Week 8: Hemolytic Disease of the Newborn

where do the antibodies that cause HDN come from?

IgG from mother that crosses placenta

for a baby to have HDN, the antigen must come from the _______________

father

when a baby’s RBCs are destroyed by the reticuloendothelial system, what type of RBC increases?

production of RBCs → nucleated RBCs

fast hemolysis in the baby causes an increase in ______________

bilirubin

before birth, fetal bilirubin is excreted how?

maternal liver

after birth, what happens to fetal bilirubin?

the newborn liver cannot conjugate such large amounts of bilirubin

unconjugated bilirubin is toxic to the _____

CNS

brain damage in babies due to unconjugated bilirubin is called what?

kernicterus

what is the greatest danger to the fetus while still in utero?

anemia

what is the greatest danger to the newborn (after birth)?

unconjugated bilirubin

the most severe HDN is associated with which antibodies?

• anti-D

• anti-K

• anti-c

what are other antibodies associated with HDN?

• anti-E

• anti-C

• anti-e

• anti-Fya

• anti-Fyb

• anti-Jka

• anti-Jkb

• anti-S

mild HDN can be caused by ABO antibodies, most commonly IgG _________

anti-A,B

what prenatal studies are done?

• ABO grouping and RH typing

• antibody screen

  • if positive → antibody ID performed

the presence of antibodies does not necessarily mean _______ will occur

HDN

the baby must have the corresponding ____________ for HDN to occur

antigen

the ___________ is phenotyped for the likelihood of the baby being positive for an antigen

father

if the father is negative for the antigen associated with the antibody, what is the chance the baby will have HDN?

0%

if the father is heterozygous for the antigen associated with the antibody, what is the chance the baby will have HDN?

50%

if the father is homozygous for the antigen associated with the antibody, what is the chance the baby will have HDN?

100%

an antibody ________ is done for any clinically significant antibodies detected

titer

an antibody titer helps clinicians decide to do more invasive procedures like what?

• amniotic fluid analysis

• intrauterine transfusions

serum is ________________ to determine the titer of an antibody

serially diluted

what is a titer?

the highest dilution at which agglutination occurs

the current titer is run in parallel with what?

previous frozen sample

an ___________ in titer could indicate HDN

increase

what does amniocentesis measure?

the level of bilirubin in the amniotic fluid

_______________ can help in the prediction of severity of fetal anemia

amniocentesis

method of amniocentesis

bilirubin is measured spectrophotometrically and correlates with degree of fetal anemia

cordocentesis is also known as what?

percutaneous umbilical blood sampling

purpose of cordocentesis

fetal blood sample is drawn to test for hematocrit and phenotype to tell severity of HDN

intrauterine transfusion

• done for severe fetal anemia

• gives fetus RBCs

• transfused through fetus’s abdomen or umbilical cord vein

in an intrauterine transfusion, the transfused cells must be compatible with what?

maternal antibodies

the blood used for intrauterine transfusions is the ____________ unit available

freshest

the blood used for intrauterine transfusions is usually no older than ________ after collection

5 days

what ABO type of blood is used for intrauterine transfusions

O negative

the blood used for intrauterine transfusions should be negative for what?

• antigens corresponding to maternal antibodies

• CMV

• hemoglobin S

is the blood used for intrauterine transfusions irradiated and plasma reduced?

yes

which anticoagulant is used with blood for intrauterine transfusions?

citrate phosphate dextrose (CPD) (no additive solutions)

if a unit for an intrauterine transfusion has __________________, it must be washed

additive

the blood used for intrauterine transfusions must be crossmatch compatible at _____ with maternal serum

AHG

newborns with the following should have what obtained from them?

• type O mothers

• mothers with allo-antibodies

• Rh negative mothers

cord blood

with ABO group cord blood testing, only the _________ type can be performed

forward

newborns do not develop antibodies until _____________ old

4-6 months

any ABO antibodies present in cord blood samples are from the __________

mother

does the strength of DAT correlate with the severity of HDN?

no

HDN due to ABO incompatibilities typically have ______ DAT reactions

weak

stronger positive DAT found in HDN are due to which non-ABO group antibodies?

• anti-D

• anti-K

• anti-c

ABO HDN can occur when?

in any pregnancy

when is ABO HDN most commonly seen?

O mother and A or B newborn

in HDN due to a low incidence antibody, the corresponding antigen may not be present on the ______________

screening cells

with a low incidence antibody causing HDN, the mother will likely have a ____________ antibody screen

negative

in HDN due to a low incidence antigen, how would the eluate from the newborn react against newborn and paternal RBCs?

positive reaction

what is wharton’s jelly?

gelatinous substance within umbilical cord

what issue can wharton’s jelly cause?

false positive reactions in cord blood testing

why should the forward type be washed several times during cord blood testing?

to get rid of wharton’s jelly

following an intrauterine transfusion, the recipient circulating blood could contain up to ______ donor cells

90%

what type of typing reactions can result from intrauterine transfusions?

