2009-2010

Historical Perspective

Overview of Blood Group

Genetics

Review of Immunology

Overview of
Immunohematology
 Historical Perspective

Overview of Blood Group

Genetics

Review of Immunology

Overview of
Immunohematology
• 1492 Pope
• Problems:
Innocent VII
– Clotting
– Incompatibility
– Methods & devices
– Availability &
preservation
– Disease transmission
– Other TR
– Circulatory overload
• 1628 English • 1665 The first
physician William recorded
Harvey discovers successful blood
the circulation of transfusion occurs
blood. Shortly in England:
afterward, the Physician Richard
earliest known Lower keeps dogs
blood transfusion is alive by transfusion
attempted. of blood from other
dogs.
• 1667 Jean-Baptiste
Denis in France and • 1795 In
Richard Lower in
England separately
Philadelphia,
report successful American physician
transfusions from Philip Syng Physick,
lambs to humans. performs the first
Within 10 yrs,
transfusing the blood of human blood
animals to humans transfusion,
becomes prohibited by although he does
law (due to reactions).
not publish this
information.
• 1818 James Blundell, a • 1840 At St. George's
British obstetrician
– first documented successful School in London,
transfusion of human blood to Samuel Armstrong
a patient
– treatment of postpartum Lane, aided by
hemorrhage
– Husband as donor (4 oz)
consultant Dr.
– Between 1825 and 1830, he Blundell, performs the
performs 5/10 beneficial
transfusions first successful whole
– Devised various instruments blood transfusion to
for transfusions and rational
indications. treat hemophilia.
Tzanck BT Set
Tzanck BT Set
Oehlecker BT
Set
Juengling BT
Set
• 1867 English • 1869 sodium
surgeon Joseph phosphate by
Lister uses Braxton Hicks
antiseptics to • 1873-1880 US
control infection physicians
during transfuse milk
transfusions. (from cows, goats,
and humans).
• 1884 Saline infusion • 1900 Karl Landsteiner,
replaces milk as a an Austrian physician,
“blood substitute” due discovers the first three
to the increased human blood groups, A,
B, and C. Blood type C
frequency of adverse
was later changed to O.
reactions to milk. His colleagues Alfred
– George Hayem (saline) Decastello and Adriano
Sturli add AB, the fourth
type, in 1902.
• 1907 Hektoen • Ottenberg also
suggests that the observed the
safety of transfusion mendelian
might be improved inheritance of
by crossmatching.
blood groups and
Reuben Ottenberg
performs the first
recognized the
blood transfusion “universal” utility
using blood typing of group O donors
and crossmatching in
New York.
• 1908 French surgeon • The procedure proves
Alexis Carrel devises a unfeasible for blood
way to prevent clotting transfusions, but paves
by sewing the vein of the way for successful
the recipient directly to organ transplantation,
the artery of the donor. for which Carrel
This vein-to-vein or receives the Nobel
direct method, known Prize in 1912.
as anastomosis, is
• Before him, multiple
practiced by a number
syringes – Edward
of physicians.
Lindemann
• 1908 Moreschi • 1912 Roger Lee, a
describes the AHG
reaction (a direct way of
visualizing an Ag-Ab
reaction that has taken
place but is not directly
visible). The Ag-Ab react
with each other, then,
after washing to remove
any unbound antibody,
the AHG reagent is
added and binds
between the Ab that are
stuck onto the Ag.
visiting physician at the
Massachusetts General
Hospital, along with Paul
Dudley White, develops
the Lee-White clotting
time. Lee’s studies lead
to the terms "universal
donor" and "universal
recipient".
• 1914 Long-term • 1915 At Mt. Sinai Hospital
in NY, Richard Lewisohn
anticoagulants, uses Na citrate as an
anticoagulant (progress
among them from direct to indirect
transfusion). Richard Weil
sodium citrate demonstrates the
feasibility of refrigerated
(Hustin), are storage of such
developed, anticoagulated blood. It
took 10 yrs for sodium
allowing longer citrate use to be accepted.
preservation of
blood.
• 1916 Francis Rous and
J.R.Turner introduce a
citrate-glu sol’n (storage
of blood for several days).
This discovery also allows
for the establishment of
the first blood depot by
the British during World
War I. Oswald Robertson,
an American Army officer,
is credited with creating
the blood depots.
• 1927-1947 The
MNSs and P systems
are discovered. MNSs
and P are two more
blood group antigen
systems.
• 1930’s – RBC
membrane was better
understood
(metabolism,
deformability &
permeability)
• 1932 The first • 1937 Bernard Fantus,
director of therapeutics at
hospital-based the Cook County Hospital
blood depot is in Chicago, establishes
established in a the first hospital blood
bank in the US. In
Leningrad hospital. creating a hospital
laboratory that can
preserve and store donor
blood, Fantus originates
the term "blood bank."
 • 1940 Edwin Cohn, a
• 1939/40 The Rh blood professor of biological
group system is chemistry at Harvard
Medical School, develops
discovered by Karl cold ethanol fractionation,
Landsteiner, Alex the process of breaking
down plasma into
Wiener, Philip Levine, components and products.
and R.E. Stetson and is Albumin, a protein with
powerful osmotic
soon recognized as the properties, plus gamma
cause of the majority of globulin and fibrinogen are
isolated and become
transfusion reactions. available for clinical use.
John Elliott develops the
first blood container
(vacuum bottle).
 Ebert-
Emerson BT
Set
• 1940 The US gov’t • The American Red
establishes a nationwide
program for the collection
Cross participates,
of blood. Charles R. Drew collecting 13
develops the “Plasma for million units of
Britain” program — a pilot
project to collect blood for
blood by the end of
shipment to the British World War II.
Isles.
• 1941 Isodor Ravdin, a
prominent surgeon from
Philadelphia, effectively
treats victims of the Pearl
Harbor attack with Cohn's
albumin for shock. Injected
into the blood stream,
albumin absorbs liquid from
surrounding tissues,
preventing BV from
collapsing, a finding
associated with shock.
• 1943 The introduction by
J.F. Loutit and Patrick L.
Mollison of acid citrate
dextrose (ACD), reduces the
volume of anticoagulant,
permits transfusions of
greater volumes of blood
and permits longer term
storage (63 ml, ratio 1.4:10,
21 days).
• 1945 Coombs, • 1947 The American
Mourant, and Race Association of Blood
Banks (AABB) is formed
describe the use of to promote common
antihuman globulin goals among blood
(later known as the banking practitioners
“Coombs Test”) to and the blood donating
identify public.
– Journal of Clinical
“incomplete” Investigation
antibodies.
• 1949-1950 The US • 1950 Audrey
blood collection Smith reports the
system includes use of glycerol
1,500 hospital blood cryoprotectant for
banks, 46 freezing red blood
community blood cells.
centers, and 31
American Red Cross
regional blood
centers.
• 1950 Carl Walter and • 1953 The AABB
W.P. Murphy, Jr.,
introduce the plastic Clearinghouse is
bag for blood collection established, providing
(safe and easy a centralized system
preparation of multiple
blood components from for exchanging blood
a single unit of whole among blood banks.
blood) Today, the
• Development of the Clearinghouse is
refrigerated centrifuge
in 1953 further called the National
expedites blood Blood Exchange.
component therapy.)
SINGLE BAG : Designed for
DOUBLE BAG : Separation
collection,
of whole
storage and transfusion of
blood into red cell and
whole
plasma.
blood.

