fibrin and Thromboembolism

Polymeric fibrin displays unique structural and biomechanical properties that contribute to its essential role of generating blood clots that stem bleeds. The aim of this review is to discuss how the fibrin clot is formed, how protofibrils make up individual fibrin fibers, what the relationship is between the molecular structure and fibrin biomechanical properties, and how fibrin biomechanical properties relate to the risk of thromboembolic disease. Fibrin polymerization is driven by different types of bonds, including knob-hole interactions displaying catch-slip characteristics, and covalent crosslinking of fibrin polypeptides by activated factor XIII. Key biophysical properties of fibrin polymer are its visco-elasticity, extensibility and resistance to rupture. The internal packing of protofibrils within fibers changes fibrin biomechanical behavior. There are several methods to analyze fibrin biomechanical properties at different scales, including AFM force spectroscopy, magnetic or optical tweezers and rheometry, amongst others. Clinically, fibrin biomechanical characteristics are key for the prevention of thromboembolic disorders such as pulmonary embolism. Future studies are needed to address unanswered questions regarding internal molecular structure of the fibrin polymer, the structural and molecular basis of its remarkable mechanical properties and the relationship of fibrin biomechanical characteristics with thromboembolism in patients with deep vein thrombosis and ischemic stroke.

Topics: Elasticity; Factor XIIIa; Fibrin; Hemostasis; Humans; Thromboembolism; Thrombosis

Fibrin formed as a result of fibrinogen polymerization is the main protein component of a clot in a test tube and intravascular thrombi in vivo. Fibrin clot structure characterized by fiber diameter and pore size differs between healthy persons and those with thromboembolic diseases, in part due to the quality and quantity of fibrinogen and the magnitude of thrombin generation. A key measure of plasma clot structure is its permeability, reflected by the Darcy constant (Ks). Reduced Ks is a typical feature of the prothrombotic fibrin clot phenotype, which is associated with faster formation of denser fibrin mesh, relatively resistant to lysis. Low Ks has been reported in patients with prior or acute myocardial infarction (MI), stroke, or venous thromboembolism (encompassing deep vein thrombosis [DVT] and pulmonary embolism [PE]), as well as in those with prothrombotic conditions (eg, in several thrombophilic states) and in the presence of cardiovascular risk factors (eg, obesity). Antithrombotic and anticoagulant agents, along with statins, have been shown to increase Ks. Growing evidence indicates associations between the properties of plasma fibrin clots and morphology of intravascular thrombi in patients with MI. Recently, reduced Ks has been shown to predict recurrent thromboembolic episodes in patients with a history of stroke, PE, DVT, and their serious complications, including postthrombotic syndrome and thromboembolic pulmonary hypertension. We discuss the current evidence for the significance of clot density measured in vitro as a prognostic marker in a number of clinical conditions associated with elevated thromboembolic risk.

Topics: Fibrin; Humans; Plasma; Thromboembolism

The formation of fibrin clots that are relatively resistant to lysis represents the final step in blood coagulation. We discuss the genetic and environmental regulators of fibrin structure in relation to thrombotic disease. In addition, we discuss the implications of fibrin structure for treatment of thrombosis. Fibrin clots composed of compact, highly branched networks with thin fibers are resistant to lysis. Altered fibrin structure has consistently been reported in patients with several diseases complicated by thromboembolic events, including patients with acute or prior myocardial infarction, ischemic stroke, and venous thromboembolism. Relatives of patients with myocardial infarction or venous thromboembolism display similar fibrin abnormalities. Low-dose aspirin, statins, lowering of homocysteine, better diabetes control, smoking cessation, and suppression of inflammatory response increase clot permeability and susceptibility to lysis. Growing evidence indicates that abnormal fibrin properties represent a novel risk factor for arterial and venous thrombotic events, particularly of unknown etiology in young and middle-aged patients.

Topics: Fibrin; Humans; Oxidative Stress; Platelet Activation; Risk Factors; Thrombin; Thromboembolism; Thrombosis

This article reviews the roles of blood platelets in haemostasis as well as in the pathogenesis of thromboembolic diseases. Besides the basic processes in primary haemostasis, platelet adhesion, platelet secretion, platelet aggregation, clot retraction, the new model of thrombin formation on the platelet surface is presented. The different signal transduction pathways in platelets are a main focus of this review.

