Plasma Exchange

POLICY NUMBER

L.8.02.402

DESCRIPTION

Plasma exchange (PE) is a procedure in which the plasma is isolated, then discarded and replaced with a fluid such as albumin. Plasma exchange is a nonspecific therapy, since 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.

Terminology

The terms therapeutic apheresis, plasmapheresis, and plasma exchange (PE) are often used interchangeably, but when properly used denote different procedures. The American Society for Apheresis definitions for these procedures are as follows:

Apheresis: A procedure in which blood of the patient or donor is passed through a medical device that separates out one or more components of blood and returns remainder with or without extracorporeal treatment or replacement of the separated component.

Plasmapheresis: A procedure in which blood of a patient or the donor is passed through a medical device that separates plasma from the other components of blood and the plasma is removed (i.e., less than 15% of total plasma volume) without the use of replacement solution.

Plasma exchange: A therapeutic procedure in which blood of the patient is passed through a medical device that separates plasma from other components of blood, the plasma is removed, and it is replaced with a replacement solution such as colloid solution (e.g., albumin and/ or plasma) or a combination of crystalloid/colloid solution.

Plasma Exchange

The rationale for PE is based on the fact that circulating substances, such as toxins or autoantibodies, can accumulate in the plasma. Also, it is hypothesized that removal of these factors can be therapeutic in certain situations. Plasma exchange is a symptomatic therapy, since it does not remove the source of the pathogenic factors. Therefore the success of PE depends on whether the pathogenic substances are accessible through the circulation, and whether their rate of production and transfer to the plasma component can be adequately addressed by the PE. For example, 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, PE is sometimes used in conjunction with cyclophosphamide.

Applications

Applications of PE can be broadly subdivided into two (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 PE does not address underlying pathology, and, due to the phenomenon of rebound antibody production, its use in chronic diseases has been more controversial than in acute self-limited diseases.

Also, plasmapheresis has been used in the setting of solid organ transplantation. It has been used as a technique to desensitize high-risk patients before transplant and also as a treatment of antibody-mediated rejection reaction occurring after transplant. Before transplant, plasmapheresis has been most commonly used to desensitize patients receiving an ABO mismatched kidney, often in combination with a splenectomy. As a treatment of antibody-mediated rejection, plasmapheresis is often used in combination with intravenous immunoglobulin or anti-CD20 therapy (ie, rituximab).

The U.S. Food and Drug Administration has a compliance program to ensure that source plasma, source leukocytes, and therapeutic exchange plasma for further manufacture into products for human use are safe, pure, potent, and appropriately labeled. The compliance program covers products intended for use both in injectable drug products (eg, immune globulin, albumin) and noninjectable products (eg, in vitro devices such as blood bank reagents).

Note:This policy addresses only plasma exchange as a therapeutic apheresis procedure.

POLICY

Plasma exchange may be considered medically necessary for any of the conditions listed below:

Autoimmune Diseases

• Severe multiple manifestations of mixed cryoglobulinemia such as cryoglobulinemic nephropathy, skin ulcers, sensory motor neuropathy, and widespread vasculitis in combination with immunosuppressive treatment;

• Catastrophic antiphospholipid syndrome.

Hematologic Conditions

• ABO-incompatible hematopoietic progenitor cell transplantation;

• Hyperviscosity syndromes associated with multiple myeloma or Waldenstrom macroglobulinemia;

• Idiopathic thrombocytopenic purpura in emergency situations;

• Thrombotic thrombocytopenic purpura; 

• 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.

Neurologic Conditions

• Acute inflammatory demyelinating polyneuropathy (Guillain-Barré Syndrome; for severely ill patients who are diagnosed with severity grade 1–2 within two (2) weeks of onset; severity grade 3-5 within 4 weeks of onset; and children younger than ten (10) years old with severe Guillain-Barré syndrome);

• Chronic inflammatory demyelinating polyradiculoneuropathy;

• Multiple sclerosis, with acute fulminant central nervous system demyelination;

• Myasthenia gravis in crisis or as part of preoperative preparation;

• IgA or IgG paraproteinemia polyneuropathy;

• N-methyl-D-aspartate receptor antibody encephalitis;

• Progressive multifocal leukoencephalopathy associated with natalizumab.

Renal Diseases

• Anti-glomerular basement membrane antibodies (i.e., Goodpasture syndrome);

• Antineutrophil cytoplasmic antibody-associated vasculitis (e.g., Wegener granulomatosis [also known as granulomatosis with polyangiitis]) with associated renal failure;

• Dense deposit disease with Factor H deficiency and/or elevated C3 nephritis factor.

Transplantation

• ABO-incompatible solid organ transplantation:

  • kidney;

  • heart (infants);

• Renal transplantation: antibody mediated rejection; human leukocyte antigen desensitization;

• Focal segmental glomulerulosclerosis after renal transplant.

