Plasmapheresis/Plasma Exchange




Medical Policy: 08.01.16 
Original Effective Date: February 2000 
Reviewed: May 2016 
Revised: May 2016 


Benefit Application:

Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy will be reviewed regularly and be updated as scientific and medical literature becomes available.


Description:

Plasmapheresis or plasma exchange (PE)/therapeutic plasma exchange (TPE) is a recognized treatment modality for multiple acute and chronic conditions. The procedure can take one to three hours and the number of treatments needed is dependent on the patient’s condition and underlying disease. The goal of plasmapheresis or PE/TPE is the removal of certain pathological substances from the plasma that will reduce further damage and may permit reversal of the pathologic process. It is hypothesized that the removal of these factors can be therapeutic in certain situations. The pathologic substance may be an autoantibody, immune complex, cryoglobulin, myeloma light chains, endotoxin, cholesterol containing lipoprotein, or other substance. 

   

Plasmapheresis/PE is essentially symptomatic therapy, because it does not remove the source of the pathogenic factors. Therefore, the success of plasmapheresis/PE will depend on whether the pathogenic substances are accessible through the circulation and whether the rate of production and transfer to the plasma component can be adequately addressed by plasmapheresis/PE. For example, plasmapheresis/PE can rapidly reduce levels of serum autoantibodies; however, through a feedback mechanism, this rapid reduction may lead to a rebound overproduction of the same antibodies. This rebound production of antibodies is thought to render the replicating pathogenic clone of lymphocytes more vulnerable to cytotoxic drugs; therefore, plasmapheresis/PE is sometimes used in conjunction with cyclophosphamide.

 

Applications of plasmapheresis/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. Because plasmapheresis/PE does not address underlying pathology, and, due to phenomenon of rebound antibody production, its use in chronic diseases has been more controversial than in acute self-limited diseases.       

In addition, plasmapheresis has been used in the setting of solid organ transplantation. It has been used as a technique to desensitize high-risk patients prior to transplant and also as a treatment of antibody-mediated rejection reaction (AMR) occurring after transplant. As a treatment of AMR, plasmapheresis is often used in combination with intravenous immunoglobulin IVIg) or anti-CD20 therapy (i.e., Rituximab). Prior to transplant, plasmapheresis has been most commonly used to desensitize patients receiving an ABO mismatched organ or hematopoietic stem cell transplant.

 

The terms plasmapheresis, therapeutic apheresis, and plasma exchange (PE)/therapeutic plasma exchange (TPE) are often used interchangeably, however there are some differences. The American Society of Apheresis (ASFA) definitions for these procedures are as follows:

 

Apheresis: is a general term describing removal of blood from a subject; a portion of the blood is separated and retained while the rest is returned to the donor.

 

Plasmapheresis: removes a smaller amount of plasma, usually less than 15% of the patient’s blood volume and therefore does not require replacement of the removed plasma.

 

Plasma Exchange (PE): is the procedure that is preformed most commonly. A large volume of plasma is removed from a patient. The volume removed is such that if it were not replaced, significant hypovolemia resulting in vasomotor collapse would occur. As a result, the removed plasma must be replaced with some form of replacement fluid such as albumin.

 

Summary
Plasmapheresis or plasma exchange (PE)/therapeutic plasma exchange (TPE) has been proposed for the treatment of multiple conditions. Its use for some conditions is uniformly supported by the evidence in the published peer reviewed medical literature and professional societies as a primary therapy with data showing that plasmapheresis or PE/TPE is as good as or better than conventional therapies.

In conditions in which plasmapheresis or PE/TPE is used an adjunctive therapy, the primary therapies for those conditions have demonstrated better outcomes (e.g. improvement in symptoms, remission, improved survival rates) and plasmapheresis or PE/TPE is only recommended if primary therapy isn’t effective.

 

Due to the limited number of studies, small patient populations, short term follow ups and/or lack of comparisons to established conventional therapies, plasmapheresis or PE/TPE is not supported by the evidence in published peer reviewed medical literature or by professional societies to be a beneficial treatment modality for various other conditions. Some studies reported mixed results or no improvement in outcomes (e.g. improvement in symptoms, remission, improved survival rates) following plasmapheresis or plasma exchange (PE)/therapeutic plasma exchange (TPE) and therefore, would be considered investigational. 

