Desensitization in allergic transfusion reactions: evidence from the Trial to Reduce Alloimmunization to Platelets

To the Editor Allergic transfusion reactions (ATRs) occur in up to 3% of platelet transfusions1, are under-reported, and range in severity from mild itching and hives to fatal anaphylaxis. Clinical data have broadly defined factors that may be involved, such as a pathogenic role for plasma. Retrospective data of plasma reduction maneuvers to prevent ATRs to blood products are confounded by selection bias: patients always receive unmanipulated platelets before being switched to volume reduced or washed platelets following ATRs. An individual's risk of ATRs might decrease with increasing numbers of platelet transfusions, independent of platelet product manipulation. Thus, plasma reduction may temporally coincide with, but not cause, a reduction in ATR risk2. To address the question of whether ATR risk varies with increasing platelet transfusion number, we analyzed severe urticarial reaction data from the Trial to Reduce Alloimmunization to Platelets (TRAP)3. There were 31 severe urticarial reactions reported in 24 subjects in the TRAP study (n=8,770 transfusions). Details about minor allergic reactions or the criteria for defining a severe urticarial reaction were not recorded in the study. Anaphylaxis was an evaluable outcome, but anaphylaxis was not reported after any platelet transfusion. However, three severe urticarial reactions were accompanied by dyspnea or bronchospasm. These reactions meet current criteria for likely anaphylaxis4. The figure shows the frequency of severe urticarial reactions by transfusion number. The risk for a severe urticarial reaction is not constant and is highest among the first 5 transfusions: 18 severe urticarial reactions in transfusions 1-5 (n=2889) vs. 13 severe urticarial reactions in the remaining transfusions (n=5881; P=0.006, Fisher exact test). We conducted a logistic regression analysis using a clustered sandwich estimator to account for subjects receiving different total numbers of transfusions. The odds ratio for a severe urticarial reaction for every additional platelet transfusion is 0.91 (95% CI 0.85-0.98, P=0.007). Five percent of platelets in TRAP were volume reduced. When these transfusions are excluded from the analysis, the findings do not materially change (OR 0.92; 95% CI 0.86-0.98). Figure The rate of severe urticarial reactions to platelets in the Trial to Reduce Alloimmunization to Platelets decreases over time It is possible that subjects with an increased ATR predisposition received fewer platelet transfusions than subjects with no predisposition to ATRs, and this would bias the results. Indeed, the 24 subjects who experienced a severe urticarial reaction had a median (range) of 7 (1-32) platelet transfusions during the study period vs. 9 (1-92) for the subjects who did not have a severe reaction (P