Multiple recipient related risk factors are noted in the literature. Most of these studies are retrospective and small. However, it is evident from clinical data that the critically ill population is at the highest risk for the development of TRALI [13]. In one multicenter, prospective trial, history of liver transplant, chronic alcohol use, active tobacco use, shock, increased IL-8 levels in serum, increased peak airway pressures of >30 cm H₂O on the ventilator, and an overall positive fluid balance were all significant risk factors for TRALI [14]. Multiple studies reveal sepsis and shock as major risk factors. Not only being critically ill, but also being on mechanical ventilation at the time of transfusion may increase risk independently. A prospective cohort study showed 33 % of patients on mechanical ventilation at the time of transfusion developed acute lung injury [15]. Multiple other studies have also shown recipient risk factors such as: major surgery within 72 h of blood transfusion, hematologic malignancy, higher APACHE II scores, and active liver disease [16]. The risk for development of TRALI also increases with the number of transfusions, as seen commonly in the trauma population where patients are receiving massive transfusions [13]. Not only critically ill patients, but cardiac and orthopedic surgery patients are also at higher risk for TRALI development [17]. The time on cardiac bypass appears to be correlated as well, with longer bypass times leading to higher risk of TRALI development [18]. Despite the multitude of recipient risk factors reported, most of which are seen in the critically ill population, TRALI is also reported in otherwise healthy individuals at the time of transfusion [19]. The development of TRALI in this healthy patient population supports the realization that the risk of TRALI is not dependent on the recipient alone.

All forms of blood products have been reported to cause TRALI, including: whole blood, packed red blood cells, apheresis platelets, fresh frozen plasma, cryoglobulin, intravenous immunoglobulin, granulocytes, and allogeneic stem cells [12]. However, blood products with higher plasma volume are at the greatest risk, specifically fresh frozen plasma, apheresis platelets, and whole blood. In the FDA reported cases of death due to TRALI, fresh frozen plasma was the most implicated [7]. In one retrospective cohort study from 2007, fresh frozen plasma and platelet transfusions led to a higher incidence of TRALI versus red blood cell transfusion in the ICU population [20]. It remains unknown the exact amount of plasma which must be transfused in order for TRALI to develop. Reports of as little as 10–20 ml of plasma transfused before TRALI development are in the literature; however, plasma volumes greater than 50–60 ml are thought to be the threshold which puts patients at a higher risk [12].

Another important risk factor is the gender of the donor, and preventive strategies in the past 15 years have focused on gender related donor deferral . Female, multiparous donors have allo-immunization from pregnancy. Blood from this particular group of donors has a much higher risk of TRALI development in the recipient secondary to the anti-HLA and anti-HNA antibodies, which bind to recipient antigens and lead to immune-mediated TRALI. The prevalence of antibodies in this population increases with parity. A 26 % approximate frequency of anti-HLA antibodies exist if a female has had more than three pregnancies [21]. Another potential risk factor where studies have shown controversial data is blood product storage time. Experts in the field hypothesize that longer storage times of red blood cells may lead to a higher incidence of TRALI. Experimental models in preclinical trials show a positive correlation between longer blood storage times and TRALI; however, there remains no overt clinical evidence to support the finding [22]. Studies done in the preemie population showed no difference in the incidence of TRALI based on blood storage time. An ongoing study in the adult intensive care unit population is underway that hopefully will help to clarify the importance of blood storage time as a potential risk factor [23].

As stated before, all blood products have been implicated in TRALI development, and the incidence of TRALI varies based on blood product components. Products with higher plasma volume have higher incidence of TRALI. Reports reveal incidences at approximately 1/432 whole blood products vs. 1/7900 fresh frozen plasma vs. 1/557,000 red blood cells [12, 22]. However, the incidence of TRALI in plasma products has decreased in the past decade secondary to risk mitigation strategies, leaving the incidence of red blood cell transfusions at a higher rate in the more recent years [26].

TRALI can present with a large variation in disease severity. By NHLBI and CCC definition 100 % of patients with TRALI have hypoxemic respiratory failure and bilateral pulmonary infiltrates on chest X-ray. Clinically, the most common complaint of patients is dyspnea. However, a large number of patients are critically ill and on mechanical ventilation at the time of blood transfusions leading symptoms to be unhelpful. Despite patients being unable to report symptoms, clinical signs of respiratory distress and failure are present, typically within one to 2 h of a blood transfusion in the majority of patients. Predominately, patients are tachypneic, and in approximately one-third of patients, fever and/or hypotension may develop. Rarely patients may develop new onset hypertension. Most notably in the vital signs, SpO2 should be decreased compared to before the transfusion. Patients on mechanical ventilation may experience a change in pulmonary compliance with an increase in peak and plateau pressures. Pink, frothy secretions from the mouth or endotracheal tube occur in roughly half of patients who develop TRALI. Physical exam should help rule out other etiologies of respiratory distress and should be thorough including a complete lung, heart, and skin exam. Lung auscultation reveals bilateral crackles. Exam findings suggestive of cardiac failure should not be present, such as jugular venous distention and an S3 on cardiac auscultation. It is important to keep in mind that very mild cases of TRALI do exist, which may not fall into the NHLBI and CCC definitions. Mild cases may go unrecognized or present with a similar presentation to the underlying disease process, albeit in a less severe form .

Practitioners should have a high index of suspicion for TRALI when administering blood products, especially in the critically ill population. Diagnosis can be difficult as there is no gold standard diagnostic test for TRALI. Any person who develops even the least amount of dyspnea or respiratory distress in temporal association with a blood product transfusion should have further clinical and diagnostic evaluation for TRALI. Patients who meet the 2004 NHLBI and CCC definition (Table 11.1) including, new hypoxemic respiratory failure with a PaO₂/FiO₂ ratio <300 and bilateral pulmonary infiltrates within a 6 h time frame from blood product transfusion, deserve further workup to confirm the diagnosis. One of the goals of the diagnostic workup should be to rule out other possible etiologies for the new development of ARDS, which would then classify the patient as possible TRALI. No diagnostic lab tests are available that confirm the diagnosis of TRALI. An arterial blood gas can be helpful to quantify the degree of hypoxemia. The most common laboratory finding is acute and transient leukopenia, which is thought to be secondary to neutrophil sequestration into the pulmonary vasculature and can be seen in 5–35 % of patients [27]. Thrombocytopenia has also been reported in TRALI. Other laboratory tests, although not diagnostic may also be helpful. In other etiologies of ARDS such as sepsis, a leukocytosis may be present. An elevated brain naturitic peptide can be seen in transfusion associated circulatory overload (TACO) and should not be elevated in TRALI alone. As stated before, a chest X-ray revealing bilateral pulmonary infiltrates is a ubiquitous finding in TRALI, and should be performed for any patient with suspicion of the diagnosis. Historically the pulmonary infiltrates in TRALI were described as “white out lungs.” This may be the scenario in extreme cases; however, both alveolar and interstitial infiltrates have been described in a spectrum from bilateral and patchy to diffuse territories of the lung fields. Despite the findings being nonspecific, the presence of bilateral infiltrates should reach 100 % in this patient population. The chest X-ray is also helpful to eliminate other etiologies of acute respiratory failure, such as pneumothorax .

In distinguishing TRALI from other disease states it is important to consider other causes of ALI/ARDS, as well as other transfusion reactions.