Fibrin D-dimer and beta-thromboglobulin as markers of thrombogenesis and platelet activation in atrial fibrillation - Effects of introducing ultra-low-dose warfarin and aspirin

Background Previous studies have demonstrated increased markers of thrombogenesis in patients with atrial fibrillation (AF), suggesting the presence of a hypercoagulable or prothrombotic state. The objective of this study was to determine the effects of introducing ultra-low-dose warfarin (1 mg), conventional warfarin, and aspirin (300 mg) therapy on thrombogenesis and platelet activation in AF. Methods and Results We measured sequential changes in plasma fibrin D-dimer (an index of thrombogenesis) and beta-thromboglobulin (beta-TG, a measure of platelet activation) in 51 patients with chronic AF before and at 2 and 6 weeks after randomization to either 1 mg warfarin or 300 mg aspirin (phase 1). Then all patients were started on conventional warfarin therapy (phase 2) with samples taken 2 and 6 weeks later. Pretreatment results were compared with those from 26 healthy control subjects in sinus rhythm. Baseline (pretreatment) beta-TG and D-dimer levels in patients with AF were elevated compared with those of control subjects (P<.001). In phase 1, there were no significant changes in median levels of fibrin D-dimer or beta-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median beta-TG at 6 weeks (P=.025) and a sequential reduction in median D-dimer levels at 2 (P=.001) and 6 (P<.001) weeks compared with baseline levels. Conclusions Patients with AF have increased intravascular thrombogenesis and platelet activation compared with patients in sinus rhythm. Introduction of ultra-low-dose warfarin (1 mg) or aspirin 300 mg does not significantly alter these markers, although conventional warfarin therapy reduces beta-TG and fibrin D-dimer levels. This is consistent with the beneficial effect of full-dose warfarin in preventing stroke and thromboembolism in AF and suggests that ultra-low-dose warfarin and aspirin may not exert similar beneficial effects.