fibrin and Cardiovascular-Diseases

Fibrinogen conversion into insoluble fibrin and the formation of a stable clot is the final step of the coagulation cascade. Fibrin clot porosity and its susceptibility to plasmin-mediated lysis are the key fibrin measures, describing the properties of clots prepared ex vivo from citrated plasma. Cardiovascular disease (CVD), referring to coronary heart disease, heart failure, stroke, and hypertension, has been shown to be associated with the formation of dense fibrin networks that are relatively resistant to lysis. Denser fibrin mesh characterized acute patients at the onset of myocardial infarction or ischaemic stroke, while hypofibrinolysis has been identified as a persistent fibrin feature in patients following thrombotic events or in those with stable coronary artery disease. Traditional cardiovascular risk factors, such as smoking, diabetes mellitus, hyperlipidaemia, obesity, and hypertension, have also been linked with unfavourably altered fibrin clot properties, while some lifestyle modifications and pharmacological treatment, in particular statins and anticoagulants, may improve fibrin structure and function. Prospective studies have suggested that prothrombotic fibrin clot phenotype can predict cardiovascular events in short- and long-term follow-ups. Mutations and splice variants of the fibrinogen molecule that have been proved to be associated with thrombophilia or increased cardiovascular risk, along with fibrinogen post-translational modifications, prothrombotic state, inflammation, platelet activation, and neutrophil extracellular traps formation, contribute also to prothrombotic fibrin clot phenotype. Moreover, about 500 clot-bound proteins have been identified within plasma fibrin clots, including fibronectin, α2-antiplasmin, factor XIII, complement component C3, and histidine-rich glycoprotein. This review summarizes the current knowledge on the mechanisms underlying unfavourable fibrin clot properties and their implications in CVD and its thrombo-embolic manifestations.

Topics: Brain Ischemia; Cardiovascular Diseases; Fibrin; Fibrinogen; Humans; Hypertension; Prospective Studies; Stroke; Thrombosis

The human contact system consists of plasma proteins, which - after contact to foreign surfaces - are bound to them, thereby activating the zymogens of the system into enzymes. This activation mechanism gave the system its name - contact system. It is considered as a procoagulant and proinflammatory response mechanism, as activation finally leads to the generation of fibrin and bradykinin. To date, no physiological processes have been described that are mediated by contact activation. However, contact system factors play a pathophysiological role in numerous diseases, such as cardiovascular diseases, arthritis, colitis, sepsis, and cancer. Contact system factors are therefore an interesting target for new therapeutic options in different clinical conditions.

Topics: Animals; Blood Proteins; Bradykinin; Cardiovascular Diseases; Fibrin; Humans; Inflammation; Neoplasms; Sepsis

Preeclampsia is a devastating medical complication of pregnancy that can lead to significant maternal and fetal morbidity and mortality. It is currently believed that there is abnormal placentation in as early as the first trimester in women destined to develop preeclampsia. Although the etiology of the abnormal placentation is being debated, numerous epidemiologic and experimental studies suggest that imbalances in circulating angiogenic factors released from the placenta are responsible for the maternal signs and symptoms of preeclampsia. In particular, circulating levels of soluble fms-like tyrosine kinase 1, an antiangiogenic factor, are markedly increased in women with preeclampsia, whereas free levels of its ligand, placental, growth factor are markedly diminished. Alterations in these angiogenic factors precede the onset of clinical signs of preeclampsia and correlate with disease severity. Recently, the availability of automated assays for the measurement of angiogenic biomarkers in the plasma, serum, and urine has helped investigators worldwide to demonstrate a key role for these factors in the clinical diagnosis and prediction of preeclampsia. Numerous studies have reported that circulating angiogenic biomarkers have a very high negative predictive value to rule out clinical disease among women with suspected preeclampsia. These blood-based biomarkers have provided a valuable tool to clinicians to accelerate the time to clinical diagnosis and minimize maternal adverse outcomes in women with preeclampsia. Angiogenic biomarkers have also been useful to elucidate the pathogenesis of related disorders of abnormal placentation such as intrauterine growth restriction, intrauterine fetal death, twin-to-twin transfusion syndrome, and fetal hydrops. In summary, the discovery and characterization of angiogenic proteins of placental origin have provided clinicians a noninvasive blood-based tool to monitor placental function and health and for early detection of disorders of placentation. Uncovering the mechanisms of altered angiogenic factors in preeclampsia and related disorders of placentation may provide insights into novel preventive and therapeutic options.

Topics: Biomarkers; Bronchopulmonary Dysplasia; Cardiovascular Diseases; Female; Fetal Death; Fetofetal Transfusion; Fibrin; Humans; Hydrops Fetalis; Placenta Diseases; Placenta Growth Factor; Placentation; Pre-Eclampsia; Pregnancy; Prognosis; Puerperal Disorders; Up-Regulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-1

The formation of an obstructive thrombus within an artery remains a major cause of mortality and morbidity worldwide. Despite effective inhibition of platelet function by modern antiplatelet therapies, these agents fail to fully eliminate atherothrombotic risk. This may well be related to extensive vascular disease, beyond the protective abilities of the treatment agents used. However, recent evidence suggests that residual vascular risk in those treated with modern antiplatelet therapies is related, at least in part, to impaired fibrin clot lysis. In this review, we attempt to shed more light on the role of hypofibrinolysis in predisposition to arterial vascular events. We provide a brief overview of the coagulation system followed by addressing the role of impaired fibrin clot lysis in acute and chronic vascular conditions, including coronary artery, cerebrovascular, and peripheral vascular disease. We also discuss the role of combined anticoagulant and antiplatelet therapies to reduce the risk of arterial thrombotic events, addressing both efficacy and safety of such an approach. We conclude that impaired fibrin clot lysis appears to contribute to residual thrombosis risk in individuals with arterial disease on antiplatelet therapy, and targeting proteins in the fibrinolytic system represents a viable strategy to improve outcome in this population. Future work is required to refine the antithrombotic approach by modulating pathological abnormalities in the fibrinolytic system and tailoring therapy according to the need of each individual.

Topics: Blood Coagulation; Cardiovascular Diseases; Fibrin; Fibrinolysis; Humans; Thrombosis

The blood coagulation factor XIII (FXIII) plays an essential role in the stabilization of fibrin clots. This factor, belonging to the class of transglutaminases, catalyzes the final step of secondary hemostasis, i.e. the crosslinking of fibrin polymers. These crosslinks protect the clots against premature fibrinolysis. Consequently, FXIII is an interesting target for the therapeutic treatment of cardiovascular diseases. In this context, inhibitors can influence FXIII in the activation process of the enzyme itself or in its catalytic activity. To date, there is no FXIII inhibitor in medical application, but several studies have been conducted in the past. These studies provided a better understanding of FXIII and identified new lead structures for FXIII inhibitors. Next to small molecule inhibitors, the most promising candidates for the development of clinically applicable FXIII inhibitors are the peptide inhibitors tridegin and transglutaminase-inhibiting Michael acceptors (TIMAs) due to their selectivity towards activated FXIII (FXIIIa). In this review, select FXIII inhibitors and their pharmacological potential are discussed.

Topics: Animals; Binding Sites; Blood Coagulation; Cardiovascular Diseases; Enzyme Inhibitors; Factor XIIIa; Fibrin; Humans; Protein Binding; Salivary Proteins and Peptides

Fibrinogen is a unique protein that is converted into an insoluble fibrin in a single enzymatic event, which is a characteristic feature of fibrinogen due to its susceptibility to fibrinolytic degradation and dissolution. Although thrombosis is a result of activated blood coagulation, no explanation is being offered for the persistent presence of fibrin deposits in the affected organs. A classic example is stroke, in which the thrombolytic therapy is effective only during the first 3-4 h after the onset of thrombosis. This phenomenon can now be explained in terms of the modification of fibrinogen structure induced by hydroxyl radicals generated during the period of ischemia caused, in turn, by the blocking of the blood flow within the obstructed vessels. Fibrinogen modification involves intra-to intermolecular disulfide rearrangement induced by the reductive power of hydroxyl radicals that result in the exposition of buried hydrophobic epitopes. Such epitopes react readily with each other forming linkages stronger than the peptide covalent bonds, thus rendering them resistant to the proteolytic degradation. Also, limited reduction of human serum albumin (HSA) generates hydrophobic polymers that form huge insoluble complexes with fibrinogen. Consequently, such insoluble copolymers can be deposited within the circulation of various organs leading to their dysfunction. In conclusion, the study of protein hydrophobic interactions induced by a variety of nutritional and/or environmental factors can provide a rational explanation for a number of pathologic conditions including cardiovascular, neurologic, and other degenerative diseases including cancer.

