Pheresis is a procedure utilizing specialized equipment to remove selected blood constituents (platelets, red blood cells, white blood cells or  plasma) from whole blood and return the remaining constituents to the individual from whom the blood was taken. Different methods of apheresis therapy include pheresis, plasmapheresis, and plasma exchange (PE).

Pheresis therapy may be considered medically necessary when performed for ANY of the following indications:

Plasma exchange for:

• Autoimmune conditions:
  • Catastrophic antiphospholipid syndrome (CAPS); or
  • Severe multiple manifestations of mixed cryoglobulinemia (MC) such as cryoglobulinemic nephropathy, skin ulcers, sensory motor neuropathy, and widespread vasculitis in combination with immunosuppressive treatment; or
  • Systemic lupus erythematosus (SLE), life threatening, as a treatment of last resort; or
• Hematologic conditions:
  • ABO incompatible hematopoietic stem cell transplantation; or
  • Atypical hemolytic-uremic syndrome; or
  • Coagulation factor inhibitors or
  • HELLP syndrome of pregnancy (a severe form of preeclampsia, characterized by hemolysis (H), elevated liver enzymes (EL), and low platelet (LP) counts); or
  • Hyperviscosity syndromes associated with multiple myeloma, Waldenstrom’s hypergammaglobulinemia, or
  • Idiopathic thrombocytopenic purpura in emergency situations; or
  • Myeloma with acute renal failure; or
  • Plasmapheresis in the treatment of pure red cell aplasia unresponsive to steroid and immunosuppressive therapy, or
  • Post-transfusion purpura; or
  • Thrombotic thrombocytopenic purpura (TTP); or
• Neurological conditions:
  • Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP); or
  • Guillain-Barré syndrome; or
  • Multiple sclerosis (MS); acute fulminant central nervous system (CNS) demyelination; or
  • Myasthenia gravis in crisis or as part of preoperative preparation; or
  • Neuromyelitis optica (NMO); or
  • N-methyl-D-aspartate receptor antibody encephalitis; or
  • Paraproteinemia polyneuropathy; IgA, IgG (aka Lamber-Eaton syndrome); or
  • Post-infectious pediatric neurological conditions (PANDAS and Sydenham’s Chorea); or 
• Renal conditions:
  • ANCA (antineutrophil cytoplasmic antibody)-associated vasculitis [e.g., Wegener’s granulomatosis, also known as granulomatosis with polyangitis (GPA)] with associated renal failure; or
  • Anti-glomerular basement membrane disease (Goodpasture’s syndrome); or
  • Dense deposit disease with factor H deficiency and/or elevated C3 Nephritic factor; or
  • IgA nephropathy (Berger’s Disease); or
• Transplant-related conditions:
  • Focal segmental glomerulosclerosis after renal transplant; or
  • Prior to solid organ transplant, treatment of individuals at high risk of antibody-mediated rejection, including highly sensitized individuals, and those receiving an ABO incompatible organ: or
  • Heart (infants); or
  • Kidney; or
• Renal transplantation:
  • Antibody mediated rejection; or
  • Human leukocyte antigen (HLA) desensitization; or
• Apheresis therapy for:
  • Treatment of chronic relapsing polyneuropathy for individuals with severe or life-threatening symptoms who have failed to respond to conventional therapy; or
  • Treatment of life-threatening scleroderma and polymyositis when the individual is unresponsive to conventional therapy; or
• Erythrocytapheresis for:
  • Hereditary Hemochromatosis; or
  • Polycythemia Vera; or
• Leukocytapheresis for:
  • Hyperleukocytosis (symptomatic) such as in chronic myelogenous leukemia (CML); or
• Red Blood Cell (RBC) exchange transfusion for:
  • Acute sickle cell disease; or
  • Non-acute sickle cell disease, stroke prophylaxis, pre-operative, in pregnancy or to reduce pain crises; or
• Pheresis therapy for:
  • Advanced prostate cancer only when used in the development of sipuleucel-T (Provenge); or
  • Atopic dermatitis, recalcitrant; or
  • Cutaneous T-cell lymphoma/mycosis fungoides/Sezary syndrome, Erythrodermic type; or
  • Idiopathic dilated cardiomyopathy; or
  • Pruritis due to hepatobiliary diseases (treatment resistant); or
  • Systemic amyloidosis due to Beta-2 microglobulin; or
  • Toxic epidermal necrolysis (TEN), Refractory; or
  • Voltage-gated potassium channel antibody disease; or
  • Wilson’s disease, fulminant Plasmapheresis therapy for the following conditions:
    • Plasmapheresis or plasma exchange in the last resort treatment of life-threatening rheumatoid vasculitis when all other conventional therapies have failed; or
    • Plasmapheresis in the treatment of pure red cell aplasia unresponsive to steroid and immunosuppressive therapy.

Contraindications/Exclusions: The following are NOT indications for plasma exchange and will be denied as not medically necessary:

• Amyotrophic lateral sclerosis; or 
• Dermatomyositis/polymyositis; or
• Inclusion Body myositis; or
• POEMS syndrome; or
• Rheumatoid arthritis; or
• Schizophrenia.

Pheresis therapy not meeting the criteria as indicated in this policy is considered not medically necessary.

Low-Density Lipid (LDL)

LDL apheresis may be considered medically necessary for ALL of the following indications:

• Individuals with homozygous familial hypercholesterolemia as an alternative to plasmapheresis; or
• Individuals with heterozygous familial hypercholesterolemia who have failed a six (6) month trial of diet therapy, and maximum tolerated combination drug therapy(*), and who meet one of the following FDA-approved indications:
  • Functional hypercholesterolemic heterozygotes with LDL cholesterol greater than 100 mg/dl without coronary artery disease; or
  • Functional hypercholesterolemic heterozygotes with LDL cholesterol greater than 100 mg/dl and documented coronary artery disease.

* Maximum tolerated drug therapy is defined as a trial of drugs from at least two (2) separate classes of hypolipidemic agents such as PSCK9 inhibitors bile acid sequestrants, HMG-CoA reductase inhibitors, fibric acid derivatives, or Niacin/Nicotinic acids.

LDL not meeting the criteria as indicated in this policy is considered not medically necessary.

Extracorporeal Photopheresis (ECP)

ECP may be considered medically necessary for ANY the following indications:

• For treatment of early stage (I or II) cutaneous T-cell lymphoma that is progressive and refractory to established nonsystemic therapies; or
• For treatment of late-stage (III or IV) cutaneous T-cell lymphoma; or
• Individuals with acute cardiac allograft rejection whose disease is refractory to standard immunosuppressive drug treatment; or
• Individuals with acute or chronic graft versus host disease whose disease is refractory to standard immunosuppressive drug treatment; or
• Prior to lung transplantation for the condition bronchiolitis obliterans syndrome.

ECP not meeting the criteria as indicated in this policy is considered not medically necessary.

A cycle of ECP consists of treatment on two consecutive days, once per month. If there is no response to the treatment within six to eight months, the treatment should be stopped.