Transfusion related acute lung injury

# Overview
Transfusion related acute lung injury (TRALI) is a serious blood transfusion complication characterized by the acute onset of non-cardiogenic pulmonary edema following transfusion of blood products.

# Definition
TRALI is defined as an acute lung injury that is temporally related to a blood transfusion; specifically, it must occur within the first six hours following a transfusion.

# Differential diagnosis
- Acute respiratory distress syndrome

# Etiology/Risks
The etiology of TRALI is currently not fully understood is thought to be immune mediated. Antibodies directed toward Human Leukocyte Antigens (HLA) or Human Neutrophil Antigens (HNA) have been implicated.   Multiparous women (women that have had more than one child) develop these antibodies through exposure to fetal blood; transfusion of blood components obtained from these donors is thought to carry a higher risk of inducing immune-mediated TRALI.  Previous transfusion or transplantation can also lead to donor sensitization.  Additional recipient risk factors include high IL-8 levels, liver surgery, chronic alcohol abuse, shock, current tobacco use, positive fluid balance and a high peak airway pressure while being mechanically ventilated  The recipient, to be at risk of TRALI via this mechanism, must express the specific HLA or neutrophil receptors to which the implicated donor has formed antibodies.  Some authors suggest a two-hit hypothesis wherein pre-existing pulmonary pathology (ie, the first-hit) leads to localization of neutrophils to the pulmonary microvasculature.  The second hit occurs when the aforementioned antibodies are transfused and attach to and activate neutrophils, leading to release of cytokines and vasoactive substances that induce non-cardiac pulmonary edema.
A non-immune mechanism has been studied and proposed by Silliman, involving the accumulation of bioactive lipids in stored blood components (red cells, platelets, plasma) that possess neutrophil priming capabilities.  This mechanism is thought to involve ~15% of TRALI cases where neither donor nor recipient antibodies are found.
TRALI is typically associated with plasma-rich products such as FFP, but can also occur in recipients of packed RBCs due to the residual plasma present in the unit.  Antiplatelet antibodies may also cause a delayed TRALI.

# Differential Diagnosis
One of the main diagnostic dilemmas of TRALI is to differentiate it from clinically similar entities.  The foremost of these is Transfusion-associated circulatory overload,(TACO).  The incidence of TACO varies between <1% to 11%; the mortality between 3.6% to 20%.  Clinically, these patients manifest tachypnea, cyanosis, dyspnea, hypertension, and tachycardia.  They show evidence of overload such as jugular venous distention, an elevated pulmonary artery occlusive pressure, and an elevated BNP (brain natriuretic peptide).  Other maladies that resemble TRALI  include anaphylactic transfusion reactions where patients show tachypnea, cyanosis and wheezing.  To differentiate it from TRALI one must see other manifestations such as hypotension and skin changes (urticaria, erythema, and facial/trunk edema).  The pulmonary symptoms come from broncholaryngeal edema instead of the interstitial pulmonary regions.  Sepsis, from bacterially-contaminated blood products, can also lead to respiratory distress along with concurrent hypotension and fever.  Hemolytic transfusion reactions, too, manifest with respiratory distress.

# Mortality & morbidity
The immune mediated form of TRALI occurs approximately once every 5000 transfusions and has a mortality of 6-9%.  TRALI is one of the leading causes of transfusion-related fatalities in the US.

# Treatment
Treatment for TRALI is primarily supportive measures.  Many patients with TRALI need mechanical ventilation.  TRALI is associated with microvascular damage and not fluid overload, so diuretics are not recommended.