fibrin and Carotid-Stenosis

For thrombus formation, three important factors, blood flow, blood component and blood vessels, have been recognized as Virchow's triad. In cardiogenic embolism with atrial fibrillation, stagnation of blood in the left atrium causes fibrin-rich thrombus. Anticoagulation is the only effective drug for prevention of this type of thrombus. In atherothrombotic and lacunar infarction, injury of endothelium and arterial vessels and platelet play a crucial role of formation of platelet-rich thrombus. Antiplatelet drugs such as aspirin, clopidogrel and cilostazole are effective for prevention of arterial thrombus and stroke recurrence, but other drugs such as statin for plaque stabilization and improvement of endothelial function could be used to reduce the recurrence of ischemic stroke.

Topics: Anticoagulants; Atrial Fibrillation; Blood Platelets; Carotid Stenosis; Cerebral Infarction; Fibrin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Platelet Aggregation Inhibitors; Secondary Prevention; Thrombosis

Slow-flow phenomenon is frequently observed during carotid artery stenting (CAS) with a filter embolic protection device. It results in technical difficulties and can lead to adverse neurological events. Flow impairment is thought to be caused by plaque entrapped by the filter and/or blood coagulation on the filter. Characteristics of heparin- or urokinase-treated polyurethanes were analyzed by surface plasmon resonance, and the fibrinolytic activity of the urokinase-treated filter of Angioguard XP was estimated by the fibrin plate assay. A filter membrane of Angioguard XP protection device was treated with a heparin or urokinase solution. In clinical studies, six and nine patients were treated by CAS using Angioguard XP modified with heparin and urokinase, respectively. Filter membranes were examined by scanning electron microscopy (SEM). From in vitro studies, it appeared that urokinase adsorbed and remained on the Angioguard XP filter, and its fibrinolytic activity was demonstrated even after washing with saline; heparin, however, was easily washed out from the surface. From clinical study, some filter pores were obstructed in all six patients in the heparin group and in three patients in the urokinase group. Fibrin net was found on the filter in five of six patients in the heparin group and in one of nine patients in the urokinase group. Treatment of an Angioguard XP filter with a urokinase solution is effective in preventing pore occlusion and may reduce occurrence of the slow-flow phenomenon.

Topics: Adsorption; Aged; Carotid Arteries; Carotid Stenosis; Fibrin; Filtration; Heparin; Humans; Male; Materials Testing; Middle Aged; Stents; Urokinase-Type Plasminogen Activator

Filter cerebral protection during carotid stenting has been proposed as a new tool to reduce brain embolism. Angiographic findings (filter patency), pathological analysis of the collected materials inside the filters and coagulation parameters were analyzed to identify potential down sides in the use of these protection devices.. 29 consecutive endovascular treatments with filter cerebral protection in 27 patients affected by symptomatic internal carotid stenosis>70% were considered. Angiographic findings, activated clotting times and histopathologic specimens were recorded and correlated.. Satisfactory dilatation of the stenosis was always achieved with a complication rate of 3% (1 transient neurological deficit). During the procedure, 9 filters (31%) appeared occluded, with temporary flow impairment. Histopathologic examination demonstrated material inside the filters in 86% of cases but this material was fibrin alone in 38% and plaque debris in 48%. Significant statistical correlation (p=0.009) was found between low activated clotting time and occlusion of the filter.. Distal protection filters can collect plaque fragments occurring during carotid stenting. Significant proportion of the debris found in the filters consisted of thrombotic material. Precise monitoring of heparin anticoagulation is recommended to prevent filter occlusion.

Topics: Aged; Aged, 80 and over; Angioplasty, Balloon; Carotid Artery, Internal; Carotid Stenosis; Cerebral Angiography; Female; Fibrin; Filtration; Humans; Intracranial Embolism; Male; Middle Aged; Prospective Studies; Stents; Treatment Outcome

