Transfusion-related acute lung injury in cardiac surgery patients is characterized by pulmonary inflammation and coagulopathy: A prospective nested case-control study

Objective: Transfusion-related acute lung injury is the leading cause of transfusion-related morbidity and mortality. Clinical data on the pathogenesis of transfusion-related acute lung injury are sparse. The objective of the present study was to determine inflammation and coagulation pathways involved in the onset of transfusion-related acute lung injury. Design: Nested case-control study. Setting: Operating theatre and intensive care department of a tertiary referral hospital. Patients: Elective cardiac surgery patients requiring postsurgery intensive care admission. Interventions: None. Measurements: Cardiac surgery patients (n = 668) were prospectively screened for the onset of transfusion-related acute lung injury. Transfusion-related acute lung injury cases (n = 16) were randomly assigned to transfused and nontransfused cardiac surgery controls in a 1: 2 ratio. Blood samples were taken pre- and postoperatively and at onset of transfusion-related acute lung injury. In addition, at onset of transfusion-related acute lung injury, bronchoalveolar lavage fluid was obtained. In plasma and bronchoalveolar lavage fluid, levels of interleukin-6, interleukin-8, elastase-alpha(1)-antitrypsin complexes, thrombin-antithrombin complexes, plasminogen activator activity, and plasminogen activator inhibitor-1 were determined by means of enzyme-linked immunosorbent assay. Main Results: In all patients, cardiac surgery was associated with systemic inflammation, evidenced by an increase in plasma levels of interleukin-6, interleukin-8, and elastase-alpha(1)-antitrypsin complexes compared with presurgery levels (p <.001). Prior to onset of transfusion-related acute lung injury, systemic interleukin-8 and interleukin-6 levels were higher compared with nontransfused controls (p <.01). In transfusion-related acute lung injury cases, bronchoalveolar lavage fluid levels of interleukin-8, interleukin-6, and elastase-alpha(1)-antitrypsin complexes were elevated compared with control groups (p <.05). Both plasma and bronchoalveolar lavage fluid levels of thrombin-antithrombin complexes were enhanced in transfusion-related acute lung injury cases compared with control groups (p <.01). Bronchoalveolar lavage fluid levels of plasminogen activator activity were decreased due to an increase in plasminogen activator inhibitor-1 levels in transfusion-related acute lung injury cases compared with control groups (p <.01), indicating suppressed fibrinolysis. Conclusions: Prior to onset of transfusion-related acute lung injury, there is systemic inflammation and neutrophil sequestration. Transfusion-related acute lung injury is characterized by both systemic and pulmonary inflammation and activation of neutrophils, as well as enhanced coagulation and suppressed fibrinolysis. (Crit Care Med 2012; 40:2813-2820)