Plasmapheresis/Plasma Exchange

• Notice
• Benefit Application
• Description
• Prior Approval
• Policy
• Procedure Codes
• Selected References
• Policy History

 

Medical Policy: 08.01.16 

Original Effective Date: February 2000 

Reviewed: May 2021 

Revised: May 2021 

 

Notice:

This policy contains information which is clinical in nature. The policy is not medical advice. The information in this policy is used by Wellmark to make determinations whether medical treatment is covered under the terms of a Wellmark member's health benefit plan. Physicians and other health care providers are responsible for medical advice and treatment. If you have specific health care needs, you should consult an appropriate health care professional. If you would like to request an accessible version of this document, please contact customer service at 800-524-9242.

 

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.  The goal of therapeutic plasmapheresis/plasma exchange is the removal of harmful plasma components. Theoretically, decreasing the concentration of the harmful plasma component, will improve the course of the disease. Abnormal components potentially removed with therapeutic plasmapheresis/plasma exchange (PE) include toxins, metabolic substances, and plasma components (i.e. antibodies, complement system [part of the immune system, consists of small number of proteins that are synthesized by the liver, and circulate in the blood as inactive precursors]). Therefore, diseases thought to be caused by these abnormal constituents might best be treated with this form of therapy. Diseases benefiting from plasmapheresis are largely autoimmune or neurological disorders. Plasmapheresis/plasma exchange techniques are not intended to be curative treatments for most indications. Rather, they are used to address related symptoms.

 

Therapeutic plasmapheresis/plasma exchange (PE) 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 (PE) can be broadly subdivided into three general categories:

• Acute self-limited diseases;
• Acute fulminant exacergations of chronic diseases; and
• Chronic diseases

 

In self-limited diseases and acute exacerbations of fulminant exacerbations of chronic diseases, therapeutic plasmapheresis/plasma exchange is used to acutely lower the circulating pathogenic substance. In chronic disease, 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 less effective than in acute, self-limiting diseases. For this reason, chronic conditions are not amendable to plasmapheresis treatment.

 

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.

 

Therapeutic plasmapheresis/plasma exchange (PE) are typically performed in outpatient settings, including blood banks, dialysis centers, hospital clinics, and physician’s offices. Reinfusion with human plasma may cause anaphylaxis and bleeding complications, and though rare, may require replacement of clotting factors. Therefore, plasmapheresis procedures should be performed by appropriately trained clinicians in a setting that can respond to medical emergencies at all times.

 

Therapeutic Plasmapheresis/Plasmas Exchange in Covid-19 Patients 

The use of therapeutic plasmapheresis/plasma exchange (TPE) in the treatment of severe COVID-19 infection has shown some positive results; however, the benefit has been limited in macrophage activation syndrome or sepsis complicated with MODS (multiple organ dysfunction syndrome) Theoretically, TPE could also remove the formed SARS-CoV-2 antibodies in addition to the “harmful” dysregulated inflammatory mediators, but it remains unclear if there is an antibody response during the cytokine storm or it develops subsequently. In this regard, the current recommendation of the American Plasma Exchange Association is as follows "the effectiveness of plasma exchange has not yet been determined and should be individually selected"

 

It is also necessary to administer TPE for the correct duration and volume, to monitor the potential drug removal of specific therapies such as immunomodulating agents and to practice the proper infection prevention and control measures. TPE is a tolerable procedure by most patients without adverse events; however, the procedure can be a challenge to perform in COVID-19 patients who are placed in a prone position.

