11 HDFN

Hemolytic disease of the fetus & newborn

Definition: Incompatibility of maternal antibody(ies) towards fetal RBCs

the maternal Ab(s) DESTROY fetal RBCs - aka Erythroblastosis Fetalis (EF)

YES

Fetal RBCs (which leak from placenta into mothers blood system) have antigens that the mothers blood recognizes as foreign, and therefore attacks

can be MILD to SEVERE - ranges

IgGs!

- IgGs can CROSS the placenta!
- IgMs are NOT an issue since they're huge

- they develop a condition called Hydrops Fetalis (HF)
- anemia,
- possible edema
- possible cardiac failure
- up to fetal death

a serious condition that causes a buildup of fluid in a fetus or newborn's organs and tissues, resulting in swelling

1. IN-utero / Prepartum (early)
2. POSTpartum (Late)

1. ABO
2. Rh
3. "other"

- It is caused by the mothers ABO incompatiability with baby
- e.g. Mother is O and baby is A - MOST common

- anti-D usually or may may be accompanied by other Rh antibodies => anti-C, -c, -E, or -e; common

- unexpected immune antibodies besides Rh
- like Jk, K, Fy, S, etc
- these are RARE

Usually this occurs: negative mother with positive baby
1st pregnancy - first exposure of Rh+ antigens to mother - she develops Abs
Between pregnancies - Anti-Rh antibodies developed
2nd pregnancy - second expure of Rh+ antigens from baby - mothers anti-Rh antibodies attack the fetus

anti-E, -c, -Kell, -Kidd, or -Duffy

- can be mild to severe
- SECOND most common form of severe HDFN

Over half of them developed anti-K due to previous multiple blood transfusions

anti-D, then anti-D AND others

❑ Fetal Severe Anemia
❑ Fetal Heart Failure
❑ Fetal Death

fetal anemia - due to maternal Ab attacking fetal RBCs

UNCONJUGATED / INDIRECT bilirubin is released into the fetal baby which can be very detrimental to the fetus in high amounts

the liver! - it helps to conjugate bilirubin

The mothers liver helps process the unconjugated biliruben

Prenatal Care

- ABO, Rh (including Du), and ABS tests

❑ If Ab screen negative, repeat at 24 weeks
❑ If Ab screen is positive, perform Ab ID & Ab Titer, if Ab is IgG
➢ 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

The higher the Ab titer, the higher the risk for HDFN

amniocentesis fluid for presence of ag (amniocytes)

Amniocentesis is the procedure of obtaining a sample of amniotic fluid from the womb

amniotic fluid bilirubin is a direct indicator of severity of HDFN

- the fluid is scanned in a spectrophotometer at increasing wavelengths to determine change in OD when 450 nm is reached (absorbance of bilirubin)
- if OD increases at a later scan, bilirubin levels are increasing

a procedure that involves injecting red blood cells from a donor into a fetus to treat anemia or other conditions

❑ MCA-PSV (Middle Cerebral Arterial-Peak Systolic Velocity) indicates anemia when using an Ultrasound Transducer device
❑ Fetal hydrops can be detected on ultrasound examination
❑ Fetal Hgb level is less than 10 g / dL (severe anemia)
❑ Amniotic fluid ∆OD 450 nm results are high (hyperbilirubinemia)

Risks and benefits of intrauterine transfusion must be weighed and evaluated.

❑ RBCs
➢ < 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 (sickle cell)
❑ Irradiated (no cyto T cell rxn)

YES! The antibodies continue postpartum which develops certain signa and symptoms

- Anemia
- hepatomegaly
- splenomegaly
- Jaundice
- Kernicterus

Gross anemia can cause fetal cardiac failure

The newborns immature liver CANT conjugate bilirubin effectively
Before, the mothers blood was able to process it
- an accumulation of unconjugated / indirect bilirubin (TOXIC) occurs leading to jaundice

- a severe condition where there is an untreated buildup of unconjugated bilirubin, which crosses the blood-brain barrier which causes brain damage or fetal death

1. Phototherapy
2. Exchange transfusion

- light wavelength is set at 460 to 490 nm
- unconjugated / indirect bilirubin is sensitive to strong light
- used to change the unconjugated / indirect bilirubin to isomers which are less lipophilic and less toxic to the brain

➢ Hgb is < 10 g / dL
➢ Bilirubin level is ≥ 20 mg / dL

ABO HDFN

NO! This can occur at the FIRST preganancy and pregnancies after

Commonly seen in an "O" mother (with IgG form of Anti-A,B) delivering an "A" neonate; "B" type neonate is less common

