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TRALI : Transfusion Related Lung Injury

Created: 22/5/2007
Updated: 22/5/2007
 

TRALI: Transfusion Related Acute Lung Injury

Dr John Griffiths DICM MRCP FRCA MA
CriticalCareUK Editor

Focus on TRALI

TRALI is a complication of transfusion particularly relevant to critical care. It is a severe acute reaction characterised by respiratory distress, hypoxia and pulmonary infiltrates soon after transfusion with no other apparent cause (Figure 1). The true incidence of TRALI is unknown. The first case of fatal pulmonary oedema following transfusion was reported in 1951. Since then a number of case reports and several case series have been reported in the literature across the medical specialities. The term ‘TRALI’ was coined by Popovosky in 1983. The reported incidence varies from 0.001% to 0.16% per patient transfused. Milder forms of the reaction that have occurred in anaesthetised or sedated patients in theatre or ICU are probably misdiagnosed and therefore not reported.




Figure 1

Top : Anteroposterior chest radiograph from a 35-year-old woman with who received 2 U of fresh-frozen plasma and acquired TRALI. The patient has an endotracheal tube in place and has diffuse bilateral alveolar infiltrates and a normal cardiac silhouette. This is a characteristic radiograph appearance for severe ALI in TRALI.

Bottom : Anteroposterior chest radiograph from the same patient 24 h later showing significant resolution of the alveolar infiltrates, as seems to occur in 80% of patients with TRALI.

Focus on implicated blood products and pathogenesis

TRALI has been reported to occur after the transfusion of all types of blood components, but is particularly likely to occur with those with a large volume of plasma such as fresh frozen plasma (FFP). However, it has been reported after transfusion of plasma-reduced red cells containing approximately 70 mls plasma, cryoprecipitate or as little as 50 mls of whole blood. To date commercially derived plasma products, including human albumin solution and plasma protein fraction, which are derived from pooled donors, have not been known to trigger a reaction.

A precise understanding of the mechanism of TRALI is at present unknown. In many cases of TRALI, preformed leucocyte antibodies have been found in the plasma of the donors, and these are thought to cause activation of complement C5a, interleukin 1b and intercellular adhesion molecule 1, pulmonary leucostasis and leucocyte activation. Protease, acidic lipids and oxygen radicals released from the leucocytes result in capillary leak and pulmonary damage. However, in about 5-15% of cases, no antibody is identified in either the donor or recipient. To account for this a “two-hit” hypothesis has been proposed to explain the pathogenesis of TRALI. The first hit is a serious illness in the patient. The second hit is the transfusion of a blood product containing:

  • leucocyte antibody directed against the patient’s white blood cells
  • biologically active lipids
  • leucocyte antibody and biologically active lipids

Biologically active lipids are lipids that develop in stored blood components that are capable of activating white cell neutrophil oxidase in the recipient. Activation of this enzyme results in degranulation and release of inflammatory mediators that can also damage the pulmonary vascular endothelium.


Focus on diagnosis and treatment of TRALI

There is no diagnostic or pathognomonic sign to confirm TRALI. TRALI is clinically indistinguishable from acute respiratory distress syndrome (ARDS), and the occurrence of ARDS with a possible association with transfusion provides grounds to consider TRALI as the cause. TRALI can be seen in a few minutes to 6 hours after transfusion (Table 1). Unlike ARDS, TRALI is self-limiting, and there is usually clinical improvement within 48-96 hours provided prompt respiratory support is provided (Figure 2). In 30% of the cases mask oxygen is sufficient and in 70% some form of ventilatory support is necessary. Treating TRALI like cardiogenic pulmonary oedema or volume overload may lead to adverse outcomes such as hypotension. Levy et al also report a case of confirmed TRALI in which diuretics were empirically administered. The patient became hypotensive, and a pulmonary catheter was inserted. After receiving 1,000 ml of crystalloid, the initial PCWP was 10 mmHg and a cardiac index 3.3L/min/m. Diuretics were discontinued, and further IV fluids were prescribed. The patient was eventually extubated and survived.


Figure 2. Flow chart for the diagnosis of possible TRALI

Adapted from Gopal 2004




For mild TRALI cases, supplemental oxygen and supportive care may be sufficient. For the most severe cases, IV fluids, mechanical or non-invasive ventilation and invasive cardiovascular monitoring may be required. A low tidal volume strategy with low plateau pressures should be employed when ventilating TRALI patients, just like other causes of ALI/ARDS. Mortality rate is 5%. Several case reports have described the treatment of TRALI with glucocorticoids. Unfortunately, there has never been a randomised, controlled trial of glucocorticoid therapy in TRALI, and thus, presently this treatment has no demonstrated therapeutic role.

