Abstract

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by the onset of acute respiratory distress within six hours following blood transfusion. In most cases, donor antibodies are suggested to be involved, however, the pathogenesis is poorly understood. A two-hit model is generally assumed to underlie TRALI pathogenesis where the first hit consists of a patient predisposing factor such as inflammation and the second hit is due to donor antibodies present in the transfused blood. We recently demonstrated that the acute phase protein C-reactive protein (CRP) could enhance murine anti-major histocompatibility complex (MHC) class I-mediated TRALI. Whether CRP is increased in human TRALI patients which would support its role as a risk factor for human TRALI, is currently unknown. For that purpose, we measured CRP levels in the plasma of human TRALI patients and found CRP levels to be significantly elevated compared to transfused control patients. These data support the notion that CRP may be a novel first hit risk factor in human TRALI and that modulation of CRP levels could be an effective therapeutic strategy for this serious adverse event of transfusion.

Highlights

  • Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and is characterized by acute respiratory distress within six hours following blood transfusions [1, 2]

  • TRALI samples were collected for C-reactive protein (CRP) analysis within 24-48 hours upon transfusion and for the control group blood samples were collected within 24 hours following transfusion

  • This first hit of inflammation signified by the increased levels of CRP together with the second hit conveyed by the specific antibodies present in the transfused blood product may be a key factor enabling TRALI reactions

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Summary

Introduction

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality and is characterized by acute respiratory distress within six hours following blood transfusions [1, 2]. Apart from supportive measures such as oxygen and ventilation, no therapy is currently available for TRALI. A two-hit model has been proposed for antibody-mediated TRALI where the first hit comprises patient predisposing factors such as inflammation and the second hit is due to donor antibodies in the transfused blood [1]. Other first-hit risk factors for TRALI include chronic alcohol abuse, liver surgery, smoking, shock, higher peak airway pressure while undergoing mechanical ventilation, and positive intravascular fluid balance [5]. Systemic inflammation characterized by elevated recipient interleukin (IL)-6 [6] and IL-8 levels [5,6,7] appears to be a major risk factor for TRALI induction

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