Potential contribution of mitochondrial DNA damage associated molecular patterns in transfusion products to the development of acute respiratory distress syndrome after multiple transfusions
| Autor: | Gina C. Capley, Viktor M. Pastukh, Cherry A. Muscat, Michael L. Marshall, David C. Muscat, Mark N. Gillespie, Yann Leei L. Lee, Jon D. Simmons, Sidney B. Brevard |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Blood Platelets Male ARDS Blood transfusion medicine.medical_treatment 030204 cardiovascular system & hematology Lung injury Critical Care and Intensive Care Medicine DNA Mitochondrial Article Proinflammatory cytokine 03 medical and health sciences Plasma 0302 clinical medicine medicine Alarmins Humans Platelet Prospective Studies Respiratory Distress Syndrome business.industry Transfusion Reaction medicine.disease 030220 oncology & carcinogenesis Immunology Wounds and Injuries Surgery Female Fresh frozen plasma Packed red blood cells business Transfusion-related acute lung injury DNA Damage |
| Zdroj: | The journal of trauma and acute care surgery. 82(6) |
| ISSN: | 2163-0763 |
| Popis: | BACKGROUND Massive transfusions are accompanied by an increased incidence of a particularly aggressive and lethal form of acute lung injury (delayed transfusion-related acute lung injury) which occurs longer than 24 hours after transfusions. In light of recent reports showing that mitochondrial (mt)DNA damage-associated molecular patterns (DAMPs) are potent proinflammatory mediators, and that their abundance in the sera of severely injured or septic patients is predictive of clinical outcomes, we explored the idea that mtDNA DAMPs are present in transfusion products and are associated with the occurrence of delayed transfusion-related acute lung injury. METHODS We prospectively enrolled fourteen consecutive severely injured patients that received greater than three units of blood transfusion products and determined if the total amount of mtDNA DAMPs delivered during transfusion correlated with serum mtDNA DAMPs measured after the last transfusion, and whether the quantity of mtDNA DAMPs in the serum-predicted development of acute respiratory distress syndrome (ARDS). RESULTS We found detectable levels of mtDNA DAMPs in packed red blood cells (3 ± 0.4 ng/mL), fresh frozen plasma (213.7 ± 65 ng/mL), and platelets (94.8 ± 69.2), with the latter two transfusion products containing significant amounts of mtDNA fragments. There was a linear relationship between the mtDNA DAMPs given during transfusion and the serum concentration of mtDNA fragments (R = 0.0.74, p < 0.01). The quantity of mtDNA DAMPs in serum measured at 24 hours after transfusion predicted the occurrence of ARDS (9.9 ± 1.4 vs. 3.3 ± 0.9, p < 0.01). CONCLUSION These data show that fresh frozen plasma and platelets contain large amounts of extracellular mtDNA, that the amount of mtDNA DAMPs administered during transfusion may be a determinant of serum mtDNA DAMP levels, and that serum levels of mtDNA DAMPs after multiple transfusions may predict the development of ARDS. Collectively, these findings support the idea that mtDNA DAMPs in transfusion products significantly contribute to the incidence of ARDS after massive transfusions. LEVEL OF EVIDENCE Prognostic study, level II; therapeutic study, level II. |
| Databáze: | OpenAIRE |
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