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Apheresis is derived from a Greek word “aphairesis,” which means “to remove forcibly.” Whole blood is removed from a subject, separated into components extracorporeally (RBCs, white blood cells, platelets, and plasma), desired blood component is removed, and remaining components are returned with or without replacement fluid(s). Therapeutic apheresis (TA) is used to remove pathogenic substances in the plasma (termed therapeutic plasma exchange [TPE]) or pathogenic cells (termed cytapheresis).
Successful use of TA as a treatment modality requires that a disease results from a substance found in plasma (e.g., antibody to acetylcholine receptor in myasthenia gravis) or by a blood component (e.g., hemoglobin S RBCs in sickle cell disease), and that the pathogenic substance or component can be removed efficiently enough to permit resolution of the disease.
McLeod’s criteria to determine TA success in disease treatment consist of three components: (1) disease pathogenesis suggests clear rationale for TA, (2) abnormality meaningfully corrected by TA, and (3) strong evidence TA confers meaningful clinical benefit. American Society for Apheresis (ASFA) publishes an evidence-based guideline for TA use, which is updated every 3 years. It provides an ASFA category ( Table 74.1 ) and grade of recommendation ( Table 74.2 ) for each disease entity. The newest edition (7th edition, 2016) describes 87 diseases and 179 clinical indications ( Table 74.3 ).
Category | Description |
---|---|
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. |
II | Disorders for which apheresis is accepted as second-line therapy, either as a standalone treatment or in conjunction with other modes of treatment. |
III | Optimum role of apheresis therapy is not established. Decision-making should be individualized. |
IV | Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. Institutional review board approval is desirable if apheresis treatment is undertaken in these circumstances. |
Recommendation | Description | Methodological Quality of Supporting Evidence | Implications |
---|---|---|---|
Grade 1A | Strong recommendation, high-quality evidence | Randomized controlled trials (RCTs) without important limitations or overwhelming evidence from observational studies | Strong recommendation, can apply to most patients in most circumstances without reservation |
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 | Strong recommendation, can apply to most patients in most circumstances without reservation |
Grade 1C | Strong recommendation, low-quality or very low-quality evidence | Observational studies or case series | Strong recommendation but may change when higher quality evidence becomes available |
Grade 2A | Weak recommendation, high-quality evidence | RCTs without important limitations or overwhelming evidence from observational studies | Weak recommendation, best action may differ depending on circumstances or patients’ or societal values |
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 | Weak recommendation, best action may differ depending on circumstances or patients’ or societal values |
Grade 2C | Weak recommendation, low-quality or very low-quality evidence | Observational studies or case series | Very weak recommendations; other alternatives may be equally reasonable |
Disease Group/Name/Condition | Therapeutic Apheresis Modality | Category | Recommendation Grade |
---|---|---|---|
Acute Disseminated Encephalomyelitis, Refractory to Steroids | |||
Therapeutic plasma exchange (TPE) | II | 2C | |
Acute Inflammatory Demyelinating Polyradiculoneuropathy (Guillain–Barre Syndrome) | |||
Primary Treatment | TPE | I | 1A |
After IVIG | TPE | III | 2C |
Acute Liver Failure | |||
TPE | III | 2B | |
Plasma exchange, high volume (not in the United States) | I | 1A | |
Age-related macular degeneration, dry | Rheopheresis | I | 1B |
Amyloidosis, systemic | |||
Β 2 microglobulin column | II | 2B | |
TPE | IV | 2C | |
