Complement Activation in Transfusion Related Acute Lung Injury (TRALI).
Authors: Ambruso Daniel R. , Silliman Christopher C. , Kelher Marguerite , Thurman Gail , Giclas Patsy 
Published: April 2020

Abstract
Background: TRALI is defined as acute lung injury occurring within six hours of a transfusion of blood products. Two major etiologies have been identified and include leukocyte antibodies activating complement. We report two patients with TRALI reactions who had documented activation of complement.
Case Studies. Case 1: A 59 year old male with Factor XI deficiency and hematochezia was given 3 units of fresh frozen plasma (FFP). During infusion of the third unit, the patient developed dyspnea and cyanosis requiring ventilator support. A chest x-ray showed new diffuse infiltrates; CVP and an echocardiogram were normal. The symptoms resolved in 3 days.
Case 2: An 87 year old female required surgical repair of a hip fracture. Four units were infused and with the last one, the patient developed chills, fever and tachypnea. On 6 l/min of O2, she had a saturation of 58%. Chest x-ray showed bilateral infiltrates; the echocardiogram was normal. The patient sustained a cardiac arrest and could not be resuscitated.
Methods: Samples from donors or FFP units were screened for HLA and granulocyte antibodies. Priming of the fMLP stimulated neutrophil oxidase activity was performed by standard assay. Plasma from products implicated in TRALI and plasma samples from patients before and during the TRALI reaction were assayed for priming of the fMLP stimulated respiratory burst in neutrophils; C3a, C4a, C5a, C5–9, and Bb were measured by standard techniques.
Results: In Case 1, HLA Class II, IgG reactivity by flow cytometry was documented with plasma from the implicated donor and recipient cells. Priming of neutrophils was detected in the implicated unit as well as the recipient’s plasma during the reaction in comparison to pre-transfusion specimen. Complement activation products were increased in samples during the reaction and the product being infused at the onset of TRALI. In the second case, HLA Class II antibodies with a specificity which would interact with the recipient’s antigens were detected in the product related to the TRALI reaction. Priming activity of the neutrophil oxidase was documented in the infused product and in post vs. pre reaction patient samples. Complement activation products were increased in the implicated FFP unit and C5a was increased in the patient’s post samples. Additional cases are being assessed for complement activation.
Conclusions: In these cases of TRALI, the implicated products exhibited priming activity as well as antibodies which reacted with recipient antigens by flow crossmatch or by documentation of the cognate antigen. Complement activation was documented in patient samples during the reaction as opposed to those collected before the transfusion. Most importantly, complement was activated in the product transfused during the onset of TRALI symptoms. Thus, complement activation in the product is the most likely cause of the TRALI reaction. Infusion of products containing activated complement components may provide an alternative mechanism for TRALI reactions.