56 Alloimmune Hemolytic Disease of the Fetus and Newborn Flashcards
Manifestations of Alloimmune Hemolytic Disease of the Newborn
Disorder in which the lifespan of fetal and/or neonatal red cells is shortened as a result of binding of transplacentally transferred maternal immunoglobulin (Ig) G antibodies on fetal red blood cell (RBC) antigens foreign to the mother, inherited by the fetus from the father
- Hemolytic anemia
- Jaundice
- Hepatosplenomegaly
in more severe cases:
* Anasarca
* Kernicterus
Race
Approximately 15% of ____________descent are RhD negative
Americans of European descent
Compared with 7% of African Americans and Hispanics, 5% of Indians, and 0.3% of Chinese individuals
The ________ phenotype is found in approximately 30% of RhD-“negative” individuals in East Asia and has been implicated in RhD HDFN
Phenotypes can exhibit quantitative reductions and sometimes qualitative variation in D antigen expression, potentially resulting in anti-D alloimmunization
DEL phenotype
Asymptomatic transplacental passage of fetal red cells occurs in _____% of pregnancies.
75%
The risk of sensitization increases with each trimester of pregnancy and is greatest (65%) at ________.
Delivery
The average volume of fetal blood in the maternal circulation after delivery is approximately _______ mL in most women and less than 1 mL in 96 % of women
0.1 mL
Maternal red cell antibodies fall into three classes:
- Antibodies directed against the D antigen in the Rh blood group
- Antibodies directed against the A or B antigens
- Antibodies directed against any of the remaining red cell antigens
Blood group system involved in most serious cases
D antigen of the Rh blood group
In ABO hemolytic disease, the mother is usually type ___ and the fetus is either type ____
Type O
Type A or B
Others:
* mothers of type B and fetuses of type A
* mothers of type A and fetuses of type B
After anti-RhD, the following blood groups are most often involved in alloimmunization:
- Rh (C, e, E, e)
- Kell
- Duffy
- Kidd
- MNS
Caused in large part by suppression of erythropoiesis rather than brisk hemolysis
Kell HDFN
- Anti-Kell antibodies inhibit the growth of Kell-positive erythroid progenitor cells
- Anti-Kell antibodies have also been associated with suppression of megakaryocyte and granulocyte colony-forming units, resulting in fetal and neonatal thrombocytopenia and pancytopenia
All maternal anti-Kell alloantibodies must be considered to be potentially clinically significant
The presence of maternal antibodies is not predictive of alloimmune hemolytic disease because
- (1) they may be IgM antibodies and not traverse the placenta
- (2) the antigens may not be present on fetal red cells or their density is very low
- (3) the concentration of antibody in maternal blood may be very low
- (4) the antibody Ig subclass may not interact with fetal red cells
- (5) other mitigating factors
TRUE OR FALSE
ABO incompatibility is present in 15% of O group pregnancies, but hemolytic disease of the fetus or newborn occurs in about 2% of births.
TRUE
ABO incompatibility is present in 15% of O group pregnancies, but hemolytic disease of the fetus or newborn occurs in about 2% of births.
Rare!
Most anti-A and anti-B being IgM antibodies, which do not easily traverse the placenta.
TRUE OR FALSE
Fetomaternal ABO incompatibility offers some protection against primary Rh immunization because incompatible fetal RBCs are destroyed rapidly by maternal anti-A and anti-B antibodies
TRUE
Fetomaternal ABO incompatibility offers some protection against primary Rh immunization because incompatible fetal RBCs are destroyed rapidly by maternal anti-A and anti-B antibodies
ABO incompatibility confers no protection against the secondary immune response after sensitization has occurred
Type of antibody
RhD Alloimmunization:
ABO Alloimmunization:
RhD Alloimmunization:IgG1 and /or IgG3
ABO Alloimmunization: IgG2
Other features of ABO Alloimmunization
- Observed higher freguency during the first pregnancy because of preexisting anti-A and anti-B in the mother (40%−50%)
- Moderate anemia and mild hepatosplenomegaly
- Early neonatal jaundice requiring phototherapy
- Rarely requires exchange transfusion
- Rarely leads to severe disease (ie, hydrops fetalis)
- Rare incidence of late anemia
The hemolytic rate can be determined by using
Exhaled carbon monoxide end-tidal breath analyzer
In RhD alloimmunization, % of newborns have mild disease and do not need intervention
50%
- 25%- born at term with moderate anemia and severe jaundice
- 25% - hydrops fetalis in utero prior to the availability of intrauterine intervention
Associated with marked extramedullary hematopoiesis in the liver, spleen, kidneys, and
adrenal glands.
