Clinical UM Guideline

 

Subject: Therapeutic Apheresis
Guideline #: CG-MED-68 Publish Date:    12/27/2017
Status: New Last Review Date:    11/02/2017

Description

This document addresses therapeutic apheresis, a procedure by which blood is removed from the body, separated into components, manipulated and returned to the individual.  There are multiple pheresis procedures that are performed.  The therapeutic apheresis procedures addressed in this document utilize devices approved by the United States (U.S.) Food & Drug Administration (FDA) and include the following subcategories:

Note: Please see the following related documents for additional information:

Clinical Indications

Medically Necessary:

  1. Plasmapheresis or plasma exchange is considered medically necessary for any of the following conditions listed in alphabetical order below:
    1. Acute inflammatory demyelinating polyradiculoneuropathy / Guillain-Barre syndrome
    2. Anti-glomerular basement membrane disease (Goodpasture's syndrome) when the individual is dialysis-independent and there is evidence of diffuse alveolar hemorrhage (DAH)
    3. Anti-neutrophil cytoplasmic antibodies (ANCA)-associated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis; and microscopic polyangiitis)
    4. Atypical hemolytic uremic syndrome (aHUS) with Factor H autoantibodies or complement gene mutation
    5. Autoimmune hemolytic uremic syndrome- severe cold agglutin disease
    6. Catastrophic antiphospholipid syndrome (CAPS)
    7. Chronic inflammatory demyelinating polyneuropathy
    8. Cryoglobulinemia, symptomatic/severe
    9. H.E.L.L.P syndrome of pregnancy (hemolysis, elevated liver enzymes, low platelets)
    10. Hyperviscosity syndromes associated with monoclonal gammopathies (such as, multiple myeloma and Waldenström’s macroglobulinemia)
    11. Multiple myeloma cast nephropathy (acute renal failure secondary to multiple myeloma)
    12. Multiple sclerosis (MS)-acute central nervous system (CNS) inflammatory demyelinating disease
    13. Myasthenia gravis that is moderate to severe or prior to thymectomy
    14. N-methyl D-aspartate receptor antibody encephalitis
    15. Neuromyelitis optica spectrum disorders, acute disease (excluding maintenance therapy)
    16. Paraproteinemic demyelinating neuropathies/ chronic acquired demyelinating polyneuropathies; associated with IgA, IgG or IgM monoclonal gammopathy of undetermined significance (MGUS) (excluding multiple myeloma, anti-myelin-associated glycoprotein (MAG) neuropathy or multifocal motor neuropathy (MMN))
    17. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) exacerbation
    18. Progressive multifocal leukoencephalopathy (nataluziamab associated)
    19. Sydenham’s chorea
    20. Systemic lupus erythematosus - for individuals with severe or life-threatening symptoms when conventional therapy has failed to prevent clinical deterioration
    21. Thrombotic microangiopathy secondary to ticlopidine or malignancy
    22. Thrombotic Thrombocytopenic Purpura (TTP)
    23. Transplantation when any of the following are met:
      1. Hematopoietic stem cell transplant
        1. ABO incompatible; or
        2. Human leukocyte antigen (HLA) incompatibility with haplo-type transplant
      2. Solid organ transplantation for any of the following:
        1. Heart transplantation recipients who are in the operating room experiencing a hyper-acute rejection episode; or
        2. Liver transplantation from a live donor with ABO incompatibility; or
        3. Renal transplant recipients who are post-transplant and experiencing recurrent focal and segmental glomerulosclerosis (FGS) or experiencing a humoral or antibody mediated rejection; or
        4. Renal transplantation in highly sensitive kidney transplant candidates (high PRA protocols) to reduce the number of antibodies reactive against human lymphocyte antigens (HLA); or
        5. Renal transplantation, from a live donor with ABO incompatibility or positive cross-match, where a non-reactive live or cadaveric donor is unavailable; or
    24. Voltage gated potassium channel antibodies
    25. Wilson’s disease – fulminant
  2. Low-density lipid (LDL) apheresis is considered medically necessary for individuals with any of the following:
    1. Homozygous familial hypercholesterolemia;
    2. Severe, refractory heterozygous familial hypercholesterolemia who have failed a 6-month trial of diet therapy and maximum tolerated combination drug therapy AND who meet either of the following FDA-approved indications:
      1. Functional hypercholesterolemic heterozygotes with low-density lipoprotein (LDL) that is greater than 300 mg/dL; or
      2. Functional hypercholesterolemic heterozygotes with LDL that is greater than 200 mg/dL and documented coronary artery disease
    3. Lipoprotein (a) hyperlipoproteinemia
  3. Cytapheresis:
    1. Erythrocytapheresis (or phlebotomy) is considered medically necessary as a treatment for any of the following:
      1. Hereditary hemochromatosis
      2. Polycythemia vera
      3. Symptomatic secondary polycythemia
      4. Porphyra cutanea tarda
    2. Leukocytapheresis is considered medically necessary for leukemias with leukostasis
    3. Lymphapheresis is considered medically necessary when used to collect autologous T-cells for chimeric antigen receptor (CAR) T cell therapy when the criteria within the specific CAR-T therapy document are met.
    4. Thrombocytapheresis is considered medically necessary for essential thrombocytosis (symptomatic, when the platelet count is greater than 1,000,000/mm3)
    5. Red blood cell exchange is considered medically necessary as treatment for any of the following:
      1. Babesiosis:
        1. Severe
        2. In the high-risk population
      2. Severe malaria
      3. Sickle cell disease, acute:
        1. Acute stroke
        2. Acute severe, chest syndrome
        3. Multi-organ failure syndrome
        4. Pre-procedure preparation (surgery or hematopoietic stem cell transplant)
        5. Pregnancy
      4. Sickle cell disease, chronic exchange or non-acute:
        1. Stroke prophylaxis (primary or secondary)
        2. Iron overload
  4. Immunoadsorption is considered medically necessary for individuals with either of the following:
    1. Thrombotic Thrombocytopenic Purpura (TTP); or
    2. Moderate to severe rheumatoid arthritis in adult patients with long-standing disease who have failed or are intolerant to disease-modifying antirheumatic drugs such are methotrexate, hydroxychloroquine, sulfasalazine, gold, azathioprine, D-penicillamine, etanercept, infliximab and leflunomide.

