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Rh iso immunization

2. RH, ABO in compatibility and Rh alloimmunization

Dajane N.

3. Presentation outline

* Introduction

* Pathophysiology

* Causes/risk factors
* Diagnosis

* Complication

* Assessment

+ Management

4. Red Cell Alloimmunization(Rh alloimmunization)

+ Exposure to foreign red cell antigens invariably results in the
production of anti-red cell antibodies

Y the process known as red cell alloimmunization, which was
formerly termed isoimmunization.

* The expression sensitization can be interchangeably used with

alloimmunization

5. Rh alloimmunization

“The Rhesus factor
+ Identified by Landsteiner and Weiner in 1940 in the RBCs of human beings.

* Rh factor (i.e. rhesus factor) is proteins (antigens) occurring only on surface
of RBC’s

«Rh+ if proteins present (85%)
*Rh- if proteins absent (15%)
* The Rh blood group systems consists of several antigens(eg D,C, c, E,e)

:,D, is by far the most common and the only preventable one

6. Rh alloimmunization

“The Rhesus factor
+ Inherited from each parent

«Rh D negative individuals may become sensitized after a single

exposure to as little as 0.1 mL of fetal erythrocytes.

7. Rh alloimmunization

OGenotype
* Depending on the zygosity, the Rh group of an individual may be
stated as:
+ D/D — homozygous Rh positive (65%)
« D/d — heterozygous Rh positive (35%)
« d/d — Rh negative

" Common genotypes: CDe/cDe and CDe/Cde

8. Rh alloimmunization

* The Rh C, c, E and e antigens have lower immunogenicity than the Rh

D antigen, but they too can cause haemolytic disease.

+ Other variants have been identified and on occasions may be

responsible for problems of blood group incompatibility.

+ However, for day-to-day clinical practice attention is focused on the

‘D’ constituent alone.

9. Rh alloimmunization: incidence

> Incidence varies in different racial and geographical groups
>It is lowest amongst the mongoloid races, and higher amongst the
Caucasians.
Y Mongoloids, Chinese and Japanese, 1-2%
Y Indians, 5%
v Africans, 5-8%
Y Caucasians, 15%

y Basques (the border of France and Spain > 25%)

10. Aetiology

+ Isoimmunization is production of antibodies to an antigen from the same species.
+ Stages of immunization:
a. Sensitization

b. Immunization

+ Aand B groups have natural antibodies, Rh group does not have natural antibody.

11. Aetiology
* Rh isoimmunization may develop as a result of:

+ Mismatched blood transfusion — transfusion of Rh-positive blood to an

Rh negative woman.

« Rh —ve woman with Rh +ve fetus — sizeable fetomaternal leak (FML)

from an Rh-positive fetus to an Rh-negative mother.

= In fact, such leaks may happen continuously throughout pregnancy.

12. * Sensitization:
« When Rh +ve cells are transfused to Rh —ve woman, there is no
immediate destruction of the Rh +ve cells as there are no natural
Rh antibodies.
+ But the Rh +ve cells sensitize the immunologically competent cells

and it takes up to 1 week

13. * Immunization
+ When second exposure to Rh +ve antigens happens,
immunologically competent cells produce anti-D antibodies.

+ Detectable antibodies usually develop after 6 months following

larger volume of fetomaternal bleed.

* Antibodies once formed remain through out life in mother.

" Immunization is unlikely unless at least 0.1 mL of fetal blood enters

mother.

14. Factors that increases risk of isoimmunization
+ Blood transfusion
+ Abortion
+ Therapeutic
+ Spontaneous
+ Molar pregnancy
+ Ectopic pregnancy
+ Placental abruption

+ Abdominal trauma

15. Cont...

Obstetric procedures
+ Amniocentesis
+ Chorionic villus sampling (CVS)
+ Percutaneous umbilical blood sampling
+ External cephalic version

+ Manual removal of the placenta

The Grandmother theory???

16. Summary of pathogenesis

For Rh alloimmunization

* Fetus should have Rh positive RBC & mother should have Rh-ve
RBC.

* Sufficient number of fetal RBC must gain access to maternal
circulation(>0.1ml enough).