It can! Can have mild to moderate jaundice

Usually it is LESS severe than Rh HDFN

it is usually NOT predictive of ABO HDFN Developmnt

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

➢ Determine ABO / Rh (including weak D)
➢ Perform DAT
✓ If baby IgG DAT is positive, may perform elution procedure
✓ To determine ABO HDFN, test eluate against A1 & B cells

- it uses baby RBCs and a supernatant media. The elution is performed using heat or chemical to "dissociate" the Ab off the baby's RBC.
- The Ab is contained in the supernatant media where Ab ID can be performed
- Ab found in eluate is of maternal origin

Some hospitals may not perform an elution on the baby RBCs (for allo Ab ID) 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*, in the patient.

It is NOT preventable (as in Rh0(D) HDFN)

- Hyperbilirubinemia / jaundice is commonely treatable using only phototherapy
- when serum bilirubin result reaches ≥ 20 mg / dL, an exchange transfusion is indicated

Rh HDFN

❑ Severe anemia may occur resulting in severe hyperbilirubinemia / jaundice
❑ Kernicterus could result
❑ Usually affects only 2nd or subsequent pregnancies* (mother alloimmunized at delivery of 1st pregnancy)

YES! - pre-formed Abs from the first pregnancy

More common is Ab directed to D Ag, but Abs to C, c, E, e antigens are seen, also

anti-D
can be mild to severe

mild disease

Anti-c can range from a mild to severe disease - is the third most
common form of severe HDFN

rare

rare

- (i.e., anti-c and anti-E Abs occur together) - can be severe

➢ ABO & Rh including Du test
➢ ABS

➢ Ab ID & Ab Titer
➢ Ag status of the father, optional
➢ Ig subclass of the maternal Ab, if indicated
❑ Determine initial Ab titer, then repeat approximately every 4 weeks. Run parallel testing on the last previous sample with current sample.

❑ Middle Cerebral Artery-Peak Systolic Velocity (MCA-PSV) - color Doppler / Ultrasound Transducer
❑ Amniocentesis

measurement of the fetal MCA-PSV can be done with the ultrasound to detect anemia in the fetus

INVASIVE procedure where the amniotic fluid is tested
- The concentration of bilirubin pigment in the amniotic fluid measured by the ∆OD 450 nm procedure as pregnancy proceeds predicts worsening of the fetal hemolytic disease

❑ Repeat ABO / Rh and ABS tests
❑ If Ab screen is positive, must do Ab ID procedure

➢ If a weak anti-D is present, it may be due to the administration of an antepartum Rh Immune Globulin shot. Check patient's OB history with RN or physician's office.
➢ If the weak anti-D Ab is due to the Rh Immune Globulin shot, the Ab ID report should state presence of a "passive" anti-D…not as an "allo" anti-D.

❑ Determine ABO / Rh (including weak D)
❑ Perform DAT
❑ Enumerate # of fetal cells present in mother's blood
❑ Fetal Hgb Screen Test / Rosette Test

➢ If baby DAT is positive, may perform elution
➢ To determine Rh HDFN (or any other allo Ab HDFN), use eluate against Ab ID panel cells

It can create iatrogenic anemia - which is anema caused by medical procedures

It is a qualitative test (Screening) which demonstrates smal number of D-positive cells in mothers D-negative cell suspension

A quantitative blood test that measures the amount of fetal hemoglobin in a mother's blood

a medical procedure that involves replacing a patient's blood with donated blood or plasma
- occurs after birth

1. When phototherapy is unsuccessful in reducing the rise of the bilirubin level and hyperbilirubinemia from unconjugated / indirect bilirubin is still present, the second choice of treatment is the Exchange Transfusion.
2. If maternal Ab is causing rapid destruction of fetal RBCs, Exchange
Transfusion is performed, instead of phototherapy.

➢ Hgb < 10 g / dL
➢ Bilirubin level is ≥ 20 mg / dL

Dependent on the age of the newborn, transfusion can occur either via the umbilical cord entry or extremities entry

- < 5 days old
- CPDA-1 or AS-3 (lacks mannitol - a diuretic)
- RBCs must also be ag negative to a corresponding allo Ab present
- O negtive
- CMV negative, OR leuko-reduced
- HgB S negative
- Irradiated

- plasma MUST be AB - lacks anti-A and anti-B
- Rh can be disregarded - no RBCs here
- doesnt need to be irradiated - no WBCs here

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