Deep venous thrombosis

The valve cusp hypoxia hypothesis

Our account of the aetiology of deep venous thrombosis (DVT), the valve cusp hypoxia hypothesis (VCHH), derives from the pathophysiological tradition of research extending from Harvey and Hunter to Virchow, Welch and Aschoff, but it also assimilates recent discoveries about the molecular biology of the vascular endothelium.

According to the VCHH, DVT may occur if there is sustained non-pulsatile (streamline) venous blood flow. Such flow leads to suffocating hypoxaemia in the venous valve pockets, resulting in hypoxic injury to the inner (parietalis) endothelium of the cusp leaflets. This injury activates the 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 swarm at the site of injury, attracted by these factors, and local blood coagulation may be initiated.

A further period of non-pulsatile flow kills the accumulated blood cells in the valve pocket. These dead cells may then form the core of a nascent thrombus. If periods of non-pulsatile and pulsatile flow continue to alternate, serial deposition of white cells and fibrin may ensue, resulting in the characteristic Lines of Zahn morphology of a venous thrombus.

Only the blood cells on the outermost layer of a thrombus are still living.

The schematic diagrams on the following pages illustrate the process in four stages.

Clinical implications

The VCHH explains the risk factors for DVT and accounts for the morphology of thrombi. It also predicts that venous thrombi will readily embolise, because the area of endothelium to which they are anchored, the valve cusp parietalis, is necrotic and is readily detached by the flow of blood past the obstruction.

The VCHH is also compatible with accepted approaches to therapy, but it suggests a new approach to prophylaxis against venous thromboembolism. Lying horizontally, the anaesthetised or unconscious patient is at risk of valve cusp hypoxia and ipso facto of DVT, notably in the lower limb veins:-

However, a slight (say 5 degree) head-downwards tilt of the bed will allow the valve pockets to empty by gravity. To prevent hypoxia and thrombogenesis in the veins of the upper body, the tilt should be reversed at intervals of one or one and a half hours. Thus, recurrent changes of slight Trendelenburg/anti-Trendelenburg tilting should help to preclude the risk of thrombosis during prolonged surgery or bed rest – without the use of anticoagulant or thrombolytic agents.