Principles of Plasma Exchange, Applications & Practical issues

Transcription

1 Workshop G07 Wednesday, 8:30 10:00 a.m. Principles of Plasma Exchange, pplications & Practical issues 1. Eisei Noiri, MD, PhD. Principles of Plasma Exchange 2. David M. Ward, MD, FCP. Practicalities of Plasma Exchange

2 Workshop G07 Wednesday, 9:15 10:00 a.m. Principles of Plasma Exchange, pplications & Practical issues 2. Practicalities of Plasma Exchange David M. Ward, MD, FCP, HP(SCP). Professor of Clinical Medicine, Division of Nephrology, UCSD. Medical Director, Therapeutic pheresis Program. ssociate Medical Director, Kidney/Pancreas Transplantation.

3 DISCLOSUES: The speaker has the following potential conflicts TerumoBCT, Inc. Honoraria, Consulting Therakos, Inc. Honoraria lexion Pharmaceuticals dvisory Board ethlon Medical Inc. Consulting

4 SVE THE DTE March 12-14, 2015 VISIT THE WEBSITE cme.ucsd.edu/apheresis 2½-day conference for MDs and Ns, from established practitioners to those starting a new program. Nationally prominent faculty. Didactic sessions on the basics. Symposia on plasma 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 mber P. Sanchez, MD Eileen Lischer, BSN, N, CNN Isagani Marquez, Jr., BSN, N Odette da, BSN, N Majella Vaughan, MPH

5 Practicalities of Therapeutic Plasma Exchange (TPE) OUTLINE: 1. Types of apheresis 2. Separation by centrifugation 3. Therapeutic applications 4. Case report 5. mount of plasma exchange 6. oice of replacement fluid 7. nticoagulation 8. Typical apheresis prescriptions

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7 Manual plasmapheresis PLSM EMOVL WITH ETUN OF COPUSCLES (PLSMPHEESIS) FIST PPE JOHN J. BEL, L. G. OWNTEE ND B. B. TUNE From the Pharmacological Laboratory of the Johns Hopkins University eceived for publication, July 16, 1914 I. In connection with our experiments on vividiffusion with a view to the ultimate use of the method for the relief of toxaemia the idea suggested itself to try the effects of the repeated removal of considerable quantities of blood, replacing the plasma by Locke s solution and reinjecting this together with the sedimented corpuscles. J. Pharmacol Exp Ther, 5:625, 1914

8 Manual plasmapheresis - still used in pediatrics pheresis methods PLSM EMOVL WITH ETUN OF COPUSCLES (PLSMPHEESIS) FIST PPE JOHN J. BEL, L. G. OWNTEE ND B. B. TUNE From the Pharmacological Laboratory of the Johns Hopkins University eceived for publication, July 16, 1914 I. In connection with our experiments on vividiffusion with a view to the ultimate use of the method for the relief of toxaemia the idea suggested itself to try the effects of the repeated removal of considerable quantities of blood, replacing the plasma by Locke s solution and reinjecting this together with the sedimented corpuscles. Centrifugal plasmapheresis and cytapheresis Membrane plasmapheresis

9 Separation by membrane filtration from patient Hollow-fiber plasma-filter Pore size: ~0.3 microns Cut-off: ~1000 kda eplacement fluid (albumin/ saline) Effluent plasma blood return Membrane specifications are those of sahi products (sahi Kasei Kuraray Medical Co., Tokyo 101-8,101, Japan)

10 Therapeutic Plasma Exchange by centrifugation (ctpe)

11 Separation by centrifugation Whole Blood in BC out WBC out Plasma out

12 Separation by centrifugation Whole Blood in BC out WBC out Specific Gravity Plasma Plasma out Plt s 1.04 Lymph s Mono s 1.06 Blasts PMN s BC s 1.095

