Here are short notes on the requested topics: 1. Classification of blood groups: - ABO blood group system: Based on presence or absence of A and B antigens on RBCs. Types - A, B, AB, O. - Rh blood group system: Based on presence (Rh+) or absence (Rh-) of Rh antigen. 2. ABO blood group system: - Antigens A and B present on RBC membrane. Type O lacks both antigens. - Plasma contains antibodies against antigens not present on own RBCs (anti-A in B individuals, anti-B in A individuals). 3. Rh factor: - Rh antigen present in 85% of Cauc

1. BLOOD GROUPS - II
Ms Veena Shriram

2. The Rh(D) Antigen:
 Rh is the most complex system, with over
45 antigens
 Discovered in 1940 after work on Rhesus
monkeys by Landsteiner & Wiener.
 Subsequently discovered to be unrelated to
monkeys.
 85% percent of whites are D-positive
and 15% are D negative; over 99% of
Asians are D-positive.

3.  Rh gene located on short arm of chromosome 1
 This is another imp. group to be matched before
transfusion.
 Thus there are two major groups of antigens
causing major mismatched blood transfusion reactions
1) ABO system discovered by Landsteiner in 1900.
2) Rh system discovered by Landsteiner in 1940.
 Unlike the antibodies of the ABO system, anti-D
antibodies do not develop without exposure of a D-
negative individual to D-positive red cells by transfusion
or entrance of fetal blood into the maternal circulation.

4. RH AGGLUTINOGENS:
 There are 6 known agglutinogens which are called Rh factors
present on the R.B.C membrane: C,D,E and c,d,e.
 They are not detected in any other tissues other than RBC.
 Inheritance: Each person inherits at least 3 of the above factors
from both groups in various combinations from both parents. e.g.
CDE, cDe, cDE,-----
 Agglutinogen D is highly antigenic. Person having D will be
called Rh+ve. irrespective of the fact whether C,E is present or not
as C,E are poor agglutinogens.
 Cde, CdE, cde.------Ag D is absent: hence even if C,E are present,
person will be labeled Rh-ve.

5. RH BLOOD GROUP SYSTEM:
 In the Rh system the most imp. antigen is the type D. This occurs
on surface of blood cells.
 The 5 most imp. genes are present on 3 diff. chromosomes
- gene ‘D’ is on first chromosome
- genes ‘C’ and ‘c’ are on the second chromosome
- genes ‘E’ and ‘e’ are on the third chromosome
 Rh antigens are present only on the surface of blood cells.

6.  Production of anti-Rh agglutinins in Rh - ve starts if Rh
+ve antigen gets into his blood
1. Rh -ve mother – Rh +ve baby
2. Rh -person – Rh +ve transfusion. (malpractice!!!)
 Rh agglutinins belong to the IgG type of antibodies –
they diffuse through the placenta – so they cause
agglutination in the foetal blood - erythroblastosis
foetalis
To prevent this we must give to the mother anti- Rh IgG
antiserum ( D antigen is the strongest antigen)

7. RH AGGLUTININS
 Person who has Ag D i.e. Rh+ve has no naturally occurring
agglutinins in the plasma. Hence Rh system follows first
part of LANDSTEINERS LAW.
 However if a PERSON is Rh -ve and has no agglutinogen D
yet has no agglutinins in his plasma.
 Hence Rh system fails to obey the second part of
Landsteiner Law.

8. RH IMMUNE RESPONSE:
 Rh-ve blood can be given to a person who is Rh+ve as it
has no agglutinins against D antigen.
 However if Rh+ve blood is given to a person who is Rh-
ve, an immune response is seen as the D antigen is foreign
to the recipient. Hence the recipient develops immune
antibodies to it. Anti Rh agglutinins develop slowly within
few hours. Maximum conc. of the antibodies is seen 2-4
months later. Hence no agglutination is seen as by the time
agglutinins are formed, the donor cells are already
destroyed.

