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Therapeutic Apheresis

by Ravindra Sarode, MD

Therapeutic apheresis includes plasma exchange and cytapheresis, which are generally tolerated by healthy donors. However, many minor and a few major risks exist. Insertion of the large IV catheters necessary for apheresis can cause complications (eg, bleeding, infection, pneumothorax). Citrate anticoagulant may decrease serum ionized Ca. Replacement of plasma with a noncolloidal solution (eg, saline) shifts fluid from the intravascular space. Colloidal replacement solutions do not replace IgG and coagulation factors.

Most complications can be managed with close attention to the patient and manipulation of the procedure, but some severe reactions and a few deaths have occurred.

Plasma exchange

Therapeutic plasma exchange removes plasma components from blood. A blood cell separator extracts the patient’s plasma and returns RBCs and platelets in plasma or a plasma-replacing fluid; for this purpose, 5% albumin is preferred to fresh frozen plasma (except for patients with thrombotic thrombocytopenic purpura) because it causes fewer reactions and transmits no infections. Therapeutic plasma exchange resembles dialysis but, in addition, can remove protein-bound toxic substances. A one-volume exchange removes about 66% of such components.

To be of benefit, plasma exchange should be used for diseases in which the plasma contains a known pathogenic substance, and plasma exchange should remove this substance more rapidly than the body produces it. For example, in rapidly progressive autoimmune disorders, plasma exchange may be used to remove existing harmful plasma components (eg, cryoglobulins, antiglomerular basement membrane antibodies) while immunosuppressive or cytotoxic drugs suppress their future production.

There are numerous indications (see Table: Indications for Plasma Exchange According to the American Society for Apheresis). (See also Guidelines on the Use of Therapeutic Plasma Exchange .) The frequency of plasma exchange, the volume to be removed, the replacement fluid, and other variables are individualized. Low density lipoprotein cholesterol can be selectively removed from plasma by adsorption over a column (called LDL apheresis). In photopheresis, mononuclear cells are selectively removed by centrifugation and treated with photoactivatable drugs (eg, 8-methoxypsoralen) that are then activated with ultraviolet light; it is a form of chemotherapy. In immunoadsorption, an antibody or antigen is removed from plasma by combining with an antigen or antibody chosen to bind the target antibody or antigen over a column. Complications of plasma exchange are similar to those of therapeutic cytapheresis.

Indications for Plasma Exchange According to the American Society for Apheresis


Plasma Exchange


I. Accepted as 1st-line therapy, either alone or with other treatment

ANCA-mediated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis, formerly Wegener granulomatosis), in patients on dialysis or with diffuse alveolar hemorrhage

Antiglomerular basement membrane antibody disease (Goodpasture syndrome), in patients on dialysis or with diffuse alveolar hemorrhage

Chronic inflammatory demyelinating polyradiculoneuropathy

Cryoglobulinemia, severe

Focal, segmental glomerulosclerosis, recurrent

Guillain-Barre syndrome

Hemolytic-uremic syndrome, atypical due to autoantibody to factor H

Hyperviscosity in monoclonal gammopathies

Liver transplantation, for desensitization, living donor when there is ABO incompatibility

Myasthenia gravis

PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) exacerbation

Paraproteinemic polyneuropathy with IgG/IgA, IgM (with or without macroglobulinemia [Waldenström macroglobulinemia])

Renal transplantation, antibody-mediated rejection (with ABO compatible donor) or for desensitization with living donor with ABO or donor-specific HLA incompatibility

Sydenham chorea

Thrombotic microangiopathy, ticlopidine-associated

Thrombotic thrombocytopenia purpura

Wilson disease, fulminant

Babesiosis, severe: RBC exchange

Cutaneous T-cell lymphoma, erythrodermic with mycosis fungoides or Sézary syndrome: Photopheresis

Familial hypercholesterolemia (homozygotes): LDL apheresis

Hereditary hemochromatosis: RBC depletion

Hyperleukocytosis with leukostasis syndrome: Leukodepletion

Polycythemia vera: RBC depletion

Sickle cell disease with acute stroke: RBC exchange

II. Accepted as 2nd-line therapy, either alone or with other treatment

Antiphospholipid syndrome, catastrophic

Autoimmune hemolytic anemia, cold agglutinin disease (life threatening)

