**4.2 The VCH thesis of aetiology: a summary**

The initial version of the VCH hypothesis was conceived in 1966 and first outlined in 1977 (Malone, 1977). Its premises were tested critically during the late 1970s and early 1980s. The full version of the validated thesis, with detailed historical and experimental support and scientific and clinical implications, was published some 20 years later (Malone & Agutter, 2006, 2008). The VCH thesis is summarised in Figs. 1-4.

Under normal (pulsatile) blood flow conditions, the venous valve pockets are emptied and refilled regularly and thus do not become hypoxaemic (Fig. 1). However, if there is sustained non-pulsatile ('streamline') venous blood flow, DVT may occur. Such flow leads to suffocating hypoxaemia in the venous valve pockets, resulting in hypoxic injury to the inner (parietalis) endothelium of the cusp leaflets (Fig. 2).

This hypoxic injury activates the pleiotropic elk-1/egr-1 pathway within the endothelial cells, which in turn activates a number of chemoattractant and procoagulant factors. When normal pulsatile blood flow is restored, even transiently, leukocytes and platelets, attracted by these factors, may swarm to the site of dead endothelial cells and initiate protective coagulant action locally (Fig. 3).

Prolongation of non-pulsatile flow for multiple hours may kill the accumulated blood cells in the unemptied valve pocket. These dead cells may then form the core of a nascent thrombus (Fig. 4). If periods of non-pulsatile and pulsatile flow continue to alternate in that abnormal sequential pattern (very protracted stasis + very brief normal flow), the ensuing

Aetiology of Deep Venous Thrombosis - Implications for Prophylaxis 143

Fig. 1. Blood movements within and around a venous valve pocket during normal (pulsatile flow) conditions. The blood in the pocket exchanges regularly with the luminal blood, so valve pocket hypoxaemia does not develop and the endothelia lining the pocket remain oxygenated.

serial deposition of white cells may contribute the most distinctive morphological characteristic of a venous thrombus, the striking Lines of Zahn.

Subsequent dehiscence of the growing thrombus, with or without the necrotic endothelial layer to which it is attached, might explain why venous thrombi embolise so readily. The VCH thesis also provides an aetiological explanation for post-thrombotic syndrome and, indeed, for chronic venous insufficiency in general (Malone & Agutter, 2009).
