Detecting alloantibodies in patients with autoantibodies

lood transfusion carries risks of both immunologic and nonimmunologic complications. ’,’ Among the immunologic complications follow ing transfusion are hemolytic transfusion reactions that can result in substantial morbidity, and even death. A number of specialized serologic techniques have been developed to minimize the potential for such reactions. These critical pretransfusion compatibility tests include ABO grouping of the recipient and donor blood, Rh typing, and methods for the detection of clinically significant red cell (RBC) alloantibodies in the recipient that could potentially cause a severe hemolytic transfusion reaction. ’ In most instances, pretransfusion testing is straightforward. Alloantibodies are detected by screening assays in which the patient’s serum is tested against two or three examples of RBCs selected as “screening cells,” after which their specificity is determined by testing against a larger panel, usually consisting of 10 examples of RBCs of varying phenotypes. RBCs that are selected for transfusion lack antigens with which the patient’s alloantibody(ies) reacts. However, when RBC autoantibodies are present, they typically react with all cells of the panel, thereby potentially masking the presence of alloantibodies. A number of publication^^-^ have discussed means of detecting alloantibodies in the presence of autoantibodies and, in this issue of TRANSFUSION, Leger and GarrattyIn report an analysis of the effectiveness of several currently recommended techniques, with emphasis on adsorption of sera in the presence of polyethylene glycol (PEG). Before discussing these various methods, it is of benefit to first review what we know about the importance of utilizing such specialized compatibility test procedures. In seven reported studies of randomly selected sera containing warm autoantibodies, including that of Leger and Garratty, investigators have found alloantibodies of potential clinical significance in 12 to 40 percent of ~ a r n p l e s . ~ ~ ~ ~ ~ ~ ’ ~ (Table 1). In some instances, the alloantibodies are evident even in the presence of broadly reacting autoantibodies because of variable reactivity in a panel; however, three report^'^-'^ indicate that, in 42 to 77 percent of sera, alloantibodies were not evident before adsorption. One additional report, by Sokol et al.,I5 regarding detection of alloantibodies in sera with autoantibodies reported finding clinically significant alloantibodies in 10 percent of sera. This percentage excludes alloantibodies reported by the authors that are generally thought to be clinically insignificant (anti-HI, -Al, -P,, -Leb, -M, -Bg, -Lea, -N, -Chido, -Lua, and -Wra). This study is impossible to compare with other reports, because it included sera with warmand cold-reactive autoantibodies. The authors did not report how many of the subjects had warm autoantibodies or how many of the patients with warm autoantibodies were alloimmunized. Further, the authors pointed out that their policy is to issue Kblood of matched Rh phenotype, and they speculate that this may have contributed to the relatively low occurrence of alloantibodies in their series. For these reasons, we have excluded this report from our analysis. The collective data indicate that alloantibodies were detected in 209 (32%) of 647 sera. The data clearly point out the need for the use of a method to detect these antibodies, to prevent alloantibody-induced hemolytic transfusion reactions. Indeed, undetected alloantibodies may be the cause of increased hemolysis following transfusion, which may be falsely attributed to an increase in the severity of autoimmune hemolytic anemia.2 Issitt et al.“ showed that some of the suspected alloantibodies are actually autoantibodies that have specificities that mimic alloantibodies. They reported that the incidence of potentially clinically significant alloantibodies went from 43 to 24 percent after the autoantibodies that mimicked alloantibodies were identified. Although it may not be necessary to provide RBCs for transfusion that lack the antigen against which a patient’s mimicking autoantibody is directed, there are no data available to document the accuracy of such speculation. ” The method used for detecting alloantibodies must be such that it will ensure the safest outcome. Although the cost and time commitment for such a method should be considered to some extent, they should not be the main TRANSFUSION 1999;39:6-10.