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.

[1]  G. Lip,et al.  Fibrin D-dimer: a useful clinical marker of thrombogenesis? , 1995, Clinical science.

[2]  D. Beevers,et al.  The role of platelets in essential hypertension. , 1995, Blood pressure.

[3]  G. Lip,et al.  Increased markers of thrombogenesis in chronic atrial fibrillation: effects of warfarin treatment. , 1995, British heart journal.

[4]  G. Lip.  Fibrinogen and cardiovascular disorders. , 1995, QJM : monthly journal of the Association of Physicians.

[5]  P. Ridker,et al.  Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. , 1994, Circulation.

[6]  H. Tunstall-Pedoe,et al.  Geographical variations in plasma viscosity and relation to coronary event rates , 1994, The Lancet.

[7]  H. Katayama,et al.  Contrast sonography for detection of vesicoureteral reflux , 1994, The Lancet.

[8]  J. Hirsh,et al.  Double-blind randomised trial of very-low-dose warfarin for prevention of thromboembolism in stage IV breast cancer , 1994, The Lancet.

[9]  F. Dunn,et al.  Treatment of atrial fibrillation in a district general hospital. , 1994, British heart journal.

[10]  A. Rumley,et al.  Cross-linked fibrin degradation products, progression of peripheral arterial disease, and risk of coronary heart disease , 1993, The Lancet.

[11]  E. Ernst,et al.  Fibrinogen as a Cardiovascular Risk Factor , 1993, Annals of Internal Medicine.

[12]  G. Lowe.  Antithrombotic treatment and atrial fibrillation. , 1992, BMJ.

[13]  D. Singer,et al.  The effect of aspirin on the risk of stroke in patients with nonrheumatic atrial fibrillation: The BAATAF Study. , 1992, American heart journal.

[14]  Lippincott Williams Wilkins,et al.  Stroke Prevention in Atrial Fibrillation Study: Final Results , 1991, Circulation.

[15]  T. Kamada,et al.  Increased intracardiovascular clotting in patients with chronic atrial fibrillation. , 1990, Journal of the American College of Cardiology.

[16]  Palle Petersen,et al.  PLACEBO-CONTROLLED, RANDOMISED TRIAL OF WARFARIN AND ASPIRIN FOR PREVENTION OF THROMBOEMBOLIC COMPLICATIONS IN CHRONIC ATRIAL FIBRILLATION The Copenhagen AFASAK Study , 1989, The Lancet.

[17]  G. Lowe.  Blood rheology in arterial disease. , 1986, Clinical science.

[18]  D. Rylatt,et al.  Serum crosslinked fibrin (XDP) and fibrinogen/fibrin degradation products (FDP) in disorders associated with activation of the coagulation or fibrinolytic systems , 1985, British journal of haematology.

[19]  H. White,et al.  Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation : stroke prevention in atrial fibrillation II study. Commentary , 1994 .

[20]  M. Blombäck,et al.  Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. , 1990, Stroke.