 

In 2020, Khamis et. al. completed a retrospective single-center, case series study evaluating the therapeutic effectiveness of therapeutic plasmas exchange (TPE) in adults (31 patients) with severe Covid-19 infection. The analysis was performed using univariate statistics. Therapeutic plasma exchange (TPE) was performed on patients admitted to the intensive care unit (ICU) with confirmed or imminent acute respiratory distress syndrome (ARDS) or severe pneumonia. The TPE group was associated with higher extubation rates than the non-TPE cohort (73% versus 20%; p = 0.018). Additionally, patients on TPE had a lower 14 days (0 versus 35%; p = 0.033) and 28 days (0 versus 35%; p = 0.033) post plasma exchange mortality compared to patients not on TPE. However, all-cause mortality was only marginally lower in the TPE group compared to the non-TPE group (9.1% versus 45%; p = 0.055; power = 66%). Laboratory and ventilatory parameters also improved post TPE (n = 11). This single-center small trial is not without limitations. Although patients might have improved naturally, the laboratory and ventilatory changes before and after plasma exchange are encouraging for the TPE group. The use of the IL-6 antagonist, tocilizumab, could have contributed to TPE's beneficial effects. The current study is a case series with a small number of patients; a larger well-powered randomized clinical trial is warranted to confirm the beneficial outcomes of TPE.

 

In 2020, Ma et. al. reported on the potential effect of blood purification which included plasma exchange in reducing cytokine storm as a late complication of critically ill Covid-19 patients. Based on this case series emerging evidence indicates the potential benefits of managing cytokine storm, via using steroid or IL-6/IL-6-receptor blocking antibodies. The capability of blood purification therapy (plasma exchange) in removing pathogenic antibodies or cytokines has been proven in multiple scenarios, but not in COVID-19 patients. 

 

Summary 

Based on the current peer reviewed medical literature regarding the treatment of Covid-19 using therapeutic plasma exchange (TPE) it is based on case series and retrospective reviews. While TPE has shown some promising results, however, the benefits have been limited in macrophage activation syndrome and sepsis complicated with MODS (multiple organ dysfunction syndrome). The capability of blood purification therapy (plasma exchange) in removing pathogenic antibodies or cytokines has been proven in multiple scenarios, but not in COVID-19 patients. The recommendation of the American Plasma Exchange Association is as follows "the effectiveness of plasma exchange has not yet been determined and should be individually selected." While TPE has been associated with improved outcomes in the treatment of Covid-19 patients, randomized controlled clinical trials (RCTs) are warranted to draw final, conclusive findings. The evidence is insufficient. 

 

Summary of Evidence

Peer reviewed published medical literature and medical society guidelines support the clinical effectiveness and safety of therapeutic plasmapheresis/plasma exchange (PE) for the indications listed in the policy statement below. There is evidence for the accepted indications that the use of this procedure can result in an improvement of symptoms, primarily for the acute self-limited conditions, and subsequently improve quality of life (QOL). However, based on the literature and society guidelines the evidence also is limited and/or the optimum role of therapeutic plasmapheresis/plasma exchange (PE) to remove specific autoantibodies, proteins and complements in the pathogenesis of many other conditions has not been established or the evidence demonstrated the therapy could be ineffective or harmful and therefore are considered investigational as indicated in the policy statement below.

 

Practice Guidelines and Position Statements

National Comprehensive Cancer Network (NCCN)

Multiple Myeloma Version 7.2021

• Supportive Care Treatment for Multiple Myeloma
  • Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity
• Management of Renal Disease in Multiple Myeloma
  • Plasmapheresis

 

Waldenstrom’s Macroglobulinemia/Lymphoplasmacytic Lymphoma Version 1.2021

Plasmapheresis should be performed for patients with symptomatic hyperviscosity, and before treatment with rituximab-containing regimen in patients with IgM ≥ 4000 mg/dl. IgM should be monitored closely in these patients thereafter and plasmapheresis should be considered again if symptomatic hyperviscosity recurs or if IgM is ≥ 4000 mg/dL while on rituximab containing therapy.

 

Primary Treatment Regimens

According to NCCN Panel, for patients requiring immediate disease control such as those with symptomatic hyperviscosity, initial plasmapheresis is recommended. After plasmapheresis, systemic therapy should be initiated as soon as possible.

