Introduction of Apheresis it is Therapeutic Process in Transfusion Medicine

1. By
Dr. Nashwa Elsayed
Clinical Pathologist, CPHQ, , Laboratory & Blood Bank Quality Manager
KFH – Medina
Introduction to
Apheresis

2. The Greek word Apheresis means,
“To Take Away From"
Disease Reflects Presence of Disease Causing Factors
in The Blood; Selective Blood Letting (apheresis)
should Initiate Cure.
Apheresis in Ancient
Medicine
Introduction to Apheresis
Dr. Nashwa Elsayed

3.  In the1950s discontinuous-flow manual procedure.
 In the 1960s, continuous-flow hemapheresis
machines introduced.
 By the end of the 20th century highly sophisticated
machines has been developed.
 In May 1981, ASFA the American Society for
Apheresis was established
ASFA is one of the most important educational and scientific
contributions to the apheresis practice,
In 20th Century
Introduction to Apheresis
Dr. Nashwa Elsayed

4. Separation & Removal of specific Blood
Component from a Donor / Patient by passing
his Blood Through a Medical device, Then
Returning the Remaining Constituents.
What is Apheresis?
Introduction to Apheresis
Dr. Nashwa Elsayed

5. Donation Apheresis: (from Healthy Donors)
1. Single Component Collection:
(RBCs, Plasma, Platelets, or WBCs)
2. Multi-Component:
a combination of components, e.g. plasma + platelets
Therapeutic Apheresis: (for Patient)
Removal of the component in the Blood is Thought to Contribute
to a Disease State,
The Component is removed, Exchanged or Modified in order to
achieve therapeutic purposes
Types of Apheresis?
Introduction to Apheresis
Dr. Nashwa Elsayed

6. 1. Centrifugation
• Intermittent Flow IFC
• Continuous Flow CFc
2. Membrane Filtration
1. Adsorption Column
2. Photopheresis
Methods of Apheresis?
Introduction to Apheresis
Dr. Nashwa Elsayed

7. Blood Components Separated by Centrifugation
Based on Density
Centrifugation Based
Introduction to Apheresis
Dr. Nashwa Elsayed

8. • Blood is Drawn from the Patient
• Immediately mixed with an Anticoagulant, Then pumped into a
bowl/belt chamber in the device.
• Blood Components Separated by Centrifugation according to their
specific gravities.
• Desired Component Harvested /Removed through Outgoing
Tubes
• Replacement fluid added to the Remaining Components
(if Plasma is Removed)
• Other Blood Components Returned to the Patient
Centrifugation Based
Introduction to Apheresis
Dr. Nashwa Elsayed

9. Intermittent vs. Continuous Flow
Centrifugation
Intermittent Flow
Procedure Performed in Cycles
(withdrawal, separation , re-infuse).
One Needle Access for Peripheral Access
Extracorporeal volume (ECV) can be high
(bad in kids and the elderly with low total
bl.vol.), fluctuations in hemodynamics
Haemonetic V50
Continuous Flow
Blood Withdrawn, Processed and
Reinfused Simultaneously
2 venipuncture sites for peripheral access
Smaller ECV,
Hemodynamic Stability, faster Procedure
COBE Spectra, Spectra Optia, Fenwal
C3000 Plus, Fresenius AS 104
Introduction to Apheresis
Dr. Nashwa Elsayed

10. Blood is Pumped to the Filter Membrane
Membrane Filtration
Introduction to Apheresis
Dr. Nashwa Elsayed

11. • Blood is Pumped to the Filter Membrane.
• Membranes with Pore Sizes that can Trap HMW
Proteins, exclude Cellular Elements.
• Cellular Components Combined with
Replacement Fluid, Returned to Patient
• Use limited to Plasma Exchange.
Membrane Filtration
Introduction to Apheresis
Dr. Nashwa Elsayed

12. • Similar efficiency and safety.
• Membrane filtration (MF) is faster: because time is
required to set up a centrifugal interface.
• Different anticoagulants:
 Membrane filtration: heparin
 Centrifugation: usually citrate
• MF cannot remove cellular elements, therefore use is
limited to plasma exchange
Membrane Filtration vs. Centrifugation
Introduction to Apheresis
Dr. Nashwa Elsayed

13. • Plasma separated from cellular elements by
centrifugation
• Perfuse plasma through a selective removal
column/filter
 Dextran Sulphate Column: Removes LDL
 Staphylococcal protein A: Removes IgG by binding to the Fc
portion.
• Return to the patient
Adsorption Column (Selective Removal)
Introduction to Apheresis
Dr. Nashwa Elsayed

