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Activated factor IX, factor XI and tissue factor identify patients with permanent atrial fibrillation treated with warfarin who are at risk of ischemic stroke

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ABSTRACT

Introduction: 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.

Material and 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.

No MeSH data available.


Related in: MedlinePlus

Univariate logistic regression analyses for the presence of active tissue factor (TF), activated factor XI (FXIa) or factor IX (FIXa). Detection of TF, FIXa or FXIa in anticoagulated patients with permanent atrial fibrillation is predicted by elevated vWF, IL-6, CAD, use of ACEI and/or aspirin, while current smoking and statin use are associated with the absence of any of these factors in circulating bloodThe graph with logarithmic scale shows point estimates of odds ratios with 95% confidence intervals. vWF – von Willebrand factor, IL-6 – interleukin-6, CAD – coronary artery disease, ASA – aspirin, ACEI – angiotensin-converting enzyme inhibitor, F – factor. *p < 0.05.
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Figure 0001: Univariate logistic regression analyses for the presence of active tissue factor (TF), activated factor XI (FXIa) or factor IX (FIXa). Detection of TF, FIXa or FXIa in anticoagulated patients with permanent atrial fibrillation is predicted by elevated vWF, IL-6, CAD, use of ACEI and/or aspirin, while current smoking and statin use are associated with the absence of any of these factors in circulating bloodThe graph with logarithmic scale shows point estimates of odds ratios with 95% confidence intervals. vWF – von Willebrand factor, IL-6 – interleukin-6, CAD – coronary artery disease, ASA – aspirin, ACEI – angiotensin-converting enzyme inhibitor, F – factor. *p < 0.05.

Mentions: The univariate logistic regression showed that a higher risk of the presence of one of the tested factors (TF, FIXa or FXIa) was observed in patients with coronary artery disease (OR = 6.27; 95% CI: 1.85–28.9). Higher VWF (OR = 1.15; 95% CI: 1.05–1.27) and IL-6 (OR = 1.29; 95% CI: 1.05–1.61) were also associated with a higher risk of presence of one of the tested coagulation factors (Figure 1).


Activated factor IX, factor XI and tissue factor identify patients with permanent atrial fibrillation treated with warfarin who are at risk of ischemic stroke
Univariate logistic regression analyses for the presence of active tissue factor (TF), activated factor XI (FXIa) or factor IX (FIXa). Detection of TF, FIXa or FXIa in anticoagulated patients with permanent atrial fibrillation is predicted by elevated vWF, IL-6, CAD, use of ACEI and/or aspirin, while current smoking and statin use are associated with the absence of any of these factors in circulating bloodThe graph with logarithmic scale shows point estimates of odds ratios with 95% confidence intervals. vWF – von Willebrand factor, IL-6 – interleukin-6, CAD – coronary artery disease, ASA – aspirin, ACEI – angiotensin-converting enzyme inhibitor, F – factor. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016572&req=5

Figure 0001: Univariate logistic regression analyses for the presence of active tissue factor (TF), activated factor XI (FXIa) or factor IX (FIXa). Detection of TF, FIXa or FXIa in anticoagulated patients with permanent atrial fibrillation is predicted by elevated vWF, IL-6, CAD, use of ACEI and/or aspirin, while current smoking and statin use are associated with the absence of any of these factors in circulating bloodThe graph with logarithmic scale shows point estimates of odds ratios with 95% confidence intervals. vWF – von Willebrand factor, IL-6 – interleukin-6, CAD – coronary artery disease, ASA – aspirin, ACEI – angiotensin-converting enzyme inhibitor, F – factor. *p < 0.05.
Mentions: The univariate logistic regression showed that a higher risk of the presence of one of the tested factors (TF, FIXa or FXIa) was observed in patients with coronary artery disease (OR = 6.27; 95% CI: 1.85–28.9). Higher VWF (OR = 1.15; 95% CI: 1.05–1.27) and IL-6 (OR = 1.29; 95% CI: 1.05–1.61) were also associated with a higher risk of presence of one of the tested coagulation factors (Figure 1).

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: 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.

Material and 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 &lt; 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.

No MeSH data available.


Related in: MedlinePlus