Topics: Blood Platelets; Endothelium, Vascular; Fibrin; Fibrinogen; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Signal Transduction; Thrombin; Thromboembolism; von Willebrand Factor

Formation of a fibrin clot is mediated by a group of tightly regulated plasma proteases and cofactors. While this system is essential for minimizing blood loss from an injured blood vessel (hemostasis), it also contributes to pathologic fibrin formation and platelet activation that may occlude vessels (thrombosis). Many antithrombotic drugs target key elements of the plasma coagulation mechanism such as thrombin and factor Xa, based on the premise that plasma elements contributing to thrombosis are primarily those involved in hemostasis. Recent studies with genetically altered mice raise questions about this paradigm. Deficiencies of the intrinsic pathway proteases factor XII and factor XI are not associated with abnormal hemostasis in mice, but impair formation of occlusive thrombi in arterial injury models, indicating that pathways not essential for hemostasis participate in arterial thrombosis. If factor XII or factor XI make similar contributions to thrombosis in humans, these proteases could be ideal targets for drugs to treat or prevent thromboembolic disease with minimal risk of therapy-associated bleeding.

Topics: Animals; Anticoagulants; Blood Coagulation; Disease Models, Animal; Factor XI; Factor XI Deficiency; Factor XII; Factor XII Deficiency; Fibrin; Hemostasis; Humans; Infarction, Middle Cerebral Artery; Mice; Mice, Knockout; Protease Inhibitors; Reperfusion Injury; Thromboembolism; Thrombosis

Topics: Adult; Aged; Aged, 80 and over; Animals; Clinical Trials as Topic; Dogs; Drug Evaluation, Preclinical; Female; Fibrin; Fibrinolytic Agents; Humans; Immunodominant Epitopes; Male; Metalloendopeptidases; Middle Aged; Multicenter Studies as Topic; Myocardial Infarction; Papio; Pilot Projects; Protein Engineering; Randomized Controlled Trials as Topic; Recombinant Proteins; Thromboembolism; Thrombolytic Therapy

Topics: Adolescent; Adult; Aging; Antithrombins; Blood Platelets; Child; Child, Preschool; Endothelium, Vascular; Fibrin; Fibrinolysis; Hemostasis; Humans; Incidence; Infant; Infant, Newborn; Thrombin; Thromboembolism; Thrombolytic Therapy

Topics: Fibrin; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Humans; Isoantibodies; Plasma; Plasminogen Activators; Recurrence; Reference Standards; Streptokinase; Thrombelastography; Thromboembolism

The present studies describe an inhibitory effect on fibrin polymerization by albumin fragments. When added to blood or plasma, SCMF or unreduced albumin CNBrF delayed clot formation, in sharp contrast to their acceleration of clotting of fibrinogen solutions. CNBrF inhibition was less marked than that of SCMF. The latter consistently prolonged the lag phase and decreased the opacity of fibrin in plasma, effects that could not be abolished by EDTA or by calcium chloride. Clots formed lacked elasticity in that clotting times were undetectable by mechanical probe in the absence of calcium. Estimated by clot free liquor, PRP clots decreased in size at much slower rates than controls and at complete retraction their volume remained at least threefold higher that of controls (n = 6). When fibrinogen was isolated from plasma or fibrinogen (approximately 5 mg/ml) solutions containing SCMF 1 to 5 mg/ml four SCMF coisolated with fibrinogen (n = 3 and n = 4, respectively), assessed by SDS-PAGE, and these could not be dissociated from fibrinogen by size exclusion chromatography (n = 2). Such fibrinogen isolates displayed prolonged clotting times, decreased clot opacity, and similarly abnormal reaggregation of their solubilized fibrin. In other experiments, limited human neutrophil elastase digestion produced large albumin fragments of which, examined unreduced, several fragments also bound to fibrin(ogen) and displayed this anticoagulant property (n = 2). These and related results suggest that the anticoagulant property is attributable at least in part to the largest SCMF.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Albumins; Anticoagulants; Blood Coagulation; Fibrin; Fibrinogen; Gels; Humans; Models, Biological; Peptide Fragments; Protein Binding; Thrombin Time; Thromboembolism; Time Factors

