**4.1.1 The vagaries of 'venous stasis'**

By the late 19th century it was clear that paralyzed patients develop DVT and PE (Malpother, 1880), and by the middle of the 20th century it was known that prolonged bed rest, e.g. in spinal injury patients, had the same consequence (Wright & Osborn, 1952; Gibbs, 1957). This association between restricted mobility and DVT was attributed to slowed venous return, i.e. reduced volume per unit time (Ochsner *et al*., 1951; Wright & Osborn, 1952). Thus, by the early 1960s, it was held to be virtually certain that 'venous stasis' contributed to the cause of DVT (Zweifach, 1963); it was imagined to promote local coagulation (Mammen, 1992). The endothelial hypoxia hypothesis (from which the VCH hypothesis was coined) directly supported this premise: if blood were to flow slowly enough to injure some part of the endothelium by hypoxaemia (even to kill that part of the tissue should flow cease altogether in an unflapped, unemptied valve pocket), local leukocyte swarming and margination, and local coagulation, would ensue through the molecular mechanisms discovered by Pinsky and his colleagues.

However, that conception seems hard to reconcile with Hewson's (1771) experiment. Hewson doubly-ligated a dog's jugular vein, and the stationary blood between the ligatures failed to coagulate after more than an hour; even after three hours, coagulation was only partial. His finding was so counter-intuitive that Lister (1863) and Baumgarten (1876) repeated it in the 19th century and Wessler (1962) in the 20th, with identical results.

Wessler's findings indicated that double ligation *did* somehow injure the vessel, directly or indirectly, because rapid coagulation followed when he introduced serum containing activated coagulation factors into the ligated portion. Importantly, however, the resulting coagula bore no morphological resemblance to autochthonous venous thrombi, so – as explained in section 3.2.1 – his world-renowned experiments were of limited relevance for understanding the aetiology of DVT.
