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Predictive Role of Coagulation, Fibrinolytic, and Endothelial Markers in Patients with Atrial Fibrillation, Stroke, and Thromboembolism: A Meta-Analysis, Meta-Regression, and Systematic Review

Alexander Weymann, Anton Sabashnikov, Sadeq Ali-Hasan-Al-Saegh, Aron-Frederik Popov, Seyed Jalil Mirhosseini, William L. Baker, Mohammadreza Lotfaliani, Tong Liu, Hamidreza Dehghan, Senol Yavuz, Michel Pompeu Barros de Oliveira Sá, Jae-Sik Jang, Mohamed Zeriouh, Lei Meng, Fabrizio D’Ascenzo, Abhishek J. Deshmukh, Guiseppe Biondi-Zoccai, Pascal M. Dohmen, Hugh Calkins, Integrated Meta-Analysis of Cardiac Cardiac Surgery and Cardiology-Group IMCSC-Group]

Department of Cardiac Surgery, University Hospital Oldenburg, European Medical School Oldenburg-Groningen, Carl von Ossietzky University Oldenburg, Oldenburg, Germany

Med Sci Monit Basic Res 2017; 23:97-140

DOI: 10.12659/MSMBR.902558

Available online: 2017-03-31

Published: 2017-03-31


BACKGROUND: The pathophysiological mechanism associated with the higher prothrombotic tendency in atrial fibrillation (AF) is complex and multifactorial. However, the role of prothrombotic markers in AF remains inconclusive.
MATERIAL AND METHODS: We conducted a meta-analysis of observational studies evaluating the association of coagulation activation, fibrinolytic, and endothelial function with occurrence of AF and clinical adverse events. A comprehensive subgroup analysis and meta-regression was performed to explore potential sources of heterogeneity.
RESULTS: A literature search of major databases retrieved 1703 studies. After screening, a total of 71 studies were identified. Pooled analysis showed the association of coagulation markers (D-dimer (weighted mean difference (WMD) =197.67 and p<0.001), fibrinogen (WMD=0.43 and p<0.001), prothrombin fragment 1-2 (WMD=0.53 and p<0.001), antithrombin III (WMD=23.90 and p=0.004), thrombin-antithrombin (WMD=5.47 and p=0.004));  fibrinolytic markers (tissue-type plasminogen activator (t-PA) (WMD=2.13 and p<0.001), plasminogen activator inhibitor (WMD=11.44 and p<0.001), fibrinopeptide-A (WMD=4.13 and p=0.01)); and  endothelial markers (von Willebrand factor (WMD=27.01 and p<0.001) and soluble thrombomodulin (WMD=3.92 and p<0.001)) with AF.
CONCLUSIONS: The levels of coagulation, fibrinolytic, and endothelial markers have been reported to be significantly higher in AF patients than in SR patients.

Keywords: Atrial Fibrillation, Blood Coagulation Disorders, Fibrinolysis