Topics: Animals; Arthritis; Cardiovascular Diseases; Diabetes Mellitus; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hydrophobic and Hydrophilic Interactions; Kidney Diseases; Lung Diseases; Models, Biological; Neoplasms; Nervous System Diseases; Polymerization; Protein Interaction Domains and Motifs; Serum Albumin, Human; Solubility; Thrombosis

This article reports current evidence on the association between Lp(a) and cardiovascular (CV) disease and on pathophysiological mechanisms. The available information on therapy for reduction of lipoprotein(a) is also discussed.. Although some evidence is conflicting, Lp(a) seems to increase CV risk through stimulation of platelet aggregation, inhibition of tissue factor pathway inhibitor, alteration of fibrin clot structure and promotion of endothelial dysfunction and phospholipid oxidation. Lp(a) 3.5-fold higher than normal increases the risk of coronary heart disease and general CV events, particularly in those with LDL cholesterol ≥ 130 mg/dl. High Lp(a) values represent also an independent risk factor for ischemic stroke (more relevant in young stroke patients), peripheral artery disease (PAD) and aortic and mitral stenosis. Furthermore, high Lp(a) levels seem to be associated with increased risk of cardiovascular events in patients with chronic kidney disease, particularly in those undergoing percutaneous coronary intervention.. Lipoprotein (a) (Lp[a]) seems to significantly influence the risk of cardiovascular events. The effects of statins and fibrates on Lp(a) are limited and extremely variable. Nicotinic acid was shown effective in reducing Lp(a) but, due to its side effects and serious adverse events during clinical trials, it is no longer considered a possible option for treatment. To date, the treatment of choice for high levels of Lp(a) in high CV risk patients is represented by LDL-Apheresis. Thanks to innovative technologies, new selectively inhibiting LPA drugs are being developed and tested.

Topics: Biomarkers; Blood Component Removal; Blood Platelets; Cardiovascular Diseases; Dyslipidemias; Endothelium, Vascular; Fibrin; Humans; Hypolipidemic Agents; Lipoprotein(a); Lipoproteins; Oxidation-Reduction; Phospholipids; Platelet Aggregation; Risk Assessment; Risk Factors

Fibrinogen is cleaved by thrombin to fibrin, which provides the blood clot with its essential structural backbone. As an acute phase protein, the plasma levels of fibrinogen are increased in response to inflammatory conditions. In addition to fibrinogen levels, fibrin clot structure is altered by a number of factors. These include thrombin levels, treatment with common cardiovascular medications, such as aspirin, anticoagulants, statins and fibrates, as well as metabolic disease states such as diabetes mellitus and hyperhomocysteinaemia. In vitro studies of fibrin clot structure can provide information regarding fibre density, clot porosity, the mechanical strength of fibres and fibrinolysis. A change in fibrin clot structure, to a denser clot with smaller pores which is more resistant to lysis, is strongly associated with cardiovascular disease. This pathological change is present in patients with arterial as well as venous diseases, and is also found in a moderate form in relatives of patients with cardiovascular disease. Pharmacological therapies, aimed at both the treatment and prophylaxis of cardiovascular disease, appear to result in positive changes to the fibrin clot structure. As such, therapies aimed at 'normalising' fibrin clot structure may be of benefit in the prevention and treatment of cardiovascular disease.

Topics: Arterial Occlusive Diseases; Blood Coagulation; Cardiovascular Agents; Cardiovascular Diseases; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Porosity; Venous Thrombosis

Accumulating evidence within the last two decades indicates the association between cardiovascular disease (CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolytic enzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronary and cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron (FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that is remarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that the persistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. We study the effects of certain amphiphilic substances on the iron- and thrombin-induced fibrinogen polymerization visualized using scanning electron microscopy. We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated with CVD. The only way to prevent iron overload is by supplementation with iron chelating agents. However, administration of free radical scavengers as effective protection against persistent presence of fibrin-like deposits should also be investigated to contribute to the prevention of cardiovascular and other degenerative diseases.

Topics: Animals; Blood Coagulation; Cardiovascular Diseases; Fibrin; Free Radical Scavengers; Humans; Iron; Thrombolytic Therapy

Direct fibrinolytics are proteolytic enzymes that degrade fibrin without requiring an intermediate step of plasminogen activation. This review summarizes the current information available for five such agents, namely, plasmin (the prototypical form), three derivatives of plasmin (mini-plasmin, micro-plasmin, and delta-plasmin), and alfimeprase, a recombinant variant of a snake venom alpha-fibrinogenase, fibrolase. Biochemical attributes of molecular size, fibrin binding and inhibitor neutralization are compared. Preclinical investigations that assess the potential for thrombolytic efficacy in vitro and in animal models of vascular occlusion and for hemostatic safety in animal models of bleeding are detailed. Clinical potential has been assessed in patients with peripheral arterial and graft occlusion, acute ischemic stroke, and access catheter and hemodialysis shunt occlusions. The direct fibrinolytic agents have impressive biochemical and preclinical foundations for ultimate clinical application. However, clinical trial results for micro-plasmin and alfimeprase have not measured up to their anticipated benefit. Plasmin has thus far shown encouraging hemostatic safety, but efficacy data await completion of clinical trials. Whether direct fibrinolytics will provide clinical superiority in major thrombotic disorders over currently utilized indirect fibrinolytics such as tissue plasminogen activator remains to be determined.

Topics: Animals; Cardiovascular Diseases; Disease Models, Animal; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Humans; Metalloendopeptidases; Peptide Fragments; Thrombolytic Therapy

South Africa is experiencing a rapid urbanization of its African population characterized by a demographic, nutrition, lifestyle, and health transition. The resultant high prevalence of high cardiovascular disease, in particular of stroke, is of concern. In this narrative review it is suggested that, together with hypertension, changes in the hemostatic system may be one of the major contributors to stroke in this population. It is further suggested that these changes are related to increased fat and animal protein intakes, decreased intakes of total carbohydrate and dietary fiber, as well as persistent suboptimal micronutrient intakes of Africans in transition. The effects of this nutrition transition on plasma fibrinogen, fibrin network structures, plasminogen activator inhibitor 1 activity levels and some other clotting and fibrinolytic factors are discussed. It is concluded that despite indications of present protective mechanisms against the development of coronary heart disease (CHD) in this population the observed changes in diet and hemostatic profiles may eventually lead to a high prevalence of both stroke and CHD in urban black South Africans. It is further suggested that timely nutritional interventions and research of effects thereof on the hemostatic system are urgently needed.

Topics: Black People; Cardiovascular Diseases; Diet; Dietary Fats; Dietary Proteins; Fibrin; Fibrinogen; Hemostasis; Humans; Nutritional Physiological Phenomena; Plasminogen Activator Inhibitor 1; Rural Population; South Africa; Stroke; Urbanization

Molecular imaging is a rapidly growing field with the potential to revolutionize cardiovascular medicine by shifting diagnostic focus from functional abnormalities which occur late in a disease process to the biochemical events which precipitate the earliest stages of disease. MRI is a modality well suited to this task as it allows a variety of contrast mechanisms for detection of epitopes of interest, as well as high-resolution anatomical localization and functional information. In this review, we discuss the widerange of available molecular MRI contrast agents and their application to diseases such as atherosclerosis, thrombus imaging, and stem cell tracking, along with opportunities for molecularly targeted drug delivery.

Topics: Animals; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Contrast Media; Fibrin; Humans; Magnetic Resonance Imaging; Nanoparticles; Staining and Labeling; Stem Cells

Tissue factor (TF) plays a role in thrombogenesis. TF initiates blood coagulation resulting in the generation of protease coagulant mediators (FVIIa, FXa, and FIIa) and fibrin production. TF hypercoagulablility directly contributes to thrombus formation resulting from the major events of fibrin deposition and FIIa-induced platelet activation/aggregation. In addition, blood coagulation indirectly promotes thrombogenicity via the coagulation-inflammation cycle in which TF plays a diverging and converging role. As the consequence of coagulation-dependent inflammation in which protease-activated receptor (PAR) mediates the coagulant signaling to elicit cytokines, selectins, and growth factors, such inflammation facilitates thrombosis by platelet aggregation and leukocyte recruitment. As TF hypercoagulability concerned, anti-thrombotic strategies involve the prevention by anticoagulation and PAR antagonism. Anticoagulants block the direct and indirect thrombotic contributions, while PAR antagonists arrest coagulation-dependent inflammation. With respect to both thrombosis and inflammation being cardiovascular risk factors, such strategies offer diverse benefits to cardioprotection.

Topics: Animals; Blood Coagulation; Blood Vessels; Cardiovascular Diseases; Factor VIIa; Factor Xa; Fibrin; Humans; Inflammation; Models, Biological; Myocardium; Peptides; Platelet Aggregation; Prothrombin; Receptors, Proteinase-Activated; Thromboplastin; Thrombosis

The adhesion receptor P-selectin has long been known to support leukocyte rolling and emigration at sites of inflammation. Recently, P-selectin was also revealed to be a key molecule in hemostasis and thrombosis, mediating platelet rolling, generating procoagulant microparticles containing active tissue factor and enhancing fibrin deposition. Elevated levels of plasma P-selectin are indicative of thrombotic disorders and predictive of future cardiovascular events. Because the interaction between P-selectin and its receptor P-selectin glycoprotein ligand-1 (PSGL-1) represents an important mechanism by which P-selectin induces the formation of procoagulant microparticles and recruits the microparticles to thrombi, anti-thrombotic strategies are currently aimed at inhibiting this interaction. Recent developments also suggest that the procoagulant potential of P-selectin could be used to treat coagulation disorders such as hemophilia A.