13 Separation by centrifugation Stoke s Law: S V = 2 w 2 r 2 (r cell - r plasma ) 9m Specific Gravity Plasma Stoke s law says that the cellular velocity of sedimentation (S V ) is proportional to: Centrifugal acceleration (w 2 ) or g Square of the cell radius (r 2 ) Difference between the density of cell and plasma (r cell - r plasma ) Inverse of the fluid viscosity (m) Centrifugal separation is a function of: S V and Dwell time (inverse of inlet blood flow rate) Plt s 1.04 Lymph s Mono s 1.06 Blasts PMN s BC s 1.095

14 Separation by centrifugation Plasmapheresis ( TPE ) (plasma removal or exchange) High G-force (= high PM s) to create a platelet-poor plasma Specific Gravity Plasma To get pure cell product: (1) interface position (2) accurate PM s (G s) (3) flow rate (dwell time) Low G-force to keep WBC s out of packed BC s Thrombocytapheresis (platelet removal) Leukocytapheresis = Leukapheresis (WBC removal) Erythrocytapheresis (red cell exchange) Plt s 1.04 Lymph s Mono s 1.06 Blasts PMN s BC s 1.095

15 Separation by centrifugation Plasmapheresis ( TPE ) (plasma removal or exchange) Specific Gravity Plasma pheresis (blood component removal or exchange) Cytapheresis (blood cell removal or exchange) Thrombocytapheresis (platelet removal) Leukocytapheresis = Leukapheresis (WBC removal) Plt s 1.04 Lymph s Mono s 1.06 Blasts PMN s Erythrocytapheresis (red cell exchange) BC s 1.095

16 Conventional Therapeutic pheresis Modalities Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) eplace with FFP (for TTP) eplace with albumin (for all other uses) Cytapheresis = cell removal or exchange (requires centrifugal machine) Erythrocyt -apheresis = red cell exchange (sickle cell, etc.) Thrombocytapheresis = platelet reduction (thrombocytosis) Leukapheresis = white cell apheresis WBC reduction (leukemia) Blood stem cells (for BM transplant) Less-Conventional pheresis Modalities (require additional equipment) from Okafor C, Ward DM, Mokrzycki M, et al. J Clin pheresis, 25: , 2010

17 Conventional Therapeutic pheresis Modalities eplace with FFP (for TTP) Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) eplace with albumin (for all other uses) Cytapheresis = cell removal or exchange (requires centrifugal machine) Erythrocyt -apheresis = red cell exchange (sickle cell, etc.) Thrombocytapheresis = platelet reduction (thrombocytosis) Leukapheresis = white cell apheresis WBC reduction (leukemia) Blood stem cells (for BM transplant) Less-Conventional pheresis Modalities (require additional equipment) Immunoadsorption Online plasma purification Filtration selective removal LDL apheresis Online WBC processing Photopheresis (= ECP) other WBC s (for ex-vivo immune modulation) Blood stem cells (for ex-vivo genetic modification) from Okafor C, Ward DM, Mokrzycki M, et al. J Clin pheresis, 25: , 2010

18 Purposes of TPE (therapeutic plasmapheresis) emoval of pathogenic macromolecules from the bloodstream: utoantibody Probable autoantibody Circulating immune complexes (antigen:antibody complexes) including mixed cryoglobulins lloantibody Paraproteins (light chains, monoclonal cryoglobulins, etc.) Non-immunoglobulin proteins Endogenous toxins Exogenous poisons lso, in a few instances, replenishment of deficient plasma components by using FFP (plasma) as the replacement fluid: DMTS 13 enzyme in Thrombotic Thrombocytopenic Purpura (TTP) Defective complement Factor H (in subtype of MPGN), etc.

