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PLASMAPHRESIS
AHMED AKL, MD, FACP
ISN EDUCATIONAL AMBASSADOR,
CONSULTANT OF NEPHROLOGY&TRANSPLANTATION
Urology & Nephrology Center
Egypt
HISTORY
❖ The term plasmapheresis is derived partly from the Greek
word apharesis, which means “taking away” or removal.
❖ It is unclear when the notion of therapeutic removal of
blood components first originated, but it was flourishing
even before Hippocrates in the fifth century bc.
❖ Bloodletting to remove evil “humors” was a commonplace
medical practice, partly because of the lack of
understanding of disease processes and the paucity of
effective therapies.
Edwin papyrus
PLASMA THERAPY
- 1902: Washing and return of blood from uraemic patient
- 1944: Frequent plasma separation possible – plasma required during the war.
- 1952: Manual plasmapheresis first used therapeutically
- 1965: First continuous flow cell separator – buffy coat removal possible.
- -1970’s Plasma exchange for Goodpastures/MG
- 1980’s Plasmapheresis programmes for routine collection of blood products.
- 1990’s Treatment of plasma components.
- 2000’s Improvement in whole blood technologies to replace some plasma
treatments.
Plasmapheresis
• It is used to remove many large-molecular-weight substances from plasma,
including pathogenic antibodies, cryoglobulins, and lipoproteins.
• Newer techniques allow more selective removal of plasma components,
such as:
-Double filtration plasmapheresis.
-Cryofiltration.
-Immunoadsorption.
Apheresis in Clinical Practice
➢ Removal Of Antibodies
-TTP
-Guillain Barre Syn.
-Myasthenia Gravis
-Goodpasture’s Syn.
-Antibody mediated graft rejection
-Cryoglobulinemia
-Immune complexes; SLE
➢ Removal Of Excessive Or Abnormal Substances
-Paraproteinemia (Waldenstrom’s M.)
-Cholesterol in Hypercholesterolemia
➢ Removal Of Toxins
-Protein-bound drugs/Toxins
-Mushroom Poisons
RBC PlasmaWBC PLT
Sickle Cell Dis.
Malaria
Leukemias
Cell Therapies
Thrombocytosis
• Blood flow rates are generally relatively low (60-100 ml/min);
20-30 ml plasma/min.
• Double lumen Femoral or Subclavian catheter.
• Needle >18 G Brachial vein.
• Anticoagulation: citrates or heparin
(Heparin 2-3,000 Units at beginning of treatment; 20-40 Units/Kg per hour during
treatment) or wash lines and filter by 15000 heparin units/200ml saline, then one cycle
wash by saline without heparin.
• Calcium replacement
[two ampule 10 cm (1000 mg calcium gluconate, 990 elemental calcium)].
Treatment Volume
Plasmapheresis (Technique)
• Theoretically: 1x Patient plasma volume
• Patient plasma volume= Body weight x [1/13] x [1- Haematocrit/100]
SUBSTITUTION OF TWO LITERS PLASMA BY FRESH FROZEN PLASMA
PREPARATION OF TWO LITERS PLASMA SUBSTITUTION BY HUMAN ALBUMIN
100 ml human
Albumin 20%
Glucose 5%
400 ml
Saline 0.9%
400 ml
Glucose 5%
400 ml
Saline 0.9%
400 ml
100 ml human
Albumin 20%
100 ml human
Albumin 20%
100 ml human
Albumin 20%
200 ml 200 ml 200 ml 200 ml 200 ml 200 ml 200 ml 200 ml
TECHNIQUES
APHARESIS TECHNIQUES
Hollow fiber Plasmafilter
Centrifugal devices
Plasma Component Separators
Immunoadsorption Column
PLASMAPHERESIS
Centrifugation
- More Common In Haematology Departments
- Continuous or Intermittent
- Citrate Anti-coagulation
Membrane Separation
- More Common In Nephrology Departments
- Continuous (Usually) or Intermittent
- Heparin Anti-coagulation
Centrifugal devices
• Allow withdrawal of plasma with either synchronous or intermittent return of blood
cells to the patient.