* Mother-immunologic capacity to produce antibody directed against

D antigen

17. Pathogenesis(Ab formation process)

Maternal immune system
recognizes foreign
antigens if fetus Rh +ve
and mother Rh — ve

Fetal RBC cross to
maternal
circulation

Antibodies are
formed against
fetal antigens

Subsequent pregnancy
with Rh+ fetus,
immune system

activated

and large amounts of Ab

formed

Fetal anemia,

IgG Ab cross
placenta & attack
fetal RBC

hydrops, etc

DAJANE N.(BSc, MSc)

18. Pathogenesis...

+ Many cells pass between maternal & fetal circulation
* Rh antigen causes > response than most

+ 0.1 ml blood in most deliveries is enough but generally not

sufficient to activate immune response

» B lymphocyte clones recognizing foreign RBC antigen are formed

NE N.(BSC, MSc 18

19. Pathogenesis...
* Initial IgM followed by IgG in 2 wks- 6 mths
+ The first baby might not be affected

* Memory B lymphocytes activate immune response in subsequent
pregnancy
+ (Once produced, maternal antibodies remain permanent)

* IgG Ab cross placenta and attach to fetal RBC’s

* Cells then sequestered by macrophages in fetal spleen where they get

hemolyzed

20. Differences between IgM and IgG antibodies

IgM (Saline Agglutinin) IgG (Albumin Agglutinin)
First to appear Late to appear

Larger Smaller

Can not cross placenta Can cross placenta

Harmless to fetus Harmful to fetus

21. Factors protective against Rh isoimmunization

+» Inborn inability to respond to Rh antigen
* Variation in strength of Rh antigenic stimulation
* Less than 0.1 mL of fetal blood entering mother

+ ABO incompatibility

23/2023 DAJANE N.{BSc, MSc

22. Rh alloimmunization: Diagnosis

The essentials of diagnosis are the following:
+ The mother must be Rh negative.

* Presence of maternal Rh antibodies as shown by a positive indirect

Coomb test on the mother’s blood.

23. Rh alloimmunization: Diagnosis

+ Maternal antibody titre posing risk to the fetus.
« History of birth of a previous affected baby.

* Fetal cord blood at birth showing the presence of Rh factor, the

presence of antibodies on the fetal cells (direct Coomb test positive)

24. Complications

* Hemolytic disease of the newborn is occurrence of progressive
anemia and hyperbilirubinemia in a newborn caused by haemolysis of

red blood cells, in most cases antibody mediated

25. Complications

QErythroblastosis fetalis is the condition in which large numbers of
nucleated red cells are seen in the fetal circulation, occurring in

response to excessive destruction of fetal red blood cells

26. Complications: Hydrops fetalis

+ It is a most serious condition

* is generalized edema in the fetus and collection of serous fluid in body
cavities of the fetus resulting from a variety of pathologic conditions

(immune hydrops and non immune hydrops).

*is due to excessive destruction of fetal RBCs leading to severe

anaemia and tissue anoxia.

27. Complications: Hydrops fetalis

+ Latter causes liver damage and hypoproteinemia which in turn results

in generalized oedema (hydrops fetalis).

* Tissue anoxia will also have adverse effect on fetal heart (induces
failure), fetal brain (leads to asphyxia) and placenta (causes
hyperplasia — hyperplacentosis).

» Fetal death is usually due to cardiac failure or fetus will be born alive

only to die.

28. Hydrops fetalis
= Diagnostic features
+ Maternal indirect Coombs test positive
+ Polyhydramnios
+ Buddha'sign on ultrasound (due to fetal ascites and scalp oedema
looking like halo around the head)
+ Pale oedematous baby
+ Pale and large oedematous placenta

29. "Fetal hydrops is easily diagnosed by the characteristic appearance of
one or more of the following:
* Ascites
+ pleural effusion
+ pericardial effusion, or

+ skin edema

30. Complications: Icterus gravis neonatorum

» Is due haemolysis
+ The fetus is born alive without jaundice but develops it within 24 hr

* Usually, there is no jaundice at birth because unconjugated bilirubin is
transferred to mother through placenta, some enter amniotic fluid

through skin and lungs.

31. Complications: Icterus gravis neonatorum

+ When bilirubin is more than 20 mg/100 mL, it crosses blood-brain
barrier and damages basal nuclei giving rise to a condition called

“Kernicterus”.

