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TPE Training

Kanoo Kidney Center

Dammam – KSA
17th -19th November 2008

Dr. Michel Helmy

Product Manager ‐ IC
Middle East & East Africa
Agenda – Day 3
• TPE on PrismaFlex

• Practice (HANDS 0N)

• Demonstration on actual patient

© 2008 – Dr. Michel Helmy / IC Product Manager 2

with PrismaFlex®

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What is Aphaeresis?

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“A separation of whole blood into
its cellular components.
A selected component
is removed and the remaining
elements are recombined
and returned to the donor”.

American Society of Aphaeresis;

Principles of Apheresis Technology

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“ Cytapheresis”
•Selective removal of any cellular component of whole blood, and
can be done with Centrifugal machinery.

For example:

•Removal of Erythrocytes (RBC).
•Used to treat life-threatening autoimmune hemolysis, and
parasitemia in Malaria.

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•Removal of platelets for patients with myeloproliferative diseases
such as polycythemia vera, primary thrombocytemia and chronic
granulocytic leukemia, who are at risk of, or symptomatic of
thrombotic or hemorrhagic complications.

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“Plasmapheresis”: “(TPE)”

•The procedures in which the patient’s plasma is separated and

removed from the whole blood.

•The removed plasma is replaced 1:1 ratio with a replacement

solution i.e. Albumin or FFP.

•To treat autoimmune conditions such as Myasthenia Gravis, TTP

and Guillian-Barre’ Syndrome.

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-Packed RBCs being the heaviest blood
component with a specific gravity of 1.75
are separated along the outside wall of
the spinning channel. The “Buffy coat”
in the center of the channel consists of
WBCs, Platelets, and Stem cells.
Platelets have a specific gravity of 1.04.
Plasma is the lightest blood component
with a specific gravity of 1.025.

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Therapeutic Plasma Exchange

often the therapy of REMOVES:

choice because its • Immune complexes
• Immunoglobulins
capabilities of removing (IgG, IgM, IgA)
very large molecules to • Cholesterol
treat various disease • Albumin
• Fibrinogen
conditions. • Urea, Creatinin
• Electrolytes
• Plasma protein bound

Common Diseases treated with TPE

Good pasture’s syndrome

•Inflammatory mediators

Poisons/drug OD
•Dilantin, mushrooms

•Replacement of plasma deficiencies

Deficiency of LDL
•Familial Hypercholesterolemia

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Indications of TPE:
Emergency Indications:
•Microagiopathic Thrombocytopenia (TTP / HUS).
•Respiratory Failure in Guillian-Barre’ Syndrome or Myasthenia
•Acute poisoning for certain mushrooms or with other strongly
protein bound poisons.
•Hyperviscosity syndrome with s&s suggesting impending stroke or
loss of vision.
•Anti – GMB disease & / or pulmonary hemorrhage in Good
Pasture’s Syndrome.

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Indications of TPE:
Primary Indications:
•Good Pasture’s Syndrome
•Hyperviscosity Syndrome
•Familial Hypercholesterolemia
•Myasthenic crisis
•SLE cerebritis (lupus)
•Myeloma cast nephropathy
•Coagulation factors inhibitor
•Systemic vasculitis

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Mechanisms of action for TPE:
Purpose of TPE Target Mediator to be Disease condition
removed Example:

Removal of abnormal • Antibody • Myasthenia Gravis

circulating factors •Monoclonal Protein • Myeloma Protein
(found in Plasma) • Circulating Immune • Cryoglobulinemia
complexes • TTP / HUS
• Toxic factor

Replenishment of • None • TTP

specific plasma factors
clotting factors)

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TPE Categorization…

Category I: Conditions for which therapeutic hemapheresis is

standard and acceptable treatment as primary or important
secondary treatment.

Category II: Conditions for which sufficient data has shown

hemapheresis effective in conjunction with other modalities.

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TPE Categorization…

Category III: Conditions for which there is insufficient evidence to

evaluate efficacy and benefit:risk ratio. TPE might be used if other
tx’s have failed or experimentally.

