APHERESIS REVIEW

SESSION 2020
 APHERESIS REVIEW SESSION 2020

TABLE OF CONTENTS
Welcome and Introduction to the Apheresis Review Session .........................................1
Basic Science in Apheresis.......................................................................................................2
Care of the Apheresis Donor and Therapeutic Apheresis Patient ................................3
Clinical Applications: Cellular Therapy...................................................................................4
Donor Apheresis Overview...................................................................................................... 5
PAT 7th Edition Overview........................................................................................................... 6
Apheresis Math.............................................................................................................................7
Apheresis Program Essentials..................................................................................................8
Apheresis Instrumentation........................................................................................................ 9
Clinical Applications: Therapeutic Apheresis.....................................................................10
Quality in Apheresis: Standards, Guidelines and Regulations........................................ 11

www.apheresis.org
 APHERESIS REVIEW SESSION 2020

PROGRAM AND SPEAKERS

DAY ONE: TUESDAY, JUNE 9TH, 2020
All times listed in Pacific Daylight Time (PDT)

WELCOME AND INTRODUCTION TO THE APHERESIS

8:30AM – 9:00AM REVIEW SESSION (TO INCLUDE OVERVIEW OF THE Christina Anderson, RN, BSN, HP(ASCP)
ASCP QUALIFICATION IN APHERESIS (QIA) EXAM)

9:00AM – 10:00 AM BASIC SCIENCE IN APHERESIS Jeff L. Winters, MD

CARE OF THE APHERESIS DONOR AND

10:00AM – 11:00AM Tina Ipe, MD, MPH
THERAPEUTIC APHERESIS PATIENT

11:00AM – 12:00PM CLINICAL APPLICATIONS: CELLULAR THERAPY Nicole Aqui, MD

12:00AM – 1:00PM DONOR APHERESIS OVERVIEW Frances Carson, BS

1:00PM – 1:30PM PAT 7TH EDITION OVERVIEW Rasheed A. Balogun, MD, FACP, FASN,
HP(ASCP)

DAY TWO: WEDNESDAY, JUNE 10TH, 2020

All times listed in Pacific Daylight Time (PDT)

9:00AM – 10:00 AM APHERESIS MATH Jay Raval, MD

10:00AM – 11:00AM APHERESIS PROGRAM ESSENTIALS David Lin, MD

11:00AM – 12:00PM APHERESIS INSTRUMENTATION Edwin A. Burgstaler, MT, HP(ASCP)

12:00AM – 1:00PM CLINICAL APPLICATIONS: THERAPEUTIC APHERESIS Nicole De Simone, MD, MPH

QUALITY IN APHERESIS: STANDARDS, GUIDELINES Margaret M. Hannan, BS, MSM/OL, CQA

1:00PM – 2:00PM
AND REGULATIONS (ASQ) &
Alicia Garcia, RN, HP(ASCP)

www.apheresis.org
 APHERESIS REVIEW SESSION 2020

WELCOME AND 1
INTRODUCTION TO
THE APHERESIS REVIEW
SESSION
Christina Anderson, RN, BSN, HP(ASCP)

Topics Covered:
1. Overview of the application and examination process.
2. The various routes of eligibility.
3. Recommendations on preparing for the exam.
ASFA is pleased to offer a Qualification in Apheresis (QIA) in partnership with The
Board of Certification (BOC) of the American Society for Clinical Pathology (ASCP). The
new credential in Apheresis excellence went into effect in December of 2015. The
review session will cover the steps necessary to apply, test, and become Qualified In
Apheresis.
An eligible applicant does not have to be a member of ASFA or ASCP but must satisfy
the requirements of at least one of the seven routes of eligibility.

www.apheresis.org
Qualification In Apheresis

Chrissy Anderson, BSN, RN, HP (ASCP)

Apheresis Review Session
Tuesday, June 9, 2020
[email protected]
ASFA partners with ASCP BOC to offer
credentialing in Apheresis Medicine

• May 2015 First meeting at

ASCP Headquarters
– Qualification In Apheresis
(QIA) is selected as title of
apheresis qualification by
working group/committee
• December 2015 application
process for QIA opens
within ASCP
 Who is the ASCP BOC ?
The ASCP Board of Certification (BOC) provides a mechanism for
individuals to be recognized as having the necessary competence
to perform the medical/laboratory roles they seek through certification or
qualification

BOC’s Qualifications recognize specific skills in several technical areas of

laboratory medicine and related fields such as apheresis.
Upon meeting specific educational and work experience requirements,
candidates are eligible to complete an online examination

Successful candidates are awarded a credential demonstrating their

proficiency
 Why is Qualification Important?
Qualification provides an opportunity to prove your competence in key
areas of medicine & related fields such as apheresis

What are the advantages of completing a Qualification?

• Visible recognition of specific skills in a technical area with the
Qualification initials after the ASCP credentials
• Recognition by state licensure. The state of Florida recognizes those
individuals certified and qualified as HT(ASCP)QIHC toward meeting the
specialist licensure requirements for histology.
• More job possibilities and career mobility throughout the country and
profession
• Professional growth and recognition
• Knowledge and education such as keeping up with state of the art
technology
WHO?

YOU!
Should physicians become Qualified?
College of American Pathology
Transfusion Medicine Guidelines (2009)
TRM.42255
Are medical personnel performing and/or supervising
therapeutic apheresis qualified by education and training?

The personnel involved in provision of therapeutic apheresis,

including operators and supervising physicians, shall be
appropriately qualified.
Examples of appropriate qualification have been established by the
American Society for Apheresis (ASFA.)
These guidelines were published and are available at
http://www.apheresis.org/asfa_guidelines/index.cfm.
 Should physicians become Qualified?

GUIDELINES FOR PHYSICIANS OVERSEEING

THERAPEUTIC APHERESIS
INTRODUCTION
The following document for the establishment of Guidelines for
Physicians overseeing Therapeutic Apheresis (TA) is intended to focus
attention on two issues important in the quality of care: the
recognition that a qualified physician is the best provider of TA services
and the importance of the maintenance of TA professional knowledge.
THERAPEUTIC APHERESIS SERVICE
A licensed physician, qualified by training and/or by experience, who
will be called the Medical Director in these Guidelines, should oversee
each TA Service.
 Should TA staff become Qualified?

GUIDELINES FOR THERAPEUTIC APHERESIS ALLIED HEALTH STAFF

INTRODUCTION
The following Guidelines for therapeutic apheresis (TA) allied health staff,
developed by the Allied Health Committee of the American Society for Apheresis
(ASFA) are intended to focus attention on two issues important in the quality of
care: the recognition that a qualified staff is the best provider of TA services and
the importance of the maintenance of professional knowledge. It is also
important to note that unlike donor apheresis procedures, TA procedures are
performed on patients with underlying disease processes and physiologic
abnormalities which have the potential to be exacerbated by the TA procedure. As
a result, different educational and training requirements are necessary for the
performance of TA procedures compared to donor procedures.
THERAPEUTIC APHERESIS STAFF QUALIFICATIONS
Therapeutic Apheresis (TA) Service staff should consist of medical personnel
qualified to perform TA procedures.
 QIA Eligibility Routes
To be eligible for this category, an applicant must satisfy the requirements of
at least one of the following routes:

• Route 1: RN, LPN, or LVN with U.S. state license, certificate, or diploma*,
AND three years full-time acceptable experience in apheresis or five years
part-time acceptable experience in apheresis within the last ten years.
• Route 2: Professional nurse diploma or equivalent received outside of the
U.S.*, AND three years full-time acceptable experience in apheresis or five
years part-time acceptable experience in apheresis within the last ten
years.
• Route 3: ASCP or ASCPi certification in the following categories: MLS/MT,
BB, SBB or MLT AND three years of full-time acceptable experience in
apheresis or five years part-time acceptable experience in apheresis
within the last ten years.
 QIA Eligibility Routes
USA
To be eligible for this category, an applicant i hin satisfy the requirements of
tmust
w
at least one of the following routes:rses
Nu
• Route 1: RN, LPN, or LVN with U.S. state license, certificate, or diploma*,
AND three years full-time acceptable experience in apheresis or five years
part-time acceptable experience in apheresis within the last ten years.
• Route 2: Professional nurse diploma or equivalent received outside of the
U.S.*, AND three years full-time acceptable experience in apheresis or five
years part-time acceptable experience in apheresis within the last ten
years. es
rs
• Routel N3:u ASCP or ASCPi certification in the following categories: MLS/MT,
BB, a or MLT AND three years of full-time acceptable experience in
nSBB
i o
rn at
apheresis or five years part-time acceptable experience in apheresis
te
In within the last ten years.
 QIA Eligibility Routes
• Route 4: Baccalaureate degree from a regionally accredited
college/university in the U.S. or an accredited/approved educational
institution** outside of the U.S. with a combination of 24 semester hours
(36 quarter hours) of biology and/or chemistry, AND three years of full-
time acceptable experience in apheresis or five years part-time acceptable
experience in apheresis within the last ten years.
• Route 5: Doctorate in medicine or equivalent of a U.S. Doctorate in
Medicine**, AND one year of acceptable experience as an apheresis
physician within the last five years.
• Route 6: Doctorate in medicine or equivalent of a U.S. Doctorate in
Medicine**, AND documented training in a relevant accredited post
graduate medical education program which includes apheresis (e.g.,
transfusion medicine, hematology/oncology, nephrology, clinical
pathology).
• Route 7: High school graduation** or equivalent, AND five years of full
time acceptable experience in apheresis within the last ten years.
* Applicants must submit a notarized copy of their official certificate, diploma, or license.
**Accredited/approved by a governing regulatory association or Ministry, or eligibility will be determined by
transcript evaluation. The baccalaureate degree must be equivalent to a U.S. baccalaureate degree. A
doctorate in medicine must be equivalent to a U.S. doctorate in medicine.
 QIA Eligibility Routes
• Route 4: Baccalaureate
for degree from a regionally accredited
s
college/university
o ute ians in the U.S. or an accredited/approved educational
2 R ysicoutside of the U.S. with a combination of 24 semester hours
institution**
(36 quarterph hours) of biology and/or chemistry, AND three years of full-
time acceptable experience in apheresis or five years part-time acceptable
experience in apheresis within the last ten years.
• Route 5: Doctorate in medicine or equivalent of a U.S. Doctorate in
Medicine**, AND one year of acceptable experience as an apheresis
physician within the last five years.
:
• Route 6: Doctorate inomedicineute or equivalent of a U.S. Doctorate in
R i s
w res s training in a relevant accredited post
Medicine**, AND edocumented
he cian program which includes apheresis (e.g.,
graduate medicalN education
p
A ni
transfusion medicine, e c hhematology/oncology, nephrology, clinical
T
pathology).
• Route 7: High school graduation** or equivalent, AND five years of full
time acceptable experience in apheresis within the last ten years.
* Applicants must submit a notarized copy of their official certificate, diploma, or license.
**Accredited/approved by a governing regulatory association or Ministry, or eligibility will be determined by
transcript evaluation. The baccalaureate degree must be equivalent to a U.S. baccalaureate degree. A
doctorate in medicine must be equivalent to a U.S. doctorate in medicine.
 Apheresis Experience
and Training
Routes 1 – 4 & 7:
To fulfill the experience requirement for the Qualification in Apheresis
examination, you must have experience within the time frame required in
at least one of the following apheresis areas:

• Therapeutic plasma exchange (TPE) h ave in

u st nce
• Red blood cell exchange M rie se
p e he
ex ft s
• Cellular depletions o
1 area
• Selective adsorptions
• Extracorporeal photopheresis (ECP)
• Mononuclear cell collections (MNC)
• Hematopoietic progenitor cell collection (HPC)
• Automated red blood cell collections (RBC)
• Donor platelet collections
• Donor plasma collections
• Granulocyte collections
 Apheresis Experience
and Training
Routes 5 & 6:
• To fulfill the experience/training requirement for the
Qualification in Apheresis examination, you must have
experience/training in all of the following areas.
• Experience must be completed within the time frame
required:
– Evaluating patients and/or donors for suitability to undergo
apheresis procedures
– Writing orders for apheresis procedures Must h
ave
– Supervising apheresis procedures ex p erienc
e
– Evaluating and managing adverse events during i n all of
these
areas
apheresis procedures
 HOW?
Identify the Qualification you’re applying for and determine
your eligibility
• Apply online www.ascp.org
• Choose a route of eligibility depending on the education and
training you've completed
Gather your education and work experience documentation
• AFTER you submit an online application, documentation
required to establish your eligibility must be submitted to our
office
• Submit all documentation required to establish eligibility to:
ASCP Board of Certification
33 W. Monroe St., Suite 1600
Chicago, IL 60603
 Schedule your examination
• Once your application and eligibility documentation
has been approved by the BOC, you’ll receive an
email admission notification containing an
authorization number to the examination
• The examination consists of a 50-question multiple
choice timed test that must be completed within a
90-minute time period
• The test is self-administered on your own computer
at the date and time of your choice within the 60 day
time period indicated on your admission. To access
the online examination, click on this link to the
testing site
 Prepare for Exam

Study for Qualification.

• To help you prepare for the qualification
examination, reading lists and topic outlines
are available by clicking on the links below:
Qualification in Apheresis, QIA
– - Reading List (PDF)
– - Topic Outline (PDF)
 Watch for your results and certificate
• You will receive an email notification to review your online score
report within 4 – 6 business days after your examination date. You
will receive your wall certificate within 3 – 4 weeks after your exam
date.

• Use of Qualification: Individuals who have been qualified may list

their credentials in the following manner:
• Christina Gallager, RN, BSN, QIA
• Bjorn Swenson, RGN, QIA
• Anand Padmanabhan, MD, PhD, QIA
• Mary Smith, MT(ASCP), QIA (for individuals who are both qualified and ASCP certified)
 TOPIC OUTLINE
The Qualification in Apheresis examination questions encompass
different topics or subtests within the area of Apheresis:
• Basic Science
• Clinical Applications
• Donor/Patient Care
• Instrumentation
• Operational Considerations
• Standards, Guidelines, and Regulations (ASFA, AABB, CAP,
FDA, FACT, HIPAA, TJC, etc.)

Each of these subtests comprises a specific percentage of the

overall 50-question qualification examination.
 TOPIC OUTLINE
The subtests for the examination are outlined below:

I. Basic Science (5-10%) II. Clinical Applications (10-20%)

2-5 Questions 5-10 Questions

A. Hematology/Coagulation A. Donor Apheresis

B. Immunohematology/ 1. Platelets
Genetics 2. Red blood cells
3. Plasma
1. Blood component therapy
2. HLA 4. White blood cells (e.g., granulocytes)
3. ABO B. Therapeutic Apheresis
C. Immunology 1. Plasma exchange
1. Antibodies 2. Red cell exchange
2. Immune complexes 3. Cell depletion
4. Selective adsorption/filtration procedures
D. Laboratory Testing
 TOPIC OUTLINE
II. Clinical Applications (10-20%) III. Donor/Patient Care (30-40%)
cont. 15-20
5-10 Questions
Questions
C. Cellular Therapy
1. Hematopoietic progenitor cells A. Assessment/Monitoring
2. Extracorporeal photopheresis B. Replacement Fluids
(ECP) C. Anticoagulation
3. Mononuclear cell collections D. Medications (e.g., calcium,
(e.g., lymphocytes, antihistamine) and Drug
monocytes) Interactions
D. Diseases Treated with Apheresis E. Venous Access
F. Fluid Balance
G. Age-Related Considerations
H. Adverse Reactions
 TOPIC OUTLINE
IV. Instrumentation (10-20%) *The majority of instrument
5-10 Questions questions will address general
processes and procedures applicable
A. Theories and Techniques of to most instruments
Separation
(e.g. alarm codes for specific
1. Centrifugation (e.g., intermittent
and continuous flow) instruments will NOT be
2. Membrane tested). The troubleshooting
3. Columns questions will address day to
B. General Principles of Automated day problems encountered on any
Instruments* instrument; they will not
1. Anticoagulation of extracorporeal be instrument specific.
circuit
2. Extracorporeal blood volume
3. Efficiencies of separation and/or
collection
4. Clinical applications (see II.A.—D.)
 TOPIC OUTLINE
V. Operational Considerations VI. Standards, Guidelines, and
(10-20%) Regulations: (ASFA, AABB,
CAP, FDA, FACT, HIPAA, TJC,
5-10 Questions etc.)
(10-20%) 5-10 Questions
A. Quality Assurance
(e.g., cGMP, cGTP, validation) A. Informed Consent
B. Quality Control B. Confidentiality
1. Product yield
C. Donor Selection
2. Instrument efficiencies
D. Facility Licensure and
C. Equipment Maintenance Accreditation
D. Safety (e.g., OSHA, CDC) E. Training & Competency
E. Infection Control
All Board of Certification examinations use conventional
and SI units for results and reference ranges
 Suggested Reading for QIA Preparation*
JOURNALS
Journal of Clinical Apheresis. American Society for Apheresis (ASFA), Wiley, British Columbia. Link to View

