"Are delayed antigen-antibody reactions investigated, as far as possible and appropriate, the same as acute reactions" per AABB Standard K3.100?" 

Here is a scenario: A patient with no detectable clinically significant alloantibodies is transfused with 2 units of crossmatch-compatible blood. 10 days later the patient is taken back to surgery and 2 units of blood are ordered. During pretransfusion testing a clinically significant alloantibody is detected. The patient also has a positive DAT and the same alloantibody is eluted from the RBCS. It is clear to me that this is a delayed transfusion reaction. The Standard actually talks about delayed hemolytic reactions. If there is no evidence of increased RBC destruction, i.e., normal bilirubin & LDH, it would not be considered hemolytic and therefore would not need to be reported as such. Is that correct? I have been reporting these as delayed reactions "omitting" the word hemolytic but do they really need to be reported on the patient's chart if there is no evidence of hemolysis? If any delayed reaction must be reported then how far does one go? If a patient with no antibodies is transfused and then comes back 2 months later with a positive DAT, serum antibody and antibody in the eluate would you initiate a reaction report for the chart? What is the cut-off? Three months?

The following ideas have been submitted in response to the posed question. These opinions are paraphrased and are being presented without attribution. They do not represent an official opinion or position of the CBBS.

1. According to one CBBS e-network panelist, the above scenario strongly suggests a delayed transfusion reaction. However, if there is no evidence of increased red cell destruction (i.e. normal bilirubin, haptoglobin, LDH, etc.), it is difficult to call such a reaction hemolytic. Therefore, in a formal sense, K3.100 would not apply. However, in practicality, the scenario outlined above would require the type of evaluation mandated in K3.100, i.e., delayed hemolytic reaction is suspected so tests to determine and confirm the cause of the reaction should be undertaken (eluate, laboratory assessment for hemolysis; in other words, the things that were already done as part of the scenario described). Some individuals have taken to calling the above a "delayed serologic reaction" - i.e. an anamnestic response to a blood group antigen that does not result in overt hemolysis. K3.100 goes on to state that "the results of the evaluation shall be reported to the patient's physician and recorded in the patient's medical record". Since even the delayed serologic reaction, at least that occurring in close proximity to transfusion, is a suspected delayed hemolytic reaction until proven otherwise (i.e. by testing), it probably should be reported on the patient's chart. It is important to make this contact with clinicians to make them aware of the serology and the potential for hemolysis so that they will actually monitor their patient and order the appropriate lab tests. Therefore, clinician reporting meets the standard (K3.100) but also helps to establish a dialogue between the physician and the blood bank.

2. A second panelist did not think there is any time limit to initiate a reaction report for the chart. It can take 5 months for a patient to make anti-D after an Rh-positive transfusion to an Rh-negative recipient! The panelist would base the "diagnosis" on the direct antiglobulin test and the delineation of an antibody specificity. The panelist would suspect there would be some signs of hemolysis, even if subtle, such as a more rapid fall in the hematocrit than expected or a low grade fever. Further, these should be worked up and reported as hemolytic, unless there is absolute evidence against any evidence of "hemolysis" which includes shortened red cell survival. The panelist points out that there was an article in the Mayo Clinic Proceedings more than 20 years ago on this. While most delayed hemolytic transfusion reactions are due to an anamnestic antibody response, the milder, often unnoticed ones, are usually due to a primary antibody response. Workup, if possible, should rule out an antibody present at a low level that rises quickly after the transfusion. All the information needs to go into the patient's chart as well as into the blood bank/transfusion service's files. By putting something in the patient's chart, it should be noted by the clinician who should be looking for clinical evidence of a delayed hemolytic reaction at the time, as well as for future reference with subsequent transfusions.

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Ira A. Shulman, MD
CBBS e-Network Forum Editor & Moderator