1. Asahi Kasei MedicalAsahi Kasei Medical
Plasma TherapyPlasma Therapy
Training ProgrammeTraining Programme

2. Asahi Kasei MedicalAsahi Kasei Medical
Biomembrane DialysersBiomembrane Dialysers
Polysulfone DialysersPolysulfone Dialysers
Polyacryronitrile HemofiltersPolyacryronitrile Hemofilters
Hemodialysers & FiltersHemodialysers & Filters
Blood Transfusion FiltersBlood Transfusion Filters Leukocyte Reduction FiltersLeukocyte Reduction Filters
Apheresis DevicesApheresis Devices
Plasma SeparatorPlasma Separator
Plasma Component SeparatorsPlasma Component Separators
Immunoadsorption ColumnsImmunoadsorption Columns
Plasma Perfusion ColumnPlasma Perfusion Column
Hemoperfusion ColumnHemoperfusion Column

3. Asahi Kasei MedicalAsahi Kasei Medical
Biomembrane Dialysers
Polysulfone Dialysers
Polyacryronitrile Hemofilters
Hemodialysers & Filters
Blood Transfusion Filters Leukocyte Reduction Filters
Apheresis DevicesApheresis Devices
Hemoperfusion ColumnHemoperfusion Column
Plasma Perfusion ColumnPlasma Perfusion Column
Immunoadsorption ColumnsImmunoadsorption Columns
Plasma Component SeparatorsPlasma Component Separators
Plasma SeparatorPlasma Separator

4. Apheresis Devices - 1Apheresis Devices - 1
Plasma SeparatorPlasma Separator
- Plasmaflo OP-05Plasmaflo OP-05
- Cell-free separation of plasmaCell-free separation of plasma
- Treatment of various diseases,Treatment of various diseases,
auto-immune, neurological, etc.auto-immune, neurological, etc.
- Separated plasma can be further treatedSeparated plasma can be further treated
Plasma Component SeparatorsPlasma Component Separators
- Cascadeflo ECCascadeflo EC
- Removal of pathogens by secondary filtrationRemoval of pathogens by secondary filtration
- Purified plasma can be returned to patientPurified plasma can be returned to patient
- Treatment of various diseases, autoimmune,Treatment of various diseases, autoimmune,
neurological, etc.neurological, etc.

5. Apheresis Devices - 2Apheresis Devices - 2
Immunoadsorption ColumnsImmunoadsorption Columns
- TR-350, PH-350 for treatment of various diseases,TR-350, PH-350 for treatment of various diseases,
autoimmune, neurological, etc.autoimmune, neurological, etc.
Plasma Perfusion ColumnPlasma Perfusion Column
- BR-350 for treatment of liver diseasesBR-350 for treatment of liver diseases
and intoxicationsand intoxications
Hemoperfusion ColumnHemoperfusion Column
- Cellsorba for whole blood perfusionCellsorba for whole blood perfusion
- Removal of LeucocytesRemoval of Leucocytes
- Treatment of IBDTreatment of IBD

6. Plasma TherapyPlasma Therapy
 19021902 Washing and return of blood from uraemic patientWashing and return of blood from uraemic patient
 19441944 Frequent plasma separation possible – plasmaFrequent plasma separation possible – plasma
required during the warrequired during the war
 19521952 Manual plasmapheresis first used therapeuticallyManual plasmapheresis first used therapeutically
 19651965 First continuous flow cell separator – buffy coatFirst continuous flow cell separator – buffy coat
removal possibleremoval possible
 1970's1970's Plasma exchange for Goodpastures / MGPlasma exchange for Goodpastures / MG
 1980's1980's Plasmapheresis programmes for routine collectionPlasmapheresis programmes for routine collection
of blood productsof blood products
 1990’s1990’s Treatment of plasma componentsTreatment of plasma components
 2000’s2000’s Improvement in whole blood technologies to replaceImprovement in whole blood technologies to replace
some plasma treatmentssome plasma treatments