14. • Photopheresis the patients blood is removed, treated with a
photosensitising agent and UV light and returned to the patient.
• A Photosensitising Agent is a drug that is activated by ultraviolet
light to treat the diseased components of the blood.
• Photopheresis used in the treatment of:
1. Graft Versus Host Disease
2. Cutaneous T Cell Lymphoma
3. Sezary syndrome
4. Solid Organ Transplant Rejection
Photopheresis
Introduction to Apheresis
Dr. Nashwa Elsayed

15. Blood components are collected from healthy volunteer
donors.
These components include:
• Stem cells : cells that can divide and form all different types of
blood cells, giving healthy cells
• Granulocytes : WBCs that fight infection. (Mostly Neutrophils)
• Lymphocytes : WBCs that help in immune defence.
• Erythrocytes
Volunteer Donor Collection
Introduction to Apheresis
Dr. Nashwa Elsayed

16.  Donors for apheresis procedure must meet the
applicable criteria for normal donation.
 Use of medications that inhibit platelet function (such
as Aspirin and Piroxicam) defers the platelet apheresis
donation for 72 hours after the last dose.
 The platelet count of prospective apheresis donor
should be more than 150,000/µl.
Criteria for Platelet Apheresis Donors
Introduction to Apheresis
Dr. Nashwa Elsayed

17. • Period of 8 weeks after whole blood donations.
• Not more than once every 48 hours.
• Not more than twice a week.
• Not more than 4 times a month.
• Not more than 24 times a year.
• Period of 8 weeks after failure to return the donor red cells during
last apheresis procedure. or the total RBC loss during last apheresis
procedure exceeds 200 ml.
Donation intervals
Introduction to Apheresis
Dr. Nashwa Elsayed

18. 1. CBC
2. ABO and Rh typing,
3. Antibody Screening
4. Testing for TTDs:
• VDRL, RPR,
• anti-HIV I & II, HIV-1 RNA,
• anti-HCV, HCV-RNA,
• anti-HTLV I & II,
• HBsAg, anti-HBc and Anti-HBs
Donor Testing
Introduction to Apheresis
Dr. Nashwa Elsayed

19. The collection of a patients own stem cells prior to high dose
chemotherapy.
These cells are then returned to the patient after chemotherapy,
(Autologous Stem Cell Transplant)
These components include:
• Multiple Myeloma
• Amyloidosis
• Lymphoma (Non-Hodgkin’s , Hodgkin’s lymphoma)
• Germ Cell Tumour
• Sarcoma
Autologous Stem Cell Collection
Introduction to Apheresis
Dr. Nashwa Elsayed

20. Removal of:
• WBCs:
 Leukocytapheresis: in the setting of high WBC count in leukemia
 Peripheral stem cell collection
• Platelets:
 Thrombocytapheresis for thrombocytosis of myeloproliferative disorders
Exchange of:
• RBC: Erythrocytapheresis (sickle cell disease, malaria)
• Plasma: therapeutic plasma exchange (TPE): Removal of antibodies, paraproteins, cholesterol,
Modification of:
• WBC
 (with UV light): Photopheresis
Therapeutic Apheresis Applications
Introduction to Apheresis
Dr. Nashwa Elsayed

21.  The Technical Staff must be properly trained to care for
donors and patients.
 Attention must be given to the Patients Medication
schedule and/or fluids replacement.
 Written Informed Consent must be obtained from the
donor & patient
Important points to be considered
Introduction to Apheresis
Dr. Nashwa Elsayed

22. • Likelihood that underlying disease will respond to primary
therapy
• Impact of apheresis on other treatment modalities for primary
disease
• Removal or interaction with concurrent medications
• Effect of blood manipulation on accuracy of diagnostic tests
• Published experience in apheresis
Factors Considered By The Apheresis
Physician In Medical Decision-making
Introduction to Apheresis
Dr. Nashwa Elsayed

23. Peripheral access
• Use peripheral veins for access (antecubital, femoral)
• Need large needle for both the draw and return lines to allow flow
rate between 60-120 ml/min for adults
• Less invasive and faster to place
• Suitable for:
 Infrequent procedures
 Pt with good veins and reasonable muscular tone to maintain blood
flow (ie. Squeeze/pump when asked) and who are able to cooperate
Vascular Access
Introduction to Apheresis
Dr. Nashwa Elsayed