32. Complications: Congenital anaemia

» Is the mildest form of disease due to slow haemolysis.
+ Jaundice is NOT evident.

* Destruction continues up to about 6 weeks, then antibodies are not

available for haemolysis.

33. Complications: Congenital anaemia

+ Nonimmune hydrops fetalis can result from maternal infection
y parvovirus 19, which is associated with transplacental transmission
in almost 33% cases
+ Hydrops fetalis results from fetal aplastic anaemia, myocarditis or

chronic liver failure.

+ It is not likely to affect the fetus 8 weeks after infection.

34. Management

* On the first prenatal visit, all pregnant women should be screened for the Rh
group.

* Possible outcomes will be either Rh- positive or negative.

+ Ifthe mother is Rh-negative, determine the Rh factor of the father of the baby.

+ If her husband’s Rh factor is negative and the mother has not had history of blood

transfusion, no need of further action

+ If the mother is Rh positive and has not had history of blood transfusion , there is

also no need of further action

35. Management...

If the mother is Rh-negative, partner Rh-positive determine indirect
comb’s test for antibody screening.
* Possible outcomes of indirect comb’s test will be either

+ Rh-negative with -ve antibody screen (unsensitized)

+ Rh-negative with +ve antibody screen(sensitized)

36. Management...
Management of unsensitized mother
* Determine indirect comb’ test at 28wks.
» If the test is negative:
+ Provide antepartum prophylaxis with 300ug of anti-D at 28wks.

+ Unless the father of the baby is known to be Rh-negative, all Rh-

negative mothers should receive prophylaxis

37. Management....

Management of unsensitized mother

* Following delivery, determine the blood group of the neonate from the

umbilical cord blood

» Anti-D immunoglobulin administered if the cord blood group is Rh
positive.
* The anti-D administration should not be delayed (as soon as possible within

72)

» Injection of anti-D is given IM— deltoid muscle

NE

38. Management...

Management of unsensitized mother
* Determine indirect comb’ test at 28wks.
+ If the test is negative:
+ Provide antepartum prophylaxis with 300ug of anti-D at 28wks.

+ Unless the father of the baby is known to be Rh-negative, all Rh-

negative mothers should receive prophylaxis

39. Management...

Management of unsensitized mother

* Following delivery, determine the blood group of the neonate from the

umbilical cord blood
» Anti-D immunoglobulin administered if the cord blood group is Rh positive.
+ The anti-D administration should not be delayed (as soon as possible within 72)

+ Injection of anti-D is given IM— deltoid muscle

40. Management
Does every Rh -ve women who delivered Rh +ve baby develop Rh isoimmunization if
not given anti-D Ig prophylaxis? ... No.
+ Without anti-D Ig prophylaxis, an Rh-ve woman delivered of an Rh +ve, newborn has
only a 16% (13% on gabbe 7th ed.) likelihood of developing alloimmunization.
+ 2% will become sensitized by the time of delivery,
+ 7 % by 6 months postpartum,
*7 % will be “sensibilized”—producing detectable antibodies only in a subsequent
pregnancy

+ With immunoprophylaxis, at 28% wks and postpartum the alloimmunization risk may be

reduced to <0.2 % (0.1 - 0.3%)

41. Management ...
Management of sensitized mother
+ Should referred to tertiary health care facility(preconception and prenatal time)
+ Should need special ANC care type with additional ANC contact:
+ Measurements anemia level at regular interval
+ Amniocentesis for bilirubin level

+ Serial U/S— for detections of hydrops and hyperbilirubinemia

42. ABO incompatibility

+ It occurs when the mother has O blood group and fetus with A, B &AB blood
group.

* Unlike RH isoimmunization, 40-50% of ABO incompatibility occur in the first

born infant

* The destruction of red cells of the fetus is much less severe than with Rh
incompatibility

+ ABO incompatibility is also thought to protect the fetus from Rh isoimmunization
as the mothers anti-A and anti-B antibodies destroy fetal red blood cells that leak
into the maternal circulation before Rh sensitization can proceed to a significant

extent.

43. 9/23/2023

GALATOOMAA!!!

DAJANE N.(BSc, MSc)