Transfusion Related Lung Injury (TRALI)

Submitted by Christopher Corkery, NZ Blood Service Nurse Specialist, Waikato. Orginally printed in March 2007 IVNNZ Inc. Newsletter

TRALI is one of the commonest major complications of blood transfusion in New Zealand and is well known within the circles of transfusion medicine, haematology and intensive care units. Unfortunately outside of these areas, TRALI is less recognised by clinical staff.

Definition

TRALI is an acute lung injury ocurring within six hours of transfusion, not due to any other cause. It is one of the causes of non-cardiogenic pulmonary oedema.

Symptoms

Symptoms include extreme respiratory distress due to bilateral pulmonary oedema, sudden desaturation, tachycardia, frothy sputum, hypertension followed by hypotension, occasionally mild fever. The pulmonary oedema is of non-cardiogenic origin. Chest x-rays will show bilateral alveolar infiltration giving a classic "white-out" picture.1 Diagnosis is a process of exclusion and is clinically indistinguishable from acute respiratory distress syndrome (ARDS).6 TRALI occurs within six hours of a transfusion, most within two hours, and usually resolves within 72 to 96 hours in 90% of cases if patients are supported during the acute phase. Mortality is estimated at 10%.2

There is no specific patient demographic which differentiates patients who have had TRALI, however there are risk groups. These include patients with haematological malignancies, multiple transfusion recipients, trauma, cardiac disease/surgery and sepsis.1 This may be due to the fact that these patients receive a large proportion of fresh components as well as being sicker. Components implicated are platelets, plasma, red cells, cryoprecipitate as well as, rarely, intravenous immunoglobulin. In one report covering a five year period Fresh Frozen Plasma (FFP) was implicated twice as often as any other component despite less FFP being administered than the other components.

Etiology

Two hypotheses attempt to explain how TRALI develops. The first is the immune mediated response where donor anti Human Leucocyte (HLA) antibodies, present in the blood component, attach themselves to circulating neutrophils and precipitate their activation. This in turn causes the release of cytokines which damage pulmonary epithelium causing leakage and eventually pulmonary oedema. Support for this theory comes from the fact that 89% of donors implicated in TRALI have such antibodies. Also many of the implicated donors are multiparous women or are individuals who have had a previous transfusion. Both groups have a greater chance of developing antibodies, having been exposed to foreign leucocytes (fetal or blood donor).3

The second hypothesis involves a "two hit neutrophil priming" sequence. The first "hit" is a major insult to the body which may be a haematology malignancy, surgery, sepsis or trauma which "primes" neutrophils but doesn't activate them. The second hit involves the transfusion of stored blood containing biologically active lipids which are thought to activate the "primed" neutrophils releasing cytokines and enzymes thought to cause pulmonary leakage. Lipids increase during storage of red cells. Support for this theory comes from the number of TRALI incidents where red cells were transfused that were older than 14 days as well as the absence of detectable antibodies in a number of TRALI cases.3 This theory does not explain all cases as FFP does not have increased amounts of biologically active lipids.

