TRALI: Risk Factors

Transfusion-related acute lung injury (TRALI) is defined as new acute lung injury (ALI) occurring within six hours of blood product administration. In addition, the diagnostic criteria (as described by a 2004 consensus panel) includes evidence of hypoxemia (PaO₂/ FiO₂ ≤ 300, SpO₂ < 90% on room air, or other clinical evidence of hypoxemia), bilateral infiltrates on frontal chest x-ray, no evidence of circulatory overload/ left atrial hypertension, and no preexisting ALI or acute respiratory distress syndrome (ARDS) prior to transfusion. Furthermore, there must not be another risk factor for ALI or ARDS present at the time of transfusion; otherwise, the term “possible TRALI” (pTRALI) should be used. Risk factors for ALI/ ARDS include direct lung injury from aspiration, toxic inhalation, pneumonia, lung contusion, or near drowning and indirect lung injury from severe sepsis, other shock states, major trauma, burn injury, acute pancreatitis, cardiopulmonary bypass, and drug overdose [1]. More recently, members of the same committee instrumental in the 2004 definition have proposed to redefine TRALI and possible TRALI as TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or existing mild ARDS but stable pulmonary status 12 hours prior to transfusion), respectively [2].

TRALI is thought to occur via a “two-hit” process, with the first hit being due to recipient factors, such as an underlying proinflammatory state, and the second hit being due to the transfusion itself. Risk factors can thus be divided into recipient (i.e. pre-transfusion) risk factors and blood component risk factors, respectively. Recipient risk factors include higher pre-transfusion plasma interleukin-8 levels (reflecting a proinflammatory state), current smoker, increased age, chronic alcohol abuse, end-stage liver disease, hematologic malignancy, thrombotic microangiopathy, cardiac surgery, liver transplant surgery, surgery requiring multiple transfusions, positive fluid balance, higher APACHE II score, postpartum hemorrhage, and mechanical ventilation with peak airway pressure > 30 cm H₂O. Furthermore, sepsis and non-cardiogenic shock, which are also known risk factors for ARDS, put the patient at additional risk of TRALI [2,3]. Notably, most recipient factors associated with TRALI have not been consistently found across all studies, which may be explained by differences in study design, differing mixes of TRALI and pTRALI, prospective versus retrospective studies, and active versus passive reporting [2].

Transfusion risks factors (i.e. the “second hit”) include receipt of plasma from female donors (increased risk with higher volumes, multiparous donors), increased volume of highly-reactive transfused cognate HLA class II antibodies (i.e. antibodies that strongly bind recipient HLA antigen, with MFI > 1500), and increased volume of transfused cognate anti-human neutrophil antigen (HNA) positive by granulocyte immunofluorescence testing (GIFT) [2,3].

Risk mitigation strategies thus include both optimization of recipient status (such as judicious fluid use) as well as transfusion risk factors. This includes judicious blood product use, avoidance of donors implicated in a TRALI reaction, avoidance of donors more likely to be alloimmunized to leukocytes (such as multiparous females), testing of multiparous apheresis donors of plasma or platelets for anti-HLA antibodies, and use of a solvent/detergent-treated plasma product in place of FFP [4].