Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model.

Transfusion-related acute lung injury is suggested to be a "2-hit" event resulting from priming and activation of pulmonary neutrophils. Activation may result from infusion of lysophosphatidylcholines (LysoPCs), which accumulate during storage of blood products. In the present study, we developed a syngeneic in vivo transfusion model to test whether storage of platelet concentrates (PLTs) results in lung injury in healthy rats as well as in a "2-hit" model using lipopolysaccharide-pretreated rats. In addition, the effect of washing of platelets was studied. In healthy rats, transfusion of aged PLTs caused mild lung inflammation. In LPS-pretreated rats, transfusion of aged PLTs, but not fresh PLTs, augmented pulmonary systemic coagulopathy. When PLTs components were transfused separately, supernatant of aged PLTs, but not washed aged platelets, induced pulmonary injury in the "2-hit" model. Supernatants of aged PLTs contained increased concentrations of LysoPCs compared with fresh PLTs, which enhanced neutrophil priming activity in vitro. We conclude that transfusion of aged PLTs induces lung inflammation in healthy rats. In a "2-hit" model, aged PLTs contribute to pulmonary and systemic coagulopathy, which may be mediated by LysoPCs, which accumulate in the supernatant of PLTs during storage.

[1]  M. Kersten,et al.  The divergent clinical presentations of transfusion-related acute lung injury illustrated by two case reports. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[2]  T. van der Poll,et al.  Nebulized anticoagulants limit pulmonary coagulopathy, but not inflammation, in a model of experimental lung injury. , 2010, Journal of aerosol medicine and pulmonary drug delivery.

[3]  J. Binnekade,et al.  Risk factors and outcome of transfusion-related acute lung injury in the critically ill: A nested case–control study* , 2010, Critical care medicine.

[4]  M. Matthay,et al.  Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury. , 2009, The Journal of clinical investigation.

[5]  T. van der Poll,et al.  Nebulized antithrombin limits bacterial outgrowth and lung injury in Streptococcus pneumoniae pneumonia in rats , 2009, Critical care.

[6]  R. Porte,et al.  Platelet Transfusion During Liver Transplantation Is Associated with Increased Postoperative Mortality Due to Acute Lung Injury , 2009, Anesthesia and analgesia.

[7]  P. Frenette,et al.  HETEROTYPIC INTERACTIONS ENABLED BY POLARIZED NEUTROPHIL MICRODOMAINS MEDIATE THROMBO-INFLAMMATORY INJURY , 2009, Nature Medicine.

[8]  E. Moore,et al.  Plasma from stored packed red blood cells and MHC class I antibodies causes acute lung injury in a 2-event in vivo rat model. , 2009, Blood.

[9]  G. Mcgwin,et al.  Age of transfused blood: an independent predictor of mortality despite universal leukoreduction. , 2008, The Journal of trauma.

[10]  M. Levi,et al.  The Role of Bronchoalveolar Hemostasis in the Pathogenesis of Acute Lung Injury , 2008, Seminars in thrombosis and hemostasis.

[11]  T. Mihaljevic,et al.  Duration of red-cell storage and complications after cardiac surgery. , 2008, The New England journal of medicine.

[12]  H. Schuitemaker,et al.  Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates , 2007, Transfusion.

[13]  M. Malinchoc,et al.  Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. , 2007, American journal of respiratory and critical care medicine.

[14]  I. D. De Cuyper,et al.  Influence of pH on stored human platelets , 2007, Transfusion.

[15]  M. Schultz,et al.  Developing specific therapeutic strategies for transfusion-related acute lung injury. An overview of potentially useful animal models. , 2007, Cardiovascular & Hematological Agents in Medicinal Chemistry.

[16]  T. van der Poll,et al.  Natural anticoagulants limit lipopolysaccharide-induced pulmonary coagulation but not inflammation , 2007, European Respiratory Journal.

[17]  P. Toy,et al.  TRALI--definition, mechanisms, incidence and clinical relevance. , 2007, Best practice & research. Clinical anaesthesiology.

[18]  T. van der Poll,et al.  Recombinant human activated protein C inhibits local and systemic activation of coagulation without influencing inflammation during Pseudomonas aeruginosa pneumonia in rats , 2007, Critical care medicine.

[19]  R. Brand,et al.  A multicenter randomized study of the efficacy of transfusions with platelets stored in platelet additive solution II versus plasma. , 2006, Blood.

[20]  C. Silliman,et al.  Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury. , 2006, Blood.

