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Title: Perioperative hypercoagulability
Author: Lyness, Craig Anthony
ISNI:       0000 0004 7227 0448
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Perioperative hypercoagulability may manifest as thromboembolic complications, such as myocardial infarction, deep vein thrombosis and pulmonary thromboembolism, which are critical pathological events that increase postoperative morbidity. Reducing the incidence of both venous and arterial thromboses are key goals of improving perioperative outcomes. A large observational cohort study comprehensively characterised the alterations in coagulation status following major intra-abdominal surgery. Results confirmed that postoperative hypercoagulability is seen up to at least postoperative day 5. This prothrombotic phenotype was diagnosed by predefined thromboelastography criteria and not by conventional coagulation tests. Goal directed fluid therapy in the immediate perioperative phase was associated with excessive fluid administration but no adverse effect in terms of haemodilution-induced TEG-defined hypercoagulability. However, patients receiving goal directed therapy showed evidence of a higher degree of glycocalyx damage. Inflammation-induced hypercoagulability and scope for potential modification by putative anti-thrombotic agents were further explored using an ex vivo experimental model in healthy subjects and preoperative surgical patients. Statin and steroid therapy attenuated, while anti-oxidant N-acetylcysteine exacerbated, the prothrombotic state in the presence of inflammation. The concept of cholinergic autonomic modulation of coagulation was supported by suppression of the hypercoagulable response by nicotine in the same model. In summary, perioperative hypercoagulability is common in the elective major surgical population and is associated with adverse outcome. Data from this thesis confirm a patient phenotype at increased risk of thromboembolic complications. Thrombotic risk may be modified by existing perioperative therapies which require further mechanistic evaluation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available