Abstract
Background: Inflammation and hypercoagulability play a pivotal role in venous thromboembolism and atherothrombosis. Since venous thrombosis increases the risk of atherothrombotic events and vice versa, common mechanisms may be involved.Objectives: To elucidate the role of neutrophils and coagulation in the occurrence of atherothrombotic events in patients with a history of deep vein thrombosis (DVT or peripheral artery disease (PAD).Materials and Methods: We studied 115 patients from two cohorts (75 DVT, 40 PAD). From those with PAD, 20 patients had progressive disease; from those with DVT, 25 patients had a recurrent DVT and 25 suffered from post thrombotic syndrome (PTS); patients were age and sex matched to DVT and PAD patients without events. Markers of neutrophil recruitment (p-selectin) and activation [nucleosomes, human neutrophil elastase- α1anti-trypsin (HNE-AT)], an anti-inflammatory marker (Lipoxin A4) and a clotting activity marker (d-dimer), were measured with ELISA. Coagulation potential was analyzed by thrombin generation (CAT method).Results: Higher nucleosome levels were found in DVT patients [11.3 U/mL (7.4–17.7)] compared to PAD patients [7.1 U/mL (5.1–13.8)], lower HNE-AT levels were found in DVT patients [33.4 ng/mL (23.5–40.5)] in comparison to PAD patients [158 ng/mL (88.1–283)]. No difference in nucleosome levels was found between DVT patients with cardiovascular (CV) events [12.6 U/mL (8.2–16.1)], and PAD patients with CV events [6.9 U/mL (4.9–11.2)]. Lipoxin A4 levels appeared to be significantly lower in DVT [2.4 ng/mL (1.7–4.8)] vs. PAD [35.6 ng/mL (16.6–80.1)], with similar results in DVT patients with CV events vs. PAD patients with CV events. Thrombin generation showed higher ETP [160.4% (141.1–215.4)], and peak height [292.1% (177.9–330)] values in DVT patients. D-dimer levels were significantly lower in the DVT cohort [330 ng/mL (220–550)] compared to the PAD cohort [550 ng/mL (369–959)].Conclusion: In DVT patients, neutrophil activity does not appear to be an important driver of CV events. Although neutrophil activity is more pronounced in PAD, its effect is partly dampened by Lipoxin A4. Moreover, no associations were found between NET products and coagulation activity, suggesting that neutrophil activation does not play a pivotal role in the risk of thrombosis in either DVT or PAD.
Highlights
There is an increased risk for atherothrombosis following deep venous thrombosis (DVT) [1,2,3]
The use of oral anticoagulants was higher in DVT patients (63%) compared to peripheral artery disease (PAD) patients (0%), while the use of antiplatelet agents was much lower in DVT (5%) than in PAD (95%)
We used highly selected markers reflecting the interplay between platelet and endothelial activation, neutrophil activation as well as an inflammation inhibiting pathway component; we explored activity of the coagulation system by probing the potential to generate thrombin and by assessing a sensitive marker of coagulation activity, utilizing d-dimer (Figure 4)
Summary
There is an increased risk for atherothrombosis following deep venous thrombosis (DVT) [1,2,3]. The increased risk of cardiovascular events following venous thrombosis has consistently been reported [6, 7], the opposite association is much less defined. Common pathophysiological mechanisms linking arterial and venous thrombosis are most likely related to inflammation and hypercoagulability. Both arterial thrombosis, and to a lesser extent venous thrombosis, have been associated with increased markers of inflammation [10, 11]. One mechanism linking inflammation and coagulation is the activation of neutrophils and the ability to adhere to platelets and endothelial surfaces. These cellular interactions are likely to contribute to a “prethrombotic state” or overt hypercoagulability. Since venous thrombosis increases the risk of atherothrombotic events and vice versa, common mechanisms may be involved
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
