hemolytic disease of fetus and newborn

chapter 20

define HDFN

destruction of fetal and or newborn RBC by maternal IgG; the lifespan of fetal RBC is shortened and RBC are removed faster than the baby can replenish them

Out of the 4 IgG subtypes, which two can cross the placenta more efficiently?

IgG 1 and IgG3

what are the major implications of HDFN on the fetus?

anemia and bilirubinemia/kernicterus

if fetal RBC are being destroyed so quickly to the point where the BM can’t keep up, other organs kick in, and this can cause the fetus to display what?

hepatosplenomegaly ( hepatocellular damage)

in severe cases of anemia, hydrops fetalis can occur in the fetus. What is this condition and what is the physiological explanation of why this occurs.

hydrops fetalis is excess fluid buildup in fetal organs. when the BM can’t keep up with the level of anemia, the liver kicks in… but becomes enlarged. Hepatosplenomegaly results in hypertension and hepatocellular damage. Since the liver cells are damaged, there is a decrease in the plasma protein production. Plasma proteins are what pull fluids into the blood, and without them, fluid stays in the tissues

where is fetal unconjugated bilirubin conjugated?

fetal unconjugated bilirubin is conjugated by the mom’s liver

why do babies get jaundice?

baby’s liver cannot yet metabolize bilirubin efficiently, unconjugated bilirubin accumulates

what condition results from high, toxic levels of bilirubin accumulation to the point where there is no more albumin to carry it?

kernicterus

kernicturus

unbound, unconjugated bilirubin crosses the BBB and settles out into the brain

what levels of bilirubin can we see in an infant’s brain with kernicterus?

greater than 20 mg/dL

T or F: bilirubin is not toxic to the brain

false! it is toxic to nerve cells

statistically, what percent chance is it that mother and baby are ABO incompatible?

1 in 5 pregnancies

ABO Ab are typically IgM… how can they cross the placenta and attack the baby?

ABO Ab can be IgG!

ABO HDFN is nearly always limited to “—or— “ infants with mothers that are “—”

A or B babies that have an O mother ( O phenotypes produce potent A,B antibodies)

If a mother will be pregnant 3 times, which pregnancies can ABO affect?

can affect any of the pregnancies, ABO is not dependent of previous foreign stimulation

what can all cause a Mother to produce and alloantibody?

previous fetomaternal hemorrhage ( delivery or during pregnancy), transfusion, transplantation

why is ABO HDFN usually mild?

ABO antigens are not fully expressed in baby’s RBC at birth OR maternal antibodies are neutralized by soluble ABO Ag.

How does ABO incompatibility between mother and fetus protect against sensitization to the D antigen?

if D + ( with ABO incompatibility) cells from baby get up into mom’s circulation, the baby cells are removed very quickly by the already present, naturallty occuring ABO antibodies. RBC are removed before the D neg mom can make an antibody against baby D pos antigens

First pregnancy affected? ABO →”——” RhD→ “—-”

ABO the first pregnancy could be affected

Rh the first pregnancy is usually not affected ( no sensitization)

Disease predicted by titers? ABO →”——” RhD→ “—-”

ABO HDFN is not predicted by titers

RhD HDFN is predicted by titers

Causitive antibody IgG? ABO →”——” RhD→ “—-”

ABO, yes anti-A,B

RhD, yes anti-D

DAT results ? ABO →”——” RhD→ “—-”

ABO pos or neg

RhD pos

Billirubin level at birth? ABO →”——” RhD→ “—-”

ABO normal range….( not a lot of hemolysis)

RhD is elevated

Anemia at birth? ABO →”——” RhD→ “—-”

ABO… no ( ABO Ag not well developed)

RhD… yes

exchange transfusion

taking out the affected baby blood and replacing it with fresh blood

What all includes prenatat testing we do in the lab?

look at transfusiona nd pregnancy history, ABO and Rh typing, Ab screen, titration studies

Do we do weak D testing for expecting mothers?

yes, if they are weak D positive, they will not produce alloanti-D, therfroe no Rhogam is required

when doing sitration studies, what indicates a significant rise?

4 fold rise or 16-32 ( our titer has doubled, antibody is still there after we diluted the samples 16 times… and there was in increase in antibody so much so that we could detect it after diluting 32 times

why wouldnt we just give a RH pos or weak D pos mom rhogam anyway?

