(Circulation. 1996;94:425-431.)
© 1996 American Heart Association, Inc.
Articles |
Fibrin D-Dimer and ß-Thromboglobulin as Markers of Thrombogenesis and Platelet Activation in Atrial Fibrillation
Effects of Introducing Ultra–Low-Dose Warfarin and Aspirin
the Departments of Medicine (G.Y.H.L., P.L.L., J.Z., R.D.S.W., D.G.B.) and Haematology (D.B.), City Hospital, Birmingham, England, and the Department of Medicine (G.D.O.L.), Royal Infirmary, Glasgow, Scotland.
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 ß-thromboglobulin (ß-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) ß-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 ß-TG, despite warfarin 1 mg or aspirin 300 mg. With standard warfarin therapy (phase 2), there was a reduction in median ß-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 ß-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.
Key Words: fibrillation • fibrin • aspirin • anticoagulants • thrombosis
This article has been cited by other articles:
 |
|
 |
|
  H. Duygu, V. Barisik, H. Kurt, U. Turk, E. Ercan, and S. Kose Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation Europace, February 1, 2008; 10(2): 210 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Choudhury, B. Freestone, J. Patel, and G. Y. H. Lip Relationship of Soluble CD40 Ligand to Vascular Endothelial Growth Factor, Angiopoietins, and Tissue Factor in Atrial Fibrillation: A Link Among Platelet Activation, Angiogenesis, and Thrombosis? Chest, December 1, 2007; 132(6): 1913 - 1919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Cohen, S. Ederhy, C. Meuleman, E. Di Angelantonio, G. Dufaitre, and F. Boccara D-dimers in atrial fibrillation: a further step in risk stratification of thrombo-embolism? Eur. Heart J., September 2, 2007; 28(18): 2179 - 2180. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Choudhury, I. Chung, A. D. Blann, and G. Y.H. Lip Platelet Surface CD62P and CD63, Mean Platelet Volume, and Soluble/Platelet P-Selectin as Indexes of Platelet Function in Atrial Fibrillation: A Comparison of "Healthy Control Subjects" and "Disease Control Subjects" in Sinus Rhythm J. Am. Coll. Cardiol., May 15, 2007; 49(19): 1957 - 1964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]
|
|
|
|
|
|
H. Inoue, T. Nozawa, K. Okumura, L. Jong-Dae, A. Shimizu, and K. Yano Prothrombotic Activity Is Increased in Patients With Nonvalvular Atrial Fibrillation and Risk Factors for Embolism Chest, September 1, 2004; 126(3): 687 - 692. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. D.O. Lowe, A. Rumley, A. D. McMahon, I. Ford, D. St. J. O'Reilly, C. J. Packard, and for the West of Scotland Coronary Prevention Study Interleukin-6, Fibrin D-Dimer, and Coagulation Factors VII and XIIa in Prediction of Coronary Heart Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2004; 24(8): 1529 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Heim, J. M. Schectman, M. S. Siadaty, and J. T. Philbrick D-Dimer Testing for Deep Venous Thrombosis: A Metaanalysis Clin. Chem., July 1, 2004; 50(7): 1136 - 1147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. G. Conway, P. Buggins, E. Hughes, and G. Y. H. Lip Relationship of interleukin-6 and C-Reactive protein to the prothrombotic state in chronic atrial fibrillation J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2075 - 2082. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sakurai, T. Hirai, K. Nakagawa, T. Kameyama, T. Nozawa, H. Asanoi, and H. Inoue Left Atrial Appendage Function and Abnormal Hypercoagulability in Patients With Atrial Flutter Chest, November 1, 2003; 124(5): 1670 - 1674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Schrecengost, R. D. LeGallo, J. C. Boyd, K. G.M. Moons, S. L. Gonias, C. E. Rose Jr, and D. E. Bruns Comparison of Diagnostic Accuracies in Outpatients and Hospitalized Patients of D-Dimer Testing for the Evaluation of Suspected Pulmonary Embolism Clin. Chem., September 1, 2003; 49(9): 1483 - 1490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Roldan, F. Marin, A. D Blann, A. Garcia, P. Marco, F. Sogorb, and G. Y.H Lip Interleukin-6, endothelial activation and thrombogenesis in chronic atrial fibrillation Eur. Heart J., July 2, 2003; 24(14): 1373 - 1380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Wakai, A Gleeson, and D Winter Role of fibrin D-dimer testing in emergency medicine Emerg. Med. J., July 1, 2003; 20(4): 319 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Wassertheil-Smoller, S. Hendrix, M. Limacher, G. Heiss, C. Kooperberg, A. Baird, T. Kotchen, J. D. Curb, H. Black, J. E. Rossouw, et al. Effect of Estrogen Plus Progestin on Stroke in Postmenopausal Women: The Women's Health Initiative: A Randomized Trial JAMA, May 28, 2003; 289(20): 2673 - 2684. