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PLASMAPHERESIS. Jiann-Horng Yeh, M.D. Department of Neurology, Blood Purification Center Shin Kong WHS Memorial Hospital. Plasmapheresis: plasma + withdrawal. History of plasmapheresis. Ancient times: blood letting technique Louis XI (1461-83) drank the blood of infant to keep healthy
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PLASMAPHERESIS Jiann-Horng Yeh, M.D. Department of Neurology, Blood Purification Center Shin Kong WHS Memorial Hospital
History of plasmapheresis • Ancient times: blood letting technique • Louis XI (1461-83) • drank the blood of infant to keep healthy • Pope Innocent VIII • blood transfusion from 3 youths to regain health • 1667: 1st modern transfusion: lamb-to-man • 1818: Human-to-human transfusion
History of modern plasmapheresis • 1909 Fleig / France • Auto & heterotransfusion of washed corpuscles • 1914 Abel / U.S. • Use the term of Plasmapheresis in his paper • Prolonged the life of dog with bilateral nephrectomy by plasmapheresis • 1970 • Invention of cell separator machine
Creatinine Antibiotic IgG, IgA Albumin Spectrum of Blood Purification Urea LDL IgM 101 102 103 104 105 106 cell • Whole blood exchange 1900 • Hemodialysis 1940 • Hemofiltration 1970 • Hemoadsorption 1960 • Plasma exchange 1970 • Double filtration PP 1980 • Plasma adsorption 1980 • Cytapheresis 1990
Metabolic disease Familiar hypercholesterolemia Hyperviscosity syndrome Multiple myeloma Macroglobulinemia Miscellaneous Malignant tumor Organ transplant rejection Neurology MG, AIDP/CIDP, MS Hematology TTP, Hemophilia Rheumatology SLE, RA, PSS Nephrology RPGN, Goodpasture S. Dermatology Pemphigus Applications of plasmapheresis
Treatment diagnosis (%)Malchelsky et al, Ther Apher. 2001 ;5:193-206. Disease Asia Europe USA S.Am Total Neurology 2723 40 29 28 Immunology 19 15 4 0 15 Endocrine 10 21 7 6 13 Circulatory 5 17 4 17 8 GI 14 2 2 0 8 Neoplasm 4 3 24 3 7 GU 8 7 1 3 7 Hematology 2 5 1017 5
Top 6 treatment diagnosis no of patientsMalchelsky et al, Ther Apher. 2001 ;5:193-206. Asia Europe USA SAm Total 1 MGH-chol Neoplasm S/S MG 2 Liver MG MS GBS GBS 3 RA Sclero MG PlateletH-chol 4 SLE GBS GBS MG Liver 5 L-GN Circulat. Breast Ca TTP RA 6 GBS GN S/S ITP ScleroD
The first 5 indications of TA in countries Country1st 2nd 3rd 4th 5th Japan/95 FH GBS Hepatitis H.failure Sepsis Germany/87 Rejection GBS H.failure HVSMG Canada/85 GBSMGM-protein SLE TTP France/94 GBSMG TTPHVS CIDP USA/91 GBSTTPMGHVS N-pathy Taiwan/00 MGGBS Hepatitis TTP C-SLE IAR/00 MG GBS Lipid Liver RA
Plasmaphresis in Neurology Investigational: Refsum disease, acquired neuromyotonia, Stiff-man syndrome, Cryoglobulinemic neuropathy, CNS lupus, ADEM
Plasma Exchange - MG • Dose: 5 exchanges over 9 to 10 days • Indications: • Acutely ill MG patient • Pre-thymectomy (respiratory/bulbar involvement) • Advantages • Very short onset of action (3 to 10 days) • Probably more effective in crisis than IVIG • Disadvantages • Requires specialized equipment & personnel • Complications more frequent in elderly • High cost with short-term effects (weeks)
Clinical responseYeh JH, Acta Neurol Scand 1999;100:305-9. Poor Fair Good 0: 2 2:12 5:3 1: 5 3:8 6:2 4:8 >:5
Favorable prognostic parametersYeh JH, Acta Neurol Scand 1999;100:305-9. • High MG score • Pathology of non-thymoma type • Young age at onset • Daily apheresis • High removal rate for IgG
Plasma exchange in GBSGBS Study Group, Neurology 1985,35,1094-104245 patients; 40-50 cc/kg for 3-5 PE Parameters PE No Tx p Improve > 1 grade at 4 wks 59% 39% * Mean grade change at 4 wks 1.1 G 0.4 G ** Median time to improve 1 G 19 D 40 D ** Median time to walk unaided 53 D 85 D ** Median time on ventilator 24 D 48 D * Failed to improve 1 G at 6M 3% 13% * Plasmapheresis appears to be of benefit in patients with GBS of recent onset (within 7 days).
