Hot on the trail of TRALI

Comment on Khan et al, page 2455

Khan and colleagues show that platelet-derived sCD40L accumulates in stored blood, primes neutrophils, and is associated with TRALI.

Transfusion-related acute lung injury (TRALI) is an acute lung injury unrelated to circulatory overload occurring within 6 hours of a transfusion,¹  and is now the leading cause of transfusion-related fatalities.²  Case reports have shown that the transfusion of leukocyte antibodies can cause TRALI; however, case-control studies have found that many cases of TRALI do not involve leukocyte antibodies.³  Other factors that cause TRALI have eluded clinical investigators.

In this issue of Blood, Khan and colleagues found that the platelet-derived proinflamatory cytokine soluble CD40 ligand (sCD40L) accumulates in stored platelet and red-cell components (see figure). Neutrophils were found to express CD40, and sCD40L in stored blood primed the neutrophil oxidative burst and induced neutrophil-mediated cytotoxicity of cultured endothelial cells. Most importantly, sCD40L levels were greater in platelet components implicated in clinically recognized TRALI reactions than in control platelet components.

Clinical investigators have followed many trails in pursuit of TRALI, but this newly recognized trail might well be a clinically important one. Patients with underlying neutrophil-mediated pulmonary endothelial damage are likely to be at risk of further pulmonary endothelial damage due to the transfusion of blood components with high sCD40L levels. In fact, the lung may be only one of several target organs, but a target organ that becomes readily apparent when these reactions occur. However, the association of TRALI with implicated blood components containing high sCD40L levels is preliminary and must be confirmed by prospective controlled studies.

Many patients who experience acute lung injury shortly after a transfusion have other clinical factors that could be responsible for the lung injury. As a result, it is often difficult to determine whether the transfusion was responsible for the lung injury. Along with testing of the donor for leukocyte antibodies, testing of blood components implicated in acute lung injury for sCD40L is likely to become an important diagnostic tool.

This study provides support of the controversial practice of transfusing only leukocyte-reduced blood components. The levels of sCD40L were much lower in red-cell components that had been filtered to remove leukocytes compared with those that had not been filtered (see figure), and hence are less likely to cause transfusion reactions.

Some experts have been advocating extending the shelf-life of platelets from 5 to 7 days to reduce the loss of platelet components due to outdating.⁴  However, sCD40L levels increase between days 5 and 7 of platelet storage, suggesting that prolonging platelet storage will increase the incidence of transfusion reactions. Whereas the risk of “old” red cells has become an area of heated controversy, large amounts of aged platelets may present a greater hazard, especially to critically ill patients.

To reduce the incidence of TRALI, some countries transfuse plasma only from male donors to avoid the transfusion of leukocyte antibodies found in the plasma of multiparous women. Although this strategy may be usefulFIG1 in preventing reactions to plasma, it will not affect the accumulation of sCD40L in platelet components, and restricting female platelet donors may not be an effective strategy. ▪