The present and future crossmatch

The crossmatch has been used as the final phase of pretransfusion testing for over half a century.’ However, during this time, there have been frequent modifications of the procedure, as well as differences of opinion as to the extent of its performance. In recent years, modifications have focused on its abbreviation. When the American Association of Blood Banks first published its standards in 1958, the crossmatch was described in relatively broad terms. The major crossmatch was specifically required, while the minor crossmatch was characterized as an optional test. The latter never has been a required procedure, although the tendency of many transfusionists to “wear a belt with their suspenders,, was illustrated by their reluctance to part with In addition, the major crossmatch was mandated to include two methods: one to demonstrate “serum or saline active” antibodies and the other to detect “incomplete or blocking” antibodies. An appendix to that edition of the standards specified the use of albumin and the indirect antiglobulin test. It must be recalled that this edition predated the general adoption of pretransfusion screening for unexpected antibodies in recipient serum, a procedure that had been introduced almost a decade b e f ~ r e . ~ By 1962, the standards declared that the antiglobulin phase of the crossmatch was optional, depending upon its inclusion in the antibody screening test. This seemingly casual approach was solidified in the 1970 edition, as demonstration of “agglutinating and coating antibodies,, was required, as was performance of an antiglobulin test. The pendulum then swung to a more permissive approach to the crossmatch so that, first, only “significant’, and later, “clinically significant” antibodies had to be detected. By 1984, the requirement for routine use of an antiglobulin test was rescinded unless “clinically significant unexpected antibodies were detectable” in the patient’s serum. This change was based on a philosophical modification of the test’s purpose. Whereas the crossmatch originally had the dual purpose of providing final verification of ABO compatibility and detecting unexpected antibodies unrecognized by the antibody screening test, in the revised edition, the latter function was eliminated. This change was permitted by the demonstration of the rarity of detection of clinically significant unexpected antibodies, that were unrecognized by the antibody screening test, by a crossmatch that incorporated an antiglobulin t e ~ t . ~ ~ Therefore, the fundamental purpose of the crossmatch currently is to prevent potentially life-threatening acute hemolytic transfusion reactions due to the transfusion of ABO-incompatible red cells. Elimination of room-temperature incubation of the mixture of the patient’s serum with red cells from the donor unit, as well as of antiglobulin testing, resulted in the idiomatic expression “immediate-spin crossmatch.” It was acknowledged that there would be instances wherein weakly reactive antibodies, or antibodies against rare antigenic specificities, would be undetected by this procedural modification, and yet these antibodies would be unlikely to result in significant patient morbidity. While the immediate-spin crossmatch is relied on for final confirmation of ABO compatibility, on rare occasion it has failed this mission. This has occurred because of the combination of a weak ABO antibody in the serum of a patient with donor red cells that represent an incompatible subgroup of In even rarer instances, a falsenegative immediate-spin crossmatch may result from a prozone phenomenon in tests incorporating very potent AT30 antibodies. This can be circumvented by suspending the test red cells in EDTA.9 In addition, ABO incompatibility will not be detected by the immediate-spin crossmatch in an infant with weak anti-A or anti-B that reacts only in the antiglobulin test. Transfusion of group 0 red cells to such infants avoids that situation. It is conceivable that other patients with weakly reactive anti-A or anti-B may be unable to manifest in vitro ABO incompatibility. As was originally anticipated, there have been, during the past decade, isolated instances of unexpected antibodies that eluded detection until they were implicated