[Hemorheological aspects of leuko-platelet activation in atheromatous diseases: clinical applications]

Atherosclerosis (and its evolution towards thrombotic accidents) is now considered to be an inflammatory disease in which the interaction among endothelium, leukocytes and platelets plays a determining role. However, large scale epidemiological studies only indirectly reveal the leukocyte activation through somewhat simplistic markers, such as elastase or leukocyte counts. Interestingly, these markers seem to be independent predictors of ischemia distal to the atheromatous lesion. This leukocyte activation is usually associated with more classical hemorheological disturbances affecting blood viscosity and fibrinogen which, on multivariate analysis, also appear to be determinants of atheromatous lesions and their ischemic and thrombotic consequences, statistically independent of the "classical risk factors". Leukocyte activation probably plays an important role in these hemorheological disturbances, because it is associated with the production of leukocyte secretory products (proteolytic enzymes, free radicals, cytokines) which can alter the red cells and make them more aggregable and more rigid, and can increase the production of fibrinogen. These interactions remain incompletely understood, as illustrated by the still unclear role of NO which, depending on the experimental conditions, can have antiatherogenic or proatherogenic effects. The production by the leukocyte of substances leading to hyperviscosity is amplified by hypoxia, while the improvement in claudication distance resulting from walking exercise is associated with a joint fall of the "classical" factors of viscosity and of leukocyte activation markers. All this suggests that leukocyte activation and hyperviscosity are closely interdependent phenomena in the course of atheromatous disease and that, despite the complexity of these interactions, relatively simple and reasonably priced biological markers of this process will become available to the clinician.