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TPE Categorization…

Category IV: Controlled trials have shown no therapeutic efficacy.

TPE is discouraged as a treatment choice.

Category V: Pending further investigation by committee.

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Mechanisms of action for TPE:

Purpose of TPE Target Mediator to be Disease condition

removed Example:
Other effects on the • Removal of Inflammatory • Sepsis
Immune system Mediators (Cytokines,

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Principles of Treatment

1. Therapy should almost always include immuno – suppression (i.e.

Cortico steroid treatment).

- this will reduce the rate of resynthesis of pathologic antibodies


2. Diseases that respond to TPE should be treated early to halt

inflammatory response that often contributes to the disease

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Principles of Treatment

3. Knowledge of the Kinetics of immunoglobulin removal;

a. Immunoglobulins have a long half life;

- 21 days for IgG
- 5 days for IgM

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Principles of Treatment
3. Knowledge of the Kinetics of immunoglobulin removal;
b. Immunoglobulins have substantial extravascular distribution.
The extent of intravascular vs. extravascular distribution will
determine how effectively they can be removed in the course of
single TPE session.

Extravascular Distribution of IgG = 50%
IgM = 20%
Therefore; depletion of IgM occurs more quickly than that of IgG.

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Technological Application to TPE



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Centrifugation Technique

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Technological Application to TPE:
Centrifugation Technique:

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Membrane Filtration

A plasma membrane separator

device is similar
to a hemodialyzer in appearances.

Both contain hollow fibers, but the

membrane properties are
significantly different.
• Dialyzer removes elements up
to 50,000 Daltons
• Plasma membrane removes
plasma and all dissolved
• components up to 3 million

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Return pressure Air detector

Syringe pump Blood pump Return Clamp


Plasma filter
Access pressure
Filter pressure


Plasma Replacement Effluent Infusion or Anticoagulant

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Size of molecules cleared by CRRT
Molecular weights
Mode of removal

Nothing above 50.000 is cleared

Large Molecules
Convection or adsorbtion

Middle Molecules
Convection better than

Small Molecules
Diffusion is better than

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CRRT vs. TPE Goals of Therapy:

CRRT TPE (Plasmafiltation)

• Electrolyte, fluid and pH balance • Removal of plasma containing large

proteins and immuno globulins.

• Removal of excess fluid and waste by- • Maintain euvolemic state by replacing
products (urea, creatinine) 1:1 plasma removed and replacement

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CRRT vs. TPE Goals of Therapy:
CRRT TPE (Plasmafiltation)

• Hemofilter • Plasmafilter

• Central venous access required • Central venous required

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Anatomy of Plasmafilter

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Filter Specification
Specification PF 2000N (TPE) M100 CRRT
• Molecular Wt. Cut-off 3 million Daltons 30,000 Daltons
• Fiber Material Polypropylene Acrylonitrile (AN69)
• Hollow Fibers 3,000 6,000
• Membrane Semi-permeable Semi-permeable
• Sterilization ETO ETO
• Effective Surface Area 0.35 m2 0.90 m2
• Maximum Pore size 0.5 um <0.01 um
• Total volume of circuit 88 ml 107 ml
• Circuitry differences • No dialysate line • Dialysate line in place
• Replacement line given • Replacement line
post-filter usually given pre-filter
• Extra fluid line attached but can be post or both
to access line.

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Filter Specification

Pre-connected filter membrane used in both CRRT & TPE. The major
differences with the TPE filter set is that it has no dialysate line connected
& replacement is always given post-filter.

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Principles of Plasmafiltration:


Sieving Coefficient

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Principles of Plasmafiltration:
Movement of fluid across the
semi-permeable membrane
driven by pressure gradient. Plasma Volume

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Principles of Plasmafiltration:

Movement of solutes along with water flow.
“ Solvent drag or Solute drag”

•Plasma is the solvent

•Solutes; electrolytes, amino acids, vitamins, albumin and
immunoglobulin are dragged along with the plasma into the drain.
•The more plasma being removed, the more solute loss will occur.