Topics: Animals; Blood Coagulation Disorders; Cardiovascular Diseases; Cell Adhesion; Fibrin; Humans; Inflammation; Leukocytes; Membrane Glycoproteins; Mice; Models, Biological; P-Selectin; Phenotype; Protein Binding; Protein Structure, Tertiary; Thromboplastin; Thrombosis

Fibrinogen binds through its gamma chains to cell surface receptors, growth factors, and coagulation factors to perform its key roles in fibrin clot formation, platelet aggregation, and wound healing. However, these binding interactions can also contribute to pathophysiologic processes, including inflammation and thrombosis. This review summarizes the latest findings on the role of the fibrinogen gamma chain in these processes, and illustrates the potential for therapeutic intervention.. Novel gamma chain epitopes that bind platelet integrin alpha IIbbeta3 and leukocyte integrin alphaMbeta2 have been characterized, leading to the revision of former dogma regarding the processes of platelet aggregation, clot retraction, inflammation, and thrombosis. A series of studies has shown that the gamma chain serves as a depot for fibroblast growth factor-2 (FGF-2), which is likely to play an important role in wound healing. Inhibition of gamma chain function with the monoclonal antibody 7E9 has been shown to interfere with multiple fibrinogen activities, including factor XIIIa crosslinking, platelet adhesion, and platelet-mediated clot retraction. The role of the enigmatic variant fibrinogen gamma chain has also become clearer. Studies have shown that gamma chain binding to thrombin and factor XIII results in clots that are mechanically stiffer and resistant to fibrinolysis, which may explain the association between gammaA/gamma' fibrinogen levels and cardiovascular disease.. The identification of new interactions with gamma chains has revealed novel targets for the treatment of inflammation and thrombosis. In addition, several exciting studies have shown new functions for the variant gamma chain that may contribute to cardiovascular disease.

Topics: Animals; Blood Coagulation; Cardiovascular Diseases; Fibrin; Fibrinogen; Fibrinolysis; Fibroblast Growth Factor 2; Humans; Integrins; Protein Binding

Topics: Acute Disease; Blood Platelets; Cardiovascular Diseases; Education, Medical, Continuing; Fibrin; Humans; Platelet Aggregation Inhibitors

Factor XIII and fibrinogen are unusual among clotting factors in that neither is a serine protease. Fibrin is the main protein constituent of the blood clot, which is stabilized by factor XIIIa through an amide or isopeptide bond that ligates adjacent fibrin monomers. Many of the structural and functional features of factor XIII and fibrin(ogen) have been elucidated by protein and gene analysis, site-directed mutagenesis, and x-ray crystallography. However, some of the molecular aspects involved in the complex processes of insoluble fibrin formation in vivo and in vitro remain unresolved. The findings of a relationship between fibrinogen, factor XIII, and cardiovascular or other thrombotic disorders have focused much attention on these 2 proteins. Of particular interest are associations between common variations in the genes of factor XIII and altered risk profiles for thrombosis. Although there is much debate regarding these observations, the implications for our understanding of clot formation and therapeutic intervention may be of major importance. In this review, we have summarized recent findings on the structure and function of factor XIII. This is followed by a review of the effects of genetic polymorphisms on protein structure/function and their relationship to disease.

Topics: Blood Coagulation; Cardiovascular Diseases; Factor XIII; Fibrin; Humans; Polymorphism, Genetic; Protein Subunits; Structure-Activity Relationship

Thrombin inhibitors from bloodsucking leeches and insects that block conversion of fibrinogen to fibrin are considered. Regulatory mechanisms influencing the fibrinogen-fibrin system in leeches include fibrinogen degradation, inhibition of factor XIIIa, and lysis of fibrin clots. The review also summarizes recent data on plasminogen activator from the vampire bat Desmodus rotundus and a role of fibrin as its cofactor.

Topics: Animals; Cardiovascular Diseases; Chiroptera; Factor XIIIa; Fibrin; Fibrinogen; Fibrinolysis; Humans; Leeches; Temperature; Thrombin; Time Factors

Topics: Arteriosclerosis; Biomarkers; Cardiovascular Diseases; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Risk Factors; Thrombin

Topics: Arteriosclerosis; Cardiovascular Diseases; Diabetes Mellitus; Diabetic Angiopathies; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen Activator Inhibitor 1; Risk Factors

Topics: Amino Acid Sequence; Apolipoproteins A; Base Sequence; Binding, Competitive; Blood Proteins; Cardiovascular Diseases; Fibrin; Fibrinogen; Humans; Lectins, C-Type; Lipoprotein(a); Lipoproteins; Lysine; Molecular Sequence Data; Molecular Structure; Plasminogen; Plasminogen Activators; Protein Binding; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator

A modern data review on the importance of fibrinolysis system is given. A considerable success has been scored during the study of molecular parameters of fibrinolysis system: the plasminogen, plasmin, its inhibitors, plasminogen activators and the mechanism of activation system have been characterized. The entrance of A, K, C, P and PP vitamins has been established to be necessary for the normal functioning of the fibrinolysis system; the dependence of the blood fibrinolytic activity upon the initial plasminogen content and concentration of its activators in blood has been revealed. The plasminogen activator depletion in tissues has been shown to be one of the reasons of some pathological states development, especially at cardiovascular diseases. The increase of fibrinolysis level by the active fibrinolytic ferment injection in blood has a medical effect at thrombosis. The ferment fibrinolysin received in the laboratory is successfully used in clinical practice. Some other activators of fibrinolytic system: tricholysine and longolytin from the culture of saprophyte fungi, plasminogen activator from the pig heart and the cells culture of the calf kidney have been received and are being studied.

Topics: Adult; Animals; Antithrombin III; Blood Coagulation Disorders; Cardiovascular Diseases; Cattle; Dogs; Enzymes, Immobilized; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Heart; Humans; Male; Plasminogen; Plasminogen Activators; Rats; Research; Swine; Thrombosis; Tissue Plasminogen Activator; Vitamins

Topics: Animals; Blood Coagulation; Blood Proteins; Cardiovascular Diseases; Factor XIII; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemostasis; Heparin; Humans; Hydrolysis; Plasminogen; Thrombosis

Topics: Animals; Autopsy; Birth Weight; Blood Coagulation Disorders; Bradykinin; Cardiovascular Diseases; Female; Fibrin; Gestational Age; Humans; Hyaline Membrane Disease; Immune System Diseases; Infant, Newborn; Nervous System Diseases; Neurotransmitter Agents; Oxygen; Pregnancy; Respiratory Tract Diseases; Steroids; Water-Electrolyte Balance

Obstructive sleep apnoea (OSA) is associated with increased cardiovascular disease (CVD) risk. In the general population, CVD events peak at 9:00-10:00 AM, associated with diurnal changes in thrombotic potential. However in OSA, these CVD events occur frequently at night. Measuring thrombotic potential across the sleep-wake cycle may provide insight into the temporal association of OSA with CVD. This study aimed to determine diurnal changes in fibrin generation in OSA and whether treatment of OSA with continuous positive airway pressure (CPAP) alters fibrin generation across the sleep-wake cycle. In a randomised placebo-controlled crossover trial, patients with OSA were assigned to two months each of therapeutic CPAP and placebo. After each treatment period, fibrin generation was determined by overall haemostatic potential assay at seven time points over 24 hours (h). Twenty-eight patients (25 men, 3 women) with severe OSA (Apnoea Hypopnoea Index = 37.9 ± 23.9/h, Oxygen Desaturation Index 31.3 ± 22.4/h) completed the study. All parameters, except lag time to fibrin generation, showed significant diurnal changes, both on CPAP and placebo. Compared to 9:00 AM, fibrin generation parameters were significantly lower at midnight and 3:00 AM for overall coagulation potential (OCP), overall haemostasis potential (OHP), maximum optical density, and maximum slope (all p≤0.001). CPAP produced no change in fibrin generation parameters compared to placebo. In severe OSA patients, fibrin generation peaked at 6:00 AM and 9:00 AM rather than during the sleep period (midnight and 3:00 AM). These findings suggest a prothrombotic shift in the morning similar to individuals without OSA. There was no difference between CPAP and placebo on fibrin generation.