 

Practice Guidelines and Position Statements

National Comprehensive Caner Network (NCCN)

  • Multiple Myeloma Version 3.2016
    •  Adjunctive Treatment
      • Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity
      • Plasmapheresis for renal dysfunction (category 2B)
  • Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lympoma Version 2.2016
    • Plasmapheresis for symptomatic hyperviscosity

Plasmapheresis should be performed for patients with symptomatic hyperviscosity, and before treatment with rituximab containing regimen in patients with IgM > 5000 mg/dl. IgM should be monitored closely in these patients thereafter and plasmapheresis should be considered again if symptomatic hyperviscosity occurs or if IgM > 5000 mg/dl while on rituximab containing therapy.

 

American Academy of Neurology
In 2011, the American Academy of Neurology (Therapeutics and Technology Assessment Subcommittee) issued an evidence based guideline on plasmapheresis in the treatment of neurological disorders. 

 

 

Classification of Recommendations:

  • A = Established as effective, ineffective, or harmful (or established as useful/predictive or not useful/predictive) for the given condition in the specified population. (Level A rating requires at least two consistent Class I studies)*.
  • B = Probably effective, ineffective, or harmful (or probably useful/predictive or not useful/predictive) for the given condition in the specified population. (Level B rating requires at least one Class I study or two consistent Class II studies).
  • C = Possibly effective, ineffective, or harmful (or possibly useful/predictive or not useful/predictive) for the given condition in the specified population. (Level C rating requires at least one Class II study or two consistent Class III studies).
  • U = Data inadequate or conflicting; given current knowledge, treatment (test, predictor) is unproven. 

 * In exceptional cases, one convincing Class I study may suffice for an “A” recommendation if 1) all criteria are met, 2) the magnitude of effect is large (relative rate improved outcome > 5 and the lower limit of the confidence interval is > 2).

 

American Society for Apheresis (ASFA)

In 2013, the American Society for Apheresis (ASFA) released updated guidelines on the use of therapeutic apheresis in clinical practice. The therapeutic apheresis procedures considered in this guideline include therapeutic plasma exchange (TPE).

The following is the description of the ASFA categories for indications for therapeutic apheresis:

 

Indications for Therapeutic Apheresis - AFSA 2013 Categories
CategoryDescription

I

Disorders for which apheresis is accepted as first line therapy, either as primary standalone treatment or in conjunction with other modes of treatment

II

Disorders for which apheresis is accepted as second line therapy, either as standalone treatment or in conjunction with other modes of treatment

III

Optimum role of apheresis therapy is not established. Decision making should be individualized

IV

Disorders in which published evidence demonstrates or suggest apheresis to be ineffective or harmful

 

Following are the indications for therapeutic plasma exchange (TPE) and the ASFA category recommended for 2007, 2010, and 2013. (Note: NC: Not Categorized)
Disease Group / Name / ConditionAFSA 2007AFSA 2010AFSA 2013
Autoimmune

Catastrophic antiphospholipid syndrome

III

II

II

Cryoglobulinemia

I

I

I

Pemphigus vulgaris

III

IV

III
Systemic lupus erythematosus

Manifestations other than nephritis

IIII

NC

NC

Severe

NC

II

II

Nephritis

IV

IV

IV
Hematologic

ABO incompatible hematopoietic progenitor cell transplantation

II

II

II

Aplastic anemia

III

III

III

Pure red blood cell aplasia

III

II

III
Autoimmune hemolytic anemia

Warm autoimmune hemolytic anemia

III

III

III

Cold agglutinin disease

III

II

II

Coagulation factor inhibitors

III

IV

IV

Hyperviscosity in monoclonal gammopathies

I

I

I
Idiopathic thrombocytopenic purpura

Refractory immunoadsorption

II

NC

NC

Refractory or non-refractory

IV

NC

NC

Myeloma and acute renal failure (in 2010 and 2013 myeloma cast nephropathy)

III

II

II

Post-transfusion purpura

III

III

III

Red blood cell alloimmunization in pregnancy

II

II

III

Thrombotic thrombocytopenic purpura

I

I

I
Metabolic

Acute liver failure

III

III

III

Sepsis (in 2010 and 2013 sepsis with multiorgan failure)