9.  However, a 2nd exposure of Rh-ve person to Rh+ve blood,
severe transfusion reaction is seen due to agglutination of
donor erythrocytes with anti Rh antibodies which had
been formed in the plasma previously.
 On multiple exposures to Rh factor, Rh-ve person gets so
sensitized, that transfusion reactions can be massive
similar to ABO incompatibility.

10. ERYTHROBLASTOSIS FETALIS:
 Also called Hemolytic Disease of the Newborn (HDN)
or Icterus Gravis neonatorum.
 Cause: It is due to Rh incompatibility when the mother
is Rh-ve and the fetus is Rh+ve. This is possible if the
father is Rh+ve DD/Dd.
 If the father is DD all the children are Rh+ve as D is
dominant in nature.
 However if the father is Dd, & the mother dd, then there
is 50% chance that the baby will be Rh negative (dd).
 Also if both parents are Rh+ve but heterozygous Dd,
there is one in four chance that the baby will be Rh-ve.

11. ERYTHROBLASTOSIS FETALIS

15. SENSITIZATION:
 Initially the mother gets sensitized to the fetal blood
carrying Rh antigens. Fetal cells enter mother’s blood at
the time of separation of placenta, when the maternal
sinuses are open.
 These fetal cells stimulate production of antibodies in
the mother. However, these antibodies cannot harm the
first baby as separation of placenta takes place after
birth of the first baby. The first baby thus escapes from
the incompatibility.

16. CONTINUED…..
 In the second pregnancy, these antibodies which
have been formed in the earlier pregnancy can
diffuse through the placental barrier (IgG) and and
cause agglutination of the fetal R.B.C’s provided
the second baby is Rh+ve.

17.  In reality 3% of the second baby suffers. While in the third
pregnancy, 10% babies suffer. Incidence rises with each
successive pregnancy.
 First born baby may be affected if
 Mixing of blood in abortions, any intrauterine manipulations-
fetomaternal bleed.
 If mother has been sensitized by previous Rh+ve blood
transfusion.
 Hence never give Rh+ve blood to a young Rh-ve female
in the reproductive age group as far as possible

18.  Clinical picture:
 Disease is called Hemolytic Disease of the Newborn because
the newborn shows haemolysis due to maternal antibodies.
 Baby looks pale and anaemic.
 Haemolysed blood then releases Hb into the circulation
which is then converted into bilirubin by macrophages.
 So Baby looks jaundiced.

19.  Icterus Gravis Neonatorum.
 Rh antibodies remain in the babies blood for 1-2 months
during which more haemolyis takes place.
 To make up for this loss, liver and spleen enlarge to increase
rate of erythropoiesis. However due to rapid rate of
production, immature nucleated R.B.Cs enter circulation and
the peripheral blood shows large nucleated R.B.C. Hence
called Erythroblastosis Fetalis.

20.  Unconjugated bilirubin then gets deposited in the basal ganglia
and cause destruction of the neuronal cells as the blood brain
barrier is not yet developed. Baby then shows permanent
damage to the motor areas and is mentally retarded.
 Conjugation of bilirubin does not take place as liver is not yet
mature. This condition is called Kernicterus.
 If the baby does survive above, then the last stage is of
generalized edema due to damage to liver & hypoprotenemia.-
Hydrops Fetalis.

21. TREATMENT : EXCHANGE TRANSFUSION
 Carried out soon after birth
 400 ml of Rh negative - ABO compatible blood is
transfused into Rh+ve baby over a period of few hours.
Simultaneously Rh+ve blood is removed from the other
hand. This procedure is repeated several times in the first
few weeks of life.

22.  Principle: Rh-ve blood is not agglutinated by
antibodies present in the fetus and hence can tide over
the period in which antibodies are circulating.
 Baby's blood containing antibodies and bilirubin is
removed hence the baby is saved from complications.
 After a few weeks when almost no antibodies are
present, baby's own marrow produces Rh+ve blood
which is now safe.

23. PREVENTION:
 Avoid giving Rh+ve blood to a young Rh-ve female in the
reproductive age group.
 Single dose Injection Anti D is given to the mother within 72
hours of delivery so that these antibodies will agglutinate the
fetal cells circulating in the maternal blood & they are
removed before they can sensitize the mother.
 Gap between 2 pregnancies so that antibody titers are low.
 Premarital counseling.

