Ch 23: Perinatal Issues Flashcards
Perinatal Issues
What does HDFN, ITP, & FNAIT stand for?
Hemolytic Disease of the Fetus and Newborn, Immune Thrombocytopenia, and Fetal/Neonatal Alloimmune Thrombocytopenia
What causes hemolytic disease of the fetus and newborn (HDFN)?
Maternal red cell antibodies specific to a paternally derived red cell antigen
Maternal IgG antibodies cross the placenta and destroy fetal red cells, leading to fetal anemia and hyperbilirubinemia.
Which antibodies are the most common clinically significant causes of HDFN?
Anti-D and anti-K
Anti-C, -c, and -E are significant but less common. ABO HDFN is common but usually mild to moderate.
What types of antibodies are clinically insignificant with respect to HDFN?
Anti-I, -P1, -Le*, and -Le’
These antibodies can generally be ignored during pregnancy.
What is the purpose of molecular typing of cell-free fetal DNA?
To predict fetal red cell antigens
Paternal testing can also help predict fetal inheritance and determine paternal RHD zygosity.
What are the requirements for Red Blood Cells used in intrauterine transfusion?
Irradiated, CMV reduced-risk, hemoglobin S negative, group O, and <7 days old
These criteria help ensure the safety and compatibility of the transfusion.
What is the rosette test used for?
Detecting fetomaternal hemorrhage (FMH) of approximately 10 mL or more
The Kleihauer-Betke (KB) test quantifies the size of FMH levels.
How does flow cytometry compare to the KB test?
It can more precisely measure fetal hemoglobin and/or RhD-positive red cells
This makes flow cytometry a more accurate method for assessing fetal blood status.
How should the calculated Rh Immune Globulin dose be rounded?
Round up if ≥0.5, round down if <0.5
An additional vial should be added to the result in either case.
When may maternal platelet antibody develop in fetal/neonatal alloimmune thrombocytopenia (FNAIT)?
As early as 17 weeks of gestation in the first pregnancy
Fetal thrombocytopenia may develop as early as 20 weeks.
What type of platelets should be given to treat neonatal thrombocytopenia?
Irradiated, CMV-reduced-risk platelets
This treatment helps avoid hemorrhage in neonates.
What should be done if ‘human platelet antigen (HPA) selected platelets are not immediately available?
Transfuse random-donor platelets
This is a temporary solution until HPA selected platelets can be obtained.
How does thrombocytopenia in neonates born to mothers with autoimmune conditions compare to those born with FNAIT?
It tends to be less severe
This difference in severity may influence treatment and monitoring strategies.
What is the primary cause of HDFN?
Destruction of fetal and newborn red cells by maternal red cell antibodies
What role does Rh Immune Globulin (RhiG) play in HDFN?
It supports the diagnosis and treatment of HDFN
What antibodies are more likely to cause early and/or severe HDFN?
IgG1 and IgG3
Increased hematopoietic drive due to HDFN causes what condition?
Erythroblastosis fetalis- liver and spleen enlargement secondary to extramedullary hematopoiesis, and portal hypertension.
What are the consequences of liver enlargement in HDFN?
It can lead to hydrops fetalis, which is decreased production of albumin and associated decreased plasma oncotic pressure with generalized edema, ascites, and effusions.
What severe condition can develop from untreated hydrops fetalis?
Fetal death
What is kernicterus?
Permanent brain damage caused by hyperbilirubinemia
How does maternal antibody levels change after birth?
Typically decreases in the neonate over 12 weeks
What is the most common cause of HDFN?
ABO incompatibility
What is the typical treatment for ABO HDFN?
Phototherapy
What percentage of the population experiences HDFN secondary to non-ABO IgG antibodies?
1%
Fill in the blank: The maternal antibody typically decreases in the neonate over _______.
12 weeks
What is the mean age for prolonged postnatal hyporegenerative anemia in Rh-isoimmunized infants?
43.3 days
True or False: Routine titration of anti-A and anti-B is required in cases of ABO HDFN.
False
What can cause prolonged neonatal anemia aside from fetal anemia?
