Anemia and Jaundice in a Newborn

Charles T. Quinn, MD, MS

Cincinnati Children's Hospital Medical Center

Copyright of the American Society of Hematology, 2006. ISSN: 1931-6860.

This case was reviewed and updated in June 2011 by The Teaching Cases Subcommittee.


  • The most important blood group system is the ABO group. Individuals can be type A, B, AB, or O.
  • The Rh blood group is a complex system that includes the major D antigen and the antigens of the CcEe series, among others. The presence or absence of the major D antigen determines whether an individual is Rh-positive (D present) or negative (D absent).
  • Alloimmunization is an immune response directed against foreign antigens that are expressed by other members of the same species. Alloimmunization can occur, for example, as a consequence of allogeneic blood transfusion or pregnancy (hemolytic disease of the newborn). In the context of this teaching case, alloimmunization refers to the formation by the mother of antibodies (alloantibodies) against fetal erythrocyte antigens, to which she is sensitized during pregnancy.
  • Isohemagglutinins are naturally occurring antibodies with specificity against the A and B antigens of the ABO blood group. These antibodies are typically IgM-class antibodies in group A and B individuals and IgG-class in type O individuals.
  • Hemolytic disease of the newborn (HDN) is classically caused by Rh(D) alloimmunization, but this form of the disease has become much less common in the developed world because of the preventive use of anti-D immunoglobulin (RhoGAM) in D- negative women. Nevertheless, Rh HDN has not been eliminated, and it remains a problem in many parts of the world.
  • HDN due to ABO isohemagglutinins is now more common than Rh (D) alloimmunization, but it is typically restricted to group A or B neonates of group O mothers. This occurs because group O individuals make predominantly IgG (rather than IgM) anti-A and anti-B isohemagglutinins, which can cross the placenta. Blood group A or B mothers produce predominantly IgM isohemagglutinins that do not cross the placenta. The anemia that occurs in ABO HDN tends to be mild, but the peripheral smear may show marked spherocytosis, nevertheless.
  • Fetomaternal mismatches for many minor blood group antigens (non-ABO, non-D) can also cause HDN. Commonly implicated minor antigens include: K1 (Kell), c (Rh), and Fya (Duffy). These minor antigens are now the most common cause of HDN in areas of the world where Rho-GAM is available.
  • HDN is a transient disease that lasts approximately 1-3 months, depending on the antibody concentration and rate of hemolysis.
  • A neonate should receive red blood cells that are compatible with both the neonate’s blood group and the mother’s blood group. Generally transfused red blood cells are O-, but they must also be crossmatch compatible with maternal serum. Thus, transfusion of O- red blood cells, without further characterization and crossmatching, may be inappropriate in cases of HDN.

Relative Incidence and Severity of Hemolytic Disease of the Fetus and Newborn (HDFN)

Blood Group Frequency as a Cause of HDFN Severity of HDFN
ABO Common Usually mild
C (Rh system) Rare Seldom severe
c (Rh system) Uncommon May be severe
D (Rh system) Uncommon (with RhoGam prophylaxis) Often severe
E (Rh system) Rare Seldom severe
e (Rh system) Rare Seldom severe
Kell Common Often severe
Kidd Very rare Usually not severe
Duffy Uncommon Occasionally severe
MNS Rare Sometimes severe
Lewis Not a cause ---
P Not a cause ---
Lutheran Not a cause ---

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