HDFN Flashcards
Hemolytic disease of the fetus and newborn (HDFN) is the destruction of the red blood cells (RBCs) of a fetus and neonate by antibodies produced by the _.
mother
initial diagnosis of maternal RBC alloimmunization
serologic
_ is caused by the destruction of the fetal RBCs by antibodies produced by the mother.
HDFN
Only antibodies of the immunoglobulin _ class are actively transported across the placenta via Fc receptors;
G (IgG)
_ has become the most common cause of HDFN
ABO incompatibility
antibody that can cross the placenta
IgG
ABO antibodies are present in the _ of all individuals whose RBCs lack the corresponding _
plasma; antigen
antibodies that result from environmental stimulus in early life
isohemagglutinins
clinically significant ABO HDFN occurs most frequently in group _ mothers who have a group_ infant in the white populations and group _ infants in the black population and appears to be more likely when these antibody titers are high
O; A; B
Group A infant RBCs [serologically more similar to =
A2 adult cells
ABO HDFN & RhD HDFN causative antibody
IgG
RhD HDFN first pregnancy can be affected
rare
ABO HDFN can be predicted by titer
no
RhD HDFN bilirubin level at birth
ABO HDFN bilirubin level at birth
elevated;
normal range
RhD HDFN Intrauterine transfusion needed
sometimes
HDFN with anemia at birth
RhD HDFN
HDFN with phototherapy beneficial
ABO HDFN and RhD HDFN
HDFN with rare exchange transfusion needed
ABO HDFN
HDFN with uncommon exchange transfusion needed
RhD HDFN
The serious consequences seen with other causes of HDFN, such as stillbirth, _ , are extremely rare in ABO induced HDFN.
hydrops fetalis, and kernicterus
FMH
Fetomaternal Hemorrhage
leading cause of maternal alloimmunization
Previous pregnancy with FMH
In Rh-negative individuals who are transfused with 200 mL of RhD-positive RBCs, approximately _ respond and form anti-D.
85%
The active transport of IgG begins in the _ trimester and continues until birth.
second
The IgG molecules are transported via the _ portion of the antibodies
Fc
_ are more efficient in RBC intravascular hemolysis
IgG1 and IgG3
common antigens in the Rh system
(C, E, and c)
most antigenic
RhD
Common Antibodies Identified in Prenatal Specimens That Can
Cause of HDFN
D, D+C, D+E, C, E, c, e, K
Rare Antibodies Identified in Prenatal Specimens That Can
Cause of HDFN
Fya, s, M, N, S, JKa
Never Antibodies Identified in Prenatal Specimens That Can
Cause of HDFN
Lea, Leb, I, IH, P1
caused severe HDFN that required intervention and treatment
Anti-E and anti-c
Of the non–Rh system antibodies, _ is considered the most clinically significant in its ability to cause HDFN.
anti-Kell
Kell blood group antigens are present on immature erythroid cells in the fetal _.
bone marrow; (destruction of RBC and precursor)
occurs when maternal IgG attaches to specific antigens of the fetal RBCs.
Hemolysis
Destruction of fetal RBCs and the resulting anemia stimulate the fetal bone marrow to produce RBCs at an accelerated rate, even to the point that immature RBCs (erythroblasts) are released into the circulation
erythroblastosis fetalis
erythropoiesis outside the bone marrow is increased in the hematopoietic tissues of the fetal _
spleen and liver
hepatosplenomegaly results in
portal hypertension and hepatocellular damage
three different phases of anemia
- early-onset anemia
- late hemolytic anemia
- late hyporegenerative anemia
anemia mechanism: antibody- mediated hemolysis
early-onset anemia
anemia mechanism: continued hemolysis, the expanding intravascular compartment, and natural decline of hemoglobin levels
late hemolytic anema
anemia mechanism: marrow suppression as a result of transfusions and IUT, antibody destruction of RBC precursors, and deficiency of erythropoietin
late hypogenerative anemia
onset of early anemia
Within / 7 days of birth
onset of late hemolytic anemia & late hypogenerative anemia
> 2 weeks of age
conjugated and rendered water soluble bilirubin
direct bilirubin
indirect bilirubin travels thru bloodstream to _ to be direct b.
liver
RBC destruction releases hemoglobin, which is metabolized to _
bilirubin
pathway of indirect to direct bilirubin
iB - bloodstream - liver - dB - gastrointestinal tract
t/f. fetal liver can metabolize indirect bilirubin
false
toxic level of indirect bilirubin
> 18-20 mg/dL
toxic bilirubin can cause
permanent damage to the brain / kernicterus
detection of ABO HDFN is best done
after birth
the material surrounding the blood vessels
Wharton’s jelly
t/f. cord blood should be anticoagulated for storage
true
most important diagnostic test for ABO HDFN
DAT on the cord or neonatal RBCs
Collecting _ blood samples on all delivered infants is highly recommended.
cord
HDFN Caused by RBC Alloimmunization
The recommended practice is to perform the _ and _ detection test at the first prenatal visit, preferably during the first trimester.