Periprocedural microembolization is a major and permanent risk for patients treated by angioplasty and stent placement of high-grade carotid stenoses. Little is known however about the characteristics and significance of these embolized particles. Our aim was to assess the volume and composition of debris captured by filters during carotid angioplasty and stent placement (CAS) of severe internal carotid artery (ICA) stenoses.. Institutional review board approval and informed consent from all subjects were obtained. Two hundred one patients (mean age, 66.2 years; range, 35-82 years) with > or = 70% stenosis of the ICA underwent filter-protected CAS. Ultrastructural and semiquantitative analysis of the volume of filters was obtained. Multifactorial statistical analysis was performed to determine factors related to debris volume and composition.. Transient ischemic attack occurred in 6 patients (3%), and a major stroke, in 1 (0.5%). Debris was found in 117 filters (58.2%), with volume <1 lambda (0.001 mL) in 71%. The number of balloon dilations, age older than 65 years, and calcified plaques in pre-CAS angiography were significantly associated with the presence of particulates inside the filters (P < .03, P < .004, and P < .05, respectively).. Vessel wall and atheromatous plaques are the main source of microemboli during CAS. Embolization is mainly related to the number of balloon dilations during CAS. Planning a proper and individualized strategy for the procedure in each patient is essential to minimize the potential effects of manipulation during CAS.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon; Blood Platelets; Carotid Artery, Internal; Carotid Stenosis; Female; Fibrin; Filtration; Humans; Intracranial Embolism; Male; Middle Aged; Prospective Studies; Stents

Protected carotid artery stent placement is currently under clinical evaluation as a potential alternative to carotid endarterectomy. The current study was undertaken to determine the incidence of new ischemic lesions found on diffusion-weighted MR imaging (DWI) in nonselected patients after protected carotid artery stent placement using a filter device and to determine the potential relationship between these new ischemic lesions and the presence or absence of a clear amount of debris captured by the neuroprotection filter device.. A nonrandomized cohort of 52 patients (40 men, 12 women) presenting with carotid occlusive disease underwent protected carotid artery stent placement using a filter device. DWI obtained 1 day before stent placement was compared with that obtained 1 day after stent placement. In addition, the macroscopic and microscopic analysis of debris captured by the filter device during the carotid stent placement procedure was assessed.. Neuroprotected carotid stent placement was technically successful in all 53 procedures but was complicated by a transient ischemic attack in 3 patients (5.6%). In 22 patients (41.5%), new ischemic lesions were found on DWI, and in 21 filter devices (39.6%), a substantial amount of atheromatous plaque and/or fibrin was found. No clear relationship between the presence of debris captured by the filter device and new lesions detected by DWI was found (P = .087; odds ratio 3.067).. Neuroprotected carotid artery stent placement will not avoid silent cerebral ischemia. Systematic microscopic analysis of debris captured by the filter device has no predictive value for potential cerebral ischemia after carotid artery stent placement.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Brain Ischemia; Carotid Artery, Common; Carotid Stenosis; Cohort Studies; Diffusion Magnetic Resonance Imaging; Equipment Design; Equipment Failure; Female; Fibrin; Filtration; Humans; Male; Membranes, Artificial; Middle Aged; Polyurethanes; Prospective Studies; Risk Factors; Stents

This study investigates a stent-less local delivery system for anti-restenotic agents utilizing antibodies to cross-linked fibrin (XLF). Heparin and low molecular weight heparin (LMWH) were conjugated to an antibody to cross-linked fibrin D-dimer (1D2). Rabbit right carotid arteries were injured with a balloon catheter, then the animals were given a bolus injection of 40 microg/kg 1D2-heparin (26-70 microg/kg heparin) or 1D2-LMWH (29-80 microg/kg LMWH) conjugates or controls of saline (0.5 ml/kg), heparin (150 U/kg), LMWH (2 mg), or 1D2 (40 microg/kg), with or without a heparin bolus and sacrificed after 2 weeks (8 groups, n = 6/group). The injured artery of rabbits given 1D2-heparin or 1D2-LMWH conjugates had reduced neointimal development, with decreased luminal narrowing and positive remodelling compared with animals given control drugs. Animals given 1D2-heparin conjugate (with a heparin bolus) had three to five times more endothelial cells than the rabbits given saline or unconjugated heparin, while rabbits given 1D2-LMWH conjugate had up to 59% fewer neointimal cells than those given unconjugated drugs. There was little difference in extracellular matrix organization or composition. Thus cross-linked fibrin-antibodies can site-deliver anti-restenotic agents to injured areas of the artery wall where they influence wall remodelling and endothelial and neointimal cell number, reducing neointimal formation without systemic complications. Local delivery of anti-restenotic agents should minimise systemic effects, bleeding complications and potentially the cost of treatment due to a single, lower dose.

