Case Report
Postpartum Du-Positive Women
and Rh Immune Globulin
Mark Shulin Cheng, MS, MT(ASCP)SBB, and Luba Lukomskyj, MT(ASCP)SBB
A
23-year-old woman (gravida III)
was admitted to a delivery ward
where she was delivered of a healthy
male neonate. With a negative direct
antiglobulin test, the cord blood of the
neonate was typed as A Rh„ (D) positive. The mother was typed as A Rh„
(D) negative Du positive with a negative antibody screening test at room
temperature, 37 °C, and in the antiglobulin phase. Her Du test gave a 3 +
reaction at the antiglobulin phase with
a proper control. The acid elution test
on her postpartum specimen showed
no evidence of fetal-maternal hemorrhage (FMH).
Seven days after the delivery, she
mentioned that she had received Rh
immune globulin (RhIG) after her first
two deliveries and questioned why no
RhIG treatment had been administered after the third delivery. A dose
of commercial RhIG was ordered and
subsequently administered.
A fresh blood specimen was collected five days after the administration of RhIG. No trace of the passively
acquired anti-D could be detected in
her serum at the antiglobulin phase,
and her direct antiglobulin test also
gave negative results.
From the Blood Center, Mount Sinai Hospital Medical
Center, Chicago, IL 60608.
748
This report will discuss whether it
is necessary to administer RhIG to Rh„
(D) negative Du-positive women who
have delivered an Rh0 (D)-positive infant and will describe the rationale
for administering or withholding the
RhIG„.
Discussion
Those who advocated the administration of RhIG to all apparent Rh„
(D)-negative women of Rh„ (D)-positive infants without performing a Du
test1 have cited the technical difficulty in the interpretation of the postpartum Du test at different institutions
and suggested that it may be simpler
and less expensive to give RhIG to all
Rh0 (D)-negative postpartum mothers
regardless of their Du status. Because
false Du-positive findings will erroneously result in the RhIG treatment
being denied, they may cause irreversible damage to the patient. Others
worried that Du-positive mothers could
be immunized by the red cells of Rh„
(D)-positive infants and thought it
would be an easy and safe way to treat
those with RhIG.
The Du test is a simple procedure,
and the result is not difficult to evaluate. Findings almost always give a
2 + to 3 + reaction for agglutination
at the antiglobulin phase, with a clear
LABORATORY MEDICINE • VOL. 17, NO. 12, DECEMBER 1986
background in the supernatant. To
avoid a possible error in falsely classifying a woman as Du positive, any
Du test on a postpartum specimen
showing a questionable microscopic
agglutination should be further investigated by a more experienced
technologist or referred to a supervisor. If a weak reaction with mixedfield result was observed after repeating the test with a new specimen,
it may be necessary to perform the
acid elution procedure2 to detect a
possible large FMH. In rare cases, one
must be aware of a hereditary tendency toward fetal hemoglobin disorder characterized by increased levels
of hemoglobin F persisting into adulthood,3 because this hemotologic disorder could lead to a wrong conclusion
of FMH.
In many cases, the Du antigen does
not differ qualitatively from the Rh„
(D) antigen, but there are fewer D sites
per cell.4p 337;5 However, in the rare
case in which the Du variant has both
a quantitative and qualitative defect,
the possibility of immunization to the
missing part of D mosaic may occur if
the patient received normal Rh0 (D)positive blood. The risk of provoking
the formation of anti-D in a Du-positive subject by transfusing Rh„ (D)positive blood or through pregnancy,
however, is extremely rare, and the
Du can be practically regarded as Rh„
(D) positive.4"339 In any event, if antiD is provoked in a D" variant mother
due to the immunization of Rh0 (D)positive fetal red cells, unlike the antiD made in the true Rh„ (D)-negative
women, the hemolytic disease of the
newborn tends to be much milder.6
It is unlikely that the administered
RhIG will selectively destroy a few of
the infant's Rh0 (D)-positive red cells
from a vast maternal Du pool. Anti-D
is almost always readily detected in
Du-negative postpartum women for at
least four weeks after the RhIG
administration. In the present case,
no detectable anti-D in the maternal
serum collected five days after the
administration of RhIG indicated that
the maternal Du-positive red cells
picked up almost all the anti-D injected but were too lightly coated to
become direct antiglobulin test positive or to be cleared immediately.
Therefore, the missing acquired antiD was probably in hiding on the maternal red cells that were still circulating.
