thromboplastin and Rupture--Spontaneous

Hyperlipidemia leads to the formation of oxidized LDL (oxLDL), vessel dysfunction, atherosclerotic disease, and ultimately to plaque rupture and thrombosis. OxLDL induces tissue factor (TF) expression in various cell types, including monocytes and macrophages. High levels of TF are present in atherosclerotic plaques and this represents that major source of TF that triggers thrombosis after plaque rupture. In addition, increased levels of "circulating TF" are observed in hyperlipidemic animals and patients. This is due to induced TF expression in monocytes and release of monocyte-derived, TF(+) microparticles, which represents a minor source of TF that likely contributes to thrombosis after plaques rupture. This review will summarize the connections between hyperlipidemia and TF expression within atherosclerotic plaques and circulating monocytes, as well as its inhibition by statins.

Topics: Animals; Coronary Artery Disease; Humans; Lipoproteins, LDL; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboplastin; Thrombosis

The acute coronary syndromes, that include unstable angina, acute myocardial infarction, and many cases of sudden cardiac death, exact a considerable price on society in terms of mortality, morbidity, and health care costs. The coronary atherosclerotic lesion is often an indolent and progressive entity that can destabilize causing an acute syndrome with or without warning. The majority of acute coronary syndromes result from events such as rupture or disruption of the atherosclerotic plaque with intracoronary thrombosis and ischemia of the distal myocardium as a result. Advances in our understanding of the process underlying the acute coronary syndromes has allowed for the identification of targets and rational therapeutic strategies for the prevention and treatment of these syndromes. Many of these therapeutic strategies involve the reversal of prethrombotic forces that often coexist with coronary atherosclerosis. Even with recent advances in our approach to atherosclerosis, intracoronary thrombosis, and the resulting acute coronary syndromes, an unacceptably high event rate persists after these syndromes. Further advances in the prevention and treatment of coronary atherosclerosis and its thrombotic complications depends on a more thorough understanding of the biology of the atherosclerotic plaque and the factors which influence its stability.

Topics: Angina, Unstable; Blood Coagulation; Coronary Vessels; Disease Progression; Humans; Life Style; Myocardial Infarction; Rupture, Spontaneous; Syndrome; Thrombolytic Therapy; Thromboplastin; Treatment Outcome

The basic mechanisms of atherosclerotic progression leading to the acute coronary syndromes (ACS) have been elucidated during the last few years. In this brief presentation, we outline 1) Definition of Atherosclerotic Lesions: eight morphologically different lesions are defined (Type I to VI) in various phases of disease. 2) Vulnerable Lipid-Rich Plaques and the ACS: The type IV and Va lesions tend to be relatively small in size, but soft or vulnerable to a "passive" phenomenon of plaque disruption; in addition, an "active" macrophage-dependent enzymatic (genesis of metalloproteinase) phenomenon of plaque disruption is evolving. 3) Thrombosis: we have shown that monocytes/macrophages in lipid-rich plaques may play a detrimental role after plaque disruption, promoting thrombin generation and thrombosis through the tissue factor pathway that can be prevented by tissue factor pathway inhibition; such pathway of thrombosis appears to be critical in the development of the ACS. 4) Effect of Lipid-Modifying Strategies and other Risk Factors on the Vulnerable Lipid-Rich Plaques: when high LDL-cholesterol is reduced therapeutically, efflux from the plaques of the liquid or sterified cholesterol, and also its hydrolysis into cholesterol crystals depositing in the vessel wall, predominate over the influx of LDL-cholesterol; consequently, there is a decrease in the softness of the plaque and so, presumably in the "passive" phenomenon of plaque disruption; modification of other risk factors presumably also favorably affect LDL-cholesterol influx and efflux. 5) Antithrombotic Strategies: the evolving antithrombotic approaches under investigation are briefly outlined.