19 TPE applications utoantibody: Thrombotic Thrombocytopenic Purpura (TTP), Myasthenia gravis (MG), Neuromyelitis Optica (NMO), nti-gbm GN (& Goodpasture s), NC-nephritis (& Wegener s), ntiphospholipid crisis, Immune Thrombocytopenia (ITP), etc. Probable autoantibody: Multiple sclerosis (MS), Guillain-Barré (GBS), ronic Inflammatory Demyelinating Polyneuropathy (CIDP), etc. ntigen-ntibody complexes (including mixed cryoglobulins): Hepatitis C vasculitis, S.L.E., etc. lloantibody: Transplant sensitization, Transplant rejection (humoral), Transfusion reactions, etc. Paraproteins: Waldenstrom s, Hyperviscosity, Light-chain neuropathy, Light-chain glomerulopathy, Myeloma cast nephropathy, etc. Non-Ig proteins: Focal Segmental Glomerulosclerosis (FSGS). Endogenous toxins: Hypercholesterolemia, Liver failure, Systemic Inflammatory esponse Syndrome (SIS), etc. Exogenous poisons: manita, drugs, etc.

20 Indications for therapeutic apheresis

21 Example page from SF 2013 guidelines

22 Example page from SF 2013 guidelines Name of the disease Grade Controlled trials/ Case series/ Case reports Category Description of the disease Current management/treatment ationale for therapeutic apheresis Technical notes Duration/ discontinuation eferences

23 TPE applications utoantibody: Thrombotic Thrombocytopenic Purpura (TTP), Myasthenia gravis (MG), Neuromyelitis Optica (NMO), nti-gbm GN (& Goodpasture s), NC-nephritis (& Wegener s), ntiphospholipid crisis, Immune Thrombocytopenia (ITP), etc. Probable autoantibody: Multiple sclerosis (MS), Guillain-Barré (GBS), ronic Inflammatory Demyelinating Polyneuropathy (CIDP), etc. ntigen-ntibody complexes (including mixed cryoglobulins): Hepatitis C vasculitis, S.L.E., etc. lloantibody: Transplant sensitization, Transplant rejection (humoral), Transfusion reactions, etc. Paraproteins: Waldenstrom s, Hyperviscosity, Light-chain neuropathy, Light-chain glomerulopathy, Myeloma cast nephropathy, etc. Non-Ig proteins: Focal Segmental Glomerulosclerosis (FSGS). Endogenous toxins: Hypercholesterolemia, Liver failure, Systemic Inflammatory esponse Syndrome (SIS), etc. Exogenous poisons: manita, drugs, etc.

24 Case report Previously healthy 49 year old woman In March 2014 noticed slurring of speech at work Then difficulty chewing and swallowing, blurred vision In pril 2014 developed right eye ptosis Diagnosed as Myasthenia Gravis. Pyridostigmine helped. Worsening. To Emergency Dept., admitted. IVIG x 5 days and high dose prednisone Temporary improvement, then relapse In late pril 2014 commenced plasma exchange (TPE) with immediate and sustained improvement Thymectomy without benefit. Started CellCept (mycophenolate), continued prednisone and TPE Gradually weaned off TPE, prednisone and pyridostigmine (months). Now well controlled on CellCept only

25 TPE for autoantibody disease Example: Myasthenia Gravis (MG) Caused by autoantibodies (auto-b s) that block the nervemuscle junction by binding to receptors on muscle that receive neurotransmitters released by nerves. Typically weakness and fatigability with repetitive physical activity, usually improving with rest. Often ptosis and diplopia; more severe cases have facial, bulbar and limb muscle involvement. Most prevalent in year old women. Myasthenic crisis is characterized by acute respiratory failure requiring intubation, or bulbar weakness causing dysphasia and high risk of aspiration. bnormalities of the thymus gland (hyperplasia or thymoma) are associated with MG; thymectomy is sometimes curative.

