Medical policy: Plasma Exchange (PE)

Policy number: MP 4.031

Effective date: 4/1/2026

Policy

Plasma exchange (PE)

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

Autoimmune diseases

• 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.

Hematologic conditions

• ABO incompatible hematopoietic progenitor cell transplantation;
• Hyperviscosity syndromes associated with multiple myeloma or Waldenström macroglobulinemia;
• Idiopathic thrombocytopenic purpura (ITP) 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.

Neurologic conditions

• Acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome: 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 Guillain-Barre syndrome);
• Chronic inflammatory demyelinating polyradiculoneuropathy;
• Multiple sclerosis, with acute fulminant central nervous system demyelination;
• Neuromyelitis optica;
• Myasthenia gravis in crisis or as part of preoperative preparation;
• Paraproteinemia polyneuropathy; immunoglobulin A and G;
• N-methyl-D-aspartate receptor antibody encephalitis;
• Progressive multifocal leukoencephalopathy associated with natalizumab.

Renal diseases

• Anti-glomerular basement membrane disease (Goodpasture syndrome);
• Antineutrophil cytoplasmic antibody-associated vasculitis (e.g., Wegener granulomatosis) (also known as granulomatosis with polyangiitis [GPA]) with associated renal failure;
• Dense deposit disease with factor H deficiency and/or elevated C3 nephritic factor.

Transplantation

• ABO incompatible solid organ transplantation:
  • Kidney;
  • Heart (infants);
• Renal transplantation: antibody mediated rejection; human leukocyte antigen desensitization;
• Focal segmental glomerulosclerosis after renal transplant.

Plasma exchange (PE) is considered investigational in all other conditions, including, but not limited to, the following:

• ABO incompatible solid organ transplant: liver;
• Acute disseminated encephalomyelitis;
• Acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome) in children younger than 10 years old with mild or moderate forms;
• Acute liver failure;
• Amyotrophic lateral sclerosis;
• Antineutrophil cytoplasmic antibody-associated rapidly progressive glomerulonephritis (Wegener granulomatosis or granulomatosis with polyangiitis [GPA]) 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;
• Dermatomyositis and polymyositis;
• 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 myasthenic syndrome;
• Multiple sclerosis with chronic progressive or relapsing remitting course;
• 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 infection;
• 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’s chorea;
• Systemic lupus erythematosus (including systemic lupus erythematosus nephritis);
• Thyrotoxicosis; and
• Hyperviscosity syndromes with renal failure (other than associated with multiple myeloma or Waldenström macroglobulinemia).

There is insufficient evidence to support a general conclusion concerning the health outcomes or benefits associated with this procedure for the above listed indications.

Policy guidelines

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.

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 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 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.

Cross-references

• MP 9.053 Hematopoietic Cell Transplantation for Autoimmune Diseases

Product variations

This policy is only applicable to certain programs and products administered by Capital Blue Cross and subject to benefit variations. Please see additional information below.

FEP PPO - Refer to FEP Medical Policy Manual.

Description/background

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 is 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 is 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., <15% of total plasma volume) without the use of replacement solution.

Plasma exchange is 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.

This evidence review addresses only PE as a therapeutic apheresis procedure.

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. PE is a symptomatic therapy, because it does not remove the source of the pathogenic factors. Therefore, the success of PE depends on whether the pathogenic substances are accessible through circulation and whether the rate of production and transfer to the plasma component can be adequately addressed by 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 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 because of 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 transplant. It has been used as a technique to desensitize high-risk patients before transplant and also as a treatment of antibody-mediated rejection reoccurring 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 (i.e., rituximab).

Regulatory status

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 (e.g., immune globulin, albumin) and noninjectable products (e.g., in vitro devices such as blood bank reagents).

Product code for therapeutic exchange plasma: 57DI-65.

Rationale

Summary of evidence

Data from published studies, clinical input and/or guidelines from the American Society for Apheresis support the use of PE for selected autoimmune, hematologic, neurologic, renal, and transplantation conditions.

In 2023, the American Society for Apheresis published an updated Ninth Special Issue of Guidelines on the Use of Therapeutic Apheresis in Clinical Practice. The update included new fact sheets, new indications, and changes in category recommendations for existing fact sheets. However, after review of this literature, there were no significant changes to alter the conclusions reached above.

Definitions

Pathogenic means capable of causing or producing a disease.

Plasma refers to the watery straw-colored fluid part of the lymph and the blood in which the leukocytes, erythrocytes, and platelets are suspended. Plasma is made up of water, electrolytes, proteins, glucose, fats, bilirubin, and gases and is essential for carrying the cellular elements of the blood through circulation, transporting nutrients, maintaining the acid-base balance of the body, and transporting wastes from the tissue.

Progenitor cell refers to a parent cell that gives rise to a distinct cell lineage by a series of cell divisions.

Platelet refers to the smallest cells in the blood, essential for coagulation and for hemostasis.

Disclaimer

Capital Blue Cross’ medical policies are used to determine coverage for specific medical technologies, procedures, equipment, and services. These medical policies do not constitute medical advice and are subject to change as permitted by law or applicable clinical evidence from independent treatment guidelines. Treating providers are solely responsible for medical advice and treatment of members. These policies are not a guarantee of coverage or payment. Payment of claims is subject to a determination regarding the member’s benefit program and eligibility on the date of service, and a determination that the services are medically necessary and appropriate. Final processing of a claim is based upon the terms of contract that applies to the member’s benefit program, including benefit limitations and exclusions. If a provider or a member has a question concerning this medical policy, please contact Capital Blue Cross’ Provider Services or Member Services.

Coding information

Note: This list of codes may not be all-inclusive, and codes are subject to change at any time. The identification of a code in this section does not denote coverage as coverage is determined by the terms of member benefit information. In addition, not all covered services are eligible for separate reimbursement.

Covered when medically necessary

References

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