MAJOR BGS: RH (7 TH AND 8 TH MEETING)

OBJECTIVES:
At the end of this unit, the learners must be able to:
1. discuss the discovery of the Rh-hr system;
2. explain the nomenclature of the Rh-hr system;
3. compare and contrast the genetic pathways for
the inheritance of the Rh antigens to those of
ABO;
4. discuss the significance of the RH phenotypes;
and
5. identify the techniques in Rh grouping.

A. Historical Perspective
a. Before 1939 - Morbidity and mortality
in ABO compatible transfusions
b. Levine and Stetson – antibody from
mother
c. Landsteiner and Weiner – antibody
from guinea pigs and rabbits
transfused with rhesus monkey RBCs
d. Levine and co-workers – said the two
antibodies are the same
e. Renaming to anti-LW
f. 1940’s – 5 antigens
g. 50 different specificities
B. Inheritance
a. Chromosome 1p36.11
b. Codominant
c. RHD and RHCE
d. Polymorphic
e. Gene codes for the antigen or
blood factor itself (Depends on the
terminology)

C. Nomenclature and Terminology

a. Postulated Genetic Mechanism
i. Fisher-Race: The DCE terminology
1. Closely-linked genes: D, d, C,
c, E, e
2. Antigens: D, d, C, c, E, e
3. “d” represents the absence of
D antigen
4. Disadvantages: Cannot report
5. Newer Rh antigens
6. Rhmod and Rhnull
ii. Wiener: The Rh-Hr terminology
 1. Rh gene produces at least 3
factors within an
agglutinogen
2. Fisher-race can be converted
to Wiener
b. Presence or absence of Ag
i. Rosenfield and Coworkers:
Alpha/Numeric Terminology
1. Rh1 – D
2. Rh2 – C
3. Rh3 – E
4. Rh4 – c
5. Rh5 – e
a. Ex: Rh: 1, 2, 3, -4
Rh: 1, 2, 3, -4, -5
c. Working Party on Terminology for
Red Cell Surface Ag
i. ISBT: Numeric Terminology

D. Antigens
A. Transmembrane polypeptides
B. Non-glycosylated proteins
C. Highly immunogenic
 D. D is most potent
E. D>c>E>C>e
F. Weak D (Du phenotype):
a. Genetic weak D
b. C in Trans with D
c. Partial D (mosaic) – must be given Rh
(D) negative
d. Del

E. Antibodies
A. Immune antibodies
B. IgG class

F. Clinical Significance
A. Delayed HTR
B. HDFN (especially on the 2nd
pregnancy), becomes severe in ABO
compatible pregnancies
i. Etiology
1. Destruction of RBCs of the fetus by
antibodies produced by the mother
2. IgG class
3. GOOD - To provide immunity against
pathogens
4. BAD – if IgG is directed against RBCs,
fatal
ii. Factors affecting severity
1. Antigenic exposure and antigenic sites
2. Host factors
3. Immunoglobulin class
a. IgG transport begins in 2nd
trimester
b. Efficiency: IgG1 and IgG3 > IgG2
and IgG4
4. Antibody specificity
 5. Rh > Kell > others
6. Influence of ABO group

iii. Diagnosis:
1. Acid elution method for fetal
hemoglobin (transplacental
hemorrhage)
2. Amniocentesis and chorionic villi
sampling
3. ABO and Rh testing
4. Antibody screen
5. Antibody identification
6. Paternal phenotype
7. Amniocyte testing
8. Antibody titers
9. Elution and DAT

iv. Pathogenesis
1. Hemolysis
2. Erythroblastosis fetalis
3. Severe anemia
4. Hypoproteinemia
5. Cardiac failure
6. Generalized edema, effusions and
ascites (hydrops fetalis)
7. Bilirubin (kernicterus)
 8. Decreases upon delivery but persists
several days up to weeks after delivery
(half-life of IgG is 25 days)

v. Management
1. Rho gam/Rh Ig
2. Exchange transfusion
3. Intrauterine transfusions
4. Premature delivery
5. Exchange transfusion
6. Phototherapy

G. Laboratory Methodology
A. Reagents
a. Saline-based
b. High protein-based
c. Low protein-based
d. Chemically modified
e. Monoclonal
f. Blends of monoclonal

H. Rare phenotypes
A. Cw
B. f(ce)
C. rhi(Ce)
 D. G
E. Rh:13, Rh:14, Rh:15, Rh:16
F. Hro
G. Rh:23, Rh:30, Rh:40
H. Rh:33
I. Rh:32
J. e Variants
K. V, VS
L. Deletions

OTHER BGS (9 TH AND 10 TH MEETING)

Objectives:
At the end of this unit, the learners must be able to:
1. explain the importance of other blood group
systems to blood transfusions; and
2. characterize the blood group system disease
associations;

Relative Importance of BGS is determined by:

1. Frequency of antibodies
2. Characteristics of antibodies
a. Subclass
 b. Thermal range
c. Ability to fix complement
d. Capacity
Tabulation of OBGS:
ISBT CS Ab Optimal Reaction Effect of
SYMBOL Class Temp phase Enzymes
in ºC
KEL Yes IgG 37 AHG No effect
DUFFY Yes IgG 37 AHG Destroyed
JK Yes IgG 37 AHG Enhanced
LU Lua – IgM RT RT No effect
No
Lub – IgG 37 AHG
Yes
LE No IgM RT, 37 AHG Enhanced
I No IgM RT RT Enhanced
M&N No IgM 37 RT Destroyed
AHG
S&s Yes IgG 37 AHG Variable

• Inactivated by enzymes
– Duffy
– MNS
– Xga
• Enhanced by Enzymes
 – Rh
– Kidd
– Lewis
– P
– I
– ABO

Note:
 See also accompanying excel file on
OBGS.

