Fibrinolytic and biochemical factors in patients with venous insufficiency

Abstract

Long-term metabolic changes in vein tissue of the limbs and feet have been reported in the course of chronic venous insufficiency (CVI). Low fibrinolytic potential was first demonstrated using fibrin-embedded vein rings (Todd's biopsy), then in blood via increased euglobulin lysis time. This defect is especially pronounced when blood is taken from foot veins of patients with grades 5 and 6 of CVI or skin lesions. Haemorrheological disorders such as increased blood viscosity and red cell aggregation, related mainly to high fibrinogen levels, have also been shown in patients with CVI. Such disorders, particularly observed in blood from foot veins, play an important role in the interaction between the blood cell components and the vessel wall.

More recently, the margination and adhesion of white cells to the endothelium and the subsequent activation of white cells have been assumed. Adhesion molecules such as ICAM-1, VCAM-1 and P-selectin have been identified surrounding skin ulceration. There is also evidence that markers of neutrophil degranulation reach high levels in blood taken from foot veins after exposure to experimental venous hypertension. White cell activation results in elevated plasma levels of L-selectin, increased production of oxygen free radicals, pseudopods, CD11b integrin, platelet-monocyte aggregates and abnormal lymphocyte L-selectin. Increased nitric oxide, presumably due to monocyte activation, as well as increased urine haemosiderin related to skin microvessel leakage have also been reported. VCAM-1 and metalloproteinase MMP9 activity have been stated as sensitive markers in relation to endothelium activation and white cell trapping, which follows hypoxia and/or alterations in wall shear stress, mainly in skin venulae and in the region of valves.