Antineutrophil Cytoplasmic Antibodies (ANCA)-Associated Rapidly Progressive Glomerulonephritis (Granulomatosis With Polyangiitis and Microscopic Polyangiitis) | |||
Dialysis dependence | TPE | I | 1A |
Diffuse alveolar hemorrhage (DAH) | TPE | I | 1C |
Dialysis independence | TPE | III | 2C |
Antiglomerular Basement Membrane Disease (Goodpasture’s Syndrome) | |||
Dialysis dependence | TPE | III | 2B |
DAH | TPE | I | 1C |
Dialysis independence | TPE | I | 1B |
Aplastic Anemia; Pure Red Cell Aplasia | |||
Aplastic anemia | TPE | III | 2C |
Pure red cell aplasia | TPE | III | 2C |
Atopic (Neuro-) Dermatitis (Atopic Eczema), Recalcitrant | |||
ECP | III | 2C | |
IA | III | 2C | |
TPE | III | 2C | |
Autoimmune Hemolytic Anemia: Warm Autoimmune Hemolytic Anemia; Cold Agglutinin Disease | |||
Warm autoimmune hemolytic anemia (severe) | TPE | III | 2C |
Cold agglutinin disease (severe) | TPE | II | 2C |
Babesiosis, Severe | |||
RBC exchange (REX) | II | 2C | |
Burn Shock Resuscitation | |||
TPE | III | 2B | |
Cardiac Neonatal Lupus | |||
TPE | III | 2C | |
Cardiac Transplantation | |||
Cellular/recurrent rejection | ECP | II | 1B |
Rejection Prophylaxis | ECP | II | 2A |
Desensitization | TPE | II | 1C |
Treatment of antibody-mediated rejection | TPE | III | 2C |
Catastrophic Antiphospholipid Syndrome | |||
TPE | II | 2C | |
Chronic Focal Encephalitis (Rasmussen Encephalitis) | |||
TPE | III | 2C | |
Chronic Inflammatory Demyelinating Polyradiculoneuropathy | |||
TPE | I | 1B | |
Coagulation Factor Inhibitors | |||
Alloantibody | TPE | IV | 2C |
Autoantibody | TPE | III | 2C |
Alloantibody | Immunoadsorption (IA) | III | 2B |
Autoantibody | IA | III | 1C |
Complex Regional Pain Syndrome | |||
Chronic | TPE | III | 2C |
Cryoglobulinemia | |||
Symptomatic/severe | TPE | II | 2A |
Symptomatic/severe | IA | II | 2B |
Cutaneous T-Cell Lymphoma; Mycosis Fungoides; Sezary Syndrome | |||
Erythrodermic | ECP | I | 1B |
Nonerythrodermic | ECP | III | 2C |
Dermatomyositis or Polymyositis | |||
TPE | IV | 2B | |
ECP | IV | 2C | |
Dilated Cardiomyopathy, Idiopathic | |||
NYHA II-IV | IA | II | 1B |
NYHA II-IV | TPE | III | 2C |
Erythropoietic Porphyria, Liver Disease | |||
TPE | III | 2C | |
REX | III | 2C | |
Familial Hypercholesterolemia | |||
Homozygotes | Low-density lipoprotein (LDL) apheresis | I | 1A |
Heterozygotes | LDL apheresis | II | 1A |
Homozygotes with small blood volume | TPE | II | 1C |
Focal Segmental Glomerulosclerosis | |||
Recurrent in transplanted kidney | TPE | I | 1B |
Steroid resistant in native kidney | LDL apheresis | III | 2C |
Graft-Versus-Host Disease | |||
Skin (chronic) | ECP | II | 1B |
Nonskin (chronic) | ECP | II | 1B |
Skin (acute) | ECP | II | 1C |
Nonskin (acute) | ECP | II | 1C |
Hashimoto’s Encephalopathy: Steroid-Responsive Encephalopathy Associated With Autoimmune Thyroiditis | |||
TPE | II | 2C | |
HELLP Syndrome | |||
Postpartum | TPE | III | 2C |
Antepartum | TPE | IV | 2C |
Hematopoietic Progenitor Cell (HPC) Transplantation, ABO Incompatible | |||
Major HPC incompatibility, Marrow | TPE | II | 1B |
Major HPC incompatibility, Apheresis | TPE | II | 2B |
Minor HPC incompatibility, Apheresis | REX | III | 2C |
HPC Transplantation, HLA Desensitization | |||
TPE | III | 2C | |
Hemophagocytic Lymphohistiocytosis; Hemophagocytic Syndrome; Macrophage Activating Syndrome | |||
TPE | III | 2C | |
Henoch–Schönlein Purpura | |||
Crescentic | TPE | III | 2C |
Severe extrarenal disease | TPE | III | 2C |
Heparin-Induced Thrombocytopenia and Thrombosis | |||
Precardiopulmonary bypass | TPE | III | 2C |
Thrombosis | TPE | III | 2C |
Hereditary Hemochromatosis | |||
Erythrocytopheresis | I | 1B | |
Hyperleukocytosis | |||
Symptomatic | Leukocytapheresis | II | 1B |
Prophylactic or secondary | Leukocytapheresis | III | 2C |
Hypertriglyceridemic Pancreatitis | |||
TPE | III | 2C | |
Hyperviscosity in Monoclonal Gammopathies | |||
Symptomatic | TPE | I | 1B |
Prophylactic or secondary | TPE | I | 1C |
Immune Thrombocytopenia | |||
Refractory | TPE | III | 2C |
Refractory | IA | III | 2C |
Immunoglobulin A Nephropathy | |||
