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 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.
Plasma exchange is considered medically necessary for specified diseases/conditions if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
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
Autoimmune hemolytic anemia; warm hemolytic anemia; cold agglutinin disease
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
Myasthenia gravis with anti-MUSK antibodies
Obsessive-compulsive disorder and tic disorder of childhood
Overdose and poisoning (other than mushroom)
Paraproteinemic polyneuropathy, (IgM)
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
Phytanic acid storage disease (Refsum’s disease)
POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)
Polymyositis and dermatomyositis
Red cell alloimmunization in pregnancy
Regional enteritis (Crohn's disease)
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
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)
ABO incompatible hematopoietic progenitor cell transplantation
Hyperviscosity syndrome and ANY ONE of the following:
Thrombotic thrombocytopenia purpura (TTP)
Idiopathic thrombocytopenia purpura (ITP) in emergency situation
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
IgA or IgG paraproteinemia polyneuropathy
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:
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 with Factor H deficiency and/or elevated C3 Nephritic factor
Acute fulminant central nervous system demyelination (e.g., Acute Multiple Sclerosis, Acute Transverse Myelitis)
Severe Guillain-Barré syndrome with ANY ONE of the following:
Inability to walk 5 meters without assistance
Confinement to bed / chair-bound
Ventilation assistance for at least part of the day or night
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 in crisis or as part of a preoperative preparation
Chronic inflammatory demyelinating polyneuropathy (CIDP) with ALL of the following:
Severe or life-threatening symptoms
Failed response to conventional therapy with prednisone or intravenous immunoglobulins (IVIg)
Meet the confirmatory criteria for CIDP developed by the American Academy of Neurology AIDS Task Force which includes ALL of the following:
Nerve biopsy showing unequivocal evidence of demyelination and remyelination of proximal nerve segments in which the predominant process is demyelination
Demyelination by either electron microscopy (greater than 5 fibers) or teased fiber studies (greater than 12% of 50 teased fibers, minimum of four internodes each, demonstrating demyelination/remyelination)
CSF study - cell count less than 10/mm3 if HIV-seronegative or less than 50/mm3 if HIV seropositive
CSF study - negative VDRL
Progressive or relapsing motor and sensory, rarely on motor or sensory, dysfunction of more than one limb or a peripheral nerve nature, developing over at least 2 months
Nerve conduction studies including studies of proximal nerve segments in which the predominant process is demyelination
Nerve conduction studies with 3 or more of the following:
Reduction in conduction velocity (CV) in two or more motor nerves with ANY ONE of the following:
Less than 80% of lower limit of normal (LLN) if amplitude greater than 80% of LLN
Less than 70% of LLN if amplitude less than 80% of LLN
Partial conduction block or abnormal temporal dispersion in one or more motor nerves: either peroneal nerve between ankle and below fibular head, median nerve between wrist and elbow, or ulnar nerve between wrist and below elbow with ANY ONE of the following:
Criteria suggestive of partial conduction block: less than 15% change in duration between proximal and distal sites and greater than 20% drop in negative peak (-p) area or peak to peak (p-p) amplitude between proximal and distal sites
Criteria for abnormal temporal dispersion and possible conduction block: greater than 15% change in duration between proximal and distal sites and greater than 20% drop in -p area or p-p amplitude between proximal and distal sites and greater than 20% drop in -p or p-p amplitude between proximal and distal sites. These criteria are only suggestive of partial conduction block as they are derived from studies of normal individuals. Additional studies, such as stimulation across short segments or recording of individual motor unit potentials, are required for confirmation.
Prolonged distal latencies in two or more nerves with ANY ONE of the following:
Greater than 125% of upper limit of normal (ULN) if amplitude greater than 80% of LLN
Greater than 150% of ULN if amplitude less than 80% of LLN
Absent F-waves or prolonged minimum F-wave latencies (10 to 15 trials) in two or more motor nerves with ANY ONE of the following:
Greater than 120% of ULN if amplitude greater than 80% of LLN
Greater than 150% of ULN if amplitude less than 80% of LLN
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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 www.ContinuumJournal.com.
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 http://www.neurology.org.
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. CMS.gov. NCD for apheresis (110.14). Retrieved January 8, 2016 fromhttps://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)
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 http://www.nccn.org.
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 Organization for Rare Disorders (NORD). (2015). Neuromyelitis optica. Retrieved July 1, 2016 from http://rarediseases.org/rare-diseases/neuromyelitis-optica/.
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 http://www.accessdata.fda.gov.
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.
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 http://www.accessdata.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: 9/14/2017
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