[21]  T. Lesnick,et al.  Transfusion‐related acute lung injury and pulmonary edema in critically ill patients: a retrospective study , 2006, Transfusion.

[22]  C. Silliman,et al.  The role of endothelial activation in the pathogenesis of transfusion‐related acute lung injury , 2005, Transfusion.

[23]  Edward Abraham,et al.  Transfusion-related acute lung injury: definition and review. , 2005, Critical care medicine.

[24]  J. Freedman,et al.  Proceedings of a consensus conference: towards an understanding of TRALI. , 2005, Transfusion medicine reviews.

[25]  Robertson Davenport,et al.  Toward an understanding of transfusion‐related acute lung injury: statement of a consensus panel , 2004, Transfusion.

[26]  Peter A Lachenbruch,et al.  Fatalities caused by TRALI. , 2004, Transfusion medicine reviews.

[27]  F. Baas,et al.  Neutrophils in Barth syndrome (BTHS) avidly bind annexin-V in the absence of apoptosis. , 2004, Blood.

[28]  N. Voelkel,et al.  Plasma and lipids from stored platelets cause acute lung injury in an animal model , 2003, Transfusion.

[29]  L. Dumont,et al.  Seven‐day storage of apheresis platelets: report of an in vitro study , 2003, Transfusion.

[30]  C. Silliman,et al.  Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. , 2003, Blood.

[31]  W. Lamorte,et al.  Effects of age of transfused blood on length of stay in trauma patients: a preliminary report. , 2002, The Journal of trauma.

[32]  M. Brockmann,et al.  Binding of activated platelets to WBCs in vivo after transfusion , 2002, Transfusion.

[33]  C. Martin,et al.  Effect of prophylactic transfusion of stored RBCs on oxygen reserve in response to acute isovolemic hemorrhage in a rodent model , 2001, Transfusion.

[34]  C. Folman,et al.  Increase in Glycocalicin Levels in Platelet Concentrates Stored in Plasma or Synthetic Medium for 8 Days: Comparison with Other Platelet Activation Markers , 2000, Vox Sanguinis.

[35]  S. Nakamura,et al.  Analysis of genes under the downstream control of the t(8;21) fusion protein AML1-MTG8: overexpression of the TIS11b (ERF-1, cMG1) gene induces myeloid cell proliferation in response to G-CSF. , 2000, Blood.

[36]  N. Voelkel,et al.  Plasma and lipids from stored packed red blood cells cause acute lung injury in an animal model. , 1998, The Journal of clinical investigation.

[37]  A. Paterson,et al.  The association of biologically active lipids with the development of transfusion‐related acute lung injury: a retrospective study , 1997, Transfusion.

[38]  C. Silliman,et al.  Analysis of the priming activity of lipids generated during routine storage of platelet concentrates , 1996, Transfusion.

[39]  T. Fuchs-Buder,et al.  Time course of procoagulant activity and D dimer in bronchoalveolar fluid of patients at risk for or with acute respiratory distress syndrome. , 1996, American journal of respiratory and critical care medicine.

[40]  J. Loos,et al.  Pooled Platelet Concentrates Prepared by the Platelet‐Rich‐Plasma Method and Filtered with Three Different Filters and Stored for 8 Days , 1995, Vox sanguinis.

[41]  C. Silliman,et al.  Partial characterization of lipids that develop during the routine storage of blood and prime the neutrophil NADPH oxidase. , 1994, The Journal of laboratory and clinical medicine.

[42]  E. Snyder,et al.  Cytokine generation in stored platelet concentrates , 1994, Transfusion.

[43]  D. Pearse,et al.  Spontaneous injury in isolated sheep lungs: role of resident polymorphonuclear leukocytes. , 1992, Journal of applied physiology.

[44]  J. T. ten Cate,et al.  Plasminogen Activation In Vivo upon Intravenous Infusion of DDAVP , 1992, Thrombosis and Haemostasis.

[45]  T. van der Poll,et al.  Activation of coagulation after administration of tumor necrosis factor to normal subjects. , 1990, The New England journal of medicine.

[46]  R. Aster,et al.  A Study of Variables Affecting the Quality of Platelets Stored at “Room Temperature” , 2003, Transfusion.

[47]  G. Geelhoed,et al.  Pulmonary effects of autotransfused blood. A comparison of fresh autologous and stored blood with blood retrieved from the pleural cavity in an in situ lung perfusion model. , 1973, American journal of surgery.

[48]  G. Geelhoed,et al.  Pulmonary injury resulting from perfusion with stored bank blood in the baboon and dog. , 1972, The Journal of surgical research.