TRIPLE BAG :
QUADRUPLE BAG : Separation
Separation into red
into
cells, platelet
red cells, platelet concentrate,
concentrate and
cryoprecipitate and plasma
plasma.
TRANSFER BAG : Designed for
subdivision of whole blood and
separation.

TRANSFUSION SET: Designed for

safe and effective transfusion
• Mid-1950s In • 1957 The AABB
response to the forms its committee
heightened demand on Inspection and
created by open- Accreditation to
heart surgery and monitor the
implementation of
advances in trauma
standards for blood
care patients, blood
banking.
use enters its most
– CPD was introduced by
explosive growth Gibson
period.
• 1958 The AABB • 1959 Max Perutz of
publishes its first Cambridge University
edition of Standards deciphers the
for a Blood molecular structure of
hemoglobin, the
Transfusion Service
molecule that
(now titled
transports oxygen
Standards for Blood and gives red blood
Banks and cells their color.
Transfusion
Services).
• 1960 The AABB begins • 1961 The role of
publication of
TRANSFUSION, the first platelet
American journal wholly concentrates in
devoted to the science of
blood banking and
reducing mortality
transfusion technology. In from hemorrhage
this same year, A. Solomon in cancer patients
and J.L. Fahey report the
first therapeutic is recognized.
plasmapheresis procedure
• 1962 The first
antihemophilic
factor (AHF)
concentrate to
treat coagulation • 1962 In the US, there were
disorders in 4,400 hospital blood banks,
123 community blood centers
hemophilia and 55 American Red Cross
blood centers, collecting a
patients is total of five to six million units
developed through of blood/yr