Hydrops fetalis
Portal and umbilical vein hypertension, hypoproteinemia (liver dysfunction), and pleural effusions and ascites can occur.
If severe anemia is present, infant displays pallor, tachypnea, and tachycardia; cardiovascular collapse and tissue hypoxia can occur if hemoglobin is less than
40 g/L
Timing of ABO and RhD typing and testing for unusual red cell alloantibodies during pregnancy
10th to 16th week
Whether RhD positive or negative, the mother should be tested again at 28 weeks’ gestation.
If alloimmunized, the mother’s antibody titer should be determined at
4-week intervals from 20 to 28 weeks and every 2 weeks thereafter
Anti-D levels and management
- 4 IU/mL: referral to fetomaternal specialist for monitoring and risk assessment
- 4 to 15 IU/mL indicates that moderate alloimmune hemolytic disease
- Greater than 15 IU/mL: high risk of alloimmune hemolytic disease
Antibody titers are reported as the reciprocal of the highest dilution at which agglutination is observed.
A difference of two dilutions is considered significant.
If the titer becomes greater than 16 (varies from 8 to 32 in different laboratories), ultrasonography and amniocentesis can be performed to test for the bilirubin level, which predicts disease severity
In pregnancies in which maternal sensitization occurs or there is a past history of alloimmunization, determining : __________ for all common antigens involved in alloimmune hemolytic disease may determine the risk to the fetus.
Paternal zygosity
- Homozygous: assume the fetal red cells will carry that antigen
- Heterozygous: 50% chance of carrying the antigen
Can distinguish maternal from fetal DNA and
then amplify fetal exons that include RhD
Fetal DNA:
Real-time quantitative polymerase chain reaction
Accuracy of RhD phenotyping using fetal DNA is 95%.
An indirect measure of degree of hemolysis in the fetus
Amniotic fluid spectrophotometry for bilirubin
Liley chart: Defines 3 zones based on ΔOD450 readings, indicating severity of fetal disease
Queenan chart: Modified Liley chart to include data from 14-40 weeks’ gestation, with 4 zones
Replaced amniocentesis for measuring fetal anemia
Middle cerebral artery Doppler ultrasound measurement
- Measuring peak blood flow, usually at 1- to 2-week intervals after week 18 until week 35, is a more accurate assessment of anemia than amniotic fluid bilirubin levels.
- After week 38 of gestation, because of a high false-positive rate with Doppler measurements, amniocentesis and measurement of amniotic fluid OD450 are required.
Allows direct measurement of fetal red cell antigens, blood hemoglobin, reticulocyte count, direct antiglobulin test, bilirubin level, blood gases, and lactate levels and can be done at 18 weeks’ gestation
PUBS (also called cordocentesis)
confirmatory
Complications of PUBS include:
- Umbilical cord bleeding
- Chorioamnionitis
- Fetomaternal hemorrhage and Maternal red cell sensitization
- Fetal death (3%)
After delivery, the cord blood of the neonate should be sampled for:
- Hemoglobin
- Bilirubin concentrations
- ABO and Rh type
- Direct antiglobulin test
- Blood film
TRUE OR FALSE
One hour after delivery, blood should be drawn from the mother to evaluate the degree of fetomaternal hemorrhage, so that an appropriate dose of anti-Rh IgG can be given.
TRUE
One hour after delivery, blood should be drawn from the mother to evaluate the degree of fetomaternal hemorrhage, so that an appropriate dose of anti-Rh IgG can be given.
Erythropoiesis may be suppressed in the newborn, but marrow recovery is usually complete by __ months.
2 months
Given to severely affected fetus, based on level of anemia, development of ascites, or a rising bilirubin concentration
Replaced exchange transfusion in some centers because it is a more rapid procedure
Intrauterine transfusion thru PUBS
O-negative, antigen-negative for any other identified antibody, cytomegalovirus-negative, irradiated packed red cells are used, cross-matched against the mother’s blood.
Fetal hematocrit for intrauterine BT
≤30%
Packed red cells are transfused to the fetus to achieve a hematocrit of
40% to 45%
The red cells are packed to about 75% and a calculation made as to what volume of red cells should be necessary to achieve the
desired hematocrit in the fetus.
