Apheresis

1. Apheresis Matthew L. Paden, MD Assistant Professor of Pediatric Critical Care Director, Pediatric ECMO

2. Disclosures • Funded by NIH/FDA for CRRT/ECMO device development • Pending grant for pediatric apheresis device • Much of this talk is stolen from others.

3. 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

4. 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

5. Apheresis Methods

6. Separation by centrifugation • 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

9. Separation by density

11. Membrane Filtration • Semi-porous membrane • Appropriate pore size for what you are trying to remove

12. 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?

13. 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

14. 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 trials

15. Description of the disease • Current management and treatment • Rationale for therapeutic apheresis

16. Common Indications • Category I • Thrombotic thrombocytopenic purpura • GuillianBarre Syndrome • Wegener’s/Goodpasteur’s (dialysis dependence or pulmonary hemorrhage at presentation) • Myasthenic crisis • Category II • Devic’s syndrome

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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)

24. 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

25. 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

26. 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

27. 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?