Reply

The above letter was sent to Heddle et al.; Ms Heddle offered the following reply. We thank Dr Blumburg and colleagues for their letter and for bringing to our attention their publications related to CD40 ligand. We agree with Dr Blumburg that reactions to platelet concentrates have a multifactorial etiology. Indeed, we have suggested in several previous publications that both the cellular and the plasma components contribute to these reactions and that the plasma supernatant represents a “soup” of biologic response modifiers that may be derived from the cellular components within the product or noncellular interactions.1-3 The soluble biologic response modifiers in the plasma that may be contributing to these reactions have been the subject of many investigations in several different countries. The initial focus was that these biologic response modifiers were WBC-derived as studies showed that WBC reduction before storage could decrease the frequency of these reactions. However, as noted in our study, there is still an overall frequency of acute febrile transfusion reactions of approximately 6 to 7 percent even when platelets that are WBC-reduced before are used. Dr Blumburg's suggestion that biologic response modifiers derived from platelets are involved in these reactions is logical, and indeed their publication suggests an association between CD40 ligand and reactions.4 There is no doubt that the plasma supernatant in stored platelet products is a soup of biologic response modifiers derived from a number of different sources, and the roles of these different components in causing reactions is not clearly understood. It is possible that the exact mechanism that causes these reactions may never be clearly defined because it is likely that these reactions represent a complex interaction between various cytokines, other biologic response modifiers, and complex clinical factors. We also agree with Dr Blumburg's suggestion that plasma removal in addition to WBC reduction may be an effective way to prevent subsequent reactions in patients who received WBC-reduced products. Their study published in Transfusion Medicine supports the concept that residual plasma removed through centrifugation or washing may be an effective mechanism for preventing these reactions.5 In 1996, we suggested a stepwise approach to treat patients who had recurrent febrile transfusion reactions, and indeed a combination of plasma removal and WBC reduction was recommended.6 For approximately 4 years our institution has used this combined intervention for patients who have repeated reactions to platelet concentrates that have been WBC-reduced before storage. Our approach was not to wash the platelets, but to simply remove the plasma supernatant from the platelet product, and I am not aware of any patient who has continued to react when this approach was used. Hence, the suggestion that plasma removal may be as effective as washing the platelets is probably correct; however, it would be useful to see some further data to confirm the effectiveness of this approach.

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