TEXTS
Linz, W., Chibber, V., Crookston, K., & Vrielink, H. (2014). Principles of Apheresis Technology (5th ed.). Vancouver,
British Columbia: ASFA. Link to Purchase
McLeod, B., Szczepiorkowski, Z., Weinstein, R., & Winters, J. (Ed.). (2010). Apheresis: Principles and Practice
(3rded.). Bethesda, MD: AABB Press. Link to Purchase

REGULATIONS
AABB. (2014). Standards for Blood Banks and Transfusion Services (29thed.). Bethesda, MD: AABB Press. Link to
Purchase
AABB. (2013). Standards for Cellular Therapy Services (6th ed.). Bethesda, MD: AABB Press. Link to Purchase
Center for Biologics Evaluation Research. (2007). Guidance for Industry and FDA Review Staff: Collection of
Platelets by Automated Methods: Food and Drug Administration. Available online: www.fda.gov
Food and Drug Administration. (published yearly). Code of Federal Regulations Title 21: Food and Drugs. Office of
the Federal Register National Archives and Records Administration Publication, Parts 210, 211, 600, 601, 606, 607,
610, 640, 1271. WashingtonD.C.: Printing Office of the Superintendent of Documents. Link to View
Food and Drug Administration. (February 2001). Guidance for Industry: Recommendations for Collecting Red Blood
Cells by Automated Apheresis Methods (Technical Correction). Rockville, MD: FDA. Available online: www.fda.gov
Food and Drug Administration. (March 10, 1995). Revision of FDA Memorandum of August 27, 1982: Requirements
for Infrequent Plasmapheresis Donors. Rockville, MD: FDA. Available online: www.fda.gov
The Joint Commission. (2015). Comprehensive Accreditation Manual for Hospitals (CAMH). Oakbrook Terrace, IL:
The Joint Commission. Link to Purchase
 Suggested Reading for QIA Preparation*
Additional O N L I N E resources:
AABB www.aabb.org
American Nephrology Nurses Association www.annanurse.org
American Society for Apheresis www.apheresis.org
American Society of Hematology www.hematology.org
American Society of Nephrology www.asn-online.org
Centers for Disease Control and Prevention www.cdc.gov
College of American Pathologists www.cap.org
Food and Drug Administration www.fda.gov
HIPAA www.cms.hhs.gov/hipa
Occupational Safety and Health Administration www.osha.gov

*This list is intended only as a partial reference source. Its distribution does not
indicate endorsement by the Board of Certification, American Society for Clinical
Pathology; nor does the Society wish to imply that the content of the examination
will be drawn solely from these publications
 Helpful Hints
• No more FACT Sheets for instruments
• Reduced Suggested Reading List
• Due to International Scope of Qualification,
focus on referenced best practices and
decreased emphasis on US regulations
 How to prepare for the test?
• See ASCP BOC Suggested Reading List

• ASFA offers*:
– Principles of Apheresis Technology
– ASFA Apheresis Review Workshop at Annual Meeting
– ASFA Virtual Apheresis Review Workshop - NEW
– ASFA is planning additional Webinars such as Series of education
webinars for those preparing for the exam

• Other on-line resources for organizations and vendors

*some may require additional registration or purchasing costs

 FAQ: What are the credentials for my
name if I pass the exam?
• Individuals who have been qualified may
indicate this qualification through the use of
initials in the following manner:
• Jennifer Wintz, RN, BSN, QIA (for individual
qualified in apheresis)
• Hans Anderssen, MLS(ASCP)CMQIA (for
individuals who are qualified and who are also
ASCP certified)
 FAQ: How long is the
Qualification valid?
Time Limits and Requalification: Candidates
who pass the exam, the qualification is valid for
three years.
• This Qualification may be requalified every
three years upon payment of a $50
application fee and completion of 6 contact
hours of acceptable continuing education /
other activities in the area of the
Qualification.
 FAQ: What if I don’t pass the exam?
• A candidate has five (5) opportunities to sit for any one
Qualification.
• If after five attempts, the candidate must meet eligibility
requirements under an alternate route of eligibility.
• An eligibility period is three (3) months. A candidate
cannot test more than one time during an eligibility period.
• A candidate can reapply at any time after they receive their
score report. The candidate will be assigned a new
eligibility period after their current eligibility period ends.
• An application fee is required after each attempt upon
reapplication
FAQ: Can Apheresis nurses and doctors in
countries outside the United States
become Qualified, if they do not have
apheresis experience in the United States?

YES!
The candidate must meet eligibility
requirements under at least one route of
eligibility and apply online to ASCP.org.
 In summary…
Apply for the Qualification!
• Spread the word….
• Be the first in your professional group to have “QIA” behind
your name!
• Application process is open:
http://www.ascp.org/Board-of-Certification/Qualification/Step-
1/Qualification-in-Apheresis-QIA.html
• Additional information available on ASFA website
www.apheresis.org
 ASCP QIA Working Group
• Challenges each of you to become QIA!
• And to tell at least 3 colleagues about the
qualification.

Professional Goal For Self:

Take Qualification Exam !
 THANK YOU!
Any Questions?

On behalf of ASCP and ASFA QIA Working Group: “GOOD LUCK!”

 Complete on-line application

• An application fee of $240 is required. Application fees are non-refundable. Be

sure you choose the correct category of examination and you meet the eligibility
requirements as stated and are able to provide the appropriate documentation
when submitting your application and application fee. If you determine that you
have applied for an incorrect certification examination, our office will be unable
to change the category of examination. If you are unable to submit your
application fee online with a credit card or PayPal, pay-by-mail instructions will be
available upon the completion of the online application process.
• Applications will be processed within 45 business days of receipt. If documentation
establishing eligibility is not received within 45 business days, you will be deleted
from the examination process. Application fees are non-refundable.
• Submit all documentation required to establish eligibility to:
ASCP Board of Certification
33 W. Monroe St., Suite 1600
Chicago, IL 60603
 APHERESIS REVIEW SESSION 2020

BASIC APHERESIS 2
SCIENCE
Jeffrey L. Winters, MD

This lecture will review the basic science of apheresis. This will include the basics of:
1. Hematology and coagulation and how these influence and are modified by various
apheresis treatments and anticoagulants.
2. The immune system including both the innate and adaptive components and HLA.
3. Blood Groups and Blood Group antigens.
4. Blood components and their use and indications as well as component modifications.
5. Electrolyte physiology and the influence of apheresis on electrolytes.
6. Testing of blood products at the time of collection and preparation for transfusion.
7. Replacement fluids.
8. Separation of blood components by apheresis including both centrifugation based
methods and filtration based methods.

www.apheresis.org
Basic Apheresis Science
Jeffrey L Winters, M.D.
Medical Director, Therapeutic Apheresis Treatment Unit
Mayo Clinic
Rochester, Minnesota

©2011 MFMER | slide-1

Basic Hematology
What is blood?
• Plasma – liquid portion of blood
• Carries the cellular elements, proteins,
nutrients, dissolved gasses, waste products
and electrolytes
• Proteins include:
• Coagulation factors
• Albumin and transport proteins
• Globulins
©2011 MFMER | slide-2
Basic Hematology
What is blood?
• Erythrocytes (Red Blood Cells)
• Transport oxygen and carbon dioxide
• Hemoglobin – binds oxygen in the lungs
and carbon dioxide in the tissues
• Carbonic anhydrase – converts carbon
dioxide into carbonic acid and
bicarbonate

©2011 MFMER | slide-3

Basic Hematology
What is blood?
• Erythrocytes (Red Blood Cells)
• Produced by bone marrow
• Erythropoietin produced by the kidneys
stimulates production
• Concentration of 4.5-6 x106 cells/µL
• Life span 120 days

©2011 MFMER | slide-4

Basic Hematology
What is blood?
• Erythrocytes (Red Blood Cells)
• Hemolysis – destruction of red blood
cells
• Extravascular – removed by the
splenic macrophages
• Intravascular – immune, mechanical,
thermal, or osmotic disruption of the
red cell

©2011 MFMER | slide-5

Basic Hematology
What is blood?
• Erythrocytes (Red Blood Cells)
• Reticulocytes – young red blood cells
• 0.5% to 1.5% of red blood cells
• Increased in hemolysis or blood loss
• Decreased in marrow production
problems

©2011 MFMER | slide-6

Basic Hematology
What is blood?
• Leukocytes (White Blood Cells)
• Part of the immune system
• Polymorphonuclear cells (PMNs) or
granulocytes
• Mononuclear cells

©2011 MFMER | slide-7

Basic Hematology
What is blood?
• Leukocytes (White Blood Cells)
• Polymorphonuclear cells (PMNs) or
granulocytes
• Neutrophils – 80-90%, phagocytize
foreign particles
• Eosinophils – 1-4%, attack parasites
• Basophils - <1%, involved in inflammation
• Mast cells when located in tissues

©2011 MFMER | slide-8

Basic Hematology
What is blood?
• Leukocytes (White Blood Cells)
• Mononuclear cells
• Monocytes – 2-8%, phagocytize cellular
debris
• Macrophages when located in tissues
• Lymphocytes – 20-40%
• B cells
• T cells
• Hematopoietic progenitor cells
©2011 MFMER | slide-9
Basic Hematology
What is blood?
• Platelets
• Fragments of megakaryocytes found in
the bone marrow
• Normal count: 150 to 400 x 109/L
• Circulating lifespan of 7 to 10 days

©2011 MFMER | slide-10

Basic Hematology
Complete Blood Count (CBC)
• Platelet count • Coulter principle
• White blood cell • A particle (e.g. cell)
passing between two
count charged electrolyte
• Differential chambers impedes
• Automated circuit in proportion
• Manual to the size of the
particle

©2011 MFMER | slide-11

Basic Hematology
Complete Blood Count (CBC)
• Hemoglobin
• Potassium ferrocyanide and potassium cyanide
convert to cyanmethemoglobin measured at 540 nm
• Females – 14.6 – 17.8 g/dL
• Males 12.1-15.9 g/dL
• Hematocrit
• Percent volume of packed red blood cells
• Females 34-47%
• Males 40-52%
• Hematocrit approximately 3x hemoglobin

©2011 MFMER | slide-12

Basic Coagulation
PRIMARY HEMOSTASIS

• Results from interactions among platelets

and between platelets and the vessel wall to
form a platelet plug (white clot).
Basic Coagulation
PRIMARY HEMOSTASIS
• Steps of primary hemostasis
• Injury exposes vWF and collagen
• Platelets bind via GPIbIX and GPIa
• Binding causes the release of calcium from
the platelet
• Calcium triggers a cascade resulting in:
• ADP release which recruits more platelets
• GPIIbIIIa expression which binds to
fibrinogen
Basic Coagulation
PRIMARY HEMOSTASIS
• Tests of primary hemostasis
• Platelet count
• Platelet aggregation tests - measures
ability of platelets to aggregate when
stimulated
Basic Coagulation
SECONDARY HEMOSTASIS
• Secondary hemostasis forms a stable clot
(red clot) following primary hemostasis
through the generation of fibrin
• Secondary hemostasis is mediated through
the coagulation cascade
• Coagulation factors are produced by the
liver (prothrombin, V, VII, IX, X, and XIII) and
endothelium (VIII).
Basic Coagulation
SECONDARY HEMOSTASIS
Basic Coagulation
SECONDARY HEMOSTASIS
• The production of g-
carboxyglutamyl
residues requires the
presence of vitamin K.
• Vitamin K dependent
factors are
prothrombin, VII, IX, X,
protein C, and protein
S.
Basic Coagulation
SECONDARY HEMOSTASIS
• PTT
• Measures factors
participating in the
intrinsic and common
pathways
• Is prolonged by heparin
• Normal value of 35
seconds
• Clotting triggered by
adding phospholipid,
calcium, and silica or clay
to citrated plasma
Basic Coagulation
SECONDARY HEMOSTASIS
• PT
• Measures factors
participating in the
extrinsic and common
pathways
• Is prolonged by Coumadin
• Normal value of 11 to 16
seconds
• Clotting triggered by
adding phospholipid,
calcium, and tissue factor
to citrated plasma
Basic Coagulation
SECONDARY HEMOSTASIS
• Prothrombin time is also reported as the
INR
• INR = (patient PT/Control PT)ISI
• INR is used to monitor patients being
treated with Coumadin
• The INR allows for comparison of
prothrombin times between labs
Basic Coagulation
INHIBITORS OF SECONDARY HEMOSTASIS
• Antithrombin (AT)
• inactivates thrombin, Xa,
XIIa, XIa, and IXa
• When bound to heparin
its activity increases!
• Protein C
• inactivates Va and VIIIa
• Protein S - cofactor that
enhances protein C
activity

©2011 MFMER | slide-22

Basic Coagulation
FIBRINOLYSIS
• Plasmin
• cleaves fibrin, fibrinogen, factor V and
factor VIII
• derived from plasminogen
• Tissue plasminogen activator (tPA)
• binds to plasminogen poorly unless it
is bound to fibrin
• Converts plasminogen to plasmin
The Immune System
Innate (Natural) Immunity
• Does not require previous exposure
• Consists of:
• Physical barriers (e.g. skin and mucus
membranes)
• Chemical barriers (e.g. antibacterial
substances in secretions)
• Phagocytic cells (PMNs, monocytes, and
macrophages)

©2011 MFMER | slide-24

The Immune System
Innate (Natural) Immunity
• Consists of:
• Natural killer cells – involved in surveillance for tumor cells and
virally infected cells. Induce apoptosis through perforin and
granzyme.
• Complement
• Plasma proteins which:
• Lyse foreign cells through generating MAC (C5-C9)
• Opsonize cells for phagocytosis
• Classical pathway – triggered by IgG or IgM
• C1, C4, C2, C3, C5-C9
• Alternate pathway – triggered by polysaccharides and
enzymes in cell walls of microorganisms
• Factor B, factor D, properidin, initiating factor, C3-C9

©2011 MFMER | slide-25

The Immune System
Adaptive Immunity
• Develops after exposure to a specific non-self
antigen
• Results in immune “memory”
• T-lymphocytes
• Formed in the thymus
• Recognize specific antigen presented in HLA
• May be directly cytotoxic (CD8 T-cells) or
drive further immune responses (CD4 T-cells)

©2011 MFMER | slide-26

The Immune System
Adaptive Immunity
• B-lymphocytes
• Formed in the bone marrow
• Surface bound immunoglobulin
recognizes specific antigens
• When stimulated differentiate into plasma
cells which secrete immunoglobuins
toward the specific antigen
• IgM, IgG, IgD, IgE, and IgA
©2011 MFMER | slide-27
Blood Groups and Blood Group
Antigens
Over 700 different blood group antigens
have been described
• Vary in frequency depending upon
ethnicity
• High-frequency or public antigens -
present in >99% of the population
• Low-frequency or private antigens -
present in <1% of the population
Blood Group Antibodies

• Most are IgM or IgG

• May be naturally occurring or immune
antibodies
• Naturally occurring - antibody is present without
previous exposure to the blood group antigen.
Usually IgM.
• Immune - antibody is present because of previous
exposure to the blood group antigen. Usually IgG.
Blood Group Antibodies
May also be classified as:
• Alloantibodies - react with a foreign
antigen not present on the individual’s
own red blood cells
• Autoantibodies - react with self antigen
present on the individual’s own red blood
cells
Blood Product Testing
• Food and Drug Administration mandates each
donation be tested for:
• Anti-treponemal
• HBsAg
• Anti-HBc
• Anti-HCV
• Anti-HTLV-I/II
• Anti-HIV-1/2 plus group O
• Anti-T cruzi
• NAT for HIV, HCV, HBV, WNV, ZikV, B. microti
©2011 MFMER | slide-31
Blood Product Testing
• Testing performed before transfusion
• Determines patient’s ABO and Rh type
• Necessary to provide ABO compatible products
• Performs antibody screen
• Necessary only if RBC transfusion is ordered and if
patient has been pregnant or transfused within the last
3 months and the test has not been performed within 3
days
• Performs crossmatch for RBC products
• Varies depending upon antibody screen results
• Modifies products to meet special needs if ordered

©2011 MFMER | slide-32

Blood Products
Red Blood Cells

• Indications: Provide oxygen

carrying capacity
• Volume: 350 mL
• Hematocrit: 55 to 85%
• Effect: One unit should
increase the hemoglobin by
1 g/dL or the hematocrit by
3%.
• Shelf-Life: 35 to 42 days at 1
to 6°C
Blood Products
Platelets

• Indications:
• Platelet count < 20x109/L (prophylaxis)
• Platelet count <50x109/L if documented
hemorrhage or planned invasive procedure.
• Documented platelet dysfunction (bleeding time
>1.5 upper limit of normal, abnormal platelet
function tests, history) with petechiae, purpura,
bleeding, or planned invasive procedure.
• 1 apheresis platelet = 6 to 10 whole blood derived
platelets
• Standard dose is ONE apheresis unit followed by repeat
platelet count
Blood Products
Platelets

• Volume: 350 mL
• Product contains
approximately 3.0x1011
platelets.
• Effect: dose should raise the
platelet count by at least
30x109/L.
• Shelf-Life: 5 days at room
temperature with agitation.
Blood Products
Fresh Frozen Plasma
• Indications:
• Clinically significant deficit in multiple labile
coagulation factors.
• Clinically significant deficit in single factors for
which a concentrate is not available.
• Not indicated for:
• Volume expansion
• Nutritional supplement
• Source of immune globulin
Blood Products
Fresh Frozen Plasma

