Therapeutic Apheresis

Therapeutic Apheresis
Basic Principles, Techniques and
Practical considerations
Outlines
•
•
•
•
•
•
Apheresis
•Derives from Greek, “to carry away”
•A technique in which whole blood is
taken and separated extracorporealy,
separating the portion desired from the
remaining blood.
•This allows the desired portion (e.g.,
plasma) to be removed and the
reminder returned.
Definitions
Mechanism of Action
Technology (ies)
Use
Practical Considerations
Apheresis Math
Apheresis- Mechanism of Action
•Large-bore intravenous catheter connected
to a spinning centrifuge bowl
•Whole blood is drawn from donor/patient
into the centrifuge bowl
•The more dense elements, namely the red
cells, settle to the bottom with less dense
elements such as white cells and platelets
overlying the red cell layer and finally,
plasma at the very top.
1
Apheresis: Principles of Separation
Platelets
(1040)
Lymphocytes
(1050-1061)
Torloni MD
Monocytes
(1065 - 1069)
Granulocyte
(1087 - 1092)
RBC
Torloni MD
Torloni MD
Cobe 
Centrifugal Separation
WB
WBC
PRBC
Plasma
Torloni MD
G
Torloni MD
a
m
as
Pl
ts
ele
at
Pl
ff y
Bu
at
Co
lls
Ce
d
Re
Principals of Apheresis
Separate blood
components is based on
density with removal of
the desired component
WBC
WBC
Plasma
Plasma
Torlo
ni MD
ts yte
tele hoc tes s
Pla ymp nocy locyte
L M o nu
Gra
RBC
Torloni MD
RBC
RBC
WBC
Plasma
G
Cobe Spectra
Graphics owned
by and courtesy
of Gambro BCT
2
Apheresis- Mechanism of Action
Apheresis- Mechanism of Action
•Large-bore intravenous catheter connected
to a spinning centrifuge bowl
•Whole blood is drawn from donor/patient
into the centrifuge bowl
•The more dense elements, namely the red
cells, settle to the bottom with less dense
elements such as white cells and platelets
overlying the red cell layer and finally,
plasma at the very top.
Plasmapheresis: Fluid Dynamics
Apheresis- Mechanism of Action (Cont.)
•In plasmapheresis, the plasma layer is
collected into a collection bag, and the red
cells and buffy coat layers are returned to the
patient mixed with plasma substitute (NS, 5%
albumin)
•Since all current apheresis equipment uses
advanced microcomputer technology, you can
adjust the system to collect platelets/red
cells/white cells/pbmc
42 L
INTRACELLULAR
K
EXTRACELLULAR
EXTRACELLULAR
Na
28 L
14 L
INTERSTITIAL
INTERSTITIAL
10 L
INTRAVASCULAR
INTRAVASCULAR
4L
Plasma Exchange : Mathematical Models
LL
yy
m
m
pp
hh
aa
tt
ii
cc Catabolism
ss
INTRAVASCULAR
Interstitial
Intracellular
Modified from: Weinstein, Apheresis:Principles and Practice- AABB press
3
Apheresis: Automated Processing
Technology
Continuous flow
•Automated centrifugal cell separators allow large of
blood to be processed in a short period of time
•Discontinuous flow: Haemonetics MSC plus, V50,
V30
•Continuous flow: Cobe spectra, CS 3000, Fresnius AS
104
Definitions
•Plasmapheresis: plasma is removed and
replaced w/plasma substitute (N.S. and/or 5%
albumin)
•Plasma exchange: plasma is removed and
exchanged w/allogeneic plasma
•TPE: therapeutic plasma exchange
Use of Apheresis (cont.)
