CP conference Hemolytic disease of the fetus and newborn

(HDFN)

1/19/12

Pathophysiology

• Maternal alloantibodies cross the placenta, enter the fetal circulation and cause hemolysis

• Alloimmnunization via – Previous transfusion– Previous pregnancy– Current pregnancy (CVS, amniocentesis, trauma,

spontaneous/elective abortion, etc.)

Pathophysiology

• Depending on severity, hemolysis can lead to bilirubin in amniotic fluid, fetal anemia and hydrops fetalis– Severity of disease determined by • IgG subclass• Amount of antibody• Number of antigenic sites on red cells

All of the following antibody classes are capable of causing

HDFN except?

• A. IgG1• B. IgG2• C. IgG3• D. IgG4• E. All of the above can cause HDN

B. IgG2

• In addition to dimeric IgA and pentameric IgM, IgG2 is unable to cause HDN because it is unable to cross the placental membrane

Subclasses of IgG

• Differ in their AA sequence on the heavy chain in the constant domain

• Ability to bind complement affects clinical significance– IgG3 > IgG1 > IgG2 > IgG4

What is the most common antigen involved in HDFN?

• A. Rh• B. ABO• C. Kell• D. c• E. Duffy

B. ABO• Anti-D prophylaxis for Rh-negative women has

dramatically reduced Rh HDFN so that ABO incompatibility is #1

ABO HDFN• Leading cause of HDFN• Usually group O mom and group A or B child– Unlike other groups, O patients have IgG (anti-

A,B antibody) that crosses the placenta into fetal circulation

– Since these ABO antibodies are naturally occurring, interaction can occur during the first pregnancy

• Hemolysis is very mild since fetal/neonatal RBC’s only have weak ABO antigen expression

Other causes of non-Rh HDFN

• HDFN due to Kell is the most common cause of severe HDFN followed by anti-c– Kell is present on fetal RBC’s, unlike other antigens

Rh HDFN

• Classic HDFN, caused by anti-D antibodies• Usually not seen in first pregnancy – Not naturally occurring, so mom must have picked

up D+ erythrocytes from prior transfusion or pregnancy

• Before introduction of anti-D immunoglobulin G (RhIg) in 1966, incidence of sensitization in an Rh- mom bearing an Rh+ child was 8%, now 0.1% with 28 wk and term ppx

Preventing Rh HDFN

• D- women should be checked for anti-D ab:– If she does not have anti-D antibodies, give

prophylactic doses of RhIg at 28 weeks gestation and anytime there is fetomaternal hemorrhage– If she does have anti-D antibodies, maternal

antibody titer is determined; if titer is high, monitor fetal hemolysis intrauterine transfusion or early delivery may be necessary

What is the titer threshold for the presence of clinically significant anti-D

antibody in pregnancy?

• A. 1: 1,000• B. 1: 100• C. 1: 50• D. 1: 16• E. 1: 4

1:16• Titers less than 1:16 have very low risk of

hemolysis• Titers greater than 1:16 warrant monitoring

for fetal hemolysis

Indications for RhIg

• D- woman with a D+ or D-unknown fetus– Ppx= 300 μg (full vial) at 28 wks and at term– Fetomaternal hemorrhage of unknown qty (ectopic,

amnio, CVS)= 50 μg (small vial) in first 12 wks of gestation and 300 μg (full vial) after 12 wks

• NOT indicated for D+ moms or D- moms who already have anti-D antibodies

Dosing RhIg

Vials of RhIg=Maternal blood volume (mL) x % fetal cells in mom’s blood

30

• Maternal blood volume can be calculated as mom’s weight (in kg) x 70 mL/kg; may also estimate 5,000 mL

• % fetal red cells calculated by Kleihauer-Betke test• Each full dose vial protects against 30 mL of whole blood or 15 mL

of red cells

Questions?