Not Medically Necessary:

  1. Plasmapheresis or plasma exchange is considered not medically necessary the criteria above are not met and all other indications including, but not limited to:
    1. Acute disseminated encephalomyelitis
    2. Acute liver failure
    3. Amyloidosis, systemic
    4. Amyotrophic lateral sclerosis (ALS)
    5. Anti-glomerular basement membrane disease (Goodpasture's syndrome) when the individuals is dialysis-dependent and there is no evidence of diffuse alveolar hemorrhage (DAH)
    6. Aplastic anemia
    7. Autoimmune hemolytic anemia (AHA) –warm autoimmune hemolytic anemia (WAHA)
    8. Burn shock resuscitation
    9. Chronic fatigue syndrome
    10. Chronic focal encephalitis (Rasmussen encephalitis)
    11. Coagulation factor inhibitors, alloantibody and autoantibody
    12. Dermatomyositis
    13. Heart (cardiac) transplantation –  for desensitization, positive cross-match due to donor specific HLA antibody or antibody mediated rejection
    14. Hemolytic Uremic Syndrome (aHUS), with MCP mutations
    15. Hemolytic Uremic Syndrome associated with infection (such as shiga toxin or Streptococcus pneumonae)
    16. Henoch-Schonlein purpura
    17. Heparin induced thrombocytopenia
    18. Hypertriglyceridemic pancreatitis
    19. Immune complex rapidly progressive glomerulonephritis
    20. Immune thrombocytopenia, refractory
    21. Immunoglobulin A nephropathy – crescentic and chronic progressive
    22. Inclusion body myositis
    23. Lambert-Eaton myasthenic syndrome
    24. Liver transplantation – desensitization from a deceased donor and for humor rejection
    25. Lung transplant allograft rejection (antibody mediated rejection)
    26. Lupus nephritis
    27. Multiple sclerosis that is chronic progressive or secondary progressive multiple sclerosis
    28. Nephrogenic systemic fibrosis
    29. Neuromyelitis optica ([NMO], also known as Devic’s disease), when used as maintenance therapy
    30. Overdose of drugs or poisoning – envenomation and mushroom
    31. Paraneoplastic neurological syndromes
    32. Paraproteinemic demyelinating polyneuropathy associated with multiple myeloma, anti-myelin-associated glycoprotein (MAG) neuropathy or multifocal motor neuropathy (MMN)
    33. Pemphigus vulgaris
    34. Phytanic acid storage disease (Refsum’s Disease) when used to rapidly lower plasmic phytanic acid levels during acute attacks
    35. POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes)
    36. Polymyositis
    37. Post transfusion purpura
    38. Psoriasis
    39. Red cell alloimmunization in pregnancy, prior to intrauterine transfusion availability
    40. Schizophrenia
    41. Scleroderma (progressive systemic sclerosis)
    42. Sepsis with multi-organ failure
    43. Stiff-person syndrome
    44. Sudden sensorineural hearing loss
    45. Thrombotic microangiopathy, for drugs other than ticlopidine: for example, clopidogrel, cyclosporine, gemcitabine, quinine, or tacrolimus
    46. Thyroid storm
    47. Toxic epidermal necrolysis
  2. Low-density lipid apheresis is considered not medically necessary for all indications not meeting the criteria above including, but not limited to:
    1. Peripheral vascular disease (PVD)
    2. Phytanic Acid Storage Disease (Refsum Disease)
    3. Sudden sensorineural hearing loss
  3. Selective high-density lipid (HDL) delipidation and therapeutic apheresis is considered not medically necessary for all indications.
  4. Cytapheresis is considered not medically necessary for all indications not meeting the criteria above including, but not limited to:
    1. Dermatomyositis
    2. Hyperleukocytosis, (asymptomatic)
    3. Inclusion body myositis
    4. Polymyositis
    5. Psoriasis
  5. Thrombocytapheresis is considered not medically necessary when the criteria above are not met and for all other indications.
  6. Immunoadsorption pheresis * is considered not medically necessary for all indications not meeting the criteria above, including, but not limited to:
    1. Autoimmune diseases other than rheumatoid arthritis
    2. Chronic focal encephalitis (Rasmussen Encephalitis)
    3. Coagulation factor inhibitors alloantibody and autoantibody
    4. Cryoglobulinemia, symptomatic or severe
    5. Immune thrombocytopenia, refractory
    6. Multiple sclerosis – acute CNS inflammatory demyelinating disease
    7. Paraneoplastic neurological syndromes
    8. Paraproteinemic demyelinating neuropathies associated with IgA, IgG or IgM monoclonal gammopathy
    9. Pemphigus vulgaris
    10. Treatment of cancer

*This refers to immunoadsorption specifically.  For indications meeting medical necessity criteria for apheresis, please refer to Medically Necessary Section I.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

Plasmapheresis, plasma exchange

CPT

 

36514

Therapeutic apheresis; for plasma pheresis

 

 

ICD-10 Procedure

 

6A550Z3

Pheresis of plasma, single

6A551Z3

Pheresis of plasma, multiple

 

 

ICD-10 Diagnosis

 

A81.2

Progressive multifocal leukoencephalopathy

B95.0-B95.1

Streptococcus group A/B, as the cause of diseases classified elsewhere [PANDAS]

C88.0

Waldenström macroglobulinemia

C90.00-C90.02

Multiple myeloma

D47.2

Monoclonal gammopathy

D59.0-D59.1

Autoimmune hemolytic anemias

D59.3

Hemolytic uremic syndrome

D68.61

Antiphospholipid syndrome

D89.1

Cryoglobulinemia

D89.89

Other specified disorders involving the immune mechanism, not elsewhere classified [when specified as PANDAS]

E83.01

Wilson’s disease

F42.8

Other obsessive-compulsive disorder [specified as PANDAS]

G04.81

Other encephalitis and encephalomyelitis [specified as NMDA receptor antibody encephalitis]

G13.1

Other systemic atrophy primarily affecting central nervous system in neoplastic disease [limbic encephalopathy, voltage gated potassium channel (VGKC) antibody syndrome)

G35

Multiple sclerosis

G36.0

Neuromyelitis optica [Devic]

G37.0-G37.9

Other demyelinating diseases of central nervous system

G60.8

Other hereditary and idiopathic neuropathies [Morvan’s disease, VGKC antibody syndrome]

G61.0

Guillain-Barre syndrome

G61.81-G61.89

Other inflammatory polyneuropathies

G70.00-G70.01

Myasthenia gravis

G71.19

Other specified myotonic disorders [neuromyotonia, VGKC antibody syndrome]

I02.0-I02.9

Rheumatic chorea [Sydenham’s chorea]

M31.0

Hypersensitivity angiitis [Goodpasture’s syndrome]

M31.1

Thrombotic microangiopathy [includes TTP]

M31.31

Wegener’s granulomatosis with renal involvement

M31.7

Microscopic polyangiitis

M32.0-M32.9

Systemic lupus erythematosus (SLE)

N01.0-N01.9

Rapidly progressive nephritic syndrome

N03.0-N03.9

Chronic nephritis syndrome

N04.0-N04.9

Nephrotic syndrome

N17.0-N17.9

Acute kidney failure

N18.1-N18.9

Chronic kidney disease

N19

Unspecified kidney failure

O14.20-O14.25

HELLP syndrome

T86.00-T86.09

Complications of bone marrow transplant

T86.10-T86.19

Complications of kidney transplant

T86.21

Heart transplant rejection

T86.40-T86.49

Complications of liver transplant

T86.5

Complications of stem cell transplant

Z94.0

Kidney transplant status

Z94.1

Heart transplant status

Z94.4

Liver transplant status

Z94.81

Bone marrow transplant status

Z94.84

Stem cells transplant status

Low density lipid apheresis and Immunoadsorption pheresis

CPT

 

36516

Therapeutic apheresis; with extracorporeal immunoadsorption, selective adsorption or selective filtration and plasma reinfusion