7. Plasma TherapyPlasma Therapy
 REMOVAL OF ANTIBODIESREMOVAL OF ANTIBODIES
 Allo-antibodies e.g. Anti - Rh(D)Allo-antibodies e.g. Anti - Rh(D)
 Auto-antibodies e.g. M.G., Goodpastures Disease.Auto-antibodies e.g. M.G., Goodpastures Disease.
 Immune Complexes e.g. SLEImmune Complexes e.g. SLE
 REMOVAL OF EXCESSIVE OR ABNORMAL SUBSTANCESREMOVAL OF EXCESSIVE OR ABNORMAL SUBSTANCES
 ParaproteinsParaproteins
 Cholesterol in HypercholesterolaemiaCholesterol in Hypercholesterolaemia
 REMOVAL OF TOXINSREMOVAL OF TOXINS
 Protein-bound Drugs / ToxinsProtein-bound Drugs / Toxins
 Mushroom PoisonsMushroom Poisons

8.  Plasma ExchangePlasma Exchange
 Double FiltrationDouble Filtration
 ImmunoadsorptionImmunoadsorption
Removal of pathogenic substance by replacingRemoval of pathogenic substance by replacing
plasma with the same volume of fresh frozenplasma with the same volume of fresh frozen
plasma (FFP) or substitution fluidplasma (FFP) or substitution fluid
Plasma TherapyPlasma Therapy

9.  CentrifugationCentrifugation
 Continuous or IntermittentContinuous or Intermittent
 More common in Haematology DepartmentsMore common in Haematology Departments
 Citrate Anti-coagulationCitrate Anti-coagulation
 Membrane SeparationMembrane Separation
 Continuous (Usually) or IntermittentContinuous (Usually) or Intermittent
 More common in Nephrology DepartmentsMore common in Nephrology Departments
 Heparin Anti-coagulationHeparin Anti-coagulation
Plasma ExchangePlasma Exchange

10.  Component collection:Component collection: Peripheral Blood Stem CellsPeripheral Blood Stem Cells
(CD34+) for bone marrow transplant, Lymphocytes, Platelets,(CD34+) for bone marrow transplant, Lymphocytes, Platelets,
 Therapeutic Procedures:Therapeutic Procedures: Plasma Exchange,Plasma Exchange,
Therapeutic Red Cell applications, Cellular DepletionsTherapeutic Red Cell applications, Cellular Depletions
e.g. Haemoneticse.g. Haemonetics MCSMCS
CentrifugationCentrifugation
e.g.e.g. Gambro BCTGambro BCT
COBE SpectraCOBE Spectra

11.  AdvantagesAdvantages
 Can be used to prepare cell subsetsCan be used to prepare cell subsets
e.g. Granulocytes, Plateletse.g. Granulocytes, Platelets
 DisadvantagesDisadvantages
 Possible cell/platelet lossPossible cell/platelet loss
 Reactions to Citrate anticoagulantReactions to Citrate anticoagulant
CentrifugationCentrifugation

12. Membrane SeparationMembrane Separation
Blood returned to patientBlood returned to patient
SubstitutionSubstitution
FluidFluid
RequiredRequired
Plasma Separation MembranePlasma Separation Membrane
The large pores of the membraneThe large pores of the membrane
allow plasma, proteins andallow plasma, proteins and
pathogens to pass through andpathogens to pass through and
be discarded.be discarded.
Cells and platelets are retained.Cells and platelets are retained.
Substitution fluid is added and theSubstitution fluid is added and the
treated blood is returned to thetreated blood is returned to the
patient.patient.
Whole Blood from patientWhole Blood from patient
Separated PlasmaSeparated Plasma

13.  AdvantagesAdvantages
 Cell-free plasmaCell-free plasma
 No Platelet lossNo Platelet loss
 Lower Protein lossLower Protein loss
 DisadvantagesDisadvantages
 No collection of cell fractionsNo collection of cell fractions
 Reactions to membraneReactions to membrane
Membrane SeparationMembrane Separation

14. Circuit Diagram for Plasma ExchangeCircuit Diagram for Plasma Exchange
Plasma ExchangePlasma Exchange
Plasma is removed
and discarded
Plasmaflo
Replacement fluid
Pump
Pump
Pump
Anticoagulant

15. e.g. Patient Weight = 52 kg and Haematocrit = 40%e.g. Patient Weight = 52 kg and Haematocrit = 40%
11 ( 40 )( 40 )
PPV = 52 x ----- xPPV = 52 x ----- x ( 1 - --------- )( 1 - --------- )
1313 ( 100 )( 100 )
= 2.4 Litres= 2.4 Litres
Treatment Volume:Treatment Volume:
THEORETICALLY: 1 X PATIENT PLASMA VOLUME *THEORETICALLY: 1 X PATIENT PLASMA VOLUME *
PATIENTPATIENT 11 ( HAEMATOCRIT )( HAEMATOCRIT )
PLASMAPLASMA = BODY WEIGHT x ----- x ( 1 - ------------------------ )= BODY WEIGHT x ----- x ( 1 - ------------------------ )
VOLUMEVOLUME 1313 ( 100 )( 100 )
* AJUSTED IN ACCORDANCE WITH PATIENT'S CONDITION AND DOCTOR'S ADVICE* AJUSTED IN ACCORDANCE WITH PATIENT'S CONDITION AND DOCTOR'S ADVICE

