Five sets of observations are presented showing the development of hemolytic anemia in group A patients as the result of prolonged administration of relatively large amounts of pooled plasma. During the hemolytic episodes, spherocytosis, increase in osmotic fragility, rising bilirubin levels and sometimes clinical jaundice and splenomegaly were observed. Antibody attached to the recipients’ erythrocytes was demonstrated by means of the direct Coombs test, and in several instances free antibody of anti-A specificity was found in the recipient’s plasma during the hemolytic episode.

Random testing of commercial pooled plasma revealed a number of instances of astonishingly high anti-A titers, indicating that neither dilution in the pool nor neutralization by natural A substance in the component A plasmas can be relied upon.

The pools implicated in the production of hemolytic reactions had anti-A1 titers of 1:64 in saline or higher, and with the usual technics showed no clear-cut "immune" characteristics except in one instance. The administration of substantial amounts of plasma pools of low titer (1:16) was not followed by adverse reactions in several instances. On the other hand, the administration of originally high titered plasmas, neutralized in vitro to a saline titer of 1:16 resulted in blood destruction, indicating that under conditions of prolonged massive administration, specific soluble substance, though effective in vitro, is inadequate in vivo. Whether the adverse effects of the moderately high and high titered plasma pools were the result of purely quantitative factors connected with the introduction of large amounts of natural anti-A agglutinins or whether special immune isoantibodies not detected by the methods used were responsible could not be determined by the data at hand.

Prolonged administration of untitered pooled plasma to recipients of blood groups A and probably B is potentially dangerous.

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