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Objectives-We sought to investigate whether patients with in-stent thrombosis (IST) display altered plasma fibrin clot properties. Key Words: angioplasty Ⅲ fibrin Ⅲ fibrinolysis Ⅲ stents Ⅲ thrombosis T here are several factors associated with increased risk of in-stent thrombosis (IST) in epicardial arteries, including the procedure itself (small final lumen dimension due to stent malapposition and/or underexpansion, stent length, placement of multiple stents, dissections), patient (low left ventricular ejection fraction [LVEF], diabetes mellitus, advanced age, stenting in acute coronary syndrome) and lesion characteristics (bifurcation, in-stent restenosis), stent design and premature cessation of antiplatelet drugs. 1-3 Autopsy studies provided evidence that lack of complete endothelialization and persistent fibrin thrombi are a primary substrate underlying IST. 4,5 Thrombin-mediated fibrinogen conversion to fibrin and fibrin monomer cross-linking result in the formation of a fibrin clot. Its structure and function are modulated by several genetic and environmental factors, predominantly those affecting levels and function of fibrinogen. 6 Effective fibrinolysis is essential for removal of intravascular clots that might otherwise be manifest as thrombosis or enhance the development of atherosclerotic plaques. A more tightly packed and less porous fibrin structure reduces transport of proteins involved in fibrinolysis and anticoagulant reactions mediated by antithrombin inside the clot. These alterations might prolong the presence of fibrin in the lumen. 6 Dense clot fiber networks with reduced susceptibility to lysis have been demonstrated in survivors of myocardial infarction (MI), 7 in the acute phase of MI, 8 and in patients with a history of the no-reflow phenomenon, defined as the absence of a complete myocardial perfusion despite successful opening of the infarct-related artery. 9 Several lines of evidence 10,11 indicate that incompletely endothelialized coronary stents predispose to fibrin deposition and persistent thrombi on the stent struts. However, it is not known whether the IST is associated with unfavorably altered fibrin clot properties that might contribute to this complication regardless of platelet reactivity. Therefore, we sought to evaluate plasma fibrin clot structure/function in patients with definite IST. Methods and Results-We

Objective-The goal of this study was to investigate whether omega-3 polyunsaturated fatty acids (n-3 PUFA) are able to alter plasma fibrin clot properties and reduce thrombin formation in stable coronary artery disease patients undergoing percutaneous coronary intervention (PCI). Methods and Results-In an investigator-initiated, prospective, double-blind, placebo-controlled, randomized study, patients undergoing PCI who received standard pharmacotherapy were assigned to the treatment with 1 g/day n-3 PUFA (nϭ30) or placebo (nϭ24) for 1 month. Plasma fibrin clot permeability (K s ); lysis time (t 50% ); prothrombin fragment 1.2; and peak thrombin generation from automated thrombogram, 8-isoprostaglandin F 2␣ (8-iso-PGF 2␣ , an oxidative stress marker), and C-reactive protein were determined at baseline, 3 to 5 days after randomization, and 30 days after randomization. At baseline, both treatment groups did not differ significantly. A 1-month treatment with n-3 PUFA compared with placebo was associated with 15.3% higher K s , indicating larger pores in the fibrin network (Pϭ0.0005); 14.3% shorter t 50% , indicating increased susceptibility to fibrinolysis (PϽ0.0001); 33.8% lower prothrombin fragment 1.2 (Pϭ0.0013); 13.4% lower peak thrombin generation (Pϭ0.04); and 13.1% lower 8-iso-PGF 2␣ (Pϭ0.009). Treatment with n-3 PUFA had no effect on fibrinogen and C-reactive protein. After 1 month of treatment, fibrinogen (rϭϪ0.53, PϽ0.0001), treatment assignment (rϭ0.29, Pϭ0.006) and 8-iso-PGF 2␣ (rϭϪ0.27, Pϭ0.015) were independently associated with clot permeability (PϽ0.0001, R 2 ϭ0.66). Conclusion-Adding n-3 PUFA to standard therapy in stable patients undergoing PCI significantly decreases thrombin formation and oxidative stress and favorably alters fibrin clot properties. These findings indicate novel antithrombotic effects induced by n-3 PUFA in humans. (Arterioscler Thromb Vasc Biol. 2011;31:1696-1702.)Key Words: angioplasty Ⅲ fibrin Ⅲ fish oils Ⅲ thrombin Ⅲ oxidative stress A ntiplatelet and antithrombotic agents are one of the cornerstones of successful therapy of coronary artery disease (CAD). Despite antiplatelet treatment with acetylsalicylic acid and clopidogrel, some patients undergoing percutaneous coronary intervention (PCI) and after acute coronary syndromes (ACS) still experience thrombotic events, including stent thrombosis and recurrent myocardial infarction. 1,2 Platelet activation is closely associated with blood coagulation activation, resulting in a surge of thrombin generation that leads ultimately to fibrin clot formation. 2 As thrombin is also a potent platelet activator, inhibition of thrombin generation, thrombin activity, or both might improve treatment outcomes of CAD patients.A relationship between the structure/function of a fibrin clot and the presence of cardiovascular disease was first demonstrated in patients with advanced CAD in 1992. 3 Fibrin clots composed of dense fiber networks, which display lower clot permeability (by approximately 30% compared with control subjects), have been...

Early post-infarction CMR-based MVO is a strong independent prognosticator in revascularized STEMI patients. Remarkably, MVO extent ≥2.6% of LV improved long-term risk stratification over traditional outcome predictors.

Altered fibrin clot structure has been reported both in patients with coronary artery disease (CAD) and those with type 2 diabetes mellitus (DM2). The aim of the present study was to evaluate plasma fibrin clot permeability and susceptibility to lysis in patients with DM2 and CAD. We studied 132 consecutive CAD patients, including 67 subjects with DM2, scheduled for elective coronary artery bypass grafting surgery. Ex vivo plasma fibrin clot permeability (Ks) and lysis time (t50%) induced by 1 μg/mL recombinant tissue plasminogen activator (tPA), along with plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tPA, von Willebrand factor (vWF), P-selectin, soluble CD40 ligand (sCD40L), were measured. Diabetic and non-diabetic patients did not differ in regard to demographics and remaining cardiovascular risk factors. Concomitant DM2 was associated with higher glucose (+24.3 %, p < 0.001), fibrinogen (+9.0 %, p = 0.037), PAI-1 (+58.7 %, p < 0.001), tPA (+24.0 %, p < 0.001) and P-selectin (+12.2 %, p < 0.001). Compared with the non-diabetic group, the CAD patients with DM2 had lower Ks (-6.1 %, p = 0.02) and prolonged t50% (+5.1 %, p = 0.04). Multiple regression analysis of the whole study group showed that vWF, PAI-1, fibrinogen and DM2 were the independent predictors of t50% (R2 = 0.58, p < 0.001), while only vWF was an independent predictor of Ks (R2 = 0.22, p < 0.001). This study indicates that DM2 is potent enough to unfavorably affect plasma fibrin clot characteristics despite abnormal clot phenotype typically observed in CAD. Of note, platelet and endothelial markers appear to contribute to fibrin clot properties in CAD concomitant with DM2.

PTA is a safe and effective method for the treatment of the subclavian/innominate artery obstruction and leads to symptom resolution in majority of patients. Restenosis is not frequent and it can be effectively treated with repeat angioplasty. Low stent diameter, implantation of two stents, and upper limb systolic blood pressure difference are independent predictors of restenosis.