Robinson, Monique Samantha Chantal; (2001) An investigation into platelet heterogeneity. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Platelet heterogeneity has been an area of controversy for many years as the relationships between platelet age, volume and function are complex. Previous research however, has been limited by the use of older techniques which are less sensitive and prone to artefactual changes. The principle aim of this thesis was to investigate the relationship between platelet volume, age and functionality as this might improve our understanding of the relevance of platelet heterogeneity to platelet physiology. Flow cytometric methods were used to allow for the sensitive and rapid analysis of platelet activation, function, age and granularity of intact human platelets within whole blood. The clinical use of reticulated platelet measurement was evaluated, and found to be sensitive, rapid and simple compared to other measures of platelet turnover (GCI and TPO). A mouse in vivo biotinylation model established that young platelets are larger and more granular than older platelets. This finding was consistent with the analysis of platelets from normal controls separated on the basis of volume. In a study of the origin of platelet production and volume heterogeneity, the platelet count was found to be greater in the pulmonary vein compared to the pulmonary artery. The measurement of reticulated platelets and MPV however, were not sensitive enough to determine that young, large platelets are released in the pulmonary circulation. In a clinical investigation, the effect of altered platelet mass on platelet heterogeneity was investigated. Patients with acute coronary syndromes were found to have increased MPV, increased platelet activation but normal platelet turnover. Patients with thrombocythaemia had increased platelet count, reduced MPV, increased platelet activation and normal platelet turnover. This study has provided a clearer understanding of the physiological interplay between platelet age, volume and function, and how this is altered in disease states.

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