4.9 - Hemolytic Disease of the Fetus and Newborn

All of the following are reasons for a positive DAT on cord blood cells of a newborn except:

A. High concentrations of Wharton jelly on cord blood cells

B. Immune Anti-A from an O mother on the cells of an A baby

C. Immune Anti-D from an Rh negative mother on the cells of an Rh-positive baby

D. Immune Anti-K from a K-negative mother on the cells of a K-negative baby

D. Immune Anti-K from a K-negative mother on the cells of a K-negative baby

• DAT (Direct Antiglobulin Test) detects IgG or complement bound to RBCs in vivo

• Positive DAT in newborns typically due to maternal IgG antibodies crossing the placenta and coating fetal RBCs

• A: Wharton jelly contamination → false-positive DAT (artifact, but can cause positivity)

• B: ABO HDN (e.g., O mother → A baby) → immune anti-A/B crosses placenta → positive DAT

• C: Rh HDN (Rh– mother → Rh+ baby) → anti-D coats fetal RBCs → positive DAT

• D: K-negative mother → K-negative baby → no antigen-antibody reaction → cannot cause positive DAT

Summary:
A K-negative mother with a K-negative baby cannot produce anti-K–mediated hemolysis; therefore, option D does not explain a positive DAT.

A fetal screen yielded negative results on a mother who is O negative and infant who is O positive. What course of action should be taken?

A. Perform a Kleihauer-Betke test

B. Issue one full dose of RhIg

C. Perform a DAT on the infant

D. Perform an antibody screen on the mother

B. Issue one full dose of RhIg

• Fetal screen (rosette test): qualitative test to detect fetal D-positive cells in maternal circulation

• Negative result → no or minimal fetomaternal hemorrhage (<30 mL whole blood / 15 mL packed RBCs)

• Standard practice: still administer one 300 µg dose of Rh immune globulin (RhIg) to all Rh– mothers with Rh+ infants as prophylaxis

• A: Kleihauer-Betke is for quantifying large hemorrhages when fetal screen is positive

• C: DAT on infant unrelated to RhIg dosing decision

• D: Antibody screen not needed post-delivery unless immune anti-D suspected

Summary:
After a negative fetal screen with Rh– mother / Rh+ infant, administer one full dose (300 µg) RhIg to prevent Rh alloimmunization.

What should be done when a woman who is 24 weeks pregnant has a positive antibody screen?

A. Perform an antibody identification panel; titer, if necessary

B. No need to do anything until 30 weeks' gestation

C. Administer RhIg

D. Adsorb the antibody onto antigen-positive cells

A. Perform an antibody identification panel; titer, if necessary

• A positive antibody screen in pregnancy indicates maternal alloimmunization — potential risk for HDFN (hemolytic disease of the fetus and newborn)

• Next step: perform antibody identification to determine antibody specificity and titer clinically significant IgG antibodies (e.g., anti-D, -c, -K, etc.)

• Titers are used to monitor for rising levels suggesting fetal risk

• B: Waiting risks missing early detection of significant antibodies

• C: RhIg only for unsensitized Rh– women; not appropriate once antibody present

• D: Adsorption used in complex antibody workups, not routine prenatal screening

Summary:
A positive antibody screen during pregnancy requires antibody identification and titer to assess potential for HDFN and guide obstetric monitoring.

All of the following are interventions for fetal distress caused by maternal antibodies attacking fetal cells except:

A. Intrauterine transfusion

B. Plasmapheresis on the mother

C. Transfusion of antigen-positive cells to the mother

D. Middle cerebral artery peak systolic velocity (MCA-PSV)

C. Transfusion of antigen-positive cells to the mother

• Fetal distress due to maternal alloantibodies (e.g., anti-D, anti-c, anti-K) is managed by reducing maternal antibody levels or supporting the fetus.

• A: Intrauterine transfusion — provides compatible RBCs to the fetus; corrects anemia.

• B: Plasmapheresis on the mother — lowers circulating maternal antibody levels.

