1. 8th Edition APGO Objectives for Medical Students
Isoimmunization

2. Rationale
The problem of fetal hemolysis from maternal D isoimmunization has decreased in the past few decades. Awareness of the red cell antigen-antibody system is important to help further reduce the morbidity and mortality from isoimmunization.

3. 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

4. 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

5. Fetomaternal hemorrhage
First trimester - 6-7%
Second trimester - 16%
Third trimester - 29%

6. Fetomaternal hemorrhage
First trimester - 6-7%
Second trimester - 16%
Third trimester - 29%

7. Fetomaternal hemorrhage
First trimester - 6-7%
Second trimester - 16%
Third trimester - 29%

8. Amount needed for sensitization
Amount needed for sensitization mL

9. Factors associated with isoimmunization
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

10. Clinical signs (in fetus)
Anemia
Erythroblastosis fetalis
Ascites
Heart failure
Pericardial effusion

11. Neonatal signs
Anemia
Hyperbilirubinemia

12. Immunoglobulin (RhoGAM) prophylaxis (RhIgG)
Mechanism
Blocks antigen
Antigen deviation
Central inhibition

13. Immunoglobulin (RhoGAM) prophylaxis (RhIgG)
300 μg anti-D neutralizes 30 mL fetal Rh-positive blood (15 mL packed fetal RBCs)
100% effective

14. Immunoglobulin (RhoGAM) prophylaxis (RhIgG)
Schedules
First trimester - 50 μg RhIgG
Amniocentesis μg RhIgG
Antepartum bleeding
If first trimester - 50 μg RhIgG
If third trimester μg RhIgG
Postpartum <72 hr μg RhIgG; 0.4% require > 300 μg RhIgG

15. Management of Rh negative mother
Maternal antibody titer negative - do serial antibodies
If titer low - little risk of anemia
If > 1:16 - perform amniocentesis and/or Doppler assessment
∆OD450 plot on Liley curve
Zone I - Rh negative or fetus mildly affected
Zone II - moderately affected
Zone III - high risk for IUFD

16. Fetal management - Rh negative, Ab positive mother
Serial sonograms
Early signs
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.

17. 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

18. Fetal management - Rh negative, Ab positive mother
Fetal antigen status
DNA analysis
PUBS at ~20 wk.

19. 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)

20. Transfusion therapy Intravascular
Goal is to have post-transfusion Hct 40-45%
Can infuse about 10 ml/min
Estimate requirement based on EFW and pre-transfusion 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

21. 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:
*O’Shaugnessy R, Kennedy M. Isoimmunization in Ling FW, Duff P. Obstetrics & Gynecology Principles for Practice, 2001:chapter 10:
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: Jackson M, Branch DW. Alloimmunization in pregnancy in Gabbe SG. Obstetrics Normal and Problem Pregnancies 4th ed., 2002:chapter 26:

22. Clinical Case
Isoimmunization

23. Objectives
At the conclusion of this exercise, the student will be able to demonstrate knowledge of the following:
Red Cell Antigens
Use of immunoglobulin prophylaxis during pregnancy
Clinical situations under which D isoimmunization are likely to occur
Management of the at-risk pregnancy

24. 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.

25. Teaching Points
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?

26. Teaching Points
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?