26 TPE for autoantibody disease Example: Myasthenia Gravis (MG) Normal nerve transmission Nerve Motor neurone terminal cetylcholine olinesterase Postsynaptic membrane (muscle)

27 TPE for autoantibody disease Example: Myasthenia Gravis (MG) Most MG patients (85%) have autoantibodies to acetylcholine receptors (), which impair neurotransmission Nerve Motor neurone terminal cetylcholine olinesterase V V V V V V V V V V V Postsynaptic membrane (muscle) V V V

28 TPE for autoantibody disease Example: Myasthenia Gravis (MG) Most MG patients (85%) have autoantibodies to acetylcholine receptors (), which impair neurotransmission cetylcholine olinesterase V V V V Nerve Motor neurone terminal V V V V V V V Postsynaptic membrane (muscle) Mestinon (pyridostygmine) and other cholinesterase inhibitors are used to boost the nerve signal V V V TPE works by removing the auto-b that is blocking transmission Prednisone, rituximab, etc. suppress auto-b production

29 Common questions patients ask about plasmapheresis. Myasthenia Gravis (MG) is an autoimmune disease. What is plasmapheresis? Plasmapheresis is a procedure. TPE for autoantibody disease Example: Myasthenia Gravis Why should I have plasmapheresis? Plasmapheresis may be recommended for a few reasons: To stabilize a rapid decrease in muscle strength. To reduce moderate to severe muscle weakness before surgery. To add to present treatment if current forms of therapy are providing insufficient control of the disease. How many plasma exchanges will I need and where will it be done? The number of plasmapheresis treatments needed depends on the protocol the physician has determined is best for the patient. Some patients are treated on a Monday/Wednesday/Friday schedule. Others are treated on a daily schedule or on a weekly or monthly schedule

30 Common questions patients ask about plasmapheresis. Myasthenia Gravis (MG) is an autoimmune disease. What is plasmapheresis? Plasmapheresis is a procedure. TPE for autoantibody disease Example: Myasthenia Gravis Why should I have plasmapheresis? Plasmapheresis may be recommended for a few reasons: To stabilize a rapid decrease in muscle strength. To reduce moderate to severe muscle weakness before surgery. To add to present treatment if current forms of therapy are providing insufficient control of the disease. How many plasma exchanges will I need and where will it be done? The number of plasmapheresis treatments needed depends on the protocol the physician has determined is best for the patient. Some patients are treated on a Monday/Wednesday/Friday schedule. Others are treated on a daily schedule or on a weekly or monthly schedule

31 Number of plasmaphereses needed Hyperviscosity syndrome (Ward DM, Updates to Harrison s Principle s of Internal Medicine, Volume V, 1984) Pemphigus vulgaris unresposive to gold, dapsone, prednisone and azathioprine. (Ward DM, ibid., 1984) Monoclonal IgM (mg/dl) IgG autoantibody (titer) 5000 IgM 1:20,480 IgG Plasmapheresis procedures Waldenstrom Macroglobulinemia: IgM is large (~970,000 Daltons) 90% of IgM stays intravascular Plasmapheresis procedures Most antibody mediated diseases: IgG is smaller (~146,000 Daltons) Only 30%-35% is intravascular

32 Dose of plasma exchange Prescribed volume of each plasma exchange procedure X Number and frequency of procedures = DOSE depends on patient s size (plasma volume) depends on disease characteristics Example: (70Kg woman) Volume to remove: 3.5 liters Example: (Myasthenic crisis) x daily x3, then reassess

33 Size of each plasmapheresis Volume exchanged depends on the patient s size: dult blood volume (BV) ~ 70ml/Kg. Plasma vol (PV) = BV x (1 - Hct/100) y = e -x Example: 70 Kg woman: BV = 70ml/Kg x 70Kg = 4.9 liter Hematocrit = 39% PV = 4.9 liter x (61%) = 3 liter PV exchange = 3 liters 1.5 PV exchange = 4.5 liters oose 3.6 liter TPE x = 3.6 / 3.0 = vol exchange removes 63%. 1.5-vol exchange removes 78%. y = e -x = e = 0.30 Therefore removes 70% From Figure 1 in: Ward DM. Conventional apheresis therapies: a review. J Clin pheresis 26: , 2011.

