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R4 林孟羣 2013/01/29 1.  Indications of therapeutic plasma exchange  Technique of therapeutic plasma exchange  Therapeutic plasma exchange in selected.

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Presentation on theme: "R4 林孟羣 2013/01/29 1.  Indications of therapeutic plasma exchange  Technique of therapeutic plasma exchange  Therapeutic plasma exchange in selected."— Presentation transcript:

1 R4 林孟羣 2013/01/29 1

2  Indications of therapeutic plasma exchange  Technique of therapeutic plasma exchange  Therapeutic plasma exchange in selected topics Acute liver support Desensitization in solid organ transplantation Acute humeral rejections Neuro AIDP/CIPD RPGN/ vasculitis 2

3 CategoryDescriptionExample IAs first-line therapy, either as a primary standalone treatment or in conjunction with other modes of treatment Guillain-Barre’ syndrome; myasthenia gravis IIAs second-line therapy, either as a standalone treatment or in conjunction with other modes of treatment Acute disseminated encephalomyelitis after high-dose IV corticosteroid failure IIIOptimum role of apheresis therapy is not established In patients with sepsis and multiorgan failure IVApheresis might be ineffective or harmful Active rheumatoid arthritis J. Clin. Apheresis 25:83–177,

4 Category I  Acute inflammatory demyelinating polyneuropathy (Guillain-Barre’ Syndrome)  ANCA- associated RPGN (Wegener’s Granulomatosis) (dialysis dependence; diffuse alveolar hemorrhage)  Anti-glomerular basement membrane disease (Goodpasture’s syndrome) (dialysis independence; diffuse alveolar hemorrhage)  Chronic inflammatory demyelinating polyradiculoneuropathy  Cryoglobulinemia (Severe/symptomatic)  Focal segmental glomerulosclerosis  Hemolytic uremic syndrome (Atypical HUS due to autoantibody to factor H)  Hyperviscosity in monoclonal gammopathies  Myasthenia gravis ( moderate to severe, pre-thymectomy )  Paraproteinemic polyneuropathies  Pediatric autoimmune neuropsychiatric disorders associated with streptoccal infections and Sydenham’s chorea  Renal transplantation: Ab mediated rejection  Thrombotic microangiopathy: Ticlopidine/Clopidogrel –associated  Thrombotic thrombocytopenic purpura  Wilson’s disease, fulminant hepatic failure with hemolysis 4

5 J. Clin. Apheresis 25:83–177, 2010 Category II  ABO incompatible hematopoietic stem cell transplantation  ABO incompatible solid organ transplantation (kidney, heart (<40 months of age))  Acute disseminated encephalomyelitis  Pure red cell aplasia  AIHA, Cold agglutinin disease (life threatening)  Catastrophic antiphospholipid syndrome  Chronic focal encephalitis  Familial hypercholesterolemia (Homozygotes with small blood volume)  Hemolytic uremic syndrome (atypical HUS due to complement factor gene mutations)  Lambert-Eaton myasthenic syndrome  Multiple sclerosis (acute CNS inflammatory demyelinating disease unresponsive to steroids)  Myeloma cast nephropathy  Neuromyelitis optica (Devic’s syndrome)  Mushroom poisoning  Phytanic acid storage disease (Refsum’s disease)  Renal transplantation (Desensitization, living donor, positive crossmatch due to donor specific HLA antibody)  Systemic lupus erythematosus, Severe (e.g. cerebritis, diffuse alveolar hemorrhage) 5

6 58008C 血漿置換術(支付點數 2475 點) Plasma exchange :限下列病患實施  SLE , CNS involvement  Myasthenia gravis crisis  Macroglobulinaemia  RPGN  Goodpasture's disease  Multiple myeloma  Guillain-Barre syndrome  Thrombocytopenic purpura  Multiple sclerosis and neuromyelitis optica  其他經專案向保險人申請同意實施者 58016C 二重過濾血漿置換療法(支付點數 2475 點) Double filtration plasmapheresis :施行本項之適應症請依支 付標準 58008C 「血漿置換術」之規定辦理。 全民健保醫療費用支付查詢網站 : 6

