New Developments in Blood Group Serology

Abstract

The last issue of INFUSIONSTHERAPIE UND TRANSFUSIONSMEDIZIN included four articles covering a wide range of developments in serology. These included a review of monoclonal antibodies used in routine and research [1], a study of antibodies to high-frequency red blood cell antigens [2], a contribution to isotypes of cold agglutinins with discussion on the rare occurrence of IgG antibodies to the Pr antigens and the rarity of Ig class switching in cold agglutinins [3] and a paper on a microplate solid-phase method for typing red blood cells [4]. In addition to the important impact of monoclonal antibodies in routine and research, the other most significant advances have been seen with the introduction of the new systems and technologies for blood typing, antibody screening and compatibility testing. Laboratories have adopted new technologies to help improve aspects of performance such as to reduce work time or to handle increased work loads in conditions of financial restraints; especially with automated or semi-automated systems staff numbers can be reduced. These new techniques must be shown by evaluation and clinical trial to be at least as good as existing techniques [5, 6] when in routine use. If new methods have greater sensitivity than standard tube tests, then this must be meaningful and cost effective, and not the detection of clinically non-significant antibodies that may not be cost effective or that may delay the issue of blood in urgent circumstances. Kretschmer et al. [7] considered that the sensitivity of the gel test versus their manual spin tube test reduced the frequency of delayed post-transfusion reactions. The move from serum to plasma samples for automated antibody screening has also raised consideration for the detection of difficult complement-requiring antibodies such as anti-Jka/Jkb. Yates et al. [8] have shown that sub-agglutinating levels of IgM anti-Jka/Jkb can far more easily be detected by anti-complement reaction than by the much weaker anti-light-chain reactions of anti-IgG reagents seen with the use of plasma samples. Different approaches have been used to evaluate new technology systems. Thus contradictory publications have appeared on the relative sensitivity of the DiaMed gel test for antibody detection (DiaMed, Cressier, Switzerland), e.g. Bromilow et al. [9] and Kretschmer et al. [7] found it more sensitive while Voak et al. [10], Phillips et al. [11] and Pinkerton et al. [12] found that the gel test had the same sensitivity as a well performed indirect spin tube antiglobulin test. The probable explanation for the gel test showing a higher performance than routine spin tube tests is due to false-negative results caused by excessive agitation at the reading phase of spin tube tests. This common fault explains most of the failures in external proficiency trials and is easily recognised and corrected by blind replicate tests [13, 14, 15] with 1+/2+ IgG antiD sensitised cells. The origin of excessive reading techniques was due to too much polyclonal anti-C3d complement in polyspecific antiglobulin reagents prior to 1987. The ISBT/ICSH working party on reagents showed that the old FDA method for assessing freedom of reaction with red blood cells with antiglobulin reagents only used washed cells. Many AHG reagents specific by this test would nevertheless give a consistent 1+ unwanted positive result in cross-match tests when the cells are incubating with fresh serum. This is because red blood cells take up more C3d when incubating the fresh serum. The FDA in 1987 altered the specificity test for AHG reagents to incorporate simulated cross-match tests. Further progress at the same time came from the use of monoclonal anti-C3d which was much easier to standardise to give clean, yet potent polyspecific reagents [15]. The use of blind replicate tests to assess staff and quality assure cell washing machines [13, 14] was included in our UK guidelines for compatibility testing from 1987. Thus from 1990 to 1992 we had the very interesting situation of new technolo-