Investigational applications of plasma exchange include, but are not limited to, the following conditions:

• ABO- incompatible solid organ transplant: liver;

• Acute disseminated encephalomyelitis;

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

• Acute liver failure;

• Amyotropic lateral sclerosis;

• Antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis (Wegener granulomatosis or granulomatosis with polyangiitis without renal failure);

• Aplastic anemia;

• Asthma;

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

• Chronic fatigue syndrome;

• Coagulation factor inhibitors;

• Cryoglobulinemia; except for severe mixed cryoglobulinemia, as noted above;

• Polymyositis and dermatomyositis;

• Focal segmental glomerulosclerosis (other than after renal transplant);

• Heart transplant rejection treatment;

• Hemolytic uremic syndrome; typical (diarrheal-related)

• Idiopathic thrombocytopenic purpura, refractory or non-refractory;

• Inclusion body myositis;

• Lambert-Eaton myastenic syndrome;

• Multiple sclerosis with chronic progressive or relapsing remitting course;

• Neuromyelitis optica (NMO);

• Mushroom poisoning;

• Myasthenia gravis with anti-MuSK antibodies;

• Overdose and poisoning (other than mushroom poisoning);

• Paraneoplastic syndromes;

• Paraproteinemia polyneuropathy IgM;

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

• Pemphigus vulgaris;

• Phytanic acid storage disease (Refsum disease);

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

• Psoriasis;

• Red blood cell alloimmunization in pregnancy;

• Rheumatoid arthritis;

• Sepsis;

• Scleroderma (systemic sclerosis);

• Stiff person syndrome;

• Sydenham chorea;

• Systemic lupus erythematosus (including systemic lupus erythematosus nephritis);

• Thyrotoxicosis;

• Hyperviscoscity syndromes with renal failure (other than associated with multiple myeloma or Waldenstrom macroglobulinemia).

POLICY EXCEPTIONS

Federal Employee Program (FEP) may dictate that all devices, drugs, biologics and imaging approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational and thus may be assessed only on the basis of their medical necessity.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Patients receiving plasma exchange (PE) as a treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) should meet the diagnostic criteria for CIDP, which were established by the American Academy of Neurology in 1991 and have not been updated since. The use of PE in patients with acute, life-threatening complications of chronic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, may need to be considered on an individual basis. An example of such a situation would be the development of a severe vasculitis, for which it is hypothesized that the use of PE can acutely lower the level of serum autoantibodies until an alternative long-term treatment strategy can be implemented. However, in these situations, the treatment goals and treatment duration 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.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

6/1993: Therapeutic Apheresis approved by Medical Policy Advisory Committee (MPAC).

11/1993: Extracorporeal Immunoadsorption Using Protein A Columns approved by MPAC.

5/1999: MPAC reviewed policies; updated, combined and renamed.

12/1999: Interim revision; new FDA-approved indication added for some stages of rheumatoid arthritis.

2/2000: Interim revisions approved by MPAC.

4/11/2001: Photopheresis for human heart transplant recipients at high risk for fatal rejection.  

8/2001: Reviewed by MPAC.

2/13/2002: Investigational definition added.

5/2/2002: Type of Service and Place of Service deleted.

10/4/2002: ICD-9 procedure code 99.76 added.

3/5/2003: Code Reference section updated.

7/2003: Reviewed by MPAC, policy aligned to be consistent with BCBSA, Sources updated.

3/17/2004: Code Reference section updated, CPT code 36520, 36521 deleted, ICD-9 diagnosis code 203.0, 273.2, 282.8, 284.8, 356.3, 356.9, 358.00 (note 358.0 was covered), 391.1, 710.1, 710.4 deleted, HCPCS Q0068 deleted, ICD-9 diagnosis 642.5 fifth digit added.

10/22/2004: Code Reference section updated, CPT 36511, 36512, 36513 deleted, ICD-9 diagnosis 202.20, 202.21, 202.22, 202.23, 202.24, 202.25, 202.26, 202.27, 202.28, 272.0, 272.2, 273.0, 273.3, 283.11, 287.3, 287.4, 289.0, 341.0, 341.1, 341.8, 341.9, 357.0, 357.81, 358.01, 446.21, 446.6, 583.81, 642.50, 642.51, 642.52, 642.53, 642.54, 714.0, 714.1, 714.2, 714.30, 714.31, 714.32, 714.33, 714.4, 714.81, 714.89, 714.9, 996.83, E878.0 note added, ICD-9 diagnosis 340 deleted, HCPCS S2120 added.

11/7/2005: Code Reference section updated, 5th digit added to ICD9 diagnosis code 287.31. 

3/10/2006: Coding updated.  CPT4/HCPCS 2006 revisions added to policy.

7/27/2006: Policy updated. Updates approved per Medical Policy Advisory Committee (MPAC).

8/31/2006: Code Reference section updated. V42.0, V42.1,V42.6, V42.7, V42.81, V42.83 added to covered table.