Encephalomyelitis, acute disseminated

Familial hypercholesterolemia (homozygotes with small blood volume)

Hematopoietic stem cell transplantation in which recipient has anti-A or anti-B antibodies incompatible with donor (bone or peripheral blood stem cells)

Hemolytic-uremic syndrome, due to complement factor gene mutation

Lambert-Eaton syndrome

Mushroom poisoning, severe (eg, Amanita phalloides poisoning)

Multiple sclerosis, acute inflammatory

Myeloma (cast nephropathy)

Neuromyelitis optica, acute

Phytanic acid storage disease (Refsum disease)

Renal transplantation, ABO incompatible with humoral rejection

SLE if severe (eg, cerebritis, diffuse alveolar hemorrhage)

Voltage gated K+ channel antibodies (eg, neuromyotonia, limbic encephalitis, Morvan syndrome)

Babesiosis in high-risk patients (eg, immunosuppressed, age > 50): RBC exchange

Cardiomyopathy, dilated (NYHA class II to IV): Immunoadsorption

Cryoglobulinemia, severe or symptomatic: Immunoadsorption

Familial hypercholesterolemia (heterozygotes): LDL apheresis

Graft vs host disease, skin (acute or chronic): Photopheresis

Heart transplant rejection (treatment or prophylaxis): Photopheresis

Lipoprotein A hyperlipoproteinemia: LDL apheresis

Lung transplant, allograft rejection (bronchiolitis obliterans syndrome): Photopheresis

Malaria, severe: RBC exchange

Phytanic acid storage disease (Refsum disease): LDL apheresis

Sickle cell disease with acute chest syndrome, for prophylaxis of stroke (primary or secondary ), or for prevention of transfusional iron overload: RBC exchange

Thrombocytosis, symptomatic: Platelet depletion

Ulcerative colitis: Adsorptive cytapheresis

III. Optimal role of apheresis is not established; decision should be individualized (IRB approval desirable)

ANCA-mediated rapidly progressive glomerulonephritis (granulomatosis with polyangiitis), dialysis-independent and without diffuse alveolar hemorrhage

Anemia, pure red cell aplasia

Aplastic anemia

Autoimmune hemolytic anemia, warm

Burn shock resuscitation

Cardiomyopathy, idiopathic dilated (NYHA class II to IV)

Coagulation factor inhibitor, autoantibody

Encephalitis, chronic focal (Rasmussen encephalitis)


Guillain-Barre syndrome (after IV immune globulin given)

Heart transplant, rejection (antibody mediated) or desensitization when incompatibility due to donor-specific HLA antibody

Hemolytic-uremic syndrome (associated with Streptococcus pneumoniae)

Immunoglobulin A–associated vasculitis (formerly, Henoch-Schönlein purpura), crescentic or severe extra-renal disease

Heparin-induced thrombocytopenia (with thrombosis or before cardiopulmonary bypass)

Hypertriglyceridemic pancreatitis

Immune complex-mediated rapidly progressive glomerulonephritis

Immunoglobulin A nephropathy (crescentic or chronic progressive)

Liver failure, acute

Liver transplantation, ABO incompatible (humoral rejection or for desensitization with a deceased donor)

Lung transplantation with antibody-mediated rejection

Multiple myeloma with polyneuropathy

Multiple sclerosis (chronic progressive)

Nephrogenic systemic fibrosis

Neuromyelitis optica, maintenance treatment

Paraneoplastic neurologic syndromes

Pemphigus vulgaris, severe

Posttransfusion purpura

Progressive multifocal leukoencephalopathy associated with natalizumab

Progressive systemic sclerosis

Red cell alloimmunization in pregnancy (before intrauterine transfusion available)

Renal transplantation with ABO compatibility (for desensitization, deceased donor with high panel reactive antibody)

Sensorineural hearing loss, sudden

Sepsis with multiple organ failure

Stiff-person syndrome

Thrombotic microangiopathy associated with clopidogrel, cyclosporine, or tacrolimus

Thrombotic microangiopathy, refractory, associated with hematopoietic stem cell transplantation