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Principles of Plasmafiltration:

Sieving Coefficient
•Solute removal mainly depends on the S.C.
•Ratio of solute between the ultra filtrate (Effluent) and the plasma.

• S.C. of 1.0; means a complete passage of solutes from the

plasma into the effluent bag.

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Principles of Plasmafiltration:

Sieving Coefficient:
Solute PF 2000 N (SC) M100 (SC)

• Albumin 0. 97 <0.01
• Total Proteins 0.92 (>) <0.02
• Potassium 1.0 1.0
• Creatinine, Urea 1.0 1.0
• Bicarbonate 1.0 1.0

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Sieving Coefficient:
Important Point:
• TPE performed with a CRRT filter would be ineffective.
• CRRT performed with dedicated TPE filter would be life endangering
due to constant albumin loss without replacement.

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Schematic Set up for TPE Circuitry:

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Components of Therapy

•Calculating the Plasma Volume to be removed.

•Replacement Solution
•Vascular Access
•Warming Device

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Estimated Plasma Volume (PV) to exchange:

• Use nomogram and equations using height, weight

and hematocrit in the literature;

• Useful Rule of thumb is to consider Plasma Volume

(PV) to be approximately: 40 ml/kg of body weight.
70 kg patient, the PV would be;
70 kg x 40 ml/Kg = 2800 ml or 3000 ml.

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Estimated Plasma Volume (PV) to exchange:

Physician’s Order;
1.0 or 1.5 Plasma Volume to be Exchanged
For a 70 Kg patient;

A 1.0 or 100% PV exchange would be 3000 ml.

A 1.5 or 150% PV exchange would be 4500 ml.

Ensure that you follow the physician’s order for PV to be exchanged.

© 2008 – Dr. Michel Helmy / IC Product Manager 42

Replacement Solutions

Two Basic types of Replacement Fluids;


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Albumin 5%

•Most commonly used replacement solution used in TPE.

•Maintains the patient’s colloid oncotic pressure.
•Best to check coagulation parameters; such as PT/PTT before the

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Fresh Frozen Plasma

•High cost, low availability and possible risk of Hepatitis and HIV,
this limits the use of FFP.

Important note:
•14% of FFP’s volume content is Citrate. If citrate anticoagulation is used,
infusion rate should be reduced.

•An anti-histamine is often used to prevent Histamine – mediated

responses that maybe associated with Plasma administration.

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Normal Saline:
•Usual treatment of Hypotension during TPE.
•Successful combination with Albumin 5%
•One third of Plasma Volume will be NSS.
•Remaining Plasma Volume will be 5% Albumin.
•Patient’s serum albumin level must be monitored and kept at >
3.5 g/dl when using this combination.

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Vascular Access

• Good working Catheter is

best required for TPE.

• Peripheral IV accesses are

not used for TPE / CRRT.

• Most common cause of

pressure alarms are due to
the vascular accesses.

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Other blood purification

Hemoperfusion, New trends


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Return pressure Air detector

Syringe pump Blood pump Return Clamp


Cartridge pressure Access pressure


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New trends
Related to sepsis
• Removal of mediators
• Timing
• Feasibility

Therapy options
• High volume
• High cut-off
• Adsorption

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WHY Sepsis

• Most important health problem

• Interaction between SIRS and infection = SEPSIS
• Human sepsis is characterized by a systemic action of inflammatory
cytokines TNF & IL6 which if persistent causes death
• Sepsis = balance between pro- and anti-inflammatory cytokines
• The objective of an extracorporeal treatment is to remove the mediators that
are involved in the cascade

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Further role in Sepsis

• A protective shield against peak of circulating mediators

• A therapy of SIRS as a causative condition for MODS
• A bridge towards native Renal/Liver function recovery
• A protective therapy against further ischemic insults
• A therapy with positive impact on other organ function
• Non specific removal
• Clinical safety: hypothermia, nutrition, vascular access, indications,…

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