Intermittent flow
Cobe 
Frezaenius 
Haemonetics
Fenwal 
(Baxter)
Use of Apheresis
•Collection - facilitate collection of a blood
component (plt, wbc) from an allogeneic
donor
•Therapy (therapeutic apheresis):
*removing undesired substances like
antibodies, lipids
*reducing excess wbc/plt in pts
w/myeloproliferative disorders
*automated exchange of sickled rbc
*collection of hematopoietic progenitor cells
Abnormal Substances Removed
From the Circulation by TPE
TPE assures the immediate removal of
abnormal substances from the circulation,
which are either:
1) Paraproteins (Waldenstorm’s Macroglobulinemia)
*present in plasma
3) Lipids (LDL in familial hypercholesterolemia;
phynatic acid in refsum’s disease
*or tightly bound to plasma proteins
2) Autoantibodies (Myasthenia Gravis, Goodpasture’s
syn.)
4) Toxins or drugs (that are bound to albumin)
5) Circulating immune complexes (CIC)
6) Soluble mediators of inflammatory response (activated
complement component, vasoactive substances)
4
Apheresis Procedural Elements
(+ Practical Considerations):
Apheresis Procedural Elements
(+ Practical Considerations):
•Venous access
•Venous access
•Replacement fluid
•Replacement fluid
•Normal/abnormal constituents removed
•Normal/abnormal constituents removed
•Anticoagulation
•Anticoagulation
•Patient history and medications
•Patient history and medications
•Frequency and number of procedures
•Frequency and number of procedures
•Complications
•Complications
Venous Access
Venous Access (cont.)
*Apheresis require large bore venous catheters to sustain the
flow rates required (50-100 ml/min)
Type of catheters:17 gauge therumo butterflies/ double lumen
dialysis catheters 10-13.5 fr (Shiley, Quinton, Vascath,
Permacath)
*Location: Peripheral: anticubital
central: femoral/subclavian/jugular
arteriovenous shunt/fistula
•Planned/occasional procedure - peripheral line and removal
after the procedure
•Few days/ bed rest- femoral line (risk of
infection/thrombosis)
•Multiple procedures for a long period of time - neck central
vein or artriovenous shunt/fistula
*Number of lines:
•Do not forget:
intermittent flow devices (draw and return via the same line):
single line
*Dressing change
*Flush
continuous -flow devices : separate lines
Apheresis Procedural Elements
(+ Practical Considerations):
Replacement Fluid
•Venous access
Must be FDA approved to use w/blood
products [ get mixed w/rbc before the return
phase]
•Replacement fluid
Replacement solutions:
•Normal/abnormal Constituents Removed
*Crystalloids – normal saline 0.9%
•Anticoagulation
*Colloids – 5% albumin; plasma
•Patient History and Medications
•Extracorporeal Volume
•Frequency and number of procedures
5
Replacement Fluid (cont.)
Replacement Fluid
*The primary function of the replacement
fluid is to maintain intravascular volume
**additional features:
- Restoration of important plasma proteins
- Maintenance of colloid osmotic pressure
*With the exception of TTP, the success of therapeutic
apheresis procedures seldom depends on the composition
of the replacement solution that is used
*Type used depends on:
• Procedure performed
• Diagnosis of patient
• Coagulation status
- Maintenance of electrolyte balance
Replacement Fluids
TTP/HUS
Neurological
GBS, MG, Stiff-man
CIDP
Renal
Comparison of Replacement Fluids
Replacement
Fluid
Advantage
Disadvantage
Crystalloid
Low cost
Hypoallergenic
No infectious risk
Hypo-oncotic
No coagulation factors
No immunoglobulins
2-3 volumes required
5% Human Albumin
Albumin/Saline (70% /30%)
Albumin
Iso-oncotic
No infectious risk
Higher cost
No coagulation factors
No immunoglobulins
5% Human Albumin
Albumin/Saline (70% /30%)
