BB Lecture 11 - Hemolytic Disease of the Fetus and Newborn (HDFN)

Incompatibility of maternal antibodies towards fetal RBCs

What is the definition of HDFN?

➢ Maternal Ab(s) destroy fetal RBCs, the medical condition called Erythroblastosis Fetalis (EF)

➢ This disease occurs both in-utero & ex-utero

Characteristics of HDFN

Fetal RBCs (that leak out into the mother's blood system) have antigen(s) that are foreign to the mother that results in the stimulation of maternal antibody(ies) production

Cause of HDFN

IgG abs; because they can cross the placental barrier

What antibody class are of concern in reference to HDFN? Why?

develops a condition called Hydrops Fetalis (HF) that includes general anemia, possible edema, possible cardiac failure, & up to fetal death

What are the effects of EF towards the fetus?

➢ In-utero / Prepartum (Early)

➢ Postpartum (Late)

What are the two conditions of HDFN

ABO

Rh

"Other"

What are the 3 classifications of HDFN?

- Caused by mother ABO incompatibility with baby

(e.g., Mother type O & Baby type A)

most common

Under the ABO classification of HDFN, what occurs to cause the disease?

- anti-D usually or may be accompanied by other Rh antibodies =>

(anti-C, -c, -E, or -e)

common

Under the Rh classification of HDFN, what occurs to cause the disease?

- unexpected immune antibodies other than Rh =>

(Jk, K, Fy, S, etc).

rare

Under the "other" classification of HDFN, what occurs to cause the disease?

➢ Disease ranges from mild to severe

➢ Over half of the maternal cases that develop this antibody are caused by previous multiple blood transfusions

➢ Is the second most common form of severe HDFN

What are the characteristics of HDFN in reference to Anti-K?

❑ Fetal Severe Anemia

❑ Fetal Heart Failure

❑ Fetal Death

What are the dangers of HDFN in-utero/prepartum?

Maternal Ab attacks fetal RBCs causing fetal anemia and Hydrops Fetalis (HF) can develop.

HDFN in-utero/prepatum mechanism of disease

Unconjugated/indirect bilirubin is related into the fetal body

What is released in HDFN in-utero/prepartum as a result of destroyed RBCs?

Mother's liver

Where is unconjugated/indirect bilirubin sequestered out?

Repeat at 24 weeks

Maternal prenatal care/Testing:

If Ab screen is negative, what do you do?

Perform Ab ID and Ab Titer

Maternal prenatal care/Testing:

If Ab screen is positive, what do you do?

➢ Retain all maternal samples

➢ Periodically, perform Ab titer to check for increase in titration (> 1:32 is significant); Must run previous titer sample in parallel with current titer sample

Maternal prenatal care testing:

Under a positive antibody screen, if the Ab identified is IgG, what do you do?

More antibodies, making the baby high risk for HDFN

Maternal prenatal care testing:

An increase in maternal Ab titration could mean what?

Physician may test amniocentesis fluid for presence of ag (aminocytes)

What is tested if the maternal serum Ab titer is high?

Amniocentesis is performed on mother at 18-20 weeks gestation

Based on maternal Ab titer results and SUSPECTED HDFN, what is performed on the mother and at one point during the pregnancy?

Amniotic fluid bilirubin

What is the direct indicator of severity of HDFN?

Bilirubin levels

If ∆ OD increases at a later scan, what is increasing?

When one or more of the following conditions exist:

- MCA-PSV

- Fetal hydrops detected on ultrasound

- Fetal Hgb level is less than 10 g/dL (Severe anemia)

- Amniotic fluid ∆OD 450 nm results are high (hyperbilirubinemia)

When does intrauterine transfusion become necessary?

❑ RBCs

➢ less than 5 days old

➢ CPDA-1 or AS-3 (lacks mannitol which is a diuretic; do not give diuretics to a

neonate)

➢ Ag negative to a corresponding maternal allo Ab(s), if present

❑ O Neg

❑ CMV neg, if tested OR product is leuko-reduced

❑ Hgb S negative

❑ Irradiated

Intrauterine blood always uses:

❑ Anemia

❑ Hepatomegaly

❑ Splenomegaly

❑ Jaundice

❑ Kernicterus

What are the signs and symptoms that can be seen as maternal antibodies continue to destroy fetal RBCs postpartum?

Neonate's immature liver cannot conjugate bilirubin efficiently; therefore, an accumulation of neonatal unconjugated / indirect bilirubin (which is toxic) occurs

Why is there jaundice in postpartum HDFN?

Untreated accumulation of unconjugated bilirubin can lead to kernicterus that can cause severe retardation; if further left untreated, fetal demise

In postpartum HDFN, what does untreated accumulation of unconjugated bilirubin lead to? What can this cause?

- Phototherapy

- Exchange transfusion

What are the two treatments for neonatal hyperbilirubinemia?

