Plasmapheresis/Plasma Exchange

 

Medical Policy: 08.01.16 

Original Effective Date: February 2000 

Reviewed: May 2018 

Revised: May 2017 

 

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:

Therapeutic plasmapheresis or plasma exchange (PE) is a procedure in which the plasma is isolated, then discarded or replaced with a substitution fluid such as albumin and is a recognized treatment modality for multiple acute and chronic conditions, as well as in the setting of solid organ and bone marrow transplantation. 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 therapeutic plasmapheresis or plasma exchange 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. 

 

Therapeutic plasmapheresis/plasma exchange is essentially symptomatic therapy, because it does not remove the source of the pathogenic factors. Therefore, the success of therapeutic plasmapheresis/plasma exchange 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/plasma exchange.

 

Applications of therapeutic plasmapheresis/plasma exchange can be broadly subdivided into 2 general categories: 1) acute self-limited diseases, in which therapeutic plasmapheresis/plasma exchange is used to acutely lower the circulating pathogenic substance; and 2) chronic diseases, in which there is ongoing production of pathogenic autoantibodies. Because therapeutic plasmapheresis/plasma exchange 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, therapeutic 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 solid organ or hematopoietic stem cell transplant.

 

The terms plasmapheresis, apheresis, and plasma exchange (PE) 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 performed 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

Therapeutic plasmapheresis/plasma exchange (PE) 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 therapeutic plasmapheresis/plasma exchange is as good as or better than conventional therapies.  In some conditions therapetic plasmapheresis/plasma exchange is used as an adjunctive therapy, the primary therapies for those conditions have demonstrated better outcomes (e.g. improvement in symptoms, remission, improved survival rates) and therapeutic plasmapheresis/plasma exchange is only recommended if primary therapy isn’t effective.  Due to data from published studies and/or clinical support, therapeutic plasmapheresis/plasma exchange is considered medically necessary for selected conditions. For conditions in which there is lack of efficacy data and clinical support, therapeutic plasmapheresis/plasma exchange is considered investigational.

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

  • Multiple Myeloma Version 3.2017
    •  Adjunctive Treatment
      • Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity
      • Plasmapheresis for renal dysfunction (category 2B)
  • Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma Version 1.2017
    • Primary Treatment Regimens: NCCN Panel recommends for patients requiring immediate disease control, such as those with symptomatic hyperviscosity, initial plasmapheresis is recommended.

 

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. The primary conclusions based on their evidence review are as follows:

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).

Acute Inflammatory Demyelinating Polyneuropathy/Guillain-Barre Syndrome
What is the efficacy of plasmapheresis in the treatment of acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barre Syndrome (GBS)?
Strong evidence

Plasmapheresis should be offered in the treatment of AIDP/GBS severe enough to impair independent walking or to require mechanical ventilation (Level A).
Good evidence

Plasmapheresis should be considered in the treatment of milder clinical presentations with AIDP/GBS (Level B).
Clinical context

IV immunoglobulin (IVIg) is an alternative treatment used in patients with AIDP/GBS. There is insufficient evidence to demonstrate the superiority of one treatment over the other.

Chronic Inflammatory Demyelinating Neuropathy
What is the efficacy of plasmapheresis in the treatment of chronic inflammatory demyelinating neuropathy (CIDP)?
Strong evidence

Plasmapheresis should be offered as a short term treatment for patients with CIDP (Level A).
Clinical context

Steroids, IVIg, and immunosuppressants also have been used in the treatment of CIDP.

Dysimmune Neuropathies
What is the efficacy of plasmapheresis in the treatment of dysimmune neuropathies?
Good evidence

Plasmapheresis should be considered in polyneuropathy associated with IgA and IgG monoclonal gammopathy of undetermined significance (MGUS) (Level B).

Plasmapheresis should not be considered in the treatment of polyneuropathy associated with IgM MGUS (Level B).

