Eyers, Paul S. G.; (2001) Activation of neutrophils, platelets and the coagulation system in intermittent claudication. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Intermittent claudication is a common condition, affecting 2-5% of the population. The prognosis for the affected limb is relatively benign, but morbidity and mortality from associated cardiovascular events is high, with up to 50% of patients suffering a myocardial infarction or stroke in the five years following diagnosis. Multivariate analysis has suggested that claudication itself may be a risk factor for these events. The pathophysiologies of claudication and cardiovascular events are reviewed, with particular emphasis on the role of neutrophils, platelets and the coagulation system. From this we developed a hypothesis that claudication may activate, or increase the potential to be activated of, neutrophils, platelets and the coagulation system; and that this may contribute to the increased cardiovascular morbidity and mortality seen in claudicants. The aim of this work was to investigate activation, and, in particular, the activation potential of these elements in claudicants, before and after exercise. We assessed cellular and humoral activation in claudicants before and after exercise; and compared this with controls. We used sensitive flow cytometric techniques to investigate neutrophil and platelet activation, with a whole blood method to reduce preparation artefact. These investigations were run alongside more established techniques. Newer, more sensitive, assays were used to assess activation of the coagulation system. We found evidence of increased potential for neutrophil activation, as shown by increased superoxide production and hydrogen peroxide generation, following exercise in claudicants. Claudicants showed increased thromboxane levels following exercise in both the neutrophil and platelet studies. However, there was no further clear evidence for activation or priming of platelets from the studies of surface glycoproteins or platelet release factors. Differences in levels of markers of activation of the coagulation system were found between claudicants and controls, but no effect of exercise was seen. From this we concluded that claudication may increase the risk of cardiovascular events by priming neutrophils. There was no equivalent evidence to suggest priming of platelets or the coagulation system in response to claudication, although neutrophil activation may in turn activate platelets and the coagulation system.

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