2. Introduction
• Isoimmunization
• A process by which immune antibodies are
produced in a person by the entry of an
antigen of another individual of same
species, the former lacking the antigen
• Rh-Isoimmunization
• Occurs when there is a different Rh blood
type between that of the pregnant mother
(Rh negative) and that of the fetus (Rh
positive)
3. Rh-antigen
• Discovered by Landsteiner
• Fetal Rh-antigen present on chromosome 1
• Fetal Rh-antigen present at 38th day of conception
• Rhesus blood group comprises 5 antigens:- C,c,D,E & e
• Among all ‘D’ is most antigenic that determine a person as
Rh-negative or positive
4. The placenta usually acts as a barrier to fetal
blood entering the maternal circulation.
5. Fetal cells can enter the maternal circulation
through a “break” in the “placental barrier”
IMMUNIZATION IS UNLIKELY TO OCCUR UNLESS AT LEAST 0.1 ML OF FETAL
BLOOD ENTERS INTO MATERNAL CIRCULATION
6. Causes of RBC Transfer
“A break in the barrier”
Abortion/Ectopic
Pregnancy
Molar pregnancy
Antepartum bleeding
Procedures
Amniocentesis
Cordocentesis
Chorionic villous
sampling
Manual removal of
placenta
External version
Platelet transfusion
Abdominal trauma
Transfusion Rh+ blood
Postpartum
Rh+ve baby
Forceps delivery
Cesarean section
7. • ABO incompatibility has a protective effect in Rh-ve pregnancy
• Red blood cells are easily destroyed, so not reaching enough to cause
antibody response and reaction
Maternal Blood Group- ‘O’ Maternal Blood Group- ‘A’ Maternal Blood Group- ‘AB’
Anti A Anti BAnti B
A+
Anti A
B+
Anti B
A+ B+
Anti B
A+ B+
COMPLETE PROTECTION NO PROTECTIONPARTIAL PROTECTION
8. IGM antibodies
Cleared by
Macrophage
Plasma
stem cells
Fetus
Mother
Placental
Primary Response
•6 wks to 6 M.
•IGM
• Following feto-maternal hemorrhage
• Initial response is forming IgM antibodies for the
short period (6wks-6month)
9. Placenta
Anti - D
Macroph. antigen
Presenting cell
T- helper cell
B cell
Fetal Anaemia
Mother
Secondary Response
•Small amount
•Rapid
•IgG
IgG
• Followed by production of IgG on subsequent
pregnancy which crosses placenta
• IgGantibodies adhere to the antigen site on the
surface of erythrocytes causing hemolysis.
10.
11. IgG antibody against Rh-antigen
Cross the placenta
Fetal RBCs have Rh-antigen
Antigen-Antibody reaction
Fetal RBC destroyed
Anemia in fetus Hepatosplenomegaly Jaundice Placentomegaly
12. Clinical Manifestations
Hydrops Fetalis Icterus Gravis Neonatorum Congenital Anemia
• Most serious
complication of rh-ve
pregnancy
• Fetal death occurs sooner
or later due to cardiac
failure
• Effect of lesser form of
fetal hemolysis
• Baby born alive without
evidence of jaundice
• Soon develops jaundice
within 24 hour
• Mildest form of disease
• Where hemolysis is going
at slow rate
• Develops slowly within 1st
few week of life
• Destruction of red cells
occurs upto 6 weeks after
which antibodies are not
available for destruction
• Liver and spleen are
enlarged
13. Hydrops Fetalis
Excessive destruction of fetal red cells
Severe Anemia
Tissue Anoxemia & Metabolic Acidosis
Effect on Placenta, Brain and Heart
Compensatory hyperplasia of placenta to increase transfer of oxygen
Extramedullary
Hematopoesis
Hepatic Dysfunction
Hypoprotinemia
Generalized Oedema
Hydrops Fetalis
HydrothoraxAscitis
14. Features of Hydrops Fetalis
• Sonography(combined with pulse Doppler)
• Oedema in skin and scalp
• Pleural effusion
• Pericardial effusion
• Echogenic bowel
• Baby at birth
• Pale
• Oedematous
• Enlarge abdomen due to ascitis
• Placenta
• Large,Pale,Edematous with fluid oozing from it
• Increase weight may be equal to fetal weight
• Swelling of villi
15.