• D: MCA-PSV — noninvasive Doppler ultrasound to monitor fetal anemia severity.

• C: Antigen-positive transfusion to the mother → would boost antibody production, worsening HDFN.

Summary:
Transfusing antigen-positive blood to the mother would intensify sensitization, not treat it—therefore, it is not an intervention for antibody-mediated fetal distress.

Cord blood cells are washed six times with saline and the DAT result and negative control are still positive. What should be done next?

A. Obtain a heelstick sample

B. Record the DAT result as positive

C. Obtain another cord blood sample

D. Perform elution on the cord blood cells

A. Obtain a heelstick sample

• Persistent positive DAT after multiple saline washes suggests contamination, most likely from Wharton jelly or maternal blood in the cord sample.

• Next step: obtain a fresh heelstick specimen directly from the newborn for accurate testing.

• This eliminates interference and confirms whether the DAT is truly positive.

• B: Recording DAT as positive without confirmation risks reporting an artifact.

• C: Another cord sample may have the same contamination issue.

• D: Elution is unnecessary until a genuine positive DAT is confirmed.

Summary:
If DAT remains positive after multiple washes, collect a heelstick sample to rule out Wharton jelly or maternal blood contamination before interpreting results.

What can be done if HDFN is caused by maternal Anti-K?

A. Given Kell immune globulin

B. Monitor the mother's antibody level

C. Prevent formation of K-positive cells in the fetus

D. Not a problem; Anti-K is not known to cause HDFN

B. Monitor the mother's antibody level

• Anti-K (Kell) can cause severe HDFN — it suppresses fetal erythropoiesis in addition to hemolysis.

• There is no immune globulin (like RhIg) available to prevent Anti-K formation.

• Management focuses on antibody identification and serial titers, with fetal monitoring (e.g., MCA-PSV Doppler) to detect anemia.

• Intrauterine transfusion may be needed if fetal anemia develops.

• A: No Kell immune globulin exists.

• C: Preventing K-positive fetal cells is biologically impossible.

• D: Incorrect — Anti-K is highly clinically significant and a well-known cause of HDFN.

Summary:
When HDFN is due to maternal Anti-K, there is no prophylaxis—management requires serial antibody titers and fetal monitoring for anemia.

Should an O-negative mother receive RhIg if a positive DAT on the newborn is caused by immune Anti-A?

A. No, the mother is not a candidate for RhIg because of the positive DAT result

B. Yes, if the baby's type is Rh negative

C. Yes, if the baby's type is Rh positive

D. No, the baby's problem is unrelated to Rh blood group antibodies

C. Yes, if the baby's type is Rh positive

• RhIg prophylaxis is indicated for Rh-negative mothers who deliver an Rh-positive infant, regardless of other antibody findings.

• A positive DAT due to anti-A reflects ABO incompatibility, not Rh sensitization—these are independent issues.

• RhIg prevents maternal formation of anti-D, not anti-A or anti-B.

• A: Incorrect—DAT positivity from ABO antibodies doesn’t affect RhIg eligibility.

• B: Incorrect—RhIg is unnecessary if baby is Rh negative.

• D: Incorrect—though the DAT is unrelated to Rh, RhIg is still needed for D prevention if infant is Rh+.

Summary:
An O-negative mother should receive RhIg if her infant is Rh positive, even if the positive DAT is due to immune anti-A and unrelated to the Rh system.

Should an A-negative woman who has just had a miscarriage receive RhIg?

A. Yes, but only if she does not have evidence of active Anti-D

B. No, the type of the baby is unknown

C. Yes, but only a mini dose regardless of trimester

D. No, RhIg is given to women at full-term pregnancies only

A. Yes, but only if she does not have evidence of active Anti-D

• RhIg is indicated for Rh-negative women after any pregnancy event (delivery, miscarriage, abortion, ectopic, etc.) that could expose them to Rh-positive fetal cells.

