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Plasmapheresis R4林孟羣 2013/01/29.

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Presentation on theme: "Plasmapheresis R4林孟羣 2013/01/29."— Presentation transcript:

1 Plasmapheresis R4林孟羣 2013/01/29

2 Outline 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 ASFA Guidelines 2010 Category Description Example I
As first-line therapy, either as a primary standalone treatment or in conjunction with other modes of treatment Guillain-Barre’ syndrome; myasthenia gravis II As 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 III Optimum role of apheresis therapy is not established In patients with sepsis and multiorgan failure IV Apheresis might be ineffective or harmful Active rheumatoid arthritis J. Clin. Apheresis 25:83–177, 2010

4 ASFA Guidelines 2010 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 J. Clin. Apheresis 25:83–177, 2010

5 ASFA Guidelines 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) J. Clin. Apheresis 25:83–177, 2010

6 健保給付之適應症 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:

7 Modalities of plasmaphoresis at NTUH
Plasma echange Sequential centrifugal seperation Hollow fiber membrane seperation Double filtration plasmapheresis

8 Devices for plasma exchnage in NTUH
Centrifugal Device Membrane apheresis (MCS+) KM8800 KPS8800 HF400

9 Centrifugal seperation of plasma
Transfus Apher Sci Apr;32(2):209-20 J Clin Apher. 2010;25(5):240-9


11 Membrane seperation of plasma
Transfus Apher Sci Apr;32(2):209-20


13 Comparison between these methods
Advantages Disadvantages 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

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

15 EvafluxTM (KURARAY MEDICAL INC.) Plasma fractionator


17 Molecular weight of removed substance

18 Target volume Portion of Plasma Volumea Exchanged (Ve/Vp)
Volume Exchanged (Ve, mL) Immunoglobulin or Other Substance Removed (MRR, %) 0.5 1,400 39 1.0 2,800 63 1.5 4,200 78 2.0 5,600 86 2.5 7,000 92 3.0 8,400 95 aPlasma volume = 2,800 mL in a 70-kg patient, assuming hematocrit = 45%. Ve, volume of plasma exchanged; Vp, estimated plasma volume; MRR, macromolecule reduction ratio. Handbook of Dialysis

19 Distribution and metabolism of plasma proteins
Am J Kidney Dis Dec;52(6):

20 IgG titer change post plasma exchange
Am J Kidney Dis Dec;52(6):

21 Which modalities? Plasma echange only
Thrombotic thrombocytopenic purpura: remove inhibitors of ADAM (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 Complications of plasma echange
J Clin Apher. 2010;25(5):240-9

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

24 Prophylactic calcium administration in TPE
Authors Prophylatic methods Sym. Rate R. Weinstein Continous 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% Kankirawatana 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% Am J Kidney Dis. 1994;23(6):817 J Clin Apher 1996;11:204–210 J Clin Apher. 2007;22(5):265-9

25 Modification of current protocol
Suggestion: Routine check serum Calcium level during procedure in critical-ill patients (ICU setting) Central vascular access via femoral vein Follow up platelet level post procedure

26 Blood purification for liver failure
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 Expert Rev. Gastroenterol. Hepatol. 5(5), 591–599

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

28 ASFA guidelines for acute liver failure
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 J Clin Apheresis 2010;25:83-177

29 Comparison of liver support devices
Liver International 2011: 31(Suppl. 3): 5–8

30 Comparison of disfferent modalities

31 ABO incompatible solid organ transplantation
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 A protocol for desensitization – kidney
Johns Hopkins Hospital Transfusion Nov;48(11):

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

34 Antibody-mediated rejection (AMR)
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 J Clin Apheresis 2010;25:83-177

35 Targets for treatment of AMR
Semin Immunol Apr; 24(2):136-42

36 ASFA guidelines for AMR of renal allografts
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 ASFA guidelines for AMR of cardiac allografts
J Clin Apheresis 2010;25:83-177

38 Treatment protocols for AMR of renal allografts
Transplantation Reviews 23 (2009) 34–46

39 ASFA guidelines for AIDP/CIDP
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 J Clin Apheresis 2010;25:83-177

40 ASFA guidelines for RPGN
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 J Clin Apheresis 2010;25:83-177

41 ASFA guidelines for RPGN
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 J Clin Apheresis 2010;25:83-177

42 Summary of current approach at NTUH
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  sessions AIDP/CIDP: 1.5 TPV QOD X 5 sessions RPGN

43 Thanks for your attention!

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