Crescentic | TPE | III | 2B |
Chronic progressive | TPE | III | 2C |
Inflammatory Bowel Disease | |||
Ulcerative colitis | Adsorptive cytapheresis | III/II | 1B/2B |
Crohn’s Disease | Adsorptive cytapheresis | III | 1B |
Crohn’s Disease | ECP | III | 2C |
Lambert–Eaton Myasthenic Syndrome | |||
TPE | II | 2C | |
Lipoprotein (a) Hyperlipoproteinemia | |||
LDL apheresis | II | 1B | |
Liver Transplantation | |||
Desensitization, ABOi LD | TPE | I | 1C |
Desensitization, ABOi DD | TPE | III | 2C |
Antibody-mediated rejection (ABOi and HLA) | TPE | III | 2C |
Lung Transplantation | |||
Bronchiolitis obliterans syndrome | ECP | II | 1C |
Antibody-mediated rejection | TPE | III | 2C |
Desensitization | TPE | III | 2C |
Malaria, Severe | |||
REX | III | 2B | |
Multiple Sclerosis | |||
Acute CNS inflammatory demyelinating disease | TPE | II | 1B |
Acute CNS inflammatory demyelinating disease | IA | III | 2C |
Chronic progressive | TPE | III | 2B |
Myasthenia Gravis | |||
Moderate–severe | TPE | I | 1B |
Prethymectomy | TPE | I | 1C |
Myeloma Cast Nephropathy | |||
TPE | II | 2B | |
Nephrogenic Systemic Fibrosis | |||
ECP | III | 2C | |
TPE | III | 2C | |
Neuromyelitis Optica Spectrum Disorders | |||
Acute | TPE | II | 1B |
Maintenance | TPE | III | 2C |
N -Methyl d -Aspartate Receptor Antibody Encephalitis | |||
TPE | I | 1C | |
Overdose, Envenomation, and Poisoning | |||
Mushroom poisoning | TPE | II | 2C |
Envenomation | TPE | III | 2C |
Drug overdose/poisoning | TPE | III | 2C |
Paraneoplastic Neurologic Syndromes | |||
TPE | III | 2C | |
IA | III | 2C | |
Paraproteinemic Demyelinating Neuropathies/Chronic Acquired Demyelinating Polyneuropathies | |||
Anti-MAG neuropathy | TPE | III | 1C |
Multifocal motor neuropathy | TPE | IV | 1C |
IgG/IgA | TPE | I | 1B |
IgM | TPE | I | 1C |
Multiple myeloma | TPE | III | 2C |
IgG/IgA/IgM | IA | III | 2C |
Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections and Sydenham’s Chorea | |||
PANDAS (exacerbation) | TPE | II | 1B |
Sydenham’s chorea, severe | TPE | III | 2B |
Pemphigus Vulgaris | |||
Severe | TPE | III | 2B |
Severe | ECP | III | 2C |
Severe | IA | III | 2C |
Peripheral Vascular Diseases | |||
LDL apheresis | II | 1B | |
Phytanic Acid Storage Disease (Refsum’s Disease) | |||
TPE | II | 2C | |
LDL apheresis | II | 2C | |
Polycythemia Vera; Erythrocytosis | |||
Polycythemia vera | Erythrocytapheresis | I | 1B |
Secondary erythrocytosis | Erythrocytapheresis | III | 1C |
Posttransfusion Purpura | |||
TPE | III | 2C | |
Prevention of RhD Alloimmunization After RBC Exposure | |||
Exposure to RhD(+) RBCs | REX | III | 2C |
Progressive Multifocal Leukoencephalopathy Associated With Natalizumab | |||
TPE | I | 1C | |
Pruritis Due to Hepatobiliary Diseases | |||
Treatment resistant | TPE | III | 1C |
Psoriasis | |||
ECP | III | 2B | |
Disseminated pustular | Adsorptive cytoapheresis | III | 2C |
Lymphocytapheresis | III | 2C | |
TPE | IV | 2C | |
Red Cell Alloimmunization in Pregnancy | |||
Before intrauterine transfusion availability | TPE | III | 2C |
Renal Transplantation, ABO Compatible | |||
Antibody-mediated rejection | TPE/IA | I | 1B |
Desensitization, LD | TPE/IA | I | 1B |
Desensitization, DD | TPE/IA | III | 2C |
Renal Transplantation, ABO Incompatible | |||
Desensitization, LD | TPE/IA | I | 1B |
Antibody-mediated rejection | TPE/IA | II | 1B |
A 2 /A 2 B into B, DD | TPE/IA | IV | 1B |
Scleroderma (Systemic Sclerosis) | |||
TPE | III | 2C | |
ECP | III | 2A | |
Sepsis With Multiorgan Failure | |||
TPE | III | 2B | |
Sickle Cell Disease, Acute | |||
Acute stroke | REX | I | 1C |
Acute chest syndrome, severe | REX | II | 1C |
Priapism | REX | III | 2C |
Multiorgan failure | REX | III | 2C |
Splenic/hepatic sequestration; intrahepatic cholestasis | REX | III | 2C |
Sickle Cell Disease, Nonacute | |||
Stroke prophylaxis/iron overload prevention | REX | I | 1A |
Recurrent vasoocclusive pain crisis | REX | III | 2C |
Preoperative management | REX | III | 2A |
Pregnancy | REX | III | 2C |
Stiff Person Syndrome | |||
