[9] CHAPTER IV LESSON 1 Flashcards
is the destruction of red blood cells (rbcs) of a fetus and neonate by antibodies produced by the mother.
Hemolytic disease of the fetus and newborn (hdfn)
: secondary to previous pregnancy or transfusion
Maternal antibody formation
Hemolytic disease of the fetus and newborn (hdfn)
Also known as
erythroblastosis fetalis
the initial diagnosis of maternal rbc alloimmunization is
serologic
After detection, the [?] of hdfn have been improved with advances in technology.
risk stratification and management
[?] have greatly increased the success of accurately diagnosing and adequately treating this disease.
Ultrasonography, doppler assessment of middle cerebral artery peak systolic velocity, cordocentesis, fetal dna analysis from amniotic fluid or maternal plasma, and intravascular intrauterine transfusion
reported a transfusion reaction from transfusing a husband’s blood to a postpartum woman.
Levine and Stetson
They postulated that the mother had been immunized to the father’s antigen through fetomaternal hemorrhage (FMH).
Levine and Stetson
The antigen was later identified as
RhD.
Maternal RBC alloimmunization can be caused by
previous pregnancy or previous transfusion.
Some authors suggest significant impact of [?] on development of future HDFN.
previous transfusion
Maternal RBC alloimmunization Causes:
- Rh BGS – anti-D
- ABO BGS – anti-A , anti-B
- Other antibodies – other Rh antibodies, Kell BGS
- Rarer antibodies – Duffy BGS, MNS BGS
- Rh BGS –
anti-D
- ABO BGS –
anti-A , anti-B
- Other antibodies –
other Rh antibodies, Kell BGS
- Rarer antibodies –
Duffy BGS, MNS BGS
Most common cause of HDFN
HDFN Caused By ABO
Maternal ABO antibodies that are IgG can cross the placenta and attach to the
ABO antigens of the fetal RBCs.
[?] are most likely to form high-titered IgG antiABO antibodies, ABO HDFN is nearly always limited to [?] with potent [?].
Group O individuals
A or B infants of group O mothers
anti-A,B antibodies
can occur in the first pregnancy and in any, but not necessarily all, subsequent pregnancies because it does not depend on previous foreign RBC stimulation.
ABO HDFN
Microspherocytes and increased RBC fragility are characteristic.
HDFN Caused By ABO
Like other forms of HDFN, the severity of the disease is independent of the presence of a positive DAT result or demonstrable anti-A, antiB, or anti-A,B in the eluate of the infant’s RBCs.
HDFN Caused By ABO
ABO HDFN causes a bilirubin peak at [?], which is later than with HDFN caused by other antibody specificities.
1 to 3 days
Phototherapy is usually sufficient for slowly rising bilirubin levels.
HDFN Caused By ABO
HDFN PATHOGENESIS
- HDFN Caused By ABO
- HDFN Caused by RBC Alloimmunization
- HEMOLYSIS, ANEMIA, AND ERYTHROPOIESIS
- BILIRUBIN
HDFN Caused by RBC Alloimmunization FACTORS:
A. Fetomaternal Hemorrhage
B. Maternal Factors
C. RBC Antibody Specificity
D. Influence of ABO Group
Previous pregnancy with [?] is the leading cause of maternal alloimmunization.
Fetomaternal Hemorrhage
Transplacental hemorrhage of fetal RBCs into the maternal circulation occurs in most women, but it is usually a very small amount (0.5 mL in 93% of women)
Fetomaternal Hemorrhage
Interventions such as amniocentesis and chorionic villus sampling and trauma to the abdomen can increase the risk of
Fetomaternal Hemorrhage
At delivery, the incidence is more than 50%; this is the time the placenta separates from the uterus, and fetal RBCs can enter the maternal circulation.
Fetomaternal Hemorrhage
Immunoglobulin class and subclass of the maternal antibody affects the severity of the HDFN.
Maternal Factors
Of the immunoglobulin classes (i.e., IgG, IgM, IgA, IgE, and IgD), only IgG is transported across the placenta.
The active transport of IgG begins in the [?] and continues until birth.
Maternal Factors
second trimester
Of all the RBC antigens, (?) is the most antigenic.
RBC Antibody Specificity
RhD
The common antigens in the Rh system (C, E, and c) are also potent immunogens and have been associated with moderate to severe cases of HDFN.