Topics: Animals; Antibodies; Anticoagulants; Carotid Arteries; Carotid Stenosis; Cross-Linking Reagents; Disease Models, Animal; Drug Delivery Systems; Fibrin; Heparin, Low-Molecular-Weight; Rabbits; Secondary Prevention; Stents; Thrombosis; Tunica Intima

Fibrin(ogen) is the major matrix ligand for beta3 integrins. If alpha(v)beta3 is the major receptor for fibrin(ogen) on intimal smooth muscle cells, we might expect to see this integrin associated with fibrin(ogen). Eighty-four specimens obtained from endarterectomies of 14 patients were studied. Fibrin was frequently observed in carotid intima even at the non-atherosclerotic areas. As for beta1 and beta3 integrins, beta1 was predominant in intima. The alpha(v)beta3 integrin expression was less frequent than alpha5beta1, another receptor for fibrin(ogen), in diffuse intimal thickening, fibrous cap and advanced plaques. Furthermore, alpha(v)beta3 was generally negative on smooth muscle cells in recent plaque ruptures. In conclusion, we suggest more attention should be paid on abundant fibrin matrix in intima. Histologically, the alpha5beta1 integrin rather than the alpha(v)beta3 is the major receptor for fibrin in intimal smooth muscle cells.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibody Specificity; Blotting, Western; Carotid Arteries; Carotid Artery Injuries; Carotid Stenosis; Endarterectomy, Carotid; Fibrin; Fibrinogen; Hemorrhage; Humans; Immunohistochemistry; Integrins; Ligands; Male; Middle Aged; Muscle, Smooth, Vascular; Receptors, Fibronectin; Receptors, Vitronectin; Thromboplastin; Tunica Intima

Dissolution of the fibrin blood clot is regulated in large part by plasminogen activator inhibitor-1 (PAI-1). Elevated levels of plasma PAI-1 may be an important risk factor for atherosclerotic vascular disease and are associated with premature myocardial infarction. The role of the endogenous plasminogen activation system in limiting thrombus formation following atherosclerotic plaque disruption is unknown. This study found that genetic deficiency for PAI-1, the primary physiologic regulator of tissue-type plasminogen activator (tPA), prolonged the time to occlusive thrombosis following photochemical injury to carotid atherosclerotic plaque in apolipoprotein E-deficient (apoE(-/-)) mice. However, anatomic analysis revealed a striking difference in the extent of atherosclerosis at the carotid artery bifurcation between apoE(-/-) mice and mice doubly deficient for apoE and PAI-1 (PAI-1(-/-)/apoE(-/-)). Consistent with a previous report, PAI-1(+/+)/apoE(-/-)and PAI-1(-/-)/apoE(-/-) mice developed similar atherosclerosis in the aortic arch. The marked protection from atherosclerosis progression at the carotid bifurcation conferred by PAI-1 deficiency suggests a critical role for PAI-1 in the pathogenesis of atherosclerosis at sites of turbulent flow, potentially through the inhibition of fibrin clearance. Consistent with this hypothesis, intense fibrinogen/fibrin staining was observed in atherosclerotic lesions at the carotid bifurcation compared to the aortic arch. These observations identify significant differences in the pathogenesis of atherosclerosis at varying sites in the vascular tree and suggest a previously unappreciated role for the plasminogen activation system in atherosclerosis progression at sites of turbulent flow. (Blood. 2000;96:4212-4215)

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Apolipoproteins E; Arteriosclerosis; Carotid Artery Diseases; Carotid Artery Injuries; Carotid Artery, Common; Carotid Stenosis; Disease Progression; Fibrin; Fibrinogen; Hemorheology; Male; Mice; Mice, Knockout; Photochemistry; Plasminogen; Plasminogen Activator Inhibitor 1

Structure and content of atherosclerotic plaque varies between patients and may be indicative of their risk for embolisation. This study aimed to construct parametric images of B-scan texture and assess their potential for predicting plaque morphology. Sequential transverse in vitro scans of 10 carotid plaques, excised during endarterectomy, were compared with macrohistology maps of plaque content. Multidiscriminant analysis combined the output of 157 statistical and textural algorithms into five separate texture classes, displayed as ultrasound (US) texture classification images (UTCI). Visual comparison between corresponding UTCI and histology maps found the five texture classes matched with the location of fibrin, elastin, calcium, haemorrhage or lipid. However, histology preparation removes calcium and lipid and, so, can affect the structural integrity of atherosclerotic plaques. Soft tissue regions smaller than the UTCI kernel, (0.87 mm x 0.85 mm x 3.9 mm), such as blood clots, are also difficult to detect by UTCI. These factors demonstrate limitations in the use of histology as a "gold standard" for US tissue characterisation.

Topics: Arteriosclerosis; Calcium; Carotid Arteries; Carotid Stenosis; Elastin; Endarterectomy, Carotid; Fibrin; Hemorrhage; Humans; Image Processing, Computer-Assisted; In Vitro Techniques; Lipids; Ultrasonography