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1 published in this issue of Haematologica on results of thrombin generation (TG) in cardiovascular disease and mortality, stemming from the Gutenberg Health Study, provides an opportunity to comment on TG as a global laboratory procedure to investigate hypoand hyper-coagulability. TG as a laboratory test was developed in the early 1950s by McFarlane and Biggs and was based on the activation of coagulation in whole blood or plasma by triggers such as tissue factor or cephaline and calcium chloride. The amount of thrombin generated over time was titrated by sampling the mixture at different time points into a fibrinogen solution and the resultant clotting times interpolated from a dose-response calibration curve to derive thrombin concentrations. Years later, Hemker et al. made substantial changes. The fibrinogen solution was replaced by a chromogenic substrate specific for thrombin, test plasma was defibrinated prior to testing and computer software was developed to derive the parameters stemming from the TG curve. These changes made identified in a large proportion of the tumors across the distinct COO subtypes (Figure 1). Applying the publicly available LymphGen algorithm on the GOYA dataset could help classify patients into well-defined molecularly and clinically distinct subgroups. These newly characterized subsets can identify patients with an unfavorable prognosis and may guide the development of new precision therapies for these aggressive lymphomas.

Thrombin generation: a global coagulation procedure to investigate hypo- and hyper-coagulability