Upload
yosef-hackworth
View
217
Download
0
Embed Size (px)
Citation preview
PLASMAPHERESIS
R4 林孟羣2013/01/29
1
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
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
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
4
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)
5
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
Plasma echange
Sequential centrifugal seperation
Hollow fiber membrane seperation
Double filtration plasmapheresis
7
Modalities of plasmaphoresis at NTUH
8
Membrane apheresis
(MCS+) KM8800
Centrifugal Device
KPS8800 HF400
Devices for plasma exchnage in NTUH
9Transfus Apher Sci. 2005 Apr;32(2):209-20J Clin Apher. 2010;25(5):240-9
Centrifugal seperation of plasma
10
11
Membrane seperation of plasma
Transfus Apher Sci. 2005 Apr;32(2):209-20
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
14
Cascade filtration technique
Transfus Apher Sci. 2005 Apr;32(2):209-20
EvafluxTM (KURARAY MEDICAL INC.)
Plasma fractionator
17
Molecular weight of removed substance
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
19
Distribution and metabolism of plasma proteins
Am J Kidney Dis. 2008 Dec;52(6):1180-96
20Am J Kidney Dis. 2008 Dec;52(6):1180-96
IgG titer change post plasma exchange
21
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
22
Complications of plasma echange
J Clin Apher. 2010;25(5):240-9
23Transfusion. 2004 Nov;44(11):1621-5
Complications of DFPP
24
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%
25
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
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
Blood purification for liver failure
Expert Rev. Gastroenterol. Hepatol. 5(5), 591–599
Hemodialysis
CRRT CVVH, CVVHD, CVVHDF
Plasma exchange
Hemoperfusion, plasma adsorption
Albumin-dialysate-based systems SPAD, MARS, Prometheus
Hybrid organ system
27
Modalities for liver support
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
29Liver International 2011: 31(Suppl. 3): 5–8
Comparison of liver support devices
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
32Transfusion. 2008 Nov;48(11):2453-60
A protocol for desensitization – kidney
Johns Hopkins Hospital
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 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
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
Antibody-mediated rejection (AMR)
J Clin Apheresis 2010;25:83-177
35Semin Immunol. 2012 Apr; 24(2):136-42
Targets for treatment of AMR
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
38Transplantation Reviews 23 (2009) 34–46
Treatment protocols for AMR of renal allografts
39
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
40
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
41
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
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
42
Summary of current approach at NTUH
Thanks for your attention !
43