Detection of a Hypercoagulable State in Nonvalvular Atrial Fibrillation and the Effect of Anticoagulant Therapy

 

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Summary

The purpose of the study was to evaluate alterations of the hemostatic system and the effect of anticoagulant therapy in nonvalvular atrial fibrillation. A set of molecular hematologic markers was measured prospectively in 69 patients with atrial fibrillation and 28 age-matched patients in sinus rhythm. Significantly elevated levels of thrombin-antithrombin III complex (8.5 ± 1.6 vs. 2.5 ± 0.3 αg/1; p <0.001), fibrin monomers (27.1 ± 3.2 vs. 13.4 ± 3.7 nM; p <0.001), D-dimers (788 ± 76 vs. 405 ± 46 αg/l; p <0.005), and tissue-type plasminogen activator (9.6 ± 0.5 vs. 7.2 ± 0.5 αg/l; p <0.05) were observed in patients with atrial fibrillation compared to those in sinus rhythm. In a subgroup of patients in whom anticoagulant therapy with oral coumadin or standard intravenous heparin was established after the initial study, hemostatic activation decreased significantly. In conclusion, molecular hematologic markers indicate a hypercoagulable state in atrial fibrillation which may characterize a group of patients at elevated risk for thromboembolic disease.

• References

• 1 Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials. Arch Intern Med 1994 154. 1449-1457
  PubMedGoogle Scholar
• 2 EAFT Study Group. Secondary prevention in non-rheumatic atrial fibrillation after transient ischemic attack or minor stroke. Lancet 1993 342. 1255-1262
  PubMedGoogle Scholar
• 3 Daniel WG, Nellesen U, Schröder E, Nonnast-Daniel B, Bednarski P, Nikutta P, Lichtlen PR. Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk. J Am Coll Cardiol 1988; 11: 1204-1211
  CrossrefPubMedGoogle Scholar
• 4 Black IW, Hopkins AP, Lee LCL, Walsh WF. Left atrial spontaneous echo contrast: A clinical and echocardiographic analysis. J Am Coll Cardiol 1991; 18: 398-404
  CrossrefPubMedGoogle Scholar
• 5 Mitusch R, Lange V, Stierle U, Maurer B, Sheikhzadeh A. Transesophageal echocardiographic determinants of embolism in nonrheumatic atrial fibrillation. Int J Card Imaging 1995; 11: 27-34
  PubMedGoogle Scholar
• 6 Mügge A, Kühn H, Nikutta P, Grotey J, Lopez JAG, Daniel WG. Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: Identification of a subgroup of patients at increased embolic risk. J Am Coll Cardiol 1994; 23: 599-607
  CrossrefPubMedGoogle Scholar
• 7 Mitusch R, Garbe M, Schmiicker G, Schwabe K, Stierle U, Sheikhzadeh A. Relation of left atrial appendage function to the duration and reversibility of non-valvular atrial fibrillation. Am J Cardiol 1995; 75: 944-947
  CrossrefPubMedGoogle Scholar
• 8 Gustafsson C, Blombäck M, Britton M, Hamsten A, Svensson J. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 1990; 21: 47-51
  CrossrefPubMedGoogle Scholar
• 9 Bauer KA, Rosenberg RD. The pathophysiology of the prethrombotic state in humans: Insights gained from studies using markers of hemostatic system activation. Blood 1987; 70: 343-350
  PubMedGoogle Scholar
• 10 Contant G, Gouault-Heilmann M, Martinoli JL. Heparin inactivation during blood storage: Its prevention by blood collection in citric acid, theophylline, adenosine, dipyridamol - C.T.A.D. Mixture. Thromb Res 1983; 31: 365-374
  CrossrefPubMedGoogle Scholar
• 11 Kistler JP, Singer DE, Millensen MM, Bauer KA, Gress DR, Barzegar S, Hughes RA, Sheehan MA, Maraventano SW, Oertel LB, Rosner B, Rosenberg RD. for the BAATAF Investigators. Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. Stroke 1993; 24: 1360-1365