Topics: Amino Acid Sequence; Antibodies, Monoclonal; Biomarkers; Epitopes; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Iodine Radioisotopes; Molecular Sequence Data; Radionuclide Imaging; Thromboembolism; Thrombosis

This review describes the use of monoclonal antibodies (MoAbs) for immunoscintigraphic detection of thrombosis and thromboembolism. Two major groups of MoAbs have been tested: Antibodies directed against platelets and antibodies directed against fibrin. Several antiplatelet antibodies have been developed that are directed against either the platelet membrane glycoprotein complex, IIb/IIIa, which binds fibrinogen, or against two different proteins, alpha granule membrane protein GMP-140 and thrombospondin (TSP) that are expressed during platelet activation. Platelets labeled with radioactive antibody or antibody fragments have characteristics similar to platelets labeled in vitro with lipophilic complexes. Studies in animal models indicate that antiplatelet antibody and antiactivated platelet factor antibody imaging have a high sensitivity for clots less than 24 hours old and that images can be positive as early as one to two hours after antibody administration. A limited number of antiplatelet antibody studies have been performed in patients. This technique appears to yield accurate results provided that active platelet deposition is occurring at the time of the study. Several antifibrin MoAbs, specific for fibrin monomers, have been developed. Compared with antiplatelet antibodies, antifibrin antibodies and antibody fragments appear to be capable of detecting older experimental clots (up to five days old). Images in experimental thrombosis models are routinely positive within two hours of antibody administration. Recently reported clinical trials indicate a high sensitivity in all anatomic locations within the extremities whether or not patients were receiving heparin.

Topics: Animals; Antibodies, Monoclonal; Blood Platelets; Fibrin; Humans; Indium Radioisotopes; Iodine Radioisotopes; Isotope Labeling; Radionuclide Imaging; Technetium; Thromboembolism; Thrombosis

Patients with cancer have an increased incidence of thromboembolic disease and haemostatic abnormalities, and there is considerable evidence that the haemostatic system is involved in the growth and spread of malignant disease. Anti-haemostatic agents have given promising results in the treatment of experimental tumours, and several clinical trials in humans have been initiated. The formation of fibrin around the tumour may be a particularly important factor in malignant dissemination. The precise mechanisms of peri-tumour fibrin deposition remain to be elucidated, but may involve alterations in local vascular permeability and the presence of tumour and/or macrophage procoagulants. In addition to their role in fibrin formation, haemostatic components may also be involved in neovascularisation and angiogenesis.

Topics: Blood Coagulation; Fibrin; Fibrinolysis; Hemostasis; Humans; Neoplasm Metastasis; Neoplasms; Thromboembolism

The fibrinolytic system comprises a proenzyme, plasminogen, which can be converted to the active enzyme plasmin, which will degrade fibrin. Plasminogen activation is mediated by plasminogen activators which are classified as either tissue-type plasminogen activator (t-PA) or urokinase-type plasminogen activator (u-PA). Inhibition of the fibrinolytic system may occur at the level of the activators or at the level of generated plasmin. Plasmin has a low substrate specificity and when circulating freely in the blood will degrade several proteins including fibrinogen, Factor V and Factor VIII. Plasma does, however, contain a fast-acting plasmin inhibitor, alpha 2-antiplasmin, which will inhibit free plasmin extremely rapidly (t1/2: 0.1 s) but which reacts much slower (10(3)-fold) with plasmin bound to fibrin. A "systemic fibrinolytic state" may, however, occur by extensive activation of plasminogen (conc. in plasma 2 microM) and depletion of alpha 2-antiplasmin (conc. in plasma 1 microM). Clot-specific thrombolysis therefore requires plasminogen activation restricted to the vicinity of the fibrin. Two physiological plasminogen activators, t-PA and single-chain u-PA (scu-PA) induce clot-specific thrombolysis, however via entirely different mechanisms. t-PA is relatively inactive in the absence of fibrin, but fibrin strikingly enhances the activation rate of plasminogen by t-PA. This is explained by an increased affinity of fibrin-bound t-PA for plasminogen and not by alteration of the catalytic rate constant of the enzyme. The high affinity of t-PA for plasminogen in the presence of fibrin thus allows efficient activation on the fibrin clot while no significant plasminogen activation by t-PA occurs in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Recombinant Proteins; Structure-Activity Relationship; Thromboembolism; Tissue Plasminogen Activator

