic acid storage disease (Refsum’s disease)

    • POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)

    • Polymyositis and dermatomyositis

    • Psoriasis

    • Raynaud's phenomenon

    • Red cell alloimmunization in pregnancy

    • Regional enteritis (Crohn's disease)

    • Rheumatoid arthritis

    • Scleroderma (systemic sclerosis)

    • Severe late left ventricular failure

    • Stiff person syndrome

    • Sydenham’s chorea (SC)

    • Systemic lupus erythematosus; manifestations other than nephritis

    • Systemic Lupus nephritis

    • Systemic vasculitis to improve renal function

    • Thyrotoxicosis









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 AIDS Task Force (1991, May) Research criteria for diagnosis of chronic inflammatory demyelinating polyneuropathy (CIPD). Neurology, 41, 617-618.

American Academy of Neurology. (2016). Continuum. Multiple sclerosis and other demyelinating diseases. Retrieved June 30, 2016 from

American Academy of Neurology. (January, 2011). Evidence-based guideline update: Plasmapheresis in neurologic disorders. Report of the therapeutics and technology assessment subcommittee of the american academy of neurology. Retrieved July 18, 2017 from

American Society for Apheresis (2013) Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the writing committee of the american society for apheresis: the sixth special issue. Journal of Clinical Apheresis, 28, 145-284.

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)

Barth, D., Nouri, M., Ng, E., New, P., & Bril, V. (2011). Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology, 76 (23), 2017-2023. (Level 2 evidence)

BlueCross BlueShield Association, Medical Policy Reference Manual. (5:2015). Plasma exchange. (8.02.02). Retrieved April 27, 2017 from BlueWeb. (54 articles and/or guidelines reviewed)

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. NCD for apheresis (110.14). Retrieved January 8, 2016 from 

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)

Khatri, B. O., Kramer, J., Dukic, M., Palencia, M., & Verre, W. (2012). Maintenance plasma exchange therapy for steroid-refractory neuromyelitis optica. Journal of Clinical Apheresis, 27 (4), 183-192. Abstract retrieved August 31, 2016 from PubMed database.

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. (2016, November). NCCN clinical practice guidelines in oncology®. Multiple myeloma - V.3.2017. Retrieved July 18, 2017 from

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

National Organization for Rare Disorders (NORD). (2015). Neuromyelitis optica. Retrieved July 1, 2016 from

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.

Sato, D., Callegaro, D., Lana-Peixoto, M., & Fujihara, K. (2012). Treatment of neuromyelitis optica: an evidence based review. Arquivos de Neuro-Psiquiatria, 70 (1). (Level 1 evidence)

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)

Trebst, C., Jarius, S., Berthele, A., Paul, F., Schippling, S., Wildemann, B., et al. (2014). Update on the diagnosis and treatment of neuromyelitis optica: recommendations of the Neuromyelitis Optica Study Group (NEMOS). Journal of Neurology, 2014; 261: 1-16. (Level 5 evidence)

Turner-Stokes, L., Thu, A., Williams, H. Casey, R., Rose, H., and Siegert, R. (2013, May) The Neurological Impairment Scale: reliability and validity as a predictor of functional outcome in neurorehabilitation. Disability and Rehabilitation, 36 (1), 23-31. (Level 3 evidence)

U. S. Food and Drug Administration. (2002, November). Center for Devices and Radiological Health. 510(k) Pre-market Notification Database. K021615 (PRISMA®). Retrieved November 10, 2010 from

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

U. S. Food and Drug Administration. (2004, July). Center for Devices and Radiological Health. 510(k) Pre-market Notification Database. K040086 (.COBE Spectra Apheresis System) Retrieved November 10, 2010 from

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)




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