We would like to thank B. Hechler and colleagues for the interest shown in our paper on the effects of the Amotosalen/UVA on platelet function, and we are pleased to take the opportunity to reply to their comments.
They note correctly that the results of our study are divergent from their previously published observation, but state that “..Stivala et al. quote our study in a way which may lead to convergent results, which is obviously not the case.” In the discussion of our paper, we refer to the publication by Hechler et al.1 in three separate instances:
Regarding the influence of the storage medium, Hechler et al. propose that it may have “inhibitory yet reversible effects on platelet responsiveness.” Undoubtedly the storage medium influences platelet response as reported by several studies,65 yet it might indeed have longer-lasting effects which are not reversible, especially after longer storage time (i.e., 3–4 days). In our study, platelets were resuspended in the same storage medium for all treatment groups (untreated and IBS-treated with or without pre-treatment with inhibitors) so the difference between untreated and Amotosalen treated platelets cannot solely be explained by a negative impact of the storage medium nor by the pH, which, even though significantly lower for the Amotosalen/UVA samples (as reported in other studies too87), was nevertheless in an acceptable range observed by others and above 7. Besides, for the in vivo analysis of platelet survival in mice, human platelets were washed and resuspended in sterile PBS before i.v. injection, therefore, any possible effect of the medium itself on the outcome (platelet survival) can be excluded.
Regarding the in vivo model itself, several studies119 have shown a correlation between platelet survival and platelet damage upon injection of human platelets in immunodeficient mice and have therefore confirmed the usefulness of this model and its reproducibility. We also agree that some studies did not report an increased usage of platelet components with Amotosalen/UVA, but others did in fact observe a decreased count increment (CI) and corrected count increment (CCI),1412 which could be explained primarily by an increased platelet clearance. Finally, we would like to emphasize again (as we state at the end of our paper) that the primary goal of our study was to better understand the effect of Amotosalen/UVA on platelet function at the molecular level in order to develop newer and better pathogen inactivation technologies.
We want to thank Hechler et al. for their constructive input and we hope that we were able to clarify it.
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