RBC Antibody Specificity
Of the non–Rh system antibodies,(?) is considered the most clinically significant in its ability to cause HDFN.
RBC Antibody Specificity
anti-Kell
When the mother is ABO-incompatible with the fetus (major incompatibility), the incidence of detectable fetomaternal hemorrhage is decreased.
Influence of ABO Group
This apparent protection from RhD immunization is likely due to the clearing and/or hemolysis of ABO-incompatible (?)in the mother’s circulation before the RhD antigen can be recognized by her immune system.
Influence of ABO Group
RhD-positive fetal RBCs
Common
Antibodies Identified in Prenatal Specimens That Can Cause HDFN
Anti-D
Anti-D + C
Anti-D + E
Anti-C
Anti-E
Anti-c
Anti-K
Rare
Antibodies Identified in Prenatal Specimens That Can Cause HDFN
Anti-Fya
Anti-s
Anti-M
Anti-N
Anti-S
Anti-Jka
Never
Antibodies Identified in Prenatal Specimens That Can Cause HDFN
Anti-Lea
Anti-Leb
Anti-I
Anti-IH
Anti-P1
Anti-e
The maternal antibody crosses the placenta and binds to the
fetal antigen-positive cells
occurs when maternal IgG attaches to specific antigens of the fetal RBCs.
Hemolysis
The antibody-coated cells are removed from the circulation by the [?] of the fetal spleen.
macrophages
- 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
When the bone marrow fails to produce enough RBCs to keep up with the rate of RBC destruction, erythropoiesis outside the bone marrow is increased in the hematopoietic tissues of the [?].
fetal spleen and liver
These organs become enlarged (hepatosplenomegaly), resulting in [?].
portal hypertension and hepatocellular damage
Severe anemia and hypoproteinemia caused by decreased hepatic production of plasma proteins leads to the development of highoutput cardiac failure with generalized edema, effusions, and ascites, a condition known as [?].
hydrops fetalis
The process of RBC destruction continues after birth as long as [?] persists in the newborn infant’s circulation.
maternal antibody
There are three different phases of anemia caused by HDFN:
i. early (within 7 days of birth) due to antibody-mediated hemolysis;
ii. late hemolytic anemia (2 weeks or more after birth) due to continued hemolysis, the expanding intravascular compartment, and natural decline of hemoglobin levels; and
iii. late hyporegenerative anemia due to marrow suppression as a result of transfusions and IUT, antibody destruction of RBC precursors, and deficiency of erythropoietin
due to antibody-mediated hemolysis;
i. early (within 7 days of birth)
due to continued hemolysis, the expanding intravascular compartment, and natural decline of hemoglobin levels; and
ii. late hemolytic anemia (2 weeks or more after birth)
due to marrow suppression as a result of transfusions and IUT, antibody destruction of RBC precursors, and deficiency of erythropoietin
iii. late hyporegenerative anemia
RBC destruction releases hemoglobin, which is metabolized to [?] in different metabolic stages.
bilirubin
During pregnancy, the [?] made by the fetus is transported across the placenta and conjugated by the maternal liver and safely excreted.
indirect bilirubin
After birth, the immature infant liver cannot yet metabolize bilirubin efficiently, and this leads to the [?].
accumulation of unconjugated bilirubin and neonatal jaundice
When a newborn infant is affected by HDFN, the levels of indirect bilirubin are higher due to the [?].
pathological RBC destruction
With moderate to severe hemolysis of HDFN, the unconjugated, or indirect, bilirubin can reach levels toxic to the infant’s brain (generally, [?]), and if left untreated can cause [?] or permanent damage to the brain.
more than 18 to 20 mg/dL
kernicterus
Levels of [?] in the fetal circulation and amniotic fluid may be elevated- does not cause clinical disease in the newborn.
total bilirubin
After birth, accumulation of [?] can become a severe problem.
metabolic by-products of RBC destruction
BILIRUBIN PATHOGENESIS
1. Fetomaternal [?]
2. Fetomaternal [?]
3. Maternal antibodies formed against [?]
4. During subsequent pregnancy, placental passage of [?]
5. Maternal antibody attaches to [?]
6. Fetal RBC [?]
incompatibility
hemorrhage
paternally derived antigens
maternal IgG antibodies
fetal RBC
hemolysis
Effect of maternal antibody on the fetus:
- Hemolysis
- Erythroblastosis fetalis
- Hepatosplenomagaly
- Hydrops fetalis
The rate of RBC destruction depends on antibody titer and specificity and on the number of antigenic sites on the fetal RBCs
- Hemolysis
Destruction of fetal RBCs and the resulting anemia stimulate the fetal bone marrow to produce RBCs at an accelerated rate.