0342T

Therapeutic apheresis with selective HDL delipidation and plasma reinfusion
Note:  apheresis with selective HDL delipidation is considered Not Medically Necessary for all indications

 

 

HCPCS

 

S2120

Low density lipoprotein (LDL) apheresis using heparin-induced extracorporeal LDL precipitation

 

 

ICD-10 Diagnosis

 

E78.00

Pure hypercholesterolemia, unspecified

E78.01

Familial hypercholesterolemia

M05.00-M05.9

Rheumatoid arthritis with rheumatoid factor

M06.00-M06.09

Rheumatoid arthritis without rheumatoid factor

M06.80-M06.9

Other specified and unspecified rheumatoid arthritis

M31.1

Thrombotic microangiopathy [TTP]

Z83.42

Family history of familial hypercholesterolemia

Cytapheresis

CPT

 

36511

Therapeutic apheresis; for white blood cells

36512

Therapeutic apheresis; for red blood cells [red blood cell exchange]

36513

Therapeutic apheresis; for platelets

 

 

ICD-10 Procedure

 

6A550Z0

Pheresis of erythrocytes, single

6A550Z1

Pheresis of leukocytes, single

6A550Z2

Pheresis of platelets, single

6A551Z0

Pheresis of erythrocytes, multiple

6A551Z1

Pheresis of leukocytes, multiple

6A551Z2

Pheresis of platelets, multiple

 

 

ICD-10 Diagnosis

 

B50.0-B54

Malaria

B60.0

Babesiosis

C82.00-C82.99

Follicular lymphoma [related to CAR-T cell therapy]

C83.30-C83.39

Diffuse large B-cell lymphoma [related to CAR-T cell therapy]

C85.20-C85.29

Mediastinal (thymic) large B-cell lymphoma [related to CAR-T cell therapy]

C90.00-C95.92

Leukemias [related to CAR-T cell therapy]

D45

Polycythemia vera

D47.3

Essential (hemorrhagic) thrombocythemia

D57.00-D57.819

Sickle-cell disorders

D75.1

Secondary polycythemia

E80.1

Porphyria cutanea tarda

E83.110

Hereditary hemochromatosis

O99.011-O99.03

Anemia complicating pregnancy, childbirth and the puerperium

Discussion/General Information

Description of Pheresis Techniques
Applications of pheresis can be broadly subdivided into three general categories: acute, self-limited diseases, acute, fulminant exacerbations of chronic diseases, and chronic diseases.  In self-limited diseases and acute exacerbations of chronic diseases, therapeutic apheresis is used to acutely lower the circulating pathogenic substance.  In chronic diseases, there is ongoing production of pathogenic autoantibodies.  Because therapeutic apheresis does not address the underlying pathology, and due to the phenomenon of rebound antibody production, its use in most chronic diseases has been less effective than in acute, self-limiting diseases.  For this reason, chronic conditions are not amenable to pheresis treatment.  As an example, individuals with chronic progressive or relapsing-remitting multiple sclerosis are unlikely to benefit from pheresis treatment.  However, individuals with an acute central nervous system inflammatory demyelinating disease (including the rare proportion of individuals with multiple sclerosis who suffer from this condition) have been found to have a reduction of symptoms.

The goal of pheresis 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 apheresis include toxins, metabolic substances, and plasma components, such as complement or antibodies.  Therefore, diseases thought to be caused by these abnormal constituents might best be treated with this form of therapy.  Diseases benefiting from these procedures are largely autoimmune or neurological disorders. Pheresis techniques are not intended to be curative treatments for most indications.  Rather, they are used to address related symptoms.  Depending on the indication, alternative treatments, such as pharmacologic therapy, may be available.

Pheresis procedures 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 clotting factors.  Therefore, pheresis procedures should be performed by appropriately-trained clinicians in a setting that can respond to medical emergencies at all times.

Evidence in peer-reviewed, published medical literature and medical society guidelines support the clinical effectiveness and safety of therapeutic pheresis modalities for the indications listed in the policy statements.  There is evidence for the accepted indications that the use of this procedure can result in an improvement in symptoms, primarily for acute self-limited conditions, and subsequently for an improvement in quality of life.  Evidence is limited regarding the role of therapeutic apheresis to remove specific autoantibodies, proteins and complements in the pathogenesis of many other conditions.  

The Guidelines on the Use of Therapeutic Apheresis in Clinical Practice (Seventh special issue) were updated by the American Society for Apheresis (ASFA) in 2016.  Therapeutic apheresis is a general term which includes all apheresis based procedures used in a therapeutic manner.  This involves the individual’s blood being passed through an external device which separates blood into components as treatment of a disease.  Specific ASFA definitions for the therapeutic modalities addressed in this document are as follows (Schwartz, 2016):

Erythrocytapheresis: procedure in which blood of the patient or donor is passed through a medical device which separates RBCs from other components of blood, the RBCs are removed and replaced with crystalloid or colloid solution, when necessary.

Immunoadsorption: A therapeutic procedure in which plasma of the patient, after separation from the blood, is passed through a medical device which has the capacity to remove immunoglobulins by specifically binding them to the active component (e.g., Staphylococcal protein A) of the device.

Leukocytapheresis: A procedure in which blood of the patient or the donor is passed through a medical device which separates out white blood cells (e.g., leukemic blasts or granulocytes), collects the selected cells and returns remainder of the patient’s or the donor’s blood with or without addition of replacement fluid such as colloid and/or crystalloid solution. This procedure can be used therapeutically or in preparation of blood components.

Low-density lipid apheresis: The selective removal of low density lipoproteins from the blood with the return of the remaining components. A variety of instruments are available which remove LDL cholesterol based upon charge (dextran sulfate and polyacrylate), size (double-membrane filtration), precipitation at low pH (HELP), or immunoadsorption with anti-Apo B-100 antibodies.

Protein A column pheresis (extracorporeal immunoadsorption [ECI]) consists of highly purified protein A bonded to a silica matrix.  Plasma is collected from the individual in a pheresis procedure and then is passed over the column (Prosorba®, Fresenius Medical Care, Lexington, MA). Circulating immune complexes and specific immunoglobulins bind to the protein A column and are thus selectively removed from the plasma.  The plasma is returned to the individual, thus eliminating the need for a plasma exchange.  Pathogenic levels of immunoglobulins and circulating immune complexes are associated with a number of diseases such as idiopathic thrombocytopenic purpura, hemolytic uremic syndrome, and red cell aplasia.

Red blood cell (RBC) Exchange:  A therapeutic procedure in which blood of the patient is passed through a medical device which separates RBCs from other components of blood, the RBCs are removed and replaced with donor RBCs and colloid solution.

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

Thrombocytapheresis:  A therapeutic procedure in which blood of the patient is passed through a medical device which separates out platelets, removes the platelets and returns remainder of the patient’s blood with or without addition of replacement fluid such as colloid and/or crystalloid solution.

The ASFA utilizes categories and grade of recommendation for various indications.  The four categories are (Schwartz, 2016):

Category I

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

Category II

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

Category III

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

Category IV

Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful.  Institutional Review Board (IRB) approval is desirable if apheresis treatment is undertaken in these circumstances.

