Amotosalen and ultraviolet A (UVA) photochemical-based pathogen reduction using the Intercept™ Blood System (IBS) 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 study herein was undertaken to identify the mechanisms responsible for the early impairment of platelet function by the IBS. Twenty-five platelet apheresis units were collected from healthy volunteers following standard procedures and split into 2 components, 1 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 IBS-treated units at day 1 of storage. Glycoprotein Ib (GpIb) levels were significantly lower in IBS samples and soluble glycocalicin correspondingly augmented; furthermore, GpIbα was significantly more desialylated as shown by Erythrina Cristagalli Lectin (ECL) binding. The pro-apoptotic Bak protein was significantly increased, as well as the MAPK p38 phosphorylation and caspase-3 cleavage. Stored IBS-treated platelets injected into immune-deficient nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice showed a faster clearance. We conclude that the IBS induces platelet p38 activation, 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 IBS increases patient safety at the expense of platelet function and survival.

Post-ischaemic silencing of p66(Shc) upon reperfusion improves stroke outcome in mice while the expression of p66(Shc) gene correlates with short-term outcome in patients with ischaemic stroke.

To cite this article: Reiner MF, Stivala S, Limacher A, Bonetti NR, M ean M, Egloff M, Rodondi N, Aujesky D, von Schacky C, L€ uscher TF, Camici GG, Beer JH. Omega-3 fatty acids predict recurrent venous thromboembolism or total mortality in elderly patients with acute venous thromboembolism. J Thromb Haemost 2017; 15: 47-56. Essentials• The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) is unknown.• Association of n-3 FAs with recurrent VTE or total mortality was investigated in 826 patients.• Whole blood n-3 FAs were inversely correlated with recurrent VTE or total mortality.• Major and non-major bleeding was not increased in patients with higher levels of n-3 FAs.Summary. Background: The role of omega-3 fatty acids (n-3 FAs) in recurrent venous thromboembolism (VTE) remains unknown. Objectives: To investigate the association of n-3 FAs with recurrent VTE or total mortality at 6 months and 3 years. Methods: N-3 FAs were assessed in 826 patients aged ≥ 65 years, categorized into low, medium and high based on the 25th and 75th percentile. Mean follow-up was 29 months. Results: At 6 months, subjects with medium (adjusted hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.62) and high n-3 FA levels (adjusted HR, 0.36; 95% CI, 0.20-0.67) were less likely to develop recurrent VTE or total mortality, compared with those with low n-3 FAs. At 3 years, medium levels (adjusted HR, 0.67; 95% CI, 0.47-0.96) were associated with lower risk of recurrent VTE or total mortality. As compared with low n-3 FAs, the adjusted subhazard ratio [SHR] of recurrent VTE was 0.39 (95% CI, 0.15-0.99) in patients with medium and 0.17 (95% CI, 0.03-0.82) in patients with high n-3 FAs. The cumulative incidence of recurrent VTE was lower in the medium and high n-3 FA groups as compared with the low n-3 FA groups, but seems to have worn off after 3 years. The incidence of major and non-major bleeding was not greater in the high n-3 FA group. Conclusion: Higher levels of n-3 FAs were associated with a lower risk of recurrent VTE or total mortality in elderly patients with VTE, but not with greater bleeding risk.