LEUKOCYTE ANTIGENS (11 TH MEETING)

At the end of this unit, the learners must be able to:

1. comprehend the concept of human leukocyte
antigens; and
2. become aware of the relevance of these
antigens in blood transfusion.

A. Historical Perspective
a. Patients who have been previously transfused
have alloantibodies
b. Alloantibodies were directed against
alloantigens not present in recipient
c. MAC – initials of the three volunteers
 d. Implicated in FNHTR
e. Advent of HLA typing
f. Genetics was elucidated

B. Nomenclature and Genetics

a. Polymorphic
b. HLA genetic region on chromosome 6
i. Determines major histocompatibility
factors
ii. Recognition and elimination of foreign
tissues
c. Also known as the MHC region
d. 35 to 40 genes physically grouped in three
regions located on the short arm of
chromosome 6
e. Related genes: Glyoxalase-1 (GLO) and
 phosphoglucomutase-3 (PGM-3) are also
linked

f. Class I region gene – classic transplantation

molecules
i. HLA-A
ii. HLA-B
iii. HLA-C
iv. HLA-E, HLA-F and HLA-G (non-classic)
g. Class II region gene
i. HLA-DR
ii. HLA-DP
iii. HLA-DQ
h. Class III region
 i. C2 and C4, Bf (complement factors)
ii. 21-hydroxylase
iii. Tumor necrosis factor
C. Significance
a. SELF vs NON-SELF
b. Pre-transfusion and transplantation
c. Platelet refractory therapy and random
platelet donors
d. Disease correlation
e. Paternity testing
f. Anthropologic studies
g. FNHTR
h. TA-GVHD
i. Clinical presentation
1. 4-30 days after the transfusion
2. Typical symptoms include: fever,
erythematous maculopapular rash,
which can progress to generalized
erythroderma, toxic epidermal
necrolysis in extreme cases
3. Other symptoms can include cough,
abdominal pain, vomiting, and
profuse diarrhea (up to 8 liters/day).
Upon transfusion of blood to someone who is not
genetically identical
(different HLA types):
1. Transfused lymphocytes mount an immune
response
2. Recipient with normal immune system
counterattacks
D. Prevention of TA-GVHD
Gamma irradiation
15-25 Gy (US, Philippines)
25-50 Gy (Australia & New Zealand)
Radioisotopes (Cesium-137 or Cobalt-60)
PLATELET ANTIGENS (11 TH MEETING)

At the end of this unit, the learners must be able to:

1. comprehend the concept of human platelet
antigens; and
2. become aware of the relevance of these
antigens in blood transfusion.

A. Definition
a. HPA are polymorphisms in platelet antigens
b. can stimulate production of alloantibodies in
recipients of transfused platelets from donors
with different HPAs
B. Significance
a. Antibodies cause:
i. neonatal alloimmune thrombocytopenia
ii. post-transfusion purpura
iii. some cases of platelet refractoriness
REFERENCES:

A. Textbook:
a. Harmening, Denise M. Modern Blood Banking and Transfusion Practices (2012). 6th
Edition. F.A. Davis Company.

B. Reference Books:
a. Blaney, Kathy D and Howard, Paula R. Basic and Applied Concepts of
Immunohematology (2008). 2nd Edition. Mosby, Inc. .
b. AABB Committee (2011). Standards of Blood Banks and Transfusion Services. 27th
Edition. USA: American Association of Blood Banks.
c. Fung, Mark K; Grossman, Brenda J; Hillyer, Christopher D; and Westhoff, Connie M
(2014). 18th Edition. Technical Manual (AABB). Maryland, USA.
d. Mcpherson, Richard A. and Pincus, Matthew (2017). Henry’s Clinical Diagnosis and
Management by Laboratory Methods. 23rd Edition. Philadelphia: Elsevier Inc.

C. Related Websites and other materials:

a. American Association of Blood Banks. Available at:
http://www.aabb.org/Pages/Homepage.aspx. Accessed on November 6, 2017.
b. American Red Cross. Available at http://www.redcross.org/ Accessed on November 6,
2017.
c. Department of Health. Available at http://www.doh.gov.ph Accessed on November 6,
2017.
d. Human Blood. Available at http://www.fi.edu/learn/heart/blood/blood.html. Accessed on
November 6, 2017.
e. Hematology-Blood Bank Links to Related Sites. Available at
http://www.lhsc.on.ca/lab/bldbank/links.htm. Accessed on November 6, 2017.
f. International Society of Blood Transfusion. Available at http://www.isbtweb.org/.
Accessed on November 6, 2017.
g. Medical Laboratory Observer. Available at http://www.mlo-online.com. Accessed on
November 6, 2017.
h. World Health Organization. Available at http://www.who.int/en/. Accessed on November
6, 2017.

Note:

Regarding the pictures presented in this document, these fall into one of the
following types: photographs personally taken by the document’s author,
downloaded from the internet under creative commons license, or
scanned/downloaded from the references listed; unless otherwise stated in the
photograph or caption.

Prepared by: CRIZELDA L. SALITA, MS, RMT