Activated factor IX, factor XI and tissue factor identify patients with permanent atrial fibrillation treated with warfarin who are at risk of ischemic stroke.
BACKGROUND
Previously, we have demonstrated that significant proportions of patients with various cardiovascular diseases have active tissue factor and active factor XIa in their plasma. In the current study, we evaluated active tissue factor and active factors (F)XI and FIX in plasma from patients with atrial fibrillation.


METHODS
In 110 consecutive patients with permanent atrial fibrillation receiving warfarin, we determined active tissue factor, together with plasma FIXa and FXIa, using clotting assays by measuring the response to inhibitory monoclonal antibodies.


RESULTS
Sixteen (14.5%) patients had detectable active tissue factor and active FXIa, including 11 subjects with both factors, while FIXa was observed in 28 (25.7%) patients. The three positive groups did not differ from the patients without these factors with regard to demographic and clinical characteristics. Von Willebrand factor was higher in the active tissue factor-positive group (p< 0.0001) and FXIa-positive group (p= 0.0037). Individuals positive for active tissue factor and FXIa had higher plasma interleukin-6 levels (p= 0.0014 and 0.0322, respectively). The presence of active tissue factor, FXIa and FIXa in anticoagulated patients with permanent atrial fibrillation correlated with elevated von Willebrand factor and interleukin-6. During a 3-year follow-up, ischemic stroke (n= 12, 10.9%) occurred more commonly among atrial fibrillation patients who had circulating TF (p= 0.002) or FXIa (p= 0.013).


CONCLUSIONS
These data suggest that circulating active coagulation factors, in particular TF and FXIa, can be detected despite oral anticoagulation in a significant proportion of patients with atrial fibrillation, and could represent novel markers of persistent prothrombotic alterations predisposing to ischemic stroke.
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland.
Piotr
P
Kusak
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland.
Danuta
D
Czarnecka
Department of Biochemistry, University of Vermont, Burlington, Vermont, USA.
Matthew
M
Gissel
Krakow Cardiovascular Research Institute, Krakow, Poland.
Krzysztof
K
Plens
Department of Biochemistry, University of Vermont, Burlington, Vermont, USA.
Saulius
S
Butenas
Institute of Cardiology, Jagiellonian University School of Medicine, Krakow, Poland.
Anetta
A
Undas
anticoagulation; arrhythmia; blood coagulation; stroke
J Clin Invest. 2012 Feb;122(2):558-68
22214850
Am J Cardiol. 2003 Aug 15;92(4):400-5
12914869
Postepy Kardiol Interwencyjnej. 2013;9(4):348-52
24570752
Thromb Res. 2011 Nov;128(5):e62-6
21820158
Eur J Clin Invest. 2003 Nov;33(11):941-8
14636296
Atherosclerosis. 1996 Feb;120(1-2):7-14
8645373
Stat Med. 2002 Aug 30;21(16):2409-19
12210625
Neurology. 1978 Oct;28(10):973-7
570666
Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):722-7
17272750
Pol Arch Med Wewn. 2011 Nov;121(11):400-7
22064373
Circulation. 2002 Oct 8;106(15):1962-7
12370220
J Biol Chem. 1983 May 25;258(10):6503-8
6406482
Arterioscler Thromb Vasc Biol. 2009 Dec;29(12):1989-96
19592470
Pol Arch Med Wewn. 2014;124(3):124-35
24556890
Stroke. 1999 Dec;30(12):2547-53
10582976
Circulation. 2006 Feb 7;113(5):722-31
16461845
Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):2489-93
11073857
Blood. 1998 Jun 15;91(12):4581-92
9616154
Int Urol Nephrol. 2012 Apr;44(2):523-33
21387085
Am J Cardiol. 2006 May 1;97(9):1346-50
16635609
Pol Arch Med Wewn. 2010 Sep;120(9):334-40
20864906
Stroke. 1991 Aug;22(8):983-8
1866765
J Thromb Haemost. 2003 Oct;1(10):2103-11
14521591
J Huazhong Univ Sci Technolog Med Sci. 2010 Oct;30(5):648-51
21063850
J Thromb Haemost. 2006 Aug;4(8):1747-55
16879217
Diabetes. 2006 Jan;55(1):202-8
16380494
Thromb Haemost. 2008 Jan;99(1):142-9
18217146
Circulation. 2001 Dec 11;104(24):2886-91
11739301
Am J Pathol. 1991 Mar;138(3):601-7
2000938
Eur J Clin Invest. 2012 Feb;42(2):123-9
21707613
Lancet. 2009 Jan 10;373(9658):155-66
19135613
Blood Coagul Fibrinolysis. 2012 Apr;23(3):189-94
22343680
Arch Med Sci. 2013 Dec 30;9(6):1071-7
24482652
J Am Coll Cardiol. 2004 Jun 2;43(11):2075-82
15172416
Europace. 2011 Jan;13(1):31-6
20852292