It occurred to us that, in addition to changes in TF expression by LPS, the process might also involve the direct binding of the lipophilic LPS to circulating plasma proteins, particularly fibrinogen, and that this (potentially rapid) binding might also cause pathological changes in the coagulation process. This would be independent of the slower TF activation, and thus an acute and relatively immediate process (figure 1). This indeed turned out to be the case. A preprint has been lodged at bioRxiv . Figure 1.High-level effects of systemic inflammation on the coagulation system and the pathologic effects of LPS when present in blood and how it influences coagulation via a direct or indirect activation. Processes 1A and B are currently known for LPS activity in blood, while process 2 is a newly proposed acute reaction effect of LPS on blood and plasma. (Online version in colour.)