34 Plasmapheresis oice of replacement solution eplace with FFP (for TTP) Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) eplace with albumin (for all other uses) e-use on-line purified plasma 1. FFP (Fresh-Frozen Plasma) To replace deficient or defective plasma constituents: use FFP for whole replacement volume. Examples: TTP (Thrombotic Thrombocytopenic Purpura), other Thrombotic Microangiopathies. To prevent exacerbating active lung hemorrhage: use FFP for all or part of replacement volume. Examples: Goodpasture s Syndrome, NC vasculitis.

35 Plasmapheresis oice of replacement solution eplace with FFP (for TTP) Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) eplace with albumin (for all other uses) e-use on-line purified plasma 2. lbumin (or other colloid) Use for most applications. Either 5% albumin for whole replacement volume. Or one-quarter saline and threequarters 5% albumin. Or other colloidal solution (France). If needed for clotting-factor depletion, give 2 units FFP as last part of replacement volume (e.g. if fibrinogen at start is <110 mg/dl).

36 Plasmapheresis oice of replacement solution eplace with FFP (for TTP) Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) eplace with albumin (for all other uses) e-use on-line purified plasma 3. Plasma regeneration The patient s own plasma is passed through a purification system on-line to remove the pathogenic molecule, and then re-infused to the patient as the replacement volume.

37 Plasmapheresis oice of replacement solution eplace with FFP (for TTP) Plasmapheresis = plasma removal or exchange (requires centrifugal machine or plasmafiltration system) Immunoadsorption eplace with albumin (for all other uses) Online plasma purification (selective plasmapheresis) (requires additional equipment) Filtration selective removal LDL apheresis 3. Plasma regeneration The patient s own plasma is passed through a purification system on-line to remove the pathogenic molecule, and then re-infused to the patient as the replacement volume. These selective plasmapheresis modalities include Immunoadsorption columns Double ( cascade ) filtration emical affinity columns etc.

38 Plasmapheresis oice of machine type Therapeutic Plasmapheresis = Therapeutic Plasma Exchange Centrifugal plasmapheresis (ctpe) TPE or PLEX Membrane plasmapheresis (mtpe) 1. Centrifugal plasmapheresis (ctpe) Usually citrate anticoagulation 2. Membrane plasmapheresis (mtpe) Usually heparin anticoagulation

39 Comparison of anticoagulants fter citrateanticoagulated hemodialysis fter heparinanticoagulated hemodialysis Scanning electron micrographs of the inner surface of polysulfone hollow fiber dialyzer membranes. Hoffbauer et al. Kidney Int. 1999;56:

40 Comparison of anticoagulants Citrate: 1. Familiar in blood-banking. 2. Used for ctpe 3. Sometimes for mtpe 4. Short-acting: prescribe ratio to blood flow 5. No systemic anticoagulant effect; risk of citrate toxicity 6. Suitable for low-flow circuits 7. Sometimes for hemodialysis 8. Increasingly for Continuous enal eplacement Therapy (CT) in intensive care. Heparin: 1. Familiar in dialysis. 2. Used for mtpe 3. Sometimes for ctpe 4. Long-acting: prescribe units/ Kg body wt/ hour 5. Systemic anticoagulant; risk of bleeding; rare HIT 6. Suitable for high-flow circuits Nafamostat mesylate: 1. vailable in Japan. 2. Used for dialysis and mtpe

41 The ionized Ca ++ in the systemic blood is never reduced far enough to inhibit clotting. Citrate is an obligatory regional anticoagulant, i.e. only the blood outside the body is anticoagulated, There is zero risk of causing systemic bleeding. Occasionally, delay in metabolizing citrate causes modest reduction of the ionized Ca ++ level in the systemic blood and cause symptoms of citrate reaction Infusing calcium to the return line or to the replacement fluid reduces the incidence of symptomatic citrate toxicity: Calcium regimen Citrate anticoagulation Symptom rate (%) uthors No calcium 9.1% I.V. 10% Ca ++ gluconate 1 % Mokrzycki M, Kaplan. m J Kidney Dis 1994 Calcium added to lbumin before infusion 2.7% Kankirawatana et al. J Clin pheresis 2007

