Hemolytic Disease of the Fetus and Newborn

Question 1

What is the name of the disorder in which the fetal and newborn red cells are destroyed by maternal IgG antibodies?

Answer 1

HDFN

Question 2

What term is used for the escape of fetal cells into the maternal circulation (usually during delivery)?

Answer 2

Fetomaternal hemorrhage

Question 3

Other than during delivery, when else can fetomaternal hemorrhage occur?

Answer 3

After amniocentesis
Abortion (spontaneous or induced)
Cordocentesis
Ectopic pregnancy
Abdominal trauma

Question 4

What is the most common cause of fetal maternal hemorrhage?

Answer 4

The separation of the placenta at birth

Question 5

Where does red cell destruction occur in the fetus in HDFN cases?

Answer 5

In the fetal liver and spleen by macrophages

Question 6

What does hemoglobin released from damaged red cells get metabolized into by the fetus in cases of HDFN?

Answer 6

Indirect bilirubin

Question 7

What is the pathway that indirect bilirubin goes from the fetus to the mom in cases of HDFN?

Answer 7

It gets transported across the placenta, conjugated by the maternal liver, and then is harmlessly excreted by the mother

Question 8

What happens to the fetus as HDFN progresses?

Answer 8

The fetus becomes increasingly anemic as RBC destruction continues. It’s liver and spleen enlarge as erythropoiesis increases to compensate for the RBC destruction and immature RBCs are released into fetal circulation. Left untreated, the fetus may suffer cardiac failure and/or Hydrops Fetalis

Question 9

What happens to an HDFN baby after delivery?

Answer 9

More indirect bilirubin gets released and because the newborn liver is deficient in the liver enzymes needed to conjugate indirect bilirubin (glucuronyl transferase), it binds to albumin instead and circulates harmlessly (only if a small amount of bilirubin is released).

Question 10

What can happen to an HDFN baby that makes more bilirubin and exceeds albumin binding capacity?

Answer 10

The indirect bilirubin instead binds to tissues and causes jaundice. This can include CNS tissues which can cause permanent brain damage (kernicterus) and can possibly result in death.

Question 11

What is the main difference in the effect of HDFN on a fetus compared to a newborn?

Answer 11

Bilirubin metabolism: before delivery, the mother can excrete the bilirubin but after delivery the baby has to excrete it.

Question 12

What 3 important factors must be present for HDFN to occur?

Answer 12

1. The red cell antibody produced by the mother must be IgG and capable of crossing the placental barrier
2. The fetus must possess the antigen that is lacking in the mother
3. The antigen must be well developed at birth

Question 13

What are the three categories of HDFN?

Answer 13

Rh (D)
ABO
OBG

Question 14

When do Rh-negative mothers become sensitized to the D antigen?

Answer 14

At delivery during their first pregnancy with a D-positive baby

Question 15

Why might an Rh HDFN newborn need an exchange transfusion?

Answer 15

To reduce bilirubin levels to prevent Kernicterus after delivery

Question 16

What are the 3 explanations as to why ABO HDFN babies show only mild RBC destruction despite high levels of maternal antibodies?

Answer 16

1. Presence of A or B substances in the fetal tissues and secretions can bind or neutralize ABO antibodies
2. Poor development of ABO antigens on fetal or infant red cells
3. Reduced number of A and B antigen sites on fetal or infant red cells

Question 17

Why does ABO HDFN occur more frequently in group A or B babies born to Group O mothers?

Answer 17

The mother likely has -A,B which is an IgG that can cross the placental barrier

Question 18

Which OBG antibodies most commonly cause HDFN?

Answer 18

Anti-c and Anti-K

Question 19

What are the 2 reasons prenatal transfusion testing is done?

Answer 19

1. To identify D-negative women who are candidates for RhIg
2. To identify women with antibodies capable of causing HDFN, which helps to assess the potential risk to the fetus

Question 20

What kind of prenatal transfusion testing is done in the first trimester?

Answer 20

ABO/Rh
Antibody screen
Look at prenatal history (para/gravida)

Question 21

Why is getting a titre of a maternal antibody helpful?

Answer 21

If the antibody is in high concentration or rapidly elevating, the risk to the baby increases

Question 22

What kinds of cells are used to test an antibody titre?

Answer 22

Homozygous and heterozygous antigen positive cells

Question 23

How do you report an antibody titre?

Answer 23

The reciprocal of the highest dilution that gives a 1+ reaction

Question 24

How do you set up an antibody titration?

Answer 24

Add an equivalent volume of saline to tubes 1:2 to 1:256
Add the same volume of serum to tubes 1 and 1:2
Transfer an equivalent volume of serum from the 1:2 tube to the 1:4 tube and so on till the last tube

Question 25

When is an antibody titre significant?

Answer 25

Any positive titre is significant and if it rises by two dilutions or greater, it's a clinically significant change

Question 26

Why would you want to test previously frozen antibody titre samples in parallel with a current specimen?

Answer 26

To ensure that any change in the titer is not the result of technical variables

Question 27

How does an amniotic fluid sample help us assess HDFN?

Answer 27

It's used to quantify bilirubin pigment which reflects the extent of fetal RBC destruction. Can decide how to proceed with the pregnancy based on these results

Question 28

What is plotted on a Lily graph?

Answer 28

Absorbance of bilirubin against gestational age

Question 29

How does a Lily graph help us asses HDFN?

Answer 29

Based on where the value lands on the graph, it tells us the severity of the HDFN. The upper zone of the graph correlates with severe HDFN and fetal death and the lower zone indicates a mildly affected or unaffected fetus. The middle zone correlates with moderate diseases and necessitates repeats testing to establish a trend.

Question 30

How does ultrasound help us assess HDFN?

Answer 30

It helps us determine the degree of fetal anemia. These fetuses have decreased cardiac output, decreased blood viscosity, and thus increased flow velocity (can see this in an ultrasound)

Question 31

What kind of sample is collected by cordocentesis?

Answer 31

A venous blood sample from the umbilical vein

Question 32

What can be tested on a cordocentesis sample in an HDFN investigation?

Answer 32

Fetal hemoglobin ABO/Rh/OBG antigen phenotyping DAT

Question 33

In severe cases of HDFN, what can you use cordocentesis for?

Answer 33

Direct intravascular transfusion to the fetus

Question 34

When could we do fetal genotyping and from what kind of sample?

Answer 34

On maternal plasma during the second trimester

Question 35

What in utero treatment is done for HDFN?

Answer 35

1. Intrauterine transfusion to maintain fetal hemoglobin. Repeated every 2-4 weeks until early delivery can be done. 2. Early delivery when fetal lungs are developed enough (34-36 weeks).

Question 36

What type of product can we issue for an intrauterine transfusion?

Answer 36

Only RBCs

Question 37

What are the steps we use to calculate RhIg dosage?

Answer 37

1) Determine FMH (FMH=65mL) 2) Divide mL of fetal WB in maternal circulation by 30 (65/30=2.2) 3) Add one vial to RhIg to dose for safety margin (2+1=3)

Question 38

Determine the RhIg dosage if the Number of fetal cells counted is 20/2000 using the Kleihauer-Betke Method

Answer 38

Number of fetal cells counted: 20/2000 = 0.01% * 0.01 x 5000= 50 * Divide the mL of Fetal WB by 30 50/30= 1.6 * 1.6 = Round up = 2 doses * Add 1 vial to calculated Dose * Give patient 3 doses in total