fibrin and Coronary-Disease

Topics: Anticoagulants; Clinical Trials as Topic; Coronary Disease; Enzyme Inhibitors; Fibrin; Humans; Macromolecular Substances; Thrombin; Thrombosis

Transplant-associated coronary artery disease (CAD) is the principal limiting factor for the long-term survival of heart transplant patients. This review discusses early risk factors for the subsequent development of transplant-associated CAD. Early risk factors associated with a prothrombogenic microvasculature, such as deposition of microvascular fibrin, depletion of vascular tissue plasminogen activator, presence of endothelial activation of the allograft arterial tree, and loss of vascular antithrombin, as well as changes in circulation (ie, detectable serum cardiac troponin I and elevated serum soluble intercellular adhesion molecule-1 levels) are presented and discussed. New therapies that could improve the status of the allograft microvasculature and may prevent or mitigate the development of transplant-associated CAD are considered.

Topics: Antithrombins; Biomarkers; Coronary Disease; Endothelium, Vascular; Fibrin; Graft Rejection; Graft Survival; Heart Transplantation; Humans; Intercellular Adhesion Molecule-1; Risk Factors; Tissue Plasminogen Activator; Transplantation Tolerance; Troponin I

Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes (ACS). However, the identification of patients at high-risk for progression of coronary thrombosis is difficult in part because we currently lack clinically meaningful laboratory methods for its detection. The most promising approaches involve the measurement in plasma of markers of fibrin formation and degradation. Thrombin activity, as reflected by plasma or urine concentrations of fibrinopeptide A, is increased in patients with ACS and is associated with adverse outcome. However, the use of fibrinopeptide A as a marker of fibrin formation is limited by the very short half-life of the compound, by artifact due to sample acquisition, and by extremely long turnaround times. To overcome these limitations, measurement of soluble fibrin has been proposed. We have recently explored the prognostic value of a new fibrin-specific ELISA assay for soluble fibrin in patients with ACS and found that patients with highest levels had a twofold increased risk of early and late cardiac events. Increases in plasma concentrations of cross-linked fibrin degradation products (XL-FDPs), which reflect increased fibrin turn-over, are a marker of risk for complications of myocardial infarction. However, until recently, assays for XL-FDPs lacked specificity, because they did not distinguish between fibrin and fibrinogen degradation products. Recently, fibrin-specific ELISAs have been described and a rapid whole blood assay for D-dimer has been developed. We recently validated the prognostic value of this whole blood agglutination assay in patients with ACS. The results suggest that: (1) the detection of significant activation of the coagulation and/or fibrinolytic system may be important for rapid risk stratification of patients with ACS; (2) patients with biochemical evidence of ongoing coronary thrombosis may particularly benefit from aggressive antithrombotic strategies; (3) sequential measurements of these markers may be useful to guide antithrombotic treatment during the unstable phase of coronary artery disease.

Topics: Acute Disease; Biomarkers; Coronary Disease; Fibrin; Hemostasis; Humans; Prognosis

Topics: Coronary Disease; Coronary Vessels; Fibrin; Heart Transplantation; Humans; Risk Factors; Transplantation, Homologous

Measurement of D-dimer (fibrin degradation product) is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulable state. However, fibrin degradation products are in variable, and the reactivity to cross-linked fibrin degradation products produced during fibrin degradation differs depending on the kind of antibody used against D-dimer. In patients with disseminated intravascular coagulation or earthquake-induced mental and physical stress and in patients after percutaneous transluminal coronary angioplasty, all of which are associated with acute fibrin formation and degradation, some discrepancies between two methods of D-dimer detection, automated latex agglutination assay (LPIA) and enzyme-linked immunosorbent assay (Stago), were found. No discrepancies in persistent fibrin formation and degradation were found among the healthy elderly, patients with lacunar stroke, and patients with coronary artery disease, almost all of whom had levels under 5.0 microg/mL, as determined by both methods. Evidence of persistently increased intravascular coagulation and fibrin turnover in patients with atherosclerotic disease was found. The cleavage of cross-linked fibrin by plasmin results in a production of fibrin degradation products, mostly contained D-dimer domains. Although the clinical utility of D-dimer can be achieved by their detection with specific antibodies, measurement of D-dimer as high-molecular-weight fragments may be useful to determine whether patients will undergo further fibrin degradation. When intermediate products of the degradation process need to be assessed, D-dimer level measurement by LPIA may serve as a suitable marker for ongoing fibrinolysis.

Topics: Adult; Aged; Aging; Angioplasty, Balloon, Coronary; Antibody Specificity; Biomarkers; Coronary Disease; Disasters; Disseminated Intravascular Coagulation; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Latex Fixation Tests; Male; Middle Aged; Molecular Weight; Risk Factors; Stress, Physiological; Stress, Psychological; Stroke; Thrombophilia

Topics: Coronary Disease; Fibrin; Fibrinolysis; Humans; Insulin Resistance; Myocardial Infarction; Plasminogen Activator Inhibitor 1; Polymorphism, Genetic; Risk Factors; Tissue Plasminogen Activator

Topics: Anticoagulants; Biomarkers; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Fibrin; Graft Occlusion, Vascular; Heart Transplantation; Humans; Muscle, Smooth, Vascular; Transplantation, Homologous

The development of transplant coronary artery disease (CAD) is directly associated with outcome in cardiac transplantation. The relationship between microvascular fibrin deposition early after transplantation and subsequent development of transplant CAD is discussed in this article. In this article the presence of microvascular fibrin and its association with other prothrombogenic changes within the cardiac microvasculature, such as loss of vascular antithrombin, depletion of arteriolar tissue plasminogen activator, and presence of arterial and arteriolar endothelium activation, as well as changes in circulation associated with prothrombogenic changes that have predictive value for subsequent transplant outcome are presented and discussed. Novel therapeutic approaches that may prevent the development of transplant CAD and consequently affect outcome are considered.

Topics: Animals; Blood Coagulation Factors; Cell Adhesion Molecules; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Fibrin; Heart Transplantation; Humans; Myocardium; Prognosis

Current thrombolytic therapy fails to induce early, complete, and sustained reperfusion in +/-50% of the patients with ST-segment elevation acute coronary syndromes. There are two complementary approaches to improve thrombolytic therapy: the development of new fibrinolytics with enhanced fibrin specificity and/or reduced plasma clearance and the coadministration of new antithrombotic agents. The results obtained so far suggest that single-bolus fibrinolytic therapy is likely to replace the current infusions in the near future. This may result in a significantly earlier (prehospital) treatment of patients. The concomitant intravenous administration of a glycoprotein IIb/IIIa receptor antagonist (in combination with a reduced dose of a fibrinolytic) appears to be able to further enhance the efficacy for clot lysis without increasing the risk for bleeding complications.

Topics: Coronary Disease; Fibrin; Fibrinolytic Agents; Hemorrhage; Humans; Injections, Intravenous; Metabolic Clearance Rate; Myocardial Infarction; Myocardial Reperfusion; Platelet Glycoprotein GPIb-IX Complex; Platelet Glycoprotein GPIIb-IIIa Complex; Platelet Membrane Glycoproteins; Receptors, Antigen, B-Cell; Receptors, Cell Surface; Substrate Specificity; Thrombolytic Therapy; Time Factors; Tissue Plasminogen Activator

Topics: Animals; Anticoagulants; Binding Sites; Coronary Disease; Fibrin; Heparin; Hirudin Therapy; Humans; Serpins; Thrombin; Thrombosis

This article is a review of recent developments of polymer-related stents mainly employed in the coronary arteries, including polymer-coated stents, biostable stents and biodegradable stents. Polymer paving is covered as well. The problems with the stents currently investigated and the development of new stents are discussed.

Topics: Adsorption; Biocompatible Materials; Biodegradation, Environmental; Coronary Disease; Coronary Vessels; Fibrin; Humans; Metals; Polyethylene Terephthalates; Polymers; Stents; Tantalum; Ultrasonography

Topics: Arteriosclerosis; Carotid Artery Diseases; Coronary Disease; Endothelium, Vascular; Fibrin; Humans; In Vitro Techniques; Lipoprotein(a); Monocyte Chemoattractant Proteins; Risk Factors; Transforming Growth Factor beta

Topics: Antithrombin III; Antithrombin III Deficiency; Capillaries; Coronary Disease; Coronary Vessels; Endocardium; Endothelial Growth Factors; Fibrin; Follow-Up Studies; Graft Survival; Heart Transplantation; Humans; Incidence; Lymphokines; Muscle, Smooth, Vascular; Prognosis; Tissue Plasminogen Activator; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Topics: Biocompatible Materials; Coronary Disease; Endothelium; Fibrin; Heparin; Humans; Microscopy, Electron, Scanning; Polymers; Stents; Thrombosis; Wound Healing

The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibitio

Topics: Antithrombin III; Antithrombin III Deficiency; Blood Coagulation; Coronary Disease; Coronary Thrombosis; Cryoglobulins; Fibrin; Fibrinolysis; Heparin Cofactor II; Humans; Myocardial Infarction; Plasminogen Activators; Protein C; Protein C Deficiency; Thrombophlebitis

Myocardial ischemia has traditionally been related to increased demand, but recent data suggest that intermittent episodes of decreased supply are also important. This article discusses the phenomena underlying the factors that produce spontaneous (non-effort-related) ischemia. These include local arterial phenomena, arterial plaques, endothelial phenomena, neural phenomena, and circadian patterns. The clinical spectrum of myocardial ischemia can be viewed as an interplay among supply, demand, local arterial reactivity, and acute plaque disruption. In addition, neural phenomena and circadian patterns of multiple cardiovascular phenomena combine to make the coronary circulation susceptible to an increased concentration of events in the morning hours, around the time of awakening. With this extension of our understanding of myocardial ischemia, we have reasonable assurance that methods of treatment will advance significantly in the near future.