Intraperitoneal fetal transfusions may be necessary if:
- (1) intravascular access is not possible because the umbilical vessels are too narrow in early pregnancy or
- (2) fetal size blocks access to the cord later in pregnancy
For a woman alloimmunized in a previous pregnancy, fetal transfusions should begin _________, but not before 18 weeks’ gestation unless hydrops is present.
10 weeks before the time of the earliest prior fetal death or transfusion
Transfusions are given to keep the hematocrit of the fetus in the 20% to 25% range and to prevent hydrops.
If possible, transfusions are given up to _____ weeks with delivery at ____ weeks’ gestation
34 weeks
36 weeks
Other treatments to desensitize the mother (maternal immunomodulation)
- Intravenous immunoglobulin with or without plasmapheresis
- Glucocorticoids
- Administration of recombinant D-specific antibodies that do not destroy RhD-positive red cells
Indications for immediate exchange transfusion in neonates:
- The cord blood hemoglobin level is significantly less than normal (perhaps a threshold of ≤110 g/L).
- The bilirubin level is greater than 4.5 mg/dL.
- Cord blood bilirubin is rising rapidly (>0.5 mg/dL per hour)
The aim of treatment is to prevent bilirubin neurotoxicity.
Blood component: ABO and Rh compatible, negative for offending antibody(ies), crossmatch compatible with maternal serum
Indications for “late” exchange transfusions
Serum bilirubin levels threatening to exceed ~20–22 mg/dL in term infants, lower levels in preterm or sick infants
Double-blood-volume exchange volume
- Term infants:
- Preterm infants:
- Term infants: 170 mL/kg
- Preterm infants: 200 mL/kg
Used to enhance recovery of the hemoglobin concentration and decrease the need for postnatal exchange transfusions.
It is also useful in Kell antigen–mediated alloimmune disease because, in that case, erythroid hypoplasia is an important factor.
Recombinant human erythropoietin, 200 U/kg, subcutaneously, three times per week for 6 weeks
Used prophylactically in any patient with moderate or severe hemolysis or in infants with bilirubin levels rising at more than 0.5 mg/dL per hour
Mainstay of treatment for unconjugated hyperbilirubinemia.
The object is to prevent bilirubin neurotoxicity
Phototherapy
Intensive phototherapy (≥30 μW/cm2) in the 430–490 nm band is delivered to as much of the infant’s surface area as possible.
Indications for initiating intensive phototherapy in full-term infants with HDFN
TSB levels
* ≥5 mg/dL at birth
* ≥10 mg/dL at 24 hours
* ~13–15 mg/dL at 48–72 hours
The effectiveness is influenced by the wavelength and irradiance of light, the surface area of exposed skin, and the duration of exposure
In preterm or sick infants, phototherapy is recommended at lower levels to avoid potentially risky exchange transfusions
TRUE OR FALSE
RhIg prophylaxis
Very effective when administered to women exposed to RhD-positive RBCs either from pregnancy or from transfusion, but not effective for preventing or reducing the severity of HDFN after alloimmunization has occurred
TRUE
Very effective when administered to women exposed to RhD-positive RBCs either from pregnancy or from transfusion, but not effective for preventing or reducing the severity of HDFN after alloimmunization has occurred
Intramuscular doses of ___________ of RhIg to nonsensitized RhD-negative mothers within ______of delivery have decreased Rh immunization by greater than 90%.
100 to 300 μg of RhIg
72 hours
In the absence of Rho(D) immunoglobulin (RhIg) prophylaxis, sensitization occurs in 7% to 16% of women at risk, within 6 months after delivery of the first RhD-positive ABO-compatible fetus
If the mother is RhD negative with an RhD-positive newborn, administration of antepartum RhIg at _________ weeks has decreased immunization to about 0.1%.
28 weeks
Rarely, sensitization may occur before the 28th week.
The standard dose of 300 μg of RhIg (1500 IU) affords protection for a fetomaternal transfusion of _______ mL of RhD-positive red cells or ______ mL or RhD-positive whole blood.
15 mL of RhD-positive red cells
30 mL or RhD-positive whole blood.
An important complication of elevated serum levels of indirect bilirubin, caused by bilirubin pigment deposition in the basal ganglia and brainstem nuclei, leading to neuronal necrosis
Kernicterus
Advocated by some for premenopausal women to prevent primary RBC alloimmunization
Transfusion of blood phenotypically matched for D and for the Kell (K1) antigen