• weak

• mixed field

• could type as donor cells (O-)

after an intrauterine transfusion, you will have to wait for what?

for the donor cells to be removed from the patient’s system to know the true blood type

in cord blood testing the newborn’s cells can be coated with _____

IgG

since newborn’s cells may have a strong positive DAT, when cord blood is tested with antisera…

there is reduced or no place for the antibodies to bind → false negative

blocked D

when maternal anti-D coat Rh positive newborn cells, and the anti-D reagent has no where to bind → false negative

resolution of blocked D

• gentle heat elution to remove maternal anti-D

• cord RBCs can be retested with anti-D reagent

exchange transfusion

• for severe HDN

• removes aliquots of neonatal blood and replaces with donor blood

what does exchange transfusion accomplish?

• lowers bilirubin

• removes antibody-coated RBCs

• lowers maternal antibody concentration in newborn

• maintains sufficient blood volume in baby

characteristics of blood used for exchange transfusion in newborns

• freshest available (< 5 days)

• O type

• negative for antigens targeted by maternal antibodies

• RBCs re-suspended in AB plasma

• CMV negative

• Hgb S negative

• irradiated

• XM compatible at AHG with mother

infant _________ or __________ can be used if maternal serum is unavailable for crossmatching for exchange transfusion

eluate, serum

RhoGAM

common brand of Rh immune globulin

Rh immune globulin

contains mostly IgG anti-D pooled from human plasma

why is Rh immune globulin used?

to prevent Rh - mothers from developing anti-D by blocking the immune system from recognizing foreign D antigen from a baby

Rh immune globulin is important in preventing HDN in __________ pregnancies

future

when is Rh immune globulin given?

• Rh negative women coming in contact with Rh positive RBCs

• Rh negative women is pregnant

Rh immune globulin must be given to Rh - pregnant women within _______ of bleeding events like abortions, miscarriage, amniocentesis, or antepartum hemorrhage

72 hours

a preventative dose of Rh immune globulin is given at the __________ of gestation

28th week

Rh immune globulin must be given within __________ of giving birth to an Rh positive newborn

72 hours

when a mother receives RhIG during pregnancy, the neonate may have a positive _______

DAT

does RhIG cause hemolysis in the baby?

no, the DAT is a weak positive

RhIG can still be present and cause a positive ________________ at the time of delivery, staying detectable up to _______________

antibody screen, 3-4 months

what testing is performed prior to the administration of RhIG?

• ABORh type

• antibody screen and identification

RhIG is given to which types of women?

• Rh negative

• partial D

why is an antibody screen and ID done prior to giving RhIG?

to see if a woman has already developed anti-D

should the following women receive RhIG?

• Rh negative and pregnant with abortion, miscarriage, amniocentesis

• Rh negative at 28th week of gestation

• Rh negative who give birth to Rh positive babies

• partial D mutation

yes

should the following women receive RhIG?

• Rh positive

• Rh negative with anti-D

• Rh negative who give birth to Rh negative babies

no

a full dose of RhIG protects against _______ of Rh positive packed RBCs

15mL

antepartum administration of RhIG is typically how much?

1 dose

postpartum administration of RhIG is typically how much?

number of doses depends on presence and volume of fetal blood cells in maternal circulation

a fetal blood screen determines if there is any ____________ fetal blood in the Rh negative mother

Rh positive

how is a fetal blood screen test done?

• anti-D is added to postpartum maternal sample to coat any Rh positive fetal RBCs present

• enzyme-treated Rh positive RBCs are added

• clumps form around Rh positive fetal cells

the fetal blood screen is also called what?

rosette test

a negative result for a fetal blood screen requires how much RhIG?

1 dose

what is FMH?

fetal maternal hemorrhage

a positive result for a fetal blood test requires what

a quantitative test to determine the dose

a positive result for a fetal blood screen detects ______ > 10 mL

FMH

Kleihauer-Betke test

• quantifies FMH

• maternal blood treated with acid

• gives % of fetal cells in maternal blood

in the kleihauer-betke test, fetal cells have higher _______ and are more resistant to acid elution

HGB F

in the kleihauer-betke test, fetal cells appear how?

intact and red

what is the formula for the KB test?

(% fetal cells * 50 mL) / 30 mL

% fetal cells * 50 gives what value?

the volume of fetal cells in maternal circulation

1 dose of RhIG protects against _______ of blood

30 mL

an extra vial of ________ is given for safety

RhIG