Myasthenia Gravis
What is the efficacy of plasmapheresis in the treatment of myasthenia gravis (MG)?
Insufficient evidence

Because of lack of randomized controlled studies with masked outcomes, there is insufficient evidence to support or refute the efficacy of plasmapheresis in the treatment of myasthenic crisis (Level U) or MG prethymectomy (Level U)

CNS Demyelinating Disease
What is the efficacy of plasmapheresis in the treatment of CNS demyelinating disease?
Strong evidence

Plasmapheresis should not be offered for chronic progressive or secondary progressive multiple sclerosis (MS) (Level A).
Good evidence

Plasmapheresis should be considered for the adjunctive treatment of exacerbations in relapsing forms of MS (Level B).
Weak evidence

Plasmapheresis may be considered in the treatment of fulminant CNS demyelinating diseases that fail to respond to high dose corticosteroid treatment (Level C).
Clinical context

No studies on the efficacy of plasmapheresis compared to other treatment options in MS are available.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection
What is the efficacy of plasmapheresis in the treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS)?
Insufficient evidence

There is insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute obsessive-compulsive disorder (OCD) and tic symptoms in the setting of PANDAS (Level U).

Sydenham Chorea
What is the efficacy of plasmapheresis in the treatment of Sydenham Chorea?
Insufficient evidence

There is insufficient evidence to support or refute the use of plasmapheresis in the treatment of Sydenham chorea (Level U).

 

American Society for Apheresis (ASFA)

In 2016, 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
Category Description
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

 