III

III

III

Thyrotoxicosis (in 2010, thyroid storm)

III

III

III
Neurological

Acute disseminated encephalomyelitis

III

II

II

Acute Inflammatory demyelinating polyneuropathy (Guillian-Barre syndrome)

I

I

I

Acute inflammatory demyelinating polyneuropathy. Post IVIG

NC

NC

III

Chronic inflammatory demyelinating poliyradiculoneuropathy

I

I

I

Lambert-Eaton myasthenic syndrome

II

II

II
Multiple Sclerosis

Acute CNS inflammatory demyelinating disease

II

II

II

Devic’s syndrome

III

NC

NC

Chronic progressive

III

III

III

Myasthenia gravis

I

I

I

Paraneoplastic neurologic syndromes

III

III

III
Paraproteinemic polyneuropathies

IgG/IgA

I

I

I

IgM

II

I

I

Multiple Myeloma

III

III

III
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; Sydenham’s chorea

Severe PANDAS (2010 exacerbations)

I

I

I

Severe SC

I

I

I

Rassmussen’s encephalitis

II

NC

III

Stiff-person syndrome

III

IV

III
Renal
ANCA-associated rapidly progressive

Glomerulonephritis (Wegener’s granulomatosis)

II

    

Dialysis dependence

NC

III

I

Dialysis independence

NC

III

III
Anti-glomerular basement membrane disease

Goodpasture’s syndrome

I

    

Diffuse alveolar hemorrhage (DAH)

NC

I

I

Dialysis dependence and no DAH

NC

IV

III

Dialysis indendence

NC

I

I
Focal segmental glomerulosclerosis

Primary

III

NC

NC

Secondary

III

NC

NC

Recurrent

NC

I

I
Hemolytic uremic syndrome (HUS); thrombotic microangiopathy; transplant-associated microangiopathy

Idiopathic HUS

III

III

NC

Transplant-associated microangiopathy

III

NC

NC

Diarrhea-associated, pediatric

IV

NC

NC

Atypical HUS due to complement factor gene mutations

NC

II

II

Atypical HUS due to autoantibody to factor H

NC

I

II

Diarrhea-associated HUS or typical HUS

NC

IV

NC

In 2013, Shiga toxin-associated

    

IV

S. pneumonae associated

    

III
Renal transplantation; antibody mediated rejection; HLA desensitization

Antibody mediated rejection

II

I

I

LA desensitization

II

NC

  

Desensitization, living donor, positive

NC

II

I
Crossmatch due to donor-specific HLA antibody

High PRI: cadaveric donor

NC

III

  
Rheumatic

Scleroderma (progressive systemic sclerosis)

III

III

III
Transplantation
ABO incompatible solid organ transplantation

Kidney

II

II

  

In 2013, densentization, living-donor

    

I

Humeral rejection

    

II

Heart (infants)

II

II

NC

Liver (2010 preioperative)

III

III

  

In 2013, desensitization living-donor

    

I

desensitization, deceased-donor

    

II

humeral rejection

    

III
Heart transplant rejection

Treatment

III

NC

NC


Prior Approval:

 

Not applicable


Policy:

Plasmapheresis and plasma exchange (PE)/therapeutic plasma exchange (TPE) may be considered medically necessary for any of the conditions listed below:

 

Autoimmune

  • Symptomatic/Severe multiple manifestations of mixed cryoglobulinemia (MC) such as cryoglobulinemic nephropathy, skin ulcers, sensory motor neuropathy, and widespread vasculitis in combination with immunosuppressive treatment
  • Catastrophic antiphospholipid syndrome (CAPS) 

Hematologic

  • ABO incompatible hematopoietic stem cell transplantation
  • Hyperviscosity syndrome associated with multiple myeloma or Waldenström's macroglobulinemia
  • Idiopathic thrombocytopenic purpura in emergency situations 
  • Thrombotic thrombocytopenic purpura (TTP)
  • Atypical hemolytic-uremic syndrome
  • 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

Neurological

  • Acute inflammatory demyelinating polyneuropathy (Guillain-Barré syndrome [GBS]; severity grade 1-2 within 2 weeks of onset; severity grade 3-5 within 4 weeks of onset; and children younger than 10 years old with severe GBS)
  • Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Multiple sclerosis; considered for the adjunctive treatment of exacerbations in relapsing forms of MS
  • Myasthenia gravis moderate-severe or as part of preoperative preparation

