Heavy breathing in the blood bank: is it transfusion‐related acute lung injury, our anxiety, or both?

A lthough considerable success has been achieved in reducing the risk of transfusiontransmitted infection, far less progress has been made in addressing the serious pulmonary reactions associated with blood transfusion. In 1957, 8 years before the Australia antigen was described and more than a quarter of a century before HIV and HCV were discovered, Brittingham reported that transfusion of some leukoagglutinins was associated with immediate faintness followed by vomiting, diarrhea, chills, fever, hypotension, severe tachypnea, dyspnea, cyanosis, and initial leukopenia preceding leukocytosis. In 1971, Thompson and colleagues suggested, somewhat presciently, either that donors be screened to interdict units containing leukoagglutinins or that blood from multiparous donors be discarded to prevent these “hypersensitivity reactions. ” This syndrome, now termed “transfusion-related acute lung injury” (TRALI), is recognized as the leading cause of transfusion-associated fatalities reported to the FDA. In the United States, the only current method of preventing TRALI involves deferral of donors implicated in a clinical case. In this issue of TRANSFUSION, Eder and colleagues from the American Red Cross (ARC) Blood Services evaluate 550 reports of suspected TRALI in their national database and reach several provocative conclusions: 1) 63 percent of fatalities were associated with plasma infusion, 2) female donors were disproportionately implicated, 3) reactions were proportional to the volume of plasma infused, and 4) limiting plasma from female donors might prevent as many as six recipient deaths annually. The authors acknowledge several limitations of their data collection and the weaknesses inherent in their retrospective analysis. Passive reporting and complex diagnostic criteria may work to underestimate the scope of the problem and the urgency of finding a solution. Ample data support adopting strategies that avoid the transfusion of plasma from multiparous females. One such study, a prospective randomized, double-blind, crossover trial, compared cardiopulmonary responses in 100 intensive care unit patients transfused with a unit of fresh-frozen plasma (FFP) from a multiparous female, to FFP from a donor with no history of previous transfusion or pregnancy. This study found that the ratio of arterial oxygen partial pressure to inspired oxygen fraction decreased after the transfusion of plasma from multiparous women, but not after control plasma infusion. Furthermore, plasma from multiparous women was more likely to cause clinical reactions. All four pulmonary reactions were associated with the transfusion of multiparous donor plasma. Neutrophil-specific, but not HLA-specific, antibodies were found in the multiparous female plasma sample that caused the single TRALI reaction and in one of three mild pulmonary reactions. This study suggests that plasma from multiparous women may lower oxygen saturation in recipients undergoing intensive care, that some clinically apparent pulmonary reactions are associated with transfusion of antibodies to white blood cells (WBCs), particularly neutrophil-specific antibodies (NSAs), and that the exclusion of plasma from multiparous women could reduce the incidence of these reactions. Numerous case reports emphasize the fact that NSA can cause pulmonary transfusion reactions and sometimes TRALI—but not in every recipient. Animal models have demonstrated that NSAs can cause acute lung injury either by directly stimulating neutrophils or by activating complement which stimulates neutrophils. Lookback studies of recipients of blood components from donors with NSA that caused TRALI have found that they precede a variety of transfusion reactions in up to 36 percent of recipients. Several case reports have likewise associated the transfusion of blood components containing HLA antibodies with TRALI. An animal model also supports a role for HLA Class I antibodies in acute lung injury. Based on these and other data, the English National Blood Service, which supplies more than 80 percent of blood in the United Kingdom, has introduced a policy of preferential use of plasma collected from male donors. Preliminary findings suggest that this intervention has reduced the incidence of TRALI and of TRALI-related deaths. It seems reasonable, as Eder and colleagues suggest, that the United States adopt a similar policy. This country has the capacity to supply frozen plasma needs using primarily male donors, although the logistical pains that will accompany this change should not be minimized; limited availability of AB plasma might require plasma from female donors, perhaps prescreened for WBC antibodies. Most centers do not routinely collect information about past pregnancies (and we are not The views expressed are those of the authors and do not necessarily represent the position of the National Institutes of Health or the Department of Health and Human Services. TRANSFUSION 2007;47:559-562.