American Society for Apheresis (ASFA) Guidelines on the Use of Therapeutic Apheresis in Clinical Practice  (Note: NC - Not Categorized)
IndicationASFA 2013ASFA 2016
Acute disseminated encephalomyelitis II II
Acute Inflammatory demyelinating polyneuropathy (Guillain-Barre Syndrome) - Primary treatment I I
Acute Inflammatory demyelinating polyneuropathy (Guillain-Barre Syndrome) - After intravenous immunoglobulin III III
Acute liver failure III III
Amyloidosis, systemic IV IV
Amyotrophic lateral sclerosis (ALS) IV IV
ANCA-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis (Wegener’s); microscopic polyangiitis) - Dialysis dependent I I
ANCA-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis (Wegener’s); microscopic polyangiitis) - Dialysis independent III III
ANCA-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis (Wegener’s); microscopic polyangiitis) - Diffuse alveolar hemorrhage (DAH) I I
Anti-glomerular basement membrane disease (Goodpasture’s syndrome) - Dialysis dependent and no diffuse alveolar hemorrhage III III
Anti-glomerular basement membrane disease (Goodpasture’s syndrome) - Dialysis independent I I
Anti-glomerular basement membrane disease (Goodpasture’s syndrome) - Diffuse alveolar hemorrhage I I
Aplastic anemia III III
Atopic (neuro) dermatitis (atopic eczema), recalcitrant (new in 2016)  - III
Autoimmune hemolytic anemia - Severe code agglutinin disease III III
Autoimmune hemolytic anemia - Severe warm autoimmune hemolytic anemia III III
Burn shock resuscitation III III
Cardiac Transplantation - Desensitization III II
Cardiac Transplantation - Treatment of antibody mediated rejection III III
Cardiomyopathy dilated idiopathic (NYHA functional class IV-IV) III III
Catastrophic antiphospholipid syndrome (APS) II II
Chronic focal encephalitis (Rasmussen encephalitis) III III
Chronic inflammatory demyelinating polyradiculoneuropathy I I
Coagulation factor inhibitors - Alloantibody IV IV
Coagulation factor inhibitors - Autoantibody III III
Complex regional pain syndrome (new in 2016)  - III
Cryoglobulinemia severe/symptomatic I II
Dermatomyositis/polymyositis IV IV
Encephalitis associated with N-methyl D-aspartate receptor antibodies (new in 2016)  - I
Familial hypercholesterolemia - Homozygotes with small blood volume II II
Focal segmental glomerulosclerosis - Recurrent in transplanted kidney I I
Hashimoto’s encephalopathy: steroid responsive encephalopathy associated with autoimmune thyroiditis (new in 2016)  - II
Hemolysis, elevated liver function tests and low platelets (HELLP) syndrome (new in 2016) - Antepartum  - IV
Hemolysis, elevated liver function tests and low platelets (HELLP) syndrome (new in 2016) - Postpartum  - III
Hematopoietic cell transplantation HLA desensitization (new in 2016)  - III
Hematopoietic cell transplantation major ABO incompatibility - Stem cells from bone marrow II II
Hematopoietic cell transplantation major ABO incompatibility - Stem cells from peripheral blood II II
Hemophagocytic lympocytosis (HLH); macrophage activating syndrome (new in 2016)  - III
Hemolytic uremic syndrome atypical - Complement gene mutations II See thrombotic microangiography
Hemolytic uremic syndrome atypical - Factor H antibodies I See thrombotic microangiography
Hemolytic uremic syndrome atypical - MCP mutations IV See thrombotic microangiography
Hemolytic uremic syndrome infection associated - Shiga toxin associated IV See thrombotic microangiography
Hemolytic uremic syndrome infection associated - S. pneumonae associated III See thrombotic microangiography
Henoch-Schonlein purpura - Crescentric III III
Henoch-Schonlein purpura - Severe extrarenal disease III III
Heparin induced thrombocytopenia - Pre-cardiopulmonary bypass III III
Heparin induced thrombocytopenia - Thrombosis III III
Hypertriglyceridemic pancreatitis III III
Hyperviscosity in monoclonal gammopathies - Symptomatic I See Monoclonal gammopathies with hyperviscosity
Hyperviscosity in monoclonal gammopathies - Prophylaxis for rituximab I See Monoclonal gammopathies with hyperviscosity
Immune complex rapidly progressive glomerulonephritis III  -
Immune thrombocytopenia – refractory IV III
Immunoglobulin A Nephropathy - Chronic progressive III III
Immunoglobulin A Nephropathy - Crescentic III III
Inclusion body myositis IV  -
Lambert Eaton myasthenic syndrome II II
Liver transplantation ABO incompatible - Desensitization live donor I I
Liver transplantation ABO incompatible - Desensitization deceased donor III III
Liver transplantation ABO incompatible - Antibody mediated rejection (includes ABO and HLA) III III
Lung transplantation – antibody mediated rejection or desensitization III III