    (pre-thymectomy)

  • Paraproteinemia polyneuropathy; IgA, IgG, (polyneuropathy associated with IgA and IgG monoclonal gammopaty of undetermined significance (MGUS)

Note: Guillain-Barre Syndrome Disability Scale

  • 0   Healthy
  • 1   Minor symptoms or signs of neuropathy but capable of manual work/capable of running
  • 2   Able to walks without support of s tick (5 m across and open space) but incapable of manual work/running
  • 3   Able to walk with a stick, appliance or support (5 m across an open space)
  • 4   Confined to bed or chair bound
  • 5   Requiring assisted ventilation (for any part of the day or night)
  • 6   Death

Renal

  • Anti-glomerular basement membrane disease (Goodpasture's syndrome)
  • ANCA-associated vasculitis (e.g. Granulomatosis with polyangiitis; Wegener's granulomatosis) with associated renal failure (serum Cr > 5.8mg/dL)
  • Dense deposit disease with factor H deficiency and/or elevated C3 nephritic factor
  • Focal segmental glomerulosclerosis after renal transplant 

Liver

  • Wilson Disease with fulminant hepatic failure

Transplantation

ABO Incompatible

  • Liver transplantation, ABO incompatible (desensitization, live donor)
  • Heart (cardiac) transplantation in infants, ABO incompatible
  • Renal transplantation ABO incompatible (desensitization, live donor)
  • Renal transplantation ABO incompatible (rejection) as second line therapy either as stand alone treatment or in conjunction with other modes of treatment
    •

ABO Compatiable

  • Renal transplantation, ABO compatible (antibody mediated rejection)
  • Renal transplantation, ABO compatible (desensitization, living donor, positive crossmatch due to donor specific HLA antibody)

Second line therapy, either as standalone treatment or in conjunction with other modes of treatment :

  • Familial hypercholesterolemia-homozygotes with small blood volume
  • Neuromyelitis optica (Devic's syndrome), acute
  • Voltaged gated potassium channel antibodies (neuromyotonia (NMT), limbic encephalitis (LE), morvan syndrome (MVS))
  • Phemigus Vulgaris as second line therapy, that is resistant to standard therapy (dapsone, corticosteroids, immunosuppressants such as azathioprine or cyclosporine)
  • Multiple sclerosis in the treatment of fulminant CNS demyelinating diseases that fail to respond to high-dose corticosteroid treatment

Plasmapheresis or plasma exchange (PE)/therapeutic plasma exchange (TPE) is considered investigational for all other conditions including, but not limited to the following : 