• No upper limit to the molecular weight of proteins removed
• Blood flow rates are generally relatively low (90 to 150 ml/min).
• Double lumen Femoral or Subclavian catheter.
• Needle >18 G Brachial vein.
• Platelet counts can decrease by as much as 50%.
AT MANSOURA UROLOGY AND NEPHROLOGY INTERVENSIONAL UNIT
Membrane plasma filtration
• Uses highly permeable hollow fibers with membrane pores of 0.2 to 0.5 ìm.
• All immunoglobulins will cross the membrane (IgG more efficiently than IgM).
• Large immune complexes and cryoglobulins may not be adequately cleared.
• Many membranes allow clearance of molecules up to 3 million daltons.
• There is no loss of platelets
• Hemolysis can occur if transmembrane pressure are too high (a rare
complication)
• Membranes used in plasma filters are polysulfone, polypropylene, cellulose
diacetate, polymethyl-methacrylate, or polyacrylonitrile.
• The adsorptive properties of the membrane for cytokines and other
biomolecules may account for some of the beneficial effects of plasma filtration.
Protein A Immunoadsorption
• Remove immunoglobulin alone from plasma, without the need for replacement
fluids and without depletion of clotting factors and complement.
• Protein A selectively binds the Fc domains of immunoglobulin Molecules.
• The Immuno-adsorption columns can be repeatedly regenerated.
• Columns have been used for 1 year for a single patient on up to 30 occasions.
• Play a key pathogenic role in place of plasma exchange in:
- Goodpasture’s disease,
- Rheumatoid arthritis, and systemic lupus vasculitis
- Remove anti-ABO or anti-HLA antibodies in highly sensitized transplant
recipients.
Protein A binds IgG
Double Filtration Plasmapheresis
(Cascade filtration)
• Membrane filtration to separate cells from plasma and then
secondary plasma filtration (pore size, 0.01 to 0.03 ìm) to remove
plasma solutes based on molecular size.
• Most albumin is returned to the patient together with lower
molecular weight proteins
Mansoura Urology and Nephrology center
DOUBLE FILTRATION
• This waste will mainly contain larger molecules
• immunoglobulins, immune complex, M-components and LDL-cholesterol
• The need of plasma or albumin transfusion is greatly reduced
• Anticoagulation: heparin or nafamostate mesylate.
Hemofenix Technology For Nanofilteration
• Modern technologies allow
producing dialysis
membranes with a pore
diameter of 20 nano-metres.
One examples of such a
membrane is a track-etched
membrane, obtained from
interaction between a
polymer film and ions
accelerated in a charged
particle accelerator.
Electron microphotograph of a track
membrane's surface (a) and chip (b).
Hemofenix Nanofilteration
•Blood plasma filtration
(plasmapheresis) machine
Hemofenix-M, whose filtering
elements are produced using
track membranes with pores up to
100 nm in diameter.
J Nephrol Ther, vol4(4),2014
Hemofenix Nanofilteration
Advantages
•Allows performing the treatment with a single and
small needle and with reduced extra-coporeal
volume(70 ml).
•Low priming and short duration of treatment.
•The exchange of low volumes allows not to use
plasma as a replacement fluid so reduces the risk of
infection and allergy as in PLE.
• CAN BE COMPARABLE OR EVEN SUPERIOR To
traditional PLE AS IT IS MORE TOLERABLE AND LESS
INVASIVE.
J Nephrol Ther, vol4(4),2014
CONCLUSION
•Early introduction of plasma exchange appears to
be effective for various immunologic kidney
diseases.
•However, plasma exchange primarily serves as an
adjunct to other immunosuppressive therapies and
is often expected to have beneficial role .
•Early diagnosis and treatment of the underlying
condition remains important.
