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Questions and Answers
What is the significance of the eluate of cord RBCs in cases of neonatal jaundice with a negative DAT result?
Which test is performed for all women in the first trimester to assess blood type and antibody presence?
Which of the following factors is NOT indicated when taking a detailed maternal history?
What is the main purpose of performing a fetal ultrasound in relation to maternal antibodies?
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What enhancing media can increase the sensitivity of the antibody detection tests?
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What role does the maternal IgG antibody play in hemolytic disease of the fetus and newborn (HDFN)?
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What condition results from the accelerated production of RBCs in the fetal bone marrow due to hemolysis?
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What happens when the fetal bone marrow can no longer keep up with the rate of RBC destruction?
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What is one of the results of hepatosplenomegaly in a fetus?
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What condition can develop due to severe anemia and hypoproteinemia from decreased hepatic production of plasma proteins?
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At what gestational age can hydrops fetalis typically develop if severe cases occur?
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What major complication can arise from the significant effects of hemolysis in a fetus?
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How has the prognosis for fetuses with hydrops fetalis changed over time?
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What is the primary immunoglobulin class transported across the placenta?
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Which of the following subclasses of IgG are most efficient in causing RBC intravascular hemolysis?
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What is the most antigenic RBC antigen associated with hemolytic disease of the fetus and newborn (HDFN)?
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Why is anti-Kell considered the most clinically significant non-Rh antibody in HDFN?
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What is the incidence of D immunization when there is a major ABO incompatibility between mother and fetus?
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Which of the following antibodies has been less commonly reported but can still cause HDFN?
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What factor influences the severity of hemolytic disease of the fetus and newborn (HDFN)?
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What follows pregnant women with anti-K RBC antibodies closely for evidence of HDFN?
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Why is antibody titer alone not a reliable predictor of HDFN severity?
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What is the significance of obtaining the father's blood specimen?
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What characteristic of homozygous fathers affects HDFN risk prediction?
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Which method is commonly used to determine fetal blood group genotype early in pregnancy?
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Why can't RhD serological testing alone predict the number of RhD genes in the father?
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What advantage does fetal DNA testing from maternal plasma provide?
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How can the severity of HDFN be reliably predicted?
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Which fetal blood group antigen can present an exception when predicting fetal risk based on antibody titer?
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What is the purpose of performing a Kleihauer-Betke test on maternal blood samples?
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Why are fetal cells resistant to acid in the Kleihauer-Betke test?
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How is the total volume of fetomaternal hemorrhage calculated?
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When should additional vials of RhIG be administered to the mother after calculating fetomaternal hemorrhage volume?
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What is a significant drawback of the Kleihauer-Betke test as mentioned?
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What is the recommended action for patients with a weak D phenotype regarding RhD typing?
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Which of the following conditions is NOT included in the differential diagnosis for hemolytic anemia as indicated?
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Which assay is mentioned as a newer technology that could provide more accurate quantification of fetomaternal hemorrhage?
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Study Notes
ABO Versus RhD HDFN
- HDFN is caused by maternal antibodies against fetal RBC antigens (primarily RhD).
- Maternal IgG antibodies cross the placenta and bind to fetal RBCs.
- Antibody-coated cells are removed from fetal circulation by macrophages in the spleen.
- Hemolysis of fetal RBCs leads to fetal anemia.
- Fetal bone marrow accelerates RBC production, but in severe cases, erythroblastosis fetalis occurs.
- Erythroblastosis fetalis is characterized by extramedullary hematopoiesis in the spleen and liver, leading to hepatosplenomegaly.
- Severe anemia and hypoproteinemia can cause hydrops fetalis, which can be fatal.
- RhIG is given to RhD-negative mothers to prevent sensitization.
- The risk of sensitization is 16% after an RhD-positive pregnancy without RhIG.
- IgG1 and IgG3 subclasses of maternal antibody are more efficient in RBC hemolysis than IgG2 and IgG4.
- RhD is the most antigenic RBC antigen.
- Anti-Kell is also clinically significant, as it can affect fetal RBC precursors, leading to severe anemia, and its titer is not predicative of fetal anemia.
- ABO incompatibility can protect against RhD immunization by clearing RhD-positive fetal RBCs in maternal circulation.
- Eluate of cord RBCs can reveal ABO antibodies in cases where ABO incompatibility is the only cause of neonatal jaundice.
Prenatal Diagnosis
- Detailed maternal history, including previous pregnancies, is essential.
- Fetal ultrasound to assess gestational age and ascites is indicated.
- All women undergo ABO, RhD typing and antibody detection testing in the first trimester.
- Antibody screening tests should be performed at least twice during pregnancy, and enhancing media can increase test sensitivity.
- Titration at the time of delivery is not recommended as it provides no clinically useful information.
Antibody Titer & Severity of HDFN
- Antibody titer alone cannot predict the severity of HDFN.
- Titer can remain moderate throughout pregnancy with severe fetal complications.
- Titer can rise rapidly, indicating increasing HDFN severity.
- Consistent titers below critical values usually predict mild or moderate fetal effects, except for anti-K.
Paternal Phenotype & Genotype
- Paternal blood should be tested to determine the presence and zygosity of the corresponding blood group antigen.
- Homozygous fathers have a 100% chance of passing the gene to their offspring, while heterozygous fathers have a 50% chance.
- Serological testing is sufficient for most blood group systems, including anti-K.
- Serological RhD testing cannot predict zygosity because there is no antithetical allele for the RhD gene.
Fetal DNA Testing
- Fetal DNA testing can be done through amniocentesis or CVS from 10-12 weeks gestation.
- Fetal DNA can also be isolated from maternal plasma to determine RhD and KEL genotype.
- Cell-free DNA (cDNA) method is used to stratify fetal risk in mothers with RBC alloimmunization.
Kleihauer-Betke Test
- Quantifies the fetal-maternal hemorrhage (FMH) volume.
- Maternal blood smear is treated with acid and stained, revealing fetal cells with Hgb F (pink).
- FMH volume estimate is calculated based on the percentage of fetal cells.
- Results are used to determine the number of RhIG vials required.
- The Kleihauer-Betke test is imprecise, and newer technologies like flow cytometry provide more accurate FMH quantification.
Maternal Weak D
- Serological reagents may not accurately detect RhD in some individuals with weak D phenotypes, which are caused by certain genetic backgrounds.
- RhD genetic testing is recommended for patients with a weak D phenotype to ensure accurate results.
Anti-D Immunoglobulin Administration
- RhIG is administered during pregnancy to prevent sensitization.
- Typically, RhIG is given at 28 weeks of gestation.
- Additional RhIG is administered after delivery and any other events causing potential fetal-maternal hemorrhage.
Differential Diagnosis
- RBC enzyme disorders: G6PD and pyruvate kinase deficiency
- Disorders of hemoglobin synthesis: alpha-thalassemias
- RBC membrane abnormalities: hereditary spherocytosis, elliptocytosis.
- Hemangiomas: Kasabach–Merritt syndrome
- Acquired conditions: sepsis, TORCH infections, parvovirus B19.
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Description
Explore the intricacies of Hemolytic Disease of the Fetus and Newborn (HDFN) caused by maternal antibodies, primarily focusing on ABO and RhD types. This quiz covers mechanisms, implications, and preventive measures, including the role of RhIG in RhD-negative mothers. Test your knowledge on this critical aspect of maternal-fetal medicine.