type; antibody
antibody-enhancing medium that can increase sensitivity of the assays
polyethylene glycol (PEG) or low ionic strength solution (LISS)
Test that must be able to detect clinically significant IgG alloantibodies that are reactive at 37°C and in the anti- globulin phase
antibody detection method, or indirect antihuman globulin test (IAT)
rather common in pregnant women but have not been reported to cause HDFN
Lewis system antibodies
can cause mild to moderate HDFN, although rarely.
anti-M and anti-N
The J-chain of IgM anti- bodies can be destroyed by _ reagent when establishing the immunoglobulin class
sulfhydryl (dithiothreitol; 2-mercaptoethanol)
Most of pregnant women have received RhIG, either after an event with increased risk of fetomaternal hemorrhage or at _ weeks’ gestation (antenatal)
28
A titer higher than _ almost always indicates active immunization;
4
The relative concentration of all antibodies capable of cross- ing the placenta and causing HDFN is determined by _
antibody titration
recommended method in antibody titration
saline antiglobulin tube test
saline antiglobulin tube test: _ -minute incubation at _ and the use of _ reagent, although other methods have also been proposed
60; 37degC; anti-IgG
critical titer in recommended method
16
If the initial titer is 16 or higher, a second titer should be done at about _weeks’ gestation
18 to 20
> 32 titer is indicator for:
<32 should be repeated after 4-week intervals, beginning at 16 to 20 weeks’ gestation and then _ during the _ trimester.
Doppler imaging to asses MCA-PSC
every 2 to 4 weeks; third
predicted copy number of the gene
zygosity
Risk stratification of the fetus can be directly carried out by obtaining fetal cells through _ as early as _ weeks’ gestation.
amniocentesis or chorionic villous sampling (CVS) ; 10 to 12
Fetal DNA Testing
To avoid an invasive procedure, fetal DNA can be isolated from _ from a peripheral blood sample to determine RHD and KEL genotype.
maternal plasma
advanced fetal risk strat- ification for mothers with RBC alloimmunization
cell-free DNA (cfDNA) method
At about 16 to 20 weeks’ gestation, the clinical diagnosis of fetal anemia can be made using an ultrasound technique called _
fetal middle cerebral artery peak systolic velocity (MCA-PSV)
invasive monitoring of fetus
Cordocentesis and Amniocentesis
sensitive enough to predict significant fetal anemia in which intervention may be needed
> 15 multiples of mean (MoM)
If the fetus has not reached an acceptable gestational age for delivery, and the hematocrit level is less than 30%, _ is usually indicated.
intrauterine transfusion
MCA-PSV replaced _ to monitor amniotic fluid bilirubin levels
amniocentesis
Intervention in the form of intrauterine transfusion becomes necessary when one or more of the following conditions exists:
• MCA-PSV indicates _ (>1.5 MoM).
• _ is noted on ultrasound examination.
• Cordocentesis blood sample has hemoglobin level _
• _ ∆OD 450 nm results are high and/or increasing.
anemia;
fetal hydrops;
> 10g/dL;
Amniotic fluid
accessing the fetal umbilical vein
cordocentesis
performed by accessing the fetal umbilical vein (cordocentesis) and injecting donor Transfusion Practices RBCs directly into the vein
Intrauterine transfusion
goal of intrauterine transfusion
maintain fetal hemoglobin > 10 g/dL
drawn at the time of birth is used to confirm HDFN and prepare for possible transfusion.
cord blood sample
most important serologic test for diagnosing HDFN
DAT with anti-IgG reagent
_ is the use of whole blood or equivalent to replace the neonate’s circulating blood and simultaneously remove maternal anti- bodies and bilirubin.
Exchange transfusion
For patients with known HDFN, close observation of _ and _ is warranted
bilirubin levels and hemoglobin
Phototherapy at _ nm is used to metabolize the unconjugated bilirubin to isomers that are less lipophilic, less toxic to the brain, and able to be excreted through urine.
460 to 490
For infants with _ or history of intrauterine transfusion, phototherapy is generally sufficient to adequately conjugate the bilirubin and lessen the need for transfusion.
mild to moderate hemolysis
used to treat hyper- bilirubinemia of the newborn caused by HDFN
Intravenous immune globulin (IVIG)
The IVIG competes with the_ antibodies for the Fc receptors on the _ in the infant’s _, reducing the amount of hemolysis.
mother’s; macrophages; spleen
RhIG should be given to RhD-negative mothers, the first dose is provided at _ weeks’ gestation,
28
RhIG immunization second dose is given after _ of an RhD-_ infant within _ hours.
delivery; positive; 78
regular-dose vial of RhIG in the United States contains sufficient anti-D to protect against 15 mL of _ or 30 mL of _
packed RBCs; whole blood
regular dose of RhIG in
WHO:
UK:
WHO 300 μg
UK 100 μg
Volume of fetomaternal hemorrhage
Number of fetal cells × Maternal blood volume / Number of maternal cells
the calculated volume of fetomaternal hemorrhage is then divided by _ to determine the number of required vials of RhIG; then add _ vial
30; 1
used to quantitate the number of fetal RhD-positive cells in the mother’s circulation as a result of a fetomaternal hemorrhage
Kleihauer-Betke test or flow cytometry
