• White cell rheology: reduction in capillary blood flow results in trapping of white blood cells in the capillaries causing plugging and release of proteolytic enzymes, cytokine and free radicals leading to tissue ulceration.

• Macromolecules & microvascular ischemia: venous ulceration sets a vicious cycle of tissue ischemia at micro vascular level by reducing the number of skin capillaries and flow thus trapping of matrix proteins and growth factors.

• Fibrin cuff: patients with chronic venous insufficiency are found to have peri-capillary fibrin cuffs acting as a barrier to oxygen perfusion.