Topics: Adult; Arousal; Cardiovascular Diseases; Circadian Rhythm; Continuous Positive Airway Pressure; Cross-Over Studies; Female; Fibrin; Humans; Male; Middle Aged; Sleep; Sleep Apnea, Obstructive; Thrombosis

Elevated homocysteine levels are associated with an increased cardiovascular disease (CVD) risk, but the underlying mechanism is still unclear. High homocysteine might affect the endothelium, and consequently lead to impaired haemostasis. In a randomized placebo controlled trial among 276 older adults with plasma total homocysteine concentrations above 13 mM at screening, we investigated the effect of homocysteine lowering by folic acid supplementation (0.8 mg/day) for 1 year on markers of endothelial function (von Willebrand factor), coagulation (tissue factor, factor VIIa, fragments 1+2), and fibrinolysis (fibrin degradation products, tissue-type plasminogen activator), and inflammation (C-reactive protein). Despite a 24% reduction in plasma homocysteine concentration and four-fold increase in serum folate concentration in the folic acid group compared to the placebo group, there was no clear change in any of the haemostasis markers, nor CRP. Although homocysteine is associated with vascular disease risk in the general population, marked lowering of slightly elevated homocysteine concentrations by one-year folic acid supplementation does not influence haemostasis markers.

Topics: Aged; C-Reactive Protein; Cardiovascular Diseases; Dietary Supplements; Factor VIIa; Female; Fibrin; Folic Acid; Hemostasis; Homocysteine; Humans; Inflammation; Male; Middle Aged; Placebos; Risk; Thromboplastin; Time Factors; von Willebrand Factor

A high intake of beta-carotene has been associated with a decreased risk for cardiovascular disease. To evaluate whether beta-carotene may exert a protective effect through an impact on haemostasis a randomized, placebo-controlled trial was conducted in male smokers (n = 149) using 20 mg/day beta-carotene for 14 weeks. For comparisons, haemostatic indicators were also evaluated in a group of non-smokers (n = 54). Smokers compared with non-smokers had higher fibrinogen (3.5 vs. 3.1 mg/ml, P < 0.01), higher tissue-type plasminogen activator antigen (t-PA; 8.03 vs. 6.60 ng/ml, P < 0.05), lower levels of soluble fibrin (3.40 vs. 5.16 micrograms/ml, P < 0.01) and slightly higher plasma levels of total degradation products of fibrin and fibrinogen (TDP; 47.0 vs. 41.3 ng/ml, P = 0.21). Within the group of smokers, there were no initial differences in the four haemostatic indicators between the placebo (n = 77) and beta-carotene (n = 72) groups, and in both groups there was virtually no change in the indicators during the 14 weeks treatment. It is concluded that the different haemostatic profile in smokers may partly explain their increased risk for cardiovascular disease. beta-Carotene has no influence on the measured haemostatic indicators, and cardiovascular protection for beta-carotene via a beneficial effect on haemostasis seems improbable.

Topics: Adult; Antioxidants; beta Carotene; Cardiovascular Diseases; Carotenoids; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Hemostasis; Humans; Male; Middle Aged; Smoking; Tissue Plasminogen Activator; Vitamins

Standard biomarkers have been widely used for COVID-19 diagnosis and prognosis. We hypothesize that thrombogenicity metrics measured by thromboelastography will provide better diagnostic and prognostic utility versus standard biomarkers in COVID-19 positive patients. In this observational prospective study, we included 119 hospitalized COVID-19 positive patients and 15 COVID-19 negative patients. On admission, we measured standard biomarkers and thrombogenicity using a novel thromboelastography assay (TEG-6s). In-hospital all-cause death and thrombotic occurrences (thromboembolism, myocardial infarction and stroke) were recorded. Most COVID-19 patients were African--Americans (68%). COVID-19 patients versus COVID-19 negative patients had higher platelet-fibrin clot strength (P-FCS), fibrin clot strength (FCS) and functional fibrinogen level (FLEV) (P ≤ 0.003 for all). The presence of high TEG-6 s metrics better discriminated COVID-19 positive from negative patients. COVID-19 positive patients with sequential organ failure assessment (SOFA) score at least 3 had higher P-FCS, FCS and FLEV than patients with scores less than 3 (P ≤ 0.001 for all comparisons). By multivariate analysis, the in-hospital composite endpoint occurrence of death and thrombotic events was independently associated with SOFA score more than 3 [odds ratio (OR) = 2.9, P = 0.03], diabetes (OR = 3.3, P = 0.02) and FCS > 40 mm (OR = 3.4, P = 0.02). This largest observational study suggested the early diagnostic and prognostic utility of thromboelastography to identify COVID-19 and should be considered hypothesis generating. Our results also support the recent FDA guidance regarding the importance of measurement of whole blood viscoelastic properties in COVID-19 patients. Our findings are consistent with the observation of higher hospitalization rates and poorer outcomes for African--Americans with COVID-19.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Black or African American; Cardiovascular Diseases; Comorbidity; COVID-19; COVID-19 Testing; Diabetes Mellitus; Early Diagnosis; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Hospitalization; Humans; Hyperlipidemias; L-Lactate Dehydrogenase; Male; Middle Aged; Obesity; Organ Dysfunction Scores; Prognosis; Prospective Studies; SARS-CoV-2; Thrombelastography; Thrombophilia; Treatment Outcome; White People

Polycystic ovary syndrome (PCOS) is characterized by increased central fat mass (CFM), hyper-inflammation, and hemostatic alterations; the risk of cardiovascular disease may also be increased. Reduced fibrin lysability is a risk factor for cardiovascular disease. The present study assessed fibrin lysability in women with PCOS and controls of similar age and body mass index.. Ninety women with PCOS and 35 controls of comparable age and body mass index were included. Hemostatic markers (fibrin lysability, fibrinogen, coagulation factor XIII, plasminogen, plasminogen activator inhibitor 1 [PAI-1], plasmin inhibitor, thrombin activatable fibrinolysis inhibitor (TAFI), D-dimer), C-reactive protein (CRP), body mass index, waist-to-hip ratio, CFM determined by Dual-energy X-ray absorptiometry scan, and sex hormones (testosterone estradiol, and sex hormone binding globulin) were determined.. TAFI and CRP were higher in women with PCOS, than controls. In women with PCOS, fibrin lysability correlated with CFM, waist-to-hip ratio, CRP, fibrinogen, and all hemostatic variables (P ≤ .004) except TAFI and D-dimer. CFM correlated with fibrinogen, CRP, coagulation factor XIII, waist-to-hip ratio, plasminogen, PAI-1, plasmin inhibitor, and TAFI (P < .02). In controls, fibrin lysability correlated with CFM, fibrinogen, coagulation factor XIII, and plasmin inhibitor (P ≤ .02). CFM correlated with PAI-1, plasmin inhibitor, coagulation factor XIII, fibrinogen, and CRP (P ≤ .05). Stepwise regression analysis revealed that fibrin lysability was associated with CFM, fibrinogen and CRP in women with PCOS (r. Fibrin lysability was comparable in women with PCOS and controls. Fibrin lysability was associated with CFM and hyper-inflammation in women with PCOS, but only with CFM in controls. These findings suggest that obese women with PCOS and augmented inflammation could have an increased risk of cardiovascular disease.

Topics: Absorptiometry, Photon; Adolescent; Adult; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Female; Fibrin; Gonadal Steroid Hormones; Humans; Inflammation; Obesity, Abdominal; Polycystic Ovary Syndrome; Risk Factors

There remains increased cardiovascular mortality in patients with acromegaly. This study aims to evaluate whether GH/IGF-1 excess increases vascular disease by adversely affecting fibrin network characteristics.. Cross-sectional study in 40 patients with acromegaly (21 males, age 53 ± 13 years) and 40 age/gender-matched controls.. Clot structure was analysed using a validated turbidimetric assay and fibrin networks were visualised by laser scanning confocal microscopy (LSCM). Metabolic profile parameters, body composition, plasma fibrinogen and PAI-1 were also assessed.. Twenty-two patients had active acromegaly and 18 were in remission. There was no difference in qualitative patient characteristics between the two groups. Both groups had less favourable body composition and cardiovascular risk profile compared with controls. Despite no difference in clot formation and lysis parameters between the two patient groups, active disease patients had higher fibrinogen and clot maximum absorbance compared with controls, after adjusting for BMI (3.8 ± 0.2 vs 2.6 ± 0.2 mg/mL, P < 0.001; and 0.39 ± 0.02 vs 0.33 ± 0.01 arbitrary units, P = 0.03, respectively). Patients in remission had higher fibrinogen compared with controls following adjustment for BMI (3.3 ± 0.2 vs 2.6 ± 0.2 mg/mL, P = 0.02) but not clot maximum absorbance (0.35 ± 0.03 vs 0.33 ± 0.02 arbitrary units, P = 0.6). LSCM showed increased fibrin network density only in active disease patients, consistent with turbidimetric analysis. In addition to active disease, BMI, fat mass and skinfold thickness were associated with higher clot density and longer lysis time.. Patients with active acromegaly have more compact clots, thus conferring increased thrombosis risk. Prothrombotic fibrin networks may represent one mechanism for enhanced vascular risk in active acromegaly.

