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PLASMAPHERESIS

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

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  1. PLASMAPHERESIS Jiann-Horng Yeh, M.D. Department of Neurology, Blood Purification Center Shin Kong WHS Memorial Hospital

  2. Plasmapheresis: plasma + withdrawal

  3. 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

  4. 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

  5. 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

  6. Possible mechanisms of TPE

  7. Monitored substance in plasma during PE

  8. Monitored substance in plasma during TPE

  9. 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

  10. 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

  11. 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 PlateletH-chol 4 SLE GBS GBS MG Liver 5 L-GN Circulat. Breast Ca TTP RA 6 GBS GN S/S ITP ScleroD

  12. 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

  13. Plasmaphresis in Neurology Investigational: Refsum disease, acquired neuromyotonia, Stiff-man syndrome, Cryoglobulinemic neuropathy, CNS lupus, ADEM

  14. 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)

  15. 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

  16. 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

  17. 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).

  18. Change of MRC-sum score during DF Plasmapheresis in GBSChen et al, J Clin Apheresis 1999;14:126-9.

  19. Plasmapheresis in GBS

  20. Plasmapheresis in GBS

  21. 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

  22. 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

  23. 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

  24. PE (qd) HD (qod) Pred. 昏亂 半昏迷狀態 (昏迷指數 E2M4Ve) 四肢癱瘓 癲癇

  25. Platelet response to PE in TaTTPYeh et al, Formosan J Med 2000;4:645-50. 20 u FFP/session

  26. 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

  27. Steroid PP HD 80-40 mg/day QOD for 23 sessions 2/wk for 34 days Platelet Hb BUN Cr Urine

  28. 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

  29. 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

  30. 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

  31. CP ChP COP VAD CP CP MP Chemotherapy Retinal bleeding Epistaxis Chest tightness Dizziness Plasmapheresis

  32. WM70Mdizziness & epistaxis for 3 M Yeh et al, Formosan J Med 1998;2:141-7.

  33. 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%

  34. 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)

  35. 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.

  36. 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

  37. Post-operative cholestasis 61MYeh et al, Formosan J Med 1999;3:538-42. Plasorba BR-350QOD*3 sessions

  38. Development of LDL apheresis

  39. 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.

  40. Regression of coronary plaque by HELP Stenosis Reference segments

  41. 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

  42. 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

  43. 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

  44. 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. *

  45. 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

  46. Changes of TG & lipase levels after PE in hyperlipidemic pancreatitis TG:1st (62-90%); 2nd (86-92%) Lipase:1st (52-92%); 2nd (62-78%)

  47. Adverse effects of hemapheresis • Problems with vascular access • Anti-coagulant related • Change of circulatory status • Apheresis material-related • Transfusion reaction

  48. 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

  49. 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

  50. Compatibility of materials

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