Topics: Animals; Circadian Rhythm; Coronary Circulation; Coronary Disease; Coronary Vessels; Endothelium, Vascular; Fibrin; Humans; Nervous System; Platelet Aggregation

Thrombosis of a coronary artery is the most common cause of myocardial infarction. Thrombolytic therapy, when instituted timely, has been shown capable of reducing morbidity and mortality. However, the use of presently available thrombolytic agents is associated with a bleeding tendency and efficacy is not optimal. This article reviews one of several lines of investigation that are presently being pursued in order to improve efficacy and specificity of thrombolytic therapy. The chemical conjugation of a fibrin specific monoclonal antibody and urokinase or tissue plasminogen activator results in markedly enhanced thrombolytic potency, both in vitro and in vivo. Specificity of the conjugates is greater than that of the parent plasminogen activators as reflected by conservation of fibrinogen, plasminogen and alpha-2 antiplasmin. A bispecific antibody, with specificity for both, fibrin and tissue plasminogen activator, has the potential of concentrating endogenous tissue plasminogen activator at the site of a thrombus. In the presence of the bispecific antibody, efficacy and specificity of tissue plasminogen activator are markedly enhanced in vitro and in vivo. The tools of molecular biology are presently being applied in order to translate these findings into better thrombolytic therapy.

Topics: Antibodies, Monoclonal; Antibody Specificity; Coronary Disease; Coronary Thrombosis; Fibrin; Humans; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Many human atherosclerotic lesions, showing no evidence of fissure or ulceration, contain a large amount of fibrin which may be in the form of mural thrombus on the intact surface of the plaque, in layers within the fibrous cap, in the lipid-rich centre, or diffusely distributed throughout the plaque. Small mural thrombi are invaded by SMCs and collagen is deposited in patterns closely resembling the early proliferative gelatinous lesions. In experimental animals, thrombi are converted into lesions with all the characteristics of fibrous plaques, and in saphenous-vein bypass grafts, fibrin deposition is the main cause of wall thickening and occlusion. There seems little doubt that fibrin deposition can both initiate atherogenesis and contribute to the growth of plaques. Epidemiological studies indicate that increased levels of fibrinogen and clotting activity are associated with accelerated atherosclerosis, and although blood fibrinolytic activity has given inconsistent results, in arterial intima both fibrinolytic activity and plasminogen concentration are decreased in cardiovascular disease. Fibrin may stimulate cell proliferation by providing a scaffold along which cells migrate, and by binding fibronectin, which stimulates cell migration and adhesion. Fibrin degradation products, which are present in the intima, may stimulate mitogenesis and collagen synthesis, attract leukocytes, and alter endothelial permeability and vascular tone. In the advanced plaque fibrin may be involved in the tight binding of LDL and accumulation of lipid. Thus there is extensive evidence that enhanced blood coagulation is a risk factor not only for thrombotic occlusion, but also for atherogenesis. Enhanced blood coagulation frequently coexists with hyperlipidaemia and, together, these may have a synergistic effect on atherogenesis.

Topics: Animals; Arteriosclerosis; Coronary Disease; Disease Models, Animal; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Lipoproteins, LDL; Muscle, Smooth, Vascular; Risk; Thrombosis

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.

Topics: Aspirin; Cell Division; Coronary Artery Bypass; Coronary Disease; Endothelium; Epoprostenol; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Muscle, Smooth, Vascular; Platelet Adhesiveness; Platelet Aggregation; Receptors, Prostaglandin; Regional Blood Flow; Thrombosis; Thromboxane-A Synthase

Topics: Animals; Clinical Enzyme Tests; Coronary Disease; Diagnosis, Differential; Dogs; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Hypertension; Lung Diseases; Myocardial Infarction; Pulmonary Embolism; Solubility; Thrombophlebitis

Topics: alpha-2-Antiplasmin; Anticoagulants; Catheterization; Coronary Disease; Drug Evaluation; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Infusions, Intra-Arterial; Infusions, Parenteral; Myocardial Infarction; Plasminogen; Plasminogen Activators; Streptokinase; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Arachidonic Acids; Arteriosclerosis; Aspirin; Blood Platelets; Calcium; Coronary Disease; Cyclic AMP; Diabetes Mellitus; Dietary Fats; Female; Fibrin; Humans; Myeloproliferative Disorders; Nephrotic Syndrome; Oxygenases; Platelet Adhesiveness; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Prostaglandins; Thrombosis

Topics: Animals; Antibodies, Bacterial; Bacteria; Blood Platelets; Coronary Disease; Endocarditis; Endocarditis, Bacterial; Endocarditis, Subacute Bacterial; Fibrin; Heart Failure; Heart Valves; Humans; Platelet Aggregation; Prognosis; Rupture, Spontaneous; Sepsis; Thrombosis

Topics: Arteriosclerosis; Aspirin; Blood Platelets; Blood Protein Disorders; Cell Survival; Coronary Disease; Endothelium; Fibrin; Humans; Lipid Metabolism; Lipoproteins; Phagocytosis; Platelet Adhesiveness; Prostaglandins; Pyrazoles; Pyrimidines; Thrombosis

Topics: Animals; Aorta; Arteriosclerosis; Blood Platelets; Calcinosis; Child; Cholesterol; Collateral Circulation; Coronary Disease; Coronary Vessels; Erythrocytes; Female; Fibrin; Fibroblasts; Glycosaminoglycans; Hemorrhage; Histocytochemistry; Humans; Lipids; Macrophages; Male; Middle Aged; Muscle, Smooth; Necrosis; Rabbits; Rupture; Thrombosis

Topics: Animals; Antibodies; Arteries; Blood Platelets; Capillaries; Coronary Disease; Coronary Vessels; Cortisone; Dogs; Endocarditis; Fibrin; Graft Rejection; Heart Failure; Heart Transplantation; Hemorrhage; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Infections; Kidney Transplantation; Male; Microscopy, Electron; Middle Aged; Myocarditis; Myocardium; Necrosis; Rabbits; Shwartzman Phenomenon; Time Factors; Transplantation Immunology; Transplantation, Homologous

Topics: Adenosine Diphosphate; Animals; Antigen-Antibody Complex; Arteriosclerosis; Blood Coagulation; Blood Coagulation Disorders; Blood Flow Velocity; Blood Platelets; Cell Membrane; Collagen; Coronary Disease; Cytoplasmic Granules; Factor VII; Factor XII; Fibrin; Fibrinolysis; Humans; Microscopy, Electron; Microtubules; Platelet Adhesiveness; Rabbits; Serotonin; Thrombosis

Circulating levels of Brain Derived Neurotrophic Factor (BDNF) are lower in coronary heart disease (CHD) than in healthy subjects and are associated with coronary events and mortality. However, the mechanism(s) underling this association is not fully understood. We hypothesize that BDNF may influence fibrin fiber structure and clot stability, favoring clot lysis and thrombus resolution. We showed that recombinant BDNF (rh-BDNF) influenced with clot formation in a concentration-dependent manner in both purified fibrinogen and plasma from healthy subjects. In particular, rh-BDNF reduced the density of fibrin fibers, the maximum clot firmness (MCF) and the maximum clot turbidity, and affected the lysis of clot. In addition, both thrombin and reptilase clotting time were prolonged by rh-BDNF, despite the amount of thrombin formed was greater. Intriguingly, CHD patients had lower levels of BDNF, greater fibrin fibers density, higher MCF than control subjects, and a negative correlation between BDNF and MCF was found. Of note, rh-BDNF markedly modified fibrin clot profile restoring physiological clot morphology in CHD plasma. In conclusion, we provide evidence that low levels of BDNF correlate with the formation of bigger thrombi (in vitro) and that this effect is mediated, at least partially, by the alteration of fibrin fibers formation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Coagulation; Brain-Derived Neurotrophic Factor; Coronary Disease; Fibrin; Humans; Male; Middle Aged

Fibrinogen is an important risk factor for atherosclerosis, stroke and cardiovascular heart disease (CHD). This risk is increased when associated with a high serum cholesterol. Furthermore, it is also believed that not only fibrinogen concentration, but also the quality of fibrin networks may be an important risk factor for the development of CHD. CHD and stroke as a result of atherosclerosis, plus the related problems of hyperinsulinaemia, hyperlipidaemia and hypertension are strongly related to diet. The "western" diet, defined by low fibre and high fat, sucrose and animal protein intakes, appears to be a major factor leading to death. It has been established that the water-soluble dietary fibre, pectin, significantly decrease the concentration of serum cholesterol levels. Evidence is also accumulating that a diet rich in fibre may protect against diseases associated with raised clotting factors. This investigation studied the possible effects of pectin on fibrinogen levels and fibrin network architecture. Two groups of 10 male hyperlipidaemic volunteers each, received a pectin supplement (15 g/day) or placebo (15 g/day) for 4 weeks. Lipid and fibrin network structure variables were measured at baseline and the end of supplementation. Pectin supplementation caused significant decreases in total cholesterol, low-density lipoprotein cholesterol, apolipoprotein A & B and lipoprotein (a). Significant changes in the characteristics of fibrin networks developed in the plasma of the pectin supplemented group indicated that networks were more permeable and had lower tensile strength. These network structures are believed to be less atherogenic. It is suspected that pectin modified network characteristics by a combination of its effects on metabolism and altered fibrin conversion. This confirms the therapeutic possibilities of dietary intervention. Furthermore, this study also showed that changes in plasma fibrinogen need not be present to induce alterations in fibrin network architecture.

