Clot structure and plasma microparticles in atrial fibrillation

• Main Author: Voukalis, Christos
• Format: Dissertation
• Language: English
• Published: University of Birmingham 2020
• Subjects: R Medicine (General)

Chronic oral anticoagulation (OAC) is an important decision related with stroke thromboprophylaxis in non-valvular atrial fibrillation (NVAF). Almost a decade after the approval of Non vitamin K oral anticoagulants (NOACs) for prevention of thromboembolic events in NVAF, there is now confidence regarding their efficacy and safety as real word evidence complements the findings from the phase III pivotal trials. NOACs favourable safety profile against warfarin have changed the threshold of starting OAC, even with lower risk for systemic thromboembolism. Apixaban, one of the four licenced NOACs for stoke prevention in NVAF, even at the higher recommended dose (5mg BID), has significantly reduced the haemorrhagic complications but there is still a considerable risk of intracranial bleeding. This MD research thesis studies the influence of antithrombotics (aspirin, warfarin and apixaban) on the fibrin polymerisation and fibrinolysis pathway. To highlight antithrombotic activity variances, this analysis is based on dynamic assays and biomarker quantification related with clot structure features. Additionally, explores possible relationship between microparticle levels and physical status in NVAF patients. My findings suggest that NVAF is associated with impaired haemostasis and each antithrombotic class is related to different clot structure characteristics. Apixaban has distinctive anticoagulation dynamics and induces a reduction of coagulation biomarkers. My results also support that microparticles levels may be a useful marker of physical status as suggested by the relation between objective (cardiopulmonary exercise test) and subjective (quality of life questionnaire - EQ5D5L) evidence of fitness level.