• Volume: 250 mL
• Contains physiologic
concentrations of all coagulation
factors.
• Standard dose: minimum of 2 units
followed by repetition of
coagulation testing.
• Shelf-Life:1 year at <-18°C
• Frozen within 8 hours of collection.
• Time required for preparation: 30
minutes to thaw
• Outdate after thawing: 24 hours,
storage at 1 to 6°C
Blood Products
“Other” Plasma
• FP24 – Plasma frozen within 24 hours of collection
• Equivalent to FFP
• Thawed plasma
• Plasma stored at 1-6º C more than 24 hours
• Shelf-life of 5 days (4 days after thawing)
• Decreased Factor V and VIII
• Pathogen reduced plasma
• Pooled plasma treated to inactivate infectious
agents
• Many different methods available world-wide

©2011 MFMER | slide-38

Blood Products
Cryoprecipitate
• Indications:
• Hemophilia A if factor VIII concentrate is not
available
• von Willebrand’s Disease if a factor VIII concentrate
high in vWF is not available*
• Hypofibrinogenemia
• Factor XIII deficiency
• Reversal of platelet defect in uremia*
* Pharmacological treatments are available
Blood Products
Cryoprecipitate
• Standard Dose: 10 units followed by repetition of
testing. Alternatively, total dose necessary to
achieve a desired level of factor VIII or fibrinogen
can be calculated.
• Time required for preparation: 30 minutes to thaw
• Outdate after thawing: 6 hours, storage at room
temperature
Blood Products
Cryoprecipitate

• Contains factors VIII, XIII,

vWF, and fibrinogen.
• Consists of the precipitate
that forms when FFP is
thawed to between 1 and
6°C.
• Volume: 10 to 15 mL per
unit
• Shelf-Life: 1 year at < -18° C
Blood Products
Plasma, Cryoprecipitate Reduced
(Cryopoor Plasma)
• “Leftovers” after production of
cryoprecipitate
• ONLY used as a replacement fluid for
Thrombotic Thrombocytopenic Purpura
(TTP)
• NOT equivalent to plasma!
©2011 MFMER | slide-42
Irradiation
• Indicated for the prevention of GVHD.
• Indicated only for products containing viable
lymphocytes.
• Dose: Unit exposed to 25 Gy of gamma
irradiation to the center of the unit with 15 Gy at
the periphery.
• Time required for preparation: 5 minutes
• Outdate: Changes red cell expiration date to 28
days, does not affect platelet outdate.
Leukocyte Reduction
• Accepted indications are to reduce:
• Alloimmunization to HLA antigens
• Infection with CMV
• Febrile nonhemolytic transfusion reactions
• Indicated for products containing intact leukocytes
(e.g. red blood cells and platelets)
Washed Products
• Indicated to remove plasma proteins (e.g. IgA,
alloantibodies) or potentially toxic substances in the
plasma (e.g. potassium, adenine).
• Indicated for cellular blood products
• Time required for preparation:
• 45 minutes for red blood cells
• 3 hours for platelets
• Outdate:
• 24 hours for red cells
• 4 hours for platelets
Separation of Blood Components
Centrifugation
Separate blood
components is based on
specific gravity.

Graphics owned
by and courtesy of
TerumoBCT

©2011 MFMER | slide-46

Separation of Blood Components
Filtration
Cell Size (µm)
• Separate blood Platelet 2-4
components is based Red blood cell 6-8
upon the size of the
Neutrophil 8-12
substance
Eosinophil 8-12
• Primary filter (plasma Basophil 8-12
separator) Small 7-10
lymphoctyte
• Secondary filter Large 14-20
(Plasma fractionator) lymphocyte
Monocyte 15-25
©2011 MFMER | slide-47
Replacement Fluids
• Albumin is the standard replacement fluid due to safety.
• Use of less than 70% albumin associated with a higher
frequency of hypotensive reactions.
• Plasma or cryopoor plasma is indicated for thrombotic
thrombocytopenic purpura.
• Partial replacement with plasma indicated to replace
coagulation factors when there is a risk of bleeding.

©2011 MFMER | slide-48

Replacement Fluids
• Normal saline – 0.9% NaCl in sterile water
• Approximates osmolarity of plasma
• Other colloid solutions are available but are rarely used due to
side-effect profile
• Red blood cells – used during a red cell exchange

©2011 MFMER | slide-49

Electrolyte Physiology
• Sodium (Na+)
• Extracellular, actively pumped from cells to create a
concentration gradient
• Influx of Na+ triggers signaling such as propagation
of potentials along nerves
• Does not change in patients undergoing plasma
exchange
• Potassium (K+)
• Intracellular, works in concert with Na+
• Significant decrease with apheresis due to
metabolism of citrate anticoagulant

©2011 MFMER | slide-50

Electrolyte Physiology
• Chloride (Cl-)
• Extracellular anion, follows Na+
• Facilitates movement of bicarbonate from inside
of red blood cells
• Rises with use of albumin as a replacement fluid
and falls when plasma is used
• Bicarbonate (HCO3-)
• Part of the pH buffer system
• Falls with use of albumin as a replacement fluid
and rises when plasma is used

©2011 MFMER | slide-51

Electrolyte Physiology
• Magnesium
• Chelated by citrate so 39% decline seen in
healthy donors
• Greater drop seen in plasma exchange with
albumin and plasma
• Calcium
• Significant declines which can lead to
symptoms characterized by spontaneous
depolarization of neurons

©2011 MFMER | slide-52

QUESTIONS?

©2011 MFMER | slide-53

 APHERESIS REVIEW SESSION 2020

CARE OF THE 3
APHERESIS DONOR
AND THERAPEUTIC
APHERESIS PATIENT
Tina Ipe, MD, MPH

Apheresis can be used for donor collections and therapeutically for patients using
different instruments. This presentation will focus on providing optimal care for both
the apheresis donor and therapeutic apheresis patient by highlighting measures that
should be considered during the different phases of the procedure. Also, donor and
patient adverse reactions and mitigation strategies will be reviewed.

www.apheresis.org
Care of the Apheresis
Donor and Therapeutic
Apheresis Patient
TINA IPE, MD, MPH
JUNE 9, 2020
I have the following disclosure:
Terumo BCT, Inc. – Research
Funding
Objectives

u Understand care strategies for blood donors undergoing

apheresis collections
u Understand care strategies for patients undergoing
therapeutic apheresis
Apheresis Donor Care
Considerations

Pre-
Procedure Procedure Post-
* Donor
* Anticoagulant Procedure
screening/eligibility * Adverse events * Post donation
* Vascular access instructions
Why collect using apheresis?
u Targeted approach
Ø Donor’s blood type
Ø TBV
Ø CBC results
u Production costs reduced
Ø Multiple components collected from 1 donor
Ø Decreased indirect and direct costs
v Screening time
v Infectious disease testing
v Recipient exposure
v Modification (LR)
u Donor reactions reduced
Donor Eligibility
u Screening
Ø Donor health questionnaire
Ø Height, weight, hemoglobin/hematocrit
u Apheresis collection
Ø Consider deferral times
Ø Pre-collection laboratory values
Ø TBV
v Platelet (double or triple)
v Multi-component collections (platelets and plasma; platelets and RBCs; RBCs
and plasma; platelets, plasma, and RBCs;)
v Red blood cells (double)
v Plasma
Donor Screening
u Age as allowed by accrediting or state regulations
u Answer questions regarding health, medications, travel, etc.
u Previous donation history
u Minimum donor weight
Ø 110 lbs or 50 kg to qualify for platelet donation
Ø 130 lbs or 150 lbs to qualify for double RBC donation
u Minimum donor height
Ø 5’1” (male) or 5’3” (female) to qualify for dRBC donation
u Hemoglobin/hematocrit
Ø 12.5 (female) and 13 (male)
Ø 13.3 mg/dL for dRBCs
u Total blood volume
Ø Safely give multiple components concurrently
Donor Deferral
u Platelet collections
Ø At least 2 days with no more than 2 in 7-day period
Ø < 24 platelet apheresis collections in 12 month rolling period
Ø 7 days between double or triple products
u RBC collections
Ø 56 days (single)
Ø 16 weeks (double)
Ø If donated RBC or WB unit in previous 8 weeks, cannot donate
apheresis platelet unless the extracorporeal volume of the
apheresis instrument is less than 100 mLs for platelets
Ø Annual RBC loss is 1540 mL within 12 month rolling period
Donor Deferral

u Plasma
Ø Total net plasma volume not exceed 500 mLs or 600 mLs for
donors (< 175 lbs or >175 lbs respectively)
Ø Total net plasma volume not exceed 600 mLs or 700 mls on
Amicus (< 175 lbs or >175 lbs respectively)
Ø Maximum volume should not exceed 12 L or 14.4 L (< 175 lbs
or >175 lbs respectively)
Ø Collection volume should not exceed 16% of estimated TBV
(Europe)
u Annual RBC and plasma loss must be monitored
u Different recommendations for incomplete procedures
Pre-donation Laboratory Testing

u Pre-platelet count of >150,000 platelets/µL (platelet donation)

u Hemoglobin of 13.3 mg/dL (dRBC donation)
u Infectious diseases testing
u HIV, HBV, HCV, Syphilis, Chagas etc.
u HLA testing
u Female with history of pregnancy
Procedure Management
u Vascular access
Ø Phlebotomists are skilled in accessing peripheral veins in donors
Ø Different needles used for donor apheresis collections
Ø Use ultrasound for difficult to access donors
u Anticoagulant
Ø ACD-A is the primary anticoagulant
Ø Prevents blood from clotting
Ø Decreases ionized calcium levels
Ø Causes citrate intolerance/toxicity/Hypocalcemic reaction
u Monitor donor throughout procedure
Ø Comfort measures
Ø Product
Mobile Apheresis Collections
u Environment considerations
u Sufficient space
u Appropriate layout
u Adequate ventilation, lighting, heating/cooling
u Procedural considerations
u Pre-donation sample testing delayed
u Collection based on previous donor testing results (except ID)
u First time donor blood type and platelet count unknown
u Avoid collecting triple platelet collections
Adverse Events in Donors
u Hypocalcemic/Citrate toxicity
Ø Binding of ionized calcium in blood
Ø Signs/Symptoms include vibration sensations, twitching,
tremors, muscle cramping, nausea, vomiting, metallic taste
in mouth, lightheadedness, and chills
u Treatment:
Ø Reduce citrate infusion rate
Ø Oral calcium intake
v Supplementation during procedure
v Pre-procedural dairy intake
Vasovagal reactions
u Parasympathetic nervous system activation
Ø Peripheral vasodilation
Ø Bradycardia
Ø Signs/Symptoms include pallor, sweating, nervousness, weakness,
nausea, lightheadedness, and dizziness
v Severe: vomiting, twitching, and loss of consciousness
v Severe (rare): tetany, convulsions, and incontinence
u Treatment
Ø Trendelenburg position, cold compresses, slow and deep breaths,
fluid intake, saline infusion
Ø Applied muscle tension exercises, sodium and fluid replacements
Infiltration

u Fluid entering surrounding tissues after leaking through veins

Ø Signs/Symptoms include pain, pressure, swelling at needle
site, and poor venous access
u Treatment
Ø Needle removal
Ø Moderate pressure application
Other Apheresis Donor Issues
u Allergic
Ø Uncommon in donor apheresis
Ø Repeated ethylene oxide exposure
Ø Mild itching
Ø Treatment with antihistamines and/or epinephrine
u Hemolysis
Ø Secondary to high draw rates, defective or improperly
used equipment and disposables, donor illness, heat, etc
Ø Stop procedure immediately
Ø Determine cause of issue
Ø Monitor donor, if needed
Other Apheresis Donor Issues
u Air embolism
Ø Rare complication
Ø Sensors can detect air that enters within extravascular
circuit
Ø Signs/Symptoms include chest pain, shortness of breath,
pallor, hypotension, diaphoresis, nausea, mental confusion,
and syncope
Ø Stop procedure immediately
Ø Clamp the return line if there is visible air; place the
Trendelenburg position on the left side
Post Donation Instructions
u Strategies to mitigate adverse reactions and injuries
u Eat a well-balanced, filling meal
u Drink fluids
u Increase sodium intake
u Practice applied muscle tension
u Avoid strenuous exercise
u Leave bandage for 4 hours
u Wait in canteen for 15 minutes
u Alert donor center staff if experience issues after leaving
center
u Go to the emergency room if continue to have issues
Therapeutic Apheresis Care
Consideration

Procedure
Pre-Procedure Post-
* Replacement fluids
* Patient suitability Procedure
* Anticoagulant
* Vascular access * Blood
* Adverse events
transfusion
* Transfusion instructions
Reactions
Patient Suitability

u Demographic information (Age, gender)

u Patient factors (height, weight, ECV, TBV)
u Medical history
Ø Disease and comorbidities
Ø Review of hematologic, cardiopulmonary, neurologic,
hepatic and renal function
Ø Medications
u Physical examination
Ø Vascular access
u Use of apheresis and modality
Evaluation of Therapeutic Apheresis
Efficacy
u Mechanistic Evidence
Ø Does the current understanding of the disease process
support a clear rationale for the use of therapeutic
apheresis?
u Corrective Evidence
Ø Can the abnormality, which makes therapeutic apheresis
plausible, be meaningfully corrected?
u Clinical Effect
Ø Is there strong evidence that therapeutic apheresis confers
benefit that is clinically worthwhile and not just statistically
significant?
Treatment Plan/Orders/Preparation
u Frequency of procedure
u Determination of TBV and ECV
u Necessity of blood prime
u Replacement fluid to be used
u Fluid balance
u Vascular access
u Medications
u Patient education
u Patient consent
Vascular options for TA
Access Type Use Advantage Disadvantage

Peripheral Vein Variable Least invasive Phlebotomy

Fewer experience
complications
Non-tunneled Short-term Better BFR Infection
CVC Thrombosis
Hemorrhage
Tunneled CVC Long-term Better BFR Infection
Thrombosis
Hemorrhage
Implantable ports Long-term Lower infection Thrombosis
rates
AVF/AVG Long term Few Maturity
complications Surgeon

Modified from Kambiz Kalantari. Journal of Clinical Apheresis 27:153-159 (2012) to illustrate the HMH Experience
Pre-Apheresis Laboratory Testing
u Electrolytes (iCa2+, K+, Mg 2+)
u CBC
Ø Hemoglobin/Hematocrit
v Needed to program the device
Ø Platelets
u Coagulation testing
u ABO and Rh
Ø Necessary if FFP or cryopoor plasma or RBCs will be used as replacement fluids
u CMP
Ø Renal and Liver function tests
u Any testing needed for disease diagnosis or management
Ø ADAMTS-13 activity and inhibitor assay
Alteration in Blood Constituents
with TPE