Topics: Animals; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Drug Evaluation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolytic Agents; Hemorrhage; Humans; Myocardial Infarction; Plasminogen Activators; Streptokinase; Thrombin; Thromboembolism

Topics: Amino Acid Sequence; Animals; Disease Models, Animal; Drug Synergism; Enzyme Activation; Fibrin; Fibrinolytic Agents; Humans; Infusions, Intravenous; Injections, Intravenous; Kinetics; Plasminogen; Plasminogen Activators; Protein Conformation; Substrate Specificity; Thromboembolism; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

Topics: Antifibrinolytic Agents; Blood Coagulation; Blood Platelets; Blood Proteins; Cell Membrane; Fibrin; Fibrinogen; Fibronectins; Humans; Macromolecular Substances; Thromboembolism; Thrombosis

Topics: Antithrombin III; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Fibrin; Fibrinogen; Fibrinolysis; Humans; Nephrotic Syndrome; Renal Veins; Thromboembolism; Thrombophlebitis; Thrombosis

From the preceding exposition it is now clear that the regulation of monocyte/macrophage PCA is dependent upon a complex network of interacting pathways, some of which amplify the response of the monocyte/macrophage, while others inhibit. In all probability many more will emerge. The construct illustrated in Figure 3, therefore, is a simplified view of the two major stimulatory pathways: the T cell-dependent pathway, activated by immune recognition and mediated by lymphokine(s); and the T cell-independent pathway, activated by direct perturbation of monocytes by such stimuli as LPS. At least 2 or 3 different PCAs can be expressed by monocyte/macrophages from different species, depending upon the anatomic site of the origin of the cell and the types of stimuli imposed. Inhibition of PCA expression is accomplished by at least one set of regulatory lipoproteins, and other inhibitory loops may be found. The result of these multiple interactions is the deposition of fibrin on the cell surface or in the surrounding milieu. It is our belief that this close relationship between coagulation reactions and inflammatory reactions, resulting in fibrin deposition, represents a fundamental host defense designed to delimit the inflammatory response. Nevertheless, the precise role of monocyte procoagulants in vivo remains unclear. A number of potential mechanisms exist for activation of coagulation in both inflammatory and neoplastic disorders, and the finding of enhanced monocyte procoagulant activity by no means establishes its importance in physiologic or, pathosphysiologic responses in vivo. Further studies, possibly with agents capable of specific inhibition of monocyte procoagulants in vivo, will be necessary to define the precise importance of these procoagulants in clinical disorders.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Blood Coagulation; Blood Coagulation Factors; Cell Line; Factor V; Factor VII; Factor X; Factor Xa; Fibrin; Fibrin Fibrinogen Degradation Products; Guinea Pigs; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Infections; Inflammation; Lipopolysaccharides; Macrophages; Mice; Monocytes; Neoplasms; Neutrophils; Rabbits; Rats; T-Lymphocytes; Thromboembolism; Thromboplastin; Warfarin

Topics: Blood Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Solubility; Thromboembolism

There are many reports in the literature of blood test abnormalities occurring in patients with venous or arterial thrombosis. Most of these have not used acceptable criteria for establishing an association between thrombosis and blood tests and, therefore, their interpretation is questionable. Recently, sensitive and specific assays have been developed for the detection of products of intravascular thrombin formation, of plasmin digests of fibrin or fibrinogen and of platelet specific proteins that are released into the plasma when platelets react with stimuli. Blood abnormalities have been sought that can either predict or detect venous thrombosis. Many of the predictive tests evaluated are nonspecific acute phase reactant responses to inflammation; of these, only reduced fibrinolytic activity has been consistently reported to be associated with postoperative venous thrombosis. Hereditary antithrombin III deficiency has been consistently shown to predispose patients to venous thrombosis. Abnormalities of the plasminogen and fibrinogen molecule have also been described in patients with familial or recurrent venous thrombosis but these are rare and the association could be coincidental. Two blood tests, the fibrinopeptide A assay and the assay for fibrin/fibrinogen fragment E are highly sensitive to acute venous thromboembolism in symptomatic patients but both are nonspecific. Elevated levels of beta thromboglobulin and platelet factor 4 have been reported in patients with arterial thromboembolism but the sensitivity and specificity of these findings is presently unknown.