fractionation.
• 1964 • 1965 Judith G. Pool
Plasmapheresis is and Angela E.
introduced as a Shannon report a
means of collecting method for
plasma for producing
fractionation. Cryoprecipitated
AHF for treatment
of hemophilia.
• 1967 Rh immune • 1969 S. Murphy
globulin is and F. Gardner
commercially demonstrate the
introduced to feasibility of
prevent Rh disease storing Platelets at
in the newborns of room temperature,
Rh-negative revolutionizing
women. platelet transfusion
therapy.
• 1970 Blood banks • 1971 Hepatitis B
move toward an surface antigen
all-volunteer blood (HBsAg) testing of
donor system. donated blood
begins.
• 1972 Apheresis is • 1979 A new
used to extract one anticoagulant
cellular preservative,
component, CPDA-1, extends
returning the rest the shelf life of
of the blood to the whole blood and
donor. red blood cells to
35 days.
• Early 1980s With the • Blood Banking –
growth of component procedures involved in
therapy, products for collecting, storing, and
coagulation disorders, processing blood and the
and plasma exchange distribution of RBCs and
blood components
for the treatment of
autoimmune disorders, • Transfusion medicine –
hospital and community medical practice and
techniques associated
blood banks enter the with replacement of RBCs
era of transfusion and blood components
medicine (doctors
trained specifically in
blood transfusion
actively participate in
patient care).
• Blood Banking – procedures • Immunohematolog
involved in collecting,
storing, and processing y – academic
blood and the distribution of
RBCs and blood components knowledge and
• Transfusion medicine – procedures
medical practice and
techniques associated with involving the study
replacement of RBCs and of the immunologic
blood components
responses to blood
components
• 1981 First • 1983 Additive
Acquired Immune solutions extend
Deficiency the shelf life of red
Syndrome (AIDS) blood cells to 42
case reported. days.
• 1984 Human
Immunodeficiency Virus
(HIV) identified as cause of
AIDS
• 1985 The first blood-
screening test to detect HIV
is licensed and quickly
implemented by blood banks
to protect the blood supply.
• 1989 Human-T-
• 1987 Two tests that
screen for indirect
evidence of hepatitis
are developed and
implemented, hepatitis
B core antibody (anti-
HBc) and the alanine
aminotransferase test
(ALT).
Lymphotropic-Virus-I-
antibody (anti-HTLV-I)
testing of donated
blood begins.
• 1990 Introduction of • 1996 HIV p24 antigen
testing of donated blood
first specific test for begins. Although the test
hepatitis C, the major does not completely close
the HIV window, it shortens
cause of “non-A, non- the window period.
B” hepatitis. • 1997 U.S. Gov’t issues two
reports suggesting ways to
• 1992 Testing of donor improve blood safety,
including regulatory reform.
blood for HIV-1 and National Blood Data
HIV-2 antibodies (anti- Resource Center founded
by AABB to collect, analyze
HIV-1 and anti-HIV-2) is and distribute data on all
implemented. aspects of blood banking
and transfusion medicine.
• 1998 HCV lookback • 1999 Blood community begins
implementation of Nucleic Acid
campaign — a public Amplification Testing (NAT) under the
health effort to alert FDA’s Investigational New Drug (IND)
application process. NAT employs a
anyone who may have testing technology that directly detects
been exposed to the the genetic materials of viruses like HCV
and HIV.
hepatitis C virus (HCV)
through blood
transfusions before July
1992 so they can
receive medical
counseling and
treatment if needed.
• 2002 West Nile • 2003 First-ever National
Blood Foundation forum
virus identified as unites leaders in blood
banking and transfusion
transfusion medicine
transmissible. • 2003 FDA issues final
guidance regarding
• 2002 Nucleic acid “Revised
amplification test Recommendations for
the Assessment of Donor
(NAT) for HIV and Suitability and Blood and
HCV was licensed Blood Product Safety in
Cases of Known or
by the Food and Suspected West Nile
Drug Virus Infection.”  
Administration.
 Window Period
HBV : 59 days
HCV : 82 days
HIV-1 : 21 days

Immune reaction

Serological positive

Infection
Time
pbcc2008eyan,
 Window Period
HBV : 34 days HBV : 59 days
HCV : 23 days HCV : 82 days
HIV-1 : 11 days HIV-1 : 21 days