Topics: Acromegaly; Adult; Aged; Blood Coagulation Tests; Cardiovascular Diseases; Cross-Sectional Studies; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Pilot Projects; Thrombosis

We report a technique to reconstruct cardiovascular tissue using multiscale scaffolds incorporating polycaprolactone fibers with double-layered hydrogels comprising fibrin hydrogel surrounded by secondary alginate hydrogel. The scaffolds compartmentalized cells into the core region of cardiac tissue and the peripheral region of blood vessels to construct cardiovascular tissue, which was accomplished by a triple culture system of adipose-derived mesenchymal stem cells (ADSCs) with C2C12 myoblasts on polycaprolactone (PCL) fibers along with human umbilical vein endothelial cells (HUVECs) in fibrin hydrogel. The secondary alginate hydrogel prevented encapsulated cells from migrating outside scaffold and maintained the scaffold structure without distortion after subcutaneous implantation. According to in vitro studies, resultant scaffolds promoted new blood vessel formation as well as cardiomyogenic phenotype expression of ADSCs. Cardiac muscle-specific genes were expressed from stem cells and peripheral blood vessels from HUVECs were also successfully developed in subcutaneously implanted cell-laden multiscale scaffolds. Furthermore, the encapsulated stem cells modulated the immune response of scaffolds by secreting anti-inflammatory cytokines for successful tissue construction. Our study reveals that multiscale scaffolds can be promising for the remodeling and transplantation of cardiovascular tissue.

Topics: Animals; Cardiovascular Diseases; Cell Line; Cytokines; Fibrin; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels; Mesenchymal Stem Cells; Mice; Myoblasts; Neovascularization, Physiologic; Phenotype; Polyesters; Tissue Engineering; Tissue Scaffolds; Tissue Transplantation

Fibrin clot lysability is associated with development of cardiovascular disease (CVD). We evaluated sex-differences in fibrin clot lysability and the association with coronary plaque composition determined by computed tomography angiography (CTA).. Middle-aged citizens without known CVD were randomly selected from a national registry. A coronary CTA assessed volumes of calcified-, non-calcified-, low-density non-calcified-, and total- plaque using a validated plaque quantification software. A non-enhanced cardiac CT scan assessed the Agatston score. Fibrin structure properties were determined using turbidimetric methods. Plasma concentrations of C-reactive protein and fibrinogen were assessed.. 138 individuals (71 women) participated. Men more frequently had coronary plaques compared to women, P < 0.05. Coronary plaque features were comparable between men and women, P > 0.05. Women with total plaque volume > 0 mm. Asymptomatic women with coronary plaques assessed by coronary CTA have reduced fibrin clot lysability compared to both women without coronary plaques and men, suggesting a sex-dependent link between coronary atherosclerosis and fibrin clot lysability.

Topics: Aged; Cardiovascular Diseases; Cohort Studies; Coronary Artery Disease; Cross-Sectional Studies; Female; Fibrin; Humans; Male; Middle Aged; Plaque, Atherosclerotic; Risk Factors; Sex Characteristics

Topics: Cardiovascular Diseases; Fibrin; Humans; Hypertension; Risk Factors; Sleep Apnea, Obstructive; Thrombosis

Type 2 diabetes is associated with faster formation of poorly lysable, denser fibrin clots and elevated cellular fibronectin (cFn), a marker of vascular injury. We investigated whether cFn affects clot properties in type 2 diabetes. In 200 consecutive patients with type 2 diabetes and 100 control subjects matched for age and sex, we determined plasma cFn along with clot formation and degradation using turbidimetric and permeability assays. Diabetic patients had elevated cFn (median, 3.99 [interquartile range, 2.87-4.81] µg/ml]), increased clot density (MaxAbsC) and prolonged lysis time (LysT) compared with those without type 2 diabetes (all p<0.01). Diabetic patients with documented cardiovascular disease (CVD, n=127, 63.5 %) had increased cFn (4.53 [3.68-4.95] µg/ml), decreased clot permeability (Ks) and increased MaxAbsC compared with those without CVD (all p<0.001). Diabetic patients with cFn in the top quartile (>4.81 µg/ml) were two times more likely to have CVD compared with those in the lowest quartile (odds ratio 1.80, 95 % confidence interval 1.41-2.46, p<0.001). No differences in cFn were observed in relation to microvascular complications. After adjustment for potential confounders, cFn accounted for 10.2 % of variance in Ks, 18.2 % of variance in clot density and 10.2 % of variance in AUC in diabetic patients. This study shows that elevated cFn is associated with unfavourably modified clot properties in type 2 diabetes, especially with concomitant CVD, which indicates novel links between vascular injury and prothrombotic alterations in diabetes. Coagulation, cellular fibronectin, type 2 diabetes, cardiovascular disease.

Topics: Aged; Biomarkers; Blood Coagulation; Cardiovascular Diseases; Case-Control Studies; Chi-Square Distribution; Diabetes Mellitus, Type 2; Female; Fibrin; Fibrinolysis; Fibronectins; Humans; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Risk Assessment; Risk Factors; Thrombosis; Up-Regulation

The increased risk of vascular complications in type 1 diabetes may in part be explained by changes in haemostatic function. In the present study, we investigated the fibrin clot properties in patients with type 1 diabetes in relation to sex and microvascular complications. The study included 236 patients (107 women) aged between 20-70 years and without any history of cardiovascular disease. Fibrin clot properties, assessed by determination of the permeability coefficient (Ks) and turbidimetric clotting and lysis assays, did not differ between men and women. Compared with men, women had worse glycaemic control as well as higher levels of prothrombin fragment 1+2 and peak thrombin generation in vitro, indicating increased thrombin generation both in vivo and in vitro. Subgroup analyses of patients younger than 30 years revealed less permeable fibrin clots and prolonged lysis time in females compared with age-matched men. Patients with microvascular complications had higher fibrinogen concentrations and denser and less permeable fibrin clots. Thus, we conclude that in vitro fibrin clot properties in patients with type 1 diabetes without cardiovascular disease are not different between the sexes, but associate with prevalence of microvascular complications. Tighter fibrin clot formation in younger women, as suggested by our results, may affect their future cardiovascular risk and should be investigated in a larger population.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Tests; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus, Type 1; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Hyperglycemia; Male; Microcirculation; Middle Aged; Nephelometry and Turbidimetry; Permeability; Risk Factors; Thrombin; Thrombosis; Young Adult

Hypercoagulability plays a key role in the progression of cardiovascular disease (CVD). Although omega-3 polyunsaturated fatty acid (PUFA) intake has been inversely related to the risk of cardiovascular events, the mechanisms are not fully understood. The aim of this study was to investigate the effects of omega-3 on novel markers of global coagulation. The generation of fibrin and thrombin, measured via overall hemostasis potential (OHP) assay and calibrated automated thrombography, respectively, was determined in 40 healthy subjects and 16 patients with CVD at baseline and after 4 weeks of 640 mg/day omega-3 PUFA. In healthy subjects, fibrin generation was significantly reduced, as measured by overall coagulation potential (p = 0.013), OHP (p < 0.001), velocity of fibrin polymerization (p = 0.002), and significant increase in delay to fibrin generation (p = 0.002). The peak of generated thrombin was significantly reduced (p = 0.043). In subjects with CVD, omega-3 PUFA significantly reduced OHP and significantly increased the lag time to thrombin generation (both p < 0.001). Treatment with omega-3 PUFA had no effect on other fibrin and thrombin generation parameters in CVD patients. Four-week omega-3 PUFA supplementation reduced thrombotic potential in healthy subjects, as shown by reduced fibrin generation and peak thrombin. There was a greater effect on fibrin generation in healthy subjects compared with those with CVD.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Case-Control Studies; Cholesterol; Fatty Acids, Omega-3; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Thrombin; Thrombosis; Young Adult

To investigate the effect of low blood glucose on thrombin generation and fibrin clot properties in type 2 diabetes (T2DM).. In 165 patients with T2DM and high cardiovascular risk, we measured ex vivo plasma fibrin clot permeation [Ks], turbidity and efficiency of fibrinolysis including clot lysis time [t50%], together with thrombin generation and platelet activation markers in relation to fasting blood glucose.. As compared to patients in medium (4.5-6.0 mmol/l, n = 52) and higher (>6.0 mmol/l, n = 75) glucose group, subjects with low glycemia (<4.5 mmol/l, n = 38) had lower Ks by 11% (p < 0.001) and 8% (p = 0.01), respectively, prolonged t50% by 10% (p < 0.001) and 7% (p = 0.016), respectively, and higher peak thrombin generation by 21% and 16%, respectively (p < 0.001 for both). There were no significant differences in Ks and t50% between patients in medium and higher glucose group. In the whole group, a J-shape relationship was observed between glycemia and the following factors: peak thrombin generation, Ks and t50%. Only in patients with HbA1c < 6.0% (42 mmol/mol) (n = 26) fasting glucose positively correlated with Ks (r = 0.53, P = 0.006) and inversely with t50% (r = -0.46, P = 0.02). By multiple regression analysis, after adjustment for age, fibrinogen, HbA1c, insulin treatment and T2DM duration, fasting glycemia was the independent predictor of Ks (F = 6.6, df = 2, P = 0.002), t50% (F = 8.0, df = 2, P < 0.001) and peak thrombin generation (F = 13.5, df = 2, P < 0.0001).. In T2DM patients fasting glycemia <4.5 mmol/l is associated with enhanced thrombin formation and formation of denser fibrin clots displaying lower lysability, especially when strict glycemia control was achieved (HbA1c<6.0%).