Topics: Antithrombin III; Arteries; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Inflammation; Platelet Adhesiveness; Platelet Aggregation; Risk; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis; Wounds and Injuries

Topics: Afibrinogenemia; Blood Platelets; Chemical Phenomena; Chemistry; Child; Diagnosis, Differential; Fibrin; Fibrinogen; Humans; Male; Thromboembolism; Thrombosis

Topics: Anticoagulants; Antifibrinolytic Agents; Arterial Occlusive Diseases; Blood Coagulation; Blood Coagulation Disorders; Blood Platelets; Coagulants; Contraceptives, Oral; Estrogens; Female; Fibrin; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thrombin; Thromboembolism; Thrombophlebitis; Thrombosis

Topics: Anemia, Hemolytic; Animals; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Blood Viscosity; Drug Resistance; Female; Fibrin; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Hemorrhage; Heparin; Humans; Hydrolysis; Iodine Radioisotopes; Peptide Hydrolases; Plasminogen; Pregnancy; Snake Venoms; Thrombin; Thromboembolism; Urokinase-Type Plasminogen Activator; Wound Healing

Topics: Aminocaproates; Anticoagulants; Antifibrinolytic Agents; Blood Coagulation; Blood Platelets; Coumarins; Cyclohexanecarboxylic Acids; Dipyridamole; Ethylestrenol; Factor XII; Factor XIII; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolytic Agents; Heparin; Heparin Antagonists; Humans; Indenes; Peptide Hydrolases; Peptides; Phenformin; Plasminogen; Protamines; Streptokinase; Thrombin; Thromboembolism; Vitamin K

Topics: Adenine Nucleotides; Animals; Anticoagulants; Blood Circulation; Blood Coagulation; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Collagen; Diet; Endotoxins; Fibrin; Fibrinolytic Agents; Humans; Leukocytes; Microscopy, Electron; Myocardial Infarction; Oral Hemorrhage; Platelet Adhesiveness; Thromboembolism; Thrombosis; Wounds and Injuries

Topics: Aminocaproates; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; In Vitro Techniques; Infusions, Parenteral; Injections, Intravenous; Nicotinic Acids; Peptide Hydrolases; Plasminogen; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Thrombosis; Trypsin

To assess the influence of a variety of HRT regimens on the haemostatic balance using markers of fibrin turnover and inhibitors of coagulation.. An open randomised study allocating women to either a control group or five different HRT treatment groups.. Gentofte Hospital, Hellerup, and Rigshospitalet, Copenhagen, Denmark.. One hundred and forty-nine postmenopausal women without previous venous thromboembolic disease.. Prothrombin fragment 1+2 (F(1+2)), fibrin degradation products, antithrombin, protein C, total protein S and activated protein C-normalised ratio were measured at baseline and after 6 and 12 months of HRT in six groups of healthy postmenopausal women: (A). no HRT (reference group), (B). continuous oestradiol valerate (E(2)V) plus cyproterone acetate, (C). cyclic E(2)V plus cyproterone acetate, (D). continuous combined oestrogen (E(2)) plus norethindrone acetate, (E). E(2) combined with local delivery of levonorgestrel and (F). E(2)V plus medroxyprogesterone. HRT-induced changes in the concentration of inhibitors of coagulation and markers of fibrin turnover during 12 months of treatment.. Significant decreases of antithrombin and protein S were found in all treatment groups, of protein C in Groups C, D, E and F and of activated protein C-normalised ratio in Groups E and F. Fibrin degradation products increased after three months of treatment, whereas F(1+2) was persistently increased after three months in Group F. The cumulative response of antithrombin was significantly lower in Groups D, E and F than in the reference group. The cumulative response of protein S and activated protein C-normalised ratio was lower, whereas that of F(1+2) was significantly higher in Group F than in the reference group.. HRT reduces the inhibitory potential of coagulation significantly. The effect is related to the type of E(2)/progestin combination administered, but seems to be oestrogen-derived as the most pronounced effect is found with only quarterly progestin intake. Such procoagulant activity of HRT may well translate into clinical manifestations in thrombosis-prone individuals.

