The ‘sudden’ onset of clotting time prolongation may be of interest

to evaluate specific coagulation factor changes during influenza infection. To evaluate the influence of a more ‘moderate’ influenza virus infection, seasonal H3N2 virus was also included in the experiments. Although this influenza virus in general NU7441 datasheet causes ‘moderate’ disease in humans and ferrets, it did cause significant procoagulant changes in the model with hemostatic alteration comparable to those of pH1N1 virus infected ferrets. However, TAT levels did not increase suggesting a more moderate procoagulant state compared to H1N1- and H5N1 virus infected animals. Since the ageing human population is prone to both an increase in cardiovascular disease and to complications during and after infection with seasonal and avian influenza viruses [34, 35], further exploration of the interplay between influenza and hemostasis would be of great interest. Most of the associations found in Table 2 show positive correlations between coagulation parameters and markers of inflammation (body weight decrease and

relative lung weight increase). This comes as no surprise since the bidirectional cross-talk between coagulation and inflammation has been studied very PF-6463922 in vivo well, www.selleckchem.com/products/Fludarabine(Fludara).html whereby inflammation in general evokes a procoagulant response [36–38]. The specific disturbances in the tightly regulated balance between clotting, anti-coagulation and inflammation could be a target for novel intervention strategies in influenza. Following our observational study, an intervention model could further evaluate

the role of coagulation in influenza virus pathogenesis and the potential processes for targeted intervention, for example by targeting protease receptor type-2 (PAR-2) activation in influenza pathogenesis. PAR-2 is an important receptor in both inflammation and coagulation, and recently Liothyronine Sodium described to have a major role in the damage seen after the inflammatory response during influenza virus infection [39, 40]. While statins may also be interesting candidates for future studies. Statins may counteract specific inflammatory responses such as seen after acute coronary syndrome, and thereby may decrease mortality when given to influenza patients. Studying the influence of statin treatment on the procoagulant changes during influenza virus infection and the role these changes have in the postulated increased risk of myocardial infarction would be of great interest [41–43]. Collectively the data generated by our study will pave the way for further exploration of novel treatment and intervention strategies for influenza and its complications. Furthermore, based on the correlation between the viral infection – and coagulation parameters in this experiment, coagulation tests could serve as valuable biomarkers predicting disease severity.