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.


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.
Lip
G Y
GY
Department of Medicine, City Hospital, Birmingham, England, UK.
Lip
P L
PL
Zarifis
J
J
Watson
R D
RD
Bareford
D
D
Lowe
G D
GD
Beevers
D G
DG
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects*; D011446:Prospective Studies; D013927:Thrombosis / Q000209:etiology*; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use; D001620:beta-Thromboglobulin / Q000378:metabolism*
D005338:Fibrin Fibrinogen Degradation Products; D001620:beta-Thromboglobulin; D014859:Warfarin; D001241:Aspirin