Consider adding FFP at the end if post op
Plasma
Immunoglobulins
Coagulation factors
Iso-oncotic
Infectious risk
Citrate
Allergic reactions
ABO compatibility
FFP
Cryodepleted FFP
Mixtures : Albumin /FFP
Albumin /FFP
5% Human Albumin
Albumin/Saline (70% /30%)
(RPGN, FSGS)
Post Transplant
Patients with hepatic failure, coagulopathy, pre-op or post-op use FFP or finish with FFP
Replacement Fluid and Balance
Apheresis Procedural Elements
(+ Practical Considerations):
3 choices of fluid balance:
•Venous access
1) 100% fB – isovolemic –volume replaced=volume
removed
•Replacement fluid
2) <100% fB – hypovolemic (“dry”) - volume replaced <
volume removed
•Anticoagulation
3) >100% fB – hypervolemic (“wet”) - volume replaced
> volume removed
•Normal/abnormal constituents removed
•Patient history and medications
•Frequency and number of procedures
•Complications
6
Normal/abnormal
Constituents Removed
Volume of Patient Plasma
Exchanged (PEX)
1pv= 63%, 2 vol=86% , 3 vol=95%
TPE:
•One volume exchange removes about 63%- 65% of most
plasma constituents
•A single two-volume exchange removes about 86% of
plasma constituents
Increasing the volume beyond 1-1.5 volumes has very
little impact on removal of plasma constituents
Volume of Patient Plasma
Exchanged (PEX)
Normal Constituents Removed
Coagulation factors:
•Most coagulation factors are lost at the same rate
•Rapidly synthesized;replacement usually is 2-3 days
following exchange
• Little advantage beyond 1.0-1.5 volumes
1pv= 63%, 2 pv=86% , 3 pv=95%
•Removal of IgG and IgM by plasma exchange:
measure
IgG
IgM
intravascular amount
45%
76%
1.0 PEX vol.
28%
48%
1.5 PEX vol.
35%
59%
2.0 PEX vol.
39%
65%
“total body” removal
•Practical: measure PT/PTT/Fibrinogen every 2-3 days
(rather then daily)
Platelets:
• 25-30% per procedure
•Endogenous synthesis replaces lost platelets within 2-4
days (except hypoplastic/aplastic marrow)
•Lab work (esp. chemistry): not immediate postprocedure; allow equilibrium intra/ extravascular space
Apheresis Procedural Elements
(+ Practical Considerations):
Anticoagulation
•Venous access
•Anticoagulation-citrate-dextrose solution (ACD-A)
•Replacement fluid
•Heparin
•Normal/abnormal constituents removed
•Combination of ACD-A and Heparin
•Anticoagulation
•Patient history and medications
•Frequency and number of procedures
•Complications
7
Anticoagulation
Anticoagulation citrate Dextrose
(ACD):
• Found in human cells, plant cells,
and citrus fruits
• Chelates positively charged
calcium ions (ionized calcium)
and blocks calcium-dependent
clotting factor reactions
• Works extracorporeally
• Metabolized in the liver almost
immediately upon return
Heparin:
• Prevents conversion of
fibrinogen to fibrin and
prothrombin to thrombin
Anticoagulation
• Systemic anticoagulation
• Metabolized slowly 1-2 hours
• Individual sensitivity and
elimination rates
• Side effects: hypocalcemia.
↑ small pts, large vol. of citrated
blood, liver dysfunction
Apheresis Procedural Elements
(+ Practical Considerations):
Patient History and
Medications
•Does patient have a disease which is amenable to
treatment by the requested apheresis procedure
•Venous Access
•Replacement Fluid
•Normal/abnormal Constituents Removed
•Does the patient/donor capable of sustaining the fluid
shifts associated with apheresis
•Patient History and Medications
•Certain medications, most notably antibiotics and
anticoagulant can be removed by apheresis - should be
given immediately after the procedure
•Frequency and Number of Procedures
•Angiotensin-converting enzymes (ACE) inhibitors
•Anticoagulation
•Complications
ACE inhibitors
ACE inhibitors
A.C.E.