 

Rituximab

Single agent rituximab is active in patients with WM. Transient increases in IgM titers (also called IgM flare) have been reported in 40% to 50% of patients after initiation of rituximab therapy, including in circumstances where rituximab has been used in combination therapy. The rituximab related IgM flare may lead to symptomatic hyperviscosity, as well as worsening of IgM related neuropathy, cryoglobulinemia and other IgM related complications. These levels may persist for months and do not indicate treatment failure, but may necessitate plasmapheresis to reduce hyperviscosity. Prophylactic plasmapheresis can be considered in patients with high IgM levels (typically 4,000 mg/dL or higher) before rituximab exposure to minimize risk of symptomatic hyperviscosity.

 

Treatment of IgM related Peripheral Neuropathy

The treatment of IgM related neuropathy may initially involve a course of plasmapheresis, particularly in patients with a more aggressive course of progressing peripheral neuropathy attributed to the IgM paraprotein. Typically, a course of 2 to 3 months of weekly plasmapheresis may be required before any impact on symptomatic neuropathy may be seen. Plasmapheresis, however should not be used as a permanent modality, and consolidation with chemotherapy should be considered. Post-plasmapheresis, IgM levels will return to baseline in 4 to 6 weeks.

 

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).

 

American Heart Association (AHA)

In 2015, the American Heart Association (AHA) issued a scientific statement regarding antibody-mediated rejection (AMR) in cardiac transplantation, which included the following:

 

The following are 10 points to remember from this American Heart Association Scientific Statement about antibody-mediated rejection (AMR) in cardiac transplantation:

1. AMR is a “clinical entity with specific histopathologic, immunopathologic, and serological characteristics.”
2. Risk factors for AMR includes: elevated PRA, CMV seropositivity, prior mechanical circulatory support, prior treatment with muromoab-CD3 and development of antibodies against mouse monoclonal muromonab-CD3, history of retransplantation, multiparity, and positive crossmatch on T-cell flow cytometery.
3. It may present hyperacutely (within 0-7 days after transplantation), early (within the first month after transplantation), or late (months to years after transplantation).
4. Key diagnostic findings includes: a) Clinical evidence of graft dysfunction, b) histopathologic evidence of acute capillary injury including changes in capillary endothelium and macrophages in capillaries, c) immunopathologic evidence for antibody-mediated injury including changes in C3d and/or C4d immunofluorescence staining or CD68 or C4d immunoperoxidase staining or severe fibrin in vessels, and d) serological evidence of anti-HLA or anti-donor antibodies.
5. The presentation of AMR may vary from mild heart failure to cardiogenic shock.
6. Endomyocardial biopsy is the gold standard for establishing the development of AMR.
7. There have been no large randomized clinical trials to evaluate therapies for AMR and hence there are no level I recommendations and all recommendations are therefore based on consensus.
8. The guiding principles for the management of AMR include removing circulating alloantibodies, reducing production of additional antibodies, and suppressing T-cell and B-cell responses.
9. Commonly used agents utilized in the treatment of AMR include: a) corticosteroids (act by suppression of T- and B-cell response), b) plasmapharesis (acts by eliminating circulating antibodies), c) IVIG (act by inhibiting residual antibodies and inhibition of complement), whereas less commonly used agents include: a) rituximab or splenectomy (act by suppression or depletion of B cells), b) bortezomib (act by suppression or depletion of plasma cells), c) eculizumab (by inhibition of complement), and d) mycophenolate mofetil, anti-lymphocyte antibodies, photopheresis, or total lymphoid irradiation (these act by suppression of T-cell response). In addition to treating AMR with cytotoxic or antibody-directed therapy, the background regimen should be optimized using potent B-cell receptors (mycophenolate and sirolimus).
10. AMR is associated with allograft failure, increased mortality, increased incidence of coronary artery vasculopathy, and overall poor prognosis.