NAT positive

Immune reaction

Serological positive

Virus
Infection
Earlier detection
Time
pbcc2008eyan,
• 2003 First West Nile • 2004 AABB
Virus-positive unit of receives $2.4
blood intercepted. Million CDC grant
• 2003 Guidance on to reduce
Implementation of transfusion-
New Bacteria
transmitted HIV in
Reduction and
Detection Standard Africa and South
issued. America.
• 2005 FDA clears apheresis
platelets collected with
certain systems for routine
storage and patient
transfusion up to 7 days
when tested with a
microbial detection system
release test. FDA’s Center
for Biologics Evaluation and
Research publishes
compliance program
guidance for inspection of
human cells, tissues, and
cellular and tissue-based
products (HCT/Ps).
•  2005 AABB founding
member Tibor
Greenwalt dies. 
• 2005 FDA approves
the first West Nile
virus (WNV) blood test
to screen donors of
blood, organs, cells
and tissues.
• New trends: – Formation of type O
– Anticoagulant RBCs
preservative – Hgb-based oxygen
solutions carriers
– Additive solutions – Perfluorochemicals
– Freezing and – Platelet
rejuvenation preservation
– Reduce/inactivate
pathogens
– RBC substitutes
• Basis of inheritance
of traits
• Overview
• Mendelian Laws: • Patterns of
– Law of Segregation inheritance:
– Independent and – Autosomal
Dependent – Sex-linked
Assortment – Recessive
– Dominant
– Co-dominant
– Amorph
• Antigen
– any substance – In the practice of
either protein or blood transfusion,
non-protein, which red cell antigens are
if introduced into an of major clinical
individual causes importance, besides
the production of an these, platelets,
antibody that will leucocytes and
plasma proteins also
react specifically
exhibit strong
with that antigen in
antigenic systems.
an observable way.
• Antibody
– are serum proteins, more
specifically
immunoglobulins in
nature.
– are recognized by their
interaction with antigen.
– usually a product of the
immune response.
– Production of specific
antibodies
– plays a significant role in
red cell serology
– In blood group serology,
the interaction of Ag-Ab is
mostly detected by
agglutination of red cells.
– On electrophoresis, plasma
proteins separate into five
main fractions, i.e
albumins, alpha-globulin,
beta-globulin, gamma-
globulin and fibrinogen.
– The antibodies are mainly
gamma-globulin in nature.
1. A recipient 2. Antigens are genetically
determined by dominant or
individual will codominant alleles, so the
produce an cells of an individual will
immune response possess all antigens
against any corresponding to the alleles
the individual has inherited
antigen that the from his parents.
individual himself
does not possess.
• Antibodies
produced in
response to RBC
antigens almost
always belong to
the IgG and/or IgM
class
 Characteristics IgG IgM
Type of heavy chains ɤ (gamma) µ (mu)
Number of units 1 5
Normal adult serum 16% 4%
conc’n
Cross placenta/cause Yes No
HDN
Serologic behavior Agglutinates RBCs Agglutinates directly in
when intracellular an isotonic saline
distance is spanned environment
Capable of fixing Variable (some Yes
complement (cause specificities and/or
intravascular subclasses)
hemolysis
Optimal temp of 37°C < 20°C
reactivity
Usual mode of Pregnancy or Exposure to
• Applications of Blood
Groups:
1.Transfusion
4. Population studies
2.Maternal-fetal
incompatibility - Phenotype
3.Loci of several frequencies
genetic disorders are 5. Parentage
linked with known exclusion
blood group loci 6. Criminology
1. An allele that
determines a
dominant trait is
often signified by a
capital letter; one
that determines a
recessive trait, is
denoted by a
lowercase letter
(note: ABO blood
groups)
2. In blood group
genetics, unlike
classical Mendelian
genetics, some
codominant traits
have been
designated with
uppercase letters
and allelic
relationships with
lowercase letters
(e.g. K and k of the
Kell BGS; C and c of
the Rh system).
3. Some
codominant traits
have identical
base symbols but
different
superscript
symbols, such as
Fya and Fyb (Duffy
system) and Lua
and Lub (Lutheran
system).
4. Some have denoted
absence of a serologic
specificity with a base
symbol devoid of
superscripts and others
use a lowercase version
of the base symbol.
Thus, in the Lutheran
system, the assumed
amorphic gene is called
Lu, not lu while the
amorph in the Lewis
system is Le.
1. Genes encoding
the expression of
blood group
antigens are
written in italics
(or underlined if
italics are not
available).
2. Names are
written in normal
(Roman) script
with numeric
designations
written on the
same line as the
letters.
Superscript
letters are
lowercase (Fya).
3. When antigen
phenotypes are
expressed using letter
designations,
phenotype results are
usually written as + or
-, set on the same line
as the letter(s) of the
antigen (e.g K+ and
K-)