A.C.E. Inhibitor
Angiotensin I
Angiotensin II
Angiotensin I
Vasoconstriction
X
Angiotensin II
No vasoconstrictive effect
8
ACE inhibitors and Pheresis
ACE Inhibitor
Kinase I & II
X
XII a
XII
Prekalikrein
Kallikrein
wn
do
ks nin
ea yki
r
d
B ra
B
Bradykinin
H.M.W.K
1- Activation of XII
2- Inhibition of Kinase II
Vasodilatation
Apheresis Procedural Elements
(+ Practical Considerations):
•Venous access
Patient History and
Medications
Angoitensin-converting enzymes (ACE) inhibitors
•Block conversion of angiotensin I to angiotensin II
•Also, inhibit the breakdown of bradykinin
•In the setting of apheresis, activation of bradykinin in
the extracorporeal circuit; potent vasodilator 
profound hypotension
•Ace-inhibitors must withheld for at least 24 hours before
apheresis
•C/I in immunosorba column (prosorba column)
↑↑ risk of anaphylaxis
Frequency and Number of Procedures
Depends on: Disease being treated
•Replacement fluid
Patient signs and symptoms
•Normal/abnormal constituents removed
Lab values
•Anticoagulation
•Patient history and medications
•Frequency and number of procedures
•Complications
Interval between Exchanges : Why we do what we do...
Target and Goals of TPE
Substance
Substance
Volume
Volume Treated
Treated
(ml/kg)
(ml/kg)
Treatment
Treatment Interval
Interval
Alteration in Blood Constituents by a 1- PV Exchange
Number
Number of
of Treatments
Treatments
(hours)
(hours)
Constituent
Constituent
Autoantibodies
Autoantibodies
40
40 –– 60
60
24
24 –– 48
48
Immune
Immune complexes
complexes
40
40 –– 60
60
24
24 –– 48
48
treat
treat to
to response
response
Clotting factors
Paraproteins
Paraproteins
40
40 –– 60
60
24
24
treat
treat to
to response
response
Fibrinogen
Cryoproteins
Cryoproteins
40
40 –– 60
60
24
24 –– 48
48
treat
treat to
to response
response
Immuneglobulins
Toxins
Toxins
TTP
TTP // HUS
HUS
40
40 –– 60
60
24
24 –– 72
72
40
40
24
24
%
% decrease
decrease
44 –– 66
treat
treat to
to response
response
to
to remission
remission
25 – 50
63
%
% recovery
recovery
48
48 hrs
hrs post
post exchange
exchange
80 – 100
65
63
45
Paraproteins
20 – 30
Variable
Liver Enzymes
55 – 60
100
Bilirubin
45
100
C3
63
60 – 100
25 – 30
75 – 100
Platelets
Modified from : Weinstein, in McLeod, Apheresis, Principles and Practice, AABB press 1997
From McLeod B, Apheresis, Principles and Practice (R. Weinstein ) p 271, AABB Press 1997
9
Apheresis Procedural Elements
(+ Practical Considerations):
•Venous access
Complications
• Hypocalcemia (citrate
toxicity)
• Vasovagal
•Replacement fluid
– ACE inhibitors increase risk
• Bleeding
– Pallor, sweating, Slow
pulse, Low BP
– Nausea/ vomiting,
syncope, convulsions
•Normal/abnormal constituents removed
•Anticoagulation
• Hypotension
• Vascular access
•Patient history and medications
– Hematoma, thrombosis
– Central lines: sepsis,
thrombosis
•Frequency and number of procedures
– Decrease in clotting factors
(40-70%)
– Decrease in platelets (1050%)
• Infection
• Anxiety/ hyperventilation
– Tingling, diaphoresis,
tachycardia, seizures
• Allergic/ anaphylactic
•Complications
Complications
Complications
2) Vasovagal syncope
S/S: B/P
1) Hypotension
S/S: lightheadedness
 pulse rate
dizziness
shallow breaths
faintness
perspiration
 pulse
feeling of apprehension, distress, doom
nausea
Treatment: same as hypotention
Treatment:
 head of bed,  foot of bed
Give NS
Monitor VS
Complications
Complications
4) Allergic reaction:
3) Hypocalcemia
Etiology: blood products/ ethylene oxide/ACE inhibitors
S/S: Parasthesia, perioral tingling
S/S: hives
swelling (eyes,lips, tongue)
Chills/vibrations of chest wall
rash
Severe citrate toxicity - tetany, heart rhythm disturbances
flushing, hypotension (m/p ACE inhibitors)
Treatment:
AC flow rate to the patient
Decrease blood flow rate
Give Ca tables (Tums)
Give dairy products
For severe citrate toxicity – stop procedure, IV Calcium
breathing difficulties
burning eyes, periorbital edema (m/p ethylene oxide)
Treatment:
Pause procedure
Give medication per order: Antihistamines, corticosteroids,
epinephrine
Discontinue procedure if no improvement
10
Complications
5) Other side effects:
*Vascular access: hematoma, phlebitis, infection
*Air embolism
*Loss of blood components:
*Thrombocytopenia (30% decrease)
*Hypofibrinogenemia (50% decrease)
Journal of Clinical Apheresis 16:3, 130
Journal of Clinical Apheresis 16:3, 130
Request for TA
Evaluate the patient
-Does the patient most
likely have the
diagnosis?