  • Acute disseminated encephalomyelitis
  • Acute inflammatory demyelinating polyneuropathy (Guillain-Barre Syndrome) except as indicated above and in children younger than 10 years old with mild to moderate forms
  • Acute liver failure, except as indicated above for Wilson Disease
  • Amyloidosis, systemic
  • Amyotrophic lateral sclerosis (ALS)
  • ANCA-associated rapidly progressive glomerulonephritis (Granulomatosis with polyangiitis; Wegener's Granulomatosis) without renal failure (dialysis independence)
  • Aplastic anemia
  • Asthma
  • Autoimmune hemolytic anemia: warm autoimmune hemolytic anemia (WAHA) and cold agglutinin disease
  • Burn shock resuscitation
  • Cardiac (heart) transplantation except as indicated above  
  • Chronic fatigue syndrome
  • Chronic focal encephalitis (Rasmussen Encephalitis)  
  • Coagulation factor inhibitors (alloantibody and autoantibody)
  • Dermatomyositis or polymyositis
  • Dilated cardiomyopathy, idiopathic (NYHA II-IV)
  • Focal segmental glomerulosclerosis except as indicated above
  • Henoch-Schonlein purpura
  • Hemolytic uremic syndrome (HUS); typical (diarrheal-related)
  • Heparin induced thrombocytopenia
    • Pre-cardiopulmonary bypass
    • Thrombosis
  • Hypertriglyceridemic pancreatitis
  • Immune complex rapidly progressive glomerulonephritis
  • Immune thrombocytopenia (refractory)
  • Immunoglobin A nephropathy
  • Inclusion body myositis
  • Inflammatory bowel disease (ulcerative colitis, Crohn's disease)
  • Lambert-Eaton myasthenic syndrome
  • Liver transplantation, ABO incompatible, except as indicated above
  • Lung allograft rejection, antibody mediated rejection
  • Multiple Sclerosis for chronic progressive or secondary progressive, except as indicated above
  • Mushroom poisoning
  • Myasthenia gravis except as indicated above  
  • Nephrogenic systemic fibrosis  
  • Neuromyelitis optica (Devic's syndrome) except as indicated above
  • Overdose, envenomation and poisoning
  • Paraneoplastic neurological syndromes  
  • Paraproteinemic demyelinating polyneuropathies-multiple myeloma
  • Paraproteinemia polyneuropathy IgM (polyneuropathy associated with IgM MGUS)
  • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
  • Phytanic acid storage disease (Refsum's disease)
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)
  • Psoriasis
  • Red cell alloimmunization in pregnancy
  • Renal transplantation ABO incompatible and ABO compatible except as indicated above
  • Rheumatoid arthritis
  • Schizophrenia
  • Scleroderma (progressive systemic sclerosis)
  • Sepsis with multiorgan failure
  • Stiff-person syndrome
  • Sudden sensorineural hearing loss
  • Sydenham chorea
  • Systemic lupus erythematous - including systemic lupus erythematous nephritis
  • Thrombotic microangiopathy, hematopoietic stem cell transplant (HSCT), refractory
  • Thyroid storm/Thyrotoxicosis
  • Toxic epidermal necrolysis, refractory

Due to the limited number of studies, small patient populations, short term follow ups and/or lack of comparisons to established conventional therapies, plasmapheresis or PE/TPE is not supported by the evidence in published peer reviewed medical literature or by professional societies to be a beneficial treatment modality for various other conditions. Some studies reported mixed results or no improvement in outcomes (e.g. improvement in symptoms, remission, improved survival rates) following plasmapheresis or plasma exchange (PE)/therapeutic plasma exchange (TPE) and therefore, would be considered investigational .


Procedure Codes and Billing Guidelines:

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS level 2) codes, Revenue codes, and/or diagnosis codes. 
  • 36514 Therapeutic apheresis; for plasmapheresis.

Selected References:

  • Brian G, et al.  A Randomized Trial of Plasma Exchange in Acute Central Nervous System Inflammatory Demyelinating Disease. The American Neurological Association Annals of Neurology 1999; 46(6):878-86.
  • Shumak KH, Rock GA. Therapeutic plasma exchange. N Engl J Med 1984; 310(12):762-71.
  • Lewis EJ, Hunsicker LG, Lan SP et al. A controlled trial of plasmapheresis therapy in severe lupus nephritis. The Lupus Nephritis Collaborative Study Group. N Engl J Med 1992; 326(21):1373-9.
  • Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet 1991; 337(8739):441-6.
  • Brashear HR, Phillips LH. Autoantibodies to GABAergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology 1991; 41(10):1588-92.
  • Sanders DB, Massey JM, Sanders LL et al. A randomized trial of 3,4-diaminopyridine in Lambert-Eaton myasthenic syndrome. Neurology 2000; 54(3):603-7.
  • Weinstein R. Therapeutic apheresis in neurological disorders. J Clin Apheresis 2000; 15(1-2):74-128.
  • Weinshenker BG, O'Brien PC, Petterson TM et al. A randomized trail of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999; 46(6):878-86.
  • Dyck PJ, Low PA, Windebank AJ et al. Plasma exchange in polyneuropathy associated with monoclonal gammopathy of undetermined significance. N Engl J Med 1991; 325(21):1482-6.
  • Kyriakidis AV, Karydakis P, Neofytou N et al. Plasmapheresis in the management of acute severe hyperlipidemic pancreatitis: report of 5 cases. Pancreatology. 2005;5(2-3):201-4. Epub 2005 Apr 22.
  • TARGET [database online]. Plymouth Meeting (PA): ECRIExternal Site 2003 June; ABO-incompatible living-donor kidney transplantation for endstage kidney disease.
  • Jordan SC, Vo AA, et al. Use of high-dose human intravenous immunoglobulin therapy in sensitized patients awaiting transplantation: the Cedars-Sinai experience. Clin Transpl 2003:193-8.
  • Ibernon M, Gil-Vernet S, et al. Therapy with plasmapheresis and intravenous immunoglobulin for acute humoral rejection in kidney transplantation. Transplant Proc 2005; 37(9):3743-5. 
  • Rockx MA, Clark WF. Plasma exchange for treating cryoglobulinemia: a descriptive analysis. Transfus Apher Sci 2010; 42(3):247-51.
  • Michael M, Elliott EJ, Craig CJ et al. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized trials. Am J Kidney Dis 2009; 53(2):259-72.
  • Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009; 361(17):1676-87.
  • Liu J, Wang W, Zhao C et al. Comparing the autoantibody levels and clinical efficacy of double filtration plasmapheresis, immunoadsorption and intravenous immunoglobulin for the treatment of late-onset myasthenia gravis. Ther Apher Dial 2010; 14(2):153-60.
  • Yuan X, Wang C, Gao W et al. Kidney transplant in highly sensitized patients after desensitization with plasmapheresis and low-dose intravenous immunoglobulin. Exp Clin Transplant 2010; 8(2): 130-5.
  • Cortese I, Chaudhry V, So YT et al. Evidence-based guideline update: Plasmapheresis in neurologic disorders. Neurology 2011; 76(3):294-300.
  • Martin LK, Werth VP, Villaneuva EV et al. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol. 2011 May; 64(5):903-8. Epub 2011 Feb 25.
  • Mehndiratta MM & Hughes RA. Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2012 Sep 12;9:CD003906.
  • Gordon PA, Winer JB, Hoogendijk JE, Choy EH. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. Cochrane Database Syst Rev. 2012 Aug 15;8:CD003643.
  • Raphael JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2012 Jul 11;7:CD001798.
  • Chhibber V & Weinstein R. Evidence-based review of therapeutic plasma exchange in neurological disorders. Semin Dial. 2012 Mar-Apr;25(2):132-9.
  • 2013 Guidelines on the use of Therapeutic Apheresis in Clinical Practice-Evidence Based Approach from the Writing Committee of the Aphersis Society for Apheresis: Sixth Special Issue; March 28, 2013: Joseph Schwartz, Jeffery L. Winters, Anand Padmanabhan, Rasheed A. Balogun, Meghan Delaney, Michael L. Linenberger, Zbigniew M. Szczepiorkowski, Mark E. Williams, Yanyun Wu, and Beth H. Shaz.
  • American Academy of Neurology: Evidence Based Guideline Update: Plasmaphoresis in Neurologic Disorders. Neurology, January 18, 2011 vol. 76 no. 3 294-300.
  • Hughes Richard, Swan Anthony, et. al. Immunotherapy for Guillain-Barre Syndrome: A Systematic Review, Brain 2007, 130, 2245-2257
  • Centers for Medicare and Medicaid ServicesExternal Site National Coverage Determination (NCD) for Apheresis (Therapeutic Apheresis) 110.14.
  • National Comprehensive Cancer Network External Site (NCCN) Version 2.2016 Waldenstrom’s Macroglubulinemia/Lymphoplasmacytic Lymphoma.