Topics: Aged; Blood Coagulation; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Fasting; Female; Fibrin; Humans; Male; Middle Aged; Risk Factors; Thrombin

The relationship between thrombin-induced platelet-fibrin clot strength (MATHROMBIN), genotype and high on-treatment platelet reactivity (HPR) is unknown. The aim of this study is to assess the influence of MATHROMBIN measured by thrombelastography on HPR and long-term major adverse cardiovascular events (MACE) in percutaneous coronary intervention (PCI)-treated patients during aspirin and clopidogrel therapy. MATHROMBIN, platelet aggregation, genotype, and two-year MACE were assessed in 197 PCI-treated patients. HPR was defined as 5 µM ADP-induced PR ≥ 46% measured by conventional aggregometry. Both high MATHROMBIN(≥ 68 mm) and CYP2C19*2 allele carriage were independently associated with ADP-induced platelet aggregation (β coefficient: 8.3% and 12.0%, respectively). The combination of CYP2C19*2 allele carriage and high MATHROMBIN increased the predictive value for the risk of HPR (odds ratio: 13.89; 95% confidence interval: 3.41 to 55.56; p < 0.001). MACE occurred in 25 patients (12.7%). HPR and high MATHROMBIN were both associated with MACE (hazard ratio: 3.09 and 2.24, respectively), and patients with both HPR and high MATHROMBIN showed an increased risk for MACE (adjusted hazard ratio: 5.56; 95% confidence interval: 1.85 to 16.67; p = 0.002). In conclusion, this is the first study to demonstrate that high platelet-fibrin clot strength is an independent determinant of HPR in PCI-treated patients. Combining the measurements of platelet aggregation and platelet-fibrin clot strength may enhance post-PCI risk stratification and deserves further study.

Topics: Aged; Aspirin; Blood Coagulation; Blood Platelets; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C19; Female; Fibrin; Genetic Testing; Genotype; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Platelet Aggregation; Polymorphism, Genetic; Predictive Value of Tests; Prognosis; Thrombelastography; Thrombin; Ticlopidine; Treatment Outcome

Cardiovascular disease (CVD) risk factors are associated with total fibrinogen concentration and/or altered clot structure. It is however, unclear whether such associations with clot structure are ascribed to fibrinogen concentration or other independent mechanisms. We aimed to determine whether CVD risk factors associated with increased total and/or γ' fibrinogen concentration, were also associated with altered fibrin clot properties and secondly whether such associations were due to the fibrinogen concentration or through independent associations.. In a plasma setting CVD risk factors (including total and γ' fibrinogen concentration) were cross-sectionally analysed in 2010 apparently healthy black South African participants. Kinetics of clot formation (lag time, slope and maximum absorbance) as well as clot lysis times were calculated from turbidity curves.. Of the measured CVD risk factors age, metabolic syndrome, C-reactive protein (CRP), high density lipoprotein (HDL)-cholesterol and homocysteine were significantly associated with altered fibrin clot properties after adjustment for total and or γ' fibrinogen concentration. Aging was associated with thicker fibres (p=0.004) while both metabolic syndrome and low HDL-cholesterol levels were associated with lower rates of lateral aggregation (slope), (p=0.0004 and p=0.0009), and the formation of thinner fibres (p=0.007 and p=0.0004). Elevated CRP was associated with increased rates of lateral aggregation (p=0.002) and consequently thicker fibres (p<0.0001). Hyperhomocysteinemia was associated with increased rates of lateral aggregation (p=0.0007) without affecting fibre thickness.. Final clot structure may contribute to increased CVD risk in vivo through associations with other CVD risk factors independent from total or γ' fibrinogen concentration.

Topics: Adult; Blood Coagulation; Cardiovascular Diseases; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogens, Abnormal; Fibrinolysis; Humans; Male; Middle Aged; Risk Factors

Fibrinogen γ' is known to influence fibrin clot structure in purified experimental models, but little is known regarding its influence on clot structure in plasma. Furthermore, the environmental and biological factors that affect its concentration are poorly described. We analyzed fibrinogen γ', total fibrinogen concentration, and fibrin clot structure in 2010 apparently healthy black South Africans and related them to traditional cardiovascular disease (CVD) risk factors. Fibrinogen γ' generally increased with increasing fibrinogen concentration, but a decreased γ'/total fibrinogen ratio was found at the highest total fibrinogen concentrations. Clot maximum absorbance increased with total fibrinogen and fibrinogen γ', but decreased with γ'/total fibrinogen ratio. Clot lysis time showed a stronger relationship with fibrinogen γ' than with total fibrinogen, whereby increased fibrinogen γ' delayed clot lysis. CVD risk factors (excluding fibrinogen) explained 20% and 3%, respectively, of the variance in fibrinogen γ' and the γ'/total fibrinogen ratio, with C-reactive protein making the biggest contribution. More than 50% of the variance in fibrinogen γ' and γ'/total fibrinogen ratio is explained by factors other than total fibrinogen or other traditional CVD risk factors. Our data show that fibrinogen γ' modulates plasma clot structure and fibrinolysis and is also influenced by factors other than fibrinogen.

Topics: Adult; Aged; Black People; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Fibrinogens, Abnormal; Fibrinolysis; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; South Africa

Diabetes is associated with increased incidence of atherothrombotic disease. The fibrin network forms the backbone of the arterial thrombus, and fibrin clot structure determines predisposition to cardiovascular events.. The aim of the study was to investigate fibrin clot structure/fibrinolysis in the largest type 2 diabetes cohort and analyze associations with cardiometabolic risk factors and vascular pathology.. Clot structure/fibrinolysis was assessed in 875 participants of the Edinburgh Type 2 Diabetes Study [age, 68 (range, 60-75) yr; 450 males] by turbidimetric assays, and clots were visualized by confocal microscopy. Four parameters of clot structure/fibrinolysis were analyzed, and plasma levels of fibrinogen and plasminogen activator inhibitor-1 were studied by Clauss assay and ELISA, respectively.. Clot maximum absorbance was increased in females compared with males (0.37 ± 0.005 and 0.34 ± 0.005 arbitrary unit, respectively; P < 0.001), and took longer to lyse (803 ± 20 and 665 ± 12 sec, respectively; P < 0.001). These gender differences in clot structure and fibrinolysis were still evident after correcting for fibrinogen and plasminogen activator inhibitor-1 plasma levels. A prothrombotic fibrin structure profile was associated with increased body mass index and low levels of high-density lipoprotein in women and with inadequate diabetes control in men. Clot formation time was related to previous cardiac ischemic events in both men and women after adjusting for traditional risk factors [odds ratio, 1.22 (95% confidence interval, 1.07, 1.38); and 1.33 (1.15, 1.50), respectively], and prothrombotic clots were associated with low ankle brachial index, renal impairment, and smoking, regardless of gender.. Women with type 2 diabetes have compact clots with compromised fibrinolysis compared with men. There are gender-specific associations between clotting parameters and cardiometabolic risk factors in this population, whereas vascular abnormalities, impaired renal function, and smoking are associated with prothrombotic clot structure profile regardless of gender.

Topics: Aged; Biomarkers; Blood Coagulation; Blood Coagulation Tests; Cardiovascular Diseases; Cohort Studies; Diabetes Mellitus, Type 2; Female; Fibrin; Fibrinolysis; Humans; Male; Metabolic Diseases; Middle Aged; Risk Factors; Sex Factors; Structure-Activity Relationship

Topics: Analysis of Variance; Blood Coagulation; Blood Coagulation Tests; Cardiovascular Diseases; Europe; Fibrin; Humans; Observer Variation; Permeability; Pilot Projects; Predictive Value of Tests; Reference Values; Reproducibility of Results

Altered fibrin clot properties have been reported in cardiovascular diseases (CVD) and inflammatory states. Given increased prevalence of CVD in patients with rheumatoid arthritis (RA), we investigated whether fibrin characteristics are also altered in RA patients.. We studied 46 consecutive RA patients versus 50 controls matched for age and gender. Ex vivo plasma clot permeability, turbidity, tissue-type plasminogen activator (tPA)-induced fibrinolysis, and scanning electron microscopy (SEM) images of clots were evaluated.. Patients with RA had lower clot permeability, faster clot formation, higher maximum clot absorbency indicating thicker fibrin fibers, maximum clot mass and prolonged fibrinolysis time than controls. Maximum rates of clot lysis were similar in both groups. SEM images showed formation of dense clots with many projections on fibrin fibers. Clot permeability inversely correlated with fibrinogen, tPA, plasminogen activator inhibitor-1 (PAI-1), CRP, platelet count, disease activity score (DAS28) and a marker of oxidative stress, 8-iso-prostaglandin F2alpha (r from -0.44 to -0.79; all, p<0.0001). Similar positive associations were found for clot lysis time (r 0.44 to 0.69; all, p<0.01). Multiple regression analysis showed that fibrinogen was the only independent predictor of clot permeability (R2=0.87, p<0.0001) and lysis time (R2=0.80, p<0.003) in RA. Maximum D-dimer levels released from clots, maximum clot turbidity and the time of clot formation were predicted by PAI-1 (all, p<0.05).. We showed unfavorably altered plasma fibrin clot structure and function in RA, which might contribute to an increased risk of thrombotic events in this disease.

