How I manage cold agglutinins

Abstract

old agglutinins have been one of the banes of blood group serologists since pretransfusion testing protocols were first implemented. Cold autoagglutinins interfere with ABO/Rh typing tests, yield unwanted positive tests for unexpected antibodies, and may mask the presence of concomitant, clinically significant alloantibodies. Cold alloagglutinins, such as anti-M, -P 1 , or -Le a rarely cause accelerated destruction of mismatched red blood cells (RBCs), and it is not necessary to detect examples of these antibodies that only react below body temperatures.The extent to which cold agglutinins can interfere with the results of pretransfusion antibody detection and compatibility tests is evident from a study by Garratty 1 on the importance of anticomplement reagents in immunohematology. With a low-ionic-strength saline (LISS) method that included room temperature incubation and polyspecific (anti-IgG+ C3) antiglobulin serum, the rate of unwanted positive tests (due primarily to the detection of cold-reactive auto-and alloagglutinins) was on the order of 1.41 percent! Omitting the room temperature incubation phase and use of anti-IgG reduced the unwanted positive rate reduced to 0.1 percent. AVOIDING COLD AGGLUTININSGiven these introductory comments, the proper handling of cold agglutinins in the transfusion service requires that pretransfusion antibody screening be performed utilizing methods that avoid their detection, namely: C 1. No reading for direct agglutination, including immediate-spin tests and direct reading after 37°C incubation. 2. No microscopic examination of tests. 3. Use of anti-IgG instead of polyspecific antiglobulin reagent.In these regards, polyethylene glycol or gel techniques 2,3 are ideal methods to use. Data supporting safety of the above recommendations are found in Trudeau and colleagues, 4 Laferriere and coworkers, 5 Judd and colleagues, [6][7][8] The one problem that can arise from omitting readings for direct agglutination when screening for unexpected antibodies is the occurrence of a positive immediate-spin cross-match when the screening tests are negative. In this situation, before implementing an electronic cross-match, our approach was to verify that blood of the correct ABO type had been selected and to crossmatch the units by the indirect anitglobulin test (IAT). If the units were compatible by IAT, they were released for transfusion. If not, an antibody identification study was initiated.

Erythrocyte‐magnetized technology: an original and innovative method for blood group serology

“…EMT detected a markedly lower number of nonrelevant or moderately relevant antibodies (anti‐M, ‐Le a , ‐Le b ) routinely detected by microcolumn methods, especially in pregnant women. Although these antibodies are known to cause delayed hemolytic transfusion reactions or hemolytic disease of the fetus and newborn in rare cases, they are typically naturally occurring unwanted IgM antibodies 14,15 . Only in a few cases of anti‐M, an IgG component can be detected and may cause fetal anemia or reduced survival of transfused M+ RBCs 16,17 .…”

Acute hemolysis of transfused A2 red cells by an auto‐HI antibody

“…Cold autoantibodies commonly complicate identification of unexpected alloantibodies to RBC antigens 7 and, aside from cold agglutinin syndrome, rarely cause clinically significant hemolysis. This case provides a rare example of a clinically significant anti‐HI autoantibody that we have implicated in an AHTR.…”

“…Since cold autoantibodies can confound an immediate‐spin cross‐match, an electronic cross‐match method can simplify selection of RBCs for those patients with cold autoantibodies 7 . Unfortunately, in this case, the RBC unit issued belonged to the A2 subgroup.…”

“…Occasionally, cold autoantibodies are reactive at room temperature and complicate interpretation of screening tests for alloantibodies to RBC antigens. Methods that avoid immediate‐spin tests and reading for direct agglutination, such as polyethylene glycol 5 and gel‐based techniques, 6 have been suggested to minimize false‐positive antibody screens due to cold autoantibodies 7 . Alternatively, a prewarming technique may be used, 8 although this method may also result in decreased reactivity of clinically significant alloantibodies 9 and therefore should be used with caution.…”

How we evaluate panagglutinating sera

“…If the DAT is positive for anti‐C3d only, an immunoglobulin M (IgM) class autoantibody is likely. One approach is to look for immunoglobulin G (IgG) alloantibodies after inactivation of the IgM autoantibody with 2‐mercaptoethanol 14 Table 7. presents IgG alloantibodies detected after 2‐mercaptoethanol treatment in our experience.…”