 

American Society for Apheresis (ASFA)

In 2019, the American Society for Apheresis (ASFA) released the eighth special issue of their guidelines on the use of therapeutic apheresis in clinical practice. The therapeutic apheresis procedures considered in this guideline include therapeutic plasma exchange (TPE).

 

 

 

 

Regulatory Status 

FDA 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).

 

Prior Approval:

Not applicable

 

Policy:

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

• Acute disseminated encephalomyelitis (ADEM) steroid refractory
• Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barre syndrome)
• Anti-glomerular basement membrane disease (Goodpasture’s syndrome)
  • Diffuse alveolar hemorrhage (DAH)
  • Dialysis independence 
• Anti-neutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis
• Autoimmune hemolytic uremic syndrome – severe cold agglutinin
• Catastrophic antiphospholipid syndrome (CAPS)
• Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)
• Cryoglobulinemia severe/symptomatic
• Familial hypercholesterolemia
• Focal segmental glomerulosclerosis after kidney transplant
• Hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP Syndrome)
• Hyperviscosity syndromes associated with monoclonal gammopathies (such as multiple myeloma and Waldenstrom’s macroglobulinemia)
• Lambert-Eaton Myasthenic Syndrome
• 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)
• Mushroom poisoning (wild mushrooms, particularly the Amanita family)
• Myasthenia gravis 
• Neuromyelitis optica (also known as Devic’s disease) acute attack/relapse
• N-methyl-D-aspartate receptor antibody
• Paraproteinemic demyelinating neuropathies with IgA, IgG or IgM monoclonal gammopathy of undetermined significance (MGUS)
• Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), exacerbation 
• Pemphigus Vulgaris as second line therapy, that is resistant to standard therapy (dapsone, corticosteroids, immunosuppressants such as azathioprine or cyclosporine)
• Phytanic acid storage disease (Refsum’s Disease)
• Post transfusion purpura
• Progressive multifocal leukoencephalopathy associated with natalizumab (tysarbi)
• Steroid responsive encephalopathy associated with autoimmune thyroiditis (Hashimoto’s encephalopathy)
• Systemic lupus erythematous (SLE) with severe complications (diffuse alveolar hemorrhage (DHA), thrombotic microangiography, hyperviscosity, cryoglobulinemia, and CNS involvement) 
• Thrombotic microangiopathy (Factor H autoantibody) and drug associated (Ticlopidine)
• Thrombotic thrombocytopenia purpura (TTP)
• Thyroid storm with severe symptoms who respond poorly to first line therapeutic measures
• Transplantation
  • Hematopoietic stem cell transplant:
    • ABO incompatible
    • Human leukocyte antigen (HLA) incompatibility with haplo-type transplant
  • Solid organ transplantation for the following:
    • Desensitization
    • Antibody-mediated rejection
    • ABO incompatible
• Voltage gated potassium channel antibodies
• Wilson Disease, fulminant

Therapeutic plasmapheresis/plasma exchange is considered investigational for all other conditions including, but not limited to the following, because the evidence is insufficient to determine the effects of the technology on net health outcomes:

• Acute liver failure, except as indicated above for Wilson Disease
• Amyloidosis, systemic
• Amyotrophic lateral sclerosis (ALS)
• Anti-glomerular basement membrane disease (Goodpasture syndrome) – dialysis dependence, no diffuse alveolar hemorrhage (DAH)
• Aplastic anemia
• Asthma
• Atopic (neuro) dermatitis (atopic exzema), recalcitrant
• Autoimmune hemolytic anemia, severe: warm autoimmune hemolytic anemia (WAHA)
• Burn shock resuscitation
• Cardiac neonatal lupus  
• Chronic fatigue syndrome
• Chronic focal encephalitis (Rasmussen Encephalitis)  
• Coagulation factor inhibitors (alloantibody and autoantibody)
• Complex regional pain syndrome
• Covid-19
• Dermatomyositis or polymyositis
• Dilated cardiomyopathy, idiopathic (NYHA II-IV)
• Erythropoietic protoporphyria, liver disease 
• Focal segmental glomerulosclerosis except as indicated above
• Henoch-Schonlein purpura
• Hemolytic uremic syndrome (HUS)
• Heparin induced thrombocytopenia (HIT) 
  • Pre-cardiopulmonary bypass; or
  • Heparin induced thrombocytopenia with thrombosis (HITT)
• Hemophagocytic hymphocytosis (HLH); Hemophagocytic syndrome; Macrophage acxtivating syndrome
• Hypertriglyceridemic pancreatitis
• Immune complex rapidly progressive glomerulonephritis
• Immune thrombocytopenia (refractory)
• Immunoglobin A nephropathy (Berger's Disease)
• Inclusion body myositis
• Inflammatory bowel disease (ulcerative colitis, Crohn's disease)
• Multiple Sclerosis, 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 (PANDAS) except as indicated above
• Pemphigus vulgaris except as indicated above
• 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
• Rheumatoid arthritis
• Schizophrenia
• Scleroderma (progressive systemic sclerosis)
• Sepsis with multiorgan failure
• Status epilepticus
• Stiff-person syndrome
• Sudden sensorineural hearing loss
• Sydenham's chorea
• Systemic lupus erythematous except as indicated above
• Thrombotic microangiopathy (except as indicated above) coagulation mediated: THBD, DGKE, and PLG mutationos; complement mediated: complement factor gene mutations; drug associated: (clopidogrel, gemcitabine or quinine); transplantation associated
• Thyroid storm except as indicated above
• Toxic epidermal necrolysis, refractory

 

Policy Guidelines

For the treatment of solid organ transplantation antibody-mediated rejection (ABMR or AMR) plasmapheresis is typically performed for this indication within the first year of the transplantation. There is a lack of evidence regarding the treatment of late onset (after the first year of transplantation) for antibody-mediate rejection with plasmapheresis.

 