7  Plasma echange Sequential centrifugal seperation Hollow fiber membrane seperation  Double filtration plasmapheresis 7

8 8 Membrane apheresis (MCS+) KM8800 Centrifugal Device KPS8800HF400

9 9 Transfus Apher Sci Apr;32(2): J Clin Apher. 2010;25(5):240-9

10 10

11 11 Transfus Apher Sci Apr;32(2):209-20


13 AdvantagesDisadvantages Membrane apheresis Fast and efficient plasmapheresis No citrate requirements Can be adapted for cascade filtration Removal of substances limited by sieving coefficient of membrane Unable to perform cytapheresis Requires high blood flows, central venous access Requires heparin anticoagulation, limiting use in bleeding disorders Centrifugal devices Capable of performing cytapheresis No heparin requirement More efficient removal of all plasma components Expensive Requires citrate anticoagulation Loss of platelets Brenner: Brenner and Rector's The Kidney, 8th ed 13

14 14 Transfus Apher Sci Apr;32(2):209-20

15 Evaflux TM (KURARAY MEDICAL INC.) Plasma fractionator


17 17

18 Portion of Plasma Volume a Exchanged (V e /V p ) Volume Exchanged (V e, mL ) Immunoglobulin or Other Substance Removed (MRR, %) 0.51, , , , , ,40095 a Plasma volume = 2,800 mL in a 70-kg patient, assuming hematocrit = 45%. V e, volume of plasma exchanged; V p, estimated plasma volume; MRR, macromolecule reduction ratio. Handbook of Dialysis 18

19 19 Am J Kidney Dis Dec;52(6):

20 20 Am J Kidney Dis Dec;52(6):

21 21  Plasma echange only Thrombotic thrombocytopenic purpura: remove inhibitors of ADAM-13 (autoantibody) + supply ADAM-13 Paraproteinemia with hyperviscosity syndrome: ex: Waldenstom macroglobinemia Liver support?  Causions High concentration of TG (>1770 mg/dl) may affect the sensitivity of sensors for detecting RBC in some devices

22 22 J Clin Apher. 2010;25(5):240-9

23 23 Transfusion Nov;44(11):1621-5

24 24 Am J Kidney Dis. 1994;23(6):817 J Clin Apher 1996;11:204–210 J Clin Apher. 2007;22(5):265-9 AuthorsProphylatic methodsSym. Rate R. WeinsteinContinous IV infusion of 10% Calcium gluconate in replace fluid (up to 25ml during 3-5L exchange) vs. - Oral CaCO3 - Boluses of IV 10% Calcium gluconate 8.6% 35.5% 29.4% Kankirawatan a et al. 1 mEq Ca in 500ml albumin fluid ( around 10 ml 10% Calcium gluconate in 1 L albumin fluid 2.7% Mokrzycki M.IV 10ml 10% Calcium gluconate 15mins after the start of PE, and another dose 1 hour later vs. No prophylaxis 1% 9.1%

25 25 Suggestion: 1.Routine check serum Calcium level during procedure in critical- ill patients (ICU setting) 2.Central vascular access via femoral vein 3.Follow up platelet level post procedure

26  An ideal liver assist device should support the three main liver functions: detoxification, regulation and synthesis  Toxic metabolites in liver failure: Water soluble: ammonia, urea Lipophilic: bilirubin, bile acids, aromatic amino acids and medium-chain fatty acids  Goal: briding to liver transplantation or until liver function recovery 26 Expert Rev. Gastroenterol. Hepatol. 5(5), 591–599

27  Hemodialysis  CRRT CVVH, CVVHD, CVVHDF  Plasma exchange  Hemoperfusion, plasma adsorption  Albumin-dialysate-based systems SPAD, MARS, Prometheus  Hybrid organ system 27

28 28 J Clin Apheresis 2010;25:  Rational: remove albumin bound and large molecular weight toxins, including aromatic amino acids, ammonia, endotoxin, indols, mercaptans, phenols and other factors which may be responsible for hepatic coma, hyperkinetic syndrome, decreased systemic vascular resistance and cerebral blood flow  Volume treated: 1 to 1.5 TPV  Replacement fluid: plasma; plasma/albumin  Frequency: daily  Duration: until transplantation or self-regeneration occurs

