Amotosalen/ultraviolet A pathogen inactivation technology reduces platelet activatability, induces apoptosis and accelerates clearance

Simona Stivala, Sara Gobbato, Laura Infanti, Martin F. Reiner, Nicole Bonetti, Sara C. Meyer, Giovanni G. Camici, Thomas F. Lüscher, Andreas Buser, Jürg H. Beer

Amotosalen and ultraviolet A photochemical-based pathogen reduction using the InterceptTM Blood System is an effective and established technology for platelet and plasma components, which is adopted in more than 40 countries worldwide. Several reports point towards a reduced platelet function after Amotosalen/UVA exposure. The current study was undertaken to identify the mechanisms responsible for the early impairment of platelet function by the InterceptTM Blood System. Twenty-five platelet apheresis units were collected from healthy volunteers following standard procedures and split into 2 components, one untreated and the other treated with Amotosalen/UVA. Platelet impedance aggregation in response to collagen and thrombin was reduced by 80% and 60%, respectively, in InterceptTM Blood System-treated units already at day 1 of storage. GpIb levels were significantly lower in Intercept™ Blood System samples and soluble glycocalicin correspondingly augmented; furthermore, GpIb alpha was significantly more desialylated as shown by Erythrina Cristagalli Lecting binding. The pro-apoptotic Bak protein was significantly increased, as well as the MAPK p38 phosphorylation and caspase-3 cleavage. Stored Intercept™ Blood System -treated platelets injected into immune-deficient NOD/SCID mice showed a faster clearance. We conclude that the Intercept™ Blood System induces platelet p38 activation and GpIb shedding, and platelet apoptosis through a caspase-dependent mechanism, thus reducing platelet function and survival. These mechanisms are of relevance in transfusion medicine, where the Intercept™ Blood System increases patient safety at the expense of platelet function and survival.