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Title: Thrombotic status of patients with atrial fibrillation
Author: Niespialowska-Steuden, Maria
ISNI:       0000 0004 9356 666X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Background: Atrial fibrillation (AF) is associated with increased risk of thrombosis. It is still not fully understood whether AF contributes to only a local prothrombotic state (in the left atrium) or whether this is a systemic phenomenon. Furthermore, it is not known whether restoration of sinus rhythm (SR) with cardioversion or catheter ablation can decrease thrombotic risk over and above that achieved with anticoagulation. The aim of my thesis was to assess the effect of restoration of sinus rhythm on thrombotic status in patients with AF. Methods: We assessed thrombotic status, both peripherally and in the cardiac chambers, in patients with different arrhythmias undergoing radiofrequency catheter ablation (RFCA) with blood samples drawn from the femoral vein and both atria (if applicable). In another study, we investigated the effect of direct current cardioversion (DCCV) and RFCA on global thrombotic status. The peripheral samples were drawn before and 4-6 weeks after DCCV and 3 months after RFCA. The effect of different types of anticoagulation, namely vitamin K antagonist and non-vitamin K oral anticoagulants, on thrombotic status was also assessed. Thrombotic status was assessed with highly physiological, point-of-care Global Thrombosis Test (GTT), which assesses both platelet reactivity (time taken to form an occlusive thrombus - occlusion time, OT) and endogenous thrombolysis (time taken to restore blood flow in the testing column – lysis time, LT) using a native, non-anticoagulated blood sample. Results: There were no significant differences in thrombotic status between intra-cardiac and peripheral blood in patients undergoing RFCA. In particular, left atrial blood samples were not more pro-thrombotic than peripheral blood samples in patients with AF. Successful restoration and maintenance of SR with RFCA led to normalization of fibrinolytic profile (as shown by decrease in LT: LT before RFCA: 1994s [1560; 2475] vs. LT after RFCA: 1477s [1015; 1878]; p<0.001). This was not seen following DCCV. Interestingly, recurrence of AF after DCCV or RFCA resulted in deterioration of thrombotic status (increase in LT), (LT before DCCV: 1819s [1453; 2208] vs. LT after DCCV: 2156s [1784; 2332]; p=0.009). Anticoagulation led to significantly enhanced occlusion time with the most significant change observed in response to rivaroxaban (OT before anticoagulation: 353s [311; 482] vs. OT on anticoagulation: 552s [464; 725]; p=0.000089). Although a similar trend was seen with all NOAC, only apixaban had a favourable effect on fibrinolysis (decrease in LT), (LT before anticoagulation: 1848s [1675; 2166] vs. LT after anticoagulation: 1471s [361; 1993]; p=0.009). Among patient taking oral anticoagulants, a short LT, with rapid endogenous fibrinolysis, with a cut-point of 1346 s, was predictive of future bleeding events with the specificity of 82% and sensitivity of 72%. Combining the LT with the HASBLED score increased specificity to 94.6%, while reducing sensitivity to 50%. Conclusion: Patients with AF appear to have a prothrombotic state that is not confined to the left atrium. Oral anticoagulation significantly reduced platelet reactivity, and demonstrated a trend to improved endogenous fibrinolysis. Restoration of SR in patients with AF, using RFCA, appears to exert a favourable effect on thrombotic status in AF patients, over and above that of anticoagulation. Rapid endogenous fibrinolysis with short LT on anticoagulation may be useful to predict bleeding in patients with AF. Further studies are required to validate these results in larger cohorts.
Supervisor: Collins, Peter ; Gorog, Diana A. Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral