Rh Isoimmunization

Nor Fayuni Binti Mohd Nozir

2008402458

Definitions• Rhesus : major blood group

antigen of importance during pregnancy. Incompatibility between mother (-) and fetus (+) may led to hemolytic disease of the newborn.

• RhoGAM® : Rh immunoglobulin given to gravidas who are Rh negative if there is suspicion of fetal maternal bleeding for example ~ if there is bleeding during any trimester, after delivery.

• Kleihauer-Betke test : blood test used to measure the amount of fetal hemoglobin transferred from a fetus to an Rh-negative mother's bloodsteram. The results of the test are used to determine the required dose of Rh immune globulin (RhIg) to inhibit formation of Rh antibodies in the mother and prevent Rh disease in future Rh-positive children.

Continued…• Rhesus isoimmunization occurs

when a maternal antibody response is mounted against fetal red blood cells.

• These IgG antibodies cross the placenta and cause fetal red blood cell destruction.

• The ensuing anemia, if severe, precipitates fetal hydrops which is often referred to as immune hydrops.

Incidence & prevalence• Incidence

– varies based on prevalance of RBC antigen in different population

• Prevalence(varies with race)– Asian 99% D-positive (either DD & Dd

genotype)– African american 92-93%– White american 87%

• Incidence higher in white due to relatively higher percentage of the population who do not carry the D-antigen on their RBC. Hence, more Rh-negative mother (dd)

How do fetal cell gain access to maternal circulation?• Disruption of usually intact feto-maternal

blood barrier (the placenta villus) & leakage fetal cells into maternal bloodstream. Thus, leading to maternal antibody formation against non-self antigen on the fetal RBCs)

• Mechanism this occurs– Placenta previae– Placenta abruptio– Spontaneous/induced abortion– Amniocetesis– Trauma – multiple pregnancy, normal delivery

Pathophysiology• Fetal cells cross into the

maternal circulation in normal pregnancy; the amount is increased during particular ‘sensitizing events’.

• The fetus may carry the gene for an antigen which the mother does not have-with rhesus D, the fetus may be Dd whilst the mother is dd.

Continued… (sensitization)• Individuals exposed to a ‘foreign’

antigen mount an immune response; initially this is IgM, which cannot cross the placenta so the pregnancy is not at risk.

• Re-exposure in a subsequent pregnancy causes the primed memory B cells produce IgG, which actively crosses into fetal circulation.

Effect of the mother’s Ab to the fetus• After anti-Rh antibodies formed

in the mother, they diffuse slowly through the placental membrane into the fetus’s blood and cause agglutination of the fetus’s blood.

• The agglutinated RBC subsequently hemolyze, releasing hb into the blood.

• The fetus macrophages then convert the hb into bilirubin, which cause the baby skin to become yellow/ jaundiced.

• The ab can also attack and damaged the other cells of the body.

Effect of the mother’s Ab to the fetus• The jaundiced or erythroblastosis newborn

baby is usually anemic at birth• The anti Rh ab from the mother usually

circulate in the infant blood for another 1 to 2 months after birth, destroying more and more RBC

• The hematopoietic tissues of the infant attempt to replace the hemolyzed RBC.

• The liver and spleen become greatly enlarged and produced RBC in the same manner that they normally produced during the middle of gestation.

• Because of rapid production of RBC, many early forms of RBC passed from the baby’s bone marrow into the circulatory system and because of the presence of these nucleated blastic RBC the disease is called erythroblastosis fetalis

Continued…• Although severe anemia of the

erythroblastosis fetalis is usully the cause of the death, many children who barely survive the anemia exhibit permanent mental impairment or damage to the motor areas of the brain because of precipitation of bilirubin in neuronal cells.

1st pregnancy

1st pregnancy

2nd pregnancy

Effects on the fetus & neonate• Hemolytic anemia• Numerous erythroblast in fetal

circulation• Generalized edema (hydrops

fetalis)• Enlargement of fetal liver &

spleen in its most severe form• Severity of the anemia resulted

in cardiac failure, with widespread edema, ascites and pleural effusion.

Hydrops Fetalis

Antibody formation & detection• When the fetal cells enter and persist in

the maternal circulation two antibodies are formed:

1. Saline antibody (IgM) --- generally appears seven days after stimulation, it is large molecule and does not cross the placenta.

2. Albumin antibody (IgG) ---formed 21 days after stimulation, it is small molecules and crosses the placenta easily and attack the Rhesus positive red cell of the baby.

Antibody formation & detection• Kleihauer-Betke test

–Estimate the presence of fetal red cells in the mother’s circulation and the dose of the anti Rhesus antibody will be adjusted accordingly.

– It depends on the fact that fetal hemoglobin is more resistant than adult’s hemoglobin to the acid elution.

Antibody formation & detection• Coomb’s test– The DIRECT test is used to an

affected fetus at birth. Cells from cord blood are suspended with the reagent and if the baby is affected( has maternal antibody attached) agglutination will occur.

– The indirect Coombs test is used to screen blood from antenatal women for IgG antibodies that may pass through the placenta and cause hemolytic disease of the newborn.

Management• 1. Rhesus negative without antibodies• (a) First visit: Rhesus group and screening

test for immune antibodies.• (b) Repeat antibody check monthly from

24 to 36 weeks.• (c) Give anti D immunoglobulin for

complications.• (d) Delivery: Mother's blood — antibody

check and Kleihauer. Cord blood — ABO and Rhesus

group,Haemoglobin,Coombs' test,Bilirubin.• (e) Give anti D if blood negative for

antibodies and baby Rhesus positive. If Kleihauer suggests bleed more than 4 ml, further anti D given.

Management2. Rhesus negative with antibodies• a) First visit — antibody identified and

measured by IAGT and, preferably, direct quantitation of antibody level.

• (b) Antibody test repeated monthly or until management decided on by other investigations e.g. amniocentesis.

• (c) Rhesus genotyping of partner — if heterozygous Rhesus positive the possibility of an unaffected child exists.

• (d) Amniocentesis — the bilirubin level in the liquor, measured by spectrophotometry, is a useful prognostic indicator as it reflects the excretion of bilirubin by the baby and thus the degree of haemolysis

Management• (e) Ultrasound — can detect fetal ascites

and oedema, indicating a severely affected fetus, at a very early stage in the pregnancy, e.g. less than 20 weeks. Such findings indicate the need for fetal blood sampling by cordocentesis.

• (f) Cordocentesis --Blood may be obtained from the fetus in patients with a history of severe early rhesus disease and in those in whom ultrasound has demonstrated ascites. A haematocrit reading is at once available and treatment by direct intravascular transfusion can be given if indicated by the result.

Management• Postnatal

–Phototherapy for neonatal jaundice in mild disease

–Exchange transfusion if the neonate has moderate or severe disease (the blood for transfusion must be less than a week old, Rh negative, ABO compatible with both the fetus and the mother, and be cross matched against the mothers serum)

Prevention • Most Rh disease can be prevented by

treating the mother during pregnancy (28wks & 34 wks) or promptly (within 72 hours) after childbirth. The mother has an intramuscular injection of anti-Rh antibodies (Rho(D) Immune Globulin), so that the fetal Rhesus D positive erythrocytes are destroyed before her immune system can discover them. This is passive immunity and the effect of the immunity will wear off after about 4 to 6 weeks (or longer depending on injected dose) as the anti-Rh antibodies gradually decline to zero in the maternal blood.

• Use of anti-D and smaller family size

Thank you