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) Waldenstrom’s Macroglubulinemia/Lymphoplasmacytic Lymphoma Version 1.2021.
• National Comprehensive Cancer Network (NCCN) Multiple Myeloma Version 7.2021.
• 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 31, 2018.
• 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. 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 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 March 14, 2019.
• UpToDate. Overview of the Treatment of Myasthenia Gravis, Shawn J Bird M.D., Topic last updated February 12, 2019.
• UpToDate. Chronic Inflammatory Demyelinating Polyneuropathy: Treatment and Prognosis. Richard A Lewis M.D., Topic last updated December 6, 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. Acquired TPP: Initial Treatment. James N. George M.D., Topic last updated March 29, 2019.
• 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. 
• UpToDate. ABO Incompatibility in Kidney Transplantation. Christina L. Klein M.D., Daniel C. Brennan M.D., FACP. Topic last updated January 28, 2019. 
• UpToDate. Approach to the Patient with Suspected TTP, HUS or Other Thromobotic Microangiopathy (TMA). James N George M.D., Carla Nester M.S., M.D., Topic last updated March 29, 2019. 
• UpToDate. Treatment and Prognosis of Shiga Toxin-Producing Escherichia Coli (STEC) Hemolytic Uremic Solution (HUS) in Children. Patrick Niaudet M.D., Olivia Boyer M.D., PhD. Topic last updated February 5, 2019. 
• UpToDate. Treatment of Acute Exacerbations of Multiple Sclerosis in Adults. Michael J. Olek D.O., Jonathan Howard M.D., October 9, 2018. 
• UpToDate. Management of Refractory Pemphigus Vulgaris and Pemphigus Foliaceus. Michael Hertl M.D., Rudiger Eming M.D., Topic last updated September 13, 2018. 
• UpToDate. HLA Desensitization in Kidney Transplantation. Edmund Huang M.D., Stanley C. Jordan M.D., FASN, FAST. Topic last updated March 20, 2019. 
• Yu X, Gan L, Wang Z, et. al. Chemotherapy with or without plasmapheresis in acute renal failure due to multiple myeloma: a meta analysis. Int J Clin Pharmacol Ther 2015 May;53(5):391-7. PMID 25816886
• Weiss PF, Klink AJ, Friedman DF, et. al. Pediatric therapeutic plasma exchange indications and patterns of use in U.S. children’s hospitals. J Clinc Apher 2012;27(6):287-94. PMID 22811262
• 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 2014 Dec 20;18(6):699 PMID 25527094
• Hildebrand AM, Huang SH, Clark WF. Plasma exchange for kidney disease. What is the best evidence? Adv Chronic Kidney Dis 2014 Mar;21(2):217-27
• Pagano MB, Murinson BB, Tobian AA, et. al. Efficacy of therapeutic plasma exchange for treatment of stiff person syndrome. Transfusion 2014 Jul;54(7):1851-6. PMID 24527774
• Click B, Ketchum AM, Turner R, et, al. The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: A systematic review. Pancreatology 2015 Jul-Aug;15(4):313-20. PMID 25800175
• Stork AC, Lunn MP, Nobile-Orazio E, et. al. Treatment of IgG and IgA paraproteinamic neuropathy. Cochran Database Syst Rev 2015 Mar 24(3):CD005376. PMID 25803231
• Kronbichler A, Brezina B, Quintana LF, et, al. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythematosus and antiphospholipid syndrome: a systematic review. Autoimmun Rev 2016 Jan;15(1):38-49. PMID 26318215
• Zeiler FA, Matuszczak M, Teitelbaum J, et. al. Plasmapheresis for refractory status epilepticus, part I: A scoping systematic review of the adult literature. Seizure 2016 Dec;43:14-22. PMID 27792912
• Zeiler FA, Matuszczak M, Teitelbaum J, et. al. Plasmapheresis for refractory status epilepticus part II: A scoping systematic review of the pediatric literature. Seizure 2016 Dec;43:61-68. PMID 27888743
• Ridel C, Kissling S, Mesnard L, et. al. Plasma exchange in nephrology: indications and technique. Nephrol Ther 2017 Feb;13(1):43-55. PMID 28110970
• Joglkar K, Brannick B, Kadaria D, et. al. Therapeutic plasmapheresis for hypertriglyceridemia-associated acute pancreatitis: case series and review of the literature. Ther Adv Endocrinol Metab 2017 Apr;8(4):59-65. PMID 2857728
• Tyler K, Vollmer T. To PLEX or not to PLEX in natalizumab-associated PML. Neurology March 21 2017;88 (12)
• Padmanabhan A, Connelly-Smith L, 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 of Apheresis: The Eighth Special Issue J Clin Apher May 2019;34:171-354
• Colvin M, Cook J, Chang P, et, al. Sensitization in heart transplantation: emerging knowledge. Circulation 20189;139:e553-e578