24. Central Access
• For repeated procedures, critically ill patients with decreased muscle tone
• Place in subclavian, femoral, internal jugular vein commonly
• Ideal: double lumen, rigid, high flow rate, staggered ports to minimize
recirculation
• Requirements similar to dialysis line. Also can use AV fistula.
• Drawbacks:
 Invasive
 Complications: sepsis, pneumothorax, hematoma, AV fistula, arterial
puncture.
Central line placement is an important risk factor for adverse events associated
with apheresis
Vascular Access
Introduction to Apheresis
Dr. Nashwa Elsayed

25. Acid Citrate Dextrose (ACD)
• Most commonly used anticoagulant for apheresis
• Citrate ion chelates free Ca++ ions and blocks calcium dependent
coagulation cascade
• Ensures that extracorporeal blood remains in a fluid state
Advantages:
• Ubiquitous compound found in all human cells, not “foreign”
• Metabolized by liver quickly to bicarbonate, little systemic effect
Drawbacks:
• Can cause transient systemic hypocalcaemia (citrate toxicity), presenting
with numbness, peri-oral tingling, tetany, cramping
ACD Anticoagulant
Introduction to Apheresis
Dr. Nashwa Elsayed

26. Citrate toxicity exacerbated by:
• Patient receiving additional citrate load due to infusion of FFP
• Patient also receiving albumin as replacement fluid, which binds Ca++
• Fast rate of infusion/return
• Longer duration of the procedure
• Pre-existing hypocalcemia
Prevention & Treatment By:
• Oral/IV calcium supplementation before or during the procedure
• Increase whole blood to citrate ratio
• Slower infusion rate
• Stop the procedure
Citrate Toxicity
Introduction to Apheresis
Dr. Nashwa Elsayed

27. Heparin
• Prevents clotting by potentiating antithrombin’s activity by 1000x
• Used alone or in combination with citrate
• Required/preferred by some instruments (Liposorber LDL, Photopheresis Instruments
Membrane Filtration)
• Degree of anticoagulation similar to DVT prophylaxis (plasma concentration 0.5 to
2.0 IU/ml)
Advantages:
• Reduce Citrate dose, avoid hypocalcaemia
Disadvantages:
• Short term systemic anticoagulation
• Risk of inducing HIT
Reverse overdose with protamine
Heparin Anticoagulant
Introduction to Apheresis
Dr. Nashwa Elsayed

28. • Can occur when blood is removed in the Beginning of Procedure
• Associated with risks of Hypovolemic and Vasovagal reactions
To minimize the risk of hypovolemia,
• limit the patients extracorporeal (ECV) to <15% of patients TBV at all times:
 ECV: the “Dead Spaces” (tubing, chambers) of an instrument. (Range 150-
500ml) that need to be filled to complete the apheresis circuit
• Priming the instrument with colloid solution
• Alternative: bolus saline/colloid
• RBCs may be necessary for a Paediatric Patients
Fluid Shifts
Calculating Total Blood Volume
TBV: ……….ml/kg x body wt (kg)
• New born 82-86 ml/kg
• Premature 89-105 ml/kg
• Infant 73-82 ml/kg
• Adult 70ml/kg
Introduction to Apheresis
Dr. Nashwa Elsayed

29. • Several litres of plasma can be removed
• Volume deficit needs to be replaced by fluid infusion.
• Replacements Options:
 Crystalloid (normal saline)
 Colloid (albumin)
 Plasma
Replacement Fluid for Therapeutic
Plasma Exchange (TPE)
Calculating Plasma Volume
TBV: ……….ml/kg x body wt (kg)
• (1–Hematocrit) × TBV = PV
Ex. (1 – 0.43) × (70 × 80 kg) = PV
0.57 × 5600 = 3129 ml
Introduction to Apheresis
Dr. Nashwa Elsayed

30. Advantages:
• Cheap
• No infectious/allergic risks
• Readily available
Disadvantages:
• Hypo-oncotic, only ~1/3 stays intravascular, this may lead to intravascular
fluid deficit, hypotension. Therefore usually used in combination with
albumin:
• start procedure with NS replacement, then finish with albumin replacement
• Lacks coagulation factors/ immunoglobulins
Replacement Fluid for (TPE)
Crystalloid (Normal Saline)
Introduction to Apheresis
Dr. Nashwa Elsayed

31. (Used for most indications of TPE)
Advantages:
• Colloid, iso-oncotic stays intravascular,
• No to very, very low allergic/ infectious risks
Disadvantages:
• Does not replace other protein fractions, such as coagulation factor
• Expensive
• Not always available, periodic national shortages of albumin can occur
Replacement Fluid for (TPE)
Albumin (5%)
Introduction to Apheresis
Dr. Nashwa Elsayed