• Always confirm she has not already formed immune Anti-D—if present, RhIg offers no benefit.

• Dose depends on gestational age: early losses (<12 weeks) usually get 50 µg, later ones 300 µg.

• B: Incorrect—fetal type need not be known; prophylaxis given empirically.

• C: Incorrect—dose depends on gestational age, not automatic mini-dose.

• D: Incorrect—RhIg is given after any sensitizing event, not just full-term.

Summary:
An A-negative woman after miscarriage should receive RhIg unle

The blood bank analyzer reports a type of O neg on a woman who is 6 weeks pregnant with vaginal bleeding. The woman tells the emergency department she is O pos and presents a blood donor card. The MLS performs a test for weak D and observes a 1+ reaction in the AHG phase. The KB test result is negative. Is this woman a candidate for RhIg?

A. Molecular testing is indicated to ascertain the type of weak D

B. Yes, she is Rh positive

C. No, there is no evidence of a fetal bleed

A. Molecular testing is indicated to ascertain the type of weak D

• A 1+ weak D result means the woman expresses a partial or variant D antigen, not a clear Rh-positive or Rh-negative status.

• Molecular genotyping distinguishes between weak D types 1, 2, or 3 (manage as Rh⁺, no RhIg needed) and partial/other variants (manage as Rh⁻, RhIg indicated).

• Without genotyping, treat as Rh-negative and give RhIg to prevent possible sensitization.

• KB test detects fetomaternal hemorrhage but does not determine RhIg eligibility.

• B: Incorrect—weak D does not confirm true Rh positivity.

• C: Incorrect—RhIg is given to prevent sensitization, not just when fetal bleed is present.

Summary:
A weak D (1+) result requires molecular typing to define D variant status; until confirmed, treat as Rh-negative and administer RhIg to prevent alloimmunization.

Which of the following patients would be a candidate for RhIg?

A. B-positive mother; B-negative baby; first pregnancy; no Anti-D in mother

B. O-negative mother; A-positive baby; second pregnancy; no Anti-D in mother

C. A-negative mother; O-negative baby; fourth pregnancy; Anti-D in mother

D. AB-negative mother; B-positive baby; second pregnancy; Anti-D in mother

B. O-negative mother; A-positive baby; second pregnancy; no Anti-D in mother

• RhIg is given to Rh-negative, unsensitized women who deliver or may have been exposed to Rh-positive fetal cells, regardless of parity.

• Purpose: prevent formation of immune Anti-D following fetomaternal hemorrhage.

• Given: within 72 hours postpartum or after any sensitizing event (amniocentesis, miscarriage, etc.).

• A: Mother is Rh positive → not a candidate.

• C & D: Mothers already have Anti-D → prophylaxis ineffective once sensitized.

Summary:
The O-negative mother with an A-positive baby and no Anti-D is the only candidate for RhIg, as she is Rh-negative and unsensitized.

The Kleihauer-Bette acid elution test identifies 40 fetal cells in 2,000 maternal RBCs. How many full doses of RhIg are indicated?

A. 1

B. 2

C. 3

D. 4

D. 4

((40/2000) x 5000) / 30 = 3.3 doses. Add 1 vial

Summary:
A 2% fetal bleed (≈100 mL) requires 4 full doses of RhIg (300 µg each) to neutralize fetal D-positive cells and prevent maternal sensitization.

Kernicterus is caused by the effects of:

A. Anemia

B. Unconjugated bilirubin

C. Antibody specificity

D. Antibody titer

B. Unconjugated bilirubin

• Kernicterus = bilirubin-induced neurologic dysfunction in newborns.

• Caused by excess unconjugated (indirect) bilirubin crossing the immature blood–brain barrier, depositing in brain tissue (especially basal ganglia).

• Seen in severe HDFN, where hemolysis overwhelms hepatic conjugation capacity.

• Leads to irreversible brain damage if untreated.

• A: Anemia contributes to HDFN severity but does not directly cause kernicterus.