16. ACCESS:ACCESS:
Blood FlowBlood Flow 60 - 100 ml/min (Plasma Flow 20 - 30 ml/min)60 - 100 ml/min (Plasma Flow 20 - 30 ml/min)
Double Lumen CatheterDouble Lumen Catheter Femoral or Subclavian VeinFemoral or Subclavian Vein
NeedleNeedle > 18G – Femoral, Subclavian or Brachial Vein> 18G – Femoral, Subclavian or Brachial Vein
ANTICOAGULATION:ANTICOAGULATION:
Heparin *Heparin * 2,000 - 3,000 Units at beginning of treatment2,000 - 3,000 Units at beginning of treatment
20 - 40 Units / kg per hour during treatment20 - 40 Units / kg per hour during treatment
* AJUSTED IN ACCORDANCE WITH PATIENT'S CONDITION AND DOCTOR'S ADVICE* AJUSTED IN ACCORDANCE WITH PATIENT'S CONDITION AND DOCTOR'S ADVICE
Access & AnticoagulationAccess & Anticoagulation

17. LOCATIONLOCATION
DIFFERENCESDIFFERENCES
METHODMETHOD
ANTI-COAGULATIONANTI-COAGULATION
EFFICIENCY FOR PLASMAEFFICIENCY FOR PLASMA
PROTEIN /PROTEIN /
REMOVALREMOVAL
MECHANISM OF SEPARATIONMECHANISM OF SEPARATION
CITRATECITRATE
CENTRIFUGATIONCENTRIFUGATION
HAEMATOLOGY,HAEMATOLOGY,
BLOOD BANKSBLOOD BANKS
CELL COLLECTION POSSIBLECELL COLLECTION POSSIBLE
EQUALEQUAL
DENSITY : CENTRIFUGAL FORCEDENSITY : CENTRIFUGAL FORCE
MEMBRANEMEMBRANE
NEPHROLOGY,NEPHROLOGY,
NEUROLOGYNEUROLOGY
HEPARINHEPARIN
CELL FREE PLASMACELL FREE PLASMA
EQUALEQUAL
SIZE : FILTRATIONSIZE : FILTRATION
Comparison of MethodsComparison of Methods

18.  Plasma ExchangePlasma Exchange
 Double FiltrationDouble Filtration
 ImmunoadsorptionImmunoadsorption
Selective removal of large molecules or pathogenicSelective removal of large molecules or pathogenic
substances by filtration of separated plasmasubstances by filtration of separated plasma
Plasma TherapyPlasma Therapy

19. Plasma TherapyPlasma Therapy
Viral Contamination in Transfusion / Substitution ProductsViral Contamination in Transfusion / Substitution Products
Plasma ProductPlasma Product Transmitted Virus / PrionTransmitted Virus / Prion YearYear CountryCountry
i.v. Igi.v. Ig Hepatitis CHepatitis C 19941994 GermanyGermany
Creutzfeld-JakobCreutzfeld-Jakob 19981998 GermanyGermany
Clotting FactorClotting Factor HIVHIV 19901990 GermanyGermany
Hepatitis BHepatitis B 19941994 GermanyGermany
Substitution Products Hepatitis ASubstitution Products Hepatitis A 19961996 GermanyGermany
Parvovirus B19Parvovirus B19 GermanyGermany
Creutzfeld-JakobCreutzfeld-Jakob 19981998 Canada/USACanada/USA
AlbuminAlbumin Creutzfeld-JakobCreutzfeld-Jakob 19981998 USAUSA
FFPFFP Parvovirus B19Parvovirus B19 19991999 USAUSA
Willkommen H, Anästhesiol Intensivmed Notfallmed Schmerzther 34: 497-500, 1999 and Dev Biol Stand 99: 131-138, 1999Willkommen H, Anästhesiol Intensivmed Notfallmed Schmerzther 34: 497-500, 1999 and Dev Biol Stand 99: 131-138, 1999
FDA USA: fda.gov/opacom/7alerts.html: Product Recalls, Alerts, and Warnings, 2000FDA USA: fda.gov/opacom/7alerts.html: Product Recalls, Alerts, and Warnings, 2000

