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Apheresis
Matthew L. Paden, MDAssistant Professor of Pediatric Critical CareDirector, Pediatric ECMO
Children’s Healthcare of Atlanta | Emory University
Disclosures
• Funded by NIH/FDA for CRRT/ECMO device development– Pending grant for pediatric apheresis device
• Much of this talk is stolen from others.
2
Children’s Healthcare of Atlanta | Emory University
Objectives
• Review the technique of apheresis
• Discuss common evidence based indications
• Few notes on technical aspects of concomitant ECMO/Plasma Exchange– Things I have learned the hard way
3
Children’s Healthcare of Atlanta | Emory University
Apheresis – what is it?
• Separation of blood into individual components based on density or molecular size– Leukopheresis– Erythrocytopheresis– Plasmapheresis– Plateletpheresis
• Common methods include– Centrifugation– Membrane filtration
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Children’s Healthcare of Atlanta | Emory University
Apheresis Methods
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Children’s Healthcare of Atlanta | Emory University
Separation by centrifugation
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• Milk separator
• Hand cranked
• Heavy milk goes to the side of the bowl
• Lighter cream stays in the middle
• Separate pathways for each to drain
Children’s Healthcare of Atlanta | Emory University 7
Children’s Healthcare of Atlanta | Emory University
Separation by density
Children’s Healthcare of Atlanta | Emory University
Children’s Healthcare of Atlanta | Emory University
Membrane Filtration
• Semi-porous membrane
• Appropriate pore size for what you are trying to remove
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Children’s Healthcare of Atlanta | Emory University
The 5 “Whats” of Apheresis
• What am I doing this for?
• What am I replacing with?
• What else am I removing?
• What is my anticoagulation?
• What is my extracorporeal volume?
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Children’s Healthcare of Atlanta | Emory University
What am I doing this for?
• Plasmapheresis / Plasma exchange– Most common apheresis procedure at our
center
• Usually for removal of auto-antibodies (IgG)– Only about 45% of your IgG is intravascular– Need for repeated therapies
• One plasma volume (~45 mL/kg) removes about 63% of intravascular IgG
Children’s Healthcare of Atlanta | Emory University
What am I doing this for?
• Category I: primary/standard therapy• Category II: adjunctive therapy• Category III: last-ditch effort (insufficient
evidence to prove efficacy)• Category IV: lack of efficacy in controlled
trials14
Children’s Healthcare of Atlanta | Emory University 15
• Description of the disease• Current management and treatment• Rationale for therapeutic apheresis
Children’s Healthcare of Atlanta | Emory University
Common Indications
• Category I– Thrombotic thrombocytopenic purpura– Guillian Barre Syndrome– Wegener’s/Goodpasteur’s (dialysis dependence
or pulmonary hemorrhage at presentation)– Myasthenic crisis
• Category II– Devic’s syndrome
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Children’s Healthcare of Atlanta | Emory University
Common Indications
• Category III– Treatment of cardiac transplant antibody
mediated rejection– Sepsis with multiple organ failure– Thyroid storm
• Category IV– Diarrheal associated HUS– SLE nephritis– Schizophrenia
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Children’s Healthcare of Atlanta | Emory University
What am I replacing with?
• Albumin or plasma?• Depends on indication and patient
condition– Auto-antibody removal – almost always
albumin– Use FFP when you need replacement of factors
• Thrombotic thrombocytopenic purpura• Liver failure• Wegener’s granulomatosis with pulmonary
hemorrhage
• Complication rate is higher with plasma– Allergic, infectious, TRALI
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Children’s Healthcare of Atlanta | Emory University
What else am I removing?
• Coagulation factors ~25-50%• Fibrinogen ~60%• Bilirubin ~45%• Platelets ~30%
• Usually recover in 48 hours in HEALTHY patients
• Drugs – low volume of distribution, small molecular size
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Children’s Healthcare of Atlanta | Emory University
What is my anticoagulation?
• Citrate– Alkalosis – less than CRRT, because not
continuous therapy– Symptomatic hypocalcemia
• Serial monitoring of ionized calcium and patient symptoms
• If present, treat.• Consider reduce citrate infusion rate, adding calcium
drip, STOPPING THE PROCEDURE
– Hypomagesemia• Some centers measure ionized magnesium levels as
well
• Heparin rarely• None
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Children’s Healthcare of Atlanta | Emory University
What is my extracorporeal volume?• Be aware of extracorporeal volume
– The disposables are made for adults not kids– Current devices range from 250-400 mL– We blood prime if > 12% of TBV is
extracorporeal
• Blood prime– 125 mL pRBC– 15 mL THAM– 25 mL 25% Albumin– 300 mg Calcium gluconate– 10 mEq NaHCO3– 50 units heparin
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Children’s Healthcare of Atlanta | Emory University
Erythrocytopheresis
• Removal/replacement of RBC• Commonly used for complications of sickle
cell disease– Acute stroke– Acute chest syndrome– Prevention of iron overload
• Rare other indications– Babesiosis / Malaria– Hereditary hemochromotosis– Polycythemia vera
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Children’s Healthcare of Atlanta | Emory University
Leukopheresis
• Removal of WBC• Typically used for acute hematogenous
cancers with evidence of end organ disease
• Thresholds are not well defined in pediatrics– Range of 200-800 WBC count in textbooks– Differential range based on disease (AML, ALL,
CML)
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Children’s Healthcare of Atlanta | Emory University
Photopheresis
• Remove buffy coat• Treat with a photoactive compound
(psoralens)• Expose to UVA light and reinfuse into
patient
• Most commonly used with GVHD / T cell lymphoma
• Less commonly with – Cardiac transplant rejection– Pemphigus– Nephrogenic systemic fibrosis 24
Children’s Healthcare of Atlanta | Emory University
Lipopheresis
• Selective removal of lipoproteins in patients with familial hypercholesterolemia– Common to have CAD by teenage years with
AMI in 30’s
• Specific column
• Treatment for life or until liver transplant
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Children’s Healthcare of Atlanta | Emory University
Concomitant use with other extracorporeal therapies
• ECMO– Circuit is already
anticoagulated with heparin
– Some devices still mandate citrate
• 10:1 is usual blood:citrate ratio
• Can increase to 50:1
• Don’t need a calcium infusion
– Duration of procedure can be shortened 26
Children’s Healthcare of Atlanta | Emory University
Things I have learned the hard way
• People are scared of this– Analogies to milk
separation, platelet donation
– Usually an outpatient procedure
• Anaphylaxis kit– Benadryl, Epinephrine,
Steroids– Calcium
• Need for central oversight– Plasma exchange for
autism?
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