TPE | III | 2C | |
Sudden Sensor.ineural Hearing Loss | |||
LDL apheresis | III | 2A | |
Rheopheresis | III | 2A | |
TPE | III | 2C | |
Systemic Lupus Erythematosus | |||
Severe | TPE | II | 2C |
Nephritis | TPE | IV | 1B |
Thrombocytosis | |||
Symptomatic | Thrombocytapheresis | II | 2C |
Prophylactic or secondary | Thrombocytapheresis | III | 2C |
Thrombotic Microangiopathy, Coagulation Mediated | |||
THBD mutation | TPE | III | 2C |
Thrombotic Microangiopathy, Complement Mediated | |||
Complement factor gene mutations | TPE | III | 2C |
Factor H autoantibodies | TPE | I | 2C |
MCP mutations | TPE | III | 1C |
Thrombotic Microangiopathy, Drug-Associated | |||
Ticlopidine | TPE | I | 2B |
Clopidogrel | TPE | III | 2B |
Calcineurin inhibitors | TPE | III | 2C |
Gemcitabine | TPE | IV | 2C |
Quinine | TPE | IV | 2C |
Thrombotic Microangiopathy; Hematopoietic Stem Cell Transplant–Associated | |||
TPE | III | 2C | |
Thrombotic Microangiopathy, Shiga Toxin Mediated | |||
Severe neurologic symptoms | TPE/IA | III | 2C |
Streptococcus pneumonia | TPE | III | 2C |
Absence of severe neurological symptoms | TPE | IV | 1C |
Thrombotic Thrombocytopenic Purpura | |||
TPE | I | 1A | |
Thyroid Storm | |||
TPE | III | 2C | |
Toxic Epidermal Necrolysis | |||
Refractory | TPE | III | 2B |
Vasculitis | |||
HBV–PAN | TPE | II | 2C |
Idiopathic PAN | TPE | IV | 1B |
EGPA | TPE | III | 1B |
Behcet’s disease | Adsorption granulocytapheresis | II | 1C |
Behcet’s disease | Plasma exchange | III | 2C |
Voltage-Gated Potassium Channel Antibodies | |||
TPE | II | 2C | |
Wilson’s Disease, Fulminant | |||
Fulminant | TPE | I | 1C |
Apheresis devices separate whole blood into component fractions, allow removal of the desired fraction, and return the remaining components. This separation can be achieved either by centrifugation or membrane filtration. Centrifugation separates based on differential density; filtration devices separate based on size. In the United States, most TA procedures are performed using centrifugation.
Apheresis procedures require high blood flow rates (up to 150 mL/minutes). Peripheral venous access or double-lumen dialysis/apheresis catheter for adults are typically utilized. For pediatric patients, access size depends on the weight of the patient. Central and femoral catheters each pose their own risks and benefits. Patients who require prolonged TA may need a tunneled catheter or other long-term access device (e.g., arteriovenous fistula, graft, or port).
Determination of exchanged volume is based on a model of an isolated one-compartment intravascular space ( Fig. 74.1 ). This model works best for components located predominantly in the intravascular compartment (e.g., IgM, RBCs), and less well for IgG (which is 45% extravascular). Frequency is determined by time for reequilibration into intravascular space and the need to minimize the risk of bleeding as a result of depletion of coagulation factors, especially fibrinogen. Reequilibration of the intravascular IgG with extravascular IgG typically occurs within 2 days. Five to six one-PV exchanges over 14 days when combined with immunosuppressive medications achieve a 70%–85% reduction in IgG. Typically, plasma exchange processes 1–1.5 total blood volume (TBV) every other day.
Calculations commonly used in TA include calculation of TBV, plasma volume, and extracorporeal volume (ECV). All approaches to calculating TBV overestimate in obese patients and underestimate in muscular patients. Nonetheless, they provide reasonable approximation. TBV is ∼70 mL/kg. Plasma volume = TBV × (1 − Hct). Total RBC volume = TBV × Hct.
ECV is the amount of blood outside the patient filling the apheresis set and tubing. ECV varies by system, type of procedure, and ancillary equipment. ECV should not exceed 15% of TBV to avoid intraprocedural volume depletion and/or anemia. Typically, ECV is not a problem in adults. If ECV exceeds 10%–15% of TBV, then blood priming with RBCs or 5% albumin is performed.
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