**McLeod C. Bruce Apheresis Principles and Practice 2nd edition 2003

Replacement Fluids
u Options for therapeutic plasma exchange
Ø 5% albumin is the standard replacement fluid
Ø 5% albumin and normal saline combination
Ø Plasma or cryopoor plasma or S/D plasma
u Indicated for TTP
u Partial replacement to replace coagulation factors when there
is a risk of bleeding
u Red cell exchange
u Cross-match compatible RBCs
u Cytapheresis
u Usually no replacement fluids
u Lipid apheresis
u Extracorporeal photopheresis
Anticoagulation
u ACD-A typically used
Ø Acts on early stages of coagulation cascade
Ø Blocks calcium-dependent platelet activation
Ø Quickly metabolized
Ø Regional (extracorporeal) anticoagulant
u Heparin
Ø Prevents conversion of prothrombin to thrombin
Ø Systemic anticoagulant
Ø Slowly metabolized (30-150 min)
u Adjust anticoagulant ratio as needed
Ø Patient on anticoagulant
Medications
u Review patient’s medication list
u Medications are removed varyingly by different TA
procedures
u Understand drug’s pharmacokinetic and pharmacodynamics
properties
u Helpful tips:
Ø Hold once daily medications until after the procedure
Ø If medication is administered during or immediately before
TA, provide additional dosage if needed (eg: Eculizumab)
Ø Delay the procedure, if possible
Ø Consult with clinical pharmacist
Ø Review literature
Patient Identification and
Monitoring
u Perform time-out prior to start of procedure
Ø Ensure correct patient and correct procedure
u Inspect catheter insertion site and patency
Ø No bleeding or infection
Ø No clots in lumen
u Monitor patient’s fluid status
Ø Check for dehydration or fluid overload
u Monitor development of AEs and transfusion reactions
Adverse Events
u In general, apheresis procedures are safe with mild complications
Ø Complications: ~4-20% procedures
Ø Mortality: rare, usually associated with underlying disease or line
placement
u Events include
Ø Hematomas
Ø Citrate toxicity/hypocalcemia
Ø Vasovagal reactions
Ø Dilutional coagulopathy
u If patient’s receiving blood products, monitor TRs
Hypocalcemia
u Symptoms
Ø Numbness and tingling
Ø Chills
Ø Nausea and vomiting
Ø Hypotension
Ø Tetany
Ø Cardiac Arrhythmias
u Prevention
Ø Check ionized calcium
Ø Infuse IV calcium
u Treatment
Ø Pause procedure
Ø Decrease inlet pump flow rate
Ø Infuse IV calcium
Vasovagal Reaction
u Symptoms
Ø Apprehension
Ø Lightheadedness
Ø Nausea
Ø Decreased pulse
Ø Hypotension
Ø Perspiration
u Prevention
Ø Talk to the patient
Ø Explain the procedure so the patient understands
Ø Divert the patient’s attention
u Treatment
Ø Pause the procedure
Ø Place patient in Trendelenburg position
Ø Infuse fluids
Dilutional Coagulopathy
u When plasma is not used a replacement fluid
Ø 25-70% reduction in clotting factor activity
v Fibrinogen most decreased
v Prolonged PT and PTT
Ø Most factors return to baseline ~24 h
v Exception fibrinogen
v Prolongedrecovery with liver disease, underlying
coagulopathy
Allergic Reactions
u Symptoms
Ø Itching
Ø Hives
Ø Rash
Ø Swelling
Ø Anaphylaxis

u Prevention
Ø Check for allergies
Ø Pre-medicate

u Treatment
Ø Pause the procedure
Ø Medicate with Diphenhydramine, Methylprednisolone, H2 blockers
Transfusion related acute lung injury
(TRALI)
u Noncardiogenic pulmonary edema
u Interaction of recipient neutrophils and donor
antibodies in the lung microvasculature
u Plasma as replacement fluid
ØSudden onset respiratory distress and hypoxia
ØMay be difficult to differentiate from underlying
disease
Post-Apheresis
Instructions/Communication
u Ask patient to call apheresis unit if issues develop post-procedure
u Remind patient to take medications they have withheld
u Document concurrently during the procedure
Ø Vital signs, pre- and post-procedure
Ø Replacement fluids (type, removed and replaced volumes)
Ø Net fluid balance
Ø Access used
Ø Anticoagulant used
Ø Medications provided during procedure
Ø AEs and TRs
Ø Billing and QA
References
1. Schwartz, J., Padmanabhan, A., Aqui, N., Balogun, R. A., Connelly-
Smith, L., Delaney, M., Dunbar, N. M., Witt, V., Wu, Y. and Shaz, B. H.
(2016), Guidelines on the Use of Therapeutic Apheresis in Clinical
Practice–Evidence-Based Approach from the Writing Committee of the
American Society for Apheresis: The Seventh Special Issue. J. Clin.
Apheresis, 31: 149–338. doi:10.1002/jca.21470.
2. Hayes C, Neyrinck M, Ulner A, et.al: Care of Patients Receiving
Therapeutic Apheresis. In: Linz W, Chhibber V, Crookston K, et al, eds.
Principles of Apheresis Technology, 6th Edition Technical Principles of
Apheresis Medicine. Vancouver, BC Canada: American Society for
Apheresis, 2017: 115-142.
3. Ferber T, Hannan MM, Kempin SM. Donor Apheresis. In: Linz W, Chhibber
V, Crookston K, et al, eds. Principles of Apheresis Technology, 6th Edition
Technical Principles of Apheresis Medicine. Vancouver, BC Canada:
American Society for Apheresis, 2017: 143-161.
 APHERESIS REVIEW SESSION 2020

CLINICAL 4
APPLICATIONS:
CELLULAR THERAPY
Nicole Aqui, MD

Cellular therapies utilize donor (autologous or allogeneic) cells to treat a wide variety of
diseases. Apheresis-derived cellular products are the starting material for the majority
of these therapies. While hematopoietic progenitor cell (HPC) collections are standard
of care, immunotherapies have expanded to include other cell types. This session
will provide an overview of cellular therapy, discuss procedural aspects of collection,
and review current developments in HPC and non-HPC therapies - T cells (CAR-T), NK
cells, mesenchymal cells and others. The participant should gain an understanding of
the critical nature of apheresis in cellular therapy.

www.apheresis.org
 ASFA 2020
Review Session
Clinical
Applications:
Cellular Therapy
Nicole Aqui, MD
Section Chief, Transfusion and
Apheresis Services
Hospital of the University of
Pennsylvania
Disclosure

u No relevant conflicts of interest.

What is cellular therapy?
u Transplantation of human cells to replace or repair damaged tissue
and/or cells (AABB)
Methods of
Collection
Mechanism of MNC collection in
modern apheresis machines
Mechanism of MNC collection in
modern apheresis machines

Fesnak, Transfus Med Rev 2016

 Peripheral blood cell
type specific gravities,
corresponding
hematocrit
 Donor
Qualification
Donor Qualification

u Donor Eligibility
u Safety of the recipient
u Donor history questionnaire, infectious disease testing
u Donor Suitability
u Safety of the donor
u History and physical exam
u Labs
Pre-Donation Evaluation
u History & Physical
u Consent(s)
u Medication review
u Vein assessment
u Labs
u CBC with diff
u CD3
u Electrolytes, including magnesium
u Differences depending on autologous vs allogeneic donation
 HPC
Collections
Hematopoietic Progenitor Cell (HPC)

https://www.anatomynote.com/human-anatomy/cell-and-tissue/blood-cell-differentiation/
Why peripheral HPC collections?

Advantages Indications
u Anesthesia not required u Multiple myeloma
u Less painful for the donor u AML, MDS
u Less blood loss u ALL
u More T cells* u NHL
u HL
u Germ cell tumors
u Multiple sclerosis#
u Gene therapy for
hemoglobinopathies

Fruehauf and Tricot. 2010 Biol Blood Marrow Transplant

Duarte et al. 2019 Bone Marrow Transplant
Mobilization: G-CSF vs Plerixafor

Fruehauf and Tricot. 2010 Biol Blood Marrow Transplant

Mobilization: G-CSF vs Plerixafor

G-CSF Plerixafor
u Standard protocol: daily dose of 5- u Single dose ~ 11 hours prior to
10 µg/kg, 4-5 days prior to collection
collection
u AEs: injection site erythema,
u Often used after chemotherapy nausea, vomiting, flatulence,
diarrhea
u AEs: headache, bony pain, splenic
rupture (RARE) u Can be used alone in sickle cell
disease
u Contraindicated in sickle cell
disease – vaso-occlusive crises,
severe acute chest
syndrome, massive splenomegaly,
death

Fruehauf and Tricot. 2010 Biol Blood Marrow Transplant

HPC Collection - Technical Notes
u Access
u Peripheral (preferred)
u Central
u Dose
u Based on fixed BV or time
u Predicted by pCD34
u Anticoagulation
u Citrate
u Citrate + heparin (LVL)
u Tips
u Quality parameters often
defined by external
sources
HPC Collection Efficiency

CE% = Cell yield in product (cell type desired) ´ product volume

average(pre-donation cell count + post-donation cell count) ´ BVP

CE2% = Cell yield in product (cell type desired) x product volume

Cell pre-count (cell type to be collected) ´ BVP

 Gene Therapy for
Hemoglobinopathies

https://magazine.nm.org/2018/08/16/new-blood-gene-therapy/
Gene Editing Technologies

Adli. Nature Communications. 2018

 Immune
Effector Cell
Collections
Apheresis for Immune Effector Cells (IECs)

u Types
u DLI, Commercial CAR-T, dendritic cell vaccine
u Large numbers of cells required for manufacturing
u Whole blood
u 1-2 million PBMC per ml
u Apheresis more efficient collection of MNCs
How are IEC collections
different from HPC
collections?
u Steady state harvest

u Target cell is smaller*

u Yield vs. purity

Donor Lymphocyte Infusion
Indications
u Mixed chimerism
u Minimal residual disease
u Relapse

https://oncohemakey.com/hematopoietic-cell-transplantation-3/
What is a CAR-T cell?

Majzner and Mackall, Nature Medicine 2019

T Cell Manufacturing

Alderton. Nature Reviews Cancer. 2017

What is a dendritic cell vaccine?

Santos and Butterfield, J Immunology 2018

Provenge
(Sipuleucel-T)
u Well-defined cancer
antigen
u Modification of APCs to
activate T cells
u 3 doses

Di Lorenzo et al. 2011 Nature Reviews Clinical Oncology

Biological Functions of NK Cells
u Specificity for target cells is not
restricted by a single antigen
receptor but, instead, is
determined by a combination of
activating and inhibitory receptors
u Several studies have shown that
the presence of intratumoral NK
cells correlates with slowed tumor
progression and better outcomes.
u Donor NK cell infusion following
transplantation functions to
protect from relapse and delay
recurrence prior to T cell
reconstitution

Vivier et al, Science 2011

Benefits of CAR-NK cells

ALLOGENEIC SOURCE SHORTER WAIT TIME FOR UNMODIFIED NK CELLS

PRODUCT HAVE PROVEN TRACK
RECORD OF SAFETY
MNC Collection – Technical Notes
u Access
u Peripheral (preferred)
u Central
u Dose
u Dependent on protocol
u Some protocols require mid-
CBC
u Anticoagulation
u Citrate
u Tips
u Protocols vary widely
u Confirm collection
parameters
u Define and monitor quality
parameters
 Apheresis
Centers and
Commercial
Manufacturing
In-House vs Commercial Manufacturing

Levine et al, Molecular Therapy: Methods & Clinical Development, 2017

Collecting for Commercial
Manufacturing: Challenges

TIME COMMUNICATION VARIABILITY

Challenges: Time
u Initial contact from clinical u Training
team u Portal
u Feasibility questionnaire
u Collection/processing
u On site visit by sponsor
u Site Initiation
u Review of protocol and u Mock
collection/processing manual
u Collection, processing,
u Qualification visit
shipment
u Respond to assessor’s
u Site opens
observations
u Process change
u Contracts
u Ongoing audits
u Master Agreement, Quality
Agreement
Challenges in Communication

Apheresis and processing facilities are notified after

clinical team has agreed to participate in study

Sponsor and clinical team do not understand the

complexities of collection and processing

Changes in donor requirements, processing

requirements not communicated
Variability - Process
COLLECTION

• Pre-collection labs
• Intra-collection labs
• Labeling

PROCESSING

• Cryopreservation
Variability - Disposition

Ship directly to manufacturer

(minimal to no processing)

Process/cryopreservation,
followed by transport to
manufacturer

Manufacture in-house
Other Challenges

NURSING/TECHNICAL BED SPACE

STAFF
What does this mean for collection
facilities?

NEED FOR APHERESIS WILL COLLECTION FACILITIES INSTITUTIONAL

ONLY GROW MUST DEVELOP PROCESSES COMMITMENT TO CELL
TO PRIORITIZE RESOURCES THERAPY PROGRAMS IS KEY
Summary

Leukocytapheresis is a relatively safe procedure that can be used to

collect MNCs for re-infusion or deplete MNCs.

Each indication for leukocytapheresis has unique challenges –

education is key!

Pre-donor assessment is critical to minimizing adverse events.

Defining and monitoring quality indicators for HPC and MNC

collections is an essential part of any apheresis collection program.
Additional Reference
**shameless plug**
 APHERESIS REVIEW SESSION 2020

DONOR APHERESIS 5
OVERVIEW
Frances Carson

The donor apheresis overview session will concentrate on providing participants

with basic knowledge of what donor apheresis collections entails. We will define the
apheresis technologies available and the products they collect. Identify the benefits
and safety considerations of an apheresis blood donation for patients and donors.
Review donor care techniques specific to apheresis donors. Outline considerations
at mobile drives and review regulations specific to apheresis donor collections. At
the end of this session, participants should have a general understanding of donor
apheresis collections.

www.apheresis.org
 Apheresis,
what’s all the hype about?

Frances Carson
Manager of Donor Centers and Apheresis Services
Carter BloodCare, Dallas-Fort Worth
 Carter BloodCare

*Headquartered in Bedford, TX (Dallas Area)

*Serve more than 200 medical facilities in over 50

counties throughout North, Central, and East Texas.

*Provide more than 300,000 units of blood products to

patients each year.

*25 fixed donor center locations

*Approx. 30 mobile drives daily

 Session Objectives

• What is apheresis all about?

• Current apheresis technologies available
• What does it mean for patients and donors
• Donor care
• Mobile considerations
• Donor apheresis guidelines

3
 Apheresis Processes

Gagan Mathur MD, MBA

4
Convalescent Plasma for Covid19 Patients

Donor/Patient Patient

5
 History Lesson
• First apheresis technology was developed by Herb Cullis in
1972

• Two arm procedure

• One arm was used to draw blood from donor and into machine
• Second arm was used to return blood components from machine to
donor.

• Apheresis machines use the process of centrifugation to

separate whole blood into blood components

6
1. Whole Blood In
2. Plasma
3. Leukocytes
4. Red Blood Cells
5. Chosen product channeled to blood bag

7
Donor Apheresis Collection Technologies

Three major manufacturers

– Haemonetics
– Fresenius Kabi
– Terumo BCT

8
Haemonetics

Double Red
RBC/Plasma

9
 Fresenius-Kabi

Double Reds Plasma Platelets

RBC/Plasma Only Platelet/Plasma
Plasma Only Platelet/RBC

Alyx Aurora Amicus

10
Terumo BCT

Platelets, plasma, RBC’s in any

combination including double
reds

Trima Accel

11
 Apheresis Technology
• Use centrifugal force to separate blood into components
• A disposable kit is loaded on machine for each individual donor
• Collection is fully automated
• Safety features are built in
• Periodic upgrades to enhance productivity, efficiency, patient
safety, donor experience/safety, and/or introduce new technology
• Connectivity to software system
• Downloadable files
• Configurable

12
 Safety Features

• Specific height/weight requirements for specific

procedures

• TBV requirements

• Post platelet count limitations

• Post hct/hgb limitations

• Time restrictions

13
 Positives For Patients

Exposed to Higher consistency of

fewer antibodies volume and content
1 apheresis platelet =
6-8 random platelets

HLA matched units

Leukocyte reduced

Decreased risk of
transfusion reaction
14
 Positives For Donors

Smaller needle Specific blood components =

Less volume loss

Help multiple patients

with one donation
Double red donors
can donate less often
Safety Features Time to relax

Platelet donors can

Lower reaction rate donate more frequently

15
Considerations for Blood Centers

Loss of ancillary Additional products with no

products Housing additional extra supplies
supplies

Can recruit fewer donors

QC requirements

Training and competency

of collection staff

16
 Donor Care

• Keep Donor Warm

• Citrate Reactions

• Interval Checks

17
 Engagement

Engagement is the key to success

18
Perks

19
 Considerations for Mobile Apheresis
• Extra room and portability of equipment
– Apheresis machines
– Cell counter
– Platelet agitator
• Electrical outlets
• Room in transport vehicles
• Time away from work

20
 Apheresis Specific
Guidelines/Regulations
• Frequency
– Platelets = Every 3 days, but no more than 2x in 7 day
period with max of 24x/rolling 12 months
– DR = every 16 weeks, no more than 3x/rolling 12 months
– Plasma (infrequent) = every 28 days

• TRALI mitigation strategies

• Apheresis donor chart review

• Consent 21
• Pre-counts > 150,000

• Manufacturers guidelines
– Height/weight requirements for certain procedures
– Entry limitations

• RBC’s not returned

– 56 day deferral

• Additional collection documentation

22
• Product QC requirements
• Bacterial testing
• Hct/ARCM
• Bag yields
• WBC
• pH

24
• Cell loss calculations
– Cumulative red cell loss
• Max = whole blood donor can give in 12 months
• Donor loses 300mLs or greater within 8 weeks, donor is
deferred for 16 weeks
– Cumulative plasma loss
• Max based on donor weight
< 175lbs = 12.5 liters
> 175lbs = 14.4 liters

25
Apheresis collections bring additional regulations,
testing requirements, costs, etc; but none of that
out ways the life saving products that are made
available to the patients that we serve.

Thank You!