Change of MRC-sum score during DF Plasmapheresis in GBSChen et al, J Clin Apheresis 1999;14:126-9.
Thrmobotic Thrombocytopenic Purpura • Microangiopathic hemolytic anemia • Negative Coombs' test • Thrombocytopenia: platelet < 100000/ul • CNS abnormalities • Headache, confusion, focal deficit & seizure • Renal involvement • Fever: temperature > 380C
Microangiopathic hemolytic anemia Hb: 8.3 g/dL Reticulocyte: 1.9% LDH: 1497 U/L Smear: schizocyte, acanthocyte negative Coombs test Thrombocytopenia Platelet 5000/uL Acute renal failure BUN: 53 mg/dL (119-D3) Cr: 2.9 mg/dL (9-D3) Biopsy: thrombotic microangiopathy CNS Confusion at D1 Seizure, semicoma at D3 TaTTP 77M anorexia and malaise for 3 DTiclopidine 100 mg bid for 1M
77 y/o male Ticlopidine-associated TTP Yeh et al, Formosan J Med 2000;4:645-50. Day 1 Confusion without focal signs Day 7 Semicoma; quadriplegia
PE (qd) HD (qod) Pred. 昏亂 半昏迷狀態 (昏迷指數 E2M4Ve) 四肢癱瘓 癲癇
Platelet response to PE in TaTTPYeh et al, Formosan J Med 2000;4:645-50. 20 u FFP/session
SLE-HUS 31F anemia & renal insufficiency • Renal • BUN/Cr: 115/8.8 • Urine protein: 1.08g/d • Thrombotic angiopathy • Hematologic • LDH: 1559 • Hb/11.3; MCHC/32.4; Fe/46; TIBC/245; reticulocyte/3% • Intravascular hemolysis • Platelet: 12000 • Immunologic • Anti-ds DNA: 512 (256) • ANA: 5120 Spe (320) • Anti-ENA:SSA(+);B(+) • Anti-ENA Sm Ab (-) • Anti-cardiolipin IgG: 8.4 • C3: 52.8 (79.9) • C4: 17.2 (16.6) • IgG/A/M:1780/313/76.7
Steroid PP HD 80-40 mg/day QOD for 23 sessions 2/wk for 34 days Platelet Hb BUN Cr Urine
SLE 49Fnephrotic syndrome for 3 weeks • Renal • Ccr: 66.4 cc/hr • Urine protein: 6.1 g/d • Path: diffuse MGN with endocapillary proliferation (III+IV) • Hematologic • LDH: 1105 • Hb: 9.5; Platelet: 84000 • aPTT: 38.7/31.7 • CNS • Stupor, seizure, coma • Immunologic • Anti-ds DNA: 512 (256) • ANA: 2560 HOM (320) • Anti-ENA SSA(+); B(-) • Anti-cardiolipin IgG: 9.8 • C3: 36.9 (107) • C4: 7.4 (21.2) • IgG/A/M:1120/653/33.8
SLE 49Fnephrotic syndrome for 3 weeks Antibiotics (2-combined) CNS Lupus D6 sluured speech D8 slow response E4M6V4 D9 E3M4V1 D10 E1M4V1 D11 seizure/status D13 improving D15 almost clear D17 extubation Overall stay: 45 days Steroid: 160-40 1000 40 AED: D+V+T D+V PP: QOD*5 Intubation Seizure D6 D17 D28
Rapid progressive glomerulonephritis 29 FSerum creatinine level during immunotherapy (96/12-97/4) PP Steroid Endoxan 5.5 G 1.2 G 1.9 G Protein loss
CP ChP COP VAD CP CP MP Chemotherapy Retinal bleeding Epistaxis Chest tightness Dizziness Plasmapheresis
WM70Mdizziness & epistaxis for 3 M Yeh et al, Formosan J Med 1998;2:141-7.
