Restenosis is associated with prothrombotic plasma fibrin clot characteristics in endovascularly treated patients with critical limb ischemia (original) (raw)
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Thrombosis Research, 2020
Introduction: Fibrin clot structure differs between healthy individuals and those following thromboembolic events. Dense and poorly lysable fibrin clots have also been reported in peripheral artery disease. We studied fibrin clot properties and its determinants in individuals with a history of acute lower limb ischemia (ALI) of unknown cause. Materials and methods: In this case-control study, we enrolled 43 patients who experienced ALI of unknown cause, and two age-and sex-matched reference groups: (1) patients with cryptogenic non-lacunar stroke (n = 43) and (2) individuals without any history of thromboembolism (n = 43, control group). Plasma fibrin clot properties, along with thrombin generation and fibrinolysis markers were assessed following ≥3 months of anticoagulation. Results: Compared with the control group, the ALI group exhibited more compact plasma fibrin clots (13.4% lower permeability [K s ], p = .001), decreased formed clot lysis (12.5% lower D-D rate , p = .001) and unaltered clot lysis potential, along with enhanced thrombin generation potential (49% higher peak thrombin concentration, p < .0001). There were no differences in these variables between ALI and stroke patients. Patients with ALI had slightly higher α 2-antiplasmin and lower plasminogen activator inhibitor 1 levels compared with the stroke and control groups (all p < .01). Conclusions: Patients who experienced ALI of unknown cause display a prothrombotic fibrin clot phenotype, including increased clot density and hypofibrinolysis associated with higher thrombin generation, which might suggest potential benefits from prolonged anticoagulation in this disease. the European population incidence of ALI is estimated at 6 to 17 per 100,000 per year and a mean age of the patients is 76 years [4,5]. Amputation rates range between 6 and 30% in 30 days and mortality reaches 9-22% at one year follow up [6,7]. The pathogenesis of ALI is complex [8]. Thrombosis accounts for approximately 60-85% of the ALI cases, most commonly in patients with advanced atherosclerotic peripheral arterial disease (PAD) in a
Circulation, 2017
Peripheral artery disease affects >200 million people worldwide and is associated with significant limb and cardiovascular morbidity and mortality. Limb revascularization is recommended to improve function and quality of life for symptomatic patients with peripheral artery disease with intermittent claudication who have not responded to medical treatment. For patients with critical limb ischemia, the goals of revascularization are to relieve pain, help wound healing, and prevent limb loss. The baseline risk of cardiovascular and limb-related events demonstrated among patients with stable peripheral artery disease is elevated after revascularization and related to atherothrombosis and restenosis. Both of these processes involve platelet activation and the coagulation cascade, forming the basis for the use of antiplatelet and anticoagulant therapies to optimize procedural success and reduce postprocedural cardiovascular risk. Unfortunately, few high-quality, randomized data to supp...
The Cochrane library, 2012
Analysis 8.1. Comparison 8 Cilostazol plus aspirin versus ticlopidine plus aspirin, Outcome 1 Occlusion/restenosis, 12 months.... Analysis 8.2. Comparison 8 Cilostazol plus aspirin versus ticlopidine plus aspirin, Outcome 2 Occlusion/restenosis, 24 months.... Analysis 8.3. Comparison 8 Cilostazol plus aspirin versus ticlopidine plus aspirin, Outcome 3 Occlusion/restenosis, 36 months.... Analysis 8.4. Comparison 8 Cilostazol plus aspirin versus ticlopidine plus aspirin, Outcome 4 Amputation, all.
Atherosclerosis, 2011
Background: A role of blood coagulation in the pathogenesis of peripheral arterial disease (PAD) and Buerger's disease, or thromboangiitis obliterans (TAO), remains unclear. Objective: To test the hypothesis that PAD and TAO are associated with prothrombotic phenotype of a fibrin clot. Patients and methods: Ex vivo plasma fibrin clot permeability, turbidimetry and efficiency of fibrinolysis were investigated in 106 patients with PAD and 20 patients with TAO and compared with the respective control groups matched for age, sex, and cardiovascular risk factors. The progression of PAD and TAO were evaluated during follow-up of 3-7.5 years. PAD patients were characterized by lower clot permeability (−18.8%, p = 0.005), shorter lag phase (−35.3%, p < 0.001), higher maximum clot absorbancy (+22.4%, p < 0.001), prolonged clot lysis time (+30.6%, p = 0.003), and lower rate of D-dimer release from clots in the presence of recombinant tissue plasminogen activator (−16.5%, p = 0.009), but twofold lower maximum D-dimer levels released from clots during lysis (p < 0.001) than the controls. Similar, but more pronounced abnormalities were observed in TAO patients versus controls (all p < 0.01). Seventeen PAD (16%) and 3 (15%) TAO patients were lost to follow-up. The progression observed in 47 (52.8%) PAD patients and 10 (59%) TAO patients was associated with lower clot permeability (−14.6%, p = 0.009, and −17.5%, p = 0.02) and prolonged clot lysis (+11.3%, p = 0.004, and +12.4%, p = 0.03, respectively). Conclusions: Unfavorably altered fibrin clot properties are observed in both PAD and TAO. Denser fibrin clots with reduced susceptibility to lysis might characterize the progression of both diseases during long-term follow-up.