• C/D: Antibody specificity or titer determines severity of hemolysis, not the mechanism of neurologic injury.

Summary:
Unconjugated bilirubin accumulation in the brain causes kernicterus, a severe neurologic complication of HDFN.

Anti-E detected in the serum of a woman in the first trimester of pregnancy. The first titer for Anti-E is 32. Two weeks later, the antibody titer is 64 and then 128 after another 2 weeks. Clinically, there are beginning signs of fetal distress. What may be done?

A. Induce labor for early delivery

B. Perform plasmapheresis to remove Anti-E from the mother

C. Administer RhIg to the mother

D. Perform an intrauterine transfusion using E-negative cells

B. Perform plasmapheresis to remove Anti-E from the mother

• Rapidly rising Anti-E titers (32 → 64 → 128) and early fetal distress indicate severe HDFN risk.

• Plasmapheresis can temporarily reduce maternal antibody levels, lowering transplacental transfer of Anti-E and alleviating fetal hemolysis.

• Often used before 20–24 weeks gestation, when the fetus is too immature for intrauterine transfusion.

• Later in gestation, intrauterine transfusion may follow if anemia persists.

• A: Inducing labor at this stage (first trimester) is not viable.

• C: RhIg targets anti-D, not anti-E.

• D: Intrauterine transfusion appropriate only when fetus is large enough (typically ≥24 weeks).

Summary:
In early pregnancy with rising Anti-E titers and fetal distress, plasmapheresis is the treatment of choice to lower maternal antibody levels until the fetus is mature enough for further intervention.

What testing is done for exchange transfusion when the mother's serum contains an alloantibody?

A. Crossmatching and antibody screen

B. ABO, Rh, antibody screen, and crossmatching

C. ABO, Rh, antibody screen

D. ABO and Rh only

B. ABO, Rh, antibody screen, and crossmatching

• For exchange transfusion, blood must be compatible with both mother and infant to prevent additional hemolysis.

• Testing includes:

  • ABO and Rh typing of mother and infant

  • Antibody screen on maternal serum to detect alloantibodies

  • Crossmatch donor units with maternal serum (preferred) to ensure antigen-negative, compatible blood

• The goal is to remove antibody-coated RBCs and bilirubin while replacing with antigen-negative RBCs.

• A: Incomplete—ABO/Rh typing always required.

• C: Missing crossmatch step, essential for antibody compatibility.

• D: Insufficient—fails to detect or account for maternal alloantibodies.

Summary:
For exchange transfusion in maternal alloimmunization, perform ABO, Rh, antibody screen, and crossmatch to ensure antigen-negative, compatible donor blood.

Which blood type may be transfused to an AB-positive baby who has HDFN caused by Anti-D?

A. AB negative, CMV negative, Hgb S negative; irradiated or O negative, CMV negative, Hgb S negative

B. AB positive, CMV negative; irradiated or O positive, CMV negative

C. AB negative only

D. O negative only

A. AB negative, CMV negative, Hgb S negative; irradiated or O negative, CMV negative, Hgb S negative

• Exchange transfusion for Anti-D HDFN: infant’s RBCs must be compatible with both mother and baby and D-negative.

• Requirements:

  • Rh negative to prevent further hemolysis

  • ABO compatible — for an AB-positive infant, use AB-negative or O-negative cells

  • CMV negative, Hgb S negative, and irradiated for neonatal safety

• B: Incorrect — Rh-positive blood worsens hemolysis.

• C: Too limited; O-negative also acceptable.

• D: Incomplete—lacks CMV-, Hgb S-, and irradiation criteria.

Summary:
For an AB-positive infant with Anti-D HDFN, use D-negative, CMV-negative, Hgb S-negative, irradiated blood—either AB-negative or O-negative units.