42 aracteristics: machine + anticoagulant eplacement volume for 3-liter exchange Plasma removal rate mtpe ctpe = Centrifugal Membrane Plasmapheresis 0.5L Sal + 2.5L 5% lb or 12 u FFP ~ 35 ml/min Plasma extraction ratio ~ 85% 80% (75-85%) Plasma flow rate Blood flow rate (Hct 40%) Vascular access ~ ml/min ~ ml/min Needles Central venous in arm veins catheter or Central venous catheter nticoagulation Citrate Heparin (CD- (usually) at ~1:12 ratio with whole blood) If citrate used 6 ml/min (to machine), minus 85% (extraction) = 1 ml/min to patient mtpe = Membrane Plasmapheresis 0.5L Sal + 2.5L 5% lb or 12 u FFP ~ 35 ml/min ~ 35% (30-50%) ~ 100 ml/min ~ 165 ml/min Central venous catheter Heparin (usually) or Citrate (at ~1:20) 8 ml/min, minus 35% = 5 ml/min

43 Figure 2. Comparison of characteristics of centrifugal and membrane plasmapheresis, with choices of plasma replacement or plasma regeneration. Centrifugal TPE Citrate (usually) Lower blood flow rate Peripheral veins or central line Process ~1.5 x blood volume Plasma extraction ~80% Membrane TPE Heparin (usually) Higher blood flow rate Central venous line Process ~3 x blood volume Plasma extraction ~30% Plasma replacement Plasma regeneration FFP for TTP 5% albumin for other indications dsorption column Cascade filtration Typical prescriptions for centrifugal plasmapheresis (ctpe) and membrane plasmapheresis (mtpe) differ markedly. The risk of hemolysis in mtpe filters requires the plasma extraction ratio to be lower; therefore more blood must be processed to extract the same amount of plasma. This requires a higher blood flow rate (and higher-flow vascular access) or may take longer than ctpe. Citrate or heparin anticoagulation can be used in either, though citrate is more suited to ctpe, and heparin to mtpe. Secondary plasma processing (plasma regeneration) is an option with either ctpe or mtpe. Ward DM, Conventional apheresis therapies: a review, J Clin pheresis, 26: , 2011

44 (a) blood return lbumin fraction (b) blood return blood return Purified plasma Purified plasma Globulin fraction #1 #2 #1 #2 from patient Effluent from patient from patient Whole plasma Whole plasma Whole plasma Fig. 3. Circuit diagrams of (a) primary membrane plasma separation plus secondary plasma fractionation, and (b) primary centrifugal plasma separation plus secondary plasma perfusion column. In the left panel (a), the primary separation of plasma from blood (#1) is in a hollow-fiber membrane plasma filter with a pore size of 0.3 microns and a molecular weight cut-off in excess of 1,000 kda. The secondary processing of plasma (#2) is in a hollow-fiber membrane plasma fractionator with a pore size of microns and a molecular weight cut-off of approximately 100 kda. lbumin (67 kda) passes through the secondary membrane and can be used as replacement fluid for the patient. Immunoglobulins, including IgG (146 kda), stay within the hollow-fiber lumen which drains to the effluent bag, thus removing most of the autoantibody present in the plasma. Membrane specifications are those of sahi products (sahi Kasei Kuraray Medical Co., Tokyo 101-8,101, Japan). In the right panel (b), the primary separation of plasma from blood (#1) is by a continuous-flow centrifuge, and the secondary processing of plasma (#2) is in a perfusion column that can contain an immuno-adsorbent or chemical adsorbent (see text). The pathogenic molecule binds to the column, which is replaced when exhausted. Other systems employ pairs of columns that can be regenerated by washing out the bound pathogenic molecule; one column is in active use while the other is being washed clean, and they switch periodically during the procedure. Either type of primary separation (#1) can in principal be coupled to any type of secondary plasma purification (#2). Many secondary devices in use in Europe and Japan, and some primary/secondary combination systems, are not FD- pproved in the US. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] Ward DM, Conventional apheresis therapies: a review. J Clin pheresis, 26: , 2011