Monoclonal gammopathies with hyperviscosity - Prophylaxis for rituximab See hyperviscosity in monoclonal gammopathies I
Monoclonal gammopathies with hyperviscosity - Treatment of symptoms See hyperviscosity in monoclonal gammopathies I
Multiple sclerosis - Acute central nervous system inflammatory demyelinating disease II II
Multiple sclerosis - Chronic progressive III III
Mushroom poisoning See overdose, envenomation and poisoning II
Myasthenia gravis - Moderate-severe I I
Myasthenia gravis - Pre-thymectomy I I
Myeloma cast nephropathy II II
Neonatal lupus, cardiac (new in 2016)  - III
Nephrogenic systemic fibrosis III III
Neuromyelitis optica spectrum disorders (Devic’s syndrome) - Acute II II
Neuromyelitis optica spectrum disorders (Devic’s syndrome) - Maintenance III III
Overdose, envenomation and poisoning - Mushroom poisoning II See mushroom poisoning
Overdose, envenomation and poisoning - Envenomation III See mushroom poisoning
Overdose, envenomation and poisoning - Natalizumab and PML III See mushroom poisoning
Paraneoplastic neurologic syndromes III III
Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies - Anti-MAG neuropathy NC III
Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies - IgA, IgG I I
Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies - IgM I I
Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies - Multifocal motor neuropathy NC IV
Paraproteinemic demyelinating neuropathies/chronic acquired demyelinating polyneuropathies - Multiple myeloma III III
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) - Exacerbation I II
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) - Sydenham’s chorea I See Sydenham’s chorea
Pemphigus vulgaris - severe III III
Phytanic acid storage disease (Refsum disease) II II
POEMS syndrome IV IV
Post transfusion purpura III III
Progressive multifocal leukoencephalopathy associated with natalizumab (new in 2016)  - I
Pruritus due to hepatobiliary disease, treatment resistant (new in 2016)  - III
Psoriasis IV IV
Pure red cell aplasia III III
Red cell alloimmunization in pregnancy - Prior to IUT (intrauterine transfusion) availability III III
Renal transplantation ABO compatible - Antibody mediated rejection I I
Renal transplantation ABO compatible - Desensitization living donor I I
Renal transplantation ABO compatible - Desensitization deceased donor III III
Renal transplantation ABO incompatible - Antibody mediated rejection II II
Renal transplantation ABO incompatible - Desensitization living donor I I
Renal transplantation ABO incompatible - Desensitization deceased donor IV IV
Schizophrenia IV IV
Scleroderma (system sclerosis) III III
Sensorineural hearing loss, sudden III III
Sepsis with multi-organ failure III III
Stiff person syndrome III III
Sydenham chorea, severe See PANDAS III
Systemic lupus erythematosus - Nephritis IV IV
Systemic lupus erythematosus - Severe (e.g. cerebritis, diffuse alveolar hemorrhage) II II
Thrombotic microangiography - Coagulation mediated: THBD mutation (new in 2016) See hemolytic uremic syndrome atypical III
Thrombotic microangiography - Complement – mediated: complement factor gene mutations See hemolytic uremic syndrome atypical III
Thrombotic microangiography - Complement – mediated: Factor H antibodies See hemolytic uremic syndrome atypical I
Thrombotic microangiography - Complement – mediated: Membrane cofactor protein (MCP) mutations See hemolytic uremic syndrome atypical III
Thrombotic microangiography - Drug associated - Calcineurin inhibitors III III
Thrombotic microangiography - Drug associated - Clopidogrel IV III
Thrombotic microangiography - Drug associated - Gemcitabine or quinine III IV
Thrombotic microangiography - Drug associated - Ticlopidine I I
Thrombotic microangiography - Hematopoietic stem cell transplant associated hemolytic uremic syndrome infection associated III
Thrombotic microangiography - Shiga toxin mediated absence of severe neurologic symptoms hemolytic uremic syndrome infection associated III
Thrombotic microangiography - Shiga toxin mediated streptococcus pnuemonia hemolytic uremic syndrome infection associated I
Thrombotic thrombocytopenic purpura (TTP) acquired, autoimmune I I
Thyroid storm III III
Toxic epidermal necrolysis, refractory III III
Vasculitis (new in 2016) - Behcet’s disease  - III
Vasculitis (new in 2016) - Eosinophilic granulomatosis with polyangiitis (EGPA))  - III
Vasculitis (new in 2016) - Hepatitis B virus associated polyarteritis nodosa (HBV-PAN)  - II
Vasculitis (new in 2016) - Idiopathic polyarteritis nodosa (PAN)  - IV
Voltage gated potassium channel antibodies II II
Wilson disease, fulminant I I

