Alloimmunized Plasma Donors Pose Greatest Risk for Transfusion-Related ALI

Key Point

In a study of transfused medical ICU patients, use of a blood product from an alloimmunized donor and other transfusion-related factors predicted development of acute lung injury within six hours.

Transfusion-related acute lung injury (TRALI) was a common occurrence in a group of critically ill patients within six hours after receiving a blood transfusion, reported researchers from the Mayo Clinic College of Medicine in Rochester, Minnesota. While some of the observed risk factors for ALI—such as sepsis and a history of chronic alcohol abuse—were not related to the transfusion itself, others were potentially modifiable, which may have important implications in the prevention and treatment of ALI in critically ill patients, suggested Ognjen Gajic, MD, and colleagues in the November 1 American Journal of Respiratory and Critical Care Medicine.

The investigative team prospectively observed over two years 901 critically ill patients admitted to the medical ICU of a single tertiary care medical center (primarily due to gastrointestinal bleeding) who had received transfusions. Seventy-four patients (8%) developed ALI within six hours of the transfusion; compared with an equal number of matched control transfusion patients who did not develop ALI, they were more likely to have sepsis (37% vs 22% of controls), a history of chronic alcohol abuse (36.5% vs 17.6% of controls), or liver disease (27.5% vs 15.1% of controls). “Hospital mortality was higher in patients who developed ALI (41%) than in matched control subjects (23%),” added the authors.

MULTIPLE TRANSFUSION FACTORS SERVE AS A "SECOND HIT" FOR ALI

Dr. Gajic and colleagues described the underlying patient characteristics that appeared to be associated with an increased occurrence of ALI as the “first hit”; however, specific transfusion factors were observed to serve as a “second hit” in ALI: Patients who developed ALI were more likely to have received plasma-rich blood products, products from female donors, and larger volumes of plasma from female donors, while the donors to ALI patients had a higher number of pregnancies and tested positive for antileukocyte antibodies more often, reported the researchers.

After adjustment for baseline APACHE III scores, sepsis, and alcohol abuse, receipt of any high plasma volume components remained significantly associated with TRALI (odds ratio [OR], 2.78); however, ALI risk after transfusion of plasma from a female donor was greater compared with transfusion of plasma from a male donor (ORs, 5.09 vs 1.60). Each additional pregnancy among the donors conferred further risk for ALI (OR, 1.19), as did each additional blood unit transfused that tested positive for antigranulocyte antibodies (OR, 4.85) or anti–HLA class II antibodies (OR, 3.08).

“The concentration of lysophosphatidylcholine was significantly higher in blood products given to ALI case subjects than to control subjects,” noted Dr. Gajic and colleagues; they reported an OR of 1.69 for each 10-mol/L increase of the biological response modifier; however, the authors cautioned that this difference appears to reflect the larger number of high plasma volume products given to patients with ALI versus control subjects.

Meanwhile, interleukin-8 concentration and storage age of red blood cells did not differ between products transfused to ALI cases or control subjects.

POSSIBLE INTERVENTIONS TO REDUCE LUNG INJURY

The research team pointed out that the UK blood system has nearly eliminated female donors from the production of fresh-frozen plasma, and they cited the first report from 2006, which suggests a significant decrease in TRALI reactions. While similar guidelines have been recommended for North American blood centers, “this intervention may be associated with costs and/or shortage of blood products in some blood centers, [therefore] further studies will need to assess whether the benefit of this intervention outweighs the costs,” said the authors.

Dr. Gajic, an Assistant Professor of Medicine in the Division of Pulmonary and Critical Care Medicine at the Mayo Clinic College of Medicine, and his coinvestigators noted that their prospective examination of transfused critically ill medical patients, rather than an examination of suspected reactions reported to blood banks, indicated that TRALI is more common than previously thought, “supporting the general notion that TRALI is grossly underrecognized and underreported.” They asserted that ongoing multicenter studies in other transfused patients with and without critical illness will provide elucidation of incidence and mechanisms of TRALI, which may lead to additional preventive strategies.           

—Jessica Dziedzic

Suggested Reading
Gajic O, Rana R, Winters JL, et al. Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007;176(9):886-891.

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