LPS, and especially its lipid A component, is highly lipophilic, and it therefore may be able to bind directly to plasma proteins, in an acute way. This might be one reason underlying the hypercoagulability , as well as a denser clot structure , as seen in various inflammatory diseases. Although we show here that exposure to even tiny amounts of LPS leads to an immediate (acute) change in the coagulability parameters, we recognize that this may happen simultaneously with chronic (longer-term) reactions (figure 1). Fibrinogen molecules are roughly 5×45 nm, and their self-assembly is a remarkable process (some 5800 are involved in generating a fibre of 80–90 nm diameter and 1 µm length). This would explain why the highly substoichiometric binding of LPS can have such considerable effects, especially as observed in WB. Following Anfinsen , it is assumed that most proteins adopt their conformation of lowest free energy. However, this is not true for amyloid fibre formation  nor in the case of the autocatalytic conversion of prion protein conformations . At present, the exact mechanisms of action of these small amounts of LPS are not known, although it is indeed simplest to recognize fibrinogen polymerization as a cascade effect, much as occurs for amyloid and prion proteins whose initial conformation is not in fact that of their lowest free energy . Specifically , the ‘normal’ conformational macrostate of such proteins is not in fact that of the lowest free energy, and its transition to the energetically more favourable ‘rogue’ state is thermodynamically favourable but under kinetic control, normally (in terms of transition state theory) with a very high energy barrier ΔG† of maybe 36–38 kcal mol−1 . Indeed, it is now known that quite a number of proteins of a given sequence can exist in at least two highly distinct conformations . Typically the normal (‘benign’) form, as produced initially within the cell, will have a significant α-helical content, but the abnormal (‘rogue’) form, often in the form of an insoluble amyloid, will have a massively increased amount of β-sheet , whether parallel or antiparallel. In the case of blood clotting, we at least know that this is initiated by the thrombin-catalysed loss of fibrinopeptides from fibrinogen monomers (e.g. ). The massive adoption of a β-sheet conformation, as revealed here for the first time by the thioflavin T staining, demonstrates directly that virtually every fibrinogen molecule in the fibrin fibril must have changed its conformation hugely; it is not just a question of static ‘knobs and holes’ as usually depicted. We also showed that LBP, and a mixture of LPS and LBP, shows decreased ThT binding, compared with LPS alone.