Pathogen inactivation technologies are photochemical treatments developed to decrease transfusion transmitted infections. However, the impact of pathogen inactivation technologies on the blood components themselves is not entirely clear. Therefore, we investigated the quality of blood components following pathogen inactivation. First, the impact of three different pathogen inactivation technologies on plasma was compared. The different methods all negatively affected ADAMTS13 activity and antigen level, but to different degrees. The pathogen inactivation technology using riboflavin as a photosensitizer had the largest effect. This effect was caused by reactive oxygen because removal of dissolved molecular oxygen prevented protein damage to occur. Next, we investigated the influence of three different pathogen inactivation technologies on platelet concentrates. For this, platelet function was assessed in microfluidic flow chamber experiments. These indicated a decreased platelet function compared to untreated controls for all pathogen inactivation technologies. Additional experiments showed that the underlying mechanisms of platelet damage were different for every pathogen inactivation technology, but all three resulted in similar thrombus formation deficiencies in flow chambers. We focused on one particular pathogen inactivation technology which combines the photosensitizer amotosalen (a psoralen) and UVA light (PUVA). The data showed a specific inhibition of the phosphatidylinositol 3-kinase signal transduction pathway caused by covalent binding of amotosalen to phospholipids during photoactivation. As the combination of a psoralen with UVA light is clinically used off-label for graft-versus-host disease treatment, phosphatidylinositol 3-kinase signal transduction in T lymphocytes of patient samples was studied and also here inhibition of phosphatidylinositol 3-kinase signal transduction was found. To conclude, research that initiated from the observation that platelet and plasma function is decreased following pathogen inactivation technologies has revealed an overall effect of PUVA on cellular phosphatidylinositol 3-kinase signal transduction by covalent modification of phospholipids.

(BELG J HEMATOL 2016;7(6):240–3)