-Are other reports of
treatments of equal
efficacy?
-Will TA harm the
patient?
ASFA Category
I/ II
III
Category III
Not
Categorized
Category IV
IV
Review new literature
Review literature
Apply McLeod’s criteria
Consider:
–Volume status
–Cardiovascular stability
–Vascular access
–Impact of TA on other treatments
Favorable
Category I/II
NC
Risk/ Benefit
Unfavorable
Accept
Deny
Treatment Plan
11
Evaluation of a new patient for TA
• Rationale
– Based on the diagnosis and history, review the
pathophysiology of disease and results of previous studies
• Impact
– Benefits and risks of the procedure
• Technical issues
– Anticoagulant, access, replacement fluid, volume processed
• End-point
– Monitoring of treatment and criteria for discontinuation
• Timing and location
Therapeutic Apheresis Math
Blood Volume Calculations
Blood/Plasma Volume
• Total Blood Volume (TBV):
-Height
-Weight
-Sex
• Plasma Volume
-TBV x (1-Hct)
TBV - Nadler’s Formula
TBV - Gilcher’s Rule of Five
12
Estimated Blood Volume
TBV Adjustments
Plasma Volume Calculation
Blood/plasma Volume Calculations
• Determine patient tolerance/safety
•Calculating % of extracorpreal volume
•Calculate treatment dose
•Cytoreduction and PBSC collections
•TPE and RBC Exchange replacement fluid volumes
Extracorporeal Volume (ECV)
Treatment Dosage
A “typical” order for plasmapheresis:
• The amount of blood outside the patient’s body at
any given time
• Should not exceed 15% of patient's total estimated
blood volume
• Depend on the technology used, it varies
between 131-284 ml
Cobe spectra set volume:
TPE 170ml
RBC exchange 170ml
PBSC 285ml
•Perform plasmapheresis
•Remove 3L of plasma (based on 1PV exchange; regular
size 70kg patient; PV ~40 mg/kg)
•Replacement per disease : for example
Replace 100% with 12 units FFP (`250 x 12 =3L)
Or replace 100% with 3L 5% albumin (each alb. 250cc
=12 bottles)
•Frequency : per disease: for example
TTP: daily; GBS: QOD x 5 treatments
13
RBC exchange Treatment dosage - FCR
• Fraction Cell Remaining (FCR):
desired HbS divided by patient’s pre HbS
For example:
desired HbS 30%; patient’s pre HbS:100%
FCR: 30/100 =0.3
desired HbS 30%; patient’s pre HbS:60%
FCR: 30/100 =0.6
• The lower the FCR – “more exchange needed”
RBC exchange Treatment dosage –
RBC volume to be exchanged
• The cobe spectra will use 3 parameters to calculate
volume of RBC needed:
- RBC volume of the patient
- Hct of the RBC units: the lower the Hct –you
will need more units
- Desired FCR
1X RBC volume exchange – FCR 35-40%
2X RBC volume exchange – FCR 15-20%
3X RBC volume exchange – FCR 5-10%
Treatment Dosage - RBC Exchange
Patient blood volume = 4000; Hct 30%
Patient RBC volume = 1200 ml
You need to raise Hgb A from 0 to 70% (FCR=30%)
1 X RBC vol. Exchange
Average unit Hct is 60% (each unit ~350 ml)
1200/.60 = 2000 ml
2000/350 = 6 units
14