2. Discovery
•The rhesus blood type named after the rhesus monkey was first
discovered in 1937 by Karl Landsteiner and Alexander S. Wiener.
•The significance of the discovery was not immediately
apparent and was only realized in 1940, after subsequent
findings by Philip Levine and Rufus Stetson
•This serum that led to the
discovery was produced by
immunizing rabbits with red
blood cells from a rhesus
macaque. The antigen that
induced this immunization was
designated by them as Rh
factor to indicate that rhesu
s blood had been used for the
production of the serum.
3. •When blood from humans was tested with the rabbit serum, the red blood cells of
85% of the humans tested agglutinated (clumped together). The red blood cells of
the 85% (later found to be 85% of the white population and a larger percentage of
blacks and Asians) contained the same factor present in rhesus monkey blood
such blood was typed Rh positive. The blood of the remaining 15% lacked the
factor and was typed Rh negative.
• From its discovery 60 years ago, it has become second in importance only to the
ABO blood group in the field of transfusion medicine. It has remained of primary
importance in obstetrics, being the main cause of hemolytic disease of the
newborn (HDN).
• In American blacks, the percentage of Rh-positives is about 95 percent, where
as in African blacks, it is virtually 100 percent.
4. • Our blood types are determined by heredity. People belong to either of eight
different blood types:
A Rh+, A Rh-, B Rh+, B Rh-, AB RH+, AB Rh-, 0 Rh+, or 0 Rh- .
• The eight blood types have different combinations of certain molecules, antigens,
on the surface of the red blood cells. The A and B antigens are sugars and the Rh
antigens are proteins. The antigens expressed in the red blood cells determine an
individual's blood type.
Also the combination of some other molecules floating around in the blood plasma
differs between the eight blood types, the so called antibodies.
5. RH Antigens
•There are six common types of Rh antigens, each of which is called
an Rh factor. These types are designated - C, D, E, c, d, and e.
•The proteins which carry the Rh antigens are transmembrane
proteins, whose structure suggest that they are ion channels.
•The main antigens are D, C, E, c and e, which are encoded by
two adjacent gene loci, the RHD gene which encodes the RhD
protein with the D antigen (and variants) and the RHCE gene
which encodes the RhCE protein with the C, E, c and e antigens
(and variants)
6. • A person who has a C antigen does not have the c antigen, but the person
missing the C antigen always has the c antigen. The same is true for the D-d
and E-e antigens. Also, because of the manner of inheritance of these
factors, each person has one of each of the three pairs of antigens.
• The type D antigen is widely prevalent in the population and
considerably more antigenic than the other Rh antigens. Anyone who has
this type of antigen is said to be Rh positive, whereas a person who does
not have type D antigen is said to be Rh negative.
• However, it must be noted that even in Rh-negative people, some of the
other Rh antigens can still cause transfusion reactions, although the
reactions are usually much milder.
8. Rh Immune Response
•When red blood cells containing Rh factor are injected into
a person whose blood does not contain the Rh factor—that
is, into an Rh-negative person—anti-Rh agglutinins develop
slowly
•reaching maximum concentration of agglutinins about 2 to
4 months later.
•This immune response occurs to a much greater extent in
some people than in others. With multiple exposures to the
Rh factor, an Rh-negative person eventually becomes
strongly “sensitized” to Rh factor
9. If an Rh-negative person has never before been exposed to
Rh-positive blood, transfusion of Rh-positive blood into:
• no immediate reaction
• anti-Rh antibodies can develop in sufficient quantities during the next 2 to 4
weeks to cause agglutination
• these cells are then hemolyzed by the tissue macrophage system
• thus, a delayed transfusion reaction occurs, although it is usually mild
• subsequent transfusion of Rh-positive blood into the same person, who is
now already immunized against the Rh factor, the transfusion reaction is
greatly enhanced and can be immediate and as severe as a transfusion
reaction caused by mismatched type A or B blood.
10. • Rh antibodies are IgG antibodies which are acquired through exposure to
Rh-positive blood (generally either through pregnancy or transfusion of blood
products). The D antigen is the most immunogenic of all the non-ABO antigens.
Approximately 80% of individuals who are D-negative and exposed to a single
D-positive unit will produce an anti-D antibody. The percentage of
alloimmunization is significantly reduced in patients who are actively e
exsanguinating.
• If anti-E is detected, the presence of anti-c should be strongly suspected (due
to combined genetic inheritance). It is therefore common to select c-negative
and E-negative blood for transfusion patients who have an anti-E. Anti-c is a
common cause of delayed hemolytic transfusion reactions.
11. Erythroblastosis Fetalis (“Hemolytic Disease
of the Newborn”)
• Erythroblastosis fetalis is a disease of the fetus and newborn
child characterized by agglutination and phagocytosis of the fetus’
s red blood cells.
