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PLASMAPHERESIS R4 林林林 2013/01/29 1

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

PLASMAPHERESIS

R4 林孟羣2013/01/29

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Page 2: R4 林孟羣 2013/01/29 1.  Indications of therapeutic plasma exchange  Technique of therapeutic plasma exchange  Therapeutic plasma exchange in selected

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

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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

ASFA Guidelines 2010

J. Clin. Apheresis 25:83–177, 2010 3

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ASFA Guidelines 2010

J. Clin. Apheresis 25:83–177, 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

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ASFA Guidelines 2010

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)

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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。

健保給付之適應症

全民健保醫療費用支付查詢網站 : http://www.nhi.gov.tw/query/query2_list.aspx 6

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Plasma echange

Sequential centrifugal seperation

Hollow fiber membrane seperation

Double filtration plasmapheresis

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Modalities of plasmaphoresis at NTUH

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Membrane apheresis

(MCS+) KM8800

Centrifugal Device

KPS8800 HF400

Devices for plasma exchnage in NTUH

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9Transfus Apher Sci. 2005 Apr;32(2):209-20J Clin Apher. 2010;25(5):240-9

Centrifugal seperation of plasma

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Membrane seperation of plasma

Transfus Apher Sci. 2005 Apr;32(2):209-20

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  Advantages DisadvantagesMembrane apheresis

Fast and efficient plasmapheresisNo citrate requirementsCan be adapted for cascade filtration

Removal of substances limited by sieving coefficient of membraneUnable to perform cytapheresisRequires high blood flows, central venous accessRequires heparin anticoagulation, limiting use in bleeding disorders

Centrifugal devices

Capable of performing cytapheresisNo heparin requirementMore efficient removal of all plasma components

ExpensiveRequires citrate anticoagulationLoss of platelets

Brenner: Brenner and Rector's The Kidney, 8th ed 13

Comparison between these methods

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Cascade filtration technique

Transfus Apher Sci. 2005 Apr;32(2):209-20

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EvafluxTM (KURARAY MEDICAL INC.)

Plasma fractionator

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Molecular weight of removed substance

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Portion of Plasma Volumea Exchanged (Ve/Vp)

Volume Exchanged (Ve, mL)

Immunoglobulin or Other Substance Removed (MRR, %)

0.5 1,400 391.0 2,800 631.5 4,200 782.0 5,600 862.5 7,000 923.0 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 18

Target volume

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Distribution and metabolism of plasma proteins

Am J Kidney Dis. 2008 Dec;52(6):1180-96

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20Am J Kidney Dis. 2008 Dec;52(6):1180-96

IgG titer change post plasma exchange

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Which modalities?

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

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Complications of plasma echange

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

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23Transfusion. 2004 Nov;44(11):1621-5

Complications of DFPP

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Prophylactic calcium administration in TPE

Am J Kidney Dis. 1994;23(6):817J Clin Apher 1996;11:204–210J Clin Apher. 2007;22(5):265-9

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%

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Modification of current protocol

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

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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

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Blood purification for liver failure

Expert Rev. Gastroenterol. Hepatol. 5(5), 591–599

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Hemodialysis

CRRT CVVH, CVVHD, CVVHDF

Plasma exchange

Hemoperfusion, plasma adsorption

Albumin-dialysate-based systems SPAD, MARS, Prometheus

Hybrid organ system

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Modalities for liver support

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28J Clin Apheresis 2010;25:83-177

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

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

Comparison of liver support devices

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Comparison of disfferent modalities

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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

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32Transfusion. 2008 Nov;48(11):2453-60

A protocol for desensitization – kidney

Johns Hopkins Hospital

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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 500mgIVIg 15g (heart lung machine)

Bortezomib (Velcade) IV slow pushIVIg 30g slowing infusion

Solumedrol 500mg + Rituximab (Mabthera) IV dripRATG + FK506

IVIg IVIg IVIg IVIg IVIg

Initial Ab X(1-78%)5

=0.0005 initial amount residual Ab X(1-86%)

A proposed protocol for desensitization - heartExperience from a heart transplantation case at NTUH

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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

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Antibody-mediated rejection (AMR)

J Clin Apheresis 2010;25:83-177

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35Semin Immunol. 2012 Apr; 24(2):136-42

Targets for treatment of AMR

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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

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ASFA guidelines for AMR of cardiac allografts

J Clin Apheresis 2010;25:83-177

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38Transplantation Reviews 23 (2009) 34–46

Treatment protocols for AMR of renal allografts

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ASFA guidelines for AIDP/CIDP

J Clin Apheresis 2010;25:83-177

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 10-14 days CIDP: 2 to 3 TPE/week until improvement, then taper as tolerated,

maintenance TPE may range from weekly to monthly

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ASFA guidelines for RPGN

J Clin Apheresis 2010;25:83-177

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

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ASFA guidelines for RPGN

J Clin Apheresis 2010;25:83-177

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

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Liver support: 1-1.5 TPV QD for 3 days (discuss with liver transplantation teams)

Desensitization: 1-1.5 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

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Summary of current approach at NTUH

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Thanks for your attention !

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