Marrow erythropoietic suppression
What antibodies can cause anemia through marrow erythropoietic suppression?
Anti-K, anti-Jra, anti-Ge, and rare cases of high-titer IgG anti-M antibodies
What is maternal alloimmunization?
The process by which females become alloimmunized to red cell antigens through pregnancy, blood transfusion, transplantation, or unknown stimuli.
Alloimmunization can lead to hemolytic disease of the fetus and newborn (HDFN) in subsequent pregnancies.
What is fetomaternal hemorrhage (FMH)?
The spontaneous occurrence of fetal blood entering the maternal circulation during gestation.
FMH happens in a significant proportion of females and increases with gestational age.
What is the likelihood of FMH in the first trimester?
3%
The likelihood increases to 12% in the second trimester and 45% in the third trimester.
What is the highest risk period for FMH?
At delivery.
This is when the likelihood of fetal blood entering the maternal circulation is the greatest.
Why is the first pregnancy rarely affected by HDFN?
Because the maternal immune system has not yet formed red cell antibodies and switched from IgM to IgG.
This switch is necessary for HDFN to become a clinically significant risk.
What factors are associated with increased risk of maternal hemorrhage (MH)?
- Abdominal trauma
- Placenta previa
- Abruptio placentae
- Ectopic pregnancy
- Threatened termination
- Fetal death
- Amniocentesis
- Fetal blood sampling (FBS)
- Intrauterine manipulation
- Abortion
These factors can lead to increased risk of FMH.
What is the most potent immunogenic red cell antigen?
RhD.
RhD is the primary cause of HDFN in areas without good access to prenatal care.
How much RhD-positive red cells can stimulate alloantibody production?
As little as 0.1 to 1 mL.
This small amount can trigger the maternal immune response.
What is the effect of ABO incompatibility on alloimmunization rates?
The alloimmunization rate for the RhD antigen is markedly diminished in ABO-incompatible, RhD-negative mothers.
This demonstrates a partially protective effect of ABO incompatibility.
Which antibody is an important cause of severe HDFN?
Anti-K.
Anti-K is a potent immunogen, but it causes less hemolysis than anti-D.
What antibodies can also cause moderate or severe disease in HDFN?
- E
- c
- C
- k
- Kpa
- Kpb
- Ku
- Jsa
- Jsb
- Jka
- Fya
- Fyb
- S
- s
- U
The presence of multiple antibodies may lead to more severe HDFN.
What is involved in the diagnosis of HDFN?
The cooperation of the patient, health-care provider, and blood bank/transfusion laboratory personnel.
A previous affected pregnancy predicts the potential for future HDFN.
What should be performed during the first prenatal visit for HDFN diagnosis?
- Maternal ABO and RhD type
- Antibody screen to detect IgG-phase antibodies
This is crucial for identifying potential risks for HDFN.
List common indications associated with FMH for which RhIG is recommended.
- Delivery of RhD-positive or serologic-weak-D infant
- Antepartum hemorrhage
- Spontaneous or therapeutic abortion
- Abdominal trauma
- Ectopic pregnancy
- Stillbirth
- Fetal demise
- Placental abruption
- Amniocentesis
- Chorionic villus sampling
- Cordocentesis
- External cephalic version
- Manual removal of placenta
RhIG is recommended to prevent HDFN in these situations.
What is fetal risk stratification through prediction?
It is accomplished by genotyping fetal DNA using amniocytes or noninvasively with cell-free fetal DNA in maternal plasma.
At what gestational age can the noninvasive test for fetal red cell antigen type be performed?
As early as 16 weeks’ gestational age.
What fetal D, C, c, E, and K status can be predicted by the noninvasive test?
It can predict the fetal D, C, c, E, and K status.
What is the sensitivity of the noninvasive test for fetal red cell antigen type?
99.8%.
How often should maternal antibody titers be monitored during an alloimmunized pregnancy?
Monthly to biweekly.
What indicates that the fetus is at risk for clinically significant HDFN?
A maternal antibody titer reaching a level above the critical titer.
What is the AABB-recommended method for titration?