FUTURE DIRECTION
The new innovation of Hemofenix
Nanofilteration using Track- Ected
Membrane may solve the problem
in selected & refractory cases and
offer superior outcome to traditional
plasmaphresis
THANK YOU

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Plasmapheresis Techniques and Clinical Applications

  • 1. PLASMAPHRESIS AHMED AKL, MD, FACP ISN EDUCATIONAL AMBASSADOR, CONSULTANT OF NEPHROLOGY&TRANSPLANTATION Urology & Nephrology Center Egypt
  • 2. HISTORY ❖ The term plasmapheresis is derived partly from the Greek word apharesis, which means “taking away” or removal. ❖ It is unclear when the notion of therapeutic removal of blood components first originated, but it was flourishing even before Hippocrates in the fifth century bc. ❖ Bloodletting to remove evil “humors” was a commonplace medical practice, partly because of the lack of understanding of disease processes and the paucity of effective therapies. Edwin papyrus
  • 3. PLASMA THERAPY - 1902: Washing and return of blood from uraemic patient - 1944: Frequent plasma separation possible – plasma required during the war. - 1952: Manual plasmapheresis first used therapeutically - 1965: First continuous flow cell separator – buffy coat removal possible. - -1970’s Plasma exchange for Goodpastures/MG - 1980’s Plasmapheresis programmes for routine collection of blood products. - 1990’s Treatment of plasma components. - 2000’s Improvement in whole blood technologies to replace some plasma treatments.
  • 4. Plasmapheresis • It is used to remove many large-molecular-weight substances from plasma, including pathogenic antibodies, cryoglobulins, and lipoproteins. • Newer techniques allow more selective removal of plasma components, such as: -Double filtration plasmapheresis. -Cryofiltration. -Immunoadsorption.
  • 5.
  • 6.
  • 7. Apheresis in Clinical Practice ➢ Removal Of Antibodies -TTP -Guillain Barre Syn. -Myasthenia Gravis -Goodpasture’s Syn. -Antibody mediated graft rejection -Cryoglobulinemia -Immune complexes; SLE ➢ Removal Of Excessive Or Abnormal Substances -Paraproteinemia (Waldenstrom’s M.) -Cholesterol in Hypercholesterolemia ➢ Removal Of Toxins -Protein-bound drugs/Toxins -Mushroom Poisons RBC PlasmaWBC PLT Sickle Cell Dis. Malaria Leukemias Cell Therapies Thrombocytosis
  • 8.
  • 9.
  • 10. • Blood flow rates are generally relatively low (60-100 ml/min); 20-30 ml plasma/min. • Double lumen Femoral or Subclavian catheter. • Needle >18 G Brachial vein. • Anticoagulation: citrates or heparin (Heparin 2-3,000 Units at beginning of treatment; 20-40 Units/Kg per hour during treatment) or wash lines and filter by 15000 heparin units/200ml saline, then one cycle wash by saline without heparin. • Calcium replacement [two ampule 10 cm (1000 mg calcium gluconate, 990 elemental calcium)]. Treatment Volume Plasmapheresis (Technique) • Theoretically: 1x Patient plasma volume • Patient plasma volume= Body weight x [1/13] x [1- Haematocrit/100]
  • 11. SUBSTITUTION OF TWO LITERS PLASMA BY FRESH FROZEN PLASMA PREPARATION OF TWO LITERS PLASMA SUBSTITUTION BY HUMAN ALBUMIN 100 ml human Albumin 20% Glucose 5% 400 ml Saline 0.9% 400 ml Glucose 5% 400 ml Saline 0.9% 400 ml 100 ml human Albumin 20% 100 ml human Albumin 20% 100 ml human Albumin 20% 200 ml 200 ml 200 ml 200 ml 200 ml 200 ml 200 ml 200 ml
  • 12. TECHNIQUES APHARESIS TECHNIQUES Hollow fiber Plasmafilter Centrifugal devices Plasma Component Separators Immunoadsorption Column
  • 13. PLASMAPHERESIS Centrifugation - More Common In Haematology Departments - Continuous or Intermittent - Citrate Anti-coagulation Membrane Separation - More Common In Nephrology Departments - Continuous (Usually) or Intermittent - Heparin Anti-coagulation
  • 14. Centrifugal devices • Allow withdrawal of plasma with either synchronous or intermittent return of blood cells to the patient. • No upper limit to the molecular weight of proteins removed • Blood flow rates are generally relatively low (90 to 150 ml/min). • Double lumen Femoral or Subclavian catheter. • Needle >18 G Brachial vein. • Platelet counts can decrease by as much as 50%.