Topics: Adult; Aged; Blood Coagulation Tests; Cardiovascular Diseases; Case-Control Studies; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Inflammation; Male; Middle Aged; Permeability; Plasminogen Activator Inhibitor 1; Thrombosis; Tissue Plasminogen Activator; Young Adult

Topics: Blood Coagulation; Cardiovascular Diseases; Family; Fibrin; Genetic Predisposition to Disease; Humans; Intermittent Claudication; Pedigree; Peripheral Vascular Diseases; Prognosis; Risk Factors

: The presence of an abdominal aortic aneurysm (AAA) independently predicts cardiovascular disease (CVD) and its complications. Levels of plasma markers of fibrin turnover are raised in men with a large AAA (at least 5.5 cm) and predict CVD risk in healthy subjects. This study examined fibrin turnover in men with a small AAA.. : Seventy-five men with a small AAA (30-55 mm) were compared with 90 controls matched for age, sex and race. Haemostatic and fibrinolytic parameters were assessed.. : Men with a small AAA had higher mean levels of fibrinogen (2.92 versus 2.59 g/l; P = 0.019), thrombin-antithrombin (TAT) complex (4.57 versus 1.89 ng/ml; P < 0.001), prothrombin F1 + 2 (1.13 versus 0.82 ng/ml; P = 0.004) and D-dimer (346.7 versus 120.2 ng/ml; P < 0.001). All markers correlated with maximum aortic diameter determined by ultrasonography. On multivariable regression the association between presence of an AAA and fibrinogen, TAT complex, prothrombin F1 + 2 and D-dimer levels remained significant after adjustment for confounding influences.. : Fibrin turnover was increased in these men with a small AAA, independently of concomitant CVD, conventional risk factors and inflammatory markers. Enhanced fibrin turnover may contribute to the risk of cardiac complications in this group.

Topics: Aged; Antithrombin III; Aortic Aneurysm, Abdominal; Cardiovascular Diseases; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Male; Peptide Hydrolases; Regression Analysis; Risk Factors

Haemodialysis patients are at an increased risk of cardiovascular (CV) morbidity and mortality. Both end-stage renal disease (ESRD) and thromboembolic coronary events have been shown to be associated with the formation of dense fibrin clots resistant to fibrinolysis. The aim of the present study was to investigate the effect of long-term haemodialysis on clot structure/function and analyse an influence of markers of inflammation, oxidative stress and lipoprotein(a). We sought also to investigate if clot features might be related to CV events and mortality in haemodialysis patients. Subjects and methods. In 33 patients (19 males, 14 females), aged 27 to 89 years, on long-term haemodialysis and 33 age- and sex-matched apparently healthy controls, we investigated fibrin clot properties and susceptibility to lysis using recombinant tissue plasminogen activator by using permeation and turbidity assays.. Haemodialysis patients produced fibrin clots that had less porous structure (P < 0.0001) were less susceptible to fibrinolysis (P < 0.0001), began fibrin protofibril formation more quickly (P < 0.0001) and showed increased overall fibre thickness (P < 0.0001) compared with controls. Clot permeability and lysis time correlated with F2-isoprostanes (P < 0.01), Lp(a) (P < 0.0001) and fibrinogen (P < 0.01). None of the clot variables showed associations with the duration of haemodialysis treatment or the cause of ESRD. During a 36-month follow-up, 10 CV deaths were recorded. Mortality was associated with reduced clot permeability (P < 0.0001), prolonged lysis time (P < 0.0001), faster fibrin protofibril formation (P = 0.0004), thicker fibres (P < 0.0001) and increased fibrin clot mass (P < 0.0001).. Unfavourably altered clot properties can be detected in haemodialysis patients and may be associated with increased CV mortality.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Cardiovascular Diseases; Case-Control Studies; Cohort Studies; Coronary Thrombosis; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Middle Aged; Nephelometry and Turbidimetry; Permeability; Probability; Reference Values; Renal Dialysis; Risk Assessment; Statistics, Nonparametric; Survival Analysis

Chicken fat clot (CFC), a fibrin-like substance, is sometimes found in the heart and large blood vessels in some autopsy cases. Reports of detailed histological findings of CFC are scant. We therefore examined CFC histologically in 53 autopsy cases and its correlation with ante-mortem or post-mortem evidence. We found three microscopic patterns of CFC: (1) wavelike fibrin fibers (WFF), (2) short fibrin fibers (SFF), and (3) short fibrin fibers mixed with wavelike fibrin fibers (SFF+WFF). WFF were found in the cases that survived less than 3 h after poisoning, burns, asphyxia, intracerebral hemorrhage, etc. SFF were found in the cases that survived more than 1 day after malignant neoplasms and acute or chronic inflammatory diseases, etc. SFF+WFF were found in the cases that died of inflammatory diseases, chronic heart failure, hemorrhagic shock, drowning, etc. About two-thirds of the SFF+WFF cases survived more than 1 day, with the rest surviving less than that. Our study confirmed three CFC patterns and their relation with survival interval. Therefore, these findings can be used as an index of the survival interval of a few acute and most chronic medico-legal death cases.

Topics: Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Female; Fibrin; Forensic Pathology; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasms; Respiratory Tract Diseases; Retrospective Studies; Survival Analysis; Thrombosis; Time Factors; Wounds and Injuries

Elevated plasma fibrinogen is a well known risk factor for cardiovascular disease. The mechanistic rationale for this is not known.. These studies were carried out to determine the fibrinogen concentration dependencies of clotting and lysis times and thereby determine whether these times rationalize the correlation between an increased risk of cardiovascular disease and elevated plasma fibrinogen.. The time courses of clot formation and lysis were measured by turbidity in systems comprising a) fibrinogen, thrombin and plasmin, or b) fibrinogen, thrombin, plasminogen and t-PA, or c) plasma, thrombin and t-PA. From the lysis times, k(cat) and K(m) values for plasmin action on fibrin were determined.. The time to clot increased linearly from 2.9 to 5.6 minutes as the fibrinogen concentration increased from 1 to 9 microM and did not increase further as the fibrinogen concentration was raised to 20 microM. In contrast, the clot lysis time increased linearly over the input fibrinogen concentration range of 2 to 20 microM. A similar linear trend was found in the two systems with t-PA and plasminogen. Apparent K(m) and k(cat) values for plasmin were 1.1 +/- 0.6 microM and 28 +/- 2 min(-1), respectively. K(m) values for plasmin in experiments initiated with t-PA and plasminogen were 1.6 +/- 0.2 microM in the purified system and 2.1 +/- 0.9 microM in plasma.. As the concentration of fibrinogen increases, especially above physiologic level, the balance between fibrinolysis and clotting shifts toward the latter, providing a rationale for the increased risk of cardiovascular disease associated with elevated fibrinogen.

Topics: alpha-2-Antiplasmin; Blood Coagulation; Cardiovascular Diseases; Fibrin; Fibrinogen; Hemolysis; Humans; In Vitro Techniques; Kinetics; Models, Cardiovascular; Nephelometry and Turbidimetry; Peptide Fragments; Plasminogen; Recombinant Proteins; Tissue Plasminogen Activator

Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation.. The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls.. This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls.. The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibrinolytic potential by venous occlusion test.. Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/ml after adjustment for baseline PAI-1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml (interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [area under the curve 3.8 (interquartile range -2.4 to 7.9) vs. 12.8 (interquartile range 2.1-19.4); P = 0.043].. Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.