A saline AHG test incubated for 60 minutes at 37 C (tube method).
What are the potential issues with other titration methods like albumin or gel?
They may result in higher titers than the recommended method.
What is the critical titer range for anti-D?
Usually 8 to 32 in the AHG phase.
Why might a titer of 8 or lower be accepted as critical for sensitization to the K antigen?
Because it may lead to hypoproliferative anemia.
What is the typical critical titer range for other antibody specificities?
Typically 16 to 32.
What indicates moderate to severe fetal anemia on a Doppler fetal ultrasound?
An increase in the velocity of the end systolic MCA blood flow to > 1.5 multiples of the mean (MoM).
What is indicated for treatment in cases of severe anemia if it is too early for delivery?
Fetal transfusion.
What is the purpose of fetal transfusion?
To suppress fetal erythropoiesis and the production of red cells with the antigen corresponding to the maternal alloantibody.
What type of RBC units are preferred for intrauterine transfusion (IUT)?
1) Group O, 2) Crossmatch compatible with maternal plasma, 3) Irradiated to prevent TA-GVHD, 4) CMV-reduced-risk.
What is the preferred age of RBC units for transfusion?
Collected within 5 to 7 days.
What hematocrit range is recommended for washed or concentrated RBC units?
70% to 85%.
What is a common practice regarding blood type for IUT?
Most institutions will routinely use group O, RhD-negative units.
How can the volume of blood to be transfused be calculated?
By multiplying the ultrasound-estimated fetal weight by 0.14 mL/g, then adjusting for hematocrit differences.
What is the estimated volume to transfuse for a fetal weight of 1000 g with a desired posttransfusion hematocrit of 40%?
41.2 mL
Calculated using the formula: [1000 g x 0.14 mL/g × (0.40 - 0.15)]/0.85
What should be checked after fetal transfusion to confirm the desired posttransfusion hemoglobin level?
Hemoglobin or hematocrit
When should intrauterine transfusion (IUT) be repeated?
When the calculated hematocrit has declined to 30% or below
What is the outcome of a successful IUT treatment in the absence of hydrops fetalis?
Generally good, with a low incidence of neurodevelopmental impairment and a low risk of fetal loss
What alternative therapies to IUT have been attempted during pregnancy?
- Maternal plasma exchange
- Intravenous immune globulin (IVIG)
What is the effect of IVIG infusion on anti-D titers?
Stabilizes anti-D titers
What can plasma exchange temporarily reduce antibody levels by?
Up to 75%
What is the most common indication for exchange transfusion in neonates?
Hyperbilirubinemia caused by HDFN
What are the two critical objectives of exchange transfusion when treating HDFN?
- Removal of unconjugated bilirubin
- Maximization of albumin-binding of residual bilirubin
What is the preferred timing for exchange transfusion to prevent kernicterus?
Before the development of kernicterus
What is the typical duration for a total double-volume exchange transfusion?
90 to 120 minutes
What is typically used to resuspend RBCs for an exchange transfusion?
ABO-compatible, thawed Fresh Frozen Plasma (FFP)
What should be monitored during the first few hours following exchange transfusion?
Infant plasma glucose levels
What is the absolute maximum volume of blood that can be removed and replaced during an exchange transfusion?
No more than 5 mL/kg body weight or 5% of the infant’s blood volume
RhD-negative and some RhD-positive females are candidates for what prophylaxis during pregnancy?
Rh Immune Globulin (RhIG)
What does RhIG primarily contain?
Predominantly IgG-subtype anti-D
What is the recommended first dose of RhIG during pregnancy?
At 28 weeks’ gestation
What is the risk reduction of an RhD-negative mother becoming immunized by an RhD-positive fetus after appropriate RhIG administration?
From about 16% to <0.1%
What should be done for females with apparent antibodies to both D and C before determining their candidacy for RhIG?
Investigated for presence of anti-G
Fill in the blank: The volume to transfuse is calculated using the formula __________.
[1000 g x 0.14 mL/g × (0.40 - 0.15)]/0.85
What should a pregnant RhD-negative female with anti-G receive?
RhIG
How may RhiG prophylactic protocols differ?