24. IMPORTANCE OF BLOOD GROUPS:
 Blood transfusions
 Rh blood typing to avoid Erythroblastosis Fetalis.
 Paternity Tests. Can rule out paternity not confirm it
 Forensic Medicine to identify criminals
 Anthropological studies to understand the racial differences
and the evolution of blood Groups.
 Correlation between blood groups and disease: e.g. Blood
group O is prone to duodenal ulcer, Blood Group A is
prone to gastric malignancy, pernicious anemia.

25. BLOOD TRANSFUSION:
 Indications: Severe anemia, hemorrhagic shock due to
wounds, accidents, maternal hemorrhage.
 Procedure: Blood is collected from a healthy Donor.
It is then stored at 40C in a bag containing ACD (Acid
Citrate Dextrose) / CPD (Citrate Phosphate Dextrose)
which act as anticoagulants & can be used within 21 days.

26. HAZARDS OF BLOOD TRANSFUSION:
 Due to immune transfusion reactions:
A) Hemolytic transfusion reaction:
 Major mismatch leads to agglutination of
Donor RBC’s. Activation of complement
system leads to sudden haemolysis and
release of Hb into circulation.

27.  Acute renal shutdown (causes):
1) Release of toxic substances during hemolytic reaction
causes powerful renal vasoconstriction .
2) Toxic substances and the loss of RBC’s makes a person
go into circulatory shock. Blood pressure falls with
reduced renal blood flow and urine output.
3) Also free Hb which is not bound to haptoglobulin
blocks renal tubules causing acute renal shutdown.-fatal

28.  Nonhaemolytic immune reaction:
1. Fever with chills due to allergic reaction to donors plasma
or ACD bag
2. Anaphylactic reaction due to release of histamine from
donors basophils
 Nonimmune transfusion reaction:
1. circulatory overload & cardiac failure due to rapid
transfusion

29. 2. stored blood transfusion reaction
a) ACD causes chelation of Calcium leading to tetany.
b) Haemolysed RBC release K+ and increased plasma levels
i.e. hyperkalemia is seen especially if the blood is more than
14 days old.
 mild thrombocytopenia because platelets and clotting
factors do not survive in stored blood
 Last but not the least, infections transmitted via blood
are viral hepatitis, HIV, malaria etc.

30. TRANSPLANTATION OF TISSUES AND ORGANS
 Antigens of red blood cells that cause
transfusion reactions are also present in other
cells of the body, and each bodily tissue has its
own additional complement of antigens.
 Consequently, foreign cells transplanted
anywhere into the body of a recipient can
produce immune reactions.

31. AUTOGRAFTS, ISOGRAFTS, ALLOGRAFTS, AND XENOGRAFTS.
 A transplant of a tissue or whole organ from one part of
the same animal to another part is called an autograft;
 from one identical twin to another, an isograft;
 from one human being to another or from any animal
to another animal of the same species, an allograft;
 And from a lower animal to a human being or from an
animal of one species to one of another species, a
xenograft.

32. TRANSPLANTATION OF CELLULAR TISSUES.
 In the case of autografts and isografts, cells in the
transplant contain virtually the same types of antigens to
live normally and indefinitely if an adequate blood supply
is provided.
 At the other extreme, in the case of xenografts, immune
reactions almost always occur, causing death of the cells
in the graft within 1 day to 5 weeks after transplantation
unless some specific therapy is used to prevent the
immune reactions.

33.  Different cellular tissues and organs that have been
transplanted as allografts: are skin, kidney, heart,
liver, glandular tissue, bone marrow, and lung. With
proper "matching" of tissues between persons,
many kidney allografts have been successful for at
least 5 to 15 years, and allograft liver and heart
transplants for 1 to 15 years.

34.  Describe the molecular basis of blood groups and
the reasons for transfusion reactions.
 Short Notes:
1. Classify blood group
2. ABO blood group system
3. Rh factor
4. Indication of blood transfusion
5. Mismatched blood transfusion