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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


TPE
with PrismaFlex®
PrismaFlex

© 2008 – Dr. Michel Helmy / IC Product Manager 3


What is Aphaeresis?

© 2008 – Dr. Michel Helmy / IC Product Manager 4


Aphaeresis
“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

© 2008 – Dr. Michel Helmy / IC Product Manager 5


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

For example:

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

© 2008 – Dr. Michel Helmy / IC Product Manager 6


Definitions:
“Thrombocytapheresis”:
•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.

© 2008 – Dr. Michel Helmy / IC Product Manager 7


Definitions:
“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.

© 2008 – Dr. Michel Helmy / IC Product Manager 8


-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.

© 2008 – Dr. Michel Helmy / IC Product Manager 9


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

10
Common Diseases treated with TPE

Good pasture’s syndrome


•Inflammatory mediators

Poisons/drug OD
•Dilantin, mushrooms

TTP
•Replacement of plasma deficiencies

Deficiency of LDL
•Familial Hypercholesterolemia

© 2008 – Dr. Michel Helmy / IC Product Manager 11


Indications of TPE:
Emergency Indications:
•Microagiopathic Thrombocytopenia (TTP / HUS).
•Respiratory Failure in Guillian-Barre’ Syndrome or Myasthenia
Gravis.
•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.

© 2008 – Dr. Michel Helmy / IC Product Manager 12


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

© 2008 – Dr. Michel Helmy / IC Product Manager 13


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
(Immunoglobulin,
clotting factors)

© 2008 – Dr. Michel Helmy / IC Product Manager 14


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 16


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 17


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,
complement)

© 2008 – Dr. Michel Helmy / IC Product Manager 18


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


production.

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


inflammatory response that often contributes to the disease
progression.

© 2008 – Dr. Michel Helmy / IC Product Manager 19


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

© 2008 – Dr. Michel Helmy / IC Product Manager 20


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.

Example:
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

¾Centrifugation

¾Plasmafiltration

© 2008 – Dr. Michel Helmy / IC Product Manager 22


Centrifugation Technique

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Technological Application to TPE:
Centrifugation Technique:

© 2008 – Dr. Michel Helmy / IC Product Manager 24


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
Daltons

© 2008 – Dr. Michel Helmy / IC Product Manager 25


TPE
Return pressure Air detector

Syringe pump Blood pump Return Clamp


Patient

Plasma filter
Access pressure
Filter pressure

BLD

Plasma Replacement Effluent Infusion or Anticoagulant

© 2008 – Dr. Michel Helmy / IC Product Manager 26


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
diffusion

Small Molecules
Diffusion is better than
convection

© 2008 – Dr. Michel Helmy / IC Product Manager 27


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
solution.

© 2008 – Dr. Michel Helmy / IC Product Manager 28


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

• Hemofilter • Plasmafilter

• Central venous access required • Central venous required

© 2008 – Dr. Michel Helmy / IC Product Manager 29


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 31


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 32


Principles of Plasmafiltration:

Filtration
Convection

Sieving Coefficient

© 2008 – Dr. Michel Helmy / IC Product Manager 33


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

© 2008 – Dr. Michel Helmy / IC Product Manager 34


Principles of Plasmafiltration:

Convection:
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.

© 2008 – Dr. Michel Helmy / IC Product Manager 35


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 36


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

© 2008 – Dr. Michel Helmy / IC Product Manager 37


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 38


Schematic Set up for TPE Circuitry:

© 2008 – Dr. Michel Helmy / IC Product Manager 39


Components of Therapy

•Calculating the Plasma Volume to be removed.


•Replacement Solution
•Anticoagulation
•Vascular Access
•Warming Device

© 2008 – Dr. Michel Helmy / IC Product Manager 40


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.
Example:
70 kg patient, the PV would be;
70 kg x 40 ml/Kg = 2800 ml or 3000 ml.

© 2008 – Dr. Michel Helmy / IC Product Manager 41


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;

•Colloids
•Crystalloids

© 2008 – Dr. Michel Helmy / IC Product Manager 43


Colloids;
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
therapy.

© 2008 – Dr. Michel Helmy / IC Product Manager 44


Colloids;
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.

© 2008 – Dr. Michel Helmy / IC Product Manager 45


Crystalloid;

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.

© 2008 – Dr. Michel Helmy / IC Product Manager 46


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.

© 2008 – Dr. Michel Helmy / IC Product Manager 47


Other blood purification
techniques

Hemoperfusion, New trends


Hemoperfusion

© 2008 – Dr. Michel Helmy / IC Product Manager 49


Hemoperfusion

Return pressure Air detector

Syringe pump Blood pump Return Clamp


Patient

Cartridge
Cartridge pressure Access pressure

Anticoagulant

© 2008 – Dr. Michel Helmy / IC Product Manager 50


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

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

© 2008 – Dr. Michel Helmy / IC Product Manager 51


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

© 2008 – Dr. Michel Helmy / IC Product Manager 52


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,…

© 2008 – Dr. Michel Helmy / IC Product Manager 53