Coagulation Factor Activity and Hemostatic Markers of Endothelial Dysfunction in Patients with Peripheral Arterial Disease

Abstract

Purpose We aimed to evaluate the impact of intrinsic coagulation factors and hemostatic markers of endothelial dysfunction on complications in patients with atherosclerotic peripheral arterial disease (PAD). Methods Materials and This prospective study enrolled 120 PAD patients at Fontaine stages 2b to 3 who underwent open surgical, endovascular, or conservative treatment. Coagulation factors (FVIII, FIX, and FXI) and endothelial hemostatic markers, including von Willebrand factor (vWF) activity and level, soluble endothelial protein C receptor, and plasminogen activator inhibitor-1 (PAI-1) levels, were assessed. Results At 3 months after open bypass grafting, activity of FVIII significantly increased from a median of 175% to 233% (P<0.001). At 3 months after endovascular treatment, the activities of FVIII, FIX, and FXI significantly increased from medians of 157%, 180%, and 156% to 184%, 218%, and 181%, respectively (P<0.05). Six patients with increased FVIII activity developed bypass graft thrombosis. Four patients in the endovascular group and three patients in the conservative treatment group with increased activity of vWF developed myocardial infarction (P=0.049). The subjects who developed restenosis had increased vWF activity (P=0.023) and decreased nitric oxide metabolite levels (P=0.003). Three subjects who received conservative treatment and developed PAD progression at 12 months had increased PAI-1 activity (P=0.028). Conclusion Patients with advanced PAD had a hypercoagulable status, and performance of open or endovascular revascularization was associated with further hypercoagulability. Increased activity of coagulation factors and altered levels of hemostatic markers of endothelial dysfunction were associated with PAD complications such as graft thrombosis, myocardial infarction, disease progression, and restenosis.

Tranexamic acid is not associated with a higher rate of thrombotic-related reintervention after major vascular injury repair

“…16,17 Additionally, the presence of foreign material, such as grafts or stents, can trigger platelet activation and coagulation cascade, potentially leading to thrombotic occlusion. 18,19 The consequences of thrombosis in patients with vascular injuries can be severe, including graft failure, compromised blood flow to vital organs or extremities, higher rates of major amputation and increased morbidity and mortality.…”

“…Plasmin activation can stimulate platelet aggregation and reocclusion during thrombolysis and the inhibitory action of TXA on plasmin may prevent platelet activation and aggregation. 18 Furthermore, plasmin is involved in coagulation, and TXA's inhibition of plasmin activity may help modulate the procoagulant effects associated with elevated plasmin concentrations. 18,23,24 Our study demonstrated an increased risk of thromboembolic events with an increase in the number of packed red blood cell transfusions.…”

“…18 Furthermore, plasmin is involved in coagulation, and TXA's inhibition of plasmin activity may help modulate the procoagulant effects associated with elevated plasmin concentrations. 18,23,24 Our study demonstrated an increased risk of thromboembolic events with an increase in the number of packed red blood cell transfusions. These findings indicate the potential impact of transfusion-related hypercoagulability in this patient population.…”

“…Vascular injuries disrupt normal blood flow and compromise the integrity of the vascular system which promotes the expression of atherogenic and thrombogenic genes and has pro-inflammatory, pro-coagulant, pro-oxidant, and pro-apoptotic effects 16,17 . Additionally, the presence of foreign material, such as grafts or stents, can trigger platelet activation and coagulation cascade, potentially leading to thrombotic occlusion 18,19 . The consequences of thrombosis in patients with vascular injuries can be severe, including graft failure, compromised blood flow to vital organs or extremities, higher rates of major amputation and increased morbidity and mortality.…”

“…This could potentially be attributed to the various mechanisms by which TXA may provide protective effects against thromboembolic events in patients with vascular injury. Plasmin activation can stimulate platelet aggregation and reocclusion during thrombolysis and the inhibitory action of TXA on plasmin may prevent platelet activation and aggregation 18 . Furthermore, plasmin is involved in coagulation, and TXA’s inhibition of plasmin activity may help modulate the procoagulant effects associated with elevated plasmin concentrations 18,23,24 …”