All of the following are routinely performed on a cord blood sample except:

A. Forward ABO typing

B. Antibody screen

C. Rh typing

D. DAT

B. Antibody screen

• Cord blood testing is performed to evaluate potential HDFN and includes:

  • Forward ABO typing — to determine the newborn’s ABO group

  • Rh typing — to determine if RhIg is needed for the mother

  • DAT (Direct Antiglobulin Test) — to detect antibody coating on neonatal RBCs

• Antibody screen is not done on cord blood because the baby’s plasma may contain maternal antibodies, making results unreliable.

Summary:
Routine cord blood testing includes ABO, Rh, and DAT, but not an antibody screen, since maternal antibodies can interfere with interpretation.

Why do Rh-negative women tend to have a positive antibody screen compared with Rh-positive women of childbearing age?

A. They have formed active Anti-D

B. They have received RhIg

C. They have formed Anti-K

D. They have a higher rate of transfusion

B. They have received RhIg

• RhIg (Rh immune globulin) is routinely administered to Rh-negative women during and after pregnancy to prevent Anti-D alloimmunization.

• Because RhIg contains passive Anti-D, it can cause a transient positive antibody screen, typically weak and nonreactive at the AHG phase.

• This is a preventive measure, not evidence of sensitization.

• A: Active Anti-D formation indicates sensitization, not a normal finding.

• C: Anti-K formation is unrelated to Rh status or prophylaxis.

• D: Transfusion history is not the reason for higher antibody detection in this group.

Summary:
Rh-negative women often have a positive antibody screen due to passively acquired Anti-D from RhIg prophylaxis, not true alloimmunization.

An O-neg mother gave birth to a B-pos infant. The mother had no history of antibodies or transfusion. This was her first child. The baby was mildly jaundiced, and the DAT result was weakly positive with polyspecific antisera. What could have caused the positive DAT result?

A. Anti-D from the mother coating the infant RBCs

B. An alloantibody, such as Anti-K, coating the infant RBCs

C. Maternal Anti-B coating the infant RBCs

D. Maternal Anti-A,B coating the infant RBCs

D. Maternal Anti-A,B coating the infant RBCs

• Group O mothers produce IgG anti-A,B that crosses placenta

• Causes ABO HDFN that is typically mild with weak/variable DAT

• Fits first pregnancy (naturally occurring antibodies; no prior sensitization needed)

• A (Anti-D): Would require maternal sensitization; tends to cause more severe HDFN

• B (Alloanti-K): Unlikely without transfusion/previous pregnancy; usually more severe anemia

• C (Anti-B only): Usually IgM, does not cross placenta effectively

Summary:
In an O-negative mother with a B-positive infant, a weakly positive DAT and mild jaundice are best explained by maternal IgG anti-A,B causing mild ABO HDFN.

SITUATION: RhIg is requested on a 28-year-old woman with suspected abortion. When the nurse arrives in the blood bank to pick up the RhIg, she asks the MLS if it is a minidose. The MLS replies that it is a full dose, not a minidose. The nurse then requests to take 50 µg from the 300 µg syringe to satisfy the physician’s orders. What course of action should the MLS take?

A. Let the nurse take the syringe of RhIg, so that she may withdraw 50 µg
B. Call a supervisor or pathologist
C. Instruct the nurse that the blood bank does not stock minidoses of RhIg and manipulating the full dose will compromise the purity of the product
D. Instruct the nurse that the blood bank does not stock minidoses of RhIg, and relay this information to the patient’s physician

D. Instruct the nurse that the blood bank does not stock minidoses of RhIg, and relay this information to the patient’s physician

• RhIg (Rho(D) Immune Globulin) is a sterile, premeasured product that must not be altered or subdivided, as this compromises sterility and dosage accuracy.

• The MLS cannot permit anyone to withdraw a smaller amount (e.g., 50 µg from a 300 µg syringe).

• The proper action is to inform the nurse that the blood bank does not carry a minidose and to notify the physician so that appropriate dosing can be ordered from the manufacturer.

Summary:
Never manipulate RhIg dosage. Do not withdraw partial volumes — inform the nurse and relay to the physician for appropriate order adjustment.