•In most instances of erythroblastosis fetalis, the mother is Rh
negative and the father Rh positive.
• The baby has inherited the Rh-positive antigen from the father,
and the mother develops anti-Rh agglutinins from exposure to the
fetus’s Rh antigen.
• In turn, the mother’s agglutinins diffuse through the placenta
into the fetus and cause red blood cell agglutination.
12. • An Rh-negative mother having her first Rh-positive child usually does not
develop sufficient anti-Rh agglutinins to cause any harm. However, about 3
percent of second Rh-positive babies exhibit some signs of erythroblastosis
fetalis; about 10 percent of third babies exhibit the disease; and the incidence
rises progressively with subsequent pregnancies.
• After anti-Rh antibodies have formed in the mother, they diffuse slowly
through the placental membrane into the fetus’s blood.
• There they cause agglutination of the fetus’s blood. The agglutinated
red blood cells subsequently hemolyze, releasing hemoglobin into the
blood.
13. • The fetus’s macrophages then convert the hemoglobin into bilirubin, which
causes the baby’s skin to become yellow(jaundiced). The antibodies can also
attack and damage other cells of the body.
• The jaundiced, erythroblastotic newborn baby is usually anemic at birth
• the anti-Rh agglutinins from the mother usually circulate in the infant’s blood
for another 1 to 2 months after birth, destroying more and more red blood cells.
• The hematopoietic tissues of the infant attempt to replace the hemolyzed red
blood cells. The liver and spleen become greatly enlarged and produce red
blood cells in the same manner that they normally do during the middle of
gestation.
14. • Because of the rapid production of red cells, many early forms of red blood
cells, including many nucleated blastic forms, are passed from the baby’s bone
marrow into the circulatory system, and it is because of the presence of these
nucleated blastic red blood cells that the disease is called erythroblastosis
fetalis.
•Although the severe anemia of erythroblastosis fetalis is usually the cause of
death, many children who barely survive the anemia exhibit permanent mental
impairment or damage to motor areas of the brain because of precipitation of
bilirubin in the neuronal cells, causing destruction of many, a condition called
kernicterus.
15.
16. • The New York Times’s first mention of the Rh factor, on Sunday, March 26,
1944, should have made bigger news than it did — in a brief article at the
bottom of the “Science in Review” column on Page 9 of Section 4, The
News of the Week in Review. “The recently discovered Rh factor in human
blood,” it said, “need not cause infant deaths and childless marriages.”
The article quoted Dr. Alexander S. Wiener, who in 1940, along with his
colleague Karl Landsteiner, first described the Rh factor in humans. “Dr.
Wiener believes that some method may be developed to desensitize mother
so that their babies may be saved,” the article said. “Research based on this
hope has already been started.”
• It was not until Sept. 11, 1965,
that the paper reported on clinical
trials of a drug treatment for Rh
disease. this was the first test of
Rh immune globulin, a solution
of antibodies derived from human
plasma.
• Injected into the Rh-negative
mother, the antibodies bind to and
destroy fetal Rh-positive blood
cells that have passed from the
fetus to the mother during birth.
17. • In the 1970s, a dramatic reduction in the incidence of erythroblastosis
fetalis was achieved with the development of Rh immunoglobulin globin, an
anti-D antibody that is administered to the expectant mother starting at 28 to
30 weeks of gestation.
• The anti-D antibody is also administered to Rh-negative women who
deliver Rh-positive babies to prevent sensitization of the mothers to the D
antigen. This greatly reduces the risk of developing large amounts of D
antibodies during the second pregnancy.
• The administered anti-D antibody also attaches to D-antigen sites on
Rh-positive fetal red blood cells that may cross the placenta and enter
the circulation of the expectant mother, thereby interfering with the immune
r esponse to the D antigen.
• Coombs test (also known as Coombs' test, antiglobulin test or A
GT) is either of two clinical blood tests used in immunohematology a
nd immunology. The two Coombs tests are the direct Coombs tes
t and the indirect Coombs test
•The indirect Coombs test is used to screen for antibodies in the p
reparation of bloodmfor blood transfusion. The donor's and recipie
nt's blood must be ABO and Rh D compatible. Donor blood for tra
nsfusion is also screened for infections in separate processes
18.
19. Inheritence
• The Rh factor genetic information is also inherited from
our parents, but it is inherited independently of the ABO
blood type alleles.
•Someone who is "Rh positive" or "Rh+" has at least one Rh+
allele, but could have two. Their genotype could be either
Rh+/Rh+ or Rh+/Rh-. Someone who Rh- has a genotype of
Rh-/Rh-.
•Just like the ABO alleles, each biological parent donates one
of their two Rh alleles to their child.
