PLASMAPHERESIS

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PLASMAPHERESIS

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

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Plasmapheresis plasma withdrawal
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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

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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

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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

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Possible mechanisms of TPE
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Monitored substance in plasma during PE
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Monitored substance in plasma during TPE
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Applications of plasmapheresis

• 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

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Treatment diagnosis ()Malchelsky et al, Ther
Apher. 2001 5193-206.

• Disease Asia Europe USA S.Am Total
• Neurology 27 23 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 10 17 5

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Top 6 treatment diagnosis no of
patientsMalchelsky et al, Ther Apher. 2001
5193-206.

• Asia Europe USA SAm Total
• 1 MG H-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

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The first 5 indications of TA in countries
Country 1st 2nd 3rd 4th
5th Japan/95 FH GBS Hepatitis
H.failure Sepsis Germany/87 Rejection GBS
H.failure HVS MG Canada/85 GBS MG
M-protein SLE TTP France/94 GBS MG
TTP HVS CIDP USA/91 GBS TTP
MG HVS N-pathy Taiwan/00 MG GBS
Hepatitis TTP C-SLE IAR/00 MG GBS
Lipid Liver RA
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Plasmaphresis in Neurology
Investigational Refsum disease, acquired
neuromyotonia, Stiff-man syndrome,
Cryoglobulinemic neuropathy, CNS lupus, ADEM
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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)

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Clinical responseYeh JH, Acta Neurol Scand
1999100305-9.
Poor Fair Good 0 2 212 53 1
5 38 62 48 gt5
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Favorable prognostic parametersYeh JH, Acta
Neurol Scand 1999100305-9.

• High MG score
• Pathology of non-thymoma type
• Young age at onset
• Daily apheresis
• High removal rate for IgG

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Plasma exchange in GBSGBS Study Group, Neurology
1985,35,1094-104 245 patients 40-50 cc/kg for
3-5 PE

• Parameters PE No Tx p
• Improve gt 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).

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Change of MRC-sum score during DF Plasmapheresis
in GBSChen et al, J Clin Apheresis
199914126-9.
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Plasmapheresis in GBS
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Plasmapheresis in GBS
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Thrmobotic Thrombocytopenic Purpura

• Microangiopathic hemolytic anemia
• Negative Coombs' test
• Thrombocytopenia platelet lt 100000/ul
• CNS abnormalities
• Headache, confusion, focal deficit seizure
• Renal involvement
• Fever temperature gt 380C

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TaTTP 77M anorexia and malaise for 3
DTiclopidine 100 mg bid for 1M

• 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

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77 y/o male Ticlopidine-associated TTP Yeh et
al, Formosan J Med 20004645-50.
Day 1 Confusion without focal signs
Day 7 Semicoma quadriplegia
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PE (qd)
HD (qod)
Pred.
??
????? (???? E2M4Ve) ????
??
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Platelet response to PE in TaTTPYeh et al,
Formosan J Med 20004645-50.
20 u FFP/session
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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-ENASSA()B()
• Anti-ENA Sm Ab (-)
• Anti-cardiolipin IgG 8.4
• C3 52.8 (79.9)
• C4 17.2 (16.6)
• IgG/A/M1780/313/76.7

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Steroid PP HD
80-40 mg/day
QOD for 23 sessions
2/wk for 34 days
Platelet
Hb
BUN
Cr
Urine
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SLE 49F nephrotic syndrome for 3 weeks

• Renal
• Ccr 66.4 cc/hr
• Urine protein 6.1 g/d
• Path diffuse MGN with endocapillary
  proliferation (IIIIV)
• 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/M1120/653/33.8

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SLE 49F nephrotic 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 DVT
DV
PP QOD5
Intubation
Seizure
D6
D17
D28
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Rapid progressive glomerulonephritis 29 FSerum
creatinine level during immunotherapy (96/12-97/4)
PP
Steroid
Endoxan
Protein loss
5.5 G
1.2 G
1.9 G
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ChP
COP
VAD
CP
CP
MP
CP
Chemotherapy
Retinal bleeding
Epistaxis
Chest tightness
Dizziness
Plasmapheresis
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WM 70M dizziness epistaxis for 3 M Yeh et
al, Formosan J Med 19982141-7.
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Reduction of serum protein by DFPYeh et al,
Formosan J Med 19982141-7.

• Globulin IgG IgA IgM
• Myeloma 9.2-3.2 1020-537 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

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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)

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Plasma/blood exchange in meningococcal sepsisvan
Deuren M et al, Clin Inf Dis 1992,15424-30

• 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.

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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(-) gt G() gt Mixed gt Fungus
• Prognostic factor admission-treatment interval

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Post-operative cholestasis 61MYeh et al,
Formosan J Med 19993538-42.
Plasorba BR-350 QOD3 sessions
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Development of LDL apheresis
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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.

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Regression of coronary plaque by HELP
Stenosis
Reference segments
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EKG changes in LDL apheresis Kroon et al,
Circulation 1996931826-35
N17
N15
Time to 1 mm ST depression (ST-time) and maximal
ST Depression (ST-max), 0.01ltplt0.05
0.001ltplt0.01 Plt0.001
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??????????

• ???????
• ?????? (???)
• ??????
• ??????? (PTCA, CABG)
• ??????
• ??????
• ?????, ?????
• ???????

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Hemodynamically significant stenoses in the
aortotibial tract - at baseline and at 2 years
Plt0.002
Kroon et al, Ann Intern Med, 1996125945-54
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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.

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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
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Changes of TG lipase levels after PE in
hyperlipidemic pancreatitis
TG1st (62-90) 2nd (86-92)
Lipase1st (52-92) 2nd (62-78)
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Adverse effects of hemapheresis

• Problems with vascular access
• Anti-coagulant related
• Change of circulatory status
• Apheresis material-related
• Transfusion reaction

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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

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Procedure-related immune modulation

• 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)

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Compatibility of materials
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TA-related immune modulation
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Apheresis in malignancyNand S, Ther Apheresis
1997129-32.

• Myeloma, solid tumor (breast, colon, melanoma,
  lung, thyroid)
• Plasmapheresis, Protein A apheresis, Photoimmune
  apheresis