Used to change the unconjugated/indirect bilirubin to isomers which are less lipophilic and less toxic to the brain

Why is phototherapy used for treating neonatal hyperbilirubinemia?

ABO HDFN

What is the most common form of HDFN?

"O" Mother delivering an "A" neonate

ABO HDFN is commonly seen in what type of mothers delivering what type of babies?

ABO HDFN

Which is LESS severe:

ABO HDFN or Rh HDFN

Mother

➢ Repeat ABO / Rh and ABS (usually performed at hospital admission prior to delivery)

Baby

➢ Determine ABO / Rh (including weak D)

➢ Perform DAT

Cord Blood Workup:

List is what is tested for the mother and the baby.

elution

In the cord blood workup, if the baby IgG DAT is positive, what may be preformed?

A1 and B cells

When performing the DAT for the baby, what is the equate tested against to determine ABO HDFN?

because of the large amount of blood needed to perform the elution.

Removing too much blood for lab tests can cause a condition called, iatrogenic anemia

Why do some hospitals NOT perform an elution on the baby RBCs?

Phototherapy

What is the choice of therapy for ABO HDFN?

Can occur at 1st delivery and subsequent pregnancies, no prior exposure needed

ABO HDFN affects what pregnancies?

Rh HDFN

What is the most severe form of HDFN?

Only the 2nd or subsequent pregnancies

What pregnancy does Rh HDFN affect?

Severe anemia resulting in severe hyperbilirubinemia

Kernicterus

What can results of Rh HDFN?

In parallel with the current sample and the last sample that you titered

Ex) If mom had 5 samples, tube 5 and tube 4 as used

When dealing with maternal cases for Ab titers, what must you perform the titers in?

Anti-D: most common form

Anti-E: mild disease

Anti-c: mild to severe

Anti-e: rare

Anti-C: rare

Rank the Rh antibodies in relation to the severity of HDFN.

➢ ABO & Rh including Du test

➢ ABS

What is the mother tested for under Rh HDFN lab testing?

➢ Ab ID & Ab Titer

➢ Ag status of the father, optional

➢ Ig subclass of the maternal Ab, if indicated

If AB screen is positive in testing for the mother under Rh HDFN lab testing, what is determined next?

MCA-PSV

Amniocentesis

If anti-D titer reaches >1:32 in Rh HDFN lab testing, what further testing is considered?

Ab ID procedure

In the cord blood work up for Rh HDFN, if the Ab screen is positive in the mother, what must be done?

❑ Determine ABO / Rh (including weak D)

❑ Perform DAT

In cord blood work up for Rh HDFN, what must be performed and determined for the baby?

Fetal Hgb Screen Test/Rosette Test

demonstrates small number of D-positive cells in mother's D-negative cell suspension.

➢ Blood sample from mother treated with acid, then stained

➢ Fetal cells are resistant to acid; mother's RBCs become "ghost

cells"

➢ Determine # of fetal cells in first 2,000 maternal cells counted

➢ Volume of fetal cells = # of fetal cells x maternal blood volume divided by 2,000

Kleihauer-Betke (KB) Test characteristics

Rh(D)

Spherocytosis is rare in which HDFN: Rh(D) or ABO

after birth

When does exchange transfusion occur?

When phototherapy is unsuccessful in reducing the rise of the bilirubin level and hyperbilirubinemia from unconjugated / indirect bilirubin is still present

Why is exchange transfusion considered the second choice of treatment?

➢ Hgb < 10 g / dL

➢ Bilirubin level is ≥ 20 mg / dL

What conditions must exist when exchange transfusion can occur?

Umbilical cord entry

Extremities entry

What entry ways can transfusion occur depending on the age of the newborn?

➢ < 5 day old

➢ CPDA-1 or AS-3

➢ RBCs must also be ag negative to a corresponding allo Ab present

➢ O negative

➢ CMV negative, if tested OR product is leuko-reduced

➢ Hgb S negative

➢ Irradiated

- Plasma must be "AB"

RBCs for the exchange transfusion must be:

1. Removes 50% of the bilirubin

2. Removes 80-90% of the infant's sensitized RBCs

3. Removes 80-90% maternal incompatible antibody

4. Replacement of incompatible RBCs with compatible RBCs

What are the beneficial effects of a 2-volume exchange transfusion? (4)

- any clinically significant hemodynamic shifts

- any metabolic abnormalities

In exchange transfusion that involve extremities entry, what do we want to avoid?

Administration of an antepartum Rh Immune Globulin shot

In a positive Ab screen of the mother under cord blood, what causes a weak anti-D to be present?

"Passive" anti-D

If a weak anti-D Ab is due to the Rh Immune Globulin shot, what should you report the presence of anti-D as?

fetal MCA-PSV with color doppler ultrasonography

What measurement can predict anemia in the fetus?

The concentration of bilirubin pigment in the amniotic fluid measured by OD 450 nm

What predicts worsening of the fetal hemolytic disease?