The Grading Recommendations include the following (Schwartz, 2016):

Recommendation

Description

Methodological quality of supporting evidence

Grade 1A

Strong recommendation, high-quality evidence

Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies

Grade 1B

Strong recommendation, moderate quality evidence

RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies

Grade 1C

Strong recommendation, low-quality or very low-quality evidence

Observational studies or case series

Grade 2A

Weak recommendation, high quality evidence

RCTs without important limitations or overwhelming evidence from observational studies

Grade 2B

Weak recommendation, moderate-quality evidence

RCTs with important limitations (inconsistent results, methodological flaws, indirect, or imprecise) or exceptionally strong evidence from observational studies

Grade 2C

Weak recommendation, low-quality or very low-quality evidence

Observational studies or case series

Plasma Pheresis and Plasma Exchange
The ASFA recommends plasmapheresis or plasma exchange as Categories I-II treatment options and the associated levels of evidence range with Grade 1A – 1C recommendations for the following indications (Schwarz, 2016):

In addition to the above ASFA recommendations, published peer-reviewed literature and/or specialty medical societies support the use therapeutic apheresis when there is evidence that a targeted component(s) of the blood or plasma is readily removed with therapeutic apheresis and there is sufficient improvement in clinical symptoms without causing serious adverse effects.

Acute inflammatory demyelinating polyneuropathy (AIDP)/ Guillain-Barre Syndrome (GBS)
The American Academy of Neurology (AAN) (Cortese, 2011) published an updated evidence-based guideline on plasmapheresis in neurologic disorders.  Plasmapheresis was recommended in the treatment of “AIDP/GBS severe enough to impair independent walking or to require mechanical ventilation (Level A).  Plasmapheresis should be considered in the treatment of milder clinical presentations (Level B).”  In a consensus statement by the American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM) Committee (Donofrio, 2009), treatment of GBS in adults, particularly those who require an aid to walk (disability grade ≥ 2) within 2 weeks of the onset of symptoms with IVIG was recommended.  The committee noted based on randomized trials, similar functional improvements in individuals treated with IVIG or plasmapheresis.  Data did not support the combination of IVIG and plasmapheresis to treat GBS.

Atypical Hemolytic Uremic Syndrome (aHUS)
Atypical HUS is a rare genetic and chronic blood disease that can lead to renal failure and is associated with increased risk of stroke and death.  Prompt diagnosis is essential, as aHUS is aggressive and treatment can be initiated for affected individuals.  According to Loirat (2011), the diagnosis of aHUS relies on: 1) no associated disease; 2) investigations for Shiga toxin E. coli infection at onset of aHUS with no evidence of a Shiga-toxin/EHEC positive test (stool culture and polymerase chain reaction for Shiga-toxins; serology for anti-lipopolysaccharides antibodies); and 3) ADAMTS 13 (A Disintegrin-like And Metalloprotease with ThromboSpondin type 1 motif 13) determination as manifestations of aHUS and TTP may overlap.  Frequent causes of aHUS involve complement regulatory abnormalities such as factor H mutations and MCP mutations.  Plasma exchange can replace mutated circulating complement factors, specifically factor H.  However, plasma exchange does not demonstrate similar efficacy for individuals with isolated MCP mutations, and plasma exchange is not recommended to treat MCP aHUS.  Based on expert consensus opinion, plasma therapy has demonstrated efficacy as the first-line treatment for aHUS and should be started as early as possible, typically within 24 hours of presentation (Ariceta, 2009; Lapeyraque, 2011; Loirat, 2011; Taylor 2010).

Autoimmune Hemolytic Uremic Syndrome – Severe Cold Agglutin Disease
Individuals with autoimmune hemolytic anemia may be classified into warm or cold autoantibody types.  Those with cold agglutin disease (CAD) have IgM autoantibodies that target red blood cells when the temperatures are typically between 0–5 degrees Celsius.  Avoiding exposure to cold temperatures is the primary treatment. However, for severe disease, immunosuppression with targeted therapy and anti-lymphoma chemotherapy may be used.  Specialty input recommends use of plasmapheresis or plasma exchange to treat autoimmune hemolytic uremic syndrome with severe cold agglutin disease.

Catastrophic Antiphospholipid Syndrome (CAPS)
ASFA (Schwartz, 2016) defines CAPS as the acute onset of multiple thromboses in at least three organ systems over a period of days or weeks, in individuals with antiphospholipid antibodies.  European Forum on Antiphospholipid Antibodies maintains a registry of individuals with CAPS due to the rarity of the disease.  Data from the registry documented higher survival rates related to the increased frequency of combination therapy including anticoagulants, glucocorticoids and plasma exchange and/or intravenous immune globulin (Cervera, 2012).  Specialty input recommends use of plasmapheresis or plasma exchange to treat CAPS.

Cryoglobulinemia
Cryoglobulins, single or mixed immunoglobulins may precipitate at low temperatures and can deposit in the vessels and tissues of the body.  The increase of cryoglobulins can increase the viscosity of the circulating blood and may cause vasculitis and obstruct vessels, causing organ damage.  Cryoglobulinemia involves the presence of cryoglobins in the blood and typically occurs concomitantly with other conditions such as viral hepatitis, lymphoproliferative and autoimmune disorders.  Treatment includes addressing the underlying concomitant disorder, suppression of the immune response, and plasmapheresis for severe or life-threatening complications. The AFSA recommendation for plasmapheresis or plasma exchange is a category II with an evidence level of 2A.

Hyperviscosity syndromes associated with monoclonal gammopathies
The National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology (NCCN Guidelines® V.2.2018) on multiple myeloma recommend plasmapheresis as an adjunctive therapy for symptomatic hyperviscosity.  The guideline also notes, “Institutions differ in their use of plasmapheresis for adjunctive treatment of renal dysfunction.”  The recommendation to improve renal function by utilizing plasmapheresis is a category 2B recommendation.

Myeloma Cast Nephropathy
The formation of casts in the distal tubules of the kidneys is thought to be due to an increase in light chain concentrations typically seen with tumor progression (Schwartz, 2016).  Primary therapy typically involves chemotherapy and intravenous fluid to increase the alkaline levels and to dissolve the light chains.  The ASFA recommendation was a category II with a level of evidence 2B.  However, specialty input recommended use of plasmapheresis or plasma exchange to treat multiple myeloma cast nephropathy.

Multiple Sclerosis – Acute CNS inflammatory demyelinating disease
The ASFA recommends the use of plasmapheresis or plasma exchange to treat acute CNS inflammatory demyelinating disease associated with multiple sclerosis (Schwartz, 2016).  The AAN has a Level B recommendation for plasmapheresis as adjunctive treatment of exacerbations in relapsing forms of MS.  Based on Level A evidence, the AAN states, “Plasmapheresis should not be offered for chronic progressive or secondary progressive MS” (Cortese, 2011).

