Associate Professor; Associate Medical Director University of California San Diego San Diego, California, United States
Background/Case Studies: Cold auto- and alloantibodies are generally IgM antibodies that react below physiologic temperature and are clinically insignificant. Rarely, IgM cold autoantibodies may cause agglutination and/or hemolysis when they have a broad thermal amplitude or when exposed to hypothermic conditions, such as cold cardioplegia. The purpose of this single-institution retrospective review was to enumerate and describe the variety of ways that cold antibodies were detected during pre-transfusion testing with column agglutination technology (CAT) over a two-year period.
Study
Design/Methods: With limited exceptions, institutional policy is to perform patient ABO/Rh typing and primary antibody screening with CAT testing on a glass bead-based platform. Suspected cold antibodies are tested and confirmed with a cold screen by tube technique. In this study, patients with cold antibodies detected at our institution from 1/1/2021 to 12/31/2022 were reviewed. The reported antibodies were assessed for their specificity and the mechanism by which they were detected. This study was exempted from Institutional Review Board requirements.
Results/Findings: During the two-year study period, cold autoantibodies were reported 760 times in 299 unique patients, of whom 67% were female and 33% were male. These antibodies were detected due to unexplained reactivity on CAT antibody screening and/or extended panels, ABO discrepancies, positive RhD typing controls, direct antiglobulin tests positive for complement, and, less commonly, unexpected incompatibility on immediate spin crossmatch testing. Of note, roughly nine percent of cases (70/760) were initially detected on CAT antibody screening by the characteristic mixed-field-like reactivity.
Cold alloantibodies were reported 80 times in 49 unique patients, of whom 71% were female and 29% were male. The most common alloantibody specificity identified was anti-M (53%), followed by anti-Lea (22%), -Lua (10%), -P1 (6%), and -Leb (4%) and -N (4%). Forty-three percent of patients with cold alloantibodies (21/49) had additional concurrent antibodies. Conclusions: Cold auto- and alloantibodies can be detected with pre-transfusion testing using CAT, regardless of their clinical significance. These antibodies demonstrate diverse patterns of reactivity and, therefore, may be incidentally detected in various ways. This retrospective review inspired the creation of a job aid (Figure 1) for transfusion medicine trainees and technologists to appreciate the various algorithms for cold antibody detection and interrogation. Recognition of cold antibody presence is important for accurate blood typing and resolution of potential concomitant clinically significant antibodies.
Importance of research: To our knowledge, this retrospective review is the most comprehensive assessment of cold antibody detection on pre-transfusion testing, specifically on column agglutination technology (gel) platforms. Understanding the nuances of the detection of cold antibodies is of importance for transfusion services and quality assurance/regulatory professionals alike. Additionally, the job aid displayed in Figure 1 may assist other institutions with their management of cold antibody detection.
