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

Abstract

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.