Rules 3 to 5 apply to
antigens and genes of
Kell, Duffy, Lutheran,
Kidd blood groups
systems.
4. When antigen
phenotypes are
expressed using
superscript letter
designations, that
letter is placed in
parentheses on
the same line as
the symbol
defining the
antigen: e.g.
Fy(a+) and Fy(a-)
5. Antibodies are
notated by the
prefix “anti-” plus
the antigen they
define (e.g. anti-K,
anti-Fya).
6. Some phenotypes are
expressed as numbers.
The symbol defining the
system is notated in
capital letters followed by
a colon followed by the
number representing the
antigen tested. Plus signs
do not appear when test
results are positive, but a
minus sign is placed
before a negative test
result (e.g. K:1, K:-1.)
7. If there has been
testing for several
antigens in one blood
group, the phenotype
is designated by the
letter(s) of the locus
or the BGS followed
by a colon, followed
by antigen numbers
separated by commas
(eg K:-1,2 - 3,4). Only
specifically tested
antigens are listed.
- six digit designation
indicates each blood group
specificity
- Numeric nomenclature
suitable for
computerization
- First three numbers
identify the BGS and the
last three identify the
individual specificity (eg.
001001 is A for ABO,
001002 is B for ABO)
No. System name System Gene name(s)* Chromosomal CD Numbers
symbol location
001 ABO ABO ABO 9q34.2  

002 MNS MNS GYPA, GYPB,4q31.21 CD235

GYPE
003 P P1   22q11.2–qter  

004 Rh RH RHD, RHCE 1p36.11 CD240

005 Lutheran LU LU 19q13.32 CD239

006 Kell KEL KEL 7q34 CD238

007 Lewis LE FUT3 19p13.3  

008 Duffy FY FY 1q23.2 CD234

009 Kidd JK SLC14A1 18q12.3  

010 Diego DI SLC4A1 17q21.31 CD233

011 Yt YT ACHE 7q22.1  

012 Xg XG XG, MIC2 Xp22.33 CD99†

013 Scianna SC ERMAP 1p34.2  

014 Dombrock DO DO 12p12.3 CD297

No. System name System Gene name(s)* Chromosomal CD Numbers
symbol location
015 Colton CO AQP1 7p14.3  

016 Landsteiner-Wiener LW ICAM4 19p13.2 CD242

017 Chido/Rodgers CH/RG C4A, C4B 6p21.3  

018 H H FUT1 19q13.33 CD173

019 Kx XK XK Xp21.1  

020 Gerbich GE GYPC 2q14.3 CD236

021 Cromer CROM DAF 1q32.2 CD55

022 Knops KN CR1 1q32.2 CD35

023 Indian IN CD44 11p13 CD44

024 Ok OK BSG 19p13.3 CD147

025 Raph RAPH CD151 11p15.5 CD151

026 John Milton Hagen JMH SEMA7A 15q24.1 CD108

027 I I GCNT2 6p24.2  

028 Globoside GLOB B3GALT3 3q26.1  

029 Gill GIL AQP3 9p13.3  

 • BB/BLOOD CENTER
Category A – plus blood
• Blood station – storage screening & testing of
transmissible diseases,
and issuance of whole provision of whole blood &
and RBCs RBCs, issuance and
• BCU – plus donor distribution of whole blood
& blood products
recruitment, education,
– Category B (& blood
counseling, screening, products)
selection and blood Note: HB category B (plus
collection comp. testing, resolution of
imcompatible Xmatch,
– Note: HB (plus comp investigation of trans rxns)
testing)
1. Same as all other 6. *Turn around time will
sections of the depend on the case
laboratory (i.e. patient’s need,
2. *Immunization of request of physician)
staff 7. *reagents & controls
3. *outdate of 8. S.O.P’s
specimen 9. *specimen collection
4. *monitoring of 10. *labelling & handling
equipment
5. *First in, first out
policy
• http://history.amedd.army.mil/bo
• Virtual Museum: Collection of
Anesthesia and Intensive
Care Medicine at the
Institute for the History of
Medicine in Vienna (Austria)
• http://www.bloodindex.org/i
mmunohaematology_intro.ph
p
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