Topics: Adult; Cholesterol; Coronary Disease; Dietary Fiber; Double-Blind Method; Fibrin; Fibrinogen; Hemostasis; Humans; Hypercholesterolemia; Lipids; Male; Middle Aged; Molecular Structure; Pectins; Risk Factors

Topics: Blood Coagulation; Cardiomyopathy, Hypertrophic; Chromatography, Agarose; Clinical Trials as Topic; Coronary Angiography; Coronary Disease; Factor XII; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Clinical Trials as Topic; Coronary Disease; Electrocardiography; Fibrin; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Humans; Male; Middle Aged; Myocardial Infarction; Plasminogen; Stanozolol

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Coronary Disease; Diabetes Mellitus, Type 2; Female; Fibrin; Humans; Hypertension; Middle Aged; Platelet Aggregation

Bare-metal stents have undergone intense pathological and clinical examination, but histological characterization of drug-eluting stent (DES) restenosis (ISR) remains unknown. We report a series of cases (n=6) with intravascular ultrasound (IVUS) and pathological examinations over 8 months after DES deployment. Tissue samples were obtained using atherectomy devices in 5 cases and a thrombectomy catheter in 1 case. Histology revealed not only smooth muscle cell proliferation, which correlated with homogeneous hypoechoic tissue by IVUS in one case, but also demonstrated delayed healing features such as organized fibrin deposition in 3 cases (one with homogeneous echolucent tissue by IVUS), macrophage and T-lymphocyte infiltration in others. IVUS appearance of ISR components varied from echolucent to echodense images. This report suggests a variable histological and IVUS pattern of ISR after DES implantation. Further investigations are necessary to define the potentially pro-thrombotic histological features of ISR after DES implantation, and the relationship between the molecular mechanisms of thrombosis and DES restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Atherectomy; Coronary Disease; Coronary Restenosis; Drug-Eluting Stents; Female; Fibrin; Humans; Macrophages; Male; Middle Aged; Muscle, Smooth, Vascular; T-Lymphocytes; Thrombectomy; Ultrasonography, Interventional

Increased levels of microparticles exposing tissue factor circulate in the blood of patients with coronary heart disease, possibly disseminating their pro-thrombotic and pro-inflammatory potential. Because diets rich in n-3 (polyunsaturated) fatty acids have been associated with reduced incidence of coronary heart disease-related events, we investigated the in vivo effects of treatments with n-3 fatty acids on levels of circulating microparticles and their tissue factor- dependent procoagulant activity in patients with a previous myocardial infarction.. Forty-six post-myocardial infarction patients were assigned to receive either 5.2 g of n-3 fatty acids daily (n=23) or an olive oil placebo (n = 23) for 12 weeks. Circulating microparticles were isolated from peripheral blood. The number of microparticles, their cellular source and tissue factor antigen were determined by flow cytometry, and their procoagulant potential assayed by a fibrin generation test.. The total number of microparticles, endothelium-derived microparticles and microparticle tissue factor antigen were not significantly different between the two groups. However, the number of platelet-derived microparticles [from a median of 431 (126-1796, range) x 10(6)/L to a median of 226 (87-677, range)] x 10(6)/L and monocyte-derived microparticles [from a median of 388 (9-1681, range) x 10(6)/L to a median of 265 (7-984, range) x 10(6)/L] in plasma were significantly (p < 0.05) decreased by n-3 fatty acids, while they were unchanged in the placebo group. Total microparticle tissue factor-procoagulant activity was also reduced in the n-3 fatty acid group compared to that in the placebo group.. Treatment with n-3 fatty acids after myocardial infarction exerts favorable effects on levels of platelet- and monocyte-derived microparticles, thus possibly explaining some of the anti-inflammatory and anti-thrombotic properties of these natural compounds.

Topics: Aged; Blood Platelets; Coronary Disease; Endothelium, Vascular; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Infarction; Placebos; Thromboplastin; Thrombosis

The role of a hypercoagulable microvasculature in the development of cardiac allograft vasculopathy (CAV) after heart transplantation in humans is not well understood. The aim of this study was to identify an animal model by which to further evaluate the role of coagulation in the pathogenesis of CAV.. Adult male PVG (RT-1(c)) rats were transplanted into ACI (RT-1(av1)) recipients (n = 29). ACI donors into ACI recipients (n = 31) and rats with a sham operation (n = 33) served as controls. All rats received cyclosporine (10 mg/kg/day) on Days 0 to 9 after surgery. Grafts and native hearts were harvested at 10 days to 3 months after surgery. Hearts were processed for immunohistochemistry and light microscopy. A hypercoagulable microvasculature was defined as presence of microvascular fibrin and capillary antithrombin. CAV was defined as the presence of concentric intimal proliferation and chronic inflammatory infiltrate in the arterial intima, and assessed by computer-assisted image analysis.. Donor and recipient hearts from PVG-ACI rats showed high levels of fibrin (donors 7.5% to 21.9%, recipients 5.1% to 20.2%) and antithrombin (donors 5.2% to 27.9%, recipients 3.3% to 20.8%) at 10 days to 3 months post-transplant. ACI-ACI donor and recipient hearts had lower deposition of fibrin (donors 0.9% to 9.9%, recipients 0% to 4.0%) and antithrombin (donors 1.4% to 15.2%, recipients 0.8% to 4.5%). Hearts from sham-operated rats had negligible amounts of fibrin (0% to 1.5%) and antithrombin (0% to 2.8%). There was a strong association (p < 0.001) between presence of fibrin and capillary antithrombin and development of CAV.. A hypercoagulable microvasculature in a rat model of heart transplantation was associated with development of CAV, as found in humans.

Topics: Animals; Antithrombins; Capillaries; Coronary Disease; Coronary Thrombosis; Coronary Vessels; Disease Models, Animal; Fibrin; Heart Transplantation; Immunohistochemistry; Male; Microcirculation; Myocardium; Rats; Rats, Inbred Strains; Transplantation, Heterotopic; Transplantation, Homologous

The purpose of the study was to determine the level of thrombus precursor protein (TrP) in patients with acute coronary syndrome (ACS). Twenty-six patients with ACS and anginal pain experienced during 2 to 12 hours (7.2 +/- 1.3 hours), admitted to cardiological intensive care unit, were enrolled in the study. Five ml of blood were sampled from a cubital vein of all the patients during the phase of the most intensive pain. TrP blood levels were measured with ELISA, Enzyme-Linked Immunoadsorbent Assay. The control group consisted of 29 healthy volunteers and 22 patients with stable exertional stenocardia. A significant increase in TpR (7.2 +/- 1.45 mcg/ml) was noted in the ACS patients as early as during the first 6 hours, vs. the healthy controls (1.01 +/- 0.12 mcg/ml) and the patients with stable stenocardia (1.21 +/- 0.06 mcg/ml), p < 0.01. A high level of TrP in the ACS patients could be noted earlier than a diagnostically significant increase in creatine phosphokinase level. No direct correlation was observed between the TrP level and the dynamics of such indices of the procoagulatory hemocoagulation chain as fibrinogen, prothrombin index, and active partial thromboplastin time. The results of the study demonstrate that the measurement of TrP level is highly informative when the intensity of intravascular blood coagulation in ACS patients is to be evaluated, which can be used to clarify indications to anticoagulation therapy. The enzyme immune method of TrP detection in the plasma of ACS patients can be recommended for clinical application.

Topics: Acute Disease; Biomarkers; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Follow-Up Studies; Humans; Male; Middle Aged; Prognosis; Severity of Illness Index; Syndrome

A cross sectional and prospective analysis of 3,745 British women aged 60-79 years at baseline was undertaken. Among these women there were 570 prevalent cases of coronary heart disease (CHD) and 151 new cases among 12,641 person-years of follow up of women who were free of CHD at baseline. Both fibrinogen and CRP were associated with indicators of socioeconomic position in childhood and adulthood and there was a cumulative effect of socioeconomic position from across the life course. The age-adjusted odds ratio (95% confidence interval) of prevalent CHD for a 1 unit (1 g/L) increase in fibrinogen was 1.29 (1.12, 1.49); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.93, 1.28). The hazards ratio for incident CHD among those free of disease at baseline was 1.28 (1.00, 1.64); with full adjustment for all potential confounding factors this attenuated to 1.09 (0.84, 1.44). Similar effects of adjustment for confounding factors were seen for the associations between CRP and both prevalent and incident CHD. By contrast, the strong positive association between smoking (an established causal risk factor for CHD) and CHD was not attenuated by adjustment for life course socioeconomic position or other risk factors. We conclude that fibrinogen and CRP predict CHD but may not be causally related to it.

Topics: Age Factors; Aged; Arteriosclerosis; C-Reactive Protein; Confounding Factors, Epidemiologic; Coronary Artery Disease; Coronary Disease; Female; Fibrin; Fibrinogen; Humans; Inflammation; Middle Aged; Models, Statistical; Odds Ratio; Prospective Studies; Risk Factors; Social Class

Global assays, such as resonance-thrombography (RTG), which measure the interaction between platelets, coagulation and fibrinolysis have been used as summary measures of risk for over two decades but have not been evaluated in epidemiological studies. We examined whether RTG indices are risk indicators for incident coronary heart disease (CHD). RTG indices, related haematological variables and other risk factors were measured between 1984 and 1988 in a cohort of 2398 British men. Reaction time (r) and amplitude of fibrin leg (AF) were associated with lifestyle risk factors. During 9 years of follow-up, 282 (12%) men developed a major new CHD event, as classified by World Health Organization criteria. On adjustment for age, only r and AF measured at baseline were related to risk of incident CHD. On multivariate adjustment in a multiple logistic regression model that included age, diastolic blood pressure, body mass index, total and high-density lipoprotein cholesterol, lifestyle risk factors and use of prescribed medicine, these associations weakened but remained significant. Additional adjustment for fibrinogen, viscosity, white cell count and fibrin d-dimer either reduced these associations to non-significance (AF) or to borderline significance (r).

