Hemolytic Disease of the Newborn and Fetus

Hemolytic Disease of the Newborn and Fetus
By:Renee Newman Wilkins, MS, MT(ASCP), CLS(NCA)
CLS 325/435 Clinical Immunohematology
School of Health Related Professions
University of Mississippi Medical Center

What is HDN?
* Destruction of the RBCs of the fetus and newborn by antibodies produced by the mother
* Only IgG antibodies are involved because it can cross the placenta (not IgA or IgM)
Mother’s antibodies
Pathophysiology
* Although transfer of maternal antibodies is good, transfer of antibodies involved in HDN are directed against antigens on fetal RBCs inherited by the father
* Most often involves antigens of the Rh and ABO blood group system, but can result from any blood group system
* Remember: The fetus is POSITIVE for an antigen and the mother is NEGATIVE for the same antigen

Pathophysiology
* HDN develops in utero
* The mother is sensitized to the foreign antigen present on her child’s RBCs usually through some seepage of fetal RBCs (fetomaternal hemorrhage) or a previous transfusion
* HDN occurs when these antibodies cross the placenta and react with the fetal RBCs

ABO HDN
* ABO incompatibilities are the most common cause of HDN but are less severe
* Usually, the mother is type O and the child has the A or B antigen…Why?
* ABO HDN can occur during the FIRST pregnancy b/c prior sensitization is not necessary
* ABO HDN is less severe than Rh HDN because there is less RBC destruction
o Fetal RBCs are less developed at birth, so there is less destruction by maternal antibodies
Diagnosis of ABO HDN
* Infant presents with jaundice 12-48 hrs after birth
* Testing done after birth on cord blood samples:
Treatment of ABO HDN
* Only about 10% require therapy
* Phototherapy is sufficient
* Rarely is exchange transfusion needed
* Phototherapy is exposure to artificial or sunlight to reduce jaundice
* Exchange transfusion involves removing newborn’s RBCs and replacing them with normal fresh donor cells

Phototherapy
Fluorescent blue light in the 420-475 nm range
Exchange transfusion
* CMV negative
* Irradiated
* Fresh Whole Blood (to avoid Ca++)
* Maternal blood if possible
* Leukoreduced

What type of blood to give fetus:

Rh HDN
* Mother is D negative (d/d) and child is D positive (D/d)
* Most severe form of HDN
* 33% of HDN is caused by Rh incompatibility
* Sensitization usually occurs very late in pregnancy, so the first Rh-positive child is not affected
o Bleeds most often occur at delivery
o Mother is sensitized
o Subsequent offspring that are D-positive will be affected

About 1 in 10 pregnancies involve an Rh-negative mother and an Rh-positive father
FetoMaternal Hemorrhage
* Sensitization occurs as a result of seepage of fetal cells into maternal circulation as a result of a fetomaternal hemorrhage

Risk
* Rh-negative women can be exposed to Rh-Positive cells through transfusion or pregnancy
* Each individual varies in their immune response (depends on amount exposed to)
Pathogenesis
* Maternal IgG attaches to antigens on fetal cells
o Sensitized cells are removed by macrophages in spleen
o Destruction depends on antibody titer and number of antigen sites
o IgG has half-life of 25 days, so the condition can range from days to weeks
* RBC destruction and anemia cause bone marrow to release erythroblasts, hence the name “erythroblastosis fetalis”)

Increased immature RBCs
Pathogenesis
* When erythroblasts are used up in the bone marrow, erythropoiesis in the spleen and liver are increased
Bilirubin
* Hemoglobin is metabolized to bilirubin
Diagnosis & Management
* Serologic Testing (mother & newborn)
* Amniocentesis and Cordocentesis
* Intrauterine Transfusion
* Early Delivery
* Phototherapy & Newborn Transfusions

Serologic testing on mother
* ABO and Rh testing
* Antibody Screen
* Antibody ID
* Paternal phenotype
* Amniocyte testing
* Antibody titration
Marsh score
Example:
Amniocentesis & Cordocentesis
* About 18-20 weeks’ gestation
* Cordocentesis takes a sample of umbilical vessel to obtain blood sample
* Amniocentesis assesses the status of the fetus using amniotic fluid
Analysis of amniotic fluid (example)
Liley graph
What to do?
* Intrauterine transfusion is done if:
* Removes bilirubin
* Removes sensitized RBCs
* Removes antibody

Other treatments
* Early Delivery
* Phototherapy (after birth)
* Newborn transfusion

Postpartum testing
* ABO – forward only
* Rh grouping – including weak D
* DAT
* Elution
Prevention
* RhIg (RhoGAM®) is given to the mother to prevent immunization to the D antigen

Postpartum administration of RhIg
Dose
Rosette Test
* A qualitative measure of fetomaternal hemorrhage

Fetomaternal Hemorrhage:
Kleihauer-Betke acid elution
Calculating KB test
Step 1) stain and count the amount of fetal cells out of 1000 total cells counted
Step 2) calculate the amount of fetal blood in cirulation by multiplying %fetal cells by 50 mL
Step 3) divide mL of fetal blood by 30 (each vial protects against a 30 mL bleed
Step 4) Round the calculated dose up and add one more vial for safety

Considerations
* RhIg is of no benefit once a person has formed anti-D
* It is VERY important to distinguish the presence of anti-D as:
o Residual RhIg from a previous dose OR
o True immunization from exposure to D+ RBCs
* RhIg is not given to the mother if the infant is D negative (and not given to the infant)

* Make sure presence of anti-D is not due to antenatal administration of Rh immune globulin
Hemolytic Disease of the Newborn and Fetus.ppt