Thyroid storm

Toxic epidermal necrolysis, refractory

Coagulation factor inhibitors (autoantibody or alloantibody): Immunoadsorption

Crohn disease: Photopheresis

Cutaneous T-cell lymphoma, non-erythrodermic with mycosis fungoides or Sézary syndrome: Photopheresis

Encephalitis, chronic focal (Rasmussen encephalitis): Immunoadsorption

Erythrocytosis, secondary: RBC depletion

Hyperleukocytosis, prophylaxis of leukostasis: Leukodepletion

Immune thrombocytopenia, refractory: Immunoadsorption

Inflammatory bowel disease (Crohn disease or ulcerative colitis): Adsorptive cytapheresis

Multiple sclerosis, acute inflammatory: Immunoadsorption

Graft vs host disease, non-skin: Photopheresis

Hematopoietic peripheral stem cell transplantation with minor ABO incompatibility (donor anti-A or anti-B antibodies): RBC exchange

Nephrogenic systemic fibrosis: Photopheresis

Paraneoplastic neurologic syndromes: Immunoadsorption

Paraproteinemic polyneuropathy with IgG/IgA, IgM (with or without macroglobulinemia): Immunoadsorption

Pemphigus vulgaris, severe: Photophoresis and/or immunoadsorption

Peripheral vascular disease: LDL apheresis

Psoriasis: Photopheresis and/or lymphocyte depletion

Psoriasis, disseminated pustular: Adsorptive cytapheresis

Progressive systemic sclerosis: Photopheresis

Sensorineural hearing loss, sudden: LDL apheresis

Sickle cell disease with hepatic or splenic sequestration, intrahepatic cholestasis, multiple organ failure, priapism, painful vaso-occlusive episode, or before surgery: RBC exchange

Tacrolimus poisoning: RBC exchange

IV. Published evidence demonstrates or suggests apheresis ineffective or harmful.

Amyloidosis, systemic

Amyotrophic lateral sclerosis

Coagulation factor inhibitors, (alloantibody)

Dermatomyositis or polymyositis

Hemolytic-uremic syndrome, atypical due to CD64 mutations or associated with Shiga toxin (diarrhea)

Immune thrombocytopenia, refractory

Inclusion-body myositis

POEMS (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome



Renal transplantation, ABO incompatible with group A2/A2b into B, deceased donor


SLE nephritis

Thrombotic microangiopathy associated with gemcitabine or quinine

Dermatomyositis or polymyositis: Leukapheresis

Inclusion-body myositis: Leukapheresis

ANCA = antineutrophil cytoplasmic antibody; IRB = institutional review board; LDL = low density lipoprotein cholesterol; NYHA = New York Heart Association.

Data from Schwartz J, Winters JL, Padmanabhan A, 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 sixth special issue. Journal of Clinical Apheresis Jul;28(3):145–284, 2013. doi: 10.1002/jca.21276.


Therapeutic cytapheresis removes cellular components from blood, returning plasma. It is most often used to remove defective RBCs and substitute normal ones in patients with sickle cell anemia who have the following conditions: acute chest syndrome, stroke, pregnancy, or frequent, severe sickle cell crises. RBC exchange achieves Hb S levels of < 30% without the risk of increased viscosity that can occur because of increased Hct with simple transfusion.

Therapeutic cytapheresis may also be used to reduce severe thrombocytosis or leukocytosis (cytoreduction) in acute leukemia or in accelerated or blast crisis phase of chronic myelogenous leukemia when there is risk of hemorrhage, thrombosis, or pulmonary or cerebral complications of extreme leukocytosis (leukostasis). Cytapheresis is effective in thrombocytosis because platelets are not replaced as rapidly as WBCs. One or 2 procedures may reduce platelet counts to safe levels. Therapeutic WBC removal (leukapheresis) can remove kilograms of buffy coat in a few procedures, and it often relieves leukostasis. However, the reduction in WBC count itself may be mild and only temporary.

Other uses of cytapheresis include collection of peripheral blood stem cells for autologous or allogeneic bone marrow reconstitution (an alternative to bone marrow transplantation) and collection of lymphocytes for use in immune modulation cancer therapy (adoptive immunotherapy).

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