PANDAS
Although ASFA (Schwartz, 2016) provides a Category II recommendation grade 1B level of evidence for plasmapheresis or plasma exchange as a treatment for PANDAS and Sydenham’s chorea, there is still conflicting information in the published literature.  The AAN guideline on plasmapheresis in neurologic disorders (Cortese, 2011) stated there is “insufficient evidence to support or refute the use of plasmapheresis in the treatment of acute obsessive compulsive disorders (OCD) and tic symptoms in the setting of PANDAS.”  Swedo and colleagues (2012) proposed a set of diagnostic criteria for Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) as modified from PANDAS criteria.  The authors noted this new set of criteria would need to be validated in large trials.  In a retrospective review in a large metropolitan area, Gabbay (2008) reported significant over diagnosis of PANDAS and subsequent therapies that included plasma exchange.

Sydenham’s chorea
ASFA (Schwartz, 2016) provides a Category III recommendation grade 2B level of evidence for plasmapheresis or plasma exchange as a treatment for Sydenham’s chorea, there is still conflicting information in the published literature. Sydenham’s chorea is an autoimmune neuropsychiatric disorder that manifests after an acute bout of rheumatic fever.  Symptoms include rapid and jerky, involuntary movements that may affect the face, trunk and extremities, which may prevent independent activities of daily living.  Chorea is usually treated with neuroleptics, valproic acid and corticosteroids.  Sydenham’s chorea is thought to be an autoimmune disorder based on the presence of antibodies that react with neuronal tissue that control motor activity (Garvey, 2005; National Institute of Neurological Disorders and Stroke [NINDS], 2007).  The AAN guideline (Cortese, 2011) noted there is “Insufficient evidence to support or refute the use of plasmapheresis in the treatment of Sydenham chorea.” The NINDS notes there is no specific treatment for Sydenham’s chorea.

Systemic Lupus Erythematosus (SLE) - Severe
Circulating autoantibodies and immune complexes along with complement deposition results in injury to the cell and tissue for individuals with SLE.  Immunosuppressive agents and targeted therapies are used to treat SLE.  Specialty input recommends therapeutic plasmapheresis or plasma exchange for those with severe or life-threatening symptoms and conventional therapies have failed to prevent clinical deterioration.

Thrombotic Microangiopathy (TMA)
TMA is a rare medical condition involving small blood vessel damage from blood clots, usually as a result of other complex and serious illnesses.  There are various syndromes such as HUS and TTP that involve TMA as a component of the specific syndrome, but are classified separately based on additional clinical indications (Loriat, 2011).

Transplantation
Approximately 20% of individuals waiting for cadaveric renal transplantation have high cytotoxic antibody titers rendering them at high risk for hyperacute and acute allograft rejection.  Plasma exchange and immunoadsorption have been utilized as a means of removing these antibodies prior to transplantation resulting in significant reductions in the level of antibodies.  When used in individuals with recurrent FSGS, pheresis induced a decrease in urinary protein.  Additionally, randomized controlled trials have been conducted establishing the efficacy of plasma exchange in the treatment of biopsy proven acute antibody mediated renal allograft rejection  The literature on pheresis for the treatment of chronic rejection is limited to a few uncontrolled studies with modest and transient results. 

Other Indications
Additional ASFA indications for plasma pheresis or plasma exchange were of lower levels of evidence and/or the optimum role of therapy could not be established; or the evidence demonstrated the therapy could be ineffective or harmful.  These indications are listed by categories:

Plasmapheresis or plasma exchange treatment options with Category I-II recommendation and levels of evidence ranging from Grade 2A – 2C include the following indications (Schwartz, 2016):

Plasmapheresis or plasma exchange treatment options with Category IV recommendations were provided for the following indications (Schwartz, 2016):

Immune thrombocytopenia
Immune thrombocytopenia has a widely accepted abbreviation, ITP, and is also known as “immune thrombocytopenic purpura and idiopathic thrombocytopenic purpura.”  The most recent name “immune thrombocytopenia” is based on an international work group to standardize the terminology and definitions of ITP (Neunert, 2011; Rodeghiero, 2009).  The 2011 evidence-based practice guideline for ITP does not include any form of therapeutic apheresis as a recommended treatment (Neunert, 2011).

Lupus Nephritis
The ASFA lists the use of plasmapheresis or plasma exchange treatment options with a Category IV recommendation and level of evidence Grade 1B.  This recommendation was based on a controlled study that showed no benefit of adding therapeutic plasmapheresis or plasma exchange to prednisone and cyclophosphamide for individuals with severe lupus nephritis, these findings were supported by smaller, later trials. (Schwartz, 2016). While a 2010 RCT suggested that adjunctive IA and TPE were equally effective in reducing systemic lupus erythrematosus Disease Activity Index (SLEDAI) scores, the ASFA did not change their recommendation. American College of Rheumatology (ACR) guidelines for screening, treatment and management of lupus nephritis do not include the use of plasmapheresis or plasma exchange as treatment modalities (Hahn, 2012).  Similarly, the Joint European League Against Rheumatism and European Renal Association-European dialysis and Transplant Association (EULAR/ERA-EDTA) (Bertsias, 2012) do not include the use of plasmapheresis or plasma exchange as a recommended treatment for the management of adult or pediatric lupus nephritis.

Phytanic Acid Storage Disease (Refsum’s disease)
Refsum Disease, or phytanic acid storage disease, is a rare genetic disease where individuals lack the enzyme to break down phytanic acid found in certain foods.  This excess phytanic acids accumulate in the brain, blood and other tissues, with can cause blindness and arrhythmias in the heart.  Avoidance of foods such as dairy products, beef, lamb, and fatty fish (e.g., tuna, cod and haddock) is the primary treatment.  When there is excessive buildup of phytanic acid, plasma exchange has been utilized with some improvement in symptoms, but vision and hearing problems persisted (NINDS, 2011).

Stiff Person (Man) Syndrome
Also known as Stiff-Man Syndrome, the classic features of this syndrome include painful muscular spasms associated with muscular stiffness, often times impairing the ability to walk.  This syndrome is a rare, chronic but usually not progressive disorder.  Published literature includes case reports with mixed results (Schwartz, 2016). 

Lipid apheresis – Low- and High-density
Low-density apheresis

Low-density lipoprotein apheresis describes a variety of technologies used to acutely remove low-density lipoprotein (LDL) from the plasma.  The individual initially undergoes an apheresis procedure to isolate the plasma.  The low-density lipoproteins are then selectively removed from the plasma by either immunoadsorption, heparin-induced extracorporeal LDL precipitation (also referred to as HELP), or dextran sulfate adsorption. In immunoadsorption, polyclonal antihuman apoB antibodies from sheep selectively bind and remove LDL.  (ApoB is the protein moiety of low-density lipoprotein.)  In HELP, LDL and other particles containing ApoB are precipitated by heparin at an acidic pH. Dextran sulfate adsorption removes LDL by binding the positively charged apoB to dextran sulfate particles bound to cellulose. LDL apheresis is a selective procedure in which only pathogenic low-density lipoproteins are removed.  The plasma is then returned to the individual.  Examples of two LDL-apheresis systems currently FDA-approved for use in the United States are the Heparin-Induced Extracorporeal LDL Cholesterol Precipitation (H.E.L.P.) system (B. Braun Medical Inc., Bethlehem, PA) and the LipoSorber® system (Kaneka Pharma America Corporation, New York, NY).