32. Advantages:
• Iso-oncotic
• Replaces coag factors, immunoglobulins and other plasma proteins
Disadvantages:
• Additional citrate load, increases risk of hypocalcaemia
• Infectious and allergic risks
• TRALI risks
• Needs to be ABO compatible
• Expensive
Replacement Fluid for (TPE)
Plasma
Indications:
• Thrombotic thrombocytopenic purpura (TTP) to
replace ADAMTS 13
• Replacing coag factors in liver failure, or in
patient undergoing repeated daily TPE
procedures with albumin as replacement fluid
Introduction to Apheresis
Dr. Nashwa Elsayed

33. Therapeutic Plasma exchange
A patients plasma is removed and replaced by plasma
from a donor or by a plasma substitute.
Indications:
1. Hyperviscosity syndrome
(Waldenstroms Macroglobulinaemia and M. Myeloma)
2. Microangiopathic Anaemia (TTP/HUS)
3. Myasthenia Gravis
4. Guillain-Barre syndrome
5. other sever autoimmune/antibody driven Neuropathies.
Introduction to Apheresis
Dr. Nashwa Elsayed

34. ASFA Guidelines
For Therapeutic Apheresis
Category I
Disorders for which apheresis is accepted as first-line therapy, either as
standalone treatment or in conjunction with other modes of treatment.
Category II
Disorders for which apheresis is accepted as second-line therapy, either as
standalone treatment or in conjunction with other modes of treatment.
Category III
Optimum role of apheresis therapy is not established. Decision making should be
individualized.
Category IV
Disorders in which published evidence demonstrates or suggests apheresis to be
ineffective or harmful.
Introduction to Apheresis
Dr. Nashwa Elsayed

35. Guidelines for Therapeutic
Plasmapheresis
Category IICategory I
• Rapidly progressive glomerulonephritis
• Chronic inflammatory demyelinating
polyneuropathy
• Cold agglutinin
• Drug overdose and poisoning (protein-
bound toxins)
• HUS
• Pemphigus vulgaris
• Systemic vasculitis (primary or
secondary to rheumatoid Arthritis or
systemic lupus Erythematosus)
• Thrombotic Thrombocytopenic
Purpra (TTP)
• Coagulation factor inhibitors
• Cryoglobulinemia
• Goodpasture’s syndrome
• Guillain-Barre syndrome
• Homozygous familial
• hypercholesterolemia
• Hyperviscosity syndrome
• Myasthenia gravis
• Postransfusion purpura
• Refsum’s disease
Introduction to Apheresis
Dr. Nashwa Elsayed

36. Guidelines for Therapeutic
Plasmapheresis
Category IVCategory III
• AIDS (for symptoms of
immunodeficiency)
• Amyotrophic lateral sclerosis
• Aplastic anemia
• Fulminant hepatic failure
• ITP (chronic) , Lupus nephritis
• Polymyositis / dermatomyositis
• Psoriasis , Renal transplant rejection
• Rheumatoid arthritis
• ABO-incompatible organ or marrow
transplantation
• Maternal treatment of Maternal-
fetal incompatibility (HDN)
• Thyroid storm, Multiple sclerosis
• Progressive systemic sclerosis
• Pure RBC aplasia , Transfusion
refractorines
• due to Alloantibodies (RBC, platelet,
HLA)
• Warm autoimmune hemolytic
anemia
Introduction to Apheresis
Dr. Nashwa Elsayed

37. Therapeutic Red cell exchange
(Therapeutic Erythrocytapheresis)
A patients RBCs are removed and replaced with donor
Red Blood Cells.
Indications:
1. Sickle Cell Disease.
2. After ABO incompatible bone marrow transplant.
3. Rh -ve female patient received Rh +ve blood with high Anti-D titer.
4. Red cell depletion in patient with high HCT >60 with serious
Introduction to Apheresis
Dr. Nashwa Elsayed

38. Therapeutic platelet apheresis
(Platelet Apheresis)
Indications:
1. Platelet count more than one million in some malignant disorder
(Myeloproliferative Disorders)
The Platelet Count can be decreased by as much as One-third to
One-half the initial value.
Introduction to Apheresis
Dr. Nashwa Elsayed