20. Second FilterSecond Filter
Double FiltrationDouble Filtration
Whole Blood from patientWhole Blood from patient
SeparatedSeparated
PlasmaPlasma
Blood returnedBlood returned
to patientto patient
Substitution
Fluid
may be
required
Substitution fluid may be addedSubstitution fluid may be added
and the treated blood / plasmaand the treated blood / plasma
is returned to the patient.is returned to the patient.
PurifiedPurified
PlasmaPlasma
First FilterFirst Filter
DiscardDiscard
The large pores of the first filterThe large pores of the first filter
membrane allow plasma, proteinsmembrane allow plasma, proteins
and pathogens to pass through andand pathogens to pass through and
into the second filter.into the second filter.
The second filter, ofThe second filter, of
smaller pore size,smaller pore size,
selectively removesselectively removes
pathogenic substancespathogenic substances
from the plasma.from the plasma.
Pathogenic substances andPathogenic substances and
some plasma are discarded.some plasma are discarded.

21. Circuit Diagram for Double FiltrationCircuit Diagram for Double Filtration
Double FiltrationDouble Filtration
Plasmaflo
Pump
Pump
Pump
Replacement
fluid
Cascadeflo
Discard
Anticoagulant

22.  AdvantagesAdvantages
 More selective than Plasma ExchangeMore selective than Plasma Exchange
 Returns purified plasma to the patientReturns purified plasma to the patient
 Minimal loss of patientMinimal loss of patient’’s own desirable non-s own desirable non-
pathogenic substancespathogenic substances
 Minimal Albumin lossMinimal Albumin loss
 Minimal substitution fluid requiredMinimal substitution fluid required –– no FFPno FFP
 Minimal risk of infection from substitution fluidsMinimal risk of infection from substitution fluids
 Reduces possible protein allergy to substitution fluidReduces possible protein allergy to substitution fluid
 Fibrinogen loss is small and regenerates within 48Fibrinogen loss is small and regenerates within 48
hourshours
Double FiltrationDouble Filtration

23.  DisadvantagesDisadvantages
 Semi-selectiveSemi-selective
 SomeSome ““goodgood”” components of similar sizecomponents of similar size
and Molecular Weight to pathogen mayand Molecular Weight to pathogen may
also be lostalso be lost
 Some Fibrinogen is lost, but loss is smallSome Fibrinogen is lost, but loss is small
and regenerates within 48 hoursand regenerates within 48 hours
 Reactions to membraneReactions to membrane
Double FiltrationDouble Filtration

24.  PromotionPromotion
 Introduced most easily where PlasmaIntroduced most easily where Plasma
Exchange is already carried outExchange is already carried out –– simplesimple
extension of the treatment principleextension of the treatment principle
 Better long-term therapy for patients thanBetter long-term therapy for patients than
Plasma Exchange or Drug therapyPlasma Exchange or Drug therapy
 May need to establish links to other treatingMay need to establish links to other treating
physicians e.g. immunologistsphysicians e.g. immunologists
Double FiltrationDouble Filtration

25.  Plasma ExchangePlasma Exchange
 Double FiltrationDouble Filtration
 ImmunoadsorptionImmunoadsorption
Selective adsorption of pathogenic substances fromSelective adsorption of pathogenic substances from
separated plasmaseparated plasma
Plasma TherapyPlasma Therapy

26.  BiologicalBiological
 AntigenAntigen –– Antibody Binding e.g. Anti-LDL Ab for LDLAntibody Binding e.g. Anti-LDL Ab for LDL
 Complement Binding e.g. C1q for Immune ComplexesComplement Binding e.g. C1q for Immune Complexes
 Fc Binding e.g. Protein A for Immune Complexes, IgGFc Binding e.g. Protein A for Immune Complexes, IgG
 PhysicochemicalPhysicochemical
 Hydrophobic e.g. Tryptophan and Phenylalanine forHydrophobic e.g. Tryptophan and Phenylalanine for
Immune Complexes, RA Factor, Anti-AchR Antibodies,Immune Complexes, RA Factor, Anti-AchR Antibodies,
Anti-DNA AntibodiesAnti-DNA Antibodies
 Ionic e.g. Ion Exchange Resin for Bilirubin adsorptionIonic e.g. Ion Exchange Resin for Bilirubin adsorption
Affinity Type AdsorbentsAffinity Type Adsorbents

