RED CELL ALLOIMMUNIZATION IN PREGNANCY:
IRREGULAR ANTIBODY SCREENING
PERFORMED BY LANCET LABORATORIES
Dr J Niemann - October 2006

Alloimmune anaemia of the fetus and the newborn is a result of haemolysis mediated by antibodies that are produced by the immune system in response to foreign red cell antigens. This phenomenon may occur in two situations: 1.) after transfusion of antigenically dissimilar fetal cells into the maternal circulation during pregnancy or labour (this most commonly result in sensitization to the rhesus system antigens [D, C, E, c, e]), or 2.) in the non-pregnant state by therapeutic blood transfusions or needle sharing among intravenous drug abusers (this often involves sensitization to irregular antigens [Kell, M, Duffy, Kidd, etc.]).

Screening for irregular antibodies is indicated in in all pregnant women with a positive indirect antiglobulin (Coombs) test.

NOTE: The indirect antiglobulin test is indicated in all pregnant women. This includes Rh-positive women, because irregular antibodies other than anti-Rh that may also be associated with haemolytic disease of the newborn (HDN) may be present.

MANAGEMENT OF A PREGNANT WOMAN WITH A (FIRST) POSITIVE INDIRECT ANTIGLOBULIN TEST

History: Identify a possible source of sensitization
· Previous pregnancy/pregnancies
· Previous blood transfusion(s)?
· Drug abuse?

Identify the offending antibody

1. As maternal-fetal D antigen incompatibility may be accompanied by other red cell antigen
incompatibilities, a full irregular antibody screen is suggested irrespective of the mother's Rh status.

2. If the antibody identified is associated with haemolytic disease in the fetus or the newborn, the titer should be determined to predict fetal risk in the first sensitized pregnancy. A critical titer is defined as the titer associated with a significant risk for fetal anaemia. In most centres, critical titers for anti-D of 16-32 and for anti-Kell of 8-16 have been used. Maternal titers are
followed monthly until approximately 24 weeks, and then every 2 weeks thereafter. If the patient's obstetric history is significant for an alloimmunized pregnancy (eg. perinatal loss related to haemolytic disease of the newborn, requirement for IU blood transfusion, or extrauterine exchange transfusion), maternal titers should not be obtained because they are not predictive of the degree of fetal anaemi.

3. Determination of paternal antigen status and zygosity is also suggested. This is particularly useful in cases of sensitization to antigens other than D. If the father is negative for the antigen, the fetus should not be at risk (sensitization may have occurred due to previous blood transfusion, for example). [NOTE: This test is performed at the National Blood Transfusion Service. Contact number: 011 761 9000]

THE IRREGULAR ANTIBODY SCREENING TEST

This test is now offered by Lancet Laboratories.

Identification of irregular blood group antibodies involve the use of a panel of group O cells which have been tested for as many blood group antigens as possible. The serum under investigation is tested against the (up to ten) cells of the panel by the antiglobulin method. Comparison of the results with the decode information relating to the panel will ultimately reveal the specificity of the irregular antibody.

TEST REQUIREMENTS:
10ml CLOTTED specimen (no gel) and 1 EDTA sample.
Details of the number of previous pregnancies as well as the gestation period should be provided.

CLINICAL SIGNIFICANCE OF IRREGULAR ANTIBODIES

NOTES:
1. Outside the ABO and Rh systems, anti-K is probably the most common cause of HDN. It may be IgG, IgM, or a mixture of both; the IgG form is most common

2. Lewis antibodies do not cause HDN as the Lewis antigen is poorly developed in newborn babies, and the anti-Le immunoglobulin type is IgM, which does not cross the placenta

3. Many of these antibodies may only cause mild HDN. Investigations to determine fetal risk (apart from antibody titer) include serial amniocenteses for delta OD450 measurements at 10-14 day intervals and MCA-PSV (middle cerebral artery peak systolic velocity), a valuable non-invasive method for detecting moderate to severe fetal anaemia

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