CLINICAL STUDIES
A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation
Foo Leong Li-Saw-Hee, MRCPa,
Andrew D. Blann, PhD, MRCPatha and
Gregory Y. H. Lip, MD, FRCPE, FACCa
a Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom
Manuscript received December 22, 1998;
revised manuscript received December 16, 1999,
accepted February 9, 2000.
Reprint requests and correspondence: Dr. Gregory YH Lip, Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Dudley Road, Birmingham B18 7QH, United Kingdom
G.Y.H.LIP{at}bham.ac.uk
OBJECTIVES
First, we sought to determine whether there is diurnal variation in hemostatic factors related to thrombogenesis and hypercoagulability among patients with chronic atrial fibrillation (AF). Second, we sought to determine whether levels of soluble thrombomodulin (sTM), a marker of endothelial function, or soluble P-selectin (sP-sel), an index of platelet activation, are altered in patients with AF as compared with subjects in sinus rhythm.
BACKGROUND
Atrial fibrillation is associated with an increased risk of stroke and thromboembolism and is known to confer a hypercoagulable state, with abnormalities of thrombosis, platelet activation and endothelial cell function. Many cardiovascular events, such as acute myocardial infarction, have thrombosis as an underlying process, and they undergo diurnal variation.
METHODS
Fifty-two patients (45 men, mean [±SD] age 66 ± 6 years) with chronic AF, none of whom received antithrombotic therapy, were studied. Baseline levels of fibrinogen, sP-sel, sTM and von Willebrand factor (vWF) were compared to those levels in matched healthy control subjects in sinus rhythm. In a subgroup of 20 patients, five venous blood samples were collected through an indwelling cannula at 6-h intervals from 12 PM to 12 PM the following day and were analyzed for the same markers.
RESULTS
Patients with chronic AF had higher plasma sP-sel, sTM, vWF and fibrinogen levels as compared with control subjects in sinus rhythm. Significant correlations were found between fibrinogen and sP-sel in patients with AF (r = 0.567 [Spearman], p < 0.001) and in control subjects (r = 0.334, p = 0.016). There was no significant diurnal variation in plasma levels of sP-sel, sTM, vWF or fibrinogen over the 24-h study period (repeated measures analysis of variance, p = NS).
CONCLUSIONS
There is no circadian or diurnal variation in the hypercoagulable state seen in AF, as assessed by plasma fibrinogen and markers of platelet (sP-sel) and endothelial function (vWF and sTM). The persistent hypercoagulable state, together with the loss of diurnal variation in various hemostatic markers, in chronic AF may contribute to the high risk of stroke and thromboembolic complications in these patients.
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Abbreviations and Acronyms
| | AF | = atrial fibrillation | | sP-sel | = soluble P-selectin | | sTM | = soluble thrombomodulin | | vWF | = von Willebrand factor |
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