 

Prior Approval:

 

Not applicable

 

Policy:

Therapeutic plasmapheresis/plasma exchange may be considered medically necessary for any of the following conditions listed below:

  • ABO incompatible hematopoietic stem cell transplantation
  • Acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome)
  • Anti-glomerular basement membrane disease (Goodpasture’s syndrome)
  • Anti-neutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis (e.g. granulomatosis with polyangiitis; Wegner’s granulomatosis) with associated renal failure (serum creatinine 5.8 mg/dL)
  • Anti-N-Methyl-D aspartate receptor encephalitis
  • Atypical hemolytic uremic syndrome
  • Autoimmune hemolytic uremic syndrome – severe cold agglutinin
  • Catastrophic antiphospholipid syndrome (CAPS)
  • Chronic inflammatory demyelinating polyneuropathy (CIDP)
  • Cryoglobulinemia severe/symptomatic
  • Dense deposit disease with factor H deficiency and/or elevated C3 nephritic factor
  • Familial hypercholesterolemia-homozygotes with small blood volume as secondary line of therapy, either as standalone treatment or in conjunction with other modes of treatment
  • Focal segmental glomerulosclerosis after renal transplant
  • Heart transplantation in infants ABO incompatible
  • HELLP syndrome of pregnancy (hemolysis, elevated liver function tests, and low platelets (HELLP) syndrome)
  • Hyperviscosity syndromes associated with monoclonal gammopathies (such as multiple myeloma and Waldenstrom’s macroglobulinemia)
  • Liver transplantation ABO incompatible - desensitization living donor
  • Multiple myeloma cast nephropathy (acute renal failure secondary to multiple myeloma)
  • Multiple sclerosis (MS)
    • For adjunctive treatment of exacerbations in relapsing forms of MS
    • In the treatment of fulminant CNS demyelinating disease that fails to respond to high dose corticosteroid treatment (as second line therapy either as standalone treatment or in conjunction with other modes of treatment)   
  • Myasthenia gravis that is moderate to severe or prior to thymectomy
  • Neuromyelitis optica (also known as Devic’s disease) acute disease
  • Paraproteinemic demyelinating neuropathies with IgA, IgG or IgM monoclonal gammopathy of undetermined significance (MGUS)
  • Pemphigus Vulgaris as second line therapy, that is resistant to standard therapy (dapsone, corticosteroids, immunosuppressants such as azathioprine or cyclosporine)
  • Post transfusion purpura
  • Progressive multifocal leukoencephalopathy associated with natalizumab (tysarbi) for the treatment of multiple sclerosis 
  • Renal Trasplantation
    • ABO incompatible desensitization living donor or antibody-mediated rejection
    • ABO compatible desensitization living donor or antibody-mediated rejection
  • Thrombotic microangiography secondary to Ticlopidine
  • Thromobtic thrombocytopenia purpura (TTP)
  • Voltage gated potassium channel antibodies
  • Wilson Disease with fulminant hepatic failure