The ASFA recommends low density lipoprotein (LDL) apheresis as Categories I-II treatment options and the associated level of Grade 1A (strong recommendation, high-quality evidence) (Schwartz, 2016). 

Familial hypercholesterolemia is an autosomal, co-dominant inherited disorder of lipoprotein metabolism that features mutations in the LDL-receptor gene.  Due to reduced or absent LDL receptors, low-density lipoprotein cholesterol (LDLc) is not effectively cleared by the liver, resulting in very high plasma concentration in the circulating blood.  LDLc deposits can be found in the tendons (tendon xanthomas) and arterial walls, and may be associated with an increased risk of early onset of atherosclerosis and premature coronary heart disease (CHD.)  The estimated frequency is 1:500 for heterozygotes, and 1:1,000,000 for homozygotes.  Recommendations noting individual selection criteria regarding when treatment should be initiated vary between sources.  

Individuals with homozygous hypercholesterolemia are treated aggressively to prevent or slow the progression of cardiovascular disease (CVD) due to the prolonged high lipid level exposure since birth (Robinson, 2013).  Statins and other agents along with diet and lifestyle modifications are recommended to lower TC. In addition, a new class of drugs, proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors were recently approved by the FDA to treat   familial hypercholesterolemia have been shown to aggressively lower LDL levels. LDL apheresis may be used to selectively lower LDLc to optimal levels. 

High-density lipid (HDL) apheresis
Autologous apheresis with selective HDL delipidation and infusion of selected preβ-HDL is being evaluated as a method to reduce atherosclerosis in individuals at high-risk for cardiovascular disease (CVD).  The selective removal of cholesterol from HDL (α-HDL), also called delipidation, involves exposing the plasma to organic solvents in the proprietary collection device and the process of returning the resulting small form of HDL (β-HDL).  A randomized, placebo-controlled study examined the safety of a device called LS PDS-2 (Lipid Sciences Plasma Delipidation System-2; Life Sciences, CA) that does not have U.S. Food & Drug Administration approval at this time.  A total of 28 individuals with acute coronary syndrome (ACS) who were scheduled for diagnostic cardiac catherization were enrolled and 26 participants completed all of the treatments and visits.  Treatment involved HDL selected apheresis once every 7 days, for a total of 7 treatments.  Fourteen individuals randomized to the treatment arm completed the 7-week selective HDL delipidation treatment period and 12 individuals assigned to the control arm completed the placebo treatment period.  Preβ-HDL was evaluated by electrophoresis and quantitative analysis.  On average, preβ-HDL was increased by 28 times in post-delipidated plasma compared to baseline volume.  Intravascular ultrasound (IVUS) of the target vessel was performed and a nonsignificant reduction in the volume of the atheroma was reported in the delipidated group versus the placebo group.  Fifteen of the participants had 1 or more adverse events, with a total of 38 reported adverse events.  Hypotension was the most common adverse event.  The authors noted limitations to the study included a small sample size and majority of the participants on the trial were also on statin therapy.  Additionally, the authors noted “It is not clear whether acute regression of atherosclerotic burden will be associated with decreased clinical cardiovascular events.” (Waksman, 2010). The evidence does not support that there are improved net clinical health outcomes in individuals treated with therapeutic apheresis combined with selective HDL delipidation.  Subedi and associates (2014) notes that further evaluation regarding the association between HDL and ASCVD is needed.  The 2016 ASFA guidelines do not address HDL lipid apheresis.

Cytapheresis
Erythrocytapheresis
The ASFA recommends erythrocytapheresis with Category I and the associated Grade 1B level of evidence (strong recommendations, moderate quality evidence) treatment options were listed for the following indications (Schwartz, 2016):

The ASFA notes management of individuals with low risk polycythemia vera (PV) include maintaining hematocrit ≤ 45% with phlebotomy and low dose aspirin.  Individuals with high risk are treated with phlebotomy, aspirin and other cytoreductive agents.  Cytapheresis is recommended to correct hyperviscosity as an alternative to emergent large-volume phlebotomy (Schwartz, 2016).

Specialty input recommends use of erythrocytapheresis to treat symptomatic secondary polycythemia vera and porphyria cutanea tarda.  Porphyria is a group of rare disorders where he process of heme production is affected.  Porphyria cutanea tarda is the most common type of porphyria. 

Leukocytapheresis
Leukocytapheresis with Category II recommendations were provided for the following indications (Schwartz, 2016):

Leukocytapheresis with Category III recommendations were provided for the following indications (Schwartz, 2016):

Leukocytapheresis with Category IV recommendations were provided for the following indications (Schwartz, 2016):

RBC exchange
The ASFA recommends RBC exchange with Category I-II and the associated Grade 1A -2C level of evidence treatment options were listed for the following indications (Schwartz, 2016):

RBC exchange with Category III and an associated Grade 2B level of evidence  was listed for the following indication (Schwartz, 2016):

Additional indications were recommended by specialty input using RBC exchange for the following indications:

Thrombocytapheresis
Thrombocytapheresis with Category II with “weak recommendation, low-quality or very low-quality evidence” or Category III recommendations were provided for the following indications (Schwartz, 2016):

Immunoadsorption Pheresis
Immunoadsorption pheresis with Category II 2b recommendations were provided for the following indications (Schwartz, 2016):

Immunoadsorption pheresis with Category III recommendations were provided for the following indications (Schwartz, 2016):

The ACR 2002 Update of the Rheumatoid Arthritis Guidelines note use of Staphylococcal protein A immunoadsorption column, “should be considered only for patients with refractory rheumatoid arthritis in whom treatment with several disease modifying anti-rheumatic drugs (DMARDs) has failed.”  This recommendation was based on the improvement in 31.9% of the participants treated with the immunoadsorption column compared to 11.4% who received sham treatment in a randomized, multicenter trial (Felson, 1999).  The 2015 ACR guidelines do not mention IA for the treatment of RA. There have been a few other older studies which support use of IA in the treatment of RA (Furst, 2000; Poullin, 2005).

The peer-reviewed medical literature supports the clinical effectiveness and safety of immunoadsorption for the indications listed in the policy statements.  Most studies to date have supported the use of this procedure for individuals with hemolytic uremic syndrome and TTP resulting in a reduction of symptoms.  Furthermore, the safety and efficacy of immunoadsorption has been well established in individuals with HUS, TTP, in post kidney transplant recipients with recurrent focal and segmental glomerulosclerosis (FGS).  The current research does not support the benefits of immunoadsorption in other immune-related disorders.

There are ongoing clinical trials reviewing the use of the various forms of therapeutic apheresis modalities for multiple indications.  Based on the data from the published studies and specialty consensus input, therapeutic apheresis modalities are considered medically necessary for selected indications.  Conditions which have been evaluated by the AFSA and have been found to be lacking data showing the efficacy or clinical utility of apheresis or conditions which have not been evaluated by the AFSA and there is a lack of published data showing improved clinical outcomes associated with apheresis when compared to alternative treatments are considered not medically necessary.

