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Iso immunization
1. ISO IMMUNIZATION
INTRODUCTION
Iso immunization is defined as a production of immune antibodies in an individual in response to
an antigen derived from another individual of the same species provided, the first one lacks the
antigen. It occurs in two stages-
Sensitization
Immunization
This is in contrast to ABO groups where there are naturally occurring iso immune anti-A and
anti-B antibodies
An Rh-negative pregnant woman is usually at risk of developing Rh isoimmunization on
exposure to Rh D antigens from her Rh positive baby through feto maternal hemorrhage
The initial exposure may be mild and asymptomatic, during subsequent Rh-positive pregnancies
the maternal baby would have a sufficient amount of antibodies to result iin various fetal
complications such as anemia, erythroblastosis, fetalis and if untreated intra uterine fetal death
Land steinir discovered ABO blood groups. Levine discovered Rh factor (1941). Clarke etal
(1963) demonstrated the effectiveness of anti-D immunization against development of Rheses
D allo immunization
DEFINITION
Rh incompatibility is a condition that develops when a pregnant woman has Rh negative
blood ( Rh D antigens absent) and the baby in her womb has Rh positive blood ( Rh D antigen
present in blood)
ABO incompatibility is an immune system reaction that occurs when blood from two
impatible types are mixed together
INCIDENCE
The incidence of Rh-negative blood group in
Chinese and Japanese is 1 %
European and American whites is 15 and 17 %
2. In Indian population 5 and 10 %
The overall risk of iso immunization in case of an Rh-negative mother with an Rh-positive infant
is about 16% of which
1.5-2% occurs intra partum
7% occurs within 6 months of delivery
7% occurs early during the second pregnancy
METHODS OF ACQUIRING Rh and ABO INCOMPATIBILTY
ABO INCOMPATIBILTY- Transfusion of mismatched blood. There are naturally occurring Anti-
A and anti-B ISO agglutinins, which results in immediate adverse reaction
RH GROUP INCOMPATIBILTY- there are no such naturally occurring antibodies and there is
no immediate reaction but the red cells carrying the Rh antigen sensitize the immunologically
competent cells of the body, provided the amount is sufficiently large
As a result of pregnancy ( Rh-negative woman bearing a Rh-positive fetus)
Normally, the fetal red cells containing the Rh antigen cannot mix with the maternal blood. But
in association with certain complications like
- Abortion
- Amniocentesis
- Ante partum hemorrhage
- Attempted version etc, there is a chance of feto-maternal blood
However, recent studies show a continuous feto-maternal bleed occurring throughout normal
pregnancies (1%)
MECHANISM OF ANTIBODY FORMATION IN THE MOTHER
If the ABO incompatible, Rh positive fetal cells enter the mother blood, they remain in
the circulation for their remaining life span. Therefore, they are removed from the
circulation by the reticulo-endothelial tissues and are broken down with liberation of the
antigen
3. The antibody production is related to not only to the responsiveness of the reticulo
endothelial system but also to the amount of Rh antigen liberated, therefore to the
number of red cells that have entered the maternal blood
Because this takes a long time, immunization in first pregnancy is unlikely
Detectable antibodies unusually develop after 6 months following larger volume of fet0-
maternal blood
If the feto-maternal blood is less than .1ml the antibody may not be detected until
boosted by further Rh stimulus
Antibodies are formed remain throughout life
The initial response in case of a woman exposed to the Rh-D antigen is weak and
primarily composed of Ig.M, a large molecule that cannot cross the placenta
However, this immune response changes to the production of Ig G within a period of 6
weeks to 6 months, which can cross the placenta, resulting in various complications in
the fetus and the mother
PATHOPHYSIOLOGY
Rh ISO immunization is generally observed in case of the second or late Rh-positive
pregnancies
As the maternal antibodies cross the placenta and destroy the fetal Rh-Positive red cells
and causes hemolytic anemia
It results in increased levels of bilirubin. Severe anemia may be followed by
erythroblastoisis fetalis, that is characterized by heart failure, edema, ascites and
pericardial effusion
DIAGNOSIS OF ISOIMMUNIZED PREGNANCY
The evaluation of pregnancies associated with isoimmunization is based on the history of
an affected fetus in the previous pregnancy and maternal antibody titres
The blood type of the father and that of the fetus is important for planning the management
The presence of the Rh factor is a simple mendelian trait, where in there is a 50:50 chance
of the fetus being Rh positive, if the father is heterogeneous Rh positive and a100 %
chance of the fetus being positive, if the father is homozygous Rh positive
Maternal titre
Amniocentesis
Ultrasonography
Doppler studies
Cordocentesis
4. Maternal Titre: The determination of the blood type and screening for antibodies is now part of
routine prenatal care
A maternal antibody titre as detected by an indirect comb’s test is used to select sensitized
patients for further fetal assessment
Amniocentesis: Analysis of amniotic fluid is to measure the bilirubin and to predict the
severity of fetal hemolytic disease after 27 weeks gestation
Ultrasonography- Ultrasonogrpahic examination is advised periodically for evaluation fo the
fetal heart size, edema, pericardial effusion, ascites and the amniotic fluid index
Doppler studies- It is a non invasive method of predicting significant fetal anemia
Cordocentesis- It also known as percutaneous umbilical blood sampling (PUBS) . it is having
a higher rate of complications than with other modalities
MANAGEMENT
All pregnant women who are Rh negative should have their serum antibody screening
Management of unsensitized pregnancy
Standard protocol is an unsensitized Rh negative pregnancy at 28 weeks should include
Repeat Rh- antibody titre
Ultrasound examination of the fetus
Intramuscular Rh- immunoglobulin
Analysis of the husband’s blood type
A small percentage of Rh-negative women become sensitized during a pregnancy that
are initially unsensitized
To prevent this from occurring, an injection of Rh O immunoglobulin is offered to all
unsensitized Rh-negative women during the 28th
week
PREVENTION: Anti- D immunoglobulin ( 300 bg of D- antibody) is given to D-negative,
non sensitized mothers to prevent the hazards of sensitization. The anti-D globulin is
provided to D- negative mothers after
Miscarriage
Abortion
5. Evacuation of a molar pregnancy
Placental abruption
Intrauterine manipulation
Placenta previa
MANAGEMENT OF SENSITIZED PREGNANCY
If the mother is sensitized during pregnancy or following first delivery, the management
involved
The delivery should be preformed near term as soon as pulmonary maturity is attained in
fetus
If the fetus is severely affected, then amniocentesis is required on a weekly basis
USG should be performed to identify fetal ascites or edema
The fetal heart rate should be closely monitored
Intrauterine transfusion of O-negative, cytomegalovirus- negative, washed, irradiated
packed red cells may be necessary to prevent fetal demise
SUMMARY
Rho iso-immunization occurs when an Rh-negative mother is sensitized with the Rh positive
blood of the fetus during the previous abortion or delivery. This results in the development of
antibodies against the Rh positive blood that can have adverse effects on the Rh positive blood
of the fetus in the following pregnancy, which can manifest with severe complication and event
end up in death. This can be prevented by administration of Rh-D immunoglobulins to the Rh-ve
mother following delivery and by continous fetal monitoring