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Marin, V. Roldan, V. Climent, A. Garcia, P. Marco, and G. Y.H. Lip Is Thrombogenesis in Atrial Fibrillation Related to Matrix Metalloproteinase-1 and Its Inhibitor, TIMP-1? Stroke, May 1, 2003; 34(5): 1181 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Ageno, S. Finazzi, L. Steidl, M. G. Biotti, V. Mera, G. Melzi d'Eril, and A. Venco Plasma Measurement of D-Dimer Levels for the Early Diagnosis of Ischemic Stroke Subtypes Arch Intern Med, December 9, 2002; 162(22): 2589 - 2593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kamath, A. D. Blann, B. S. P. Chin, F. Lanza, B. Aleil, J. P. Cazenave, and G. Y. H. Lip A study of platelet activation in atrial fibrillation and the effects of antithrombotic therapy Eur. Heart J., November 2, 2002; 23(22): 1788 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S.G. Conway, L. A. Pearce, B. S.P. Chin, R. G. Hart, and G. Y.H. Lip Plasma von Willebrand Factor and Soluble P-Selectin as Indices of Endothelial Damage and Platelet Activation in 1321 Patients With Nonvalvular Atrial Fibrillation: Relationship to Stroke Risk Factors Circulation, October 8, 2002; 106(15): 1962 - 1967. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kamath, A. D. Blann, B. S. P. Chin, and G. Y. H. Lip A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation J. Am. Coll. Cardiol., August 7, 2002; 40(3): 484 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kamath, A. D. Blann, G. J. Caine, D. Gurney, B. S.P. Chin, and G. Y.H. Lip Platelet P-Selectin Levels in Relation to Plasma Soluble P-Selectin and {beta}-Thromboglobulin Levels in Atrial Fibrillation Stroke, May 1, 2002; 33(5): 1237 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakagawa, T. Hirai, N. Shinokawa, S. Takashima, T. Nozawa, H. Asanoi, and H. Inoue Aortic Spontaneous Echocardiographic Contrast and Hemostatic Markers in Patients With Nonrheumatic Atrial Fibrillation Chest, February 1, 2002; 121(2): 500 - 505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kamath, A.D. Blann, and G.Y.H. Lip Platelets and atrial fibrillation Eur. Heart J., December 2, 2001; 22(24): 2233 - 2242. [PDF]
|
|
|
|
|
|
Guidelines for the management of patients with atrial fibrillation. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology Eur. Heart J., October 2, 2001; 22(20): 1852 - 1923. [PDF]
|
|
|
|
|
|
V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1266 - 1266. [Full Text] [PDF]
|
|
|
|
|
|
N.M. Al-Saady and M. Sopher Prothrombotic markers in atrial fibrillation: what is new? Eur. Heart J., September 2, 2001; 22(18): 1635 - 1639. [PDF]
|
|
|
|
|
|
J. Danesh, P. Whincup, M. Walker, L. Lennon, A. Thomson, P. Appleby, A. Rumley, and G. D.O. Lowe Fibrin D-Dimer and Coronary Heart Disease : Prospective Study and Meta-Analysis Circulation, May 15, 2001; 103(19): 2323 - 2327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sagedal, A. Hartmann, K. Sundstrom, S. Bjornsen, and F. Brosstad Anticoagulation intensity sufficient for haemodialysis does not prevent activation of coagulation and platelets Nephrol. Dial. Transplant., May 1, 2001; 16(5): 987 - 993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fukuchi, J. Watanabe, K. Kumagai, Y. Katori, S. Baba, K. Fukuda, T. Yagi, A. Iguchi, H. Yokoyama, M. Miura, et al. Increased von Willebrand factor in the endocardium as a local predisposing factor for thrombogenesis in overloaded human atrial appendage J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1436 - 1442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Bew, A. E. Bryant, J. P. Desborough, and G. M. Hall Epidural analgesia and arterial reconstructive surgery to the leg: effects on fibrinolysis and platelet degranulation Br. J. Anaesth., February 1, 2001; 86(2): 230 - 235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Frost, G. Engholm, S. Johnsen, H. Moller, E. W. Henneberg, and S. Husted Incident Thromboembolism in the Aorta and the Renal, Mesenteric, Pelvic, and Extremity Arteries After Discharge From the Hospital With a Diagnosis of Atrial Fibrillation Arch Intern Med, January 22, 2001; 161(2): 272 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Cote, C. Wolfson, S. Solymoss, A. Mackey, J. R Leclerc, D. Simard, F. Rouah, F. Bourque, and B. Leger Hemostatic Markers in Patients at Risk of Cerebral Ischemia Stroke, August 1, 2000; 31(8): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L. Li-Saw-Hee, A. D. Blann, and G. Y. H. Lip A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1926 - 1931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. L. Li-Saw-Hee, A. D. Blann, and G. Y. H. Lip Effects of Fixed Low-Dose Warfarin, Aspirin-Warfarin Combination Therapy, and Dose-Adjusted Warfarin on Thrombogenesis in Chronic Atrial Fibrillation Stroke, April 1, 2000; 31(4): 828 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. M. Feinberg, L. A. Pearce, R. G. Hart, M. Cushman, E. S. Cornell, G. Y.H. Lip, and E. G. Bovill 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 Stroke, December 1, 1999; 30(12): 2547 - 2553. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minamino, M. Kitakaze, S. Sanada, H. Asanuama, T. Kurotobi, Y. Koretsune, M. Fukunami, T. Kuzuya, N. Hoki, and M. Hori Increased Expression of P-Selectin on Platelets Is a Risk Factor for Silent Cerebral Infarction in Patients With Atrial Fibrillation : Role of Nitric Oxide Circulation, October 27, 1998; 98(17): 1721 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minamino, M. Kitakaze, H. Sato, H. Asanuma, H. Funaya, Y. Koretsune, and M. Hori Plasma Levels of Nitrite/Nitrate and Platelet cGMP Levels Are Decreased in Patients With Atrial Fibrillation Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3191 - 3195. [Abstract] [Full Text]
|
|