Hemolytic Disease of the Newborn

Rh inheritence

- Rh locus on chromosome 1 codes for several antigens, but D antigen is most antigenic - each parents contribute either a D allele at the Rh locus, or not

Bilirubin Encephalopathy

- aka kernicterus - unconjugated bilirubin enters the brain - neurotoxicity

Universal receiver blood group

AB

Why cant Rhogam itself cause HDN

Amount of Rhogam in one vial (300 ug IgG) is INSUFFICIENT to cause the fetus harm. This amount of antibody raises the maternal titer int he indirect Coombs test to <1:4; a titer of Rh antibody that cannot cause significant hemolysis in the fetus

Clinical Symptoms of HDN?

Anemia Jaundice (excessive bilirubin) For infants minimally affected --> pallor, splenomegally For GRAVELY ill infants --> intense jaundice, widespread edema, signs of neurologic involvement *HYDROPS FETALIS)

Hemolytic disease of the newborn

Approximately 85% of the human population carries Rh antigen, which is also found in rhesus monkeys. If an Rh-negative pregnant woman is carrying an Rh-positive fetus, the fetus may be at risk of hemolytic disease of the newborn, in which antibodies made by the mother against the Rh antigen may cross the placenta and destroy the fetus's red blood cells. RhoGAM administered to pregnant Rh- women may prevent this disease.

What ethnic groups are most likely to inherit Rh- ?

Basque, Caucasians

During HDN, why are Rh-negative RBC's used for intrauterine transfusion?

Because they will not be hemolyzed by IgG Rh antibodies that have crossed the placenta already from the mother

How does Rh incompatibility cause maternal antibodies in Rh- mothers carrying Rh + fetus?

During childbirth, fetal RBC may escape into the mother circulation. Once here, they are perceived as foreign and therefore provoke an antibody response. Repeated pregnancies can provoke HIGH antibody titer levels in the mother

When Rh-negative women is ABO compatible w/ her husband, the risk of RH alloimmunization is GREATER than when they are ABP incompatible; why the difference?

If fetal blood is of the same type ABO, then it stands a greater chance once entering the mothers circulation of staying around (b/c it is not hemolyzed by anit A/B antibodies) --> thus it stands a longer chance of inducing anti-Rh antibodies.

What type of maternal anti-Rh Ig type can cross the fetus?

IgG

What would bilirubin levels be in a case of HDN?

Increasing amounts

What Coombs test would signify alloimmunized mother?

Indirect test > 1.4

What would hematocrit be during HDN if taken from the umbilical vein?

LOW

Universal done blood group

O

How many alleles of the Rh locus need to be present for a Rh+ person>

Only one --> it is a dominant gene

Women of what Rh type are at risk of having this HDN?

Rh- mothers, giving birth to Rh+ children

What drug is given to prevent this?

Rhogam is given to the Rh- mother

Hydrops fetalis

heart failure and generalized edema in the fetus secondary to severe anemia resulting from destruction of erythrocytes

Coombs test

lab test to identify antibodies on the RBC's; a direct Coomb's test determines if there are maternal anti-Rh antibodies in the fetal cord blood, while an indirect Coombs identifies anti-Rh antibodies in the mothers blood.

Why does Rhogam work?

prevents mother B cell activation & memory cell formation

Rhogam

sterile preparation of IgG specific for the D blood group antigen, manufactured from human plasma, RhoGam prevents the development of maternal RH antibodies. 2. RhoGam is given to Rh-negative mothers who have an Rh-positive fetus and who have not developed antibodies to Rh factor. 3. It is also given to Rh-negative women who have abortions or miscarriages even if the Rh factor of the fetus is not known. 4. RhoGam must be given within 72 hours of delivery or abortion. 5. RhoGam is also given at 28 weeks gestation.

Why does ABO blood group antigens not cause HDN (generally - it can occur in some rare cases)

1. Most anti- ABO antibodies are IgM, and they do not cross the placenta 2. Fetal RBCs do not express high levels of A or B 3. Many other cells express A and B antigens, and "sop op" transferred antibodies