CLS 306 (BB) - Lecture 11: Hemolytic Disease of the Fetus and Newborn

Erythroblastosis Fetalis

Disease when maternal antibodies destroy fetal RBCs, either in-utero or ex-utero (postpartum); fetal RBCs have antigens foreign to the mother that results in teh stimulation of maternal antibody production

Hydrops Fetalis

The effect of erythroblastosis fetalis on the fetus that includes general anemia, possible edema, possible cardiac failure, and up to fetal death

• anti-E

• anti-c

• anti-K

• anti-Jk

• anti-Fy

Immune allo (“other”) Abs that cause HDFN are usually due to which antibodies? (5)

Anti-K

Second most common form of severe HDFN; disease ranges from mild to severe; over half of the maternal cases that develop this antibody are caused by previous multiple blood transfusions

• Fetal severe anemia

• Fetal heart failure

• Fetal death

Dangers of HDFN in-utero (pre-partum)

Unconjugated (indirect) bilirubin

As a result of the destroyed RBCs in HDFN, (——) is released into the fetal body

Unconjugated bilirubin is sequestered out via the mother’s liver

Why is unconjugated bilirubin not as harmful in in-utero HDFN, as opposed to post-partum HDFN?

• ABO, Rh, ABS tests performed on first obstetrical visit

  • ABS (-) → repeat 24 weeks

  • ABS (+) → AB ID, if IgG → AB titer

Maternal prenatal care/testing (3)

>1:32

Ab titer significant for HDFN maternal prenatal testing

Last previous titer sample

(Maternal prenatal testing) When performing the current titer, mist run (——) in parallel with current titer sample

amniocentesis at 18-20 weeks gestation

Based on maternal Ab titer results, if HDFN is suspected then a (——) is performed

Amniotic fluid bilirubin

(——) is a direct indicator of the severity of HDFN

ΔOD at 450 nm

What is observed when testing for bilirubin (risk of HDFN) in amniotic fluid through a spectrophotometer?

• Liley’s graph

• Queenan curve

What is used to help interpret the data from spectrophotometric analysis of bilirubin in amniotic fluid (2 charts)

• Fetal hydrops detected on ultrasound

• Fetal Hb <10 g/dL (severe anemia)

• ΔOD 450 is high on Liley’s graph or Queenan curve (hyperbilirubinemia)

Intrauterine transfusion is necessary when one or more of the collowing conditions are met (3)

• <5 days old

• CPDA-1 or AS-3 additive only

• Ag negative to maternal allo Ab

• O neg

• CMV neg

• Hb S neg

• Irradiated

Intrauterine blood requirements (7)

• Anemia

• Hepatomegaly

• Splenomegaly

• Jaundice

• Kernicterus

Maternal Ab(s) continue to destroy fetal RBCS postpartum during HDFN. What are the signs and symptoms that occur? (5)

• Phototherapy (at 460-490 nm)

• Exchange transfusions

Choices of treatment for neonatal hyperbilirybinemia are… (2)

• Lipophilic

• Toxic to the brain

Phototherapy is used to change unconjugated bilirubin to an isomer which is less (——) and less (——)

ABO HDFN

Most common form of HDFN; can occur at the 1st delivery and subsequent pregnancies; no prior exposure needed

O type mother with Anti-A,B IgG, delivering A neonate (B less common)

How is ABO HDFN commonly caused?

Less

ABO HDFN is usually (more/less/equal to) Rh HDFN severity

It is not predictive of HDFN (not significant, no titers done)

What is the significance of maternal prenatal testing in predicting ABO HDFN?

• Repeat ABO/Rh and ABS (mother)

• Determine ABO/Rh, including weak D (baby)

• Perform DAT (baby)

  • if IgG DAT positive → elution procedure against A1 and B cells

Postpartum lab testing (cord blood workup) for ABO HDFN (cord blood work-up) (3)

heat/chemicals dissociate Ab from baby RBCs, and supernatant used for Ab ID (Ab found is of maternal origin)

What is the elution procedure during postpartum testing of ABO HDFN?

• Not preventable

• Commonly treatable by phototherapy only

• ≥20 mg/dL serum bilirubin (rare) requires exchange transfusion

ABO HDFN prevention and treatment (3)

• anti-D

• C, c, E, e

Most common cause of Rh HDFN is (——), but Abs against (—4—) antigens are known to cause it as well

Rh HDFN

Most severe form of HDFN; severe anemia may occur resulting in severe hyperbilirubinemia and jaundice; kernicterus could result

• 2nd or subsequent pregnancies

  • Must consider miscarriage, abortion, prenatal fetal/maternal bleed

When does Rh HDFN typically manifest

• Anti-C = rare

• Anti-c = mild to severe

• Anti-E = mild

• Anti-e = rare

  • Ab combinations can be severe

Severity of Rh HDFN due to anti- C, c, E, and e

• ABO, Rh (Du), ABS

• if ABS (+)

  • AB ID and titer (repeat titer every 4 weeks)

  • Ag status of father (optional)

  • Ig subclass of maternal Ab

Rh HDFN prenatal testing (4)

• Middle Cerebral Artery-Peak Systolic Velocity (MCA-PSV)

• Amniocentesis

If anti-D (or anoy other Rh AB) titer reaches >1:32, consider further testing… (2)

Middle Cerebral Artery-Peak Systolic Velocity (MCA-PSV)

(Rh HDFN testing) color doppler/ultrasound transducer that is a reliable predictor of fetal anemia; favored over amniocentesis because it is noninvasive and gives tehe same information

• Repeat ABO/Rh and ABS

• If ABS positive, must do Ab ID

  • weak anti-D may be due to Rh Immune Globulin shot (Rhogam) = “passive” anti-D

• Enumerate # fetal cells in mother’s blood

Postpartum testing for Rh HDFN in mother (3)

• Determine ABO/Rh (including weak D)

• Perform DAT

  • DAT + → elution test against Ab ID panel cells

Postpartum lab testing (cord blood work-up) on the baby for Rh HDFN (2)

Iatrogenic anemia

Some hospitals may not perform an elution test on baby RBCs for allo Ab ID because it can cause…

Fetal Hgb Screen Test/Rosette Test

Qualitative test that demonstrates small number of D positive cells in mother’s D negative cell suspension

Kleihauer-Betke test

Quantitative test where the blood sample from the mother is treated with acid and stained to show any present fetal red cells (resistant to acid); determine # of fetal cells in first 2,000 maternal cells counted

Fetomaternal hemorrhage = # fetal cells * maternal blood volume / 2,000

Equation used for the Kleihauer-Betke test

# of syringes = (Fetomaternal / 30) + 1

Calculation to find out how much Rh immune globulin is given to the mother

• Hb < 10 g/dL

• Bilirubin ≥20 mg/dL

Exchange transfusion can occur when either conditions exist… (2)

• Type AB

• Rh can be disregarded

• No irradiation

Requirements of plasma transfusion for neonate (3)

• Removes 50% bilirubin

• Removes 80-90% infant’s sensitized RBCs

• Removes 80-90% maternal incompatible Ab

• Replacement of incompatible RBC with compatible RBC

Beneficial effects of a 2-volume exchange transfusion in an HDFN neonate (4)

• Avoid clinically significant hemodynamic shifts

• Avoid any metabolic abnormalities

The neonatal exchange transfusion process is very slow in order to…

• Donor blood → venous catheter

• Arterial catheter → drainage/waste container

Direction of blood entering/exiting the baby during exchange transfusion