Fibrin d -Dimer and β-Thromboglobulin as Markers of Thrombogenesis and Platelet Activation in Atrial Fibrillation

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 β-thromboglobulin (β-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) β-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 β-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median β-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 β-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.