Transfusion-Related Acute Lung Injury (TRALI) Occurrence, Risk Factors, and Outcome: A Nested Case-Control Study

摘要

Background and Objectives:Transfusion-Related Acute Lung Injury (TRALI) is a serious complication of blood transfusion characterized by hypoxemia and pulmonary edema. Our study assessed TRALI occurrence, potential risk factors using a large administrative database and medical charts.Materials and Methods:This nested case-control study identified individuals with claims evidence of transfusion and TRALI occurrence from 1/1/07 through 12/31/09 using HealthCore’s Integrated Research Database (HIRDSM). Potential cases were ascertained by ICD-9-CM diagnosis code 518.7 and matched to controls who were transfused individuals without TRALI. Medical charts were evaluated and univariate conditional logistic regression was used to compare cases and controls by potential risk factors.Results:The study identified 346,972 transfused individuals with majority being females (59.8%), elderly (53.3%), and in the inpatient setting (85.3%). TRALI rates were higher in the inpatient setting, and lower for persons 80 years and over. TRALI rates by blood components ranged from 0.7 to 21.4 per 10,000 persons, with highest rate for platelets and plasma recipients (95% CI, 0.5-119.3). Of 10 confirmed cases, 2 persons died of TRALI. Confirmed cases were more likely to have direct or indirect lung injuries, cardiac surgeries, hematologic malignancies, other malignancies, and history of smoking.Conclusion:Our study highlights an important role that large administrative databases with medical charts can have in assessing TRALI occurrence and potential risk factors. Overall, this hypothesis-generating study suggests the need for further population-based investigations in the inpatient hospital setting to assess the effects of aging, health conditions, and other potential risk factors on TRALI occurrence. Source of Support This study was funded by the U.S. Food and Drug Administration, Center for Biologics Evaluation and Research Conflict of interest The authors declare that they have no conflicts of interest relevant to the manuscript submitted to Internet Journal of Hematology. Introduction Transfusion-Related Acute Lung Injury (TRALI) is a serious, life threatening complication of blood transfusion defined as acute lung injury occurring within the first six hours of transfusion and characterized by respiratory distress, hypoxemia, and dyspnea [1-5]. According to the FDA’s Summary Fatality reports following Blood Collection and Transfusion, during the six-year period, 2005-2010, nearly half (about 47%) of all transfusion-related fatalities reported to Center for Biologics Evaluation and Research (CBER) were due to TRALI [1].TRALI is thought to be caused by two major immune-mediated mechanisms, which lead to neutrophil activation, damage to endothelial cells and pulmonary edema that are responsible for the clinical presentation of TRALI. Leukocyte antibodies, biologically active substances including lipids and cytokines as well as underlying recipient conditions have been implicated in the major development mechanisms for TRALI [6-8]. One hypothesis is that leukocyte antibodies in donors, mainly multiparous women [2] who may have developed these due to exposure to fetal blood, can activate recipient’s neutrophils in pulmonary capillaries and cause pulmonary damage and capillary leak [6-8]. Another hypothesis for TRALI occurrence is the ‘two-hit mechanism’ with the first hit being underlying patients conditions (e.g., active infection, malignancy, surgery) at the time of transfusion that may prime and attract neutrophils to the endothelial surface of the lung followed by the second event, transfusion of the recipient-specific leukocyte antibodies or release of other biologically active substances (e.g. lipids, cytokines) leading to pulmonary damage and TRALI occurrence [6-8].The reported U.S. incidence of TRALI is based mostly on single and multi-center non-population-based studies and therefore, varies considerably across studies, with critically ill persons