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Title: Prothrombotic phenotype in morbidly obsese patients and in individuals with sleep apnoea
Author: Chitongo , Paradzai Boniface
ISNI:       0000 0004 5351 4726
Awarding Body: University of the West of England, Bristol
Current Institution: University of the West of England, Bristol
Date of Award: 2014
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Morbid obesity is associated with increased cardiovascular risk and thrombosis is a critical component of cardiovascular risk. Although obesity is considered a modifiable risk factor for venous thromboembolism (VTE) , the mechanism and impact of fat distribution is not clearly defined. This is the first comprehensive study to assess the prothrombotic phenotype in morbidly obese patients as well as linking with abdominal fat distribution markers and obstructive sleep apnoea. A cross-sectional study on morbidly obese patients aged 18 -65 years was initiated to characterise the prothrombotic phenotype in this patient group. Eighty nine patients with a BMI >30kgm-2 and no history of VTE were recruited from the obesity clinic at King's college hospital. Seventy-seven age and sex matched ambulatory control subjects were also recruited from volunteers. The study also investigated the impact of obesity comorbidities; sleep apnoea and metabolic syndrome on the hypercoagulable state. Obesity was assessed by BMI and abdominal fat distribution was determined by analysing computerised tomography (CT) images taken at lumber 4 (L4). Fasting samples were obtained for thrombophilia screening, thrombin generation test, plasminogen activator I inhibitor (PAl), free tissue plasminogen activator inhibitor (TFPI), factor VII, factor VIII, D Dimer (DD), glucose, insulin, full lipid profile and adiponectin. Thrombin generation as measured by endogenous thrombin potential (ETP) was significantly increased in the patient group (p<0.001). The thrombin lag time was unexpectedly extended in the patient group (p< 0.001) suggesting some unexplained attenuation. Other prothrombotic markers such as fibrinogen and factor VIII were also raised. Visceral abdominal adipose tissue area (VAT) was directly associated with haemostatic markers and there was no association with subcutaneous abdominal adipose tissue area (SAT). Obstructive sleep apnoea prevalence and severity was directly associated with VAT but not with SAT. The study concludes that morbid obesity confers a prothrombotic phenotype characterised by raised prothrombotic markers and hypofibrinolysis. The study demonstrates for the first time that VAT is much more significant in defining the hypercogulability state and SAT may not be significant in defining the prothrombotic state. The study also confirms that VAT is the more pathologic fat compartment in OSA prevalence and severity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available