  CrossrefPubMedGoogle Scholar
• 12 Kumagai K, Fukunami M, Ohmori M, Kitabatake A, Kamada T, Hoki N. Increased intracardiovascular clotting in patients with chronic atrial fibrillation. J Am Coll Cardiol 1990; 16: 377-380
  CrossrefPubMedGoogle Scholar
• 13 Uno M, Tsuji H, Sawada S, Toyoda T, Nakagawa M. Fibrinopeptide A (FPA) levels in atrial fibrillation and the effects of heparin administration. Jpn Circ J 1988; 52: 9-12
  CrossrefPubMedGoogle Scholar
• 14 Asakura H, Hifumi S, Jokaji H, Saito M, Kumabashiri I, Uotani C, Mori-shita E, Yamzaki M, Shibata K, Mizuhashi K. Prothrombin fragment F1 + 2 and thrombin-antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation. Blood Coagul Fibrinolysis 1992; 3: 469-473
  CrossrefPubMedGoogle Scholar
• 15 Bauer KA, Weiss LM, Sparrow D, Vokonas PS, Rosenberg RD. Aging-associated changes in indices of thrombin generation and protein C activation in humans. Normative aging study. J Clin Invest 1987; 80: 1527-1534
  CrossrefPubMedGoogle Scholar
• 16 Black IW, Chesterman CN, Hopkins AP, Lee LCL, Chong BH, Walsh WF. Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol 1993; 21: 451-457
  CrossrefPubMedGoogle Scholar
• 17 Takano K, Yamaguchi T, Ucida K. Markers of a hypercoagulable state following acute ischemic stroke. Stroke 1992; 23: 194-198
  CrossrefPubMedGoogle Scholar
• 18 Bounameaux H, de Moerloose P, Perrier A, Reber G. Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: An overview. Thromb Haemost 1994; 71: 1-6
  PubMedGoogle Scholar
• 19 Elias A, Bonfils S, Daoud-Elias M, Gauthier B, Sié P, Boccalon H, Boneu B. Influence of long term oral anticoagulants upon prothrombin fragment 1+2, thrombin-antithrombin III complex and D-dimer levels in patients affected by proximal deep vein thrombosis. Thromb Haemost 1993; 69: 302-305
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Takano K, Lino K, Ibayashi S, Tagawa K, Sadoshima S, Fujishima M. Hypercoagulable state under low-intensity warfarin anticoagulation assessed with hemostatic markers in cardiac disorders. Am J Cardiol 1994; 74: 935-939
  CrossrefPubMedGoogle Scholar
• 21 Millensen MM, Bauer KA, Kistler JP, Barzegar S, Tulin L, Rosenberg RD. Monitoring “mini-intensity” anticoagulation with warfarin: Comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment Fl+2 levels. Blood 1992; 79: 2034-2038
  PubMedGoogle Scholar
• 22 Bounameaux H, Lijnen HR, Hellemans H, Verstraete M. Effect of standard and low-molecular weight heparin fractions on fibrinolysis and platelet aggregation in patients undergoing hysterectomy. Thromb Haemost 1986; 55-298
  PubMedGoogle Scholar
• 23 Agnelli G, Borm J, Cosmi B, Levi M, ten Cate JW. Effects of Standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis. Thromb Haemost 1988; 60: 311-313
  Article in Thieme ConnectPubMedGoogle Scholar
• 24 Grulich-Henn J, Loechelt K, Speiser W, Miiller-Berghaus G. Increased tissue-plasminogen activator levels in patients under oral anticoagulant therapy. Blut 1989; 58: 39-42
  CrossrefPubMedGoogle Scholar
• 25 Falanga A, Barbui T, Rickies FR, Levine MN. Guidelines for clotting studies in cancer patients. Thromb Haemost 1993; 70: 540-542
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Zabalgoitia M. on behalf of the SPAF Investigators. Stroke Prevention in Atrial Fibrillation III and transesophageal echo study. Design and progress report (abstr). Eur Heart J 1994: 15-28
  PubMedGoogle Scholar