RH Blood Group System

Rh blood group system
MUHAMMAD ASIF ZEB

Lecturer MLT (KMU)
Master in health and professional education (MHPE in
progress)
M.Sc. Hematology
B.Sc. MLT
Certificate in health and professional education
(CHPE)
Certificate in health research (CHR)
BACKGROUND INFORMATION:
 History:
o In 1939, a mother who had just given birth to a still-born child

needed a blood transfusion. The ABO blood group system had
been discovered almost 40 years previously, and the
importance of giving an ABO-compatible blood transfusion was well
established. However, although the mother was transfused with
ABO compatible blood from her husband, she still experienced
an adverse reaction to the transfusion.
o Her serum was found to contain antibodies that agglutinated

her husband's RBCs, even though they were ABO compatible.
During the pregnancy, the mother had been exposed to an
antigen on the fetal RBCs that was of paternal origin.
o Her immune system attacked this antigen, and the destruction
of the fetal RBCs resulted in fetal death. The mother re-
encountered the same paternal antigen when she received a blood
transfusion from her husband.
o This time her immune system attacked the transfused RBCs,

causing a hemolytic transfusion reaction.
o The antibodies responsible led to the discovery of the Rh blood

group.
 Landsteiner and Wiener:
o Rh system IDENTIFIED by Landsteiner and Wiener in 1940.
o Immunized animals to Rhesus macaque monkey RBCs.
o Antibody agglutinated 100% of Rhesus and 85% of human
RBCs.
o Reactivity paralleled reactivity of sera in women who
delivered infant suffering from hemolytic disease.
Rh FACTOR
 What does Rh refers to?
o Rh is the most important blood group system after ABO in

transfusion medicine.
o One of the most complex of all RBC blood group systems

with more than 50 different Rh antigens.
o The genetics, nomenclature and antigenic interactions are

unsettled.
o There are two genes, RHD and RHCE

 RHD: What does the term D-positive and
D-negative refers to?

o If Protein (D antigen) is present on the surface of Red blood
cell, the blood will be termed as D-positive.
o If Protein (D antigen) is absent on the surface of Red blood cell,

the blood will be termed as D-negative.
RHCE: Four additional antigens: C, c, E, e:
o The RhCE protein encodes the C/c antigen (in the 2nd
extracellular loop) and the E/e antigen (in the 4th extracellular
loop).
 PROTEINS WITH UNKNOWN
FUNCTIONS:
o The RhD and RhCE proteins are both transmembrane,
multipass proteins that are integral to the RBC membrane.
o Unlike most cell surface molecules, the Rh proteins are

not glycosylated (they do not contain oligosaccharides) but
they are closely associated with a RBC membrane
glycoprotein called RhAG.
o The function of the Rh-RhAG complex might involve

transporting ammonium or carbon dioxide. The RhD protein
encodes the D antigen.
Rh Blood Group System
• Fisher-Race (DCE terminology)
– Suggested 3 sets of closely linked alleles (D and d, C and c,

E and e)
– Each gene (except d, which is an amorph) causes
production of an Ag
– Inherited from parents in linked fashion as haplotypes
Rh Blood Group System
 D, d, C, c, E, and e.
 (d ) -is considered an amorph (silent allele) or the absence of

D antigen.
 The phenotype (blood type observed during testing) of a

given red cells is define by the presence or absence of D, C, c,
E, and e.
 C, c, E, e represent actual Ags recognized by specific
antibodies.
Variation of the Rho (D) Antigen
 Weak D overview
 Some cells require addition of AHG (IDAT) to

demonstrate agglutination with Anti-D
 3 mechanisms causing weak D expression
▪ Genetic - inheritance of D genes which result in lowered

densities of D Ags on RBC membranes
▪ C trans - position effect; the D gene is in trans to the C
gene, eg., Dce/dCe (C and D Ag arrangement causes
steric hindrance weakening D expression)
▪ D mosaic - 1 or more parts of the D Ag is missing; may
result in production of Anti-D
Determination of Du Status
There are instance when an accurate Rh type can not be

determined through routine testing
 1- If the new-born’s cell are coated with maternal IgG
anti-D in utero, very few D Ag sites will be available to react
with reagent anti-D.
 Elution of the sensitizing Ab (removing the Ab) and
identifying it as anti-D will verify that the infant’s red cell
are D positive
 2- Warm autoimmune hemolytic anemia, Abs are directed
against the patient’s own red cell and react as though they
are Rh specific.
Determination of D Status
 Is essential when test donor blood sample.

 Blood considered Rh positive if either the D or Du test is
positive
 If any donor blood sample that types Rho(D) negative by
either slide or rapid method must be tested further by
indirect anti-globulin test (IDAT).
 If both test results are negative, the donor sample is
considered Rh negative.
Detection of Rh antibodies and Antigens
 Immune IgG Abs (IgG1 and IgG3 most important)
 React optimally at 37oC or with AHG
 Order of immunogenicity:
D>c>E>C>e
 Do not bind complement (RBC destruction by Rh Abs is

extravascular)
 Exposure to less than 1 ml of Rh positive red cells can stimulate

Ab production in an Rh negative person
Clinical Significance:
o The Rh antigens are highly immunogenic, and most of the Rh

antibodies should be considered as potential causes of
hemolytic transfusion reactions and HDN.
o D antigen, after A and B, is the most important RBC antigen in

transfusion practice.
o Has been reported that 80%> of D neg individuals who receive

single unit of D pos blood can be expected to develop immune
anti-D.
o Rh antibodies rarely, if ever, bind complement, and

therefore RBC destruction is mediated almost exclusively via
macrophages in the spleen (extravascular hemolysis).
• Thank you

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Rh blood group system

MUHAMMAD ASIF ZEB

o In 1939, a mother who had just given birth to a still-born child

o Her serum was found to contain antibodies that agglutinated

o This time her immune system attacked the transfused RBCs,

o The antibodies responsible led to the discovery of the Rh blood

o Rh is the most important blood group system after ABO in

o One of the most complex of all RBC blood group systems

o The genetics, nomenclature and antigenic interactions are

o There are two genes, RHD and RHCE

D-negative refers to?

o If Protein (D antigen) is absent on the surface of Red blood cell,

o Unlike most cell surface molecules, the Rh proteins are

o The function of the Rh-RhAG complex might involve

• Fisher-Race (DCE terminology)

– Suggested 3 sets of closely linked alleles (D and d, C and c,

 (d ) -is considered an amorph (silent allele) or the absence of

 The phenotype (blood type observed during testing) of a

 Some cells require addition of AHG (IDAT) to

▪ Genetic - inheritance of D genes which result in lowered

There are instance when an accurate Rh type can not be

 Is essential when test donor blood sample.

 Immune IgG Abs (IgG1 and IgG3 most important)

 React optimally at 37oC or with AHG

 Do not bind complement (RBC destruction by Rh Abs is

 Exposure to less than 1 ml of Rh positive red cells can stimulate

o The Rh antigens are highly immunogenic, and most of the Rh

o D antigen, after A and B, is the most important RBC antigen in

o Has been reported that 80%> of D neg individuals who receive

o Rh antibodies rarely, if ever, bind complement, and

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