HDFN

Question 1

How does Rhogam help to prevent the mother from making the anti-D antibody?

Answer 1

Rhogam contains anti-D which attaches to any fetal Rh positive RBCs in maternal circulation so the mother cannot be sensitized to them.

Question 2

Why does Rh HDFN not usually affect the first pregnancy?

Answer 2

Many times the exposure to the D+ cells happens at birth. If it happens earlier, the initial antibodies produced by the mother are IgM and cannot cross the placenta to cause HDFN.

Question 3

What is Erythroblastosis fetalis?

Answer 3

Anemia stimulates the bone marrow to produce RBCs at an accelerated rate. The release of immature red cells into circulation is referred to as Erythroblastosis fetalis.

Question 4

What is Hydrops fetalis (or fetal hydrops)?

Answer 4

Since the bone marrow can’t produce red cells fast enough, the spleen and liver also increase RBC formation in hematopoietic tissues causing them to become enlarged. This leads to Hydrops fetalis which is an abnormal accumulation of fluid causing swelling including edema (fluid beneath the skin), ascites (fluid in the abdomen), and effusion (fluid around the lungs).

Question 5

Describe the pathogenesis of hemolytic disease of the newborn from attachment of maternal antibody to fetal red cells to Hydrops fetalis.

Answer 5

Maternal IgG anti-D antibody crosses the placenta to the fetus and attaches to Rh(D)+ fetal red cells. The red cells are destroyed at an accelerated rate and the bone marrow attempts to produce more red cells at a faster rate. This causes the bone marrow to release immature red cells into circulation (erythroblastosis fetalis). Since the bone marrow can’t keep up, the liver and spleen also increase RBC production causing them to become enlarged. This leads to swelling and accumulation of fluid found in Hydrops fetalis.

Question 6

How long will destruction of infant red cells continue after birth?

Answer 6

It will continue as long as maternal antibody persists. This is usually a couple weeks after birth since the half-life of IgG is 25 days.

Question 7

What is kernicterus and why does it occur?

Answer 7

Kernicterus is toxic levels of bilirubin accumulation in the newborn’s brain. This occurs after birth. Before birth, the mother’s liver was removing the baby’s bilirubin from circulation. The newborn liver however, cannot conjugate bilirubin effectively causing it to accumulate in the newborn.

Question 8

What factors affect the immunization and severity of HDFN?

Answer 8

Antigenic exposure, host factors, immunoglobulin class, antibody specificity, and influence of ABO group

Question 9

What are some situations during which a mother may be exposed to fetal red cells?

Answer 9

Amniocentesis, cordocentesis, trauma to abdomen, birth

Question 10

Which subclasses of IgG are most efficient at hemolysis and therefore most likely to cause HDFN?

Answer 10

IgG1 and IgG3

Question 11

Which antibody is most clinically significant in HDFN after the D antibody? Why?

Answer 11

Anti-K. The K antigen is found on all precursor red cells as well as mature red cells. Therefore, not only are mature red cells being destroyed, but the immature red cells are also destroyed.

Question 12

Why is a mother who has an ABO incompatible fetus less likely to experience D immunization?

Answer 12

ABO incompatible red cells are destroyed in the mother’s circulation before the D antigen can be recognized. There is therefore not enough time for sensitization to the D antigen to occur.

Question 13

What blood type of the mother is the most likely to cause ABO HDFN? Why?

Answer 13

It is usually group O mothers because they make the antibody anti-A,B which is the only ABO antibody that is usually an IgG antibody that can cross the placenta.

Question 14

What antibody is the most common cause of HDFN since Rhogam?

Answer 14

ABO

Question 15

What are the common symptoms of ABO HDFN in the newborn?

Answer 15

Hyperbilirubinemia and jaundice 12-48 hours after birth. Rarely severe anemia

Question 16

Describe how Rh HDFN differs from ABO HDFN.

Answer 16

ABO affects the 1st pregnancy, Rh the 2nd. Rh can be predicted by titers, ABO cannot. Bilirubin at birth is normal for ABO and elevated for Rh. There is no anemia at birth for ABO, there is for RH. Exchange transfusions and intrauterine transfusions are usually only used for Rh HDFN.

Question 17

What testing is performed on a pregnant mother?

Answer 17

ABO, Rh, antibody screen, weak D if Rh negative, antibody titer if antibody screen is positive

Question 18

What is the purpose of an antibody titer and when is it performed?