2
 APHERESIS REVIEW SESSION 2020

PAT 7TH EDITION

OVERVIEW
6
Rasheed A. Balogun, MD, FACP, FASN, HP(ASCP)

The Principles of Apheresis Technology is intended to provide the user with a basic
overview of the theory and applications of apheresis. The Principles of Apheresis
Technology is intended to increase the reader’s awareness and understanding
regarding apheresis technologies and applications. This tool with the companion Study
Guide may be used to supplement current or past education and experience in the
field of apheresis and allow the reader to assess their current level of understanding.
These invaluable textbooks, published by ASFA, provide a basic, yet expansive
overview of the theory and applications of apheresis technology and can serve as a
basis for developing training programs for those new to the field of apheresis medicine.
Topics covered include:
• Basic Science
• Apheresis Instrumentation
• Therapeutic Apheresis Procedures
• Clinical Decision Making and the American Society for Apheresis Guidelines
• Vascular Access
• Care of Patients Receiving Therapeutic Apheresis
• Donor Apheresis
• Apheresis for Cellular Therapies
• Apheresis Program Management Essentials
• Quality Management for the Apheresis Manager
• Special Considerations in Pediatric Apheresis
• Ethical Considerations for the Apheresis Practitioner – An Introduction
• Self-Study Answers Appendix
• Mathematics in Apheresis
• Therapeutic Apheresis in Organ Transplantation (NEW)
• Therapeutic Apheresis in Pregnancy (NEW)
Principles of Apheresis Technology, 7th Edition and Apheresis Study Guide: A Companion
to Principles of Apheresis Technology, 7th Edition will be available for pre-order shortly.

www.apheresis.org
Principles of Apheresis Technology 7th Ed.
Overview: New Content, New Format, New Study Guide

Virtual Apheresis Review Session

American Society for Apheresis.
June 9-10, 2020

Rasheed Abiodun Balogun, MBBS(Ib) FACP FASN HP(ASCP) FMCP

Professor of Medicine
Division of Nephrology, University of Virginia
Charlottesville, Virginia USA

Tues Jun 9, 2020 4:00PM Eastern

Disclosures
Relevant Financial Relationships
None

Relevant Non-Financial Relationships

Board Member, American Society for Apheresis 2013-16, 16-19
Senior Editor, Principles of Apheresis Technology 7th Edition 2019-
Member, JCA Special Issue Committee 2012-2019

Slides (some modified from collaborators)

Earnest Ho (ASFA)

Off Label Usage

None
Learning Objectives: Presentation Outline

• At end of the session, audience will be able to:

• Identify “Educational Resources” from ASFA
• Recognize historical patterns of use of PAT7
• Identify the link between the ARV Curriculum,
PAT7 & ASG
• Note the Pedagogical to Androgogical Format of
PAT7 & ASG
• Review sample chapters and questions
Mission: To advance apheresis medicine for
patients, donors and practitioners through
education, evidence-based practice,
research and advocacy.

Vision: To be the leader in apheresis

medicine.
 HISTORY AND FACTS
Founded in 1982
• Society for Hemapheresis Specialists
• American Society for Apheresis
Society of physicians, scientists, and allied
health professionals
• Current membership is approximately
1,000 members
 BECOMING INVOLVED
ASFA Committees
ASFA members are invited to actively participate in the Society by joining a Committee.
Simply send an email to [email protected], stating which Committee you are interested
in taking part in. Send a brief CV as an attachment to your email.

Abstract Committee Education Committee

Allied Health Committee International Affairs Committee

Annual Meeting Organizing Committee Journal of Clinical Apheresis Committee

Apheresis Physicians Committee Nominating Committee

Awards Committee Public Affairs and Advocacy Committee

Bylaws Committee Regional Meeting Organizing Committee

Clinical Applications Committee Research Committee

Communications Committee
 MEMBERSHIP BENEFITS
Electronic or printed subscription to the Journal of Clinical Apheresis
Members will receive six issues of the journal in electronic format.
• Journal Subscription Value: $421
Complimentary Webinars
Participate in presentations given by apheresis experts from the
convenience of your home or office.
• Members Save $525 annually if they participate in 7 webinars per year
Reduced rates for the ASFA Annual Meeting
Be part of the key educational and networking event for physicians,
scientists, and allied health professionals in the field of apheresis. ASFA is
considering of having a virtual conference in 2020.
Reduced Rates for Educational Resources and Materials
Journal of Clinical Apheresis (Special Issue) – Clin. Applications of Apheresis
Principles of Apheresis Technologies Textbook;
Apheresis Standard Operating Procedures Manual
• Members save up to 40% on ASFA publications
 JOURNAL FOR
CLINICAL APHERESIS SUBSCRIPTION
The JCA, the official publication of ASFA, provides the
world's premier source of current information in the field
of apheresis. The Journal presents work in all aspects of
basic and clinical research, practical applications,
emerging technologies and regulation in apheresis and
related fields including hematology, nephrology, neurology,
rheumatology, transplantation, cellular therapies, blood
banking, transfusion medicine and others.

*The 2019 Special Review Issue: Clinical Applications of

Therapeutic Apheresis, An Evidence-Based Approach

Systematic review and evidence-based approach in the Jeffrey L. Winters, MD

Editor-in-Chief
grading and categorization of indications. This Journal of Clinical Apheresis
publication will serve as the key resource for information
on medical conditions treated by therapeutic apheresis.
 APHERESIS STANDARD OPERATING
PROCEDURES MANUAL
The Apheresis Standard Operating Procedures Manual is
intended to provide the reader with a collection of sample
SOPs that can be adapted for their institution’s use. It
contains representative examples of apheresis practice
SOPs from a variety of hospitals and/or blood centers. This
tool may be used to assist in writing and revising SOPs by
institutions that perform, or plan to perform, apheresis
procedures.

This invaluable SOP manual, published by ASFA, provides

sample SOPs for the following areas: general apheresis
practice including management of adverse events, donor
apheresis, therapeutic apheresis, cell therapy apheresis, YanYun Wu, MD, PhD, QIA
research apheresis, and special procedures. Senior Editor
PRINCIPLES OF APHERESIS TECHNOLOGY
ASFA is pleased to announce the impending release of the
Principles of Apheresis Technology - 7th Edition. It
includes major updates and streamlining of practical and
clinically useful content, addition of more chapters and,
for the first time ever, a separate companion volume of
high impact self-study questions, the Apheresis Study
Guide. The main book is a very complete practical review
of Apheresis medicine with nearly 300 pages and this is
reinforced by the Apheresis Study Guide with nearly 170
pages of questions and answers.

Senior Editor:
Rasheed A. Balogun, MD, FACP, FASN, HP(ASCP)

Associate Editors:
Rasheed A. Balogun
Nicole Aqui, MD MD, FACP, FASN, HP(ASCP)
Alicia Garcia, RN HP(ASCP)
Senior Editor
Huy P. Pham, MD, MPH
Antonio S. Torloni, MD
Gay Wehrli, MD, MBA, MSEd
Chisa Yamada, MD
PAT7 : Practical Purpose
In Apheresis Medicine
• provide the reader with a basic overview of the
theory and applications of apheresis technology
• Not intended to be an exhaustive review of
apheresis
• A tool to supplement past education and
experience or to introduce the novice to these
principles.
• Used as a basis for developing training programs
for new practitioners
PAT1 : First Edition. Compiled in 1992 by:

• Christina (Branhan) Anderson, RN, HP(ASCP)

• Vickie (Mullenhagen) King, BHS, RN; and
• Wanda (Vados) Koetz, RN, HP(ASCP).
Edited by
• David Ciavarella, MD; Jeannie Gardner, RN;
Jeanne Hester, MD; Samuel Pepkowitz, MD;
Thomas Price, MD; Ronald Strauss, MD; and
James Smith, MD, PhD.
PAT5 : Fifth Edition. 2014:

• First ISBN numeration (ISBN No.978-0-9936850-

0-2)

• Edited by Walter Linz, MD, MBA; Vishesh

Chhibber, MD; Kendall Crookston, MD, PhD; and
Hans Vrielink, MD, PhD.
PAT6 to PAT7: What’s New? …briefly

• More Content (New Chapters): Bigger, better

• Streamlined Content (removed duplications)

• Evidence based reformating

Pedagogy vs Andragogy
• Apheresis Study Guide
Pedagogy and Andragogy ?
In an Apheresis Meeting?
• The method, and practice, of teaching:
– Pedagogy: Children (Greek children, guide)
– Andragogy: Adults (Adults, guide)

• It encompasses:
Pedagogy Andragogy

• Teaching styles 6 assumptions about adult learners

(1) need to know, (2) self-concept,
• Teaching theory (3) prior experience, (4) readiness to
• Feedback and learn, (5) learning orientation, and
assessment (6) motivation to learn.
Andragogy : Practical
In Apheresis Medicine
• instruction for adults, focus more on the
process and less on the content being taught

• Strategies such as case studies, role playing,

simulations, and self-evaluation are most useful.

• Instructors? facilitator or resource (vs lecturer or

grader)
PAT7 and ASG Were Put Together with
Knowles’ Concepts in Andragogy in Mind
• Interviewed past users of PAT6 (+/-, what to add,
etc)
• Learning Objectives: added to all chapters
• Easy semi-formal writing style
• Visual (Figures, Tables, Pictures etc)
• Apheresis Study Guide (simulates strategies
such as case studies, role playing, simulations,
and self-evaluation)
PAT6 to PAT7: What’s New? So much….1

• Stand-alone volume, Apheresis Study Guide: A

Companion to PAT7.
• Expanded content (2 additional chapters)
• Systematically removed reported duplications
across chapters
• Identified and clearly stated Learning Objectives
(LO)
• Systematically mapping clinical and practical
questions to stated LO
PAT6 to PAT7: What’s New? So much….2

• ASG questions brought up to the 5 possible

answers (one correct and 4 distractors), the
international standard in medical and nursing
education.
• Streamlined authorship to be limited to no more
than two per chapter; and no author contribute
more than one chapter
• PAT7 @ 282 pages; ASG @166 pages ie almost
500 pages of content . For comparison PAT 6
290 pages of content)
QUESTIONS?
 2020 VIRTUAL MEETING
Virtual Apheresis Review Session:
Led by Allied Health Committee: Peggy Reid (Chair), Lindsay
Palomino, RN, BSN, HP (Co-Chair), Jennifer Collins (Co-Chair)
Taking place over two half days on June 9th and 10th 2020,
this educational session provides a review of basic
education in apheresis – including instrumentation, clinical
applications, donor eligibility, regulatory considerations,
donor and patient care, donor and therapeutic access
issues, and more!
Registration will include presentation slides, Certificate of
Attendance, and access to recordings
 APHERESIS REVIEW SESSION 2020

APHERESIS 7
MATH
Jay Raval, MD

In this session, we will review relevant numerical facts and mathematical calculations
that can be utilized for performance and monitoring of therapeutic plasma exchange,
red cell exchange, and apheresis stem cell collections. By the end of the session, the
participant will be able to understand these important principles and perform these
routinely used calculations.

www.apheresis.org
 Mathematics
in Apheresis
Jay S. Raval, MD
Associate Professor
Senior Director, Transfusion Medicine & Therapeutic Pathology
University of New Mexico
 Disclosures
— Consultant/Medical Advisory Board Member for
— Terumo BCT, Inc.
— Sanofi Genzyme, Inc.

— I am a stickler for making sure units are written

down when performing calculations
 Overview
— Total Blood Volumes — Extracorporeal Volume
— Ideal and Adjusted Body — Hemoglobin Hematocrit
Weight
— Removal and Collection
— Red Blood Cell Volume Efficiencies
— Plasma Volume — Cellular Product Yield
— Body Mass Index — Volume Mass
 Total Blood Volumes
— How to determine how much whole blood is
circulating in a person?

— How to determine how many total blood volumes to

process when collecting specific types of cells?
 Multiple Methods
— Nadler’s Formula
— Gilcher Rule of Fives
— Body Mass Index
— General Approximations
— Linderkamp’s Nomogram for Pediatrics
 Nadler’s Formula
— Male:
— TBV (L) = (0.3669 x Ht3) + (0.03219 x Wt) + 0.6041

— Female:
— TBV (L) = (0.3561 x Ht3) + (0.03308 x Wt) + 0.1833

TBV = Total Blood Volume; Ht = Height (m); Wt = Weight (kg)

 Gilcher Rule of Fives

Total Blood Volume (mL/kg of body mass)

Obese Thin Normal Muscular
Male 60 65 70 75
Female 55 60 65 70
Infant/Child ---- ---- 80/70 ----
 Body Mass Index
Calculations

Total Blood Volume (mL/kg of body mass)

BMI <18.5 18.5-24.9 25-29.9 >30
TBV 80 70 65 55

BMI = Body Mass Index; TBV = Total Blood Volume

 General Approximations
Total Blood Volumes (mL/kg)
Preterm baby at birth 100 – 110 mL/kg
Term baby at birth 85 – 105 mL/kg
Children > 3 months 75 – 80 mL/kg
Male adults 70 mL/kg
Female adults 65 mL/kg
Pregnant females (3rd trimester) 80 mL/kg
 Linderkamp’s Nomogram
for Pediatric Patients
— Blood volumes in 160 infants and children between
1 hour and 14 years of age were assessed

— Linear and logarithmic regression equations relating

total blood volume, height, weight, and surface area
were calculated

— Nomograms were constructed

 Example
— 6-year-old male
— Height = 45 inches = 115 cm
— Weight = 45 pounds = 20 kg

Pounds to Kg: divide by 2.2 Inches to Cm = multiply by 2.54

Kg to Pounds: multiply by 2.2 Cm to Inches = divide by 2.54

 Actual, Ideal, and Adjusted
Body Weight Calculations
— Actual = Actual
— Possibility of over-estimation (too big)

— Ideal Body Weight

— Possibility of under-estimation (too little)

— Adjusted Body Weight

— Attempt at most accurate estimation (just right)
 Ideal Body Weight
Calculation
Male (kg) Female (kg)
48 kg for the first 152.4 cm 45 kg for the first 152.4 cm
+ +
1.1 for each additional cm 0.9 kg for each additional cm
106 pounds for the first 5 ft 100 pounds for the first 5 ft
+ +
6 pounds for each additional inch 5 pounds for each additional inch

Pounds to Kg: divide by 2.2 Inches to Cm = multiply by 2.54

Kg to Pounds: multiply by 2.2 Cm to Inches = divide by 2.54

Adjusted Body Weight
Calculations

Adjusted Body Weight =

Ideal Body Weight

0.25 x (Actual Weight – Ideal Body Weight)

Red Blood Cell and Plasma
Volume Calculations

Red Blood Cell Volume =

Total Blood Volume x (% Hematocrit/100)

Plasma Volume =

Total Blood Volume x (1 – % Hematocrit)/100

Body Mass Index Calculation

— BMI = Wt ÷ Ht2

BMI = Body Mass Index (kg/m2); Wt = Weight (kg); Ht = Height (m)

 Extracorporeal Volume
Calculations
— Extracorporeal Volume is comprised of
— Blood taken for laboratory testing
— Volume in the apheresis disposable kit (all tubing)
— Volume removed during apheresis procedure

— % ECV = (ECV ÷ TBV) x 100

— Typically should not exceed 15% without other

modifications, e.g., red blood cell prime
 Converting Between
Hemoglobin and Hematocrit
— Hemoglobin (g/dL) is the amount of the oxygen-carrying
protein within the red blood cells
— Hematocrit (%) is the volume of red blood cells in whole
blood

— Hematocrit = Hemoglobin x 3
— Importantly, the ‘rule of 3’ holds true only when
erythrocytes are normal
— Patients with sickle cell anemia, red blood cell disorders,
or abnormal red blood cell shape or size will not
necessarily have this relationship hold true
 Removal and Collection
Efficiencies
— Mathematical relationships between plasma
volumes processed and removal of substance within
plasma

— Mathematical relationships between cells of interest

in the patient’s blood versus cells of interest in the
collection bag
 1.0
Y/Y0 = e-X
Fraction Remaining (Y/Y0)

0.8

0.6

0.4

0.2

0
0 0.5 1.0 1.5 2.0 2.5 3.0

Plasma Volumes Exchanged (X)

 TPE Kinetics
Plasma Volume Fraction Fraction
Removed Removed (%) Remaining (%)

0.5 40 60
1.0 63 37
1.5 78 22
2.0 86 14
2.5 91 9
3.0 94 6
 Collection Efficiency
— Collection Efficiency is the number of cells
processed by the apheresis instrument that are
actually collected

— Two different calculations are available:

— Having BOTH the pre- and post-procedure counts of
the cells of interest in the donor/patient (CE1)
— Having ONLY the pre-procedure count of the cells of
interest in the donor/patient (CE2)
 Collection Efficiency
Calculations
— Collection Efficiency1 (%) (CE1) =

Product Cell Count

x 100
(CellsPRE + CellsPOST) X (Processed Volume – AC Volume)
2

— Collection Efficiency2 (%) (CE2) =

Product Cell Count

x 100
(CellsPRE) X (Processed Volume – AC Volume)

CellsPRE = Cells of interest in donor/patient prior to collection

CellsPOST = Cells of interest in donor/patient after collection
AC = Anticoagulant
 Examples
— Patient collected 4 x106/kg CD34+ cells
— Weight of recipient = 70 kg
— Total Blood Volume processed = 15.75 L
— Total Anticoagulant Volume used = 0.75 L
— Pre-procedure CD34+ = 30 x106 /L
 Collection Efficiency
Calculations
— CE2 (%) =
Product Cell Count
x 100
(CellsPRE) X (Processed Volume – AC Volume)

4 x 106/kg x 70 kg
x 100
(30 x106/L) x (15.75 L – 0.75 L)

= (280 x 106/450 x 106) ÷ (450 x 106/L) x 100 = 62.2%

 Collection Efficiency
Calculation
— Post-procedure CD34+ =20 x106 /L
— Collection Efficiency1 (%) (CE1) =
Product Cell Count
x 100
(CellsPRE + CellsPOST) X (Processed Volume – AC Volume)

2
280 x106 280 x106
x 100 = x 100
(30 x106 + 20 x106) x (15 L) (25 x106) x 15
2

= (280 x106) ÷ (375 x106) x 100 = 74.7%

 Estimating Cells Collected When
Processing Specific Total Blood Volumes
— If an order for collection only specifies the number
of total blood volumes to process, the number to
total cells of interest collected can be estimated.
— Cells in product =
Cells in person x Total Blood Volumes processed x CE
Example: Process 3x TBV in a donor; use same values
as in CE2 calculation
= (30 x106/L) x (3 x 5L) x (0.622)
= 280 x106 CD34+ cells÷70kg = 4 x106 CD34+cells/kg
Converting Between Volume
and Mass
— When ordering red blood cells for a RCE procedure,
the formulas calculate a volume

— For the blood bank to know that they are giving you
the proper volume, specific gravity is used.