  • National Comprehensive Cancer NetworkExternal Site (NCCN) Version 3.2016 Multiple Myeloma.
  • UpToDateExternal Site Treatment and Prognosis of Thrombotic Thrombocytopenia Pupura-Hemolytic Uremic Syndromes in Adults, Andre A Kaplan, M.D., Jamens N. George, M.D., Topic last updated February 3, 2015.
  • UpToDateExternal Site Therapeutic Apheresis (Plasma Exchange or Cytapheresis): Indications and Technology, Joy L. Fridey, M.D., Andre A. Kaplan, M.D., Topic last updated July 29, 2015.
  • UpToDateExternal Site Wilson Disease: Treatment and Prognosis, Michael L. Schilsky, M.D., FAASLD, Topic last updated April 23, 2014.
  • UpToDateExternal Site Treatment and Prognosis of Guillain-Barre Syndrome in Adults, Francine J. Vriesendorp, M.D., Topic last updated March 9, 2015.
  • UpToDateExternal Site Treatment and Prognosis of Guillain-Barre Syndrome in Children, Robert P. Cruse, D.O., Topic last updated October 27, 2014.
  • UpToDateExternal Site Approach to the Patient with Suspected Thrombotic Thrombocytopenic Purpura (TTP) or Other Thrombotic Microangiopathy (TMA), James N. Geroge, M.D., Carla Nester, MS, M.D., Topic last updated May 22, 2015.   
  • UpToDateExternal Site Treatment of Mixed Cryoglobulinemia Syndrome. Fernando C. Fervenza, M.D., PhD, Michael D Leise, M.D., Dario Raccatello, M.D., Robert A Kyle M.D., Topic last updated January 6, 2016.
  • UpToDateExternal Site Treatment of Antiphospholipid Syndrome. Peter H Schur M.D., Andre A Kaplan M.D., Topic last updated April 4, 2016.
  • UpToDateExternal Site Treatment of the Complications of Multiple Myeloma. S Vincent Rajkumar M.D., Topic last updated July 17, 2014.
  • Pagano MB, Murinson BB, Tobian AA, et al. Efficacy of therapeutic plasma exchange for treatment of stiff-personsyndrome. Transfusion. Jul 2014;54(7):1851-1856. PMID 24527774
  • Michael M, Elliott EJ, Craig JC, et al. Interventions for hemolytic uremic syndrome and thromboticthrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009;53(2):259-272. PMID 18950913
  • Raphael JC, Chevret S, Hughes RA, et al. Plasma exchange for Guillain-Barre syndrome. Cochrane Database Syst Rev. 2012;7:CD001798. PMID 22786475
  • El-Bayoumi MA, El-Refaey AM, Abdelkader AM, et al. Comparison of intravenous immunoglobulin and plasma exchange in treatment of mechanically ventilated children with Guillain Barre syndrome: a randomized study. Crit Care. 2011;15(4):R164. PMID 21745374
  • Barth D, Nabavi Nouri M, Ng E, et al. Comparison of IVIg and PLEX in patients with myasthenia gravis. Neurology. Jun 7 2011;76(23):2017-2023. PMID 21562253
  • Ebadi H, Barth D, Bril V. Safety of plasma exchange therapy in patients with myasthenia gravis. Muscle Nerve. Apr 2013;47(4):510-514. PMID 23322564
  • Abboud H, Petrak A, Mealy M, et al. Treatment of acute relapses in neuromyelitis optica: Steroids alone versus steroids plus plasma exchange. Mult Scler. Apr 28 2015. PMID 25921047
  • Bonnan M, Valentino R, Olindo S, et al. Plasma exchange in severe spinal attacks associated with neuromyelitis optica spectrum disorder. Mult Scler. Apr 2009;15(4):487-492. PMID 19324982
  • Merle H, Olindo S, Jeannin S, et al. Treatment of optic neuritis by plasma exchange (add-on) in neuromyelitis optica. Arch Ophthalmol. Jul 2012;130(7):858-862. PMID 22776923
  • Walsh M, Catapano F, Szpirt W, et al. Plasma exchange for renal vasculitis and idiopathic rapidly progressive glomerulonephritis: a meta-analysis. Am J Kidney Dis. 2011;57(4):566-574. PMID 21194817
  • Walsh M, Casian A, Flossmann O, et al. Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. Aug 2013;84(2):397-402. PMID 23615499
  • Gubensek J, Buturovic-Ponikvar J, Kandus A, et al. Plasma exchange and intravenous immunoglobulin in the treatment of antibody-mediated rejection after kidney transplantation: a single-center historic cohort study. Transplant Proc. May 2013;45(4):1524-1527. PMID 23726611
  • Rimmer E, Houston BL, Kumar A, et al. The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis. Crit Care. Dec 20 2014;18(6):699. PMID 25527094  

Policy History:

  • May 2016 - Annual Review, Policy Revised
  • June 2015 - Annual Review, Policy Revised
  • July 2014 - Annual Review, Policy Revised
  • September 2013 - Annual Review, Policy Revised
  • October 2012 - Annual Review, Policy Renewed
  • October 2011 - Annual Review, Policy Revised
  • September 2010 - Annual Review, Policy Renewed

Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

*Current Procedural Terminology © 2012 American Medical Association. All Rights Reserved.