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Coronary Disease; Fibrin; Humans; Incidence; Logistic Models; Male; Middle Aged; Nephelometry and Turbidimetry; Odds Ratio; Predictive Value of Tests; Prospective Studies; Risk Factors; Wales

Transplant coronary artery disease is the leading cause of long-term morbidity and mortality in cardiac transplantation. We developed a model for early identification of patients who subsequently develop coronary artery disease and graft failure. Serial biopsies obtained from 141 cardiac allografts (5.5 +/- 0.1 biopsies/patient) during the first 3 months post-transplant were evaluated immunohistochemically for deposition of myocardial fibrin, depletion of arteriolar tissue plasminogen activator, presence of arterial/arteriolar endothelial activation markers, and changes in vascular antithrombin. An immunohistochemical risk score was developed with a minimum value of 0 (normal) and a maximum value of 4 (most abnormal). Scores of 0 (low risk), 0.5-3.0 (moderate risk), and 3.5-4.0 (high risk) were analyzed for association with graft failure and development, severity, and progression of coronary artery disease detected using serial coronary angiograms (3.9 +/- 0.2/patient). Allografts with high immunohistochemical risk scores in the first 3months post-transplant developed more coronary artery disease (p<0.001), developed coronary artery disease earlier (p<0.001), developed more severe disease (p<0.001), and showed more disease progression (p<0.001) than allografts with moderate or low scores. Allografts with high immunohistochemical risk scores in the first 3 months post-transplant failed more (p<0.001) and failed earlier (p<0.001) than allografts with moderate or low scores. The present study demonstrates that early changes in the microvasculature are associated with impending coronary artery disease and graft failure in cardiac allograft recipients and suggests that treatment needs to be instituted early after transplantation in order to improve outcome.

Topics: Actins; Adult; Antibodies, Monoclonal; Biopsy; Cardiomyopathy, Dilated; Coronary Disease; Fibrin; Heart Transplantation; HLA-DR Antigens; Humans; Immunohistochemistry; Middle Aged; Postoperative Complications; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Tissue Plasminogen Activator; Transplantation, Homologous

Previous studies have yielded conflicting data regarding whether a relationship exists between elevated cardiac troponin levels and acute allograft rejection in patients who have received heart transplants.. To determine whether cardiac troponin I levels after heart transplantation were associated with a procoagulant microvasculature and long-term allograft outcome.. Prospective cohort study with a mean (SE) follow-up of 45.1 (2.5) months. Serum troponin I levels were measured 9.9 (0.2) times per patient during the first 12 months after heart transplantation.. Heart transplant center in the United States.. A total of 110 consecutive patients who received a heart transplant between 1989 and 1997 and survived at least 1 year after transplantation.. Histological and immunohistochemical biopsy findings, development of coronary artery disease (CAD), and graft failure in patients with vs without elevated serum cardiac troponin I levels.. All recipients had elevated troponin I levels during the first month after transplantation. Troponin I levels remained persistently elevated during the first 12 months in 56 patients (51%) and became undetectable in 54 patients (49%). Persistently elevated troponin I levels were associated with increasing fibrin deposits in microvasculature and cardiomyocytes (P<.001). Patients with persistently elevated levels of troponin I had significantly increased risk for subsequent development of CAD (odds ratio [OR], 4. 3; 95% confidence interval [CI], 1.8-10.1; P<.001) and graft failure (OR, 3.4; 95% CI, 1.2-9.7; P =.02), and also developed more severe CAD (OR, 4.2; 95% CI, 1.9-9.3; P<.001) and showed more disease progression (OR, 3.7; 95% CI, 1.3-10.4; P =.009).. In this study, elevated cardiac troponin I levels, which are considered to be a noninvasive surrogate marker of a procoagulant microvasculature, identified a subgroup of patients with high risk for developing CAD and graft failure after cardiac transplantation. JAMA. 2000;284:457-464

Topics: Adult; Coronary Disease; Fibrin; Graft Rejection; Heart Transplantation; Humans; Immunohistochemistry; Male; Microcirculation; Middle Aged; Myocardium; Prognosis; Prospective Studies; Regression Analysis; Risk; Troponin I

It has been suggested that blood coagulation be activated and fibrinolytic activity be impaired in patients with coronary artery disease (CAD). With regard to the activation of coagulation and fibrinolysis occurring during exercise in healthy individuals, we examined the hypothesis that rehabilitative exercise in patients with CAD might give rise to an exaggerated activation of coagulation. In 12 patients with angiographically documented CAD without myocardial infarction within the preceding 6 months (male, age 55+/-9 years [SD]) and in 12 healthy controls (male, 52+/-7 years), molecular markers of thrombin, fibrin, and plasmin formation were determined before and after a rehabilitative group exercise session lasting 1 hour. Resting levels of prothrombin fragment 1+2 were lower in patients with CAD (0.67+/-0.2 [SE] vs 1.04+/-0.2 nmol/L, p <0.001) and remained unchanged after exercise, whereas a significant increase was noted in controls (p <0.01). After exercise, plasma levels of thrombin-antithrombin III complexes and of fibrinopeptide A increased significantly in both groups, although there were more pronounced changes in controls. Exercise resulted in a marked generation of plasmin as indicated by plasmin-alpha2-antiplasmin complexes increasing 2.5-fold in patients (p <0.001) and threefold in controls (p <0.001). Repeated experiments in control subjects after administration of aspirin (day 1: 500 mg; days 2 to 5: 100 mg) documented that differences between groups could not be attributed to aspirin medication (100 mg/day) in patients with CAD. We concluded that rehabilitative exercise in patients with CAD beyond the immediate postinfarction period has no detrimental effects on thrombin, fibrin, and plasmin formation.

Topics: Adult; Aged; Aspirin; Blood Coagulation; Coronary Disease; Exercise Therapy; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Secondary Prevention; Thrombin

To determine whether fibrin deposition during the first month following cardiac transplantation predicts development of coronary artery disease and graft failure in cardiac allograft recipients.. We prospectively studied 121 consecutive adult patients who received cardiac transplants between 1988 and 1995. Serial endomyocardial biopsies obtained during the first month posttransplant (2.3 + 0.6 biopsies/patient) were studied immunohistochemically for fibrin deposits. Patients were followed up with annual angiograms (3.2 + 1.7/patient) evaluated with side-by-side comparisons for the presence and progression of coronary artery disease.. All pretransplant biopsies were fibrin-negative; 60 allografts (50%) remained without fibrin, and 61 (50%) contained fibrin during the first posttransplant month. Of allografts with fibrin, 72% developed coronary artery disease, while 27% of allografts without fibrin developed the disease (P <0.001). Coronary artery disease was progressive in 61% of allografts with fibrin, and in 25% of allografts without fibrin (P <0.001). Graft failure was more frequent and time-to-graft-failure occurred earlier in patients whose allografts had fibrin during the first month after transplantation (P <0.001).. Fibrin in biopsies during the first month after transplantation identifies patients at high risk for developing coronary artery disease or graft failure, thereby allowing the opportunity to initiate preventive procedures.

Topics: Adult; Biopsy; Coronary Angiography; Coronary Disease; Diagnosis, Differential; Female; Fibrin; Graft Occlusion, Vascular; Heart Transplantation; Humans; Male; Middle Aged; Myocardium; Risk; Time Factors

Development of coronary artery disease in cardiac allograft recipients is the major cause of graft failure after the first year of transplantation. Unfortunately, there is no noninvasive method of identifying patients at greatest risk of developing this disease. We have asked whether serum concentrations of cardiac troponin-T predict development of coronary artery disease.. Annual coronary angiograms, serial endomyocardial biopsies, and serum cardiac troponin-T concentrations were obtained from 68 cardiac transplant patients who were followed for 68.8+/-11.9 months after surgery. Troponin-T concentrations were measured by using an enzyme-linked immunosorbent assay, and biopsies were assessed histologically for rejection grades and immunohistochemically for cellular infiltrates, arteriolar endothelial activation, fibrin deposits, and vascular fibrinolytic and anticoagulant components.. Troponin-T values did not associate with demographic, clinical, or laboratory findings, but they significantly associated with arteriolar endothelial activation (P<0.001), fibrin deposition (P<0.001), depletion of vascular fibrinolytic (P=0.007) and anticoagulant components (P=0.02), and infiltration of macrophages (P <0.001) but not T lymphocytes (P=0.36). Troponin-T concentrations also significantly associated with future development of coronary artery disease (P<0.001). Patients with persistent troponin-T values of 0.10 ng/ml or greater were found to develop the disease within 8.7+/-2.1 months, whereas patients who had initial troponin-T values of 0.10 ng/ml or greater and subsequently fell and remained below 0.10 ng/ml did not develop coronary artery disease in 40 months.. Troponin-T concentrations significantly associated with macrophage infiltrates, microvascular fibrin deposits, arteriolar endothelial activation, depletion of vascular fibrinolytic and anticoagulant components, and the future development of coronary artery disease. The troponin-T assay is an outpatient procedure performed on small amounts of blood at little cost, risk, or inconvenience, and it appears to be the first biochemical predictor of transplant-induced coronary artery disease.

Topics: Adult; Coronary Disease; Female; Fibrin; Heart Transplantation; Humans; Male; Middle Aged; Reperfusion Injury; Risk Factors; Troponin T

In a porcine coronary model, fibrin film soaked for 3 h in heparin was used as a circumferential coating on a tantalum stent to assess the effect of this naturally occurring biopolymer on arterial healing. The results were compared with those obtained with medical grade polyurethane-coated stainless steel stents.. Thrombus plays an important role in healing after arterial injury and may affect the development of neointimal hyperplasia. Manipulation of the initial thrombus may alter the healing response. To study this, we placed a template of fibrin in a porcine coronary artery restenosis model.. Thirty-four fibrin film stents were delivered in 20 swine. Oversizing was avoided, to prevent deep arterial injury, by placement of optimally sized stents. Initial patency of the stented vessel was confirmed by angiography.. Three fibrin-stented swine died within 48 h; in each, the stent was occluded with a fibrin/red blood cell mass. In two of these three, a portion of the exogenous fibrin had become detached from the stent and partially occluded the lumen. Of the remaining 31 stents, all were patent at elective sacrifice at 28 days. Eighty-four percent had a diameter stenosis < 50%, and the mean (+/- SD) diameter stenosis was 32.3 +/- 13%. There was no evidence of significant foreign-body giant-cell reaction. These results contrasted with the medical grade polyurethane-coated stents placed according to the same protocol without oversizing. Twelve of these stents were placed; six swine died of thrombotic occlusion within the 1st 48 h. At elective sacrifice at 28 days, the remaining polyurethane-coated stents were occluded by marked neointimal hyperplasia.. Fibrin film-coated stents seem promising as a template for modifying the local response to arterial injury and for potentially decreasing restenosis rates.