Topics: Adult; Estrogen Replacement Therapy; Female; Fibrin; Humans; Middle Aged; Peptide Fragments; Postmenopause; Prospective Studies; Protein C; Protein S; Prothrombin; Risk Factors; Thromboembolism; Venous Thrombosis

To investigate perioperative coagulation in morbidly obese (MO) patients with the thromboelastograph (TEG) and Sonoclot analyzer.. Twenty-six consecutive morbidly obese and 26 consecutive lean patients presenting for elective surgery were enrolled in this prospective, observational study. Blood was sampled for TEG and Sonoclot analysis immediately after anaesthetic induction and at the end of surgery in the MO group, and immediately after anaesthetic induction in the lean group. The R and K times, alpha angle, maximum amplitude and percentage fibrinolysis at 30 and 60 min were recorded from the TEG. The Sonoclot ACT, initial clot rate, peak amplitude and time to peak amplitude were recorded from the Sonoclot.. The TEG in the MO group demonstrated decreased R and K times (8.6 +/- 4.8 vs 11.7 +/- 3.9 mm, and 2.8 +/- 1.2 vs 3.5 +/- 0.9 mm respectively (P < 0.05)), and increased alpha angle (73.7 +/- 6.0 vs 66.7 +/- 6.0 degrees, P < 0.05) and maximum amplitude (72.0 +/- 5.4 vs 67.9 +/- 4.4 mm, P < 0.05), without change in fibrinolysis. Sonoclot variables in the MO group included increased clot rate (37.5 +/- 11.5 vs 23.9 +/- 7.7%, P < 0.05) and decreased time to peak impedance (11.7 +/- 5.0 vs 17.5 +/- 7.2 min, P < 0.05), without change in Sonoclot ACT or peak signature impedance.. The MO group demonstrated accelerated fibrin formation, fibrinogen-platelet interaction, and platelet function compared with lean controls but no difference in fibrinolysis. Viscoelastic measures of coagulation may be useful in MO patients, who are at increased risk of thromboembolic events.

Topics: Adult; Anesthesia, General; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Blood Viscosity; Body Mass Index; Elasticity; Elective Surgical Procedures; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Monitoring, Intraoperative; Obesity, Morbid; Platelet Activation; Prospective Studies; Risk Factors; Thrombelastography; Thromboembolism; Time Factors; Ultrasonics

The purpose of the study was to evaluate alterations of the hemostatic system and the effect of anticoagulant therapy in nonvalvular atrial fibrillation. A set of molecular hematologic markers was measured prospectively in 69 patients with atrial fibrillation and 28 age-matched patients in sinus rhythm. Significantly elevated levels of thrombin-antithrombin III complex (8.5 +/- 1.6 vs. 2.5 +/- 0.3 micrograms/l; p < 0.001), fibrin monomers (27.1 +/- 3.2 vs. 13.4 +/- 3.7 nM; p < 0.001), D-dimers (788 +/- 76 vs. 405 +/- 46 micrograms/l; p < 0.005), and tissue-type plasminogen activator (9.6 +/- 0.5 vs. 7.2 +/- 0.5 micrograms/l; p < 0.05) were observed in patients with atrial fibrillation compared to those in sinus rhythm. In a subgroup of patients in whom anticoagulant therapy with oral coumadin or standard intravenous heparin was established after the initial study, hemostatic activation decreased significantly. In conclusion, molecular hematologic markers indicate a hypercoagulable state in atrial fibrillation which may characterized a group of patients at elevated risk of thromboembolic disease.