45 TPE: typical treatment courses cute indications: TTP Daily or q.o.d. x wks; slow taper. Guillain Barré Daily x 3, q.o.d. x 3+; rarely repeat. Myasthenia crisis Daily x 3+, q.o.d. x 3+. nti GBM nephritis Daily x 6-7, q.o.d., taper Hep C vasculitis/f 3 per wk for 2-6 weeks Hyperviscosity One or two procedures ronic indications: Hyperviscosity Weekly, or q. 2-3 weeks, for years Myasthenia unremitting 1-3 per week, for weeks or months CIDP (polyneuropathy) 1-2 per week, for months or years FSGS in renal trnsplnt 2-3 per week for 2-3 months

46 Typical TPE prescription Diagnosis: ronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) 1. nticoagulant: CD- (cid Citrate Dextrose-) at 1:14 ratio with blood 2. Machine type: Centrifugal machine 3. Vascular access: Bilateral antecubital vein needles or IJ catheter or V fistula 4. Dose of plasmapheresis Volume of each procedure: 3.5 liter plasma removal Frequency of procedures: 3 per week for 3 weeks, then reassess 5. eplacement solutions: 1 liter saline, 2.5 liter 5% albumin. djust to fluid balance of 115%. or (if start fibrinogen <110mg/dl) 1 liter saline, 2 liter albumin, 2 units FFP. 6. Medications: (1) Give Calcium chloride or gluconate (dilute solution containing 1 meq / 10 ml) to return 80ml/hour (= 8 meq/hr) (2) If FFP: Premed with diphenhydramine (Benadryl) 25 mg I.V., and acetaminophen (Tylenol, paracetamol) two 325mg tablets p.o. 7. Labs: Fibrinogen at start each time, or at start and end a few times Pre-apheresis weekly: CBC, em Panel + Mg + Phos. Post-apheresis weekly: K, Ca, Mg, Phos, or one time only

47 pheresis modality Centrifugal plasmapheresis (ctpe) Typical apheresis prescriptions /C (ratio) Citrate 1:12 (1:14) Volume exchanged/ removed 1.2 (to 1.5) x PV Membrane plasmapheresis (mtpe) Heparin 1.2 (to 1.5) x PV Blood volume processed 1.5 (to 1.9) x TBV 3.5 (to 4.5) x TBV LDL-apheresis (Kaneka M-03 ) Heparin adsorbed 1.5 x TBV BC exchange (erythrocytapheresis) Platelet depletion (thrombocytapheresis) WBC depletion (leukocytapheresis) Hematopoietic Stem Cell collection Citrate 1:13 Citrate 1:6 (+) Citrate 1:12 (1:14) Citrate 1:12 (1:14) 4 to 8 units PBC 1.2 to 1.9 x TBV > 300 ml 1.0 to 1.5 x TBV 500 ml to >1800 ml 50 ml to 500 ml 2 x TBV (2 to) 4 x TBV Photopheresis (ECP) (Therakos CellEx ) Heparin ~240 ml 1500 ml Citrate = CD- PV = patient s total plasma volume TBV = patient s total blood volume

48 Practicalities of Therapeutic Plasma Exchange (TPE) SUMMY: 1. Types of apheresis 2. Separation by centrifugation 3. Therapeutic applications 4. Case report 5. mount of plasma exchange 6. oice of replacement fluid 7. nticoagulation 8. Typical apheresis prescriptions

49 Thank you for your attention

50 SVE THE DTE March 12-14, 2015 VISIT THE WEBSITE cme.ucsd.edu/apheresis 2½-day conference for MDs and Ns, from established practitioners to those starting a new program. Nationally prominent faculty. Didactic sessions on the basics. Symposia on plasma 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 mber P. Sanchez, MD Eileen Lischer, BSN, N, CNN Isagani Marquez, Jr., BSN, N Odette da, BSN, N Majella Vaughan, MPH