Transfusion-associated lung injury: Put it on the watch list

Advances in veterinary transfusion medicine and development of canine and feline blood donor programs have increased the availability of blood products to the veterinary market. An increasing number of small animal practices are routinely using commercial blood banks and providing their patients with valuable transfusion medicine services. It is important when administering these products to understand and recognize the most-common signs of a reaction. Side effects such as vomiting, fever and urticaria have been well described in veterinary patients.

In human medicine, many of the infectious transfusion complications (HIV, hepatitis, etc.) have been largely eliminated in developed countries through adequate screening and blood-banking practices. A syndrome of acute respiratory distress associated with administration of blood transfusions has been described in human medicine since the 1980s. As blood-banking practices have improved, this syndrome of transfusion-associated lung injury (TRALI) has emerged as the leading cause of transfusion-related death in human medicine. The syndrome has been widely reported in human medicine and is now a very active area of research. While documented cases of TRALI have not been reported in the veterinary field, some anecdotal reports do exist. As we learn more about the syndrome and its pathogenesis, it seems likely that this is a condition that may affect our veterinary patients that should be considered in any patient receiving blood transfusions.

Many patients receiving blood transfusions will have other conditions predisposing them to acute lung injury and acute respiratory distress syndrome, so all factors must be considered when treating these patients.

Areas to watch

What is transfusion-associated lung injury?

TRALI is characterized by an acute onset of non-cardiogenic pulmonary edema temporally associated with a blood transfusion. Assigning a standard definition to TRALI has been difficult due to the complex disease processes present in the critically ill patient populations receiving transfusions. Many patients receiving blood transfusions will have other conditions predisposing them to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Most consensus groups agree that to define a patient with TRALI, there should be no evidence for the presence of acute lung injury due to other risk factors. One group (Working Party on Definitions of Adverse Transfusion Events) has suggested the following criteria for making a clinical diagnosis of TRALI:

1) occurrence of acute respiratory distress during or within six hours of transfusion;

2) absence of signs of circulatory overload;

3) radiographic evidence of bilateral alveolar pulmonary infiltrates. Other groups restrict this definition to all-of-the above plus: the presence of hypoxemia (PaO2/FiO2 ratio ≤300 or pulse ox<90% on room air); no pre-existing acute lung injury or presence of ALI risk factors. Certainly patients with risk factors for ALI may also develop TRALI, but this patient population has been specifically excluded in most TRALI consensus statements to better describe this particular form of lung injury. Future studies may better characterize the population of patients with ALI risk factors that develop TRALI.

What causes TRALI?

Transfusion-associated lung injury has been reported in humans administered plasma-containing components: platelet concentrate, fresh frozen plasma, cryoprecipitate as well as packed red blood cells. There are two predominant theories why these components may result in adverse patient reactions. Evidence for the "antibody hypothesis" suggests that HLA class I, HLA class II and neutrophil-specific antibodies in the plasma of blood donors and recipients contribute to the pathogenesis of TRALI. It has been postulated that the interaction of these antibodies with neutrophils, monocytes and/or endothelial cells leads to direct or complement-mediated activation of these cells resulting in endothelial damage, capillary leak and the subsequent development of TRALI.

The second theory is referred to as the "two-hit or two-event phenomenon." This theory suggests that TRALI results from at least two clinical insults. The first insult is related to the clinical condition of the patient that results in activation of the pulmonary epithelium, sequestration of neutrophils within the pulmonary vasculature. The second event is the introduction of specific antibodies in transfused blood that is directed against the antigens on these primed neutrophils within the pulmonary vasculature. This abnormal antigen-antibody response results in neutrophil-mediated endothelial damage, capillary leak and the development of TRALI. There are merits to both theories and ongoing research is focused on the elucidation of pathways and mediators responsible for the development of TRALI.

Ongoing research is focused on the elucidation of pathways and mediators responsible for the development of transfusion-associated lung injury.

How is TRALI treated?

The treatment for TRALI is similar to that for ALI and ARDS. Hypoxemia should be managed with the administration of supplemental oxygen to maintain SpO2 > 92% or a PaO2 >85 mmHg. Several methods for oxygen administration have been described (intranasal, intratracheal, oxygen cage). If these methods fail to maintain adequate arterial oxygenation, positive pressure ventilation with positive end-expiratory pressure (PEEP) are indicated. Corticosteroid therapy has not been shown to be beneficial in the treatment of ALI, ARDS or TRALI. Antibiotic therapy is generally not indicated as infection is not part of the pathogenesis of the disorder. Secondary bacterial infections may develop in patients with TRALI and should be treated with antimicrobial therapy based on culture and sensitivity results from bronchoalveolar lavage samples or a transtracheal/endotracheal wash.

Patients with TRALI may be hypotensive, and treatment with diuretics may exacerbate hypovolemia in the absence of volume overload.

Other differentials?

One of the more common differentials for TRALI is circulatory overload associated with the administration of a blood transfusion (transfusion-associated circulatory overload or TACO). This complication of transfusion may be difficult to differentiate from TRALI, although presence of underlying heart disease, overhydration, and lack of other predisposing factors for ALI may be supportive. Invasive hemodynamic monitoring may provide additional evidence for transfusion-associated circulatory overload, such as a pulmonary wedge pressure >18 mmHg or a CVP exceeding 8 cm/H20. Non-invasive volume assessment of pulmonary vasculature on a standard lateral thoracic radiograph may also provide supportive evidence of volume overload.

Echocardiography may identify left atrial volume overload or diminished cardiac function that would support a diagnosis of TACO. People with circulatory overload tend to have a lower pulmonary fluid protein than patients with TRALI, although this may vary depending on time of fluid collection and may be unreliable if pulmonary fluid collection is delayed.

Other differentials to consider in any patient developing respiratory distress while receiving a blood transfusion include: anaphylaxis with bronchoconstriction, ALI/ARDS from comorbid conditions, pulmonary thromboembolism, acute hemolytic reaction and bacterial sepsis associated with contamination of blood products.

What is the prognosis?

Unlike ALI and ARDS, the prognosis with TRALI tends to be good (40-50 percent mortality rate for ALI/ARDS compared with less than 10 percent mortality rate for TRALI). Most cases of TRALI also have a shorter clinical course (less than 72 hours) than ALI/ARDS.

Final thoughts

TRALI is an acute lung injury temporally associated with transfusion of plasma-containing blood products. Most authorities agree that the syndrome generally develops within six hours of transfusion and tends to carry a better prognosis than ALI/ARDS syndrome. It is important to make the distinction between transfusion-associated lung injury and transfusion-associated circulatory overload, as treatments for each will vary.

Although this phenomenon has not been reported in veterinary patients, it should be on the mind of every clinician that administers blood products to their veterinary patients. It should be understood that with aggressive treatment that may include oxygen therapy and mechanical ventilation, this condition tends to carry a good prognosis for a full recovery.

Dr. Woosley, Dipl. ACVECC (Emergency & Critical Care) completed a small animal internship at The Animal Medical Center before pursuing a dual residency there in Emergency/Critical Care and Small Animal Internal Medicine. She has been on staff at Red Bank Veterinary Hospital in Tinton Falls, NJ since 2006.