Topics: Animals; Biocompatible Materials; Coronary Disease; Coronary Vessels; Disease Models, Animal; Equipment Design; Fibrin; Hyperplasia; Materials Testing; Polyurethanes; Recurrence; Stents; Swine; Tunica Intima

The prothrombotic state of patients with coronary artery disease (CAD) can be attributed partially to platelet activity. Management of such patients is hindered by a lack of techniques to assess hemostatic function. This study used a sensitive technique to monitor platelet function by measuring platelet force development during clot retraction. This technique allowed simultaneous measurement of clot elastic modulus on the same sample. Fibrin mass-length ratio (mu), fibrinopeptide A, D-Dimer, von Willebrand's factor, thromboxane A2, platelet aggregation studies, and bleeding times also were performed. Fourteen patients with CAD were compared with 10 healthy volunteers. Despite more than 95% suppression of thromboxane B2 and prolongation bleeding times in patients taking aspirin, force development remained significantly elevated over healthy control patients (8,279 +/- 476 dynes versus 4,857 +/- 380 dynes, p < 0.0006). Patients not taking aspirin had normal bleeding times and force development of 19,110 +/- 3,700 dynes. Clot elastic moduli were enhanced in patients with CAD whether taking or not taking aspirin. Adenosine diphosphate and ristocetin-induced platelet aggregation were insensitive to the effect of aspirin in patients with CAD. Fibrinopeptide A, von Willebrand's factor, and D-Dimer levels were significantly elevated, and fibrin mass-length ratios were significantly larger in patients with CAD. Therefore, despite aspirin therapy, patients with severe CAD have evidence of persistent platelet activation and rigid clot structure. Monitoring of platelet force development may prove useful in delineating enhanced platelet function.

Topics: Adult; Aspirin; Blood Coagulation; Blood Platelets; Coronary Disease; Fibrin; Humans; Platelet Activation; Thrombin

The native fibrin gel structure formed in vitro from plasma samples was examined by liquid permeation of the hydrated fibrin gel networks in 18 men who had suffered a myocardial infarction before the age of 45 years and in 20 control subjects. Patients with an elevated plasma fibrinogen concentration had a considerably lower fibrin gel porosity (permeability coefficient, Ks) compared with patients with a normal plasma fibrinogen level and with controls. The calculated fiber mass-length ratio of the fibrin gel networks was decreased in both patient groups. Gel porosity differed markedly between individuals at a given plasma fibrinogen concentration. Fairly strong inverse correlations were found between plasma orosomucoid level on the one hand and Ks (r = -0.617, p less than 0.01) or fiber mass-length ratio (r = -0.499, p less than 0.05) on the other. The low density lipoprotein (LDL) cholesterol concentration also correlated inversely with Ks (r = -0.471, p less than 0.05) and fiber mass-length ratio (r = -0.522, p less than 0.05). Significant inverse relations, which were independent of plasma fibrinogen and lipoprotein concentrations, were detected between Ks (r = -0.519, p less than 0.05) and calculated fiber mass-length ratio (r = -0.723, p less than 0.001) and number and severity of coronary artery stenoses determined by angiography. A proneness to formation of tight, rigid and space-filling fibrin network structures with small pores thus appears to be associated with premature coronary artery disease.

Topics: Acute-Phase Proteins; Adult; Coronary Artery Disease; Coronary Disease; Fibrin; Fibrinogen; Gels; Humans; In Vitro Techniques; Lipoproteins; Male; Molecular Structure; Myocardial Infarction; Polymers

To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital.. Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction.. The coronary care unit of a district general hospital.. 44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3-9) days later.. Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35).. Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = -0.43, p < 0.005) and left ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or = 31 seconds (p < 0.01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables.. Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.

Topics: Aged; Cardiac Catheterization; Coronary Disease; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Prospective Studies; Streptokinase; Stroke Volume; Thrombin Time; Thrombolytic Therapy; Ventricular Function, Left

Since currently available thrombolytics still show disadvantages, such as administration by infusion, occurrence of intracranial hemorrhage, major hemorrhagic complications, allergic reactions, and high price, a novel tissue plasminogen activator has been developed. BM 06.022 is a t-PA mutant produced in Escherichia coli by DNA technology. It has no oligosaccharide side-chains and comprises the kringle 2- and protease domains of t-PA. Like t-PA, the enzymatic activity of BM 06.022 can be stimulated by fibrin. However, BM 06.022 binds to neither endothelial cells nor fibrin. Despite this, BM 06.022 demonstrates the same fibrin selectivity in vivo as t-PA. Investigation of the pharmacokinetic properties in rats, rabbits, dogs, and primates reveals, depending on species, a 4.5- - 10.4-fold longer dominant half-life and 3- - 8.4-fold slower plasma clearance than t-PA (alteplase). In spite of its lower specific activity in vitro, BM 06.022 has a thrombolytic potency which is 4.6 - 11.5 times higher in vivo than that of alteplase in the rabbit model of venous thrombosis and the canine model of coronary artery thrombosis. BM 06.022 achieves reperfusion significantly more rapid than long-acting anistreplase. Therefore, because of its improved pharmacokinetic properties, BM 06.022 might be administered to infarct patients by i.v. injection in the pre-hospital phase to achieve rapid lysis. Due to its lack of fibrin- and endothelial-cell-binding, combined with retained fibrin selectivity, BM 06.022 further promises to induce fewer hemorrhagic complications than either t-PA or streptokinase.

Topics: Animals; Coronary Disease; Coronary Thrombosis; Dogs; Escherichia coli; Fibrin; Fibrinolytic Agents; Humans; Mutation; Rabbits; Recombinant Proteins; Tissue Plasminogen Activator

Hydrated fibrin gels were studied by confocal laser 3D microscopy, liquid permeation and turbidity. The gels from normal fibrinogen were found to be composed of straight rod-like fiber elements which sometimes originated from denser nodes. In gels formed at increasing thrombin or fibrinogen concentrations, the gel networks became tighter and the porosity decreased. The fiber strands also became shorter. Gel porosity of the network decreased dramatically in gels formed at increasing ionic strengths. Shortening of the fibers were observed and fiber swelling occurred at ionic strength above 0.24. Albumin and dextran, when present in the gel forming system, affected the formation of more porous structures with strands of larger mass-length ratio and fiber thickness. This type of gels were also formed in plasma. Albumin and lipoproteins may be among the determinants for the formation of this type of gel structure in plasma. Gels formed when factor XIIIa instead of thrombin was used as catalyst for gelation showed a completely different structure in which lumps of polymeric material were held together by a network of fine fiber strands. Our studies have also shown that the methodologies employed may be useful in studies of gel structures in certain dysfibrinogenemias as well as in other diseases. We give examples of two patients with abnormal fibrinogen and of patients with ischaemic heart disease.

Topics: Adult; Afibrinogenemia; Blood Coagulation; Coronary Disease; Factor XIII; Fibrin; Fibrinogen; Fluorescein-5-isothiocyanate; Fluoresceins; Fluorescent Dyes; Gels; Humans; Kinetics; Lasers; Microscopy; Nephelometry and Turbidimetry; Permeability; Reference Values; Thiocyanates; Thrombin

To evaluate the thrombolytic effects of the native tissue-type plasminogen activator (t-PA), the authors used a thrombus model simulating clinical situations. The native t-PA (AK-124) was obtained from human-derived normal cells. Experimental canine coronary thrombosis was produced by partial constriction and endothelial denudation of the vessel. In 19 dogs, coronary occlusive thrombus was produced. Three hours after total occlusion of the coronary artery with thrombus, the authors attempted the thrombolytic therapy in 16 dogs. Histologically, three-hour thrombus was composed of a mixture of platelet aggregates, fibrin, and blood cells. They infused 0.375 mg/kg t-PA intravenously in 7 dogs and 20,000 IU/kg urokinase (UK) in 9. Coronary recanalization was achieved in 5 (71%) with t-PA infusion and 6 (67%) with UK infusion. Plasma fibrinogen levels decreased to 76% of preinfusion value in the dogs with t-PA infusion and to 34% in those with UK infusion. Coronary reocclusion occurred in 2 dogs with t-PA and 3 with UK. Thus, the native t-PA (AK-124) can provide coronary thrombolysis without severe depletion of plasma fibrinogen levels.

Topics: Animals; Coronary Disease; Coronary Thrombosis; Dogs; Fibrin; Fibrinogen; Humans; Platelet Aggregation; Recurrence; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

The frequency and clinical significance of platelet/fibrin microemboli in the microcirculation were investigated in 24 patients whose deaths (before and during hospital admission) were associated with acute myocardial infarction. An acute coronary thrombus was present in all the hearts. In nine hearts an acute thrombus was found in more than one major epicardial coronary artery. A total of 35 acute thrombi were found in the 24 hearts. Platelet/fibrin microemboli were found in 19 (79%) hearts. Eighteen patients died in hospital. The hearts of 16 of these cases showed microemboli; 16 had important arrhythmias or various forms of heart block; 13 showed acute pathological changes in the conduction system. Fourteen of the deaths in hospital were primarily the result of cardiogenic shock and four were primarily caused by arrhythmia. Six of the deaths that occurred before admission to hospital were regarded as being arrhythmic in origin. Three of these showed microemboli and the other three had acute pathological changes in the conduction system. Microemboli were found in two (24%) of 12 control hearts. Coronary thrombosis was found in most deaths caused by acute myocardial infarction and platelet/fibrin microemboli were present in the majority of such hearts. These may arise from the coronary thrombus in the larger upstream vessel supplying the microcirculation.

Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; Coronary Disease; Coronary Thrombosis; Female; Fibrin; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium

Topics: Antigens; Coronary Disease; Fibrin; Humans

The effect of pacing-induced myocardial ischemia on platelet activation and fibrin formation was investigated in seven patients with severe proximal lesions of the left anterior descending coronary artery to determine if acute ischemia activates the coagulation system. Fibrin formation was assessed from plasma levels of fibrinopeptide A. Platelet activation was assessed by levels of platelet factor 4, beta-thromboglobulin and thromboxane B2. Plasma levels were measured before, during and after acute myocardial ischemia induced by rapid atrial pacing. Blood samples were collected from the ascending aorta and from the great cardiac vein through heparin-bonded catheters. The occurrence of anterior myocardial ischemia was established by electrocardiography and by myocardial lactate extraction. No significant transmyocardial gradients in the levels of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 were found at rest, during ischemia or in the recovery period, and levels in the great cardiac vein did not change in response to ischemia. These data indicate that pacing-induced myocardial ischemia does not result in release of fibrinopeptide A, platelet factor 4, beta-thromboglobulin or thromboxane B2 into the coronary circulation, and imply that acute ischemia does not induce platelet activation or fibrin formation in the coronary circulation.

Topics: Aged; beta-Thromboglobulin; Blood Platelets; Calcium; Cardiac Pacing, Artificial; Coronary Circulation; Coronary Disease; Female; Fibrin; Fibrinopeptide A; Humans; Male; Middle Aged

In this study, betathromboglobulin (BTG) and fibrinopeptide A (FPA) in peripheral venous blood were measured in 20 patients with stable angina pectoris before and immediately after exercise-induced myocardial ischaemia; in 5 of the 20 patients stable angina was associated with typical peripheral artery disease. A total of 10 patients with angiographically documented peripheral artery disease without angina and 10 normal volunteers were taken as control groups. BTG and FPA in the 15 patients with stable angina before exercise were 41 +/- 14 ng ml-1 and 2.3 +/- 0.9 ng ml-1 and were not statistically different from the values in normal controls; after exercise-induced myocardial ischaemia no significant increase occurred in these patients. Conversely, in the 5 patients with stable angina associated with peripheral artery disease BTG and FPA before exercise were 61 +/- 10 ng ml-1 and 3.5 +/- 0.8 ng ml-1 and increased to 114 +/- 14 ng ml-1 (P less than 0.001) and 4.1 +/- 0.5 ng ml-1 (P less than 0.01): These results were similar to those found in the 10 patients with isolated peripheral artery disease. We conclude that BTG and FPA in peripheral venous blood in patients with stable angina are not elevated either at rest or after exercise-induced myocardial ischaemia. Elevated values of BTG and FPA in patients with stable angina may reflect a major interaction between blood and atherosclerotic vessel wall, suggesting the presence of associated atherosclerotic lesions in peripheral artery disease.

Topics: Angina Pectoris; beta-Thromboglobulin; Coronary Disease; Fibrin; Fibrinopeptide A; Humans; Male; Physical Exertion; Platelet Aggregation

Topics: Coronary Disease; Coronary Thrombosis; Coronary Vessels; Fibrin; Fibrinolytic Agents; Humans; Infusions, Intravenous; Myocardial Infarction; Plasminogen; Recombinant Proteins; Time Factors; Tissue Plasminogen Activator

The discovery of a fast-acting plasminogen activator inhibitor has resulted in the notion that the balance between tissue-type plasminogen activator and its inhibitor determines the net fibrinolytic activity of blood. The inhibitor shows a rapidly fluctuating acute-phase pattern, which may be important in relation to thrombosis in acute disease. Other newly discovered modulators of the fibrinolytic system include histidine-rich glycoprotein, tetranectin and thrombospondin. The role of fibrin as a cofactor in its own dissolution is further elucidated with emphasis on local aspects. Therapeutic inhibition of overactive fibrinolysis by various drugs needs careful monitoring. Prophylactic stimulation of fibrinolysis is possible, e.g. by stanozolol or other drugs that lower inhibitor levels, but its proven value is as yet limited. Results of clinical trials with activators of the fibrinolytic system as thrombolytic agents are discussed in relation to the physiology of the fibrinolytic system.

Topics: Coronary Disease; Factor XII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Glycoproteins; Humans; Plasminogen; Plasminogen Activators; Plasminogen Inactivators; Tissue Plasminogen Activator

We studied the role of von Willebrand factor in coronary thrombosis in normal, heterozygous, and homozygous von Willebrand's disease pigs by producing coronary stenosis with a Goldblatt clamp positioned around the left anterior descending coronary artery. Flow velocity was assessed by a 20-MHz Doppler velocity probe distal to the Goldblatt clamp. Myocardial extracellular potassium levels were measured by potassium-sensitive electrodes in myocardium supplied by the left anterior descending artery. Whereas stenosis sufficient to block reactive hyperemia to a 20-second occlusion produced an elevation of myocardial extracellular potassium, it produced neither spontaneous cyclic flow reductions nor permanent cessation of coronary blood flow velocity. Injury of the coronary artery at the stenosis site with spring-loaded forceps produced cyclic flow reductions or permanent cessation of flow in eight of nine phenotypically normal pigs. On the other hand, flow variations occurred in none of the 10 von Willebrand's disease pigs, including four given purified von Willebrand factor at a dose that failed to correct the bleeding time (p less than 0.001, chi 2 test). Permanent cessation of flow was caused by an occlusive platelet-fibrin-red-blood-cell thrombus. Scanning electron micrographs from pigs with cyclic flow variations and from von Willebrand's disease pigs showed injured endothelium covered by adherent platelets, red and white blood cells, and fibrin. These data suggest an important role of native von Willebrand factor in sudden occlusive arterial thrombosis following stenosis and intimal injury.

Topics: Animals; Blood Flow Velocity; Constriction; Constriction, Pathologic; Coronary Circulation; Coronary Disease; Coronary Vessels; Fibrin; Microscopy, Electron, Scanning; Myocardium; Platelet Aggregation; Potassium; Swine; von Willebrand Diseases; von Willebrand Factor

Two groups of male patients with CHD were examined. The first group (30 persons) was treated with a 30-day therapeutic course of physical training on a bicycle ergometer, the second group received nitrates of prolonged action and beta-blocking agents. Eleven healthy men receiving a course of physical training were entered into the control group. The content of fibrinogen, soluble fibrin and fibrinogen degradation products in the blood plasma was investigated prior to and after a therapeutic course. An analysis of the blood plasma protein spectrum was performed using gel-filtration on a chromatographic column as well as separate disk-electrophoresis of the blood plasma proteins and isolated fractions in polyacrylamide gel. Regular physical training of the CHD patients resulted in a significant decrease in the content of fibrinogen, soluble fibrin and fibrin degradation products in the blood that might be conducive to the improvement of microcirculation and hence to lessening the number of angina attacks in these patients.

Topics: Adult; Angina Pectoris; Blood Protein Electrophoresis; Chromatography, Gel; Coronary Artery Disease; Coronary Disease; Exercise Therapy; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Male; Middle Aged; Myocardial Infarction; Physical Exertion

Topics: Animals; Coronary Circulation; Coronary Disease; Fibrin; Fibrinolysis; Humans; Myocardial Infarction; Plasminogen; Recombinant Proteins; Urokinase-Type Plasminogen Activator

To specify indications for isovolumic hemodilution, hemostatic parameters (fibrinogen, soluble fibrin, fibrin decomposition products, platelet aggregation, thromboelastograms) were compared with clinical manifestations of coronary heart diseases (CHD) and coronarographic and bicycle-ergometric findings in 41 coronary patients. The increased blood viscosity syndrome was found in 63% of the patients. Isovolumic hemodilution was performed to control the detected disorders in 17 patients. Hemodilution was shown to be an effective means of controlling hemostatic disorders in coronary patients, hemostatic normalization being accompanied with clinical improvement in part of the cases.

Topics: Adult; Aged; Blood Coagulation; Blood Viscosity; Coronary Disease; Exercise Test; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemodilution; Humans; Male; Middle Aged; Platelet Aggregation

The hypothesis that exercise-induced myocardial ischemia is associated with abnormal platelet activation and fibrin formation or dissolution was tested in patients with coronary artery disease undergoing upright bicycle stress testing. In vivo platelet activation was assessed by radioimmunoassay of platelet factor 4, beta-thrombo-globulin and thromboxane B2. In vivo fibrin formation was assessed by radioimmunoassay of fibrinopeptide A, and fibrinolysis was assessed by radioimmunoassay of thrombin-increasable fibrinopeptide B which reflects plasmin cleavage of fibrin I. Peripheral venous concentrations of these substances were measured in 10 normal subjects and 13 patients with coronary artery disease at rest and during symptom-limited peak exercise. Platelet factor 4, beta-thromboglobulin and thromboxane B2 concentrations were correlated with rest and exercise catecholamine concentrations to determine if exercise-induced elevation of norepinephrine and epinephrine enhances platelet activation. Left ventricular end-diastolic and end-systolic volumes, ejection fraction and segmental wall motion were measured at rest and during peak exercise by first pass radionuclide angiography. All patients with coronary artery disease had documented exercise-induced myocardial ischemia manifested by angina pectoris, ischemic electrocardiographic changes, left ventricular segmental dyssynergy and a reduction in ejection fraction. Rest and peak exercise plasma concentrations were not significantly different for platelet factor 4, beta-thromboglobulin, thromboxane B2, fibrinopeptide A and thrombin-increasable fibrinopeptide B. Peripheral venous concentrations of norepinephrine and epinephrine increased significantly (p less than 0.001) in both groups of patients. The elevated catecholamine levels did not lead to detectable platelet activation. This study demonstrates that enhanced platelet activation, thromboxane release and fibrin formation or dissolution are not detectable in peripheral venous blood of patients with coronary disease during exercise-induced myocardial ischemia.