29 29 Liver International 2011: 31(Suppl. 3): 5–8

30 30

31 31  Rational: as an adjunct therapy to reduce anti-A or anti-B antibody titers in the peri-transplant period  Volume treated: 1 to 1.5 TPV  Replacement fluid: albumin; plasma  Frequency: daily, or every other day  Duration: the antibody titer (IgM and IgG) to < 8 in liver transplantation < 4 in renal transplantation ( heart transplantation in children age < 40 months)  F/u: antibody titers may increase 3-7 days after transplantation  daily antibody titer for the first 2 weeks post-transplantation J Clin Apheresis 2010;25:83-177

32 32 Transfusion Nov;48(11): Johns Hopkins Hospital

33 33 D-9 D-7 D-5 D-3 D-1 OP day D1 D3 D5 2 PV TPE (OR) 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP 1.5 PV DFPP TIW 1.5 PV DFPP Solumedrol 500mg IVIg 15g (heart lung machine) Bortezomib (Velcade) IV slow push IVIg 30g slowing infusion Solumedrol 500mg + Rituximab (Mabthera) IV drip RATG + FK506 IVIg IVIg IVIg IVIg IVIg Initial Ab X(1-78%) 5 = initial amount residual Ab X(1-86%) Experience from a heart transplantation case at NTUH

34 Diagnosis:  Documentation of donor specific antibody (DSA)  Histologic evidence of acute tissue injury, such as acute tubular injury, neutrophils in peritubular capillaries and/or glomeruli, and/ or capillary thrombosis, or intimal arteritis/ fibrinoid necrosis/ intramural or transmural inflammation in arteries  C4d in peritubular capillaries or immunoglobulin and complement in arterial fibrinoid necrotic areas by immunohistology 34 J Clin Apheresis 2010;25:83-177

35 35 Semin Immunol Apr; 24(2):136-42

36 36  Rational: remove donor-specific antibody (DSA), in combination with other immunosuppressive drugs  Volume treated: 1 to 1.5 TPV  Replacement fluid: albumin  Frequency: daily, or every other day  Duration: usually 5-6 sessions or improvement in renal function and decrease in DSA titers J Clin Apheresis 2010;25:83-177

37 37 J Clin Apheresis 2010;25:83-177

38 38 Transplantation Reviews 23 (2009) 34–46

39 39 J Clin Apheresis 2010;25:  Rational: AIDP: antoantibody-mediated damage to the peripheral nerve myelin CIDP: autoimmune attack on the peripheral nerves  Volume treated: 1 to 1.5 TPV  Replacement fluid: albumin  Frequency and duration: AIDP: every other day, 5-6 sessions over days CIDP: 2 to 3 TPE/week until improvement, then taper as tolerated, maintenance TPE may range from weekly to monthly

40 40 J Clin Apheresis 2010;25:  Rational: remove ANCA or anti-GBM antibody  Replacement fluid: albumin; plasma when DAH present  Frequency and duration: ANCA: daily procedures in fulminant cases or with pulmonary hemorrhage then continuing every 2-3 days for total of 6-9 procedures Anti-GBM: the minimum course of TPE should be 14 until resolution of ongoing glomerular or pulmonary injury, antibody can not be used as a disease activity marker

41 41 J Clin Apheresis 2010;25:  Rational: TPE may be beneficial for dialysis-dependent patients presenting with severe renal dysfunction; however, there is no therapeutic benefit over immunosuppression in milder disease  Disease with potential benefit: IgA nephropathy and cryoglobulinemia  Disease with no documented benefit: lupus nephritis  Replacement fluid: albumin  Frequency: every other day  Duration: treatment for 1–2 weeks followed by tapering The duration of therapy is not well defined in the literature

42  Liver support: TPV QD for 3 days (discuss with liver transplantation teams)  Desensitization: TPV QOD X 5 time then BIW until transplant  AMR: 1.5 TPV QD (TPE + IVIg after final session) or (DFPP+ divided IVIg) X 5 sessions  AIDP/CIDP: 1.5 TPV QOD X 5 sessions  RPGN 42

43 Thanks for your attention ! 43

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