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A study of platelet aggregation in whole blood from normal and prothrombotic subjects

Mackie, Ian James; (1991) A study of platelet aggregation in whole blood from normal and prothrombotic subjects. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The aim of this thesis was to study platelet function in whole blood, in an environment close to normal physiology. It was anticipated that such studies in whole blood would be more sensitive to in vivo changes than studies on isolated platelets, since all of the formed elements are present, there is less risk of in vitro activation, and labile substances should still be present. This approach was thought to be particularly applicable to platelet studies in blood from patients with prothrombotic states where the mechanism of thrombosis is unclear, and for examining anti-platelet drug efficacy. Existing methods were inadequate and it was first necessary to develop new techniques using electrical impedance. Sensitive and reproducible impedance methods were developed, and these were especially useful for blood samples with platelet counts below 50*10⁹/1. A particular type of aggregate was detected, requiringirreversible aggregation, thromboxane A2 generation, but not ADP secretion. Measurements in non-anticoagulated blood allowed a global view of haemostasis, reflecting interactions of platelets, neutrophils, thrombin, and fibrin. In the presence of calcium++, neutrophils and thrombin potentiated the aggregation response. There was excessive aggregation in non-anticoagulated blood from patients with multi-organ failure. This was related to increased neutrophil count, enhanced thrombin generation, and reciprocal cell activation. Such patients may benefit from eicosanoid antagonists and protease inhibitors to prevent unwarranted activation of coagulation and cellular defense mechanisms. Chronic arteriopaths showed reduced aggregation compatible with in vivo activation. Prostacyclin analogue infusions were less effective as judged ex vivo in whole blood compared to traditional techniques; continuous infusion resulted in progressively decreasing platelet sensitivity, rebound hyperaggregability, and increased serum thromboxane B2. Cigarette smoking caused increased platelet aggregation and adherence to vascular endothelium. Increased aggregation was seen in multi-organ failure, which traditional methods would not have detected. There appear to be multiple interactions between leucocytes and platelets.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: A study of platelet aggregation in whole blood from normal and prothrombotic subjects
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Platelets
URI: https://discovery.ucl.ac.uk/id/eprint/10124762
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