The misfits of blood coagulation

Dear friends and colleagues, One could think of the blood coagulation cascade as an organized and orderly event that involves steps and proteins that are highly similar. For instance, proteins such as coagulation factors FVII, FIX, FX and APC are highly homologous and largely work in a similar fashion. Fortunately, there will always be proteins that do not “stick to the rules”. This makes things more complicated, but also more interesting. One such “misfit” is coagulation factor FXI. It does not look like any of the other coagulation factors (apart from prekallikrein) and it does not function like any other coagulation factor. In this issue of Thrombosis Research, Gailani and co-workers provide an extensive review of the structure and function of FXI [[1]Maufus M. Elias A. Barrellier M.T. G. Pernod, Diagnosis of deep vein thrombosis recurrence: Ultrasound criteria.Thromb. Res. 2017; 161: 129Google Scholar]. In another paper in this issue, Kanse and colleagues investigate the link between Neutrophil Extracellular Traps (NETs) and Factor VII activating protease (FSAP) [[2]Grasso S. Neumann A. Lang I.M. Etscheid M. von Köckritz-Blickwede. M. Kanse S.M. Interaction of factor VII activating protease (FSAP) with neutrophil extracellular traps (NETs).Thromb. Res. 2017; 161: 36-42Abstract Full Text Full Text PDF PubMed Scopus (22) Google Scholar]. FSAP was long thought to be the upstream activator of FVII. However, compelling evidence to support this is lacking, making FSAP a somewhat enigmatic protein. In this paper, Kanse and colleagues show that FSAP is activated by degraded NETs, the latter being expulsed neutrophil-derived chromatin that is used to capture pathogens in the blood. Upon activation, FSAP degrades cytotoxic histones, even more potently than APC does. Thus, activation of FSAP is likely to neutralize the cytotoxic effect of histones towards the endothelium, thus limiting the damaging effect of NETosis. Finally, the editors would like to wish you a productive, misfit-free and thrombosis-free 2018!