— Specific gravity = ratio of density of a substance

relative to the density of water (g/mL)

— After converting the request for volume to grams of

red blood cells, a scale can be used to weigh the
necessary number of units
 Plasma
1.025-1.029

Platelets
1.040

WBCs
1.050-1.092

RBCs
1.078-1.114

Courtesy Dr. Sergio Torloni

Converting Between Volume
and Mass
— For a RCE, 2,000 mL of red blood cells are required.
How many grams is this?

— Use the specific gravity of packed red blood cells

(1.0971 g/mL) to convert this volume to grams.

— 2,000 mL x 1.0971 g/mL = 2,194 grams

— The blood bank scale is tared with the weight of an
empty blood bag, and then units are weighed and
added together until the requested volume is
obtained.
 Fraction of Cells Remaining
— The fraction of cells remaining (FCR) is an important
parameter in RCE calculations.
— In addition to the patient gender, height, weight, and
starting and ending hematocrit, the FCR is a critical
consideration. It represents the fraction of
remaining cells after a procedure has completed.
— FCR = Target post-RCE Hgb S ÷ pre-RCE Hgb S
— This value should always be less than 1. While FCR
may be simply entered at 30%, more precise
calculations can optimize the RCE procedure.
 Fraction of Cells Remaining
Calculation
— Example: If the target Hgb S = 15%, and the pre-
RCE Hgb S = 30%, what is the FCR?

— FCR = Target post-RCE Hgb S ÷ pre-RCE Hgb S

= 15% ÷ 30% = 0.5
 References
— Neyrinck MM, Vrielink H. “Mathematics in Apheresis.” In Principles of Apheresis
Technology, 6th ed. American Society for Apheresis: Vancouver, BC, Canada. 2017:p
273-282.

— Reyes C, Raval JS. “Mathematics in Apheresis.” In Principles of Apheresis

Technology, 7th ed. American Society for Apheresis: Vancouver, BC, Canada. 2020.

— Neyrinck M, Vrielink H. “Calculations in Apheresis.” Journal of Clinical Apheresis,

2015 (30):28-42.

— Wong ECC, Punzalan RC. “Neonatal and Pediatric Transfusion Practice.” In Technical
Manual, 19th ed. Eds: Fung MK, Eder AF, Spitalnik SL, Westhoff CM. AABB Press:
Bethesda, MD. 2017:p 613-640.

— Linderkamp O, Versmold HT, Riegel KP, Betke K. “Estimation and prediction of blood
volume in infants and children.” European Journal of Pediatrics, 1977 (125):227–
234.

— George TI. “CAP Today Q&A.” August 2010.

http://www.captodayonline.com/Archives/0810/0808_QA.html
 APHERESIS REVIEW SESSION 2020

APHERESIS 8
PROGRAM
MANAGEMENT ESSENTIALS
David Lin, MD

This interactive session will draw upon real-life scenarios to cover a wide range of topics
in Apheresis Program Management Essentials, including quality plan, regulations,
standards, finances, recruitment, retention, training, competency, schedules, surge
volumes, inventory management.

www.apheresis.org
 ASFA 2020 Virtual Meeting
Apheresis Program Management Essentials

David Lin, MD, MHA ‡

Medical & Executive Director of WA Center for Apheresis Therapy
Technical Director of the Cell Processing Laboratory
Bloodworks, Seattle, WA

Email: [email protected]

1 ‡ I have no conflict of interest

 Presentation Summary

This interactive session will draw upon real-life scenarios to cover a

wide range of topics in Apheresis Program Management Essentials,
including quality program, regulations, standards, finances,
recruitment, retention, training, competency, schedules, surge
volumes, and inventory management.

2
 Imagine
1. You have been recruited to start a new apheresis service
2. You provide 24/7/365 service to 1 fixed site and 5 mobile sites
• At the fixed site, you perform MNC apheresis collections for
both clinical and non-clinical use
• At the mobile sites, you perform therapeutic apheresis
3. You have the power to hire whomever you desire
4. Your staff will have 28 weekdays of PTO per calendar year
5. You have the $$$ to buy as many instruments as you please
6. You are able to bill mobile sites for services at fixed rates
7. You are expected to provide a monthly financial analysis
8. You are responsible for the Quality Program, including
compliance with applicable laws, regulations, and standards
9. Furthermore, you are expected to… <fill in the blank>

3
 How would you staff this new service?

4
 One approach to staffing the weekdays
Median Volume Mon Tue Wed Thu Fri
Per Month 18 16 16 12 14
Per Week 4.5 4 4 3 3.5

Median weekday volume = 4.5 + 4 + 4 + 3 + 3.5 = 19 procedures

Assuming an apheresis RN @ 1.0 full time equivalent (i.e. 1.0 FTE = 4 x 10 hour
shifts) can perform 2 procedures per day (or 8 per week)
= (19 ÷ 8) = 2.38 FTEs

Adjust FTEs to account for 28 weekdays of PTO

= {1.0 FTE – [28 weekdays ÷ (5 x 52)]} = 0.89 “effective” FTE

To have capacity to meet the median weekday volume

= 2.38 / 0.89 = 2.67 FTEs (“skeleton staff”)

5
 How would you handle surges in volume?

Consecutive months since 20XX

RBCX Bonus Pay = {Base x [1 + (3 - trained staff) / 3]} x (relative difficulty factor)
= {$100 x [1 + (3 -2)/3]} x (1.05)
= $139.65!

6
 Staff Training, Competency, Retention

7
 Inventory Management

8
 Financial Analysis
Median Volume Mon Tue Wed Thu Fri
Per Month 18 16 16 12 14

Total Labor Expense

= 3.0 FTEs x $40/hour x 2080 Income Budget
hours/year = Labor Expense / (Labor Expense-to-Revenue Ratio)
= $249,600 plus 20% fringe = $299,520 / 0.40
= $299,520 plus “premium” = $748,800

Income per procedure to probably breakeven

= $748,800 / (76 * 12)
= $748,800 / 912
= $821 per procedure

If Net Operating Income (NOI) target is 20%

= $821 x 120%
= $985.20 per procedure

9
 21 CFR §1271.3 (hh) Quality program means an organization's comprehensive system for
manufacturing and tracking HCT/Ps in accordance with this part. A quality program is
designed to prevent, detect, and correct deficiencies that may lead to circumstances that
increase the risk of introduction, transmission, or spread of communicable diseases.

10
 https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?CFRPart=1271

11
12
 21 CFR §1271.3 (kk) Validation means confirmation by examination and provision of
objective evidence that particular requirements can consistently be fulfilled. Validation of
a process, or process validation, means establishing by objective evidence that a process
consistently produces a result or HCT/P meeting its predetermined specifications.

13
 Biomedical Engineering

14
 Understand and Care… Trust

15
 APHERESIS REVIEW SESSION 2020

APHERESIS 9
INSTRUMENTATION
Edwin A. Burgstaler, MT, HP(ASCP)

Instruments are a part of apheresis. Without instruments, apheresis could not be

performed. Early apheresis equipment used centrifuge separators that resembled the
cream separator, but those designs have continually evolved into more sophisticated
separators. Apheresis employs three principles of operation: 1) Draw and separate
the blood, 2) remove the desired component, and 3) return or replace the remaining
components. This is done using centrifugation, filtration, or a combination of
both. Components are separated by size or specific gravity (weight). Apheresis
instruments have common features such as pumps, valves, sensors, separators,
and microprocessors. Cleaning and maintenance is very important in ensuring the
instruments are safe and efficient.
Selective removal therapy allows removal of specific elements in the plasma or blood
and the return of the remaining components by means of filtration or adsorption.
Extracorporeal photopheresis allows the collection of patient cells, photoactivation,
and then return to the patient as treatment. Immunotherapy and bone marrow transplant
are rising as a major form of treatment in the future and apheresis instruments are
essential in collecting the initial cells, as well as provide hematopoietic progenitor cells
for bone marrow transplants. A good team of apheresis instruments and operators
provides a valuable resource in the practice of medicine.

www.apheresis.org
Apheresis Instrumentation

Edwin A. Burgstaler MT, HP(ASCP)

Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic, Rochester, MN

ASFA 2020 Webinar

June 10,2020

©2016 MFMER | slide-1

Conflict of Interest

• No Conflict of Interest

©2016 MFMER | slide-2

Objectives
• Introduction
• Historical events
• Principles of operation
• Types of separation
• Selective removal
• Common features of apheresis equipment
• Maintenance & cleaning
• Safety
• Extracorporeal photopheresis
• Stem cell collections
• Apheresis vs. Hemodialysis ©2016 MFMER | slide-3
 Reference Book

• Principles of Apheresis Technology :Technical

Principles of Apheresis Medicine 7th Edition
• Rasheed Balogun,MD,FCAP, FASN, HP(ASCP):
Senior Editor
• Chapter 2: Apheresis Instrumentation
Edwin A. Burgstaler MT,HP(ASCP)
Amber P. Sanchez, MD
Dobri D. Kiprov MD, HP (ASCP)

Associate Editor: Alicia Garcia, RN, HP(ASCP)

ASFA, 2020
©2016 MFMER | slide-4
©2016 MFMER | slide-5
©2016 MFMER | slide-6
©2016 MFMER | slide-7
©2016 MFMER | slide-8
©2016 MFMER | slide-9
©2016 MFMER | slide-10
©2016 MFMER | slide-11
©2016 MFMER | slide-12
©2016 MFMER | slide-13
Principles of Operation
Three Steps

• Draw and separate the blood

• Remove the target component

• Return or replace the remaining components

©2016 MFMER | slide-14

Types of Separation

• Centrifugation

• Elutriation

• Filtration

• Combination of filtration and centrifugation

©2016 MFMER | slide-15

©2016 MFMER | slide-16
 Specific Gravities

Linz W (ed). Principles of Apheresis Technology, Technical

Principles of Apheresis Medicine, Fifth Edition. ASFA
©2016 MFMER | slide-17
CENTRIFUGATION

©2016 MFMER | slide-18

Centrifuge
Apheresis

Permission of Dr. Dobri Kiprov

©2016 MFMER | slide-19

Sedimenting
Agents

• 6 % Hydroxyethyl
Starch (HES)
• Pentastarch
• Dextran
• Modified Gelatin

Permission of Dr. Dobri Kiprov

©2016 MFMER | slide-20

Centrifugation
Separation by weight (specific gravity)

• Can be used for cells or plasma

• G force defined by RPM and rotor radius
• Dwell time is important
• High viscosity can affect
• RBC size can affect
• Dual stage channels= multiple G forces
• Continuous flow versus intermittent flow

©2016 MFMER | slide-21

©2016 MFMER | slide-22
©2016 MFMER | slide-23
©2016 MFMER | slide-24
©2016 MFMER | slide-25
©2016 MFMER | slide-26
©2016 MFMER | slide-27
©2016 MFMER | slide-28
Component Separation- TPE

Ramp

Outlet
Plasma (low platelets)
Low-G Wall

Ramp
Outlet Inlet
High-G Wall
Packed Red Whole Blood
Blood Cells

Platelets/White Cells G- Force

©2016 MFMER | slide-29

ELUTRIATION

©2016 MFMER | slide-30

Basic Principles of MNC Collection

1. Whole blood enters the

channel
2. Blood separates in the
connector
3. Buffy coat layer is
pumped 4
into the chamber
4. Platelets are returned to 3
the patient and MNC 1
cells are pumped into
the collection bag 2

31 Home | Introduction | Protocol Value | Performance | Comparison | Appendix

©2016 MFMER | slide-31
2. Chamber Fills
Centrifugal force

Separation in the
chamber
• Target cells accumulate in
the chamber
• Platelets are continuously
pumped back to the
patient
Collect pump
flow rate

32 Home | Introduction | Protocol Value | Performance | Comparison | Appendix

©2016 MFMER | slide-32
©2016 MFMER | slide-33
FILTRATION

©2016 MFMER | slide-34

Whole Blood

←Air (Pressure)

←Plasma

←Cells
©2016 MFMER | slide-35
 Membrane
Apheresis

Permission of Dr. Dobri Kiprov

©2016 MFMER | slide-36

FILTRATION & CENTRIFUGATION

©2016 MFMER | slide-37

©2016 MFMER | slide-38
Continuous-Flow vs Intermittent-Flow

Shorter procedure times Single access in required

Lower ECV

Double access required Longer procedure times

Higher ECV
©2016 MFMER | slide-39
SELECTIVE REMOVAL THERAPY

©2016 MFMER | slide-40

Membrane Differential Filtration

Plasma

Whole Blood
Treated Plasma

©2016 MFMER | slide-41

 Blood Cell Adsorption by Adacolumn®

• The Adacolumn is filled cellulose acetate beads that adsorb approx

50% of granulocytes and 40% of monocytes from patient’s blood for
each passage.
• The effects on RBC is minimal.
©2016 MFMER | slide-42
 Adacolumn
Venous
Adacolumn Pressure
Monitor
P
Adacircuit
Adacolumn
Adamonitor
Air sensor

Blood return
Pump

Blood draw
Adastand
Vein

Anticoagulant Port

Vein

Graphics courtesy of Otsuka America Pharmaceutical, Inc

©2016 MFMER | slide-43
Immunosorba PA
Anticoagulation
Buffer PA Eluant PA
Plasma
separation
via
centrifuge

Fraction Waste
bag bag

Graphics courtesy of Fresenius HemoCare

©2016 MFMER | slide-44

Immunosorba PA

• Immunoglobulins adsorbed
with Staph Protein A bound
to Sepharose
• Column regenerated with
sodium citrate 0.13 M
buffer at a pH of 2.2
• Removes:
• 97% IgG1
• 98% IgG2
• 40% IgG3
• 77% IgG4
• 56% IgM
Graphics courtesy of Fresenius HemoCare
• 55% IgA
©2016 MFMER | slide-45
Liposorber® System

©2016 MFMER | slide-46

COMMON FEATURES of
APHERESIS EQUIPMENT

©2016 MFMER | slide-47

PUMPS

©2016 MFMER | slide-48

©2016 MFMER | slide-49
©2016 MFMER | slide-50
©2016 MFMER | slide-51
©2016 MFMER | slide-52
©2016 MFMER | slide-53
VALVES

©2016 MFMER | slide-54

©2016 MFMER | slide-55
©2016 MFMER | slide-56
©2016 MFMER | slide-57
SENSORS

©2016 MFMER | slide-58

©2016 MFMER | slide-59
©2016 MFMER | slide-60
SEPARATORS

©2016 MFMER | slide-61

MICROPROCESSORS

©2016 MFMER | slide-62

MAINTENACE & CLEANING

©2016 MFMER | slide-63

Maintenance

• Follow manufacturer recommendations

• Annual or semiannual PM
• Routine maintenance
• Watch for worn or damaged parts
• Keep the equipment clean

©2016 MFMER | slide-64

 Cleaning

• Very important
• Blood, plasma, albumin, ACD-A,HES = sticky
• Also contaminating agents
• Saline is corrosive
• Follow manufacturer recommendations
• Use appropriate cleaning agents
• Extreme spills may require service personnel

©2016 MFMER | slide-65

SAFETY

©2016 MFMER | slide-66

Safety

• Follow manufacturer operating instructions

• Watch for hemolysis
• Kinked tubing
• Wrong fluids
• Hot centrifuge
• High TMP during filtration
• Prevent large spills- fluids & electricity=bad day
• Keep safety sensors and latches in place
• Prevent loose items near centrifuges
©2016 MFMER | slide-67
EXTRACORPOREAL
PHOTOPHERESIS

©2016 MFMER | slide-68

Therakos CELLEX

©2016 MFMER | slide-69

©2016 MFMER | slide-70
Fenwal Amicus Photopheresis

©2016 MFMER | slide-71

TerumoBCT Spectra Optia

©2016 MFMER | slide-72

PERIPHERAL BLOOD
STEM CELLS (HPC)
& MNC COLLECTIONS

©2016 MFMER | slide-73

Hematopoietic Progenitor Cells

• Autologous
• Allogeneic
• Long procedures
• Mobilized patients/donors
• Difficult to get the specific cells
• Consider extra corporeal volume (ECV)
• Consider citrate toxicity

©2016 MFMER | slide-74

Mononuclear Cell Collections

• Chimeric antigen receptor T cells (CAR T)

• Dendritic cell collections

• Donor lymphocyte infusions (DLI)

• Research collections

©2016 MFMER | slide-75

 Apheresis versus Hemodialysis
Apheresis Hemodiaylsis

Removal Cell or protein pathogens Small to midsized diffusible

molecules

Large molecular mass Spares proteins and cells

Slow rate of formation

Low volume of
distribution
Mechanism Separates by blood Uses semi-permeable
fractions, removes or membranes and concurrent
replaces fractions flow, small molecules and
electrolytes exchanged
Technique Primarily Centrifugation Membrane separation (filter)
separates by density separates by size