• Kobashigawa J, Patel J, Kittleson M, et. al. The long-term outcome of treated sensitized patients who undergo heart transplantation. Clin Transplant 2011;25(1)
• Colvin M, Cook J, Chang P. Antibody mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management. Circulation 2015;131:1608-1639
• Kittleson M, Kobashigawa J. Management of the healthy sensitized patient awaiting heart transplant. American College of Cardiology.
• Kobashigawa J, Colvin M, Potena L, et. al. The management of antibodies in heart transplantation: an ISHLT consensus document. The Journal of Heart and Lung Transplantation May 2018 Volume 37 Issue 5 537-547
• Abdo AS, Cook DJ, McCarthy JF, et. al. The Journal of Heart and Lung Transplantation February 2001 Volume 20 Issue 2 194
• Leech SH, Lopez-Cepero M, LeFor WM, et. al. Management of the sensitized cardiac recipient: the use of plasmapheresis and intravenous immunoglobulin. Clin Transplant 2006 Jul-Aug;20(4):476-84. PMID 16842525
• Crabbe A, McNeil J, Deshpande S, et. al. Therapeutic plasma exchange in heart transplantation: role of coagulation assessment with throboelastometry. JA Clin Rep 2016;2(1):31
• Chih S,  Patel J. Desensitization strategies in adult heart transplantation will persistence pay off? The Journal of Heart and Lung Transplantation Vol 35 No 8 August 2016
• Geft D, Kobashigawa J. Current concepts for sensitized patients before transplantation. Curr Opin Organ Transplant 2017 Jun;22(3):236-241. PMID 28306593
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• UpToDate. Acute Cardiac Allograft Rejection: Diagnosis. Howard J. Eisen M.D., FACC, FAHA, FAST. Topic last updated June 27, 2018.
• UpToDate. Prevention and Treatment of Antibody Mediated Rejection of the Renal Allograft. Arjang Djamali M.D., MS, FASN, Daniel C. Brennan M.D., FACP.
• UpToDate. Evaluation and Treatment of Acute Lung Transplant Rejection. Joseph Pilweksi M.D. Topic last updated October 9, 2018.
• UpToDate. Evaluation and Treatment of Antibody Mediated Lung Transplant Rejection. Ramsy R. Hachem M.D.. Topic last updated July 15, 2019.
• UpToDate. Acute Cardiac Allograft Rejection: Treatment. Howard J. Eisen M.D., FACC, FAHA, FAST. Topic last updated January 5, 2018.
• UpToDate. Pancreas Allograft Rejection. Tarek Alhamad M.D., MS, FACP, FASN, Aleksandra Kukla M.D., Robert J. Stratta, M.D., Topic last updated May 24, 2018.
• UpToDate. Babesiosis: Treatment and Prevention. Peter J. Krause M.D., Edouard G. Vannier PhD. Topic last updated January 30, 2020. 
• Colvin MM, Cook JL, Chan P, et. al. Antibody-mediated rejection in cardiac transplantation emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation 2015;Apr 2
• American Society for Apheresis. Covid-19 Connections.
• UpToDate. Therapeutic Apheresis (Plasma Exchange or Cytaphersis): Indications and Technology. Joy L. Fridey M.D., Andere A. Kaplan M.D.. Topic last updated February 5, 021.
• Khamis F, Al-Zakwani I, Hashmi S, et. al. Therapeutic plasma exchange in adults with sever Covid-19 infection. Int J Infect Dis 2020 Oct;99:214-218. PMID 32585284
• Felsenstein S, Herbet J, McNamara P, et.al. COVID-19 Immunology and Treatment Options. Clin Immunol 2020 Jun;215:108448. PMID 32353634
• Keith P, Wells A, Hodges J. et. al. The therapeutic efficacy of adjunct therapeutic plasma exchange for septic shock with multiple organ failure: a single-center experience. Crit Care 2020;24:518 PMID 32831133
• Ma J, Xia P, Zhou Y, et.al. Potential effect of blood purification therapy in reducing cytokine storm as a last complication of critically ill Covid-19. Clin Immunol 2020 May:214:108408. PMID 32247038
• Shi J, Zhou C, He P, et. al. Successful treatment with plasma exchange followed by intravenous immunoglobulin in a critically ill patient with Covid-19. Int J Antimicrob Agents 2020 Aug;56(2): 105974
• Yang XH, Sun RH, Zhao MY, et. al. Expert recommendations on blood purification treatment protocol for patients with sere Covid-19. Chronic Dis Transl Med 2020 Jun;6(2): 106-114. PMID 32346492
• Zhang L, Zhai H, Ma S, et. al. Efficacy of therapeutic plasma exchange in severe Covid-19 patients. Br J Haematol 2020 May 26: 10.1111/bjh. 16890. PMID 32453903 

 

Policy History:

• May 2021 - Annual Review, Policy Revised
• May 2020 - Annual Review, Policy Revised
• September 2019 - Interim Review, Policy Revised
• May 2019 - Annual Review, Policy Revised
• 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.

 

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