8th Edition APGO Objectives
for Medical Students
Isoimmunization
Rationale
The problem of fetal hemolysis from
maternal D isoimmunization has
decreased in the past few decades.
Awareness of the red cell antigenantibody system is important to help
further reduce the morbidity and mortality
from isoimmunization.
Objectives
The student will demonstrate knowledge of the
following:
 Red blood cell antigens
 Use of immunoglobulin prophylaxis during
pregnancy
 Clinical circumstances under which
isoimmunization is likely to occur
 Methods used to determine maternal
isoimmunization and severity of fetal
involvement
Red blood cell antigens
Three genetic loci - C, D, E
 Possible alleles - Cc, Dd, Ee
 d = absence of discernible allelic product
 Minor antigens not as frequent as anti-D

Fetomaternal hemorrhage
First trimester - 6-7%
 Second trimester - 16%
 Third trimester - 29%

Fetomaternal hemorrhage
First trimester - 6-7%
 Second trimester - 16%
 Third trimester - 29%

Fetomaternal hemorrhage
First trimester - 6-7%
 Second trimester - 16%
 Third trimester - 29%

Amount needed for
sensitization

Amount needed for sensitization - 0.1 mL
Factors associated with
isoimmunization








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Amniocentesis; CVS
Threatened abortion, previa, abruption
Trauma to abdomen
External cephalic version
Multiple pregnancies
Cesarean delivery
Fetal death
Percutaneous umbilical blood sampling
Manual removal of placenta
Clinical signs (in fetus)
Anemia
 Erythroblastosis fetalis

 Ascites
 Heart
failure
 Pericardial effusion
Neonatal signs
Anemia
 Hyperbilirubinemia

Immunoglobulin (RhoGAM)
prophylaxis (RhIgG)
Mechanism
 Blocks antigen
 Antigen deviation
 Central inhibition
Immunoglobulin (RhoGAM)
prophylaxis (RhIgG)
300 μg anti-D neutralizes 30 mL fetal Rhpositive blood (15 mL packed fetal RBCs)
 100% effective

Immunoglobulin (RhoGAM)
prophylaxis (RhIgG)
Schedules
 First trimester - 50 μg RhIgG
 Amniocentesis - 300 μg RhIgG
 Antepartum bleeding
first trimester - 50 μg RhIgG
 If third trimester - 300 μg RhIgG
 Postpartum <72 hr - 300 μg RhIgG; 0.4%
require > 300 μg RhIgG
 If
Management of Rh negative
mother


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Maternal antibody titer negative - do serial
antibodies
If titer low - little risk of anemia
If > 1:16 - perform amniocentesis and/or
Doppler assessment



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∆OD450 plot on Liley curve
Zone I - Rh negative or fetus mildly affected
Zone II - moderately affected
Zone III - high risk for IUFD
Fetal management - Rh
negative, Ab positive mother
Serial sonograms
 Early signs
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Thickened placenta
Liver span
Increased umbilical vein diameter
Increased blood velocities in UV, aorta and middle
cerebral artery
Severe disease - scan every week if hydropic
changes. If hydropic changes, consider fetal
transfusion.
Fetal management - Rh
negative, Ab positive mother
Serial amniocentesis
 ∆OD450 measurement
 Liley curve
 Low
- Zone II and lower - deliver at fetal
maturity
 High - Zone II and higher - deliver before
maturity
Fetal management - Rh
negative, Ab positive mother
Fetal antigen status
 DNA analysis
 PUBS at ~20 wk.
Transfusion therapy
Intraperitoneal
 First done in 1963
 Instill blood through needle or epidural catheter
 Volume to transfuse = (G.A.-20) x 10ml
 Generally, repeat in ~ 10 days, then every 4 wk.
 Risk of death about 4% per procedure
 Not effective in hydropic fetus
 Some advocate combined approach (IPT and
IVT)
Transfusion therapy
Intravascular
 Goal is to have post-transfusion Hct 40-45%
 Can infuse about 10 ml/min
 Estimate requirement based on EFW and pretransfusion Hct
 Repeat in 1 wk., then about every 3 wk.
 Hct falls about 1%/day
 Goal: keep Hct > 25%
 Smaller volumes, therefore more procedures compared
to IPT
 Fetal loss about 1.5% per procedure
References
(*Texts targeted to medical students and general womenﾕs health
care providers)
 *Beckmann CRB, Ling FW, Abnormal obstetrics in Obstetrics and
Gynecology, 4th ed, 2002; chapter 11: 165-172.
 *O’Shaugnessy R, Kennedy M. Isoimmunization in Ling FW, Duff P.
Obstetrics & Gynecology Principles for Practice, 2001:chapter 10:
308-326.
 Cunningham FG, Gant NR, Leveno KJ, Gilstrap LC, Hauth JC,
Wenstrom KD. Diseases and injuries of the fetus and newborn in
 Williams Obstetrics 21st ed., 2001: chapter 39:1039- 1091.
Jackson M, Branch DW. Alloimmunization in pregnancy in Gabbe
SG. Obstetrics Normal and Problem Pregnancies 4th ed.,
2002:chapter 26:893-927.
Clinical Case
Isoimmunization
Objectives
At the conclusion of this exercise, the student will
be able to demonstrate knowledge of the
following:
1. Red Cell Antigens
2. Use of immunoglobulin prophylaxis during
pregnancy
3. Clinical situations under which D
isoimmunization are likely to occur
4. Management of the at-risk pregnancy
Patient Presentation
A 32-year-old woman, P1101, and her new husband
present for prenatal care at 20 weeks’ gestation. Her
past obstetric history is significant for a first child
delivered at term following an abruption. Her second
child died of complications of prematurity following in
utero transfusions for Rh isoimmunization. Her initial
prenatal labs this pregnancy indicate her blood type as
A negative and an antibody screen positive for anti-D
with a titer of 1:64. You discuss any additional
evaluation needed, her risks in this pregnancy, and the
plan of management with her and her husband.
Teaching Points
1.
2.
3.
4.
5.
What is Rh isoimmunization and what are the
red cell antigens involved?
What are the risk factors for Rh
isoimmunization?
What is the mechanism for RhoGAM
prophylaxis against Rh disease?
What is the dose of RhoGAM?
What is the recommended schedule for
RhoGAM administration?
Teaching Points
6.
7.
8.
9.
Could this patient’s Rh isoimmunization have
been prevented?
Is there any further blood work that should be
obtained before you counsel this patient on
her risks in this pregnancy?
Discuss the management of the Rh-sensitized
mother in an at-risk pregnancy.
What are some ultrasound findings that may
suggest Rh disease?