Answer 18

It determines the concentration of antibodies that is able to cross the placenta. It is performed each month during pregnancy to determine if the concentration of the antibody is increasing (suggesting the baby is positive for the antigen).

Question 19

How often should titers be performed?

Answer 19

Once a month

Question 20

At what point is a titer considered critical?

Answer 20

A titer of 16 is critical or an increase of 2 dilutions in one month

Question 21

What additional information can be gained by phenotyping the father for the antigens the mother has an antibody to?

Answer 21

If the father is also negative, the fetus must be negative as well and HDFN is not a concern. If the father is positive, then there is a possibility the fetus is also positive for the antigen.

Question 22

What does the MCA-PSV test determine and when would it be performed?

Answer 22

Predicts anemia in the fetus by detecting blood flow in the brain. It should be performed at 16-20 weeks if anemia is suspected.

Question 23

What additional information is gained by performing a cordocentesis?

Answer 23

Blood can be taken from the umbilical cord and tested for hemoglobin, hematocrit, bilirubin, ABORh, DAT, and antigen phenotypes

Question 24

What additional information is gained by performing an amniocentesis?

Answer 24

Measures concentration of bilirubin pigment in amniotic fluid estimating the extent of fetal hemolysis (really same information as MCA-PSV which is less invasive)

Question 25

What are the indications that it is necessary to perform an intrauterine transfusion?

Answer 25

MCA-PSV indicates anemia, Fetal hydrops noted on ultrasound, cordocentesis sample has a hemoglobin of <10g/dL, amniotic fluid results are high.

Question 26

How often are intrauterine transfusions performed?

Answer 26

When determined they are needed, they should be performed every 2-4 weeks until delivery.

Question 27

What type of red cells are transfused during intrauterine transfusions?

Answer 27

O negative RBCs, <7 days old, CMV negative Hgb S negative, antigen negative for maternal antibody, irradiated

Question 28

What information will performing a DAT and eluate on the cord blood give you about the newborn?

Answer 28

If the DAT is positive, this suggests that maternal antibody is coating the fetal red cells, the eluate can then determine what specific antibody is coating the fetal red cells.

Question 29

What different treatment options exist for newborns suffering from HDFN?

Answer 29

Phototherapy, transfusion, IVIG, exchange transfusion

Question 30

How does phototherapy help treat HDFN?

Answer 30

The fluorescent light is absorbed by the baby’s skin which converts unconjugated bilirubin to isomers that are less toxic to the brain and more easily excreted.

Question 31

How does IVIG work to treat HDFN?

Answer 31

IVIG will block the FC receptors on phagocytes so they can’t bind the antibody that is coating the fetal red cells and are therefore unable to destroy the red cells. This helps treat hyperbilirubinemia of the newborn.

Question 32

What are the benefits to the newborn of performing an exchange transfusion?

Answer 32

By replacing circulating blood, the high levels of unconjugated bilirubin are being removed which will prevent kernicterus. This also removes maternal antibodies and sensitized cells and replaces incompatible fetal cells with compatible ones that maternal antibody will not bind to.

Question 33

At what point of fetal life is the mother first given Rhogam?

Answer 33

28 weeks

Question 34

When is the second dose of Rhogam given (assuming the mother does not experience any trauma after the first dose)?

Answer 34

Given after birth within 72 hours

Question 35

What Rh type are mothers that receive Rhogam?

Answer 35

Rh negative

Question 36

Is there any benefit in giving a mother Rhogam that has already made an anti-D?

Answer 36

No, the purpose of Rhogam is to prevent the formation of anti-D. If anti-D is already formed, the Rhogam will not be helpful.

Question 37

How much anti-D is one dose of Rhogam?

Answer 37

300µg of anti-D (enough to protect against 15 mL of packed cells or 30 mL of whole blood)

Question 38

One dose of Rhogam will protect against what amount packed red cells and whole blood?

Answer 38

15 mL of packed red cells and 30 mL of whole blood

Question 39

What information is obtained from the Rosette test?

Answer 39

It is a screen to determine if fetal red cells are present in the mother’s circulation

Question 40

What information is obtained from performing a Kleihauer-Betke test?

Answer 40

This test determines how large the bleed is and how many fetal cells are present in the mother’s circulation so that an appropriate amount of Rhogam can be administered.