Outside of the United States
What type of testing can determine if a fetus is RhD-positive?
cffDNA testing
What can fDNA obtained from maternal blood samples identify?
Pregnancies with RhD-negative fetuses
What is the typical outcome of RhIG administration during pregnancy on antibody screening results?
Positive antibody screening result in the mother
What is the risk level of the anti-D titer to the fetus after RhIG administration?
Low risk
Occasionally, RhIG will cause a positive result in which newborn test?
DAT result
What is the mechanism of action of RhIG?
Opsonizes RhD-positive red cells and clears them by macrophages in the spleen
What is the primary immunoglobulin class found in RhIG?
IgG
What component does active RhD immunization have that is significant?
IgM component
How can new anti-D produced by the mother be detected?
In the saline phase
What treatment can completely or partially inactivate new anti-D?
2-mercaptoethanol or DTT treatment
What is the typical titer level for passively acquired anti-D from RhIG?
Rarely achieves a titer >4
How were pregnant women with serologic weak D historically treated?
As RhD negative and deemed eligible for RhIG
What is the underlying RHD genotype for most individuals with serologic weak D phenotype in populations of European ancestry?
Weak D types 1, 2, or 3
What does genotyping pregnant females with serologic weak D phenotype allow for?
Selective administration of RhIG
What should be done if a female is found to have serologic weak D phenotype at the time of delivery?
Administer RhIG and perform subsequent RHD genotyping
What is important to counsel females found to have weak D genotypes 1, 2, or 3 about?
Their RHD status and that they do not need RhIG in the future
What should females with RHD genotypes other than weak D types 1, 2, or 3 be considered for transfusion?
RhD negative
What should RhD-negative mothers without alloanti-D receive after delivering an RhD-positive infant?
RhIG
What percentage of the RhIG dose given at 28 weeks’ gestation is present in the mother at delivery?
About 10%
What is used to determine the correct RhIG dose for postpartum administration?
Maternal blood sample screened for FMH
What are the three tests available to test for FMH?
- Rosette screening test
- Kleihauer-Betke (KB) test
- Flow cytometry test
What does the rosette test indicate when positive?
More than 10 mL of RhD-positive fetal red cells in maternal circulation
When should the maternal specimen for the rosette test be collected?
1 to 2 hours after all products of conception are delivered
What is the purpose of the rosette test?
To detect fetal-maternal hemorrhage (FMH) and count rosettes microscopically
What is the standard dose of RhiG given if the screening test result is negative?
300 µg
What does a positive screening test result indicate?
FMH may be > 15 mL of fetal red cells
What can cause false-positive results in the rosette test?
Variant RHD genes and positive maternal DAT result
Which assays are used to quantify the volume of FMH?
- KB test
- Flow cytometric assessment
What is the KB test based on?
The resistance of fetal hemoglobin to acid treatment
How is the volume of FMH calculated using the KB test?
(Fetal cells/total cells counted) × maternal blood volume (mL) = FMH, whole blood (mL)
What is a potential confounding factor in the KB test results?
Presence of fetal hemoglobin (HbF) in maternal cells
What is flow cytometry used for in this context?
To differentiate between FMH and alternate causes
What is the risk of FMH >30 mL at the time of delivery?
Approximately 1 in 1250 with singleton births
How is the dose of RhiG calculated based on FMH volume?
FMH volume is estimated, then calculated as FMH/30 mL per vial of RhiG
What is the rounding rule for RhiG dosage calculation using the KB test?
Round up if the decimal point is ≥5, otherwise round down
When should postpartum RhiG be administered?
Within 72 hours of delivery
What should be done if prophylaxis with RhiG is delayed?
RhiG treatment should still be provided
What is the route of administration for RhiG?
- Intramuscular (IM)
- Intravenous (IV)
What factors can lead to failure of RhiG to prevent immunization to RhD?
- Increased FMH volumes
- High maternal body weight
What is the goal of red cell selection in HDFN prevention?
To reduce exposure of females of childbearing potential to red cell alloantigens
What type of RBCs are used initially for females in life-threatening hemorrhage?
