P4744Patients with atrial fibrillation exhibit a systemic prothrombotic state attributable to impaired endogenous fibrinolysis

Abstract

Abstract Background The association of atrial fibrillation (AF) with thromboembolic stroke due to stasis in the left atrium and left atrial appendage is well described. Whether AF is associated with a systemic prothrombotic state, detectable in peripheral blood, unclear. Previous studies have been inconsistent, with some very small previous studies (<30 patients each) variably indicating that patients with AF may have raised platelet reactivity and levels of antithrombin III, d-dimer, PAI-1 and t-PA-PAI complexes. These cumbersome laboratory tests of coagulation and fibrinolysis are not readily available in the clinical setting. Purpose It was our aim to compare, in peripheral venous blood, thrombotic and endogenous fibrinolytic profile of healthy volunteers and patients with newly diagnosed nonvalvular atrial fibrillation (NVAF), using a point-of-care technique. Methods In a prospective observational study, venous blood samples were taken from 98 healthy volunteers and 100 patients with newly diagnosed NVAF in the out-patient setting. Patients with newly diagnosed NVAF had venous blood tested before any treatment was initiated with aspirin or oral anticoagulation. Thrombotic status was assessed using the Global Thrombosis Test (GTT), a point-of-care test using native non-coagulated blood, assessed within 15 sec of blood withdrawal. The time to form an occlusive venous thrombus in native (non-citrated) blood, a measure of platelet reactivity (occlusion time, OT) and the time taken to spontaneous endogenous fibrinolysis to restore flow (lysis time, LT) were assessed. Results Basic blood tests (full blood count, renal and liver function, inflammatory markers) were normal in all subjects. The groups were matched for sex and race. Mean age of the healthy cohort was 34±8 years and patients 65±10 years. Endogenous fibrinolysis was markedly impaired in patients with NVAF compared to healthy individuals as shown by markedly prolonged LT (median 2015s [interquartile range IQR 1555–2507] vs. 1124s [IQR 919–1554], p<0.ehz745.11201). There was no difference in platelet reactivity between patients and normal volunteers (369s [IQR 308–445]vs 368s [IQR 309–441], p=0.704). Sensitivity analysis was performed on a subgroup matched for age, sex and race. LT remained significantly longer in patients with NVAF compared to controls (1569s [IQR 1499–2244] vs. 1219s [IQR 943–1560], p=0.03), with no difference in platelet reactivity (p=NS). Conclusion In the largest study to date and using a clinically-friendly automated point-of-care technique, we show that patients with NVAF exhibit a systemic prothrombotic state, attributable to significantly impaired endogenous fibrinolysis compared with healthy volunteers. Further studies are needed to see if this could become a screening test for the prothrombotic state in patients with NVAF. Acknowledgement/Funding None