International Wound Journal, 2018
Fibronectin (FN) may be involved in time‐ and stage‐dependent and inter‐related controlled processes of inflammation, coagulation, and wound healing accompanying peripheral arterial disease (PAD). In the present study, FN and FN‐containing extra‐domain A (EDA‐FN), macromolecular FN‐fibrin complexes, and FN monomer were analysed in the plasma of 142 PAD patients, including 37 patients with restenosis, for 37 months after revascularisation. FN concentration increased significantly in the plasma of PAD patients within 7 to 12 months after revascularisation, whereas the high concentration of EDA‐FN was maintained up to 24 months, significantly higher in the group 7 to 12 months after revascularisation with recurrence of stenosis and lower in the PAD groups 1 to 3 months and 4 to 6 months after revascularisation with comorbid diabetes and ulceration, respectively. The relative amounts of FN‐fibrin complexes up to 1600 kDa and FN monomer were significantly higher, within intervals of 4 to 24 months and 4 to 6 months after revascularisation, respectively. Moreover, the relative amounts of 750 to 1600 kDa FN‐fibrin complexes within 13 to 24 months after revascularisation were higher in comparison with those in the group without restenosis. In conclusion, high levels of EDA‐FN and FN‐fibrin complexes could have potential diagnostic value in the management of PAD patients after revascularisation, predicting restenosis risk.
European Journal of Vascular and Endovascular Surgery, 2011
Objectives: Few data are available on thrombophilic risk factors and clinical outcome in patients undergoing percutaneous transluminal angioplasty (PTA) for peripheral arterial disease (PAD). We investigated the role of homocysteine, fibrinogen, Factor VIII (FVIII), lupus anticoagulant (LAC) and FII G20210A, and FV R506Q (FV Leiden) mutations as prognostic factors in 230 patients who underwent PTA for PAD (Fontaine's stages: IIb through IV; aged 69 AE 1 years). Design and methods: A prospective study. Major adverse cardiovascular events (MACE) were the composite 'end' point. Results: During the follow-up (24.3 AE 1.5 months), 96 (41.7%) patients reached the 'end' point. According to Cox regression analysis, diabetes and critical limb ischaemia were predictors of MACE, whereas each single thrombophilic alteration was not. Thrombophilic alterations were more frequent in patients that reached the 'end' point, and the patients with two alterations (hazard ratio (HR) 2.55 confidence interval (CI): 1.20e5.46, p Z 0.015) and those with three or more alterations (HR 2.91 CI: 1.31e6.45, p Z 0.009) had an increased risk for MACE versus those without alterations. Thrombophilic alterations were not associated with limb loss during the follow-up. Conclusion: The presence of multiple thrombophilic alterations in patients who underwent PTA for PAD is associated with increased risk of arterial thrombotic events. ª
Thrombosis research, 2012
The mechanisms of restenosis, the recurrence of luminal narrowing, are complex and incompletely understood to date. Thrombin, the pivotal enzyme in haemostasis, presumably contributes to the formation of in-stent restenosis (ISR). It was therefore the aim of our study to investigate whether blood coagulation/thrombin generation plays a critical role in the formation of ISR in peripheral artery disease patients with stent angioplasty in the superficial femoral artery. We aimed to examine in this retrospective study whether patients with high-degree restenosis (50-75% lumen diameter reduction, n=20) are in a hypercoaguable state implying enhanced readiness to generate thrombin compared to patients with low-degree restenosis (<50% lumen diameter reduction, n=14). The coagulation tests calibrated automated thrombography, activated partial thromboplastin time, platelet aggregation, platelet adhesion, fibrinogen, and microparticles' procoagulant activity did not indicate a differen...
Relevance of hemostasis on restenosis in clinically stable patients undergoing elective PTCA
Thrombosis Research, 2008
Background: Secondary coronary thrombus formation is considered to be co-factor in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Therefore systemic factors indicating a hypercoagulable disease state may be relevant for the process of coronary renarrowing. Even though experimental data suggest that in particular thrombin may be of major relevance for restenosis induced by mechanical injury, only little clinical data has been presented so far. Methods and results: In 60 consecutive patients, who had been clinical stable for at least 2 months, and who underwent elective and primarily successful PTCA, follow-up films were evaluated by means of quantitative coronary angiography in respect to a categorical and a continuous definition of restenosis, luminal narrowing N50% and late luminal loss respectively. Of the chosen laboratory variables prothrombin fragment 1 + 2 (1.3 ± 0.5 vs. 0.9 ± 0.4 mmol/l, p b 0.001) red blood cell aggregation at low shear stress (13.5 ± 2.9 vs. 11.6 ± 2.8 units, p b 0.05), and plasminogen-activator inhibitor (3.7 ± 1.8 vs. 5.3 ± 3.2 U/ml p b 0.05) differentiated between patients with (n = 18) and without restenosis (n = 42). Late luminal loss correlated positively with prothrombin fragment 1 + 2 (r = 0.41, p b 0.001), plasminogen-activator inhibitor (r = −0.28, p b 0.05) and plasmin-α 2 -antiplasmin complex (r = 0.39, p b 0.01). Conclusions: A hypercoagulable disease state and in particular thrombin generation characterize a high-risk group prone for restenosis in clinically stable oronary artery disease.
Slovenian Medical Journal
Background. Patients with peripheral arterial disease (PAD) are routinely prescribed antiplatelet treatment (APT) after revascularisation. An exception are patients who receive anticoagulant treatment (ACT) due to comorbidity. We set out to determine possible differences in the effectiveness and safety between ACT and APT in patients who underwent endovascular revascularisation of the lower limb arteries. Methods. In a single-centre retrospective study, we analysed the data of 1,587 consecutive patients with PAD who underwent successful endovascular revascularisation of the lower limb arteries due to disabling intermittent claudication or chronic critical limb ischemia in a 5-year period. Patients were divided in the ACT and APT group based on their prescribed treatment. After balancing both groups' baseline characteristics and cardiovascular risk factors with propensity score matching (PSM), we compared the effectiveness and safety of both treatment regimens in the first year...
Scientific Reports
Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3–4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31–68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59–1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univari...