Reduction of serum protein by DFPYeh et al, Formosan J Med 1998;2:141-7. Globulin IgG IgA IgM Myeloma 9.2-3.21020-537 43-38 9090-2450 n= 1 65% 47% 12% 73% Control 2.5-1.2 1092-415 248-69 122-16 n= 54 52% 62% 72% 87%
Adjuvant therapy in sepsis • Immune products • High dose IV immunoglobulin • Endotixin antibody • Anti-mediator agents: Il-1 receptor antagonist, TNF-a antibody • Plasmapheresis • Plasma or blood exchange • Charcoal hemoperfusion • Plasmaleukapheresis • Polymyxin B hemoperfusion (Toray-Myxin)
Plasma/blood exchange in meningococcal sepsisvan Deuren M et al, Clin Inf Dis 1992,15:424-30 • PE was started after a delay over 40 hrs in 2 fatal cases under PE. • Early initiation of PE may improve the rate of survival among pts with meningococcal infection and hypotension.
Polymyxin B adsorption column • History • 1983: first applied in animal • 1994: phase III human trial • Clincal results • Survival rate: 65% • Reduce endotoxin, IL-6, IL-10 & TNF. • Survival rate: G(-) > G(+) > Mixed > Fungus • Prognostic factor: admission-treatment interval
Post-operative cholestasis 61MYeh et al, Formosan J Med 1999;3:538-42. Plasorba BR-350QOD*3 sessions
Liposorber study groupGordon et al, Am J Cardiol 1998 • 70-80% of acute lipoprotein lowering maintained overtime. • Support the long-term safety & clinical efficacy in patients with FH (heter/homozygote) inadequately controlled with diet and medications.
Regression of coronary plaque by HELP Stenosis Reference segments
EKG changes in LDL apheresis Kroon et al, Circulation 1996;93:1826-35 N=17 N=15 Time to 1 mm ST depression (ST-time) and maximal ST Depression (ST-max), * 0.01<p<0.05; ** 0.001<p<0.01; ***P<0.001
血脂淨化療法之適應症 • 遺傳性高脂血症 • 冠狀動脈堵塞 (冠心症) • 藥物控制不佳 • 不適侵襲性療法 (PTCA, CABG) • 術後恢復不佳 • 末稍動脈堵塞 • 急性腦梗塞, 血管性癡呆 • 視網膜動脈堵塞
Hemodynamically significant stenoses in the aortotibial tract - at baseline and at 2 years P<0.002 Kroon et al, Ann Intern Med, 1996;125:945-54
Influence of 1st, 5th, & 10th HELP on VaD * * MMSE * ADL Scale * * * Mathew Scale * * • Improvement were achieved until the 5th treatment. • Between the 5th and 10th treatment, no further improvement was observed. *
Hyperlipidemic pancreatitis Age PE Triglyceride Lipase RS date Pre 1st 2nd Pre 1st 2nd 36 D2 1501 33% 14% 2894 33% 22% Good 40 D2 1835 38% ND 7965 8% ND Good 43 D5 2348 22% 10% 1537 48% 38% Dead 37 D3 2240 10% 8% 5285 NC NC Op All male; ND: not done/only 1 PE; NC: not checked
Changes of TG & lipase levels after PE in hyperlipidemic pancreatitis TG:1st (62-90%); 2nd (86-92%) Lipase:1st (52-92%); 2nd (62-78%)
Adverse effects of hemapheresis • Problems with vascular access • Anti-coagulant related • Change of circulatory status • Apheresis material-related • Transfusion reaction
Adverse transfusion reaction JAMA,1988 • Infectious reaction • HBV : 1/200-1/300 • HIV : 1/40000-1000000 • CMV : asymptomatic • HTLV : delayed ? • Immunological reaction • Fever, chill & urticaria: 1/100 • Hemolytic reaction: 1/6000
Direct effect Extracorporeal circulation Blood exposure to system Effect of leachable molecule Additive Anticoagulant Fluid or macromolecule Indirect effect Cellular Humoral Seconday impact to patients (eg. hypotension) Procedure-related immune modulation