49.Hemolytic disease. Rh isoimmunization

Question 1

what is Rhesus (Rh) alloimmunization?

Answer 1

an immune-mediated disorder that occurs in pregnant, Rh-negative woman who is carrying an Rh-positive fetus

due to sensitization, in 2nd pregnancy baby is at risk

Question 2

the disease process hemolytic disease of the newborn (HDN)

Answer 2

Maternal antibodies crossing the placenta attack the fetal RBCs, resulting in fetal RBC hemolysis.

The hemolysis causes significant fetal anemia, resulting in fetal heart failure and death

Question 3

the most serious condition associated with severe Rh incompatibility between the mother and fetus?

Answer 3

Fetal hydrops (erythroblastosis fetalis)
defined when fluid collects in ≥ 2 body cavities: scalp edema, pleural effusion, pericardial effusion, ascites.

Question 4

mechanism of Fetal hydrops (erythroblastosis fetalis)

Answer 4

Fetal anemia secondary to blood incompatibility result in extramedullary hematopoiesis, portal hypertension, excessive fluid shift into the extracellular space of the fetus, heart failure (severe anemia → hyperdynamic circulation → high-output HF), and eventual fetal death.

Question 5

what is sensitization?

Answer 5

the development of maternal antibodies against D antigens on the fetal RBC. Sensitization may occur whenever fetal blood enters the maternal circulation.

Question 6

why in the 1st pregnancy (sensitization) the fetus is not harmed, but the subsequent have a high risk for HDN?

Answer 6

in the fetus of the pregnancy when sensitization occurred, the maternal antibody titers are low. in subsequent pregnancies with a D-positive fetus, the mother has already developed memory cells that rapidly produce anti-D antibodies (IgG) against the fetus RBCs

Question 7

what conditions can lead to sensitization?

Answer 7

Conditions associated with a potential risk of fetal-maternal blood mixing): chorionic villus sampling, amniocentesis, spontaneous/induced abortion, threatened/incomplete abortion, ectopic pregnancy, placental abruption, bleeding placenta previa, vaginal or cesarean delivery, abdominal trauma.

Question 8

when is a maternal antibody screening preformed?

Answer 8

at the initial prenatal visit

and 28 weeks

Question 9

A critical antibody titer is defined as?

Answer 9

a titer 1:16 or higher

Question 10

Antibodies potentially causing hemolytic disease

Answer 10

• No harm to the fetus → anti-Lewis.
• May cause HDN → anti-D, anti-Duffy, anti-Kell.

“D Deadly, Kell Kills, Duffy Dies, Lewis Lives”.

Question 11

Potential non-immune causes of hydrops fetalis

Answer 11

1. Iron deficiency anemia
2. Cardiac arrhythmias
3. Parvovirus B19 infection
4. Inborn errors of metabolism
5. CMV infection
6. Maternal syphilis
7. Twin-to-twin transfusion syndrome
8. Maternal diabetes

Question 12

what is the management of an unsensitized patient? (D-negative mother, Negative Ab’s screen)

Answer 12

1. If antibody screen is negative, the fetus is
   presumed to be D-positive → single dose of
   anti-D IgG immunoglobulin is given to the
   mother at 28 weeks to prevent the development
   of maternal antibodies.
2. At birth, the infant’s D status is assessed:
   ˃ If the infant is D-negative → no further
   anti-D IgG is given to the mother.
   ˃ If the infant is D-positive → anti-D IgG is
   given to the mother within 72 h’ of delivery.

*Anti-D immune globulins last for approx. 12 weeks.
*

Question 13

how is the dose of anti-D IgG is determined?

Answer 13

by KB test (Kleihauer-Betke) which estimates the number of fetal
RBCs in the maternal circulation.

Question 14

what is the management of a sensitized mother (D-negative mother, Positive Ab’s screen)

Answer 14

1. Check antibody titer:
   ˃ Titer remains stable at < 1:16 → likelihood
   of HDN is low; F/U antibody titer q4 weeks.
   ˃ Titer ≥ 1:16 and/or rising → likelihood of
   HDN is high; amniocentesis indicated.
2. Amniocentesis → fetal RBCs are analyzed for D
   status. Alternatively, perform serial MCA Doppler
   to assess for fetal anemia.
3. Serial US monitoring:
   ˃ Anatomy scan for hydrops fetalis.
   ˃ MCA Doppler for the presence and severity
   of anemia.
4. If there is US evidence of fetal hydrops, or if the
   MCA peak systolic velocity is > 1.5 → indication
   for fetal blood sampling if the fetus is at less than
   35 w’ gestation.
   *PUBS allows measurement of fetal Hgb, HCT,
   blood gases, pH, and bilirubin levels → guiding
   further clinical decision-making.
5. Delivery:
   ˃ Mild anemia → induction at 37-38 weeks.
   ˃ Severe anemia: deliver at 32-34 weeks.
   Most babies > 32 weeks do well in the
   neonatal intensive care unit (NICU).
   *Administer steroids to mother to enhance fetal lung
   maturity.
6. Treatment options for fetal anemia not amenable to delivery:
   ˃ Transfusions (PUBS approach).
   ˃ Plasma exchange.
   ˃ IVIG.
   ˃ Phenobarbital (induces fetal hepatic
   microsomal activity, thus accelerating
   bilirubin elimination).