5/1/2008: Policy description updated with acute and chronic conditions; photopheresis, extracorporeal immunoadsorption, and lipid apheresis removed from policy. IgA or IgG paraproteinemia polyneuropathy added as a medically necessary indication. Inclusion body myositis and asthma added as investigational. Code reference section reviewed; CPT codes 36515, 36516, 36522, 86960 removed; ICD-9 procedure codes 99.76, 99.88 removed; ICD-9 diagnosis codes 202.20-202.28, 272.0-272.2, 714.0-714.9 removed; HCPCS S2120 removed. ICD-9 diagnosis codes 203.00, 203.01, 341.0, 341.20-341.22, 996.81, 996.82, 996.84-996.85 added.

9/11/2008: Annual ICD-9 updates applied.

06/23/2010: Policy Title changed, removed "Plasmapheresis." Policy Description section was revised for multiple reasons: definitions of apheresis, plasmapheresis and plasma exchange was added; addition applications of PE related to cryoglobulinemia, PANDAS and SC.  Policy Statements (medically necessary and investigational) were revised to include conditions that may be considered medically necessary and conditions that are considered investigational. FEP verbiage was added to the Policy Exceptions section. ICD-9 Diagnosis codes: 282.8, 340 and 446.4 were added to the Covered Codes Table.

10/14/2010: Annual ICD-9 code update: 287.4 deleted/expanded to the fifth digit. Added 287.41 and 287.49 to the Covered Codes table.

04/20/2011: Policy reviewed; no changes.

07/12/2012: Policy statement revised as follows: Myeloma with acute renal failure and catastrophic antiphospholipid syndrome were changed from investigational to medically necessary. Dense deposit disease with Factor H deficiency and/or elevated C3 nephritis factor and focal segmental glomerulosclerosis after renal transplant were added as medically necessary. The investigational statement on focal segmental glomerulosclerosis was revised to indicate that it applied to situations other than after renal transplant. Hyperviscoscity syndromes with renal failure (other than associated with multiple myeloma or Waldenstrom’s macroglobulinermia) was added as investigational. The serum creatinine threshold was removed from the policy statement on ANCA-associated vasculitis. Deleted outdated references from the Sources section. Added ICD-9 codes 289.81, 582.1, and 583.2 to the Covered Codes table.

08/14/2013: Policy reviewed; no changes.

06/14/2014: Policy reviewed; no changes.

07/10/2015: Neuromyelitis optica (NMO) added as an investigational application.

09/01/2015: Code Reference section updated for ICD-10. Removed deleted ICD-9 diagnosis code 287.4.

05/27/2016: Policy number A.8.02.02 added. Policy Guidelines updated to add medically necessary and investigative definitions.

02/22/2018: Policy description updated regarding plasmapheresis. Medically necessary statement updated with the following changes: 1) statement regarding hyperviscosity syndromes updated to remove "other conditions;" 2) removed "atypical" from "thrombotic thrombocytopenic purpura;" 3) added "atypical" to hemolytic uremic syndrome;" 4) for chronic inflammatory demyelinating polyneuropathy, removed "for patients with severe or life threatening symptoms who have failed to respond to conventional therapy with prednisone or intravenous immunoglobulins (IVIg)." Added N-methyl-D-aspartate receptor antibody encephalitis and progressive multifocal leukoencephalopathy associated with natalizumab as medically necessary. For ABO-incompatible solid organ transplantation, added kidney and heart (infants). Investigational statement updated with the following changes: 1) added granulomatosis with polyangiitis without renal failure; 2) for paraproteinemic polyneuropathy, removed "including monoclonal gammopathy of undetermined significance (MGUS);" 3) indication for systemic lupus erythematosus revised to include systemic lupus erythematosus nephritis 4) removed "regional enteritis (Crohn's disease)." Policy Guidelines updated regarding patients receiving plasma exchange as treatment. Code Reference section updated to add ICD-10 diagnosis code A81.2.

09/30/2020: Code Reference section updated to add new ICD-10 diagnosis codes N00.A, N01.A, N02.A, N03.A, N04.A, N05.A, N06.A, and N07.A, effective 10/01/2020.

10/01/2021: Code Reference section updated to add new ICD-10 diagnosis codes M31.10, M31.11, and M31.19 effective 10/01/2021.

09/19/2022: Code Reference section updated to add new ICD-10 diagnosis codes D59.30, D59.31, D59.32, D59.39, and I77.82, effective 10/01/2022.

07/24/2023: Policy number changed from "A.8.02.02" to "L.8.02.402." Policy reviewed. Policy statements unchanged. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity." Code Reference section updated to remove deleted ICD-10 diagnosis code M31.1.

09/29/2023: Code Reference section updated to add new ICD-10 diagnosis codes G37.81 and G37.89, effective 10/01/2023.

06/24/2024: Policy reviewed. Policy statements unchanged. Code Reference section updated to remove deleted ICD-10 diagnosis code D59.3.

10/01/2024: Code Reference section updated to add new ICD-10 diagnosis codes C81.7A, C88.00, and C88.91.

10/01/2025: Code Reference section updated to add new ICD-10 diagnosis codes G35.A, G35.B0, G35.B1, G35.B2, G35.C0, G35.C1, G35.C2, and G35.D.

SOURCE(S)

Blue Cross Blue Shield Association policy # 8.02.02

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Covered Codes 

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