Courtesy of Amber Sanchez MD

©2016 MFMER | slide-76
 Apheresis versus Hemodialysis (cont)
Apheresis Hemodiaylsis

Reduce Fluid Very limited Ultrafiltration to restore fluid

balance

Flow Rates 15-165 mL/min, can use 100-500 mL/min, requires

peripheral or IV catheter high flow catheter

Duration Usually short term Usually long term treatment,

treatment, days-months up to years

Anticoagulant Usually citrate or Heparin only

citrate/heparin combined

Courtesy of Amber Sanchez MD

©2016 MFMER | slide-77
©2016 MFMER | slide-78
SUMMARY

• Can’t do apheresis without the instruments

• Need operator and instrument team work to

help the patient/donor

• Remember: the instruments are your friends

©2016 MFMER | slide-79

 APHERESIS REVIEW SESSION 2020

CLINICAL 10
APPLICATIONS:
THERAPEUTIC APHERESIS
Nicole De Simone, MD, MPH

Apheresis is a general term that refers to the removal of whole blood from a donor or
patient, separation into individual components with the removal of a specific component
and the return of the remaining components. This session will review indications for
extracorporeal photopheresis, leukocytapheresis, red cell exchange, and therapeutic
plasma exchange The presentation and pathophysiology of the certain disease
entities, as well as the specifics of procedure used for treatment will be discussed.
Particular emphasis will be placed on how to approach requests for apheresis and
the use of the 2019 American Society for Apheresis Guidelines, including the ASFA
categories and recommendation grades.

www.apheresis.org
Clinical Applications
of Therapeutic
Apheresis
NICOLE DE SIMONE, MD, MPH
 What is Apheresis? 2

A procedure in which blood of a patient or donor is

passed through a medical device which separates one
or more components of blood and returns the remainder
with or without extracorporeal treatment or replacement
of the separated component
Types of Apheresis: Plasmapheresis

Plasmapheresis:
• Therapeutic plasma exchange

• Donor plasma collection

• Selective column adsorption

• LDL apheresis
• Extracorporeal immunoadsorption

https://www.slideshare.net/ektataparia/apheresis
Types of Apheresis: Ctyapheresis

Plateletpheresis
• Platelet Depletion
• Donor platelet collection

Leukapheresis
• WBC depletion
• Stem Cell collection/BM
processing
• Granulocyte collection
• Photopheresis

Erythrocytopheresis
• RBC exchange
• Donor RBC collection

https://www.slideshare.net/ektataparia/apheresis
 6
Category Description

I Disorders for which apheresis is accepted as first-line

therapy, either as a primary stand-alone treatment or in
conjunction with other modes of treatment.

II Disorders for which apheresis is accepted as second- line

therapy, either as a stand-alone treatment or in
conjunction with other modes of treatments.

III Optimum role of apheresis therapy is not established;

decision-making should be individualized.

IV Disorders in which published evidence demonstrates or

suggests apheresis to be ineffective or harmful.
Institutional review board approval is desirable if
apheresis is undertaken in these circumstances.
GRADE
Table 1: Category and Grade Recommendations
for Therapeutic Apheresis
Fact Sheets
Fact Sheets
Fact Sheets
Mechanism of Action of TPE
u Non-selective “bulk” removal
u Pathologic antibodies
u Immune Complexes
u Cryoglobulins
u Toxins
u Lipids

u Premise: physical removal of substance(s) will reverse/stabilize

the disease process

u Often used in conjunction with immunosuppressive medication

to limit further synthesis of pathogenic substance
 TPE Category I: First-line therapy
• Neurologic Disorders: • Solid Organ Transplantation:
• Myasthenia gravis-acute short term treatment • ABO Desensitization prior to kidney/liver
• AIDP/ Guillain Barré syndrome transplantation
• Desensitization prior to kidney
• Chronic Inflammatory Demyelinating transplantation, ABO compatible
Polyradiculoneuropathy (CIDP)
• Antibody Mediated Rejection of Kidney
• NMDA receptor encephalitis
• Paraproteinemic Demyelinating Neuropathies • Others:
(IgA, IgM, IgG) • Vasculitis, ANCA-associated
• Fulminant Wilson’s Disease
• Hematologic Disorders:
• Thrombotic microangiopathy, TTP
• Hyperviscosity in hypergammaglobulinemia
• Catastrophic antiphospholipid syndrome
(CAPS)
TPE Category II: Second-line therapy
u Neurologic Disorders:
u Acute disseminated encephalomyelitis (ADEM)
u Acute MS/NMO exacerbation
u Myasthenia Gravis long-term treatment
u Lambert-Eaton Myasthenic Syndrome
u Steroid responsive encephalopathy associated with autoimmune thyroiditis (Hashimoto’s
encephalopathy)
u Voltage-gated potassium channel (VGKC) antibody related diseases

u Others:
u Major ABO Incompatibility in Stem Cell Transplantation
u Myeloma cast nephropathy
u Systemic Lupus Erythematosus (SLE) severe complications
u Cryoglobulinemia severe/symptomatic
u Thyroid Storm
TPE Category III-Optimum Role of
apheresis is not established. Decision
making should be individualized

HUGE LIST!!!!
TPE Category IV-Ineffective or Harmful

u Dermato-/Polymyositis
u Rheumatoid arthritis
u Gemcitabine associated TMA
u Quinine associated TMA
u Schizophrenia
u Disseminated pustular psoriasis
u Vasculitis-Idiopathic polyarteritis nodosa
Effectiveness of Plasma Exchange
u Effectiveness depends on:
u Volume of exchange
u Distribution of substance to be removed (intra- v extravascular
compartments)
u Rate of equilibrium of the substance between compartments
u Rate of synthesis of substance

u Most antibodies are IgG

u Half-life: 21 days
u 45% intravascular and 55% extravascular
u Post-PLEX re-equilibration 24-72 hours

u IgM is almost entirely intravascular

u Half-life: 7 days
u Less treatments required since there is little re-equilibration between
compartments
Volume exchanged-What’s the
Difference?
• Removal of substance in the
plasma is limited by:
• Distribution in the
intravascular space
• Use of a replacement fluid
which dilutes substance in the
plasma

• Y/Y0=e-x
• Y=final concentration of a
substance
• Y0=initial concentration
• X=number of times the
patient’s plasma volume is
exchanged
• Assumption: no exchange
between intra- and
extravascular compartments
during procedure
Brecher, ME. AABB Technical manual, 14th Ed. Bethesda, MD 2002.
IgG in Intra- and Extravascular
Compartments: Baseline
Intravascular Space Extravascular Space

IgG: 45% is Intravascular and 55% is Extravascular (~50:50)

 IgG in Intra- and Extravascular
Compartments: Immediately After 1 TPE

Intravascular Space Extravascular Space

With one procedure, we remove ~ 63% of IgG from the intravascular compartment
and ~ 32% of total body IgG
IgG Transfer Between Vascular
Compartments: Intra-Procedure
Intravascular Space Extravascular Space

Re-equilibration between the compartments occurs

IgG in Intra- and Extravascular
Compartments: Prior to Next TPE
Intravascular Space Extravascular Space

Re-equilibration has occurred

IgG in Intra- and Extravascular
Compartments: End of Treatment Course

Intravascular Space Extravascular Space

With 5 procedures ~85% reduction in IgG can
frequently be achieved when combined with
immunosuppression

Brecher et al. Plasma Exchange: Why We Do What We DO. JCA 17:2002

Plasma Exchange Frequency and
Length
u We typically perform 1.0-1.5 volumes exchanges daily

u Length of course:
u Most autoimmune diseases are treated with 5-7 procedures
u TTP-daily PLEX until platelet count >150 for two consecutive days
with a taper
u MODS-daily until clinical improvement achieved
TPE: Non-selective Removal

“Bad” “Good”
Other
Anti- Anti- Meds
Proteins
bodies bodies
Plasma Component Losses and
Recovery

Parameter Percent Decrease from Baseline Percent Recovered at 48 hours

Clotting Factors 25-50 80-100
Fibrinogen 63 65
Immunoglobulins 63 ~45
Liver Enzymes 55-60 100
Bilirubin 45 60-100
Platelets 25-30 75-100
McLeod. Apheresis: Principals and Practice
• Other Proteins:
• Antithrombin
• Pseudocholinesterase needed for drug metabolism
• Complement
 Drugs removed by TPE
u ANTIBIOTICS:/ANTIMICROBIALS:
Ø Effect of TPE on majority of u Ceftriaxone
meds is unknown due to u Ceftazidime
limited pharmacokinetic u Gentamycin
studies u Vancomycin
u ANTI-HYPERTENSIVES:
Ø In general, drugs are more u Propanolol
likely to be removed if u Verapamil/ Diltiazem
they have: u CHEMOTHERAPUETUIC DRUGS:
Ø Low Volume of distribution u Cisplatin
Ø High rate of protein binding u Vincristine
u ANTIBODY THERAPIES:
Wood GJ, Hall GM. Plasmapheresis and plasma cholinetserase. Br J Anaesth. 1978;50:945-950 u Basiliximab
Ibrahim RB, Liu C, Cronin SM, et al; Drug Removal by Plasmapheresis: AN evidence-based
review. Pharmacotherapy. 2007;27: 1529-1549. u Rituximab
Kintzel PE, Eastlund T, Calis KA. Extracorporeal removal of antimicrobials during
plasmapheresis. J Clin Apher. 2003;18:194-205. u IVIG
Kale-Pradhan PB, Woo MH: A review of the effects of plasmapheresis on drug clearance.
Pharmacotherapy. 1997;17:684-695.
Replacement Fluids
u Crystalloid (Normal Saline)
u Cheap
u Hypo-oncotic
u Does not contain coagulation factors or immunoglobulins
u 5% albumin
u Most commonly used RF
u Isotonic and mildy hyper-oncotic
u Does not contain coagulation factors or immunoglobulins
u Plasma
u Iso-oncotic
u Contains all coagulation factors
u Used when plasma factor replacement necessary
Replacement Fluids

u S/D treated plasma

u Approved for patients with TTP
u Cryo-poor plasma
u An alternative to plasma for patients with severe allergic reactions
u Hetastarch
u Was used as RF in patients who would refuse blood products
u 2013: black box warning-severe renal injury and coagulopathy
u Now used as a sedimenting agent for granulocyte collections
 Management of Extracorporeal
Volume
u Extracorporeal volume (ECV) is the
volume of blood outside of the patient’s
circulation at any given time during an
apheresis procedure
u ECV of the Spectra Optia is 185 mL
u ECV of blood warmer tubing 40 mL
u If ECV exceeds 10-15% of the TBV, a blood
prime is necessary

u Blood prime may be necessary in patients

with very low hematocrits
u Hct <18% in adults, higher in pediatric
patients
u Allows patient to remain isovolemic at all
times
u Albumin primes may also be performed
Anticoagulant
u ACDA: Acid Citrate Dextrose, formula A
u Anticoagulation effect by Ca2+ chelation
u Not systemic anticoagulation
u Most citrate (80%) is removed with plasma; only 20% reaches patient
u Short half-life of ~5 minutes
u Metabolism is mainly by liver but also by skeletal muscle and kidneys
u Completely eliminated in 30 minutes
u WB:AC Ratio
u Default ratio is 12:1
u Higher ratio means LESS anticoagulation
u Ratio may be adjusted based on platelet count, Hct, liver function
u Heparin may be used as an alternative AC
 Types of Erythrocytapheresis
u RBC Exchange
u Exchange circulating RBC with donor RBCs

u RBC Depletion
u Depletion of circulating RBC without use of
replacement fluid

u RBC Depletion/Exchange
u Combination of both
u Isovolemic Exchange depleting circulating
RBC and replacing with non-cellular fluid
u 5% albumin
u Normal Saline
 RBCx programming requirements
u Patients sex, height, weight are entered into the
apheresis instrument which then calculates the total
blood volume

u Average hematocrit of replacement RBC

u 0% for NS

u Patient hematocrit

u Target post-RBCx hematocrit

u FCR=fraction of cells remaining

u How many original patient RBCs will remain in
circulation
u Default: 30%
 Fraction of cells remaining
u In plasma exchange, a one volume exchange
removes approximately 67% of circulating
proteins
u Similarly, an exchange equivalent to a patient’s
red cell volume will remove 70% of circulating
RBCs and leave behind 30%
u Default: 30%

u In an acute RBCx for sickle cell, the goal is to

acutely lower HbS to <30%
u In patient with no recent transfusion, we assume
HbS to be 100% if there is no current
electrophoresis
u If a patient was recently transfused, we can use
a higher FCR to avoid removing HbA cells
Erythrocytapheresis:
ASFA Categories
u Category I
u Sickle cell disease, acute: Acute stroke
u Sickle cell disease, non-acute: Stroke prophylaxis
u Hereditary hemochromatosis (RBC depletion)
u Polycythemia vera (RBC depletion)

u Category II
u Sickle cell disease, acute: Acute chest syndrome
u Sickle cell disease, non-acute: Recurrent vaso-occlusive pain crisis
u Sickle cell disease, non-acute: Pregnancy
u Babesiosis, severe
Erythrocytapheresis:
ASFA Categories
u Category III
u Sickle cell disease, acute: Other complications
u Sickle cell disease, non-acute: Pre-operative management

u Erythropoietic porphyria, liver disease

u Malaria, severe
u Minor ABO Incompatible Stem Cell Transplantation
u Red Cell Alloimmunization, prevention and treatment after exposure to Rh+
RBCs
u Erythrocytosis, secondary (RBC depletion)
Sickle cell disease

u HbS cells have shortened lifespan (10-20 days) resulting in chronic hemolytic anemia
u HbS polymerizes, upon deoxygenation, causing RBC to become rigid and deformed
Complications of Sickle Cell Disease
Isovolemic hemodilution RBCX
u First phase consists of removing RBCs while replacing with
isovolemic normal saline (~100-300 cc)
u Second phase is standard RBCx

u IHD removes HbS and iron containing cells less iron

accumulation
u IHD decreases RBC utilization: 1-2 units per procedure
u Increased interval between procedures:7-8 weeks with
IHD compared with 4-5 weeks with standard
u Less venipunctures
u Improved quality of living
Babesiosis and Malaria
Photopheresis: background
The ancient Egyptians recognized that
a common weed found along the
banks of the river Nile had medicinal
properties when activated by sunlight
Extracorporeal Photopheresis (ECP)
Overview
u Healthy immune systems maintain a fine balance between effector
cells, which allow us to fight infections, and tolerogenic cells, which
regulate these responses

u Overactive effector immune responses, or insufficient tolerogenic

response to autologous or allogeneic antigens can result in
immune-mediated diseases

u Extracorporeal photopheresis is believed to reinforce the tolerance

arm of the immune system
 Extracorporeal Photopheresis (ECP)
• Extracorporeal photopheresis is a leukapheresis-based
immunomodulatory therapy
u separation of WBC by
apheresis
u addition of 8-MOP to
collected “buffy coat” (WBC
concentrate)
u ultraviolet light A irradiation
u UV-A photoactivates WBC
u Photoactivated WBC
reinfused to patient

u Ensuing in vivo events result

in immunomodulatory effect
Psoralen - mode of action
✧ 8-MOP

✧ Planar structure
8-MOP
✧ Passes freely through
cytoplasmic and
nuclear membrane

✧ 8-MOP intercalates
between DNA strands

✧ When activated by
specific wavelength UV-A
of UV-A light, 8-MOP
cross-links DNA
ECP - indications
u Category I
u CTCL; MF; Sezary syndrome (erythrodermic)

u Category II
u GvHD, skin (acute/chronic)
u Lung allograft rejection (bronchiolitis obliterans syndrome)

u Category III
u GvHD, non-skin (acute/chronic)
u CTCL; MF; Sezary syndrome (non-erythrodermic)
u Crohn’s disease
u Nephrogenic fibrosing sclerosis
u Pemphigus vulgaris (severe)
u Psoriasis
u Scleroderma (progressive systemic sclerosis)
Skin changes in a patient with CTCL after
treatment with ECP

Before After
 Hyperleukocytosis
• AML: WBC > 100x 109/L
• ALL: WBC > 400x 109/L

• Usually associated with large myeloblast

cells-myelomonocytic, monocytic or
promyelocytic types

• Typical Symptoms: of Leukostasis:

• Lung: SOB, hypoxemia, diffuse alveolar
hemorrhage
• CNS: Confusion, somnolence,
headache, focal neurologic deficits
• Eye: Impaired vision, retinal hemorrhages
• Vascular: Myocardial infarction, priapism

• Patients can present in DIC or Tumor Lysis

Syndrome
Leukodepletion-Urgent Treatment!

u 1.5-2.0 blood volume processing

u Watch for fluid balance: Replacement fluid may be needed to
ensure that net fluid balance of ±15% of TBV

u Efficiency of procedure – 30-70% WBC reduction

u Organomegaly = poor response due to pooling of WBC in spleen
u Goal for symptomatic AML: <50-100x 109/L + Resolution of
Symptoms
u Goal for symptomatic ALL: WBC < 400x 109/L + Resolution of
Symptoms
u May need more than one procedure
Questions???
 APHERESIS REVIEW SESSION 2020