27. First FilterFirst Filter
Blood returnedBlood returned
to patientto patient
Purified PlasmaPurified Plasma
AdsorptionAdsorption
ColumnColumn
ImmunoadsorptionImmunoadsorption
No
Substitution
Fluid
required
The treated blood / plasmaThe treated blood / plasma
is returned to the patient.is returned to the patient.
SeparatedSeparated
PlasmaPlasma
Whole Blood from patientWhole Blood from patient The large pores of the firstThe large pores of the first
filter membrane allow plasma,filter membrane allow plasma,
proteins and pathogens toproteins and pathogens to
pass through and into thepass through and into the
adsorption columnadsorption column
The adsorptionThe adsorption
column selectivelycolumn selectively
removes pathogenicremoves pathogenic
substances from thesubstances from the
plasma.plasma.

28. Circuit Diagram for ImmunoadsorptionCircuit Diagram for Immunoadsorption
ImmunoadsorptionImmunoadsorption
Plasmaflo
Pump
Pump
Immusorba
Particle
Filter
Anticoagulant

29.  AdvantagesAdvantages
 More selective than Plasma ExchangeMore selective than Plasma Exchange
 Wide area of applicationWide area of application
 Selective removal based on Hydrophobic adsorptionSelective removal based on Hydrophobic adsorption
 Ligand is harmless, physiological Amino AcidLigand is harmless, physiological Amino Acid
 Returns purified plasma to the patientReturns purified plasma to the patient
 Minimal loss of patientMinimal loss of patient’’s own desirable non-s own desirable non-
pathogenic substancespathogenic substances
 No substitution fluid requiredNo substitution fluid required
 No risk of infection from substitution fluidsNo risk of infection from substitution fluids
 Eliminates possible protein allergy to substitution fluidEliminates possible protein allergy to substitution fluid
 Suitable for patients with protein allergySuitable for patients with protein allergy
ImmunoadsorptionImmunoadsorption

30.  DisadvantagesDisadvantages
 Semi-selectiveSemi-selective
 Some Fibrinogen is lost, but loss is small andSome Fibrinogen is lost, but loss is small and
regenerates within 48 hoursregenerates within 48 hours
ImmunoadsorptionImmunoadsorption

31.  PromotionPromotion
 Introduced most easily where PlasmaIntroduced most easily where Plasma
Exchange is already carried outExchange is already carried out
 Better long-term therapy for patients thanBetter long-term therapy for patients than
Plasma Exchange or Drug therapyPlasma Exchange or Drug therapy
 May need to establish links to other treatingMay need to establish links to other treating
physicians e.g. immunologistsphysicians e.g. immunologists
 May need education programmeMay need education programme
ImmunoadsorptionImmunoadsorption

32. • Immune Thrombocytopenic Purpura (ITP)
• Thrombotic thrombocytopenic purpura (TTPP) or hemolytic uremic syndrome (HUS)
• AIDS-related ITP
• Cryoglobulinemia with symptomatic hyperviscosity
• Goodpasture’s syndrome in crisis
• ABO-incompatible bone marrow transplant
• Pure Red Cell Aplasia unresponsive to immunosuppressives
• Myasthenia gravis causing severe disability
• Chronic demyelinating gammopathy
• Chronic relapsing polyneuropathy for severe, disabling, or life-threatening unresponsive to conventional therapy
• Guillain Barre for severely ill patients (Grades 3-5)
• Myeloma kidney
• Waldenstrom’s macroglobulinemia
• Refsum’s disease
• Rheumatoid Arthritis
• Severe bullous pemphigoid
• Multiple Sclerosis
• Severe sclerodema
• Pemphigus
• Polymyositis (cerebritis, myocarditis, nephritis, etc.)
• Systemic Lupus Erythematosis
• Lipid-apheresis / familial hypercholesterolemia / lipoprotein (a)
• Chronic Idiopathic Demyelinating Polyneuropathy
Some ApplicationsSome Applications

33. More selective than Plasma ExchangeMore selective than Plasma Exchange
Better long-term therapy for patients thanBetter long-term therapy for patients than
Plasma Exchange or Drug therapyPlasma Exchange or Drug therapy
Wide are of applicationWide are of application
Easy to performEasy to perform
Plasma TherapyPlasma Therapy