39. Therapeutic leukapheresis
Indications:
1. Platelet count more than one million in some malignant disorder
(Myeloproliferative Disorders)
Introduction to Apheresis
Dr. Nashwa Elsayed

40. Adverse Effects of Apheresis
1- Citrate toxicity
2- Vascular complications
(hematoma, sepsis, phlebitis, neuropathy).
3- Vasovagal reaction.
4- Hypervolemia.
5- Allergic reaction.
6- Haemolysis.
7- Air embolus.
Introduction to Apheresis
Dr. Nashwa Elsayed

41. Adverse Effects of Apheresis
8- Depletion of clotting factors.
9- Circulatory and respiratory distress.
10- transfusion transmitted diseases.
11- loss of lymphocytes.
12- depletion of proteins and immunoglobulin
Introduction to Apheresis
Dr. Nashwa Elsayed

42. Signs and Symptoms, Possible Causes, and Treatment of Adverse
Effects during Therapeutic Apheresis
Signs and Symptoms Possible Cause(s) Suggested Treatment(s)
Bradycardia, hypotension,
diaphoresis, pallor,
nausea,feeling of doom
Vasovagal
reaction,
anxiety, full
bladder,
or unknown
cause
Put patient in Trendelenburg’s position or
elevate feet, administer saline bolus, offer bedpan,
fan patient, stimulate patient (ie, have patient
move extremities as much as possible),
administer ammonia spirit, aromatic (be sure to
protect patient’s eyes)
Tingling in fingertips or
toes,flushing,
diaphoresis,hypotension/hype
rtension,
tachycardia, seizures
Hyperventilation,
anxiety
Have patient breathe in paper bag, offer fan,
encourage very slow deep breathing. If patient is
hypotensive, place patient in Trendelenburg’s
position and administer saline bolus.
Introduction to Apheresis
Dr. Nashwa Elsayed

43. Signs and Symptoms Possible Cause(s) Suggested Treatment(s)
Tachycardia, hypotension,
diaphoresis
Antihypertensive
Rx:
Beta blockers
Ca channel
blockers
Hypovolemia
Hold antihypertensive Rx before next procedure.
Administer saline bolus, put patient in
Trendelenburg’s position, increase fluid balance,
review type and volume of replacement fluids,
increase % of colloid if using crystalloid
replacement.
Circumoral paresthesias
that may progress over
entire body, chest tightness,
nausea,
vomiting, flatus, diarrhea,
hypotension, prolonged QT
interval, tetany
Citrate toxicity,
Hypocalcemia
Decrease whole blood flow rate, increase WB:ACD
ratio, switch to
ACD/heparin anticoagulation, slow FFP infusion
rate, administer calcium PO or IV (slow push or
drip), add calcium to replacement fluid
(continuous flow procedures only & not FFP or
Cryo poor plasma)
Burning eyes, periorbital
Edema
Ethylene oxide
allergic reaction
Discontinue procedure, perform setup with double
prime, use oldest tubing kits
Introduction to Apheresis
Dr. Nashwa Elsayed

44. Signs and Symptoms
Possible
Cause(s)
Suggested Treatment(s)
Hives, urticaria, wheezing,
facial edema, SOB,
hypotension, tachycardia
Allergic
reaction
Administer Benadryl IVP, epinephrine sub q,
and/or solumedrol IV
Back pain, hematuria,
tachycardia, hypotension,
hemolysis, SOB
Acute
transfusion
Reaction
Discontinue blood component and order
transfusion reaction work-up
Flushing, hypotension ACE inhibitor
reaction
Change albumin lot number, switch to FFP or
colloid starch replacement, hold or
discontinue ACE inhibitor, delay therapeutic
apheresis for 24-48 hours after ACE inhibitor
administration
The procedure should be paused when a reaction occurs and the physician should be
notified. All medical interventions should be prescribed by a physician.
The physician will determine if the procedure should be restarted or aborted.
SOB = shortness of breath; WB = whole blood; ACD = acid citrate dextrose;
FFP = fresh frozen plasma; ACE = angiotensin-converting enzyme.
Introduction to Apheresis
Dr. Nashwa Elsayed

45. CONCLUSION
Donation & Therapeutic Apheresis is safe and easy effective
methods to be used when needed.
A well-trained and experienced team can overcome the technical
difficulties in order to complete the procedures without
complications.
Policy and procedure of Donors Apheresis
And Therapeutic Apheresis should be in place.
Apheresis Procedures are effective and safe methods as
supportive therapy or management for patients in need.
Introduction to Apheresis
Dr. Nashwa Elsayed

46. Thank You