title: Transfusion-related acute lung injury in cardiac surgery patients is characterized by pulmonary inflammation and coagulopathy: a prospective nested case-control study.
abstract: 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.
  
  
  METHODS
  Nested case-control study.
  
  
  METHODS
  Operating theatre and intensive care department of a tertiary referral hospital.
  
  
  METHODS
  Elective cardiac surgery patients requiring postsurgery intensive care admission.
  
  
  METHODS
  None.
  
  
  METHODS
  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-α1-antitrypsin complexes, thrombin-antithrombin complexes, plasminogen activator activity, and plasminogen activator inhibitor-1 were determined by means of enzyme-linked immunosorbent assay.
  
  
  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-α1-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-α1-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.
authors: Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands. a.p.vlaar@amc.uva.nl
authors: Alexander P J
authors: AP
authors: Vlaar
authors: Jorrit J
authors: JJ
authors: Hofstra
authors: Rogier M
authors: RM
authors: Determann
authors: Denise P
authors: DP
authors: Veelo
authors: Frederique
authors: F
authors: Paulus
authors: Marcel
authors: M
authors: Levi
authors: Sacha
authors: S
authors: Zeerleder
authors: Margreeth B
authors: MB
authors: Vroom
authors: Marcus J
authors: MJ
authors: Schultz
authors: Nicole P
authors: NP
authors: Juffermans
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology* / Q000503:physiopathology*; D000368:Aged; D000369:Aged, 80 and over; D001777:Blood Coagulation / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D016022:Case-Control Studies; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007378:Interleukins / Q000276:immunology; D019272:Leukocyte Elastase / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011014:Pneumonia / Q000378:metabolism*; D011446:Prospective Studies; D000515:alpha 1-Antitrypsin / Q000276:immunology
chemical_list: D007378:Interleukins; D000515:alpha 1-Antitrypsin; C037741:alpha 1-antitrypsin-leukocyte elastase complex; D019272:Leukocyte Elastase