**5.3 Why is DVT not even more common than it is?**

The evidence reviewed in section 4 testifies to the correctness of the VCH thesis, but the imaginative reader might raise this question. Sustained non-pulsatile flow in the deep limb veins with short episodes of pulsatile flow are quite common in the daily lives of some humans, and is certainly common among carnivores, which sleep and remain immobile for many hours per day. In this context, the proposal of Brooks *et al.* (2009) that the valve pocket endothelia are more resistant than the luminal endothelium to the induction of coagulation could be of interest.

These authors proposed, on the basis of preliminary evidence, that the levels of von Willebrand factor (vWF), thrombomodulin (TM) and endothelial protein C receptor (EPCR) change with depth in the valve pocket, so that the endothelial cells express less of the procoagulant (vWF) and more of the anticoagulant (TM and EPCR) factors. Trotman *et al.*  (2011) pursued this hypothesis and found that the level of vWF did indeed decrease with depth in the pocket, but so did the level of EPCR; the TM level showed no significant change. There was extensive inter-individual variation in all three of these proteins, so the patterns were not entirely clear, but the hypothesis advanced by these authors could in principle help to explain 'why DVT is not even more common than it is'. In principle, The Brooks *et al.* proposal could be tested critically by a study on a large experimental animal group. The incidence of thrombogenesis under conditions similar to those used by Hamer & Malone (1984) could be correlated with the expression of vWF (and perhaps TM and EPCR), as assessed e.g. by immunostaining in the valve pocket endothelia after the end of the experiment. However, the most important factor in thrombogenesis is without doubt the duration of the valve pocket hypoxaemia.
