During a major crossmatch for additional units, a 3+ reaction occurs and there is a previously uninvestigated positive screening cell. What is the cause and recommended action?

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A strong positive crossmatch with a positive but uninvestigated screening cell means there is a clinically significant antibody in the patient’s plasma reacting with donor red cells. The next step is to identify the antibody so you know its specificity. Once you know the antibody’s target antigen, you can select donor units that lack that antigen (antigen-negative units) and perform compatibility testing with them. This approach prevents transfusion reactions by avoiding the antigen that the patient’s antibody recognizes. Proceeding with the current units would risk a hemolytic reaction, and a general statement about a positive screen doesn’t tell you which antigen to avoid. Identifying the antibody provides the specific information needed to choose safe, compatible units.