TRALI due to granulocyte‐agglutinating human neutrophil antigen‐3a (5b) alloantibodies in donor plasma: a report of 2 fatalities

Davoren, Anne; Curtis, Brian R.; Shulman, Ira A.; Mohrbacher, Ann; Bux, Juergen; Kwiatkowska, Barbara; McFarland, Janice G.; Aster, Richard H.

doi:10.1046/j.1537-2995.2003.00374.x

Cited by 148 publications

(146 citation statements)

References 28 publications

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“…Because anti-HNA-3a antibodies cause the most severe TRALI, 3,18,19 we tested whether such antibodies could promote NET formation by human neutrophils. IgG were purified from 2 blood donors with anti-HNA-3a antibodies whose plasma caused a TRALI reaction in patients and control IgG were purified from a control donor's plasma.…”

Section: Antineutrophil Antibody Linked To Trali Promotes Net Formatimentioning

confidence: 99%

Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice

Thomas

Carbó

Curtis

et al. 2012

Blood

273

229

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Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related death. The biologic processes contributing to TRALI are poorly understood. All blood products can cause TRALI, and no specific treatment is available. A "2-event model" has been proposed as the trigger. The first event may include surgery, trauma, or infection; the second involves the transfusion of antileukocyte antibodies or bioactive lipids within the blood product. Together, these events induce neutrophil activation in the lungs, causing endothelial damage and capillary leakage. Neutrophils, in response to pathogens or under stress, can release their chromatin coated with granule contents, thus forming neutrophil extracellular traps (NETs). Although protective against infection, these NETs are injurious to tissue. Here we show that NET biomarkers are present in TRALI patients' blood and that NETs are produced in vitro by primed human neutrophils when challenged with anti-HNA-3a antibodies previously implicated in TRALI. NETs are found in alveoli of mice experiencing antibody-mediated TRALI. DNase 1 inhalation prevents their alveolar accumulation and improves arterial oxygen saturation even when administered 90 minutes after TRALI onset. We suggest that NETs form in the lungs during TRALI, contribute to the disease process, and thus could be targeted to prevent or treat TRALI. IntroductionTransfusion-related acute lung injury (TRALI) is a rare but serious complication of blood transfusion that occurs within 6 hours of transfusion and is characterized by hypoxemia, respiratory distress, and pulmonary infiltrates. 1 Over the years, prevention measures have resulted in a significant reduction in cases. However, TRALI is still the leading cause of transfusion-related mortality, and its prevalence is likely underestimated; one study suggested that more than 2% of cardiac surgery patients are affected. 2 Only supportive treatment is available to the patient, including mechanical ventilation and oxygen supplementation. Many of the severe cases have been linked to the presence of antineutrophil antibodies in the transfused product. 3,4 These antibodies bind to the recipients' neutrophils, activate them, and induce sequestration in the pulmonary capillaries, resulting in tissue injury. 5 Activated neutrophils can release neutrophil extracellular traps (NETs) 6 that are composed of DNA fibers decorated with histones and antimicrobial proteins 7 originally contained in the neutrophil granules. The structure and the composition of NETs allow them to trap and prevent the spread of pathogens and also to kill Gram-negative and Gram-positive bacteria, as well as yeast. 6 NET formation follows a specific pattern characterized by histone hypercitrullination, 8 chromatin decondensation, dissolution of the granular and nuclear membranes, and cytolysis. 9 Despite NETs' beneficial antimicrobial function, 6,10 their formation at the wrong time, in the wrong place, or in the wrong amount can have a negative effect on the host. NETs and their c...