In a survey of 31 hospital blood
banks in the Chicago area in May
1984, 28 were performing Du tests
routinely on all apparent Rh0 (D)-negative patients and transfusing all Dupositive patients with Rh„ (D)-positive blood regardless of age and sex.
Two of these 31 blood banks only occasionally administered RhIG to
mothers who were postpartum Dupositive by following the physicians'
orders. Due to the inconsistency of Du
testing on Rh„ (D)-negative patients
between hospital blood banks, the
same woman may receive a dose of
RhIG after giving birth to an Rh„ (D)positive infant in a hospital not testing for D" and yet may undergo transfusion with several units of Rh„ (D)positive blood in surgery in another
hospital that routinely performs Du
testing on all apparent Rh„ (D)-negative patients.
Rh„ (D) antigen is most important
in the clinical practice because its antigenicity is more potent than any
other red cell-related antigen. For instance, about 80% Rh„ (D)-negative
individuals will produce anti-D after
a transfusion of one unit of Rh„ (D)positive blood.4-p 353 Also, it is the most
complicated single antigen because it
consists of a mosaic structure, which
was discovered through the study of
rare occurrence of "D with anti-D"
phenomenon. Two systems of
nomenclature7 were proposed for the
mosaic structure of Rh0 (D). Wiener
subdivided it into RhA, RhB, Rh c , and
RhD, but Tippett subgrouped them into
six categories. Furthermore, Rh„ (D)
antigen may be phenotypically subtyped into the following four types: (1)
normal D, composed of all mosaic parts
and showing direct agglutination with
all anti-D tested; (2) D variant (extremely rare), which lacks one or more
mosaic parts and is directly agglutinated by a majority of anti-D sera except a few; (3) normal Du, a weak form
of D, is composed of all mosaic parts
and reacts with all anti-D sera tested
only at antiglobulin phase; and (4) D"
variant, which lacks one or more mosaic parts and reacts with some but not
all anti-D sera tested at the antiglobulin phase.
According to current convention,2 a
u
D antigen is designated as one that
failed to agglutinate with commercial
anti-D serum at room temperature but
reacted at the antiglobulin phase. On
the other hand, Du was classically defined as an antigen agglutinated by
some anti-D sera and not by others.7
Therefore most Du by classic definition will belong to category VI of Tippett and may be equated to a Du
variant.
Attempting to differentiate normal
Du from the Du variant is impractical
in a routine blood bank. Most reported Du variants in these individuals were discovered through the
detection of unexpected anti-D antibodies. However, most variants could
be detected in a few sophisticated research or reference laboratories where
rare anti-D sera are available.
Conclusion
The Technical Manual of the American Association of Blood Banks2 states
that Du-positive women are not candidates for RhIG. The circular of a
major commercial RhIG manufacturer8
states that Rh„ (D) immune globulin
should not be administered to Du-positive individuals. In addition, an
overwhelming majority of blood
bankers4, p 399;9 have taken a position
of not administering RhIG to Du-positive mothers. It was concluded that
there are no sound reasons to deviate
from the current practice or justified
benefits to give RhIG to postpartum
Du-positive women who are delivered
of Rh„ (D)-positive infants.
References
1. Soloway HB: Should Du positive mothers receive
Rh immune globulin? MLO 1982;14:21.
2. Widmann FK (ed): Technical Manual, ed 9. Arlington, Va, American Association of Blood Banks,
1985.
3. White P, Hendrick E, Kolins MD: Fetal-maternal
hemorrhage revisited. Lab Med 1985;16:428.
4. Mollison PL: Blood Transfusion in Clinical Medicine, ed 7. Oxford, England, Blackwell, 1983.
5. Cunningham NA, Zola AP, Hui HL, et al: Binding characteristics of anti-Rh0 (D) antibodies to
Rh„ (D)-positive and D u red cells. Blood
1985;66:765.
6. Lacey PA, Caskey CR, Werner DJ, et al: Fatal
hemolytic disease of a newborn due to anti-D in
an Rh-positive Du variant mother. Transfusion
1983,23:91.
7. Race RR, Sanger R: Blood Groups in Man, ed 6.
Oxford, England, Blackwell, 1975.
8. Rh,, GAM, Ortho Diagnostic System, Raritan, NJ.
9. Konugres AA, Polesky HF, Walker RH: Rh immune globulin and the Rh-positive, Du variant,
mother. Transfusion 1982:22:76.
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