16. Icterus gravis neonatorum
Jaundice don’t occur before delivery because bilirubin produced
by the destruction of cells in the fetal spleen passes via placenta to
maternal circulation and then to maternal liver from where it is
conjugated by glucronyl transferase and excreted
Liver of neonate don’t produce glucronyl transferase and
cant convert bilirubin t an excretable form, consequently
bilirubin accumulates in tissues causing jaundice and brain
tissue damage
17. Kernicterus
• If the Concentration of bilirubin in the newborn blood
exceeds 20mg/100ml
• Billirubin crosses the BBB and damage the basal
nuclei of brain
• Signs of kernicterus
• Poor suck, lethargy, hypotonia and seizures
• Then hypertonia and fever
18. Effects on Mother
Rh isoimmunization is suspected in utero when mother develops:
• Polyhydraminos
• Pre eclampsia
• Maternal syndrome:
• generalized edema
• proteinuria
• pruritus due to cholestasis
• Post partum hemorrhage: big placenta and blood coagulopathy
• DIC: retention of dead fetus in utero
19. Fetomaternal hemorrhage as a reason of
Rh–isoimmunization has been documented in:
• 5% in the first trimester.
• 13.9% in the second trimester
• 29% in the third trimester
• Highest at the time of delivery
20. PreventionAim:-
• To prevent active immunization
• To prevent fetomaternal bleed
• To avoid mismatched transfusion
• To prevent active immunization of unimmunized, Rh anti-D immunoglobulin(IgG) administered IM to mother
following child birth
• Anti-D is also given in other condition associated with fetomaternal bleed
• Mechanism of action of Anti-D
• Blocks Rh-antigen of fetal cell
• Intact antibody cells are removed by spleen and kidney
• When to administer
• Within 72 hour or earlier following delivery or abortion (in case, can be given upto 14-28 days but not as
effective)
• Given in Rh+ve baby of Rh-ve mother with direct comb test negative
• Similarly if Rh-status can’t be determined, give Anti-D without harm
• Dose
• 1st trimester abortion/MTP- 50 mcg
• 1st trimester ectopic pregnancy- 50 mcg
• 2nd trimester abortion/MTP- 300 mcg
• 2nd trimester amniocentesis- 300 mcg
• Prophylaxis at 28 weeks- 300 mcg
• After delivery- 300 mcg
• Generally 300micrograms of AntiD will protect from 30 ml of fetal blood
21. During pregnancy:-
• Due to antepartum hemorrhage and sensitization(1-2%)
• If mother is Rh-negative and no antibody formed- prophylactic 300mcg of
Anti-D at 28 weeks
To prevent fetomaternal bleed:-
• During CS
• Prevent blood spilling into peritoneum
• Manual removal of placenta should not be done as routine
• Prophylactic ergomatrine should be withheld as may cause more
fetoplacental bleed
• Amniocentesis after localization of placenta by sonography
• Manual removal of placenta should be done gently
22. Calculation of dose:- by Kleihauer Betke test/Acid Elution Test
• Performed on maternal blood to assess amount of fetomaternal bleed
• Principle- HbF is more resistant to acid elution than HbA
• No. of fetal red cells in 50 low power fields is assessed
• 80 cells in 50 fields indicates- 4ml of fetomaternal bleed
• 100 mcg will neutralize 4 ml of fetomaternal bleed is >30 ml then dose is
calculated as 10 mcg/ml
• Alternative method- Flow cytometry-more accurate result
Maternal blood is subjected to acid solution
Acid will elute adult hemoglobin, but not fetal hemoglobin
Dark red- fetal cells, light coloured- maternal red cells