Therapeutic plasmapheresis/plasma exchange is considered investigational for all other conditions including, but not limited to the following, because their safety and/or effectiveness cannot be established by review of the available published peer reviewed medical literature:

  • Acute disseminated encephalomyelitis
  • Acute liver failure, except as indicated above for Wilson Disease
  • Amyloidosis, systemic
  • Amyotrophic lateral sclerosis (ALS)
  • Anti-neutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis (Granulomatosis with polyangiitis; Wegener's Granulomatosis) without renal failure (dialysis independence)
  • Aplastic anemia
  • Asthma
  • Atopic (neuro) dermatitis (atopic exzema), recalcitrant
  • Autoimmune hemolytic anemia: warm autoimmune hemolytic anemia (WAHA)
  • Burn shock resuscitation
  • Cardiac (heart) transplantation except as indicated above
  • Cardiac neonatal lupus  
  • Chronic fatigue syndrome
  • Chronic focal encephalitis (Rasmussen Encephalitis)  
  • Coagulation factor inhibitors (alloantibody and autoantibody)
  • Complex regional pain syndrome
  • Dermatomyositis or polymyositis
  • Dilated cardiomyopathy, idiopathic (NYHA II-IV)
  • Focal segmental glomerulosclerosis except as indicated above
  • Hashimoto's encephalopathy
  • Henoch-Schonlein purpura
  • Hemolytic uremic syndrome (HUS)
  • Heparin induced thrombocytopenia
    • Pre-cardiopulmonary bypass; or
    • With thrombosis
  • Hemophagocytic hymphocytosis (HLH); macrophage acxtivating syndrome
  • 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, 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 (excedpt as indicated above) - multiple myeloma; Anti-MAG neuropathy; multifocal motor neuropathy)
  • Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)
  • Pemphigus vulgaris except as indicated above
  • Phytanic acid storage disease (Refsum's disease)
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)
  • Progressive multifocal leukoencephalopathy associated with natalizumab (tysarbi), except as indicated above
  • Pruritus due to hepatobiliary diseases
  • Psoriasis
  • Pure red cell aplasia
  • 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 (except as indicated above), hematopoietic stem cell transplant (HSCT), associated; coagulation mediated: THBD; complement mediated: complement factor gene mutations; drug associated (calcinerin, clopidogrel, gemcitabine or quinine); Shiga toxin mediated (absence of severe neurologic symptoms, with severe neurologic symptoms and streoptococcus pneumonia)
  • Thyroid storm/Thyrotoxicosis
  • Toxic epidermal necrolysis, refractory
  • Vasculitis (Bechet’s disease; hepatitis B virus associated polyarteritis nodosa (HBV-PAN); eosinophilic granulomatosis with polyangiitis (EGPA); and idiopathic polyarteritis nodsa (PAN)

 

