Managing risk of over-transfusion

The ‘over-transfusion’ of blood and blood components has long been recognised by the medical and surgical professions as a contributory factor in adverse patient outcomes. As long ago as 1957, Arkansas M.D. John W. Downs, in his paper The Problem of Over-transfusion in Massive Hemorrhage, which first appeared in The Annals of Surgery, commented that circulatory overloading was regarded as probably the most common cause of death from blood transfusion. Downs went on to state that autopsy evidence had revealed frequent instances in which the over-enthusiastic use of blood had probably contributed to patient death, although the incidence and dangers of over-transfusion did not seem to be generally well recognised at the time. Today, however, transfusion-associated circulatory overload or ‘TACO’, as it has become known, is regarded as a relatively common, but serious complication of transfusion resulting from a rapid or massive transfusion of blood or blood products. TACO usually occurs within six hours after the completion of a transfusion but can occur for up to 24 hours later. Its symptoms include acute respiratory distress, tachycardia, acute or worsening pulmonary oedema, chest tightness and a rapid increase in blood pressure. It has been estimated that TACO occurs in approximately 1 in 100 to 1 in 10,000 transfusions, with certain patient groups being at an increased risk. These include infants, elderly patients typically over 60 years of age, patients with cardiac, pulmonary or renal failure, and also patients suffering from chronic anaemia. In suspected cases, there is often evidence of a positive fluid balance while chest X-rays typically reveal the presence of pulmonary oedema and cardiomegaly. Although rapid infusion or massive transfusion are frequently the initiating factors of TACO, relatively small volume transfusions of one or two units of blood are often sufficient to trigger the congestive heart failure associated with the condition, with fresh frozen plasma (FFP) also often implicated. Consequences of TACO to the patient often include major morbidity associated with an increased hospital stay, which also invariably involves prolonged intensive care treatment before recovery. However, approximately 1% to 3% of TACO cases prove fatal, although the actual figure may be higher.

TACO versus TRALI

TACO is frequently confused with another pulmonary complication of transfusion, namely transfusion-related acute lung injury or ‘TRALI’, and both conditions continue to be a common cause of death in patients, being frequently observed in surgical, ICU and massive transfusion settings. TRALI is now regarded as a serious and life-threatening complication of transfusion therapy, being particularly linked with the use of donor plasma based products such as FFP and platelet concentrate. TRALI is characterised by severe acute respiratory distress, typically within one to two hours of transfusion or in the following 24 hours. Other symptoms include hypotension, fever and chills – especially in patients with existing respiratory problems. Severity can range from mild to severe, but is usually related to the degree of hypoxia. Although there is, as yet, no definitive diagnostic test for the condition, radiological findings invariably show bilateral pulmonary infiltrates appearing as shadowing at the time of the reaction, which normally resolve within 96 hours in around 80% of affected patients. However, the infiltrates may persist for as long as a week in the remaining 20% of cases. Treatment usually consists of immediate respiratory and circulatory support, primarily ventilation. As a result, most affected patients recover completely without any long-lasting or permanent damage. Despite this, according to SHOT data, TRALI has become the second largest cause of UK patient morbidity and mortality, second only to ABO incompatibility itself. Further studies of SHOT data have revealed that the TRALI risk is five to seven fold greater in components containing high volumes of plasma, and the majority of TRALI cases involved leukocyte-antibody positive female donors. In October 2003, the UK moved to male-only plasma and, as a result, there has been a significant reduction in TRALI cases in the UK ever since. This supports the previous belief that TRALI is thought to be the result of donor white cell antibodies present in the plasma of the transfused component, which then react with the recipient’s own white blood cells. In most documented cases it is HLA class I antibodies that are the cause, but granulocyte specific antibodies have also been associated with the condition. These complement activating antibodies set off an acute immune response in the recipient, which result in granulocyte aggregation in the pulmonary microvasculature. This quickly leads to the accumulation of fluid and protein in the alveoli, which then displays all the clinical signs of respiratory distress. Outwardly, and on X-ray, however, these findings and symptoms are very similar to those of acute respiratory distress syndrome (ARDS) or other forms of acute lung injury such as TACO. Ideally, the donors of all implicated transfused components should be screened for the presence of HLA class I antibodies. As HLA antibodies are produced as a result of alloimmunisation during pregnancy or a transfusion event, then initially only female donors with children and previously transfused male donors are investigated. Demonstrating a positive cross-match between donor serum and the patient’s leucocytes gives confirmation of TRALI. The use of male-only donated fresh frozen plasma for transfusion has dramatically reduced, but not eliminated TRALI – thereby saving many lives, but TACO, as yet, shows no sign of decreasing. As with TRALI, early recognition of TACO should lead to better clinical outcomes for patients.