Practical Issues in Plasmapheresis: Set-up and Troubleshooting, Combined CRRT and Apheresis

Transcription

1 Workshop G14 Wednesday, 10:15 11:45 a.m. Practical Issues in Plasmapheresis: Set-up and Troubleshooting, Combined CRRT and Apheresis 1. David M. Ward, MD, FRCP Use of Hybrid Apheresis/CRRT circuits 2. Isagani ( Jhun ) Marquez, RN, BSN and Noel Oabel, RN, BSN, CNN Hands-on demonstration of simultaneous Plasma Exchange and CRRT

2 Workshop G14 Wednesday, 10:15 11:45 a.m. Practical Issues in Plasmapheresis: Set-up and Troubleshooting, Combined CRRT and Apheresis 1. Use of Hybrid Apheresis / CRRT circuits David M. Ward, MD, FRCP, HP(ASCP). Professor of Clinical Medicine, Division of Nephrology, UCSD. Medical Director, Therapeutic Apheresis Program. Associate Medical Director, Kidney/Pancreas Transplantation.

3 DISCLOSURES: The speaker has the following potential conflicts TerumoBCT, Inc. Honoraria, Consulting Therakos, Inc. Honoraria Alexion Pharmaceuticals Advisory Board Aethlon Medical Inc. Consulting WARNING: Some uses are discussed that are not FDA-approved

4 Use of Hybrid Apheresis / CRRT circuits OUTLINE: Case reports: patients requiring simultaneous TPE (therapeutic exchange ) + CRRT (continuous hemodiafiltration) Citrate-anticoagulated CRRT In parallel circuit deign: TPE + CRRT In series circuit design: TPE + CRRT TPE + secondary purification + CRRT Other methods of secondary processing

5 Case reports The first 3 patients at UCSD ( ) - who received liver transplants that were ABO incompatible ( A liver into O recipient) - and developed post-operative acute renal failure. All required continuous renal replacement therapy (CRRT) - we used the UCSD citrate-a/c system to avoid bleeding*. All required therapeutic exchange (TPE) for removal of anti-a antibodies to overcome antibody-mediated rejection - we used centrifugal separation. All recovered renal function and survived with good function of the liver transplant. * Ward DM, Mehta RL. Extracorporeal management of acute renal failure at high risk of bleeding. Kidney International 43:S , 1993.

6 Citrate-CRRT was originally Arterio-Venous ( ) Arterial from patient Case reports Citrate Prefilter Dilution Venous blood return Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CONTINUOUS HEMODIAFILTRATION Citrate-anticoagulated CRRT was first used in February Ward DM, Mehta RM. Kidney Int. 37:323, 1990.

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8 Firsts in citrate a/c of external blood circuits 1961: Apheresis (leukapheresis). Bierman HR, et al. Br J Haematol 7:51, : Intermittent hemodialysis (IHD) acute (with zero Ca ++ dialysate). Morita Y, et al. Am J Med Sci 242:32, : IHD acute and chronic (with zero Ca ++ dialysate). Pinnick RV, et al. N Engl J Med 308:258, : Continuous arterio-venous hemodiafiltration (CAVHDF). Ward DM, Mehta RM. Kidney Int. 37:323, Mehta RL, McDonald BR., Aguilar MM, Ward DM. Kidney Int. 38: , : Continuous veno-venous hemodiafiltration (CVVHDF). Mehta RM, Bestoso JT, Ward DM. J A S Nephrol 4:368, : Continuous veno-venous hemofiltration (CVVH). Palsson R, Niles JL: Kidney Int. 55:1991, : Review Article: Citrate Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Patients: Success and Limits Mariano F, et al. Int J Nephrol 10:4061, 2011

9 Since 1992 at UCSD, CRRT has been veno-venous (CVVHDF) from patient Case reports Citrate Prefilter Dilution blood return Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CONTINUOUS HEMODIAFILTRATION Mehta RL, Bestoso JT, Ward DM. Citrate anticoagulation for continuous renal replacement therapy (CRRT). J Am Soc Nephrol, 4:368, 1993.

10 Our 3 liver transplant patients received TPE plus CRRT from patient Case reports Citrate Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

11 Our 3 liver transplant patients received TPE plus CRRT from patient Case reports Citrate Transfuse with Group O red cells blood return Remove Plasma Anti-A FFP Replacement: replacement Group Albumin/FFP A or AB Prefilter Dilution Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

12 We used a TPE circuit in parallel with the CRRT circuit from patient Case reports Citrate Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

13 IN PARALLEL: Centrifugal Plasmaseparator and CVVHDF Blood flow splits here - Need higher total blood flow - Need higher anticoagulant dose Blood pump (roller pump of CRRT machine) can run whether or not apheresis machine is running Citrate Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

14 IN PARALLEL: Centrifugal Plasmaseparator and CVVHDF Blood flow splits here - Need higher total blood flow - Need higher anticoagulant dose Blood pump (roller pump of CRRT machine) can run whether or not apheresis machine is running 200 ml/min Citrate Prefilter 100 ml/min Dilution 100 ml/min blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

