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8th Edition APGO Objectives for Medical Students. Isoimmunization. Rationale.

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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.


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
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
Fetomaternal hemorrhage
  • First trimester - 6-7%
  • Second trimester - 16%
  • Third trimester - 29%
fetomaternal hemorrhage6
Fetomaternal hemorrhage
  • First trimester - 6-7%
  • Second trimester - 16%
  • Third trimester - 29%
fetomaternal hemorrhage7
Fetomaternal hemorrhage
  • First trimester - 6-7%
  • Second trimester - 16%
  • Third trimester - 29%
amount needed for sensitization
Amount needed for sensitization
  • Amount needed for sensitization - 0.1 mL
factors associated with isoimmunization
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
clinical signs in fetus
Clinical signs (in fetus)
  • Anemia
  • Erythroblastosis fetalis
    • Ascites
    • Heart failure
    • Pericardial effusion
neonatal signs
Neonatal signs
  • Anemia
  • Hyperbilirubinemia
immunoglobulin rhogam prophylaxis rhigg
Immunoglobulin (RhoGAM) prophylaxis (RhIgG)


  • Blocks antigen
  • Antigen deviation
  • Central inhibition
immunoglobulin rhogam prophylaxis rhigg13
Immunoglobulin (RhoGAM) prophylaxis (RhIgG)
  • 300 μg anti-D neutralizes 30 mL fetal Rh-positive blood (15 mL packed fetal RBCs)
  • 100% effective
immunoglobulin rhogam prophylaxis rhigg14
Immunoglobulin (RhoGAM) prophylaxis (RhIgG)


  • First trimester - 50 μg RhIgG
  • Amniocentesis - 300 μg RhIgG
  • Antepartum bleeding
    • If first trimester - 50 μg RhIgG
    • If third trimester - 300 μg RhIgG
    • Postpartum <72 hr - 300 μg RhIgG; 0.4% require > 300 μg RhIgG
management of rh negative mother
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
fetal management rh negative ab positive mother
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.
fetal management rh negative ab positive mother17
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 mother18
Fetal management - Rh negative, Ab positive mother

Fetal antigen status

  • DNA analysis
  • PUBS at ~20 wk.
transfusion therapy
Transfusion therapy


  • 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 therapy20
Transfusion therapy


  • 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

(*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

Clinical Case



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
patient presentation
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
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?
teaching points26
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?