Definitions

Antibodies: Immunoglobulins (a specialized immune protein) produced as a result of the introduction of an antigen into the body.

Autoimmune disease: An illness occurring when the body tissues are attacked by its own immune system; as a result, individuals with these diseases frequently have unusual antibodies circulating in their blood that target their own body tissues. 

Bullous pemphigoid: A disease characterized by tense blistering eruptions of the skin, generally caused by antibodies abnormally accumulating in a layer of the skin.

Cerebritis: Inflammation of the brain.

Cryoglobulinemia: The presence of abnormal proteins called cryoglobulins that, by definition, have the unusual properties of precipitating from the blood serum when it is chilled and re-dissolving upon rewarming.

Cytapheresis: Subtype of therapeutic apheresis in which the white blood cells are isolated and retained (leukapheresis or lymphocytopheresis) or red blood cells are isolated and retained (erythrocytapheresis).

Guillain-Barre: A condition that usually occurs after an infection; the signs and symptoms include loss of sensation in the arms and legs and increasing weakness.

Heterozygotes: A person possessing two different forms of a particular gene, one inherited from each parent.

Homozygotes: A person who has two identical forms of a particular gene, one inherited from each parent.

Immune complex: A combination of an antibody (immunoglobulin), and an antigen (the target that the antibody is attacking).

Immune thrombocytopenic purpura: A condition in which antibodies destroy the cells in the body that is responsible for blood clotting (platelets).

Immunoglobulin: A protein produced by plasma cells and lymphocytes; immunoglobulins are an essential part of the body's immune system which attach to foreign substances, such as bacteria, and assist in destroying them.

Myocarditis: Inflammation of the heart muscle.

Nephritis: Inflammation of the kidney.

Pemphigus vulgaris: An autoimmune disease of the skin, with blistering.

Polymyositis: A chronic inflammatory disease of muscle that begins when white blood cells spontaneously invade muscles, which may result in severe muscle pain, tenderness and weakness.

PRA: Panel reactive antibodies.

Pure red cell aplasia: A condition where an individual has an inability to produce red blood cells.

Regional enteritis: Also called Crohn’s disease, a chronic inflammatory disease of the intestine primarily in the small and large intestines but which can occur anywhere in the digestive system between the mouth and the anus.

Scleroderma: A disease of connective tissue resulting in formation of scar tissue in the skin and at times other organs of the body.

Segmental glomerulosclerosis: An illness that occurs when scar tissue forms in some of the glomeruli (structures involved in the filtration of blood) of the kidney.

Thymectomy: Removal of the thymus gland.

Vasculitis: A general term for a group of uncommon diseases characterized by inflammation of the blood vessels.

Waldenström’s macroglobulinemia: A disease where abnormal white blood cells produce excessive amounts of antibodies; bleeding and enlarged liver and spleen may be seen.

References

Peer Reviewed Publications:

