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Stroke. 1999;30:2547-2553

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(Stroke. 1999;30:2547.)
© 1999 American Heart Association, Inc.


Original Contributions

Markers of Thrombin and Platelet Activity in Patients With Atrial Fibrillation

Correlation With Stroke Among 1531 Participants in the Stroke Prevention in Atrial Fibrillation III Study

William M. Feinberg, MD1; Lesly A. Pearce, MS; Robert G. Hart, MD; Mary Cushman, MD; Elaine S. Cornell, BA; Gregory Y.H. Lip, MD; Edwin G. Bovill, MD for the Stroke Prevention in Atrial Fibrillation Investigators

From the Department of Neurology, the University of Arizona, Tucson, Ariz (W.M.F.); Axio Research Corporation, Seattle, Wash (L.A.P.); University of Texas at San Antonio (R.G.H.); Laboratory for Clinical Biochemical Research, Department of Pathology, University of Vermont, Burlington, Vt (M.C., E.S.C., E.G.B.); and Haemostasis Thrombosis and Vascular Biology Unit, City Hospital, Birmingham, UK (G.Y.H.L.).

Correspondence to Robert G. Hart, MD, Department of Medicine (Neurology), University of Texas HSC, 7703 Floyd Curl Dr, San Antonio, TX 78284. E-mail HartR{at}uthscsa.edu

Background and Purpose—Markers of thrombin generation and platelet activation are often elevated in patients with nonvalvular atrial fibrillation, but it is unclear whether such markers usefully predict stroke. Therefore, we undertook the present study to assess the relationship between prothrombin fragment F1.2 (F1.2), ß-thromboglobulin (BTG), fibrinogen, and the factor V Leiden mutation with stroke in atrial fibrillation.

Methods—Specimens were obtained from 1531 participants in the Stroke Prevention in Atrial Fibrillation III study. The results were correlated with patient features, antithrombotic therapy, and subsequent thromboembolism (ischemic stroke and systemic embolism) by multivariate analysis.

Results—Increased F1.2 levels were associated with age (P<0.001), female sex (P<0.001), systolic blood pressure (P=0.006), and heart failure (P=0.001). F1.2 were not affected by aspirin use and were not associated with thromboembolism after adjustment for age (P=0.18). BTG levels were higher with advanced age (P=0.006), coronary artery disease (P=0.05), carotid disease (P=0.005), and heart failure (P<0.001), lower in regular alcohol users (P=0.05), and not significantly associated with thromboembolism. Fibrinogen levels were not significantly related to thromboembolism but were associated with elevated BTG levels (P<0.001). The factor V Leiden mutation was not associated with thromboembolism (relative risk 0.5, 95% CI 0.1 to 3.8).

Conclusions—Elevated F1.2 levels were associated with clinical risk factors for stroke in atrial fibrillation, whereas increased BTG levels were linked to manifestations of atherosclerosis. In this large cohort of patients with atrial fibrillation who were receiving aspirin, F1.2, BTG, fibrinogen, and factor V Leiden were not independent, clinically useful predictors of stroke.


Key Words: atrial fibrillation • coagulation • fibrinogen • platelet activation • thrombin




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