Case Study

15 year male diagnosed with a haematoloy disorder. Patient had received first course of chemotherapy which included L-Asparaginase. This is known to effect liver function and the production of coagulation enzymes therefore coagulation studies are done on a daily basis following administration of L-Asparaginse. The patient was neutropenic and receiving IV Tobramycin and Tazoscin. The patient was also on an alternate day regime of Ambisome as prophylaxis for fungal infections. On the morning of the transfusion the patient's coagulation results showed an Anti Thrombin III level of 68% and it was decided to transfuse 2 units of FFP. The patient's observations were stable prior to the transfusion (BP=110/70, Temperature=36, Pulse 80, pO2=98% at room air, Respiration rate=20). The first unit of FFP was commenced and at 15 minutes observations were recorded with no obvious change. Approximately 30 minutes after starting the transfusion the patient complained of a dry cough, chest pain and chest tightness. The nurse stopped the transfusion and called for assistance. The patient's saturations decreased to 85% on air with respiration rate increasing to 30/min. Blood pressure dropped to 90/40 and heart rate increased to 130/min. Despite receiving oxygen which was increased to 10L the patient continued to complain of difficulty in breathing and was now producing copious amounts of frothy yellowish sputum. Chest x-ray showed bilateral infiltrates with a classic "white-out" picture. Blood bank was informed of a suspected transfusion reaction as well as the transfusion specialist as TRALI was also suspected. Respiration rate was now 40. Ventolin nebules, hydrocortisone and phenegan were given in an attempt to alleviate symptoms but were unsuccessful. ICU staff were contacted and the patient was transferred to the intensive care unit for closer monitoring. The patient's condition progressively deteriorated and eventually required full intubation and inotropic support. The patient stabilised and slowly improved over the following 2 days ending in a full recovery and transfer back to the ward.

HLA antibody investigations involving the donor of the implicated FFP unit have not been completed at time of writing.

Nursing and medical staff were confronted with the sudden deterioration of a patient with at least five possible causes; allergic reaction, cardiac overload, sepsis, pulmonary embolism and TRALI. Blood samples for CBC, U&Es, blood cultures and tissue typing were performed.

Nursing Implications

Nurses are in a prime position to enable early identification of a transfusion reaction. By noting the patient's symptoms, when they commenced, start times of the transfusion as well as a history of the patient, all will assist in a timely diagnosis, as well as timely treatment. In the case study, cardiogenic pulmonary oedema was quickly ruled out as the nurses were able to provide information regarding the patient's fluid status which suggested that overload wasn't the cause and there was no history of cardiac disease in this 15 year old. This is important as diuretics are of little use in TRALI and may exacerbate the situation. The symptoms of yellowish frothy sputum with acute onset of dyspnea and the timing of the transfusion points to TRALI. The chest X-Ray showed "white-out" features which is also typical of TRALI. The absence of a fever, although not ruling out, suggested that it wasn't an infective process. Repeat cross-match, U & Es and CBCs, blood gases need to be performed as well as, in suspected TRALI cases, samples are required for tissue typing purposes.

Treatment is largely supportive including adequate oxygenation and maintaining hydration as patients can become intravascularly depleted due to the loss of fluid through the lungs. Diuretics should be avoided. The patient may need to be ventilated. Most patients will recover after 2-4 days with this support.

Blood components and products in New Zealand are processed under the highest of international standards, and are among the safest in the world, however there is a risk associated with transfusion. The haemovigilance programme operated by the New Zealand Blood Service is in to its second year and is beginning to provide useful information regarding adverse events. In the 2005 report (8 months only) there were 10 reports of TRALI, which represents 3.7% of all reported adverse events.4 The UK SHOT report highlights that TRALI is one of the most common causes of fatal transfusion reactions but that it is under-reported and poorly recognised.5 Because this is a truly terrifying experience for the patient, nurses should be aware of the appropriate intervention for this potentially life threatening reaction.

References

1. Mintz, P.D. (2005) Transfusion Therapy: Clinical Principles and Practice. 2nd Ed. AABB Press. Maryland.
2. 2002-2003 Scientific Section Coordinating Committee. (2004) Guidelines for the Management of Transfusion Related Acute Lung Injury. AABB Press. Maryland.
3. Knippen, M.A. (2006) Transfusion Related Acute Lung Injury. American Journal of Nursing. Vol 106. 61-65.
4. NZBS Haemovigilance Steering Group (2006) Haemovigilance Annual Report-2005. New Zealand Blood Service.
5. Serious Hazards of Transfusion Steering Group (2005). Serious Hazards of Transfusion(SHOT) annual report 2004. (http://www.shotuk.org/)
6. Teague, G., Hughes, A. & Gaylard, D. (2005) Transfusion- related Acute Lung Injury (TRALI). Anaesthetic Intensive Care. 33. Pp124-127