The role of platelets in vascular surgery patients

Abstract

To sustain life, efficient transport of metabolites is required for continuous metabolism. In higher animals, active transport of metabolites is performed by blood, which flows through an advanced closed vascular system and is powered by the pump function of the heart. Problems in blood composition, the cardiac pump function or the vascular system can result in insufficient transport of metabolites. Significant circulation insufficiency leads to ischemia which can rapidly cause damage to end organs and ultimately results in death.

In humans, vascular health is threatened by progressive atherogenesis, responsible for atherosclerosis and subsequent narrowing of vascular lumina. Atherosclerosis is a chronic inflammatory disease which progresses through an interplay of several factors such as: endothelial cell dysfunction, hyperlipidemia, hypertension, diabetes mellitus, smoking, elevated plasma homocysteine concentrations and the hemostatic system. Atherosclerosis is complicated by intravascular thrombosis, initiated by plaque rupture, which can occlude arteries and cause acute ischemic damage. Abnormal platelet function with an increased tendency to aggregate is implicated in the pathogenesis of atherosclerosis and development of superimposed acute ischemic events.

The main objective of this thesis was to evaluate the factors that predict morbidity and mortality in vascular patients and to study one of the modifiable predictors: platelet function. We developed a platelet reactivity test for in depth platelet function research, to analyze its prognostic value and to identify possible targets for improved antiplatelet therapy.

Chapter 1 describes the relation between sex and post peripheral bypass surgery prognosis and shows a relatively bad prognosis for young women with PAD. Chapter 2 focusses on the development and validation of a risk chart for future mortality and ischemic events following peripheral bypass surgery. A meta-analysis on the prognostic value of currently available platelet function tests on future cardiovascular events is described in chapter 3. The platelet activation test (PACT), capable of analyzing major platelet activation pathways and quantifying the different platelet activation results, we developed is described in chapter 4. In chapter 5-8 this PACT is applied to analyze platelet function in patients with atherosclerosis. In contrast to our expectations, we observed lower platelet reactivity in patients with end stage peripheral arterial disease and this effect was stronger in patients with several cardiovascular risk factors. Furthermore patients with unstable coronary arterial disease (CAD) had lower platelet reactivity then patients with stable CAD. (Chapter 6) In contrast, baseline platelet activation was higher in patients with more severe PAD. (Chapter 5)

Chapter 7 describes the difference in platelet reactivity following evening and morning administration of aspirin and suggests that the evening administration of the polypill resulted in lower overall platelet reactivity in the morning then morning administration of the polypill. Chapter 8 describes the rationale and design of the MESCEA study on platelet function and micro embolic signals during carotid endarterectomy. We conclude that platelet function analysis in vascular patients to compose and monitor an antiplatelet therapy regimen consisting of inhibitors of different platelet receptors will be key to achieve an optimal balance between atherothrombosis and hemostasis in the future.