15 IN SERIES : Centrifugal Plasmaseparator and CVVHDF Lower total blood flow - lower anticoagulant dose Blood pump (roller pump of CRRT machine) can run whether or not apheresis machine is running from patient 100 ml/min Citrate Prefilter 100 ml/min Dilution 100 ml/min blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

16 IN SERIES : Centrifugal Plasmaseparator and CVVHDF Lower total blood flow - lower anticoagulant dose Blood pump (roller pump of CRRT machine) can run whether or not apheresis machine is running from patient blood by-pass line Citrate Use the apheresis machine s citrate pump. (Switch to CRRT citrate pump when apheresis is stopped and bypass line is in use.) blood return Plasma Replacement: Albumin/FFP Prefilter Dilution Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

17 IN SERIES : Centrifugal Plasmaseparator and CVVHDF from patient Citrate Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ CENTRIFUGAL PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

18 IN SERIES : Membrane Plasmaseparator and CVVHDF from patient Citrate Replacement: Albumin/FFP Prefilter Dilution Hemofilter blood return Plasma Ca ++ - free Postfilter Replacement Ultrafiltrate + Ca ++ MEMBRANE PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

19 IN SERIES : Membrane Plasmaseparator and CVVHDF from patient Heparin Replacement: Albumin/FFP Prefilter Dilution Hemofilter blood return Plasma Postfilter Replacement Ultrafiltrate + MEMBRANE PLASMAPHERESIS CONTINUOUS HEMODIAFILTRATION

20 DFPP and CRRT from patient Additional colloid (optional) Heparin Albumin fraction Prefilter Dilution Hemofilter blood return Whole globulin fraction Postfilter Replacement Ultrafiltrate + #1: Plasma-filter Pore size: ~0.3 microns Cut-off: >2000 kda Specifications are those of Asahi products DOUBLE FILTRATION PLASMAPHERESIS #2: Plasma-fractionator Pore: microns Cut-off: ~ 100 kda (Albumin ~ 67 kda) (IgG ~ 140 kda) CONTINUOUS HEMODIAFILTRATION

21 Coupled Plasmafiltration Adsorption (CPFA) Continuous Plasmafiltration with Adsorption Column + Continuous High-volume Hemodiafiltration from patient Plasmafilter Heparin Whole Purified Prefilter dilution Resin column Hemofilter Ultrafiltrate + effluent dialysate blood return Bellomo R, Tetta C, Ronco C. Coupled filtration adsorption. Intensive Care Med. 29:1222-8, 2003

22 Secondary processing (a) blood return Albumin fraction (b) blood return blood return Purified Purified Globulin fraction #1 #2 #1 #2 from patient from patient from patient Whole Whole Whole Ward DM, Conventional Apheresis Therapies: A Review. J Clin Apheresis 26: , 2011

23 Plasma regeneration (on-line purification) blood return Centrifugal TPE Purified blood return Membrane TPE Purified Centrifugal apheresis machine? Plasmaseparator (hollow fiber membrane with large pore size)? from patient from patient Whole Whole

24 Plasma regeneration (on-line purification) blood return from patient Purified? Whole DFPP (cascade filtration) adsorption columns containing Staphylococcal Protein A immobilized antibodies (Ab) adsorption resins immobilized antigen (Ag) covalently-bound peptide ligands

25 Cascade Plasmafiltration (Double-Filtration) blood return Additional colloid (optional) Albumin fraction Globulin fraction #1: Plasma-filter Pore size: large Cut-off: >1000 kd #2: Plasma-fractionator Pore size: medium Cut-off: ~ 100 kd #1? #2 (Albumin ~ 67 kd) (IgG ~ 140 kd) (IgM ~ 970 kd) from patient Whole Membrane specifications are those of Asahi products (Asahi Kasei Kuraray Medical Co., Tokyo 101-8,101, Japan)

26 Protein-A Immunoadsorption (PA-IA) blood return from patient Purified Whole Staphylococcal Protein A immuno-adsorption column (Prosorba ) (Immunosorba ) Staph Protein A has high avidity for Fc portion of IgG (IgG 1, IgG 2, IgG 4 ) Removal of antibody or antigenantibody complexes ITP: FDA-approved. RA: Double-blind sham-controlled - trial positive (Felson, 1999). Refractory TTP (Mitomycin): - anecdotal successes. But columns no longer available. Also controversy: super-antigen (pharmacological) mechanism?