  1. Allen ES, Stroncek DF, Ren J, et al. Autologous lymphapheresis for the production of chimeric antigen receptor T cells. Transfusion. 2017; 57(5):1133-1141.
  2. Ariceta G, Besbas N, Johnson S, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009; 24(4):687-696.
  3. Bayraktaroğlu Z, Demirci F, Balat O, et al. Plasma exchange therapy in HELLP syndrome: a single-center experience. Turk J Gastroenterol. 2006; 17(2):99-102.
  4. Bunchorntavakul C, Reddy KR. Pruritus in chronic cholestatic liver disease. Clin Liver Dis. 2012; 16(2):331-346.
  5. Carr RA, Rejowski BJ, Cote GA, et al. Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology? Pancreatology. 2016; 16(4):469-476.
  6. Cervera R. 8th International Congress on Autoimmunity: new perspectives for refractory catastrophic antiphospholipid syndrome. Expert Rev Clin Immunol. 2012; 8(7):617-619.
  7. Cervera R, Espinosa G. Update on the catastrophic antiphospholipid syndrome and the “CAPS Registry.” Semin Thromb Hemost. 2012; 38(4):333-338.
  8. Clark WF. Plasma exchange for renal disease: evidence and use 2011. J Clin Apher. 2012; 27(3):112-116.
  9. Clark WF. Thrombotic microangiopathy: current knowledge and outcomes with plasma exchange. Semin Dial. 2012; 25(2):214-219.
  10. Donofrio PD, Berger A, Brannagan TH 3rd, et al. Consensus statement: the use of intravenous immunoglobulin in the treatment of neuromuscular conditions report of the AANEM AD HOC committee. American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Muscle Nerve. 2009; 40(5):890–900.
  11. Eser B, Guven M, Unal A, et al. The role of plasma exchange in HELLP syndrome. Clin Appl Thromb Hemost. 2005; 11(2):211-217.
  12. Felson DT, LaValley MP, Baldassare AR, et al. The Prosorba column for treatment of refractory rheumatoid arthritis: a randomized, double-blind, sham-controlled trial. Arthritis Rheum. 1999; 42(10):2153-2159.
  13. Gabbay V, Coffey BJ, Babb JS, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcus: comparison of diagnosis and treatment in the community and at a specialty clinic. Pediatri. 2008; 122(2):273-278.
  14. Gendreau RM.; Prosorba Clinical Trial Group. A randomized double-blind sham-controlled trial of the Prosorba column for treatment of refractory rheumatoid arthritis. Ther Apher. 2001; 5(2):79-83.
  15. Habermalz B, Sauerland S. Clinical effectiveness of selective granulocyte, monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis. Dig Dis Sci. 2010; 55(5):1421-1428.
  16. Jaben EA, Winters JL. Plasma exchange as a therapeutic option in patients with neurologic symptoms due to antibodies to voltage-gated potassium channels: a report of five cases and review of the literature. J Clin Apher. 2012; 27(5):267-273.
  17. Kohler W, Bucka C, Klingel R. A randomized and controlled study comparing immunoadsorption and plasma exchange in myasthenic crisis. J Clin Apher. 2011; 26(6):347-355.
  18. Lapeyraque AL, Malina M, Fremeaux-Bacchi V, et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med. 2011; 364(26):2561-2563.
  19. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011; 6:60.
  20. Morgan SM, Shaz BH, Pavenski K, et al. The top clinical trial opportunities in therapeutic apheresis and neurology. J Clin Apher. 2014; 29(6):331-335.
  21. Ramos-Casals M, Stone JH, Cid MC, Bosch X. The cryoglobulinaemias. Lancet. 2012; 379(9813):348-360.
  22. Subedi BH, Joshi PH, Jones SR, e al. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions. Vasc Health Risk Manag. 2014; 10:205-216.
  23. Swedo SE, Leckman JF, Rose NR. From research subgroup to clinical syndrome: modifying the PANDAS criteria to describe PANS (Pediatric Acute-onset Neuropsychiatric Syndrome). Pediatr Therapeut. 2012; 2(2):113.
  24. Tan J., Smith CH, Goldman, RD. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections. Can Fam Physician. 2012; 58(9):957-959.
  25. Taylor CM, Machin S, Wigmore SJ, Goodship TH. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol. 2010; 148(1):37-47.
  26. Uslu-Gökceoğlu A, Doğan CS, Comak E, et al. Atypical hemolytic uremic syndrome due to factor H antibody. Turk J Pediatr. 2013; 55(1):86-89.
  27. Waksman R, Torguson R, Kent KM, et al. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010; 55(24):2727-2735.
  28. Weiss PF, Klink AJ, Friedman DF, Feudtner C. Pediatric therapeutic plasma exchange indications and patterns of use in U.S. children's hospitals. J Clin Apher. 2012; 27(6):287-294.
  29. 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; 53(5):391-397.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. American College of Rheumatology. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. 2015 Available at: http://www.rheumatology.org/Portals/0/Files/ACR%202015%20RA%20Guideline.pdf. Accessed on October 9, 2017.
  2. Ariceta G, Besbas N, Johnson S, et al.; European Paediatric Study Group for HUS. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009; 24(4):687-696.
  3. Carless PA, Rubens FD, Anthony DM, et al. Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011;(3):CD004172.
  4. Centers for Medicare and Medicaid Services. National Coverage Determination for Apheresis (Therapeutic Pheresis). NCD#110.14 Effective July 30, 1992. Available at: http://www.cms.hhs.gov/mcd/index_list.asp?list_type=ncd#PP. Accessed on October 9, 2017.
  5. Colvin MM, Cook JL, Chang P, et al; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiopulmonary Critical Care, Perioperative and Resuscitation; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Disease in the Young; American Heart Association Heart Failure and Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiovascular and Stroke Nursing; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Radiology and Intervention; American Heart Association Heart Failure and Transplantation Committee of the Council on Cardiovascular Surgery and Anesthesia. Antibody-mediated rejection in cardiac transplantation: emerging knowledge in diagnosis and management: a scientific statement from the American Heart Association. Circulation. 2015; 131(18):1608-1639.
  6. Cortese I, Chaudhry V, So YT, et al. Evidence-based guideline update: plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.  Neurology. 2011; 76(3):294-300.
  7. Costanzo MR, Dipchand A, Starling R, et al. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010; 29(8):914-956.
  8. Furst D, Felson D, Thoren G, Gendreau RM. Immunoadsorption for the treatment of rheumatoid arthritis: final results of a randomized trial. Prosorba Trial Investigators. Ther Apher. 2000; 4(5):363-373.
  9. Gabbay V, Coffey BJ, Babb JS, et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcus: comparison of diagnosis and treatment in the community and at a specialty clinic. Pediatrics. 2008; 122(2):273-278.
  10. Gordon PA, Winer JB, Hoogendijk JE, Choy EH. Immunosuppressant and immunomodulatory treatment for dermatomyositis and Polymyositis. Cochrane Database Syst Rev. 2012;(8):CD003643.
  11. Hahn BH, McMahon MA, Wilkinson A, et al. American College of Rheumatology Guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken). 2012; 64(6):797-808.
  12. Hughes RA, Bouche P, Cornblath DR, et al. European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2006; 13(4):326-332.
  13. Ito MK, McGowan MP, Moriarty PM; National Lipid Association Expert Panel on Familial Hypercholesterolemia. Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on familial hypercholesterolemia. J Clin Lipidol. 2011; 5(3 Suppl):S38-S45.
  14. Jacobson TA, Maki KC, Orringer CE, et al; NLA Expert Panel. National Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2. J Clin Lipidol. 2015; 9(6 Suppl):S1-S122.e1.
  15. Medical Advisory Secretariat. Low density lipoprotein apheresis: an evidence-based analysis. Ontario Health Technology Assessment Series. 2007; 7(5).
  16. Mehndiratta MM, Hughes RA, Pritchard J. Plasma exchange for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2015;(8):CD003906.
  17. National Heart Lung and Blood Institute (NHLBI). Integrated guidelines for cardiovascular health and risk reduction in children and adolescents. January 2013. Available at: http://www.nhlbi.nih.gov/guidelines/cvd_ped/index.htm. Accessed on November 3, 2017.
  18. National Institutes of Health (NIH). Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Panel III). 2002. Available at: http://www.nhlbi.nih.gov/files/docs/guidelines/atp3xsum.pdf. Accessed on November 3, 2017.
  19. NCCN Clinical Practice Guidelines in Oncology® (NCCN). © 2017 National Comprehensive Cancer Network, Inc. Multiple Myeloma (V.2.2018). Revised October 2, 2017. For additional information visit the NCCN website: http://www.nccn.org. Accessed on November 2, 2017.
  20. Neunert C, Lim W, Crowther M, et al. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood. 2011; 117(16):4190-4207.
  21. Nordestgaard BG, Chapman MJ, Humphries SE, et al.; European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013; 34(45):3478-3490.
  22. Poullin P, Announ N, Mugnier B, Guis S, Roudier J, Lefèvre P. Protein A-immunoadsorption (Prosorba column) in the treatment of rheumatoid arthritis. Joint Bone Spine. 2005; 72(2):101-103.
  23. Robinson JG. Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Manag Care Pharm. 2013; 19(2):139-149.
  24. Schwartz J, Padmanabhan A, Aqui N, Balogun RA, Connelly-Smith L, Delaney M, Dunbar NM, Witt V, Wu Y, Shaz BH. 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; 31(3):149-162.
  25. Smith JW, Weinstein R, Hillyer KL.; AABB Hemapheresis Committee; American Society for Apheresis. Therapeutic apheresis: a summary of current indication categories endorsed by the AABB and the American Society for Apheresis. Transfusion. 2003; 43(6):820-822.
Websites for Additional Information
  1. National Institute of Medicine. MEDLINEplus. Medical Encyclopedia. Available at: https://medlineplus.gov/encyclopedia.html. Accessed on October 10, 2017.
  2. National Institute of Neurological Disorders and Stroke (NINDS). NINDS Disease Information. Available at:  https://www.ninds.nih.gov/Disorders/All-Disorders. Accessed on October 10, 2017.
    • Polymyositis Information Page
    • Refsum Disease Information Page
    • Sydenham Chorea Information Page
Index

Adacolumn
Apheresis, therapeutic
Cellsorba®
Cytapheresis
Immunoadsorption
LDL apheresis
Lipsorb®
Pheresis
Plasma Exchange
Plasmapheresis
Prosorba®
Protein A column
Selective HDL delipidation

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

New

11/02/2017

Medical Policy & Technology Assessment Committee (MPTAC) review. Initial document development.

New

11/01/2017

Hematology/Oncology Subcommittee review. Initial document development. Moved content of MED.00113 Therapeutic Apheresis to new clinical utilization management guideline document with the same title. Added medically necessary indications for N-methyl D-aspartate receptor antibody encephalitis, progressive multifocal leukoencephalopathy and apheresis as a component of CAR-T therapy. Revised medically necessary indications for polyneuropathy, glomerulonephritis, neuromyelitis optica disorders and paraproteinemic demyelinating neuropathies. Updated Coding section with 01/01/2018 CPT descriptor change for code 36516 and removed code 36515 deleted 12/31/2017.