Topics: Adult; Aged; Blood Platelets; Blood Proteins; Catecholamines; Coronary Disease; Exercise Test; Fibrin; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Middle Aged; Physical Exertion; Renin; Thromboxane B2

A pulmonic valve cardiac papilloma was found in a patient with coagulopathy and disturbed right ventricular hemodynamics. Fibrin was demonstrated within the cores of the papillae, lending further support to the thrombotic derivation of these lesions. The tumor's papillary configuration was thought to be the result of molding by the turbulent blood flow at that site.

Topics: Coronary Disease; Fibrin; Heart Neoplasms; Humans; Immunoenzyme Techniques; Male; Middle Aged; Papilloma; Pulmonary Valve

The presence of extravasated erythrocytes (EE), iron (I), and fibrin (F) within coronary atherosclerotic plaques and their relation to intraluminal coronary thrombus was determined in 2958 five-mm segments of 224 major epicardial coronary arteries in 57 patients with fatal coronary heart disease and in 1290 five-mm segments of 103 coronary arteries in 27 control (c) subjects. Intraplaque EE were present in 10% of the segments (controls [c] = 1%), in 35% of the arteries (c = 5%), and in 84% of the patients (c = 19%); I was present in 4% of the segments (c = less than 1%), in 14% of the arteries (c = 4%), and in 57% of the patients (c = 22%); intraplaque F was present in 2% of the segments (c = less than 1%), in 17% of the arteries (c = 3%), and in 63% of the patients (c = 7%). Intraluminal thrombus, present only in the patients with acute myocardial infarction and in none of the controls, occurred in 3% of the segments, in 8% of the arteries and in 26% of the patients. Intraplaque hemorrhage or EE occurred usually in the absence of intraluminal thrombus and conversely intraluminal thrombus occurred more frequently without than with underlying plaque hemorrhage. The frequency of intraplaque EE, I, and F was proportional to the amount of coronary atherosclerotic plaque present. Intraplaque I and F infrequently were observed in the absence of EE. The significance of extravasated erythrocytes, iron, and fibrin in atherosclerotic plaques remains unclear.

Topics: Adult; Aged; Autopsy; Coronary Disease; Coronary Vessels; Erythrocytes; Female; Fibrin; Humans; Iron; Male; Middle Aged; Myocardial Infarction

Topics: Blood Viscosity; Chronic Disease; Coronary Disease; Erythrocyte Aggregation; Female; Fibrin; Fibrinogen; Humans; In Vitro Techniques; Male; Rheology

Elevation in the plasma concentration of fibrinogen in coronary heart disease (CHD) and in stroke has been found to be due to increased biosynthesis and turnover. The pathway of the increased turnover of fibrinogen is via formation of fibrin. A new method for detecting and measuring intravascular fibrin has shown a highly significant elevation in these patients. These elevated levels of fibrin formation, or intravascular clotting, are associated with depressed fibrinolysis or clot lysis. This increased formation of fibrin in the patient is not responsive to conventional oral anticoagulant therapy with Coumadin (Na Warfarin). Prospective studies on over 1,500 patients have shown elevated plasma fibrinogen to have at least as strong an association with cardiovascular death as raised cholesterol. Increased plasma fibrin is highly susceptive to control with low dose heparin and urokinase. These discoveries should provide the health care field with a new basis for detecting early warning signs of CHD and thrombotic stroke and for more effective preventive therapy.

Topics: Coronary Disease; Fibrin; Fibrinogen; Hemostasis; Humans; Thromboembolism

Patients with ischaemic heart disease of severe forms with congested insufficiency of the circulation have chronic latent disseminated intravascular blood coagulation, which is confirmed by the increased level of soluble fibrin, products of breakdown of fibrinogen-fibrin, decreased activity of antithrombin III, marked sludging of erythrocytes at the microcirculatory level. A high degree of the correlation between the content of soluble fibrin and the marked sludge-phenomenon was found. Thromboembolic complications arising in this group of patients were accompanied by marked progress of the disorders found, which permitted one to isolate a limited as the the number of parameters coagulogram for the diagnosis of acute intravascular thrombosis in the patients with ischaemic heart diseases with congested insufficiency of the circulation. The important role of a preserved plasmin system for the prognosis in patients with congested insufficiency of the circulation with thromboembolic complications is shown.

Topics: Aged; Antithrombin III; Coronary Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heart Failure; Humans; Male; Middle Aged; Syndrome; Thromboembolism

Topics: Arteriosclerosis; Blood Coagulation; Coronary Disease; Estrogens; Female; Fibrin; Humans; Male; Prospective Studies; Risk; Sex Factors

Topics: Animals; Anti-Inflammatory Agents; Arteriosclerosis; Aspirin; Blood Platelets; Blood Vessels; Carotid Artery Diseases; Coronary Disease; Dipyridamole; Female; Fibrin; Humans; Male; Prostaglandins; Sex Factors; Sulfinpyrazone; Thrombosis

The coronary microcirculation was examined for platelet and fibrin thrombi in hearts from 21 normal subjects and 244 cardiac patients, including 168 with ischemic heart disease (IHD) and 76 with other types of heart disease. Seventy-seven cases were sudden cardiac death (SCD). No microthrombi were present in any of the normal hearts, whereas platelet and fibrin thrombin were present in the coronary microcirculation in 32 of 244 cardiac cases (13.1%), including 19 with IHD and 13 with other types of heart disease and after cardiac surgery. The microthrombi were either embolic or represented in situ thrombosis, depending upon the underlying pathologic process. There was no significant difference in the incidence of microthrombi in SCD patients, with IHD (10 of 50, 20%) compared with patients who survived longer (nine of 93, 10%). In SCD patients, however, platelet microthrombin were more frequent in patients less than 45 years of age compared with those older than 45 years of age (p = 0.0002). We concluded that coronary microcirculatory thrombi are not uncommon in heart disease. A subgroup of SCD in young patients with IHD has been identified in whom microcirculatory platelet thrombosis is the main cardiac pathologic process. The significance of this process is emphasized by the associated myocardial damage.

Topics: Adult; Aged; Blood Platelets; Cardiac Surgical Procedures; Coronary Circulation; Coronary Disease; Death, Sudden; Endocarditis; Female; Fibrin; Humans; Male; Microcirculation; Middle Aged; Myocardium; Thromboembolism

46 patients with ischaemic heart disease were treated with Micristin (20-40 mg/kg) or a combination of Micristin and Propranolol (80-120 mg/die). The values of bleeding time, the platelet factor 4 in lysate of thrombocytes or in plasma of patients as well as the soluble fibrin monomer complexes were investigated. They showed no obvious correlation to the clinical findings.

Topics: Adenosine Diphosphate; Aspirin; Blood Coagulation Tests; Blood Platelets; Coronary Disease; Fibrin; Humans; Platelet Adhesiveness; Platelet Aggregation; Platelet Factor 4; Propranolol

Signs of dysfunction of the coagulation system and fibrinolysis were determined in 45 healthy young individuals who had such risk factors in relation to ischemic heart disease as arterial hypertension, hypercholesterolemia, smoking, aggravated heredity, permanent emotional overstress, etc. These signs were manifested by a tendency to augmentation of blood coagulation and compensatory activation of fibrinolysis. Ischemic-type changes were detected on the ECG after a physical load. It is assumed that dysfunction of the coagulation system and fibrinolysis is an additional risk factor in relation to ischemic heart disease, while derangement of compensatory fibrinolysis tension with the subsequent tension of its components may lead to the development of coronary thrombosis.

Topics: Adult; Antithrombin III; Blood Coagulation; Coronary Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Male; Plasminogen Activators; Risk

Immunofluorescent analysis was used to study the topography of plasma proteins and beta-lipoproteins in the wall of human coronary arteries in cases of atherosclerosis. The dynamics of protein fractions deposits is not uniform in the process of the formation of the disease. Along with the progress of atherosclerosis, the infiltration of proteins, lipoproteins and lipids is increasing. A regular combination of beta-lipoproteins and gamma-globulin localizations was established. The role of the examined components in the wall of the coronary arteries and their participation in the formation of atherosclerotic plaques is discussed.

Topics: Adolescent; Adult; Aged; Aging; Albumins; Autopsy; Blood Proteins; Child; Coronary Disease; Coronary Vessels; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Humans; Lipoproteins, LDL; Middle Aged; Plasma

Topics: Chronic Disease; Coronary Disease; Fibrin; Glomerulonephritis; Humans; Hypertension; Pyelonephritis; Solubility

The status of the native coronary arteries at necropsy in the vicinity of the coronary anastomoses of saphenous vein aortocoronary bypass grafts in 20 patients with severe coronary heart disease is presented. Of the 37 graft systems (graft plus coronary artery into which graft inserted) analyzed, the lumina of 44% of the native coronary arteries within the first 2 cm distal to the anastomoses were greater than 75% narrowed in cross-sectional area by atherosclerotic plaques, and the native coronary artery at the site of the anastomosis was greater than 50% narrowed in cross-sectional area already by atheroclerotic plaque in 25% of the graft systems. The mean coronary arterial size distal to the site of the coronary graft anastomosis, even after correction for heart weight, was greater in the 13 men than in the seven women. The residual luminal areas squared per gram of heart weight, however, were similar in both men and women. These results suggest that 1) relative coronary vessel size is greater in men than women; 2) the luminal area squared per gram myocardial mass (a relative estimation of flow) is the same in the two groups of patients; and 3) less atherosclerotic plaque is necessary in women then in men to produce similar limitation to coronary flow. Thus, vessel size alone cannot account for the higher reported frequency of unsuccessful aortocoronary bypass procedures in women.