  • 15. AT MANSOURA UROLOGY AND NEPHROLOGY INTERVENSIONAL UNIT
  • 16. Membrane plasma filtration • Uses highly permeable hollow fibers with membrane pores of 0.2 to 0.5 ìm. • All immunoglobulins will cross the membrane (IgG more efficiently than IgM). • Large immune complexes and cryoglobulins may not be adequately cleared. • Many membranes allow clearance of molecules up to 3 million daltons. • There is no loss of platelets • Hemolysis can occur if transmembrane pressure are too high (a rare complication) • Membranes used in plasma filters are polysulfone, polypropylene, cellulose diacetate, polymethyl-methacrylate, or polyacrylonitrile. • The adsorptive properties of the membrane for cytokines and other biomolecules may account for some of the beneficial effects of plasma filtration.
  • 17.
  • 18. Protein A Immunoadsorption • Remove immunoglobulin alone from plasma, without the need for replacement fluids and without depletion of clotting factors and complement. • Protein A selectively binds the Fc domains of immunoglobulin Molecules. • The Immuno-adsorption columns can be repeatedly regenerated. • Columns have been used for 1 year for a single patient on up to 30 occasions. • Play a key pathogenic role in place of plasma exchange in: - Goodpasture’s disease, - Rheumatoid arthritis, and systemic lupus vasculitis - Remove anti-ABO or anti-HLA antibodies in highly sensitized transplant recipients.
  • 20.
  • 21. Double Filtration Plasmapheresis (Cascade filtration) • Membrane filtration to separate cells from plasma and then secondary plasma filtration (pore size, 0.01 to 0.03 ìm) to remove plasma solutes based on molecular size. • Most albumin is returned to the patient together with lower molecular weight proteins
  • 22. Mansoura Urology and Nephrology center DOUBLE FILTRATION • This waste will mainly contain larger molecules • immunoglobulins, immune complex, M-components and LDL-cholesterol • The need of plasma or albumin transfusion is greatly reduced • Anticoagulation: heparin or nafamostate mesylate.
  • 23. Hemofenix Technology For Nanofilteration • Modern technologies allow producing dialysis membranes with a pore diameter of 20 nano-metres. One examples of such a membrane is a track-etched membrane, obtained from interaction between a polymer film and ions accelerated in a charged particle accelerator. Electron microphotograph of a track membrane's surface (a) and chip (b).
  • 24. Hemofenix Nanofilteration •Blood plasma filtration (plasmapheresis) machine Hemofenix-M, whose filtering elements are produced using track membranes with pores up to 100 nm in diameter. J Nephrol Ther, vol4(4),2014
  • 25. Hemofenix Nanofilteration Advantages •Allows performing the treatment with a single and small needle and with reduced extra-coporeal volume(70 ml). •Low priming and short duration of treatment. •The exchange of low volumes allows not to use plasma as a replacement fluid so reduces the risk of infection and allergy as in PLE. • CAN BE COMPARABLE OR EVEN SUPERIOR To traditional PLE AS IT IS MORE TOLERABLE AND LESS INVASIVE. J Nephrol Ther, vol4(4),2014
  • 26. CONCLUSION •Early introduction of plasma exchange appears to be effective for various immunologic kidney diseases. •However, plasma exchange primarily serves as an adjunct to other immunosuppressive therapies and is often expected to have beneficial role . •Early diagnosis and treatment of the underlying condition remains important.
  • 27. FUTURE DIRECTION The new innovation of Hemofenix Nanofilteration using Track- Ected Membrane may solve the problem in selected & refractory cases and offer superior outcome to traditional plasmaphresis