In a retrospective study on samples from 10,000 recently transfused pa
tients, 35 samples were found to contain an antibody that reacted with
ficin-treated red cells but was not demonstrable by low-ionic-strengt
h saline solution and indirect antiglobulin test (LISS-IAT). In those
35 patients, the specificity of the antibody was such that each patien
t would have been transfused with antigen-negative blood had the antib
ody reacted in LISS-IAT. Tests on red cells from the units already tra
nsfused showed that 19 patients had among them received, by chance, 32
antigen-positive and 74 antigen-negative units. The remaining 16 pati
ents had among them received 57 units that were, again by chance, all
antigen negative. One patient given antigen-positive blood suffered a
delayed transfusion reaction; in two others the antibodies became LISS
-IAT active after transfusion. However, similar changes to the LISS-IA
T-active state were seen with two antibodies of patients given only an
tigen-negative blood. Also found in the 10,000 patients were 28 clinic
ally insignificant antibodies, 77 sera in which the antibody was too w
eak to identify, and 216 autoantibodies that reacted only with ficin-t
reated red cells. These data support a belief, generally held in the U
nited States but not necessarily elsewhere, that the use of protease-t
reated red cells for routine pretransfusion tests creates far more wor
k than the accrued benefits justify.