A PRIMER ON APHERESIS MEDICINE

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1 A PRIMER ON APHERESIS MEDICINE Nicole Aqui, M.D. Assistant Professor Division of Transfusion Medicine Department of Pathology and Laboratory Medicine University of Pennsylvania

2 What is Apheresis? Apheresis is Greek for to take away or subtract Plasmapheresis remove plasma Cytapheresis remove cells Leukopheresis remove white blood cells Erythropheresis remove red blood cells Plateletpheresis remove platelets Originally performed discontinuously Now performed with continuous removal and separation of blood components

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5 Modern Apheresis Edwin Cohn Developed cold ethanol fractionation to produce albumin Alan (Jack) Latham, Jr.

6 Outline of an Apheresis Procedure IV access obtained (single vs. double needle) Drawn blood is anticoagulated (citrate or heparin) prior to entry into separator Blood is separated and component removed Remaining blood is returned, mixed with replacement fluid if required.

7 Single Stage Collection From McLeod; Apheresis: Principals and Practice (2003)

8 Cobe Spectra

9 Spectra Optia

10 LIPOSORBER SYSTEM Heparin Pump Re-Priming Solution Regeneration Solution Regeneration Pump Blood Pump Plasma Pump Plasma Separator LIPOSORBER Column s Blood Return Plasma Line Waste Line Kanaka Pharma America Corporation

11 Indications for Therapeutic Apheresis ASFA 2013 Categories Category I II III IV Description Disorders for which apheresis is accepted as first-line therapy, either as stand-alone treatment or in conjunction with other modes of treatment Disorders for which apheresis is accepted as second-line therapy, either as a standalone treatment or in conjunction with other modes of treatment Optimum role of apheresis therapy is not established. Decision making should be individualized Disorders in which published evidence demonstrates or suggests apheresis to be ineffective or harmful. IRB approval is desirable if apheresis treatment is undertaken in these circumstances

12 Level of Evidence Evidence level Type I Type II-1 Type II-2 Type II-3 Type III Evidence quality Obtained from at least one properly designed randomized controlled trial Obtained from a well-designed controlled trials without randomization Obtained from well-designed cohort or casecontrol analytic studies, preferably from more than one center or research group Obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments could also be regarded as this type of evidence Opinions of respected authorities, based on clinical experience, descriptive studies, or reports of expert committees Journal of Clinical Apheresis 25: (2010)

13 Recommendation Description Methodological quality of supporting evidence Implications Grade 1A Strong recommendation, high-quality evidence 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 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 lowquality evidence Journal of Clinical Apheresis 25: (2010) Observational studies or case series Very weak recommendations; other alternatives may be equally reasonable

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15 Category I Diseases - Examples Cryoglobulinemia (symptomatic) Hyperviscosity - monoclonal gammopathy Myasthenia gravis Thrombotic thrombocytopenia purpura (TTP) Postransfusion Purpura (PTP) Sickle cell disease (crisis) Leukocytosis (with leukostasis)

16 Examples of Other Categories Category II Thrombocytosis (primary, over 1,000,000/ml) RBC alloimmunization in pregnancy Category III Paraneoplastic neurological syndromes Heart transplant rejection (TPE) Autoimmune hemolytic anemia Category IV SLE nephritis RA

17 Depletion of an Ideal Solute From McLeod; Apheresis: Principals and Practice (2003)

18 Alteration in Blood Constituents From McLeod; Apheresis: Principals and Practice (2003)

19 Adverse Events/Problems Vascular Access Hematoma Clotting of line Insufficient for pressures required Central line Fistula Graft Infection More problematic with lines than with anticubital access

20 Peripheral Stem Cell Collection Autologous vs. Allogeneic Mobilization G-CSF Mozobil Cytoxan, other chemotherapy Processing CD34 stem cell marker Infusion Usually after high dose chemotherapy +/- TBI Mini-allo

21 Adverse Events/Problems Vaso-vagal reactions Pallor Hypotension Diaphoresis Bradycardia Nausea/vomiting More common with plasmapheresis than with cytopheresis ACE inhibitors exacerbate

22 Adverse Events/Problems Citrate hypocalcemia Temporary decrease in Ca i 2+ Tingling, numbness, nausea Coagulation alterations Daily TPE without plasma replacement can deplete coagulation factors and increase bleeding Consider FFP replacement with daily exchange and in patients with coagulation abnormalities Monitor fibrinogen

23 Acknowledgments UPENN Transfusion Medicine Faculty Don Siegel, MD PhD Bruce Sachais, MD PhD Una O Doherty, MD PhD Taku Kambayashi, MD PhD UPENN Apheresis Staff Leah Irwin, Nurse Manager Christa Eisenmann Lita Jamensky Melissa Murter Jane Mason Felicia Jennifer Marsha

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