No specific laboratory tests are available for TRALI and initial diagnosis depends on a high degree of clinical suspicion. In patients with bilateral pulmonary infiltrates and severe hypoxia clinical classification of pulmonary oedema as cardiogenic or non-cardiogenic is difficult. In one study clinical diagnosis of cardiogenic and non-cardiogenic pulmonary oedema was correct in only 62% and 85% respectively compared with the classification determined from pulmonary artery catheterization. The PA catheter data changed the diagnosis in over 30% of patients, most often changing the diagnosis from cardiogenic to non-cardiogenic pulmonary oedema. The subsequent finding of leucocyte antibodies in a donor unit, matching a recipient leucocyte antigen, may be taken as strongly supportive evidence in a suspected case.

Focus on The Serious Hazards of Transfusion and Better Blood Transfusion.

A case of suspected TRALI should be reported to The Serious Hazards of Transfusion (SHOT) scheme. SHOT was established in 1996 to collect reports of major adverse events associated with the transfusion of blood components in the UK. SHOT receives about 15 reports each year of TRALI, for which red cells have been implicated as the causative unit in about one third, and FFP and platelets in just under half. In their 2000-2001 annual review, SHOT reported receiving 70 cases of TRALI resulting in 18 deaths over a 5-year period. This ranks TRALI as the second commonest cause of transfusion-related major morbidity and mortality after ABO incompatibility in the UK.

Better blood transfusion is an initiative led by the Chief Medical Officers to improve the safety and effectiveness of transfusion practice. Its output has been two Health Service Circulars (HSC’s) setting out a number of recommended actions to hospital Chief Executives. An audit of the implementation of the HSC 1998/224 Better Blood Transfusion showed that most hospitals had established Hospital Transfusion Committees, were participating in the SHOT scheme, and had protocols for the administration of blood. The Chief Medical Officer’s National Blood Transfusion Committee (NBTC) was established in England in 2001. It oversees the national better blood transfusion initiative, and acts as the Steering group for an initiative for national comparative audit of clinical transfusion practice. The NTBC reviews the findings of the SHOT scheme, and supports its recommendations. Specific measures that could be considered in critical care practice include better compliance with evidence based triggers for transfusion, greater use of near patient testing to determine the need for transfusion, and minimising blood loss due to sampling. Recent evidence suggests that transfusion triggers in the critically ill may be safely lowered without increasing significant morbidity. The production of FFP from only male donors, and reducing the volume of plasma in platelet concentrates are under consideration as measures to reduce the risk of TRALI.


Learning points

  • Anaesthetists and Intensivists who regularly see and mange patients with acute respiratory failure may falsely diagnose TRALI as acute pulmonary oedema or ALI/ARDS
  • The diagnosis of TRALI should be considered in any patient meeting the criteria for ALI/ARDS who has recently undergone a recent blood product transfusion
  • TRALI is currently ranked as the second most common cause of transfusion-related death in the UK
  • A high index of clinical suspicion is required as TRALI is a diagnosis of exclusion
  • It is important to report all suspected or confirmed transfusion related adverse events in line with the recommendations from the SHOT and Better Blood Transfusion initiatives.


Table 1. ARDS versus TRALI


ARDS

TRALI

Onset

Insidious

May be acute

Acute

Always within 1-6 hours of transfusion

Clinical presentation

Hypoxic respiratory failure;

High PaO2/ Fi02 ratio

Reduced lung compliance

Diffuse infiltrates on CXR

If severe may mimic ARDS

Management

Maintain adequate oxygenation but prevent iatrogenic lung injury: protective ventilatory strategy with low tidal volume ventilation and permissive hypercapnoea . Consider prone ventilation

As for ARDS

Prognosis

Prolonged ventilation associated with

multi-organ failure.

Resolution with fibrosis may cause permanent impairment of gas exchange

Improvement occurs in 48-96 hours with correction of

PaO2/ Fi02 ratio

Mortality

30-60%

5%

 

Key References


Popovsky MA, Moore SB.
Diagnostic and pathogenetic considerations in transfusion-related acute lung injury.
Transfusion. 1985 25(6):573-7.

Barrett NA, Kam PC.
Transfusion-related acute lung injury: a literature review.
Anaesthesia. 2006 61(8):777-85.

Urbaniak SJ.
Transfusion related acute lung injury (TRALI).
Br J Haematol. 2005 130(3):463-4.

Florell SR, Velasco SE, Fine PG.
Perioperative Recognition, Management, and Pathologic Diagnosis of Transfusion-related Acute Lung Injury.
Anesthesiology. 1994 81:508-510


ArticleDate:20070522
SiteSection: Article
 
   
    
                                            
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