- Erythroblastosis fetalis
Resulting in portal hypertension and hepatocellular damage
- Hepatosplenomagaly
Severe anemia and hypoproteinemia leads to the development of high-output cardiac failure with generalized edema, effusions, and ascites.
- Hydrops fetalis
is best done after birth.
Detection of ABO HDFN
No single serologic test is diagnostic for
a. Postnatal Diagnosis
ABO HDFN.
When a newborn develops jaundice within (?) after birth, various causes of jaundice need to be investigated.
a. Postnatal Diagnosis
12 to 48 hours
is the most important diagnostic test.
a. Postnatal Diagnosis
DAT on the cord or neonatal RBCs
on all delivered infants is highly recommended.
a. Postnatal Diagnosis
Collecting cord blood samples
The sample should be collected by venipuncture to avoid contamination with maternal blood and Wharton’s jelly and should be anticoagulated for storage.
a. Postnatal Diagnosis
If the neonatal infant develops jaundice, (?) can be carried out and the results can be assessed.
a. Postnatal Diagnosis
ABO, RhD, and DAT testing
The recommended practice is to perform the type and antibody detection test at the first prenatal visit, preferably during the first trimester.
HDFN Caused by RBC Alloimmunization
At that time, a maternal history must be taken to understand if there is a history of HDFN, the previous pregnancy outcomes, and whether there is a history of prior transfusions.
HDFN Caused by RBC Alloimmunization
The prenatal specimen must be typed for
a. ABO, RhD and Antibody Screen
ABO and RhD.
The antibody detection method, or (?), must be able to detect clinically significant IgG alloantibodies that are reactive at 37°C and in the antiglobulin phase.
a. ABO, RhD and Antibody Screen
indirect antihuman globulin test (IAT)
If the antibody screen is nonreactive, repeat testing is recommended before RhIG therapy in RhD-negative prenatal patients and in the third trimester if the patient has been transfused or has a history of unexpected antibodies.
a. ABO, RhD and Antibody Screen
To establish the immunoglobulin class, the serum can be treated with a sulfhydryl reagent, such as (?), and then retested with appropriate controls.
b. Antibody Identification
dithiothreitol or 2mercaptoethanol
The J-chain of IgM antibodies will be destroyed by this treatment; IgG antibodies will remain reactive.
b. Antibody Identification
Sulfhydryl reagents
If the antibody specificity is determined to be clinically significant and the antibody is IgG, further testing is required.
b. Antibody Identification
Other than anti-D, the most common and most significant antibodies are anti-K, anti-E, anti-c, anti-C, and anti-Fya.
b. Antibody Identification
The relative concentration of all antibodies capable of crossing the placenta and causing HDFN is determined by
c. Antibody Titers
antibody titration
The patient serum or plasma is serially diluted and tested against appropriate RBCs to determine the highest dilution at which a reaction occurs.
c. Antibody Titers
The method must include the indirect antiglobulin phase using antiIgG reagent.
c. Antibody Titers
The result is expressed as either the reciprocal of the titration endpoint or as a titer score.
c. Antibody Titers
The recommended method is the [?], with 60-minute incubation at 37°C and the use of anti-IgG reagent.
c. Antibody Titers
saline antiglobulin tube test
For the recommended method, 16 is considered the critical titer.
c. Antibody Titers
If the initial titer is 16 or higher, a second titer should be done at about (?).
c. Antibody Titers
18 to 20 weeks’ gestation
A specimen of the father’s blood should be obtained and tested for the presence and zygosity (predicted copy number of the gene) of the corresponding blood group antigen to predict fetal risk of being affected by HDFN.
d. Paternal Phenotype and Genotype
If the mother has anti-D and the father is RhD-positive, the paternal genotype determined by DNA methods is the only way to definitively determine how many copies of the RHD gene an RhD-positive person carries.
d. Paternal Phenotype and Genotype
is the recommended test for RhD-positive fathers when the mother has anti-D antibody.
d. Paternal Phenotype and Genotype
RHD zygosity genotype testing