Topics: Adult; Aged; Arteries; Coronary Artery Bypass; Coronary Disease; Coronary Vessels; Female; Fibrin; Humans; Male; Middle Aged; Saphenous Vein; Sex Factors; Thrombosis; Transplantation, Autologous; Veins

Topics: Adult; Aged; Antifibrinolytic Agents; Coronary Disease; Coronary Vessels; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Protease Inhibitors

Following routine coronary arteriography, surface irregularities and thrombogenesis of the inner and outer wall of six Ducor polyurethane and six RPX polyethylene coronary catheters were studied by scanning electron microscopy. Polyurethane catheters had rough and highly irregular external and internal surfaces. All catheters showed adherent thrombi on their external surface. The internal surface of three catheters showed evidence of thrombosis. Polyethylene differed from polyurethane in several respects. Although the external surface had an irregular and wavelike appearance, the internal surface was smooth and regular. Two polyethylene catheters showed thrombi on their external surface. The internal surface of one catheter showed single platelets in one area. These results confirm recent reports showing that internal and external surface irregularities play a major role in the initiation of thrombosis in and on intravascular catheters. They stress the need for high quality catheter materials with smooth and regular surfaces in the prevention of thromboembolic complications from coronary arteriography.

Topics: Adult; Angiocardiography; Blood Platelets; Cardiac Catheterization; Coronary Disease; Erythrocytes; Female; Fibrin; Humans; Male; Microscopy, Electron, Scanning; Middle Aged; Polyethylenes; Polyurethanes; Thrombosis

To develop a thrombus localizing tracer which has characteristics superior to labeled fibrinogen for external detection, we evaluated radioiodinated soluble fibrin. Labeled soluble fibrin was prepared by clotting and dissolving radioiodinated (131I) canine fibrinogen under specified conditions. Biological clearance studies revealed rapid clearance of the labeled soluble fibrin from the blood with a half-life of 5 hours. The accumulation of labeled soluble fibrin and fibrinogen in induced venous thrombi, coronary artery thrombi, and the myocardium was compared in dogs. In venous thrombi, soluble fibrin and fibrinogen exhibited maximum thrombus-blood ratios when they were injected 4 hours after thrombus induction; the thrombus-blood ratio was greater for soluble fibrin than it was for fibrinogen when these agents were injected 4, 8, or 24 hours after thrombosis induction. In induced coronary artery thrombi, soluble fibrin and fibrinogen accumulated to the same extent. Since the blood clearance of soluble fibrin is faster than that of fibrinogen, a higher thrombus-blood ratio was obtained with soluble fibrin in coronary artery thrombi. The thrombus-infarcted myocardium, thrombus-normal myocardium, and infarcted myocardium-normal myocardium ratios obtained with soluble fibrin were slightly higher than those obtained with fibrinogen. Thus, soluble fibrin offers some advantages when it is compared with fibrinogen as a thrombus detecting agent.

Topics: Animals; Coronary Disease; Disease Models, Animal; Dogs; Evaluation Studies as Topic; Fibrin; Fibrinogen; Half-Life; Iodine Radioisotopes; Isotope Labeling; Solubility; Thrombophlebitis; Thrombosis

Topics: Arteriosclerosis; Blood Specimen Collection; Cardiac Catheterization; Coronary Disease; Coronary Vessels; Electric Countershock; Enzyme Activation; Enzyme Repression; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Heparin; Humans; Hypertension; Myocardial Infarction; Plasminogen; Radiography

Topics: Adolescent; Autopsy; Collagen; Coronary Angiography; Coronary Artery Bypass; Coronary Disease; Endoplasmic Reticulum; Erythrocytes; Fibrin; Humans; Leukocytes; Male; Microscopy, Electron; Myocardium; Myofibrils; Saphenous Vein; Time Factors; Transplantation, Autologous

Topics: Angiocardiography; Blood Platelets; Cardiac Catheterization; Coronary Disease; Coronary Vessels; Embolism; Fibrin; Humans; Male; Methods; Middle Aged

Topics: Adolescent; Adult; Aged; Aorta; Child; Coronary Disease; Fibrin; Fluorescent Antibody Technique; gamma-Globulins; Humans; Immune Complex Diseases; Lipoproteins, LDL; Middle Aged; Proteins

Topics: Adult; Aged; Arteriosclerosis; Coronary Disease; Coronary Vessels; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Myocardial Infarction

Topics: Acute Disease; Arteriosclerosis; Blood Platelets; Cardiac Output; Coronary Disease; Death, Sudden; Erythrocytes; Fibrin; Humans; Leukocytes; Myocardial Infarction

Topics: Adult; Aged; Arteriosclerosis; Autopsy; Blood Platelets; Calcinosis; Cholesterol; Coronary Disease; Coronary Vessels; Embolism; Erythrocytes; Female; Fibrin; Heart Ventricles; Hemorrhage; Humans; Leukocytes; Male; Middle Aged; Myocardial Infarction; Myocardium; Thrombosis; Time Factors

Topics: Blood Platelets; Coronary Disease; Coronary Vessels; Erythrocytes; Fibrin; Fibrinolytic Agents; Humans; Myocardial Infarction; Thrombosis

Topics: Coronary Disease; Fibrin; Fibrinolysis; Humans; Male; Stanozolol

Topics: Adult; Arteriosclerosis; Coronary Disease; Diagnosis, Differential; Fibrin; Fibrinogen; Fibrinolysis; Humans; Middle Aged; Myocardial Infarction; Prognosis; Protamines; Serum Globulins

Topics: Aortic Valve; Autopsy; Coronary Disease; Fibrin; Follow-Up Studies; Heart Auscultation; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Prosthesis Design; Thromboembolism; Time Factors

Topics: Adult; Aged; Biguanides; Clofibrate; Coronary Disease; Ethylestrenol; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Hemostasis; Humans; Immunoassay; Immunodiffusion; Immunoelectrophoresis; Liver Cirrhosis; Male; Metformin; Middle Aged; Neoplasm Metastasis; Nicotinic Acids; Physical Exertion; Plasminogen; Prostatic Neoplasms; Stimulation, Chemical; Time Factors; Tolazamide

Topics: Adult; Arteriosclerosis; Blood Coagulation Disorders; Coronary Disease; Diffuse Cerebral Sclerosis of Schilder; Fibrin; Fibrinolysis; Genetic Diseases, Inborn; Germany, East; Humans; Intracranial Arteriosclerosis; Male; Middle Aged

Topics: Adult; Aged; Angina Pectoris; Aorta; Arteriosclerosis; Coronary Disease; Female; Fibrin; Fluorescent Antibody Technique; Humans; Immune Sera; Male; Microtomy; Middle Aged; Myocardial Infarction

Topics: Animals; Benzopyrans; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelet Disorders; Budd-Chiari Syndrome; Coronary Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Mice; Microscopy; Microscopy, Electron; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Pulmonary Embolism; Renal Veins; Thrombosis; Veins

Topics: Adult; Animals; Antifibrinolytic Agents; Arthritis, Rheumatoid; Blood Sedimentation; Coronary Disease; Erythrocytes; Fibrin; Fibrinogen; Humans; Middle Aged; Multiple Sclerosis; Neurotic Disorders; Protamines; Rabbits; Rats; Staphylococcal Infections

Topics: Antifibrinolytic Agents; Blood Proteins; Coronary Disease; Fibrin; Fibrinolysin; Fibrinolysis; Plasminogen

Topics: Animals; Chemical Precipitation; Colorimetry; Coronary Disease; Dogs; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Methods; Protamines; Rabbits; Solubility; Streptokinase; Thrombin

Topics: Animals; Blood Coagulation; Coronary Disease; Coronary Vessels; Embolism, Air; Fibrin; Heparin; Injections, Intravenous; Male; Mice; Myocardium; Pulmonary Artery; Rabbits; Veins

Topics: Arteriosclerosis; Blood Chemical Analysis; Blood Sedimentation; Coronary Disease; Female; Fibrin; Glycoproteins; Haptoglobins; Humans; Lipoproteins; Male; Myocardial Infarction

Topics: Adult; Aged; Blood Coagulation Disorders; Coronary Disease; Female; Fibrin; Humans; Male; Middle Aged

Topics: Arteriosclerosis; Atherosclerosis; Coronary Disease; Fibrin; Fibrinolysin; Humans; Thrombosis

Topics: Aspartate Aminotransferases; Blood Proteins; C-Reactive Protein; Clinical Enzyme Tests; Coronary Disease; Fibrin

Topics: Blood; Castration; Coronary Disease; Coronary Thrombosis; Fibrin; Heart; Humans; Male; Orchiectomy

Topics: Blood; Blood Coagulation; Coronary Artery Disease; Coronary Disease; Diet; Fibrin; Fibrinolysis; Humans; Nutritional Physiological Phenomena; Nutritional Sciences

Topics: Castration; Coronary Disease; Coronary Occlusion; Eating; Fats; Fibrin; Hormones; Humans; Lipid Metabolism; Lipids; Sex Characteristics

Topics: Blood Coagulation; Coronary Artery Disease; Coronary Disease; Coronary Thrombosis; Fibrin; Fibrinolysis; Heart; Humans; Sclerosis

Topics: Arteriosclerosis; Coronary Disease; Fats; Fibrin; Fibrinolysis; Humans; Hyperlipidemias; Thrombosis

Topics: Coronary Disease; Fibrin; Fibrinogen; Humans; Myocardial Infarction; Plasma