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).

Principle

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 ).

Table 74.1
American Society for Apheresis Category Indications
From Schwartz, J., et al. (2016). Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the apheresis applications committee of the American Society of Apheresis. J Clin Apher, 31 , 149–338.
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.

Table 74.2
Grading Recommendations
From Schwartz, J., et al. (2016). Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the apheresis applications committee of the American Society of Apheresis. J Clin Apher, 31 , 149–338.
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

Table 74.3
Clinical Indications for Therapeutic Apheresis
From Schwartz, J., et al. (2016). Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the apheresis applications committee of the American Society of Apheresis. J Clin Apher, 31 , 149–338.
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

Methods

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.

Vascular Access

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).

Volume Exchanged and Frequency

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.

Figure 74.1, Relationship of removal of plasma constituents to plasma volume processed in therapeutic plasma exchange, assume the constituent is an ideal solute.

Calculations

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.

You're Reading a Preview

Become a Clinical Tree membership for Full access and enjoy Unlimited articles

Become membership

If you are a member. Log in here