Is it time to give up the crossmatch?

Blood groups A, B, and O were described by Landsteiner in 1901 and the serological crossmatch between the blood donor and the recipient, as a means of preventing ABO incompatibility, was first described by Ottenberg in 1908. In 1941, Rh antibodies were found to be the cause of haemolytic disease of the newborn. The earliest detected forms of anti-D antibodies were very strong and found by saline agglutination. The clinical importance of the discovery quickly led to the development by Coombs and others of the antiglobulin test. In what might be regarded in retrospect as a golden age of red blood cell serology, discovery of other clinically important red cell antigens followed quickly. Extra eVort was then put into the crossmatch, aimed at detection of atypical antibodies, with the result that by the 1960s red blood cell transfusions were being given only after extensive crossmatching performed in saline, at room temperature and body temperature, by enzyme methods, by albumin addition, and by the indirect antiglobulin test. Over the subsequent two decades there has been a slow but steady serological retreat until by the 1990s most laboratories were concentrating on a well performed indirect antiglobulin test alone for the detection of both atypical antibodies and ABO incompatibility. If we consider the role of the crossmatch as a test for atypical antibodies it is clear that it has limitations. The donor cells, of varying age, are stored at varying haematocrit in a small plastic tag and usually diluted by eye to roughly the right cell concentration. The test is then performed once only and without a positive control. When serologists were happy that all clinically important red blood cell antigens had been recognised it was possible to choose a red blood cell screening panel that covered all the important antigens and to test for atypical antibodies using these cells rather than donor cells. This logical step was first described by Grove-Rasmussen in 1964. In comparison with the crossmatch, the atypical antibody screen uses carefully chosen cells, optimally diluted, and stored in a preservative solution. It can and should be routinely controlled, preferably with every batch performed, by inclusion of a control antibody such as a weak anti-D. Technically, the crossmatch is a poor substitute for a well performed antibody screen. Its benefits are that it acts as a double check, should the screen have been performed badly or misread, and that it might pick up antibodies to antigens present on the donor red blood cells but not present on the screening cells. As serologists became confident in the atypical antibody screen, it was possible to revert to the use of the crossmatch for the detection of ABO mismatch alone, the so called “Quick spin crossmatch”. Large studies of Quick spin crossmatch techniques have confirmed that when the antiglobulin phase of the crossmatch is omitted few, if any, unexpected reactions occur. 6 Those that do are rarely recorded to be of clinical relevance. Schulman, in a postal survey, also noted that most haemolytic reactions occurring after a Quick spin crossmatch were because of missed positives in the antibody screen rather than recipient antibodies to rare donor antigens not present on the screening cells. Despite these findings, most blood banks in the UK still perform an indirect antiglobulin test as part of a crossmatch. Notwithstanding, theory and practice point in the same direction. We can rely on the atypical antibody screen, as long as it is well performed, well controlled, and uses a cell panel covering all relevant red blood cell antigens. It is a matter of argument whether it should include Kp, Lu, and C, but it should not include Wr. This leaves the crossmatch where it started as a test to exclude ABO incompatibility. Wallace, McClelland and Phillips, and Williamson and colleagues all look at the occurrence of ABO incompatible transfusions and conclude that most occur because of errors of sampling or errors at the point of blood administration. Errors of administration will rarely involve more than one unit. Although they are potentially fatal they are less dangerous than misgrouping of the patient because of sampling or laboratory errors, which can lead to several units of the wrong group being transfused. These laboratory and sampling errors can be virtually removed if we insist on two separate samples, taken on diVerent occasions, from each patient. Assuming that the laboratory information system has the appropriate checks and safeguards inbuilt, discrepancies in the two ABO or Rh groups will prevent acceptance of that record and require further investigation. If the two ABO and Rh groups are in agreement, the chance of persistent error is extremely small. This assumes that the reader and interpreter of the second group is not influenced by a previous result and for this reason it is advisable that groups are read and interpreted electronically, as is often the case now, or that the second group if read or interpreted manually is entered blind to the knowledge of the previous group. This latter might be more diYcult to achieve. Having obtained two concordant ABO and Rh groups, as above, we can be confident that the patient is correctly grouped. Assuming the blood bank computer will only allow the issue of compatible units after bar code entry of donor unit details, the remaining question is J Clin Pathol 2000;53:673–675 673