Topics: Anticoagulants; Arteriosclerosis; Aspirin; Clinical Trials as Topic; Coronary Thrombosis; Disease Progression; Drug Therapy, Combination; Endothelium, Vascular; Fibrinolytic Agents; Humans; Lipids; Models, Biological; Platelet Aggregation Inhibitors; Rupture, Spontaneous; Thromboembolism; Thromboplastin; Warfarin

It remains uncertain why some plaque ruptures trigger acute coronary syndrome (ACS), whereas others do not. We investigated the anatomic features and tissue factor (TF) expression at the sites of plaque rupture in 42 patients presenting with ACS (n = 23) or stable angina (n = 19). Intravascular ultrasound examination was performed before directional coronary atherectomy. Specimens were stained with antibodies against TF, CD68 positive phagocytic cells, and smooth muscle cells; and intravascular ultrasound and immunohistochemistry results were compared. Baseline demographic and clinical characteristics, as well as vessel and lumen sizes at both reference and lesion sites, were comparable in the two groups. However, the remodeling index and plaque burden at lesion sites were significantly greater in the ACS than in the stable angina group. The TF-immunopositive areas were significantly greater in the ACS than in the stable angina group (0.07%; IQR [0.02-0.16%] vs. 0.02%; IQR [0.01-0.05%], P = 0.022), whereas the proportions of CD68-positive and smooth muscle cell areas were similar. There was a significant correlation between areas positive for TF and those positive for CD68 (r = 0.83, P < 0.001). In conclusion, ruptured plaques in patients with ACS show stronger TF expression, a greater plaque burden, and a higher remodeling index than do plaques in those with stable angina, suggesting that both lesion morphology and local thrombogenicity are related to clinical symptoms after plaque rupture.

Topics: Acute Coronary Syndrome; Adult; Aged; Angina Pectoris; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Female; Gene Expression Regulation; Humans; Male; Middle Aged; Myocytes, Smooth Muscle; Phagocytes; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboplastin

Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now.. Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure.. The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.

Topics: Analysis of Variance; Case-Control Studies; Coronary Thrombosis; Coronary Vessels; Extracellular Traps; Female; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Myocardial Infarction; Myocardial Revascularization; Neutrophils; Percutaneous Coronary Intervention; Plaque, Atherosclerotic; Platelet Activation; Rupture, Spontaneous; Thrombin; Thromboplastin

Atherothrombosis is the main cause of myocardial infarction and ischemic stroke. Although the extrinsic (tissue factor-factor VIIa [FVIIa]) pathway is considered as a major trigger of coagulation in atherothrombosis, the role of the intrinsic coagulation pathway via coagulation FXII herein is unknown. Here, we studied the roles of the extrinsic and intrinsic coagulation pathways in thrombus formation on atherosclerotic plaques both in vivo and ex vivo.. Plaque rupture after ultrasound treatment evoked immediate formation of subocclusive thrombi in the carotid arteries of Apoe(-/-) mice, which became unstable in the presence of structurally different FXIIa inhibitors. In contrast, inhibition of FVIIa reduced thrombus size at a more initial stage without affecting embolization. Genetic deficiency in FXII (human and mouse) or FXI (mouse) reduced ex vivo whole-blood thrombus and fibrin formation on immobilized plaque homogenates. Localization studies by confocal microscopy indicated that FXIIa bound to thrombi and fibrin particularly in luminal-exposed thrombus areas.. The FVIIa- and FXIIa-triggered coagulation pathways have distinct but complementary roles in atherothrombus formation. The tissue factor-FVIIa pathway contributes to initial thrombus buildup, whereas FXIIa bound to thrombi ensures thrombus stability.

