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2348 Part XIII: Transfusion Medicine Chapter 136: Erythrocyte Antigens and Antibodies 2349

TABLE 136–6. Common Causes of Abo Discrepancies screening cells and antibodies that are not apparent at 37°C and in the
antiglobulin phase.
RED CELLS MAY APPEAR TO HAVE
Weak or missing Weak subgroup of A or B antigen DIRECT ANTIGLOBULIN TEST
antigens Excess soluble A or B antigen in plasma The direct antiglobulin test (often referred to as the direct Coombs test,
Disease-associated loss (leukemia) a term discouraged by Robin Coombs because he said that Race and
ABO nonidentical marrow transplantation Mourant were also key to the description of the test) detects antibody or
ABO nonidentical red blood cell (RBC) complement bound to RBCs in vivo. Red cells are washed free of serum
transfusions and then mixed with an antiglobulin reagent that agglutinates RBCs
coated with IgG or the C3 component of complement.
Extra antigens Positive direct antiglobulin test Positive direct antiglobulin test results are associated with the fol-
Antibody to reagent additive or dye lowing: (1) transfusion reactions, in which recipient alloantibody coats
Rouleaux or cold agglutinin on cells transfused donor RBCs or transfused donor antibody coats recipient
Disease-associated acquisition RBCs; (2) HDFN, in which maternal antibody crosses the placenta
(polyagglutination) and coats fetal RBCs; (3) autoimmune hemolytic anemias, in which
SERUM MAY APPEAR TO HAVE autoantibody coats the patient’s own RBCs; (4) drug or drug–antibody
complex interactions with RBCs that sometimes lead to hemolysis;
Weak or missing Age related (newborns or the very elderly) (5) passenger lymphocyte syndrome, in which transient antibody
antibody Disease-associated immunosuppression produced by passenger lymphocytes from a transplanted organ coats
Congenital hypogammaglobulinemia recipient RBCs; and (6) hypergammaglobulinemia, in which Ig nonspe-
ABO nonidentical marrow transplantation cifically adsorb onto circulating RBCs.
A positive direct antiglobulin test result does not always indicate
Extra antibody Alloantibodies (A Le , Le , P M, N)
a
b
1 1 decreased red cell survival. As many as 10 percent of hospital patients
Autoantibodies (I, i, H, Pr, P) and 0.1 percent of blood donors have a positive direct antiglobulin test
Rouleaux result with no clinical indication of hemolysis. 11
Antibodies to additives in reagent RBCs
Passive antibody acquisition from trans- COMPATIBILITY TESTING
fusion or from passenger lymphocytes in
organ transplantation Compatibility testing refers to a set of donor and recipient tests that
are performed prior to red cell transfusion. The collecting facility tests
donors for ABO, Rh, and unexpected antibody. However, transfusing
hospitals retest the ABO (and D on Rh-negative units) to verify the
Rh-positive. Testing for weak D is optional for transfusion recipients accuracy of the blood label. Routine recipient testing includes an ABO,
56
and pregnant women. 56 D, and antibody screening on a blood sample collected within 3 days of
the intended transfusion. Results are checked against historical records
EXTENDED ANTIGEN PHENOTYPING to verify ABO, D, and antibody status. 56
Reagent antisera to detect other common antigens (e.g., CcEe, MNSs, If the recipient has a negative antibody screening test result and no
Kk, Fy Fy , Jk Jk ) are available and used when identification of the red history of clinically significant antibodies, a serologic immediate spin
b
a
b
a
cell phenotype is essential to antibody identification, blood compatibil- crossmatch between recipient serum and donor red cells or a “computer
ity, determination of zygosity, or paternity or forensic issues. Extended crossmatch” (wherein computer software compares the ABO test results
phenotyping is especially important to patients who are at high risk for of both donor and recipient) is required to confirm ABO compatibility. 11
alloimmunization from chronic blood transfusion, for example, those If clinically significant antibodies are detected in a recipient’s serum
with sickle cell anemia or thalassemia. Ideally, an extended RBC phe- or previously were identified, red cell components should test negative for
notype of patients who are likely to be chronically transfused should the corresponding antigens and be crossmatch compatible at 37°C by the
be determined prior to initiation of transfusion therapy. Prediction of a antiglobulin test. The chance of finding compatible units usually reflects
blood group antigen can be made by testing DNA of a patient, even in the antigen prevalence in the population, that is, 91 percent of units should
the presence of transfused RBCs. 27 be compatible with a patient making anti-K because 9 percent of the pop-
ulation is K+. This reasoning will not be valid if the local donor population
varies significantly from the general population. When more than one anti-
body is present, the probability of finding compatible blood is the prod-
ANTIBODY SCREEN uct of the prevalence (probability) of each independent antigen tested. For
The antibody screen, or indirect antiglobulin test, detects “atypical” or example, only 21 percent of units will be compatible for the recipient having
“unexpected” antibodies in the serum (i.e., other than anti-A and both anti-K and anti-Jk : (0.91 for K–) × (0.23 for Jk[a–]) = 0.21.
a
anti-B) using group O reagent red cells that are known to carry var- When multiple clinically significant antibodies or an antibody
ious combinations of antigens. The methods used must be able to detect directed against a high-prevalence antigen are present, finding com-
clinically significant antibodies. Typically, serum or plasma and screen- patible RBC components can be extremely difficult. Such antibody
ing cells are incubated at 37°C with an additive to potentiate antibody– producers should be encouraged to give autologous donations prior to
antigen reactions, then an indirect antiglobulin test is performed. their elective blood needs. If the patient is not a candidate for autolo-
Hemagglutination or hemolysis at any point is a positive reaction, indi- gous donation, compatible units may be found by testing the patient’s
cating the presence of naturally occurring or immune alloantibody or siblings or by asking regional blood suppliers to check their rare
autoantibody. The antibody screen will not detect all atypical antibodies donor inventories and files. Such procurement requires additional
in serum, such as antibodies to low-prevalence antigens not present on time.

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