Topics: Aged; Anticoagulants; Antithrombin III; Aspirin; Atrial Fibrillation; Biomarkers; Blood Coagulation; Blood Proteins; Echocardiography, Transesophageal; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Male; Mitral Valve; Partial Thromboplastin Time; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prospective Studies; Prothrombin; Risk; Thromboembolism; Tissue Plasminogen Activator; Warfarin

In a 6-month, randomized, double-blind study the effects of two combined oral contraceptives containing 150 micrograms desogestrel and either 20 or 30 micrograms ethinylestradiol on hemostatic parameters were investigated in 1633 healthy women. Compared with baseline, the 30 micrograms ethinylestradiol formulation increased prothrombin fragment 1 + 2 (+72.2%), D-dimer (+42.4%) and protein C activity (+6.1%), whereas antithrombin-III activity (-6.3%) and protein S activity (-19.7%) were decreased. The use of the 20 micrograms ethinylestradiol formulation was associated with the same pattern of changes, but with lower magnitude (F1+2 + 61.1%, D-dimer +36.0%, antithrombin III -5.3%, protein C +4.6% and protein S-16.0%). The changes from baseline were significantly smaller in the 20 micrograms ethinylestradiol group for D-dimer, antithrombin III and protein S than in the 30 micrograms ethinylestradiol group (p = 0.019, p = 0.038 and p = 0.001, respectively). One woman with a combined deficiency of proteins C and S developed deep venous thrombosis while using the 20 micrograms ethinylestradiol formulation. Use of both formulations was associated with a shift of the coagulation-fibrinolysis balance to an enhanced fibrin-generating and fibrin-degradating activity. The less-pronounced effect on hemostasis with the 20 micrograms ethinylestradiol preparation is reassuring with regard to thromboembolic risk in general. However, women with coagulation inhibitor deficiency should be advised not to use oral contraceptives.

Topics: Adolescent; Adult; Blood Coagulation Factors; Cohort Studies; Contraceptives, Oral, Combined; Contraceptives, Oral, Synthetic; Desogestrel; Double-Blind Method; Estradiol Congeners; Ethinyl Estradiol; Female; Fibrin; Hemostasis; Humans; Middle Aged; Prospective Studies; Thromboembolism

The relationship between tumor stage and the concentration of circulating heparin achieved after subcutaneous administration and its effect on fibrin generation were studied in 24 women with gynecologic malignancy. A single subcutaneous injection of 5000, 7500, and 10,000/U of sodium heparin was given in random order on different days. Plasma specimens for antithrombin III, fibrinopeptide A, and heparin were obtained serially over an 11-hour interval. Women with a Stage III or IV malignancy had significantly lower circulating heparin after the 5000 and 10,000/U doses. There was a significant decline in fibrinopeptide A as the concentration of circulating heparin increased. Thirty-three percent of women with a Stage III or IV malignancy had no detectable circulating heparin at any point examined over the 11 hours after 5000/U of heparin. Likewise, 16.7% and 8.4% had no detectable circulating heparin after 7500 and 10,000/U, respectively. A similar percentage was noted in a smaller group of women with Stage II malignancy. Next, a known quantity of heparin was added to the plasma from these patients and the concentration of heparin was determined. A significant amount of heparin-neutralizing activity was documented. We conclude that a large percentage of women with an advanced gynecologic malignancy are able to neutralize heparin administered for the prevention of thromboembolic disease. This heparin-neutralizing activity may account for the failure of low-dose heparin to prevent thromboembolic complications in this patient population.

Topics: Antithrombin III; Female; Fibrin; Fibrinopeptide A; Genital Neoplasms, Female; Heparin; Humans; Thromboembolism

