To what extent might deep venous thrombosis and chronic venous insufficiency share a common etiology?

According to the valve cusp hypoxia hypothesis (VCHH), deep venous thrombosis is caused by sustained non-pulsatile (streamline) venous blood flow. This leads to hypoxemia in the valve pockets; hypoxic injury to the inner (parietalis) endothelium of the cusp leaflets activates the elk-1/egr-1 pathway, leading to leukocyte and platelet swarming at the site of injury and, potentially, blood coagulation. Here, we propose an extension of the VCHH to account for chronic venous insufficiency. First, should the foregoing events not proceed to frank thrombogenesis, the valves may nevertheless be chronically injured and become incompetent. Serial incompetence in lower limb valves may then generate "passive" venous hypertension. Second, should ostial valve thrombosis obstruct venous return from muscles via tributaries draining into the femoral vein, as Virchow illustrated, "active" venous hypertension may supervene: muscle contraction would force the blood in the vessels behind the blocked ostial valves to re-route. Passive or active venous hypertension opposes return flow, leading to luminal hypoxemia and vein wall distension, which in turn may impair vasa venarum perfusion; the resulting mural endothelial hypoxia would lead to leukocyte invasion of the wall and remodelling of the media. We propose that varicose veins result if gross active hypertension stretches the valve "rings", rendering attached valves incompetent caudad to obstructed sites, replacing normal centripetal flow in perforating veins with centrifugal flow and over-distending those vessels. We also discuss how hypoxemia-related venous/capillary wall lesions may lead to accumulation of leukocytes, progressive blockage of capillary blood flow, lipodermosclerosis and skin ulceration. [Int Angiol 2009;28:254-68]