27 Antibody Immunoadsorption with Anti-IgG blood return Purified Perfusion columns containing immobilized polyclonal antibody to human IgG. from patient Whole Rinse Waste Removes IgG (all subclasses) Used in Europe and Japan for - autoimmune diseases - transplant alloimmunization Brands: - TheraSorb (Miltenyi Biotec) - others

28 Dextran adsorption (Kaneka Liposorber ) blood return Purified 5% Saline 0.9% Saline Perfusion columns containing Dextran sulfate Whole Removes LDL, Lp(a), and VLDL. Minimal effect on HDL or albumin. from patient Effective LDL apheresis Waste LDL-Apheresis Kaneka system is FDA-approved

29 Braun HELP System (Heparin-induced Extracorporeal Lipoprotein Precipitation) blood return Purified Whole Acid buffer/ heparin LDL-Apheresis Braun HELP system is FDA-approved Acidity (ph 5.12) plus heparin causes precipitation of lipoprotein complexes from patient Bicarbonate dialysis and ultrafiltration to correct ph and volume Precipitate filter captures lipoprotein complexes Ultrafilter Heparin adsorber

30 Antigen (Ag) columns for Immunoadsorption (IA) blood return from patient Purified Whole Perfusion columns containing immobilized antigen can extract specific autoantibodies for anti-gbm nephritis Terman DS, Durante D, Buffaloe G, McIntosh R. Attenuation of canine nephrotoxic glomerulonephritis with an extracorporeal immunoadsorbent. Scand J Immunol. 6: , 1977 for SLE Terman DS, Buffaloe G, Mattioli C, Cook G, Tillquist R, Sullivan M, Ayus JC. Extracorporeal immunoadsorption: initial experience in human systemic lupus erythematosus. Lancet (2):824-7, 1979 Clinically unsuccessful due to Ag leaching

31 Covalently-bound peptide ligands for Immunoadsorption (IA) blood return from patient Purified Whole Peptide ligands covalently linked to sepharose mimic the epitope and specifically immuno-adsorb pathogenic autoantibodies. effective in Autoimmune type Idiopathic Dilated Cardiomyopathy which is due to autoantibodies with (1) agonist-like effect on the Beta-1 adrenergic receptor (2) now known to cross-react with and damage cardiac myosin. But Ab s against different epitopes may cause similar disease Wallukat G, Reinke P, Dorffel WV, et al. Removal of autoantibodies in dilated cardiomyopathy by immunoadsorption. Int J Cardiol. 1996; 54:

32 Covalently-bound ligands for Immunoadsorption (IA) blood return Purified Column containing synthetic terminal trisaccharide A or B blood group antigen linked to a Sepharose matrix Glycosorb ABO column (Glycorex Transplantation AB), from patient Whole Kumlien G, Ullstrom L, Losvall A, Persson LG, Tyden G: Clinical experience with a new apheresis filter that specifically depletes ABO blood group antibodies. Transfusion 46: , 2006.

33 Secondary purification + CRRT from patient Glycosorb ABO column Prefilter Dilution Hemofilter blood return PLASMA FILTER PLASMA PURIFIER Postfilter Replacement Ultrafiltrate + CONTINUOUS HEMODIAFILTRATION

34 Secondary purification + CRRT from patient Glycosorb ABO column Prefilter Dilution Hemofilter blood return CENTRIFUGAL SEPARATION PLASMA PURIFIER Postfilter Replacement Ultrafiltrate + CONTINUOUS HEMODIAFILTRATION

35 Secondary purification + CRRT from patient Prefilter Dilution blood return CENTRIFUGAL SEPARATION? PLASMA PURIFIER Hemofilter Postfilter Replacement Ultrafiltrate + CONTINUOUS HEMODIAFILTRATION

36 IN SERIES : Centrifugal Plasmaseparator and CVVHDF from patient Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + CENTRIFUGAL PLASMA EXCHANGE CONTINUOUS HEMODIAFILTRATION

37 IN PARALLEL: Centrifugal Plasmaseparator and CVVHDF from patient Prefilter Dilution blood return Plasma Replacement: Albumin/FFP Hemofilter Ca ++ - free Postfilter Replacement Ultrafiltrate + CENTRIFUGAL PLASMA EXCHANGE CONTINUOUS HEMODIAFILTRATION

38 Use of Hybrid Apheresis / CRRT circuits SUMMARY: Case reports: patients requiring simultaneous TPE (therapeutic exchange ) + CRRT (continuous hemodiafiltration) Citrate-anticoagulated CRRT In parallel circuit deign: TPE + CRRT In series circuit design: TPE + CRRT TPE + secondary purification + CRRT Other methods of secondary processing

39 Thank you for your attention

40 SAVE THE DATE March 12-14, 2015 VISIT THE WEBSITE cme.ucsd.edu/apheresis A 2½-day conference for MDs and RNs, from established practitioners to those starting a new program. Nationally prominent faculty. Didactic sessions on the basics. Symposia on exchange, cell apheresis, disease applications, special patient populations, new science, program management, etc. Hands-on workshops. Breakfasts with the experts, etc. Conference Organizing Committee: David M. Ward, MD Amber P. Sanchez, MD Eileen Lischer, BSN, RN, CNN Isagani Marquez, Jr., BSN, RN Odette Ada, BSN, RN Majella Vaughan, MPH