1. The purpose of fluid administration is not only the restoration of blood volume but also the normalization of impaired nutritive flow. 2. Plasma oncotic (colloid osmotic) pressure is the only force which can draw water into the circulation. In shock the infusion of colloid solutions is able to normalize nutritive flow and peripheral resistance almost at once. 3. Five per cent solutions of pasteurized plasma protein or albumin and 6 per cent dextran 70 yield a volume expansion corresponding to the amount infused. 4. The decrease in hematocrit produced by the infusion of these three colloidal solutions is accompanied by a decrease in whole blood viscosity resulting in a rise in cardiac output as well as in nutritional tissue flow. 5. Hemodilution improves oxygen supply as long as the hematocrit does not fall below 30 per cent, although normovolemia is the critical requirement. 6. Transmission of viral hepatitis is still the greatest danger of blood transfusion. 7. The use of large amounts of Ringer's lactate is not advised, as this solution does not reduce the total number of units of blood which need to be given. Pulmonary edema may become a problem. 8. Dextrans are best suited to initial volume replacement in shock. They increase plasma volume, improve blood flow, have antithrombotic properties, and are easily available and relatively cheap. Anaphylactoid reactions are rare. 9. Every third patient undergoing general surgery and every other patient having hip surgery develops a deep venous thrombosis. Widespread prophylaxis to prevent thromboembolic complications is mandatory. 10. The antithrombotic properties of dextran are due to a reduction in platelet adhesiveness, a change in fibrin clot structure, and the increased lysability of thrombi and the improvement of blood flow. 11. In a personal controlled, prospective, randomezed trial comparing subcutaneous heparin and intravenous dextran 40, 35.8 per cent of the controls (n=95), 13.2 per cent of the 83 patients in the heparin group, and 20.5 per cent in the dextran group (n=83) developed deep venous thrombosis. The difference between dextran and heparin is not significant; however, both treatment groups show a statistically significant effect compared to the controls.

Topics: Blood Coagulation Tests; Blood Transfusion; Bone and Bones; Coumarins; Dextrans; Female; Fibrin; Genital Diseases, Female; Heparin; Humans; Microscopy, Electron, Scanning; Molecular Weight; Phlebography; Postoperative Complications; Prospective Studies; Pulmonary Embolism; Thromboembolism

The effect of a low-dosage regimen of ancrod in the prevention of postoperative deep vein thrombosis was assessed in 24 patients having surgical repair of fractured neck femur and compared with 25 control patients who did not receive therapy. The objective of the therapy was to lower the preoperative fibrinogen level and produce a low concentration of fibrin degradation products yet avoid the haemorrhagic complications of total defibrination. Ancrod therapy proved feasible to carry out, was not associated with haemorrhagic complications, and produced sustained, predictable reductions in fibrinogen concentration. There were seven thromboembolic complications in the control patients compared to one such complication in the ancrod-treated patients. Five deaths occurred in the control group and one in the treated group. Though the incidence of deep vein thrombosis was not apparently affected by ancrod it appeared on venography that the thrombi in the treated patients were less extensive than those in the control patients. Finally, some discrepancies in the diagnosis of deep vein thrombosis by the three techniques of clinical examination, (125)I-fibrinogen scanning, and ascending venography were identified.

Topics: Aged; Anticoagulants; Clinical Trials as Topic; Female; Femoral Neck Fractures; Fibrin; Fibrinogen; Hemagglutination Inhibition Tests; Humans; Injections, Intravenous; Iodine Radioisotopes; Peptide Hydrolases; Phlebography; Postoperative Complications; Radionuclide Imaging; Thromboembolism; Thrombophlebitis; Venoms

In cases of acute ischemic stroke (AIS), mechanical thrombectomy (MT) can be used to directly remove lodged thromboemboli. Despite improvements in patient outcomes, one of the key factors affecting MT success is the mechanical properties of the occlusive thrombus. Therefore, the goal of this study was to investigate the viscoelastic properties of embolus analogs (EAs) and determine the influence of EA hematocrit and loading frequency. Bovine blood EAs were created over a range of physiological hematocrits (0-60%) and cyclic uniaxial compression testing was performed at three loading frequencies to mimic in vivo loading conditions, followed by stress-relaxation testing. It was found that EAs exhibited behaviors typical of hyper-viscoelastic materials and that EA hematocrit played a large role in both EA stiffness and relaxation, with both parameters decreasing as hematocrit increased from 0 to 60%. The viscoelastic behavior of the EAs was also affected by the frequency at which they were loaded, with significant increases in peak stresses between the 0.5 and 2 Hz loaded EAs. Lower hematocrit EAs had very dense fibrin networks while the higher hematocrit EAs consisted of closely packed RBCs with little fibrin present. These results suggest that fibrin contributes to EA stiffness and relaxation behaviors while RBCs play a role in decreasing the overall viscous response and strain-rate dependency. An Ogden hyperelastic model was found to best reproduce the EA loading data while a 3