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): ECRI 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 Services. National Coverage Determination (NCD) for Apheresis (Therapeutic Apheresis) 110.14.
  • National Comprehensive Cancer Network (NCCN) Version 1.2017 Waldenstrom’s Macroglubulinemia/Lymphoplasmacytic Lymphoma.
  • National Comprehensive Cancer Network (NCCN) Version 3.2017 Multiple Myeloma.
  • UpToDate. 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.
  • UpToDate. Therapeutic Apheresis (Plasma Exchange or Cytapheresis): Indications and Technology, Joy L. Fridey, M.D., Andre A. Kaplan, M.D., Topic last updated January 30, 2017.
  • UpToDate. Wilson Disease: Treatment and Prognosis, Michael L. Schilsky, M.D., FAASLD, Topic last updated November 29, 2016.
  • UpToDate. Guillain-Barre Syndrome in Adults - Treatment and Prognosis, Francine J. Vriesendorp, M.D., Topic last updated April 19, 2017.
  • UpToDate. Guillain-Barre Syndrome in Children - Treatment and Prognosis, Monique M. Ryan FRACP. Topic last updated August 29, 2016.
  • UpToDate. 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 January 12, 2018.   
  • UpToDate. 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.
  • UpToDate. Treatment of Antiphospholipid Syndrome. Peter H Schur M.D., Andre A Kaplan M.D., Topic last updated February 23, 2017.
  • UpToDate. Treatment of the Complications of Multiple Myeloma. S Vincent Rajkumar M.D., Topic last updated August 1, 2016.
  • 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  
  • Schwartz J, Padmanabhan A, Aqui N, et. al. 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. J Clin Apher 2016 Jun;31(3):149-62. PMID 27322218
  • The Anti-NMDA Receptor Encephalitis Foundation
  • ECRI. Custom Rapid Response Guideline. Plasmapheresis for Treatment of Multiple Sclerosis. Published April 2004, Updated October 2015.
  • UpToDate. Hashimoto Encephalopathy. Devon I Rubin M.D., Topic last updated June 17, 2015.
  • UpToDate. Acquired TPP: Initial Treatment. James N George M.D., Adam Cuker M.D., MS. Topic last updated November 6, 2017.
  • UpToDate. Recurrent and De Novo HUS after Renal Transplantation. Christina L. Klein M.D., Anuja Java M.D., Daniel C. Brennan M.D., FAC  Topic last updated November 30, 2016.
  • UpToDate. Initial Immunosuppressive Therapy in Granulomatosis with Polyangitis and Microscopic Polyangiitis. Peter A Merkel M.D., MPH, Andre A Kaplan, Ronald J Falk M.D., Topic last updated January 4, 2017.
  • UpToDate. Treatment of Anti-GBM Antibody (Goodpasture’s Disease). Andre A Kaplan M.D., Gerald B. Appel M.D., Charles D Pusey M.D. Topic last updated January 12, 2016.
  • UpToDate. Treatment and Prognosis of Waldenstrom Macroglobulinemia. S Vincent Rajkumar M.D., Topic last updated May 15, 2017.
  • UpToDate. Treatment and Prognosis of Kidney Disease in Multiple Myeloma and other Monoclonal Gammopathies. S Vincent Rajkumar M.D., Andrea A Kaplan M.D., Nelson Leung M.D. Topic last updated January 13, 2017.
  • UpToDate. Treatment of Myasthenia Gravis, Shawn J Bird M.D., Topic last updated September 15, 2017.
  • UpToDate. Chronic Inflammatory Demyelinating Polyneuropathy: Treatment and Prognosis. Richard A Lewis M.D., Topic last updated February 13, 2017.
  • UpToDate. Cold Agglutinin Disease. Stanley L Schrier M.D., Topic last updated October 5, 2016.
  • UpToDate. Treatment of Lambert-Eaton Myasthenic Syndrome. David H. Weinberg M.D., Topic last updated April 26, 2016.
  • UpToDate. Hypertriglyceridemia-Induced Acute Pancreatitis. Andres Gelrud M.D., MMSc, David C Whitcomb M.D., PhD. Topic last updated July 20, 2015.
  • UpToDate. Nephrogenic Systemic Fibrosis/Nephrogenic Fibrosing Demopathy in Advanced Renal Failure. Dana Miskulin M.D., Michael R Rudnick M.D. Topic last updated July 18, 2016.
  • UpToDate. Paraneoplastic and Autoimmune Encephalitis. Joseph Dalmau M.D., PhD, Myrna R. Rosenfeld M.D., PhD. Topic last updated April 7, 2017.
  • UpToDate. Overview of Paraneoplastic Syndromes of the Nervous System. Joseph Dalmau M.D., PhD, Myrna R. Rosenfeld  M.D., PhD. Topic last updated December 6, 2016.
  • UpToDate. Progressive Multifocal Leukoencephalopathy: Treatment and Prognosis. Igor J Koralnik M.D., Topic last updated April 13, 2017.
  • UpToDate. Treatment and Prognosis of Polyarteritis Nodosa. Peter A. Merkel M.D., MPH. Topic last updated November 3, 2015.
  • UpToDate. Renal Disease Associated with Hepatitis B Virus Infection. Tak-Mao Chan M.D., FRCP, Anna SF Lok M.D., Topic last updated January 11, 2016.
  • Jacobs-Kosim D, Diamond H. Polyarteritis Nodsa. January 12, 2016
  • Chen H, Masharani M. Hashimoto’s Encephalopathy.
  • Lasoff D, Corbett-Detig J, et. al. Anti-N-Methyl-D-Aspartate Receptor Encephalitis, an Underappreciated Disease in the Emergency Department. Western J Emerg Med 2016;17(3):280-282.
  • Barry H, Byrne S, et. al. Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Review of the Clinical Presentation, Diagnosis and Treatment. BJPsych Bulletin (2015) 39 19-23   
  • Singh J, Saag K, Bridges L, et. al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis.
  • Hahn B, McMahon M, Wilkinson A, et. al. American College of Rheumatology Guidelines for Screening, Treatment and Management of Lupus Nephritis.
  • Carr RA, Rejowski BJ, Cote GA, et. al. Systematic review of hypertriglyceridemia-induced acute pancreatitis: a more virulent etiology? Pancreatology 2016 Jul-Aug;16(4);469-76. PMID 27012480
  • Bayraktaroglu Z, Demirci F, Balat O, et. al. Plasma exchange therapy in HELLP syndrome: a single center experience. Turk J Gastroenterol 2006 Jun;17(2):99-102 PMID 16830290 
  • Clark WF. Plasma exchange for renal disease: evidence and use 2011. J Clin Apher 2012;27(3):112-6. PMID 22535650
  • Clark WF. Thrombotic microangiography: current knowledge and outcomes with plasma exchange. Semin Dial 2012 Mar-Apr;2592):214-9. PMID 22509967
  • Kohler W, Bucka C, Klingel R. A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis. J Clin Apher 2011 Dec;26(6):347-55. PMID 22095647
  • UpToDate. Acute Disseminated Encephalomyelitis in Children: Treatment and Prognosis. Timothy E. Lotze M.D., Donald J. Chadwick M.D. Topic last updated March 8, 2018. 
  • UpToDate. Acquired TTP: Treatment of Refractory or Relapsed Disease. James N. George M.D., Adam Cuker M.D., M.S. 
  • UpToDate. Evulation and Treatment of Antibody Mediated Lung Transplant Rejection. Ramsey R. Hachem M.D., Topic last updated September 7, 2017. 
  • UpToDate. Treatment of Anti-GBM Antibody (Goodpasture’s) Disease. Andre A. Kaplan M.D., Gerald B. Appel M.D., Charles D. Pusey M.D.. Topic last updated December 12, 2017. 
  • UpToDate. Initial Immunosuppressive Therapy in Granulomatosis with Polyangitis and Microscopic Polyangitis. Peter A. Merkel M.D., MPH, Andre A. Kaplan M.D., Ronald J. Falk M.D., Topic last updated January 4, 2017.

 

Policy History:

  • May 2018 - Annual Review, Policy Renewed
  • May 2017 - Annual Review, Policy Revised
  • 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.

 

*CPT® is a registered trademark of the American Medical Association.