Rhogam can bind to her own D pos cells

besides RhD, what other common antibodies can cause HDFN?

anti-c and anti- kell

What is the main way we monitor the baby?

Dooppler Fetal Ultrasonography

What artery do the doctors analyze in a doppler fetal ultrasonography?

middle cerebral artery

what is the purpose of doing a doppler fetal ultrasonography?

looks at level of anemia based of the amount of blood flow in the middle cerebral artery ( less ammount of RBC, heart will pump harder to try and circulate the remaining RBC)

blood viscosity is a measure of how thick or thin the blood is. Blood gets thinner when there is low hematocrit ( less RBC) if blood is moving very fast, does that mean it is more or less viscous?

less viscous, ( high velocity= less viscous= less hematocrit= more blood loss)

cordocentesis

aspirating blood off the cord with the use of an ultrasound

What can we all test blood obtained by a cordocentesis for?

Hemoglobin, hematocrit, bilirubin, DAT, ABO/Rh typing, other blood group systems, genotyping/ phenotying

What are the risks of a cordocentesis

• fetal maternal hemmhorage

• premature birth

what use does an ultrasound have?

• used to help guide the needle for cordocentesis sampling

• used to detect if the baby is endemic/ has hydrops fetalis

placental thickening and excess amniotic fluid are symptoms of what condition in the baby?

hydrops fetalis

in a sample of amniotic fluid on a liley curve graph, where do we see the bilirubin bump?

450 nm

do we run a contaminated ( blood or meconium) sample of amniotic fluid on Liley curve?

no, interference

what zone on the liley graph is likely indicative that the fetus needs and intrauterine transfusion?

top zone (anything before 32 weeks is not deliverable)

at how many weeks gestation do we consider intrauternine transfusion over delivery?

24-26

if one of the following occurs at 24-26 weeks gestation

• MCA indicates baby has high level of anemia so we do a cordocentesis

• the cordocentesis displays a hemoglobin of less than 10 mg/dL

• ultrasound indicates that the baby is edemic

what is the next course of action?

intrauterine transfusion

if one of the following occurs at 32-34 weeks gestation

• MCA indicates baby has high level of anemia so we do a cordocentesis

• the cordocentesis displays a hemoglobin of less than 10 mg/dL

• ultrasound indicates that the baby is edemic

AND lungs are fully developed

what is the next course of action?

deliver the baby

when an intrauterine transfusion in needed, how are the RBC delivered to the baby?

via fetal umbilical vein

what ABO Rh type cells are used for intrauterine transfusion?

O neg and antigen neg for any implicated Ab

Once the baby is delivered and HDFN is suspected, how do we go forward with testing?

mom: ABO/Rh and Ab screen ( if positive ID … if IgG, test baby for bili and and Hgb)

baby: cord blood ABO/Rh and DAT

why at birth does hyperbilirubinemia occur?

baby is cut of from moms liver that conjugated the bili

why do we test the cord blood upon birth?

confirm HDFN and prepare for possible transfusion

after birth: what lab findings are significant to affirm that HDN was caused by an ABO incompatibility?

spherocytes, positive spontaneous agglutination, mild anemia with weak pos or neg DAT

after birth: what lab findings are significant to affirm that HDN was caused by an Rh or other system antigen incompatibility?

bilirubin levels greatly increased, anemia, pos DAT, jaundice within first 24 hours

what are the 4 goals of an exchange transfusion?

decrease bili to prevent kernicterus

remove babys sensitized RBC

increase hemoglobin levels

decrese the level of incompatible Ab in the baby

what percentage of the infants sensitized RBC are removed by a double vloume exchange?

80-90%

what percentage of bilirubin is removed from an infant who receives a double volume exchange transfusion?

50%

why do we need fresh (no more than 7-10 days old) blood when doing exchange transfusion?

we want to give baby full functional cells! the older the RBC are, the worse shape they are in. we dont want to give the baby too much potassium from the lysed RBC that could lead to cardiac irregularities . also the fresher, the more maximized 2,3 DPG is

what kind of blood should we select for an exchange transfusion

O neg, antigen neg for moms Ab, hemoglobin S neg, fresh, irradiated, WBC reduced, irradiated

at 460-490 nm phototherapy, unconjugated bilirubin is turned to…

isomers

Intraravenous Immune Globulin

used to treat hyperbilirubinemia in the baby IVIG competes with mom’s Ab for the Fc receptors in the baby’s spleen. this reduces the amount of hemolysis