TPE

Dr. Michel HelmyProduct Manager ‐ ICMiddle East & East Africa

TPETPE TrainingTrainingKanoo Kidney Center

Dammam – KSA17th -19th November 2008

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

AgendaAgenda – Day 33

• TPE on PrismaFlex

• Practice (HANDS 0N)

• Demonstration on actual patient


TPETPEwithwith PrismaFlexPrismaFlex®


What is 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

Aphaeresis


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

For example:

Definitions:

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


“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.

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.

Definitions:


-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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REMOVES:• Immune complexes• Immunoglobulins

(IgG, IgM, IgA)• Cholesterol• Albumin• Fibrinogen• Urea, Creatinin• Electrolytes• Plasma protein bound

often the therapy of choice because itscapabilities of removing very large molecules to treat various disease conditions.

Therapeutic Plasma Exchange


Good pasture’s syndrome •Inflammatory mediators

Poisons/drug OD •Dilantin, mushrooms

TTP •Replacement of plasma deficiencies

Deficiency of LDL •Familial Hypercholesterolemia

Common Diseases treated with TPE


Indications of TPE:

•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.

Emergency 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

Indications of TPE:Primary Indications:


Mechanisms of action for TPE:Purpose of TPE Target Mediator to be

removedDisease conditionExample:

Removal of abnormal circulating factors (found in Plasma)

Replenishment of specific plasma factors (Immunoglobulin, clotting factors)

• Antibody•Monoclonal Protein• Circulating Immune complexes• Toxic factor

• None

• Myasthenia Gravis• Myeloma Protein• Cryoglobulinemia• TTP / HUS

• TTP


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.



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.



Category IV: Controlled trials have shown no therapeutic efficacy. TPE is discouraged as a treatment choice.

Category V: Pending further investigation by committee.


Mechanisms of action for TPE:

Purpose of TPE Target Mediator to be removed

Disease conditionExample:

Other effects on the Immune system

• Removal of Inflammatory Mediators (Cytokines, complement)

• Sepsis


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 haltinflammatory response that often contributes to the disease progression.


a. Immunoglobulins have a long half life;- 21 days for IgG - 5 days for IgM


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.

3. Knowledge of the Kinetics of immunoglobulin removal;


Centrifugation

Plasmafiltration

Technological Application to TPE


Centrifugation Technique


Technological Application to TPE:

Centrifugation Technique:


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


Effluent Infusion or Anticoagulant

Plasma filter

PatientReturn ClampSyringe pump

Air detector

BLD

Blood pump

Access pressureFilter pressure

Return pressure

TPE

Plasma Replacement


Size of molecules cleared by CRRTMolecular weights

Small MoleculesDiffusion is better than convection

Middle MoleculesConvection better than diffusion

Nothing above 50.000 is clearedNothing above 50.000 is cleared

Mode of removal

Large MoleculesConvection or adsorbtion


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-products (urea, creatinine)

• Maintain euvolemic state by replacing 1:1 plasma removed and replacement solution.


CRRT vs. TPE Goals of Therapy:

CRRT TPE (Plasmafiltation)

• Hemofilter • Plasmafilter

• Central venous access required • Central venous required


Anatomy of Plasmafilter


Filter SpecificationSpecification PF 2000N (TPE) M100 CRRT

• Molecular Wt. Cut-off• Fiber Material• Hollow Fibers• Membrane• Sterilization• Effective Surface Area• Maximum Pore size• Total volume of circuit• Circuitry differences

3 million DaltonsPolypropylene3,000Semi-permeableETO0.35 m20.5 um88 ml• No dialysate line• Replacement line given post-filter• Extra fluid line attached to access line.

30,000 DaltonsAcrylonitrile (AN69)6,000Semi-permeableETO0.90 m2<0.01 um107 ml• Dialysate line in place• Replacement line usually given pre-filter but can be post or both


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.


Principles of Plasmafiltration:

Filtration

Convection

Sieving Coefficient


Filtration:

Movement of fluid across the semi-permeable membrane driven by pressure gradient.

Plasma Volume Reduction



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.



•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.


Sieving Coefficient



Sieving Coefficient:

Solute PF 2000 N (SC) M100 (SC)

• Albumin• Total Proteins• Potassium• Creatinine, Urea• Bicarbonate

0. 970.92 (>)1.01.01.0

<0.01<0.021.01.01.0


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.

Sieving Coefficient:


Schematic Set up for TPE Circuitry:


Components of Therapy

•Calculating the Plasma Volume to be removed.•Replacement Solution•Anticoagulation•Vascular Access•Warming Device


Estimated Plasma Volume (PV) to exchange:

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

• 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.


Physician’s Order; 1.0 or 1.5 Plasma Volume to be ExchangedFor 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.

Estimated Plasma Volume (PV) to exchange:


Replacement Solutions

Two Basic types of Replacement Fluids;

•Colloids•Crystalloids


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.


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.

Colloids;


•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.

Crystalloid;

Normal Saline:


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.

Other blood purification techniques

Hemoperfusion, New trends


Hemoperfusion


Anticoagulant

Return ClampSyringe pumpPatient

Air detector

Blood pump

Access pressureCartridge pressure

Return pressure

Cartridge

Hemoperfusion


Related to sepsis• Removal of mediators• Timing• Feasibility

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

New trends


• 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

WHY 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,…

Further role in Sepsis

TPE

Documents

michelhelmy icproductmanager

indications of tpe

removed plasma

patients plasma

guillianbarre syndrome

prismaflex prismaflex

primary indications

removal of platelets