QUALITY IN 11
APHERESIS:
STANDARDS, GUIDELINES
AND REGULATIONS
Margaret M. Hannan, BS, MSM/OL, CQA (ASQ)

It is important for apheresis practitioners to have a thorough and accurate understanding

of regulations affecting apheresis programs in order to ensure donor and patient safety.
During this session, the regulatory agencies having oversight of apheresis processes will
be reviewed, in addition to the requirements for informed consent and donor selection
(eligibility) of apheresis donors. Also covered will be a review of registration, licensure, and
accreditation requisites, as well as the requirements for the training and competence for
apheresis personnel.
Alicia Garcia, RN, HP(ASCP)

This brief talk describes regulatory compliance approaches in the cellular therapy and
bone marrow transplant setting and focuses on ways to incorporate quality concepts
into everyday therapeutic and cellular therapy practices with a focus on FACT and AABB
standards.

www.apheresis.org
Quality in Apheresis: Standards, Guidelines and Regulations
Donor Apheresis
Margaret Hannan
[email protected]
 Objectives
• Articulate the regulatory agencies having oversight
of apheresis processes
• Describe standards, guidelines, regulations
regarding apheresis donors
• Explain requirements for facility registration &
licensure (FDA) and accreditation (AABB)
• Discuss operational considerations for apheresis
programs
• Understand the training and competency
requirements for apheresis personnel
 Standards & Regulations
– FDA:
• Code of Federal Regulations (CFR)
• Guidance for Industry
– CLIA: Clinical Laboratory Improvement Amendments
of 1988 (CMS)
• Regulatory standards that apply to clinical lab testing
performed on humans

– State:
• Typically written as public health laws (Code)
 Standards & Regulations
– AABB:
• Standards for Blood Banks and Transfusion
Services
• Quality System Essentials

qOrganization q Deviations, Non-Conformances, and

qResources Adverse Events
qEquipment q Assessments
q Process Improvement Through
qSupplier and Customer Issues
Corrective & Preventive Action
qProcess Control q Facilities & Safety
qDocuments and Records
 Quality 101
The Quality Management System
o Quality Plan – written strategy that defines how quality will be achieved, from
the design of policies and procedures through program oversight, and includes
all components necessary to ensure quality products and services
o Quality & Process Control – testing or activities performed to ensure that
products or processes meet specified standards. process for verifying reliability,
accuracy, and reproducibility in the collection, processing, and storage of blood
products (reactive).
o Quality Assurance – Process-based activities designed to provide confidence
that quality requirements will be met on an ongoing basis (proactive).
o Quality Improvement – Formal approach to the implementation of changes
intended to result in higher quality and more consistent outcomes.

“Say what you do, and do what you say”

 Quality Assurance
• Process-based activities designed to provide confidence that quality requirements
will be met on an ongoing basis
• Proactive & process-based
• CGMP
• Address the qualification (validation), tracking, and documentation of all critical
equipment. Validation includes:
o Installation Qualification (IQ)
o Operational Qualification (OQ)
o Process or Performance Qualification (PQ)
• Processes to monitor
o Errors, deviations, or non-conformances
o Audits & inspection findings
o Staff competency
o Proficiency testing
o Quality control data
o Customer complaints
• Describes the actions or processes taken to monitor for deficiencies
 Quality & Process Control

Purpose: Ensure that work is performed consistently in order to produce a

predefined outcome

q Quality Control
• Product QC testing (platelet yield, residual WBCs, pH)
• Instrument QC testing (controls for analyzers, scale checks)
• Instrument efficiencies – monitor performance for acceptability &
consistency

q Process control
• Process control applies to all departments within an organization, including
departments with ancillary or support functions.
• Management of documents & records
• Contracts & agreements
• Change Control
 Equipment Maintenance
• The quality plan should include a process for identifying all
critical equipment and assigning each piece a unique identifier
• Performance checks
o Calibration and preventive maintenance
o Routine maintenance & service, repairs
• Validation
o Equipment
o Product – collection devices
o Record keeping
 Safety
• COVID impact: physical distancing & cleaning procedures
• Electrical
• Ambient temperature
• Equipment
• Adverse reactions
• Kit integrity
• Donation criteria (protects donor and patient)
• Fire & evacuation
• Biohazard & chemical
• Blood products
 Infection Control
• Skin prep / scrub
o Solutions
o Aseptic technique
• Phlebotomy
• Aseptic technique
• Palpation
• Diversion pouch
• Manufacturing process
o Sampling
o Dividing products
• Kit integrity
• Bacterial detection – platelets
• Monitor for adverse transfusion events (sepsis, possible bacterial contamination)
 Informed Consent
• AABB (applies to all donations – not specific
just to apheresis) Std 5.2.3
– Obtain day of donation
– Explain in understandable terms
– Include risks of the procedure, tests performed to
reduce TTDs, requirements for reporting test
results
– Must have opportunity to have questions
answered and refuse consent
– Follow applicable laws for consent of minors and
legally incompetent adults
 Informed Consent
• FDA 21 CFR 640.21
– Obtain on the first day of donation and at
subsequent intervals no longer than 1 year
– Risks and hazards of the procedure must be
explained
– Use lay terms to ensure donor understanding
– Consent process must include:
• Donor may give consent
• Has a clear opportunity to refuse procedure or withdraw
at any time
– Must be approved by FDA (language and process)
 Confidentiality
• AABB
– 5.3.1 – policy to ensure that the donor
qualification process is private and
confidential
• Visual and auditory privacy – white noise, screens,
distance between screening booths
– 6.2.2 System to ensure unauthorized access
and ensure confidentiality of records is
established and followed
 Confidentiality – FDA
• 630.6(c) protect donor confidentiality regarding
deferral
• 606.40(a)(1)
–Provide an appropriate environment for completion of donor
questionnaire in a private setting
–Ensure that the donor is answering the questions in a confidential
setting
 Donor Selection
• Donors not meeting allogeneic criteria can only undergo
apheresis when particular value to intended recipient and
with approval by medical director
• Plasmapheresis
– Infrequent – no more often than every 4 weeks
– Frequent plasmapheresis program – specific FDA
requirements for donor testing and evaluation by physical
exam (includes total protein testing)
– Donor weight at each donation
– Plasma collected concurrently with a platelet stored in
platelet additive solution (PAS) – plasma loss will not impact
determination of plasmapheresis frequency (requires FDA
variance (5.5.2.))
 Donor Selection
• Plateletpheresis
– At least 2 days apart and no more than twice in 7 days
– Double or triple products – only once in 7 days
– No triple product on 1st time donor without pre-platelet count
– No more than 24 times in 12 months (rolling)
– RBC losses cannot exceed max permitted for WB collections
– A blood sample shall be collected before each procedure for the
determination of the donor’s platelet count. If the result is
available, it shall be used as the platelet count to qualify the
donor.
– Platelet count minimum 150,000/µL. No max but many centers set
high limit ~500,000-600,000
– No platelet inhibitory drugs: ASA, Piroxicam – 2 days, Plavix - 14
– Donor weight at each donation if collecting concurrent plasma
 Donor Selection
• Double Red Cell Apheresis
– Must meet specific hemoglobin/hematocrit and weight
requirements for the device cleared by the FDA
– Deferred from all donations for 16 weeks following double RBC
– The volume of red cells removed not to cause predicted post
hematocrit of <30% or a hemoglobin <10 g/dL

• Multiple Concurrent Apheresis Collection

– Interval between donations shall meet FDA criteria
– Combined volume limits of red cells and plasma removed shall
follow criteria for the FDA-cleared device used.
 FDA Registration
• Who must register?
– Section 510 of the Federal Food, Drug, and Cosmetic Act:
• Within 5 days of manufacture, preparation, or processing of a
drug or drugs (includes biologics)
• Annually between November 15 and December 31.
• Every June and December – update blood product listings
• Unless exempt under 21 CFR 607.65
– Licensed to prescribe or administer drugs and manufacture
blood products solely for use in their practice
– Those who manufacture blood products solely for use in
research, teaching, or analysis
– Transfusion services which are a part of a facility that is certified
under the Clinical Laboratory Improvement Amendments of 1988
 Product Licensure
• Licensure
– Facilities that manufacture / distribute products must be licensed to ship
products out of state (interstate commerce)
• Facilities can distribute products within the state as unlicensed
products
– Does not apply for facilities that collect product solely for internal use
– Product licensure
• Submit SOPs, validation data, QC data, etc. for review
• May include a site inspection
• Timeframe ~12-18 months
 Changes to FDA Registration
• Prior Approval Supplement (PAS) [aka licensure]
– Significant changes that will impact donor or product safety – approval takes months or
more than a year
• New manufacturing process or a change in a procedure that is less restrictive
than a previously approved process

• Changes Being Effected (CBE or CBE-30)

– Moderate changes that may have moderate impact on donor or product safety – can
begin immediate (CBE) or after 30 days (CBE30) if no word from FDA
• Automation of a process

• Alternate Procedure (Variance)

– Request approval for not following a specific regulation – approval can take 6-12 mos

• Annual Report
– Notification of minor changes made throughout the year
• Addition or closure of a new collection site, minor process changes, changes
more restrictive than a previously approved process
 Training and Competency - AABB
• Employ adequate number of staff qualified by education, training,
and/or experience.
• Maintain job descriptions that define appropriate qualifications for
position.
• Those performing critical tasks shall be qualified to perform
assigned activities on the basis of appropriate education, training,
and/or experience.
• Process for identifying training needs and shall provide training for
personnel performing critical tasks.
• Perform competency assessment before independent performance
of activities and at specified intervals. Taken action when fail to
demonstrate competence
 State Regulatory Agencies
qClinical or Medical Lab Permit
qLaboratory License
qBlood Bank License
qTissue Bank Permit
• Requirements differ from state to state
• May need multiple if services provided to
surrounding states
 AABB Accreditation
• Voluntary
• Peer review
• Accreditation Types
o Donor Activity o Cell Therapy Clinical Program
Activity
o Transfusion Activity
o Out of Hospital Transfusion
o Transfusion Apheresis Activity
o CLIA Accreditation o HPC Activity
o Somatic Cell Activity
 Regulatory Inspections
FDA State Accreditation CLIA

Unannounced Unannounced Announced Announced

“CLIA Provider”

Biennial Annual Biennial Biennial

Local FDA or State Peer Review Peer Review
CBER
Observations – Deficiencies – Findings - Findings -
FDA 483 survey report assessment assessment
report report
Establishment Closure letter Accreditation Certificate
Inspection Certificate
Report [EIR]
 Training and Competency - FDA
AABB Standard 211.25 Personnel qualifications

• Training in cGMPs shall be conducted by qualified

individuals on a continuing basis and with sufficient
frequency to assure that employees remain familiar with
CGMP requirements
• Those supervising the manufacture, processing,
packing, product shall have the education, training, to
assure the product has the safety, identity, strength,
quality, and purity that it is represented to possess.
• There shall be an adequate number of qualified
personnel to perform and supervise the manufacture,
processing, packing of each product.
 Training and Competency – FDA
21 CFR PART 820 -- QUALITY SYSTEM REGULATION
• Must have sufficient personnel with the necessary education,
background, training, and experience to assure that all
activities are correctly performed.

• Establish procedures for identifying training needs and ensure

that all personnel are trained to adequately perform their
assigned responsibilities. Training shall be documented.

• As part of their training, personnel shall be made aware of

device defects which may occur from the improper
performance of their specific jobs.

• Personnel who perform verification and validation activities

shall be made aware of defects and errors that may be
encountered as part of their job functions.
 Resources
• AABB (2018). Standards for Blood Banks and Transfusion Services (31st ed.).
Bethesda, MD: AABB Publications.
• ASCP (2018). Qualification in Apheresis (QIA) Examination Topic Outline.
https://www.ascp.org/content/docs/default-source/boc-pdfs/boc-us-
guidelines/qia_topic_outline.pdf?sfvrsn=8
• Code of Federal Regulations Title 21: Food and Drugs Parts 210, 211, 600, 601, 606,
607, 610, 640, 1271.
• Center for Biologics Evaluation and Research. (2007). Guidance for Industry and
FDA Review Staff: Collection of Platelets by Automated Methods: Food and Drug
Administration.
• Center for Biologics Evaluation and Research. (2001). Guidance for Industry:
Recommendations for Collecting Red Blood Cells by Automated Apheresis
Methods. (Technical Correction). Rockville, MD: FDA.
• Center for Biologics Evaluation and Research (March 10, 1995). Revision of FDA
Memorandum of August 27, 1982: Requirements for Infrequent Plasmapheresis
Donors. Rockville, MD: FDA.
• Linz, W. et al. (2017) Principles of Apheresis Technology (6th ed.). Vancouver,
British Columbia: ASFA
• McLeod, B.C. et al. (Eds.). (2010). Apheresis: Principles and Practice (3rd ed.).
Bethesda, MD: AABB Press.Wu, Y. et al. (2018)
• Apheresis Standard Operating Procedures Manual 1st ed. (2018). Vancouver,
British Columbia: ASFA
 Blood Center Enterprises
innovation • experience • expertise
Regulatory Considerations:
Cellular Therapy Collections
Objectives
— Define Cellular therapy
— List the regulatory and accreditation
agencies that govern cellular therapy
activities
— Outline standards for BMT and Cellular
therapy collection centers
— Demystify regulatory considerations:
provide concrete examples of how we
practice quality management in day to day
practice
Quality Management
— Standards can seem
abstract and
overwhelming
— Describe measures
that we all do as part
of our due diligence
in caring for patients
and donors
Cellular therapy
— Stem Cell Transplant-Generally, the infusion of
pluripotent stem cells with the intent of restoring
normal hematopoiesis after myeloablative therapy.

— Gene Therapy -The aim of genome editing is

disrupt a disease causing mutation or correct
faulty genes at the chromosomal DNA.1

— Immune Effector Cell Therapy- A cell that has

differentiated into a form capable of modulating
or effecting a specific immune response.2
Differ from standard blood
donations
— Much more recipient specific
— Life saving or curative therapy
— Donors are generally autologous
(self), a first or second degree
relative, or chosen from a registered
pool of donors
— The specific product collected can
represent a lifeline for the recipient
Collections involve 2 important
patients:
The Donor The Product
Regulations governing Cell Therapy
collections
— FDA (21CFR1271)
— Foundation for the Accreditation of
Cellular Therapy (FACT)
— American Association of Blood Banks
(AABB)
— ICCBBA (labeling)
— cGMP, JCAH
Standards Overview
• AABB Standards for Cellular Therapy Services 8th Ed
(July 2017)
• FACT-JACIE International Standards for
Hematopoietic Cellular Therapy 7th Ed (March 2018)
• FACT Immune Effector Cell Standards 1st ed
• FDA Title 21 CFR1271
Organizational Structure
Staff who provide oversight for collection
activities must
— Be qualified by specific experience and
training
— Have well defined roles and
responsibilities
— Have ongoing education in the area of
cellular therapy collection
— Work within a predefined reporting
structure
Facilities
Sites must have processes for:
— Performing and documenting* cleaning
and sanitation practices
— Maintaining donor comfort, safety and
privacy
◦ Space for evaluation, availability of emergency
services and blood products, air quality, etc
— Staff safety
Equipment & Supplies
— Storage: specific conditions such as
temperature and humidity must be
maintained
— Critical equipment must have an initial
validation, ongoing calibration, regular
cleaning and maintenance
— There must be processes to confirm that
all supplies are suitable prior to use.
Document Control
— Written guidelines that govern SOP
management
— A mechanism of version control
— Policies and procedures that ensure
patient and donor records are maintained
in a private, orderly, retrievable fashion
Donor Management
— Suitability: refers to measures required to
protect the health of the donor
— Eligibility: refers to measures required to
ensure that the donor does not pose a
risk to the recipient
◦ Infectious Disease Risk assessment
— Privacy, Informed consent, protection
◦ Donor advocate, unbiased evaluation
— Care during and after collection and
mobilization
Product Purity & Potency
— Outcome parameters must be established
and evaluated
◦ Viability, Sterility, Engraftment data
— Specific interventions for products that
do not meet those parameters
◦ Investigation
◦ Reporting to regulatory agencies and
recipient’s care team
◦ CAPA (Corrective Action Preventative
Action) must be identified
Product Traceability & Trackability
— Specific standards for labeling (ICCBA
standards or ISBT labeling required)
◦ Standard format and terminology
— Facilities must validate that product
management practices result in the ability
to trace the product from donor
collection, through processing and
storage, to infusion in the correct recipient
Quality Management
— Formalizes and standardizes all regulated
activities
— Establishes standards for documentation
of all activities
— Evaluates donor, patient, and product
outcomes
— Investigates errors and deviations
— Implements and validates process changes
Quality Management Committee
— Must consist of qualified members who
participate in all aspects of cellular
therapy: Collection, Processing, Infusion
— Must meet quarterly at minimum
— Must review donor and product
outcomes, adverse events, problems
References
— FDA Title 21 CFR 1271
— AABB Standards for Cellular Therapy 8th ed, July
2017.
— FACT-JACIE International Standards for
Hematopoietic Cellular Therapy Product
Collection, Processing, and Administration,
March 2018.