Topics: Adult; Cardiovascular Diseases; Case-Control Studies; Circadian Rhythm; Endothelium, Vascular; Female; Fibrin; Fibrinolysis; Growth Disorders; Growth Hormone; Homeostasis; Humans; Male; Plasminogen Activator Inhibitor 1; Risk Factors; Tissue Plasminogen Activator

Topics: Cardiac Tamponade; Cardiovascular Diseases; Echocardiography; Fibrin; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged

The precise mechanisms underlying the increased risk of cardiovascular disease (CVD) in type 2 diabetes are unclear. Fibrin clot structure has been related to CVD risk in the general population. We therefore assessed this in type 2 diabetic patients as a potential mechanism whereby diabetes influences CVD risk.. Fibrin clots were formed from fibrinogen purified from 150 subjects with type 2 diabetes and varying degrees of glycaemic control (assessed by HbA1c), and from 50 matched control subjects. Clot structure was assessed by turbidity, permeation and confocal microscopy. The specific effect of glucose itself was assessed by analysing the structure of clots formed from purified fibrinogen in the presence of increasing concentrations of the sugar.. Clots formed by fibrinogen purified from type 2 diabetic subjects had a denser, less porous structure than those from control subjects. The structural changes found were related to the individual's glycaemic control; HbA1c correlated negatively with permeation coefficient (Ks) values (indicates clot pore size) (r = -0.57, p < 0.0001) and positively with maximum absorbance (indicator of fibre size) (r = 0.33, p < 0.0001), branch point number (r = 0.78, p < 0.0001) and fibre density (r = 0.63, p < 0.0001). The ambient glucose level influenced clot structure; hypo- (< 5 mmol) and hyperglycaemia (> or = 10 mmol/l) were both associated with a reduction in Ks values and maximum absorbance, and with increased fibre density and branch point number within clots.. The structural differences found to occur in type 2 diabetes and in association with hypo- and hyperglycaemia may confer increased resistance to fibrinolysis, and in consequence contribute to the increase in CVD risk in diabetic patients.

Topics: Blood Coagulation; Body Mass Index; Body Size; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Factor XIII; Female; Fibrin; Fibrinogen; Humans; Hypoglycemic Agents; Lipids; Male; Middle Aged; Reference Values; Risk Factors

The underlying cause of acute functional disorders of the inner ear (sudden hearing loss) is usually not detectable with clinical diagnostic measures. It is assumed that functional disorders of the inner ear are merely symptoms and not a disease entity in itself. In particular regional perfusion disturbances, but also autoimmune phenomena, viral infections and micromechanical disorders of the cochlea are seen as pathogenetic principles in inner ear disturbances. Although numerous effective therapeutic options and prophylactic measures for such diseases as myocardial infarction and stroke are available to cardiovascular medicine, they have so far not been applied to the treatment of inner ear problems. Here there is a promising and wide field of options for such diseases that can be traced back to regional perfusion disorders.

Topics: Blood Component Removal; Cardiovascular Diseases; Combined Modality Therapy; Ear, Inner; Fibrin; Hearing Loss, Sudden; Hemodilution; Humans; Ischemia; Lipoprotein(a); Lipoproteins, LDL; Randomized Controlled Trials as Topic; Risk Factors; Thrombolytic Therapy

The clustering of impaired glucose metabolism, elevated triglycerides, low HDL cholesterol, and abdominal obesity is known as the metabolic syndrome. Individuals with this syndrome suffer an excess of cardiovascular disease (CVD) for reasons that are unclear.. We randomly sampled 1276 adults of South Asian, Chinese, European, and Native Indian ancestry from 4 communities in Canada. Participants provided fasting blood samples for glucose, lipids, and fibrinolytic measurements; had an oral glucose tolerance test; and underwent a B-mode carotid ultrasound examination. CVD was determined by history and ECG. The prevalence of the metabolic syndrome was 25.8% (95% CI, 23.5 to 28.2) and varied substantially by ethnic group: 41.6% among Native Indians, 25.9% among South Asians, and 22.0% among Europeans, compared with 11.0% among the Chinese (overall, P=0.0001). People with the metabolic syndrome had more atherosclerosis (maximum intimal medial thickness, 0.78+/-0.18 versus 0.74+/-0.18 mm; P=0.0005), CVD (17.2% versus 7.0%; P=0.0001), and elevated plasminogen activator inhibitor-1 (24.2 versus 14.6 U/mL; P=0.001) compared with levels among people without the metabolic syndrome. For the same amount of atherosclerosis, people with the metabolic syndrome had a greater prevalence of CVD, even among nondiabetic individuals. This difference in CVD prevalence among the groups was attenuated after adjustment for plasminogen activator inhibitor-1 levels, suggesting that fibrinolytic dysfunction mediates the increased risk of CVD in individuals with the metabolic syndrome.. CVD among people with the metabolic syndrome is explained by their excess of atherosclerosis and impaired fibrinolysis. Interventions to prevent atherosclerosis progression and improve fibrinolytic function require evaluation in this high-risk group.

Topics: Adult; Arteriosclerosis; Asia; Asian People; Blood Glucose; Canada; Cardiovascular Diseases; Carotid Arteries; Comorbidity; Electrocardiography; Europe; Female; Fibrin; Fibrinolysis; Glucose Tolerance Test; Humans; Indians, North American; Lipids; Male; Metabolic Syndrome; Middle Aged; Prevalence; Risk Assessment; Risk Factors; Ultrasonography; White People

Among users of low-dose oral contraceptives (OC), cardiovascular diseases occur mainly in smokers. The mechanisms by which OC and smoking increase the risk for arterial thrombotic risk have not been adequately explained. Epidemiological evidence suggests that changes in blood coagulation and fibrinolysis may play an important role as determinants of thrombotic events. Therefore, we have investigated the associations of OC and smoking with haemostatic variables among 194 premenopausal healthy women. Fourty women were current users of low-dose OC and 62 women were smokers. After adjustment for age and body mass index, mean values of factor XIIa, factor VII activity and antigen, fibrinogen, D-dimer, global fibrinolytic capacity were significantly higher in OC users than in non-users. Mean levels of PAI activity and t-PA antigen were significantly lower in OC users than in non-users. Smokers had significantly higher mean values of fibrinogen than non-smokers. Two-way analysis of variance showed that the differences in mean levels of fibrinogen and D-dimer between OC users and non users were restricted to smokers. The positive and significant interactions between OC use and smoking in their effects on haemostatic variables were consistent with respect to age and type of OC. These preliminary data suggest that elevated plasma levels of fibrinogen and intravascular fibrin deposition may play a role in the pathogenesis of arterial thrombotic disease among women who are both low-dose OC users and smokers.

Topics: Adult; Cardiovascular Diseases; Contraceptives, Oral; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemostasis; Humans; Middle Aged; Risk Factors; Smoking

There is growing evidence that fibrin D-dimer is associated with coronary and peripheral atherosclerosis. Using data from the Edinburgh Artery Study, we examined the distribution of fibrin D-dimer in 1592 men and women 55 to 74 years old and assessed its relationship with a range of cardiovascular risk factors. Fibrin D-dimer levels were higher in women than in men (P < or = .05) and increased with age (P < or = .001). Current cigarette smokers had higher levels than ex-smokers, who, in turn, had higher levels than those who had never smoked. On multiple regression analyses with age and plasma fibrinogen as covariates, only lifetime smoking in men and systolic blood pressure in women were independent predictors of fibrin D-dimer levels. Since fibrin D-dimer does not appear to be independently related to many of the common cardiovascular risk factors, it may be a useful index of the thrombotic contribution to arterial disease.

Topics: Aged; Cardiovascular Diseases; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Sex Factors

Topics: Cardiovascular Diseases; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Gels; Humans; Risk Factors

Alterations characteristic of the hypercoagulation syndrome such as changes in fibrinogen content, in FDP concentration and platelet counts as well as the presence of fibrinogen complexes were demonstrated by laboratory findings in 175 patients with severe diseases and disturbances of haemostasis. Twenty per cent of the patients showed no clinical signs of disturbances of haemostasis, in 32.5 per cent pronounced venous thrombosis occurred, bleeding complications arised in 28 per cent and microthrombosis developed in 20 per cent. The different findings in the individual groups are assumed to be due not only to haemostatic factors but also to other ones.

Topics: Blood Coagulation Tests; Cardiovascular Diseases; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Neoplasms; Partial Thromboplastin Time; Platelet Count; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Thrombosis

Topics: Adult; Antigen-Antibody Reactions; Biopsy; Cardiovascular Diseases; Cesarean Section; Female; Fibrin; Humans; Hypertension; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Lysosomes; Obstetric Labor Complications; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Pyelonephritis; Serotonin

Topics: Adolescent; Adult; Age Factors; Aged; Animals; Anticoagulants; Arthritis, Rheumatoid; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cardiovascular Diseases; Cattle; Child; Child, Preschool; Dogs; Electrophoresis; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Hemorrhagic Disorders; Humans; Infant; Male; Menstruation; Methods; Middle Aged; Neoplasms; Plasminogen; Pregnancy; Rabbits; Sex Factors; Thromboembolism; Thrombosis; Uremia

Topics: Aspartate Aminotransferases; Cardiovascular Diseases; Fibrin; Myocardial Infarction; Myocardium; Potassium; Transaminases

Topics: Cardiovascular Diseases; Fibrin; Fibrinolysis; Humans; Myocardial Infarction

Topics: Animals; Cardiovascular Diseases; Female; Fibrin; Obstetric Labor Complications; Pregnancy; Rabbits; Rh-Hr Blood-Group System; Vaccination