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We have a 42 y.o. Caucasian female with chronic anemia and cellulitis/sepsis needing debridement who has anti-D (2+) & anti-C (3+) by Ortho MTS gel. She was transfused elsewhere in 2021 and here in 2022, all Rh neg units. Two units each time. Screens were negative then. She has a history that suggests she may have shared IV drug needles at some point. I don't think there is a pregnancy history but not ruled out. She is A neg. Her initial testing in Ortho gel was clearly anti-D with C (could include G) but she had some 1+ reactivity with 4 of 5 D and C negative panel cells. The cell that didn't react was E+, D-, C-. Fya+, Fyb-, heterozygous for Kidd and MNS, but Lea- & Leb-. Auto control is negative. Three percent panel cells were then selected, diluted with Ortho diluent 2 to a 0.8% suspension and run in gel with a 30-minute incubation. By this method, we detected the anti-D and C antibodies in 2 cells that were D+, C- and 2 that were D-, C+ respectively. We were able to rule out all other typical specificities on 7 non-reactive cells and did not detect the weak reactivity previously found, suggesting that it was antibody to the pre-diluted 0.8% cells' diluent. One A neg, C neg unit was crossmatch compatible by gel that day and was transfused. Only that unit was crossmatched that day. Two days later (today), they requested more blood. All antiglobulin crossmatches in gel were incompatible--some units were A neg, some O neg. The reactions in gel were all 2+ or weaker with an atypical appearance of having one to two "stripes" from bottom to top, something we usually associate with cold reactive antibodies. Their strength appeared variable from weakly positive to 2+. We tried washing the donor cells, prewarming cells/plasma before combining them, 30 min. incubation in gel, and performing PEG XM's in tube which did not help. PEG was a bit weaker on the 2 units tested by that method (one the strongest reaction in gel and one the weakest), but still positive. We redrew the patient and got the same results with the new specimen. We did not test reagent cells by PEG. We ended up crossmatching about 20 A neg and O neg RBC units by gel and there were 3 that were truly compatible (not including the one from the first day). She got her second unit of this visit in the past few hours with no problems. What might cause reactions with AS-1 donor units but not with reagent red cells? Both are made up in the same diluent and tested by the same process. Some of the donor units were O cells like the reagent cells. Is there anything we should be considering? I expect she will be back for more blood in coming days to years (with our luck, probably with new alloantibodies since she is a responder who was transfused again). Thanks for your wisdom.

As an aside, I would suggest that an anti-G is almost certainly present, indeed, it may ONLY be an anti-G, with no or very weak anti-D and/or anti-C present, as the antibody is reacting stronger with the C antigen, than the D antigen. This is a common finding with anti-G. Turning to your real question, we have found in the past that people can have a "naturally occurring" antibody to an antibiotic added to the cell preservative by the manufacturers. This is NOT easy to wash off from the reagent red cells, as they seem to adsorb it onto their surface almost as strongly as the Lewis antigens are adsorbed. It could be that this patient has made just such an antibody, but this is a very tenuous explanation, and other members will probably come up with something a lot more probable!