ABNORMAL FIBRIN CLOT STRUCTURE IN ATRIAL FIBRILLATION

Abstract

In atrial fibrillation (AF), there may be unequal burden of thrombosis and bleeding risk due to altered fibrin clot structure. This has implications for Vitamin K Antagonist (VKA) use. Coagulation and clot lysis can be assessed by Thrombelastography (TEG), fibrinolysis and turbidimetric assay. Plasma samples from 53 AF patients on VKA and 15 controls in sinus rhythm were analysed by TEG, fibrinolysis assay and turbidimetric assay. From TEG significant abnormalities in indices were seen in AF compared to controls: elevated mean R-time (19.9 minutes vs 5.95 minutes, p <0.0001) and increased mean K-time (4.28 minutes vs 1.84 minutes, p =0.002), while α-angle was reduced (46.1° vs 69.8°, p<0.0001). Maximum Amplitude and Percentage of Clot Lysed at 60 minutes were not significantly different. Turbidimetric analysis revealed increased absorbance of light through fibrin clot in AF patients (0.576 vs 0.487, p=0.004). Fibrinolysis assay showed prolonged time to lyse 50% of clot (29.9minutes vs 18.4 minutes, p<0.0001) and a less steep slope of fibrin clot lysis in AF subjects (-0.92 vs -1.79, p<0.0001). Thromboelastography confirms VKA activity in delaying coagulation, as illustrated by increased R and K times.Abnormal thrombogenesis in AF is illustrated by the reduced rate of fibrin build-up and reduced fibrinogen levels, as represented by the less acute α-angle. Fibrin clot formed in presence of AF are made of thicker protofibril monomers (represented by increased absorbance), which is also more resistant to fibrinolysis (prolonged time and reduced rate of lysis). This may potentially explain the abnormal thrombosis and haemorrhage risk associated with AF.