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Section: Antineutrophil Antibody Linked To Trali Promotes Net Formatimentioning

confidence: 99%

Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice

Thomas

Carbó

Curtis

et al. 2012

Blood

273

229

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“…1,4,[11][12][13][14] Although a number of neutrophil-specific antibodies have been reported, the most common is directed at the 5b (HNA3a) antigen. 6,15 In a small percent of cases, the leukoagglutinating antibody appears to be from the recipient and is directed at the transfused neutrophils. [16][17][18] Most of the donors implicated in TRALI have been multiparous women who became alloimmunized during pregnancy.…”

Section: Immune (Antibody)-mediated Tralimentioning

confidence: 99%

Transfusion-Related Acute Lung Injury: An Update

Triulzi

2006

Hematology

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Transfusion-associated acute lung injury (TRALI) has emerged as a leading cause of transfusion-related morbidity and mortality. TRALI is characterized by acute non-cardiogenic pulmonary edema and respiratory compromise in the setting of transfusion. The study of TRALI has been hampered by inadequate case definitions and an incomplete understanding of the pathologic mechanisms. Recent consensus conferences took an important first step by providing a framework for case definition. Recent advances in the understanding of the pathogenesis of TRALI have also occurred. TRALI has been primarily attributed to donor leukocyte antibodies that are thought to interact with recipient neutrophils, resulting in activation and aggregation in pulmonary capillaries, release of local biologic response modifiers causing capillary leak, and lung injury. An alternate mechanism termed the "two hit" or "neutrophil priming" hypothesis postulates that a pathway to neutrophil activation and aggregation can occur without leukocyte antibodies. A first event such as sepsis or trauma can induce pulmonary endothelial activation, release of cytokines, and priming of neutrophils. A subsequent second event such as exposure to lipids, cytokines or antibodies in a blood component would then cause activation of adherent neutrophils and a release of bioreactive molecules leading to lung injury. There are limited clinical and animal studies to support the "two hit" model. These proposed mechanisms are not mutually exclusive in that donor leukocyte antibody can be pathogenic in both models and have implications for new strategies to prevent TRALI.Advances in blood safety have greatly reduced the risk of transfusion-associated infectious disease transmission. As a result, noninfectious serious hazards of transfusion have come to the forefront as increasingly important blood safety issues. Transfusion-associated acute lung injury (TRALI) has emerged as a leading cause of transfusion related morbidity and mortality.1 This report will summarize recent consensus conferences that have provided practical clinical definitions of TRALI to aid the clinician in diagnosis and to facilitate its study. Recent advances in understanding of the pathogenesis of TRALI will be presented with a potential unifying hypothesis. DefinitionA lack of a standardized definition of TRALI has hindered accurate clinical diagnosis, epidemiology, and research investigation. A recent NHLBI working group convened to identify research needs addressed this critical issue by providing the following definition: "new acute lung injury (ALI) occurring during or within 6 hours after a transfusion, with a clear temporal relationship to transfusion, in patients without or with risk factors for ALI other than transfusion."2 Limitations to the proposed NHLBI working group definition are the exclusion of patients with preexisting ALI, excluding cases with onset more than 6 hours after transfusion, lack of laboratory diagnostic criteria, and a required severity of hypoxia that would miss cases of mil...

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“…Blood components with a high plasma fraction (typically fresh-frozen plasma, apheresis platelets and whole blood) should not be prepared from blood donated by donors with leucocyte antibodies. In the case of HNA-3a antibodies, deferral of the donor from blood donation should be considered, as these antibodies have been frequently implicated in fatal TRALI reactions [12,16] and one fatal TRALI reaction occurred even after transfusion of red blood cells [12]. Donors with negative test results for leucocyte antibodies should be retested only after re-exposure to leucocyte antigens.…”

Section: Leucocyte Antibody Screening In Blood Donorsmentioning

confidence: 99%

Recommendations of the ISBT Working Party on Granulocyte Immunobiology for leucocyte antibody screening in the investigation and prevention of antibody‐mediated transfusion‐related acute lung injury

Bierling¹,

Bux

Curtis

et al. 2009

Vox Sanguinis

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TRALI due to granulocyte‐agglutinating human neutrophil antigen‐3a (5b) alloantibodies in donor plasma: a report of 2 fatalities

Cited by 148 publications

References 28 publications

Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice

Extracellular DNA traps are associated with the pathogenesis of TRALI in humans and mice

Transfusion-Related Acute Lung Injury: An Update

Recommendations of the ISBT Working Party on Granulocyte Immunobiology for leucocyte antibody screening in the investigation and prevention of antibody‐mediated transfusion‐related acute lung injury

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