RhD-negative RBCs
What is the incidence of maternal thrombocytopenia during pregnancy?
5% to 10% of pregnant individuals
What are the main causes of maternal thrombocytopenia?
- Incidental thrombocytopenia of pregnancy
- Thrombocytopenia complicating hypertensive disorders
- Immunologic disorders
What is FNAIT?
Fetal and Neonatal Alloimmune Thrombocytopenia caused by maternal antibodies to fetal platelets
What is the most common cause of FNAIT in people of European ancestry?
Antibodies to human platelet antigen (HPA)-1a
What percentage of FNAIT cases are caused by antibodies to HPA-1a?
Approximately 79%
What is the reported incidence of affected pregnancies for FNAIT?
Ranges from 0.3 to 1 in 1000
What are the two categories of immune-mediated thrombocytopenia?
- Alloantibodies (FNAIT)
- Autoantibodies (e.g., ITP, SLE)
What are common symptoms of FNAIT seen at birth?
- Petechiae
- Bleeding
- Intracranial hemorrhage (ICH)
What is the incidence of FNAIT-related ICH in live births?
0.02 to 0.1 in 1000 live births
When do more than 50% of ICHs occur?
In utero, often before 28 weeks’ gestation
What percentage of ICH events are fatal?
Thirty-five percent
What is one of the most important predictors of thrombocytopenia in a fetus?
A history of antenatal ICH or FNAIT in a sibling
What should the mother and father be genotyped for?
Platelet antigen genes
What is the purpose of screening the mother for alloantibodies?
To detect antibodies to platelet antigens
What are the methods for direct fetal platelet antigen genotyping?
- Amniocentesis (18-20 weeks) * Chorionic villus sampling (8-10 weeks) * Fetal DNA in maternal blood sample for HPA-1a antibodies
What is the associated risk of pregnancy loss with amniocentesis?
0.5% to 1.0%
Why is chorionic villus sampling not recommended?
It increases the risk of alloimmunization
What does noninvasive prenatal testing utilize?
fiDNA techniques
What confirms a diagnosis of FNAIT?
- Maternal HPA antibody * Maternal/paternal or maternal/neonatal HPA incompatibility * Fetal or neonatal thrombocytopenia or hemorrhage
What is the protective factor against alloimmunization in mothers?
The absence of the HLA-DRB3*01:01 allele
What is a recommended threshold for transfusion in nonbleeding, asymptomatic newborns?
30,000/uL
What platelet count threshold is suggested for neonates with bleeding symptoms?
Initially above 100,000/uL, then above 50,000/uL for at least 7 days
What type of platelet transfusions lead to better outcomes?
HPA-selected platelet transfusions
What is the typical platelet nadir period after delivery?
Within 48 hours of delivery
What is the incidence of ITP in pregnant individuals?
1 in 1000 to 1 in 10,000
What do ASH guidelines state about obtaining intrapartum fetal platelet counts?
There is no evidence to support routine obtaining
What is the recommended treatment approach for symptomatic ITP patients?
Initiate treatment when platelets are <20,000 to 30,000/uL or before a procedure
What is the incidence of severe neonatal thrombocytopenia in infants of mothers with ITP?
9% to 15%
What should be performed for all infants born to mothers with a history of ITP?
An early postnatal platelet count
What should be avoided until the platelet count is known to be normal in newborns?
IM injections such as vitamin K
What is the typical timing for the nadir of platelet counts in neonates?
2 to 5 days after birth
What is the common treatment for neonates with clinical hemorrhage or platelet counts <30,000/uL?
- IVIG * Platelet transfusion
What is the general approach to treating maternal thrombocytopenia secondary to SLE?
Similar to the approach for ITP patients
If RhIg is given to a pregnant D negative mom at 28wks and the anti- titer is 16, in how many weeks will the titer fall to 4?
7
The half-life of IgG = 23-25 days (~3.5 wks)
16 to 8= 3.5, 8 to 4= 3.5
3.5 + 3.5=7
In HDFN cases where the offending red cell ag is very rare, the blood exchange transfusion can most easily be obtained from the?
Mother