Topics: Animals; Aorta, Thoracic; Aortic Diseases; Apolipoproteins E; Atherosclerosis; Blood Coagulation; Blood Platelets; Carotid Arteries; Carotid Artery Diseases; Cholesterol, Dietary; Disease Models, Animal; Factor VIIa; Factor XI; Factor XII; Factor XII Deficiency; Factor XIIa; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Rupture, Spontaneous; Thromboplastin; Thrombosis; Time Factors

Topics: Arteriosclerosis; Coronary Thrombosis; Death, Sudden, Cardiac; Disease Progression; Endothelium, Vascular; Female; Glutathione; Humans; Hypochlorous Acid; Inflammation Mediators; Macrophages; Male; Models, Biological; Peroxidase; Rupture, Spontaneous; Thrombophilia; Thromboplastin

Oncostatin M (OSM) is a cytokine of the interleukin-6 (IL-6) family secreted by activated monocytes, and is expressed in atherosclerotic plaque. Smooth muscle cells (SMC), by expressing tissue factor (TF) and tissue factor pathway inhibitor (TFPI) can contribute to the thrombogenicity of atherosclerotic plaque. Consequently, the aim of this study was to evaluate the effects of OSM on the procoagulant activity of SMC. We observed that OSM induced in a concentration-dependent manner a potent procoagulant activity (PCA) that was related in part to an increased synthesis of TF, both at the cell membrane and in SMC lysates. The increased expression of TF on SMC membrane induced by OSM was sustained and was still observed 24 h after stimulation by OSM. IL-6 and leukaemia inhibitory factor (LIF), two OSM-related cytokines, did not significantly modify TF expression at the surface of SMC. In addition to its effects on TF, OSM decreased the secretion of TFPI in the supernatants of SMC, as well as in the lysates, but was devoid of effect on TFPI bound at the membrane of SMC. IL-6 and LIF reduced also TFPI secretion, which could explain why the PCA of SMC lysates treated by IL-6 or LIF was increased, despite an absence of effect on TF expression. In conclusion, these data support the hypothesis that by increasing the PCA of SMC, OSM might be involved in the thrombotic complications associated with plaque rupture.

Topics: Aorta; Arteriosclerosis; Cell-Free System; Cells, Cultured; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Regulation; Growth Inhibitors; Humans; Interleukin-6; Leukemia Inhibitory Factor; Lipoproteins; Lymphokines; Membrane Proteins; Muscle, Smooth, Vascular; Oncostatin M; Peptides; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; Risk Factors; Rupture, Spontaneous; Thromboplastin

Utilizing a disposable unit, intraoperative autotranfusion was employed during surgery in 53 patients admitted to the Bexar County Teaching Hospital at the University of Texas Health Science Center at San Antonio. During the two-year period of study, 26 patients underwent surgery for major traumatic injuries, 8 for ruptured ectopic pregnancy and 19 for miscellaneous emergency or elective conditions. The indication for intraoperative autotransfusion was an anticipated blood loss of 1,000 ml or more. Contraindications for its use were colon injury or localized infection. Over 325 units of blood were salvaged and returned directly to these patients during surgery. One death related to the use of the autotransfusor unit was due to massive air embolism. Twenty other deaths were associated with severe injuries and irreversible shock requiring greater than 3,600 ml of both autologous and homologous blood. Eight of these patients demonstrated severe pancoagulopathies. In the remaining patients, clotting factors and plasma or urine hemoglobin levels were transiently abnormal. However, there were no clinically apparent bleeding defects or renal problems detected. Postoperative blood cultures were consistently negative. It is concluded that intraoperative autotransfusion, when properly employed, is a safe, practical and technically feasible procedure.

Topics: Abdominal Injuries; Adult; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Blood Transfusion, Autologous; Blood Volume; Disposable Equipment; Emergencies; Female; Humans; Male; Pregnancy; Pregnancy, Ectopic; Prothrombin Time; Rupture, Spontaneous; Surgical Procedures, Operative; Thoracic Injuries; Thromboplastin; Time Factors; Wounds and Injuries; Wounds, Gunshot

Topics: Aminocaproates; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Fibrinolysis; Humans; Intracranial Aneurysm; Liver Function Tests; Male; Potassium; Rupture, Spontaneous; Sodium; Subarachnoid Hemorrhage; Thromboplastin