However, the number of PCs and RBCs transfused was similar in the two study arms, and the authors raised the question of whether the CCI is a reliable surrogate marker for bleeding risk assessment.

As shown by the studies discussed above, the results of the published clinical studies should be interpreted with caution, and their characteristics and possible biases should be taken into account. Results obtained with one method cannot be extrapolated to those obtained by other methods. In the first published meta-analysis that included the HOVON trial, Vamvkas concluded that there was a clinically significant increase in mild and moderate bleeding complications in the arm receiving treated-platelets [85]. However, this meta-analysis Cabozantinib ic50 contained a serious methodological bias: it combined the results of clinical studies of amotosalem/UVA with the results of a clinical study of riboflavin/broad spectrum UV. In a second meta-analysis, which was recently published by Cid et al., although the CCIs were lower after INTERCEPT, the hemostatic

efficacy of INTERCEPT-treated PCs was maintained. These findings support the results of previously published hemovigilance data, which did not show an increase in the number of PC transfusions after INTERCEPT [86]. The beneficial effects of INTERCEPT-treated platelets have been clearly demonstrated. Indeed, they reach beyond the original scope: in addition to the reduction in infectious risk, INTERCEPT-treated platelets obviate the need for γ-inactivation for GvHD prophylaxis and extend the maximum shelf life of platelets from 5 to 7 days. Furthermore, a reduction

in the transfusion MEK phosphorylation reaction rate has been observed, due either to partial plasma substitution Loperamide by additive solution or to a specific PI effect. Although platelet recovery, as measured by CCI or survival studies with radiolabeled platelets, is lower after PI treatment, the hemostatic efficacy, as measured by clinical outcomes, is maintained. The results of prospective clinical trials have been confirmed by retrospective hemovigilance data. However, the heterogeneity of these clinical trials complicates their comparison. At the laboratory level, PI-treated platelets seem to present an increased activation status, and moderate changes at the level of mitochondrial metabolism are expressed in increased metabolic parameters; however, the results are discordant among studies. These modifications might explain the reduced survival and decreased recirculation level of PI-treated platelets, although the increased activation status of PI-treated platelets does not lead to a decrease in hemostatic efficacy. Activated fibrinogen receptor expression appears to be increased after PI, perhaps through a direct effect of PI on this integrin. These data relate mainly to the amotosalen/UVA technique and, to a lesser extent, to the riboflavin/UV method.