A new “initial” case of transfusion-related acute lung injury

To the editor:

In their landmark characterization of transfusion-related acute lung injury (TRALI), Popovsky et al¹  credited Barnard²  with the first description of TRALI. We discovered a report by Lanman et al,³  published in Blood in 1950, which we believe should be considered the first documented case of TRALI. We write to share this finding with the hematology community, although we have briefly included it in our recently published review on TRALI.⁴ 

This description is remarkable because the authors speculated quite accurately on the currently understood mechanism of TRALI. They described the signs and symptoms that followed transfusion of whole blood from a 68-year-old male with chronic lymphocytic leukemia (CLL) to a 54-year-old male with esophageal carcinoma:

“In Experiment 5 (fig. 5), a second transfusion of leukemic blood eighteen days later from the same donor into the same recipient resulted in an immediate, severe reaction, with dyspnea and cyanosis, followed in a few minutes by asthmatic breathing, musical and moist rales, a chill and fever. The recipient's total white cell count fell from a pretransfusion level of 18,430/cu.mm. to 1,700/cu.mm. within 5 minutes, during which time 35 billion white cells (95 per cent mononuclear) were infused. Polymorphonuclear neutrophil cells fell to 8 per cent of pretransfusion levels, mononuclears to 32 per cent, and eosinophils to 2 per cent. A count taken fifteen minutes after the start of the transfusion showed a slight rise toward the pretransfusion level.”³ 

The authors hypothesized that transfusion of leukemic blood led to leukocytes' margination in the lungs, causing the respiratory symptoms! Before transfusion of the 35 billion leukocytes, the recipient had 121 billion cells in circulation, which dropped to 12 billion posttransfusion. Thus, this seems to be the first description of “acute transient leukopenia” in TRALI. Until now, Brittingham was considered the first to describe leukopenia in this reaction after a leukoagglutinin infusion.⁵ 

We speculate that the signs and symptoms described were due to leukocyte antibodies in either the donor or the recipient. The latter could have been induced during the previous transfusion and reacted with the large number of donor leukocytes. It is unknown whether the recipient had prior transfusions, perhaps making a high-titer leukoagglutinin more likely eighteen days after the first transfusion. It seems probable, however, that the antibodies were against the recipient leukocytes because the posttransfusion neutrophil count decreased more than 10-fold and the donor's cells were mostly lymphocytes. Two caveats must be considered. The “whole blood” consisted of a high load of leukemic cells that may have contributed to pulmonary insufficiency. In addition, the authors do not describe the method of blood storage raising the possibility of an endotoxin reaction (presumably from glass bottles).

Despite these caveats, the clinical symptoms are most consistent with TRALI. It is unfortunate that a chest radiograph was not documented, as an abnormal result would have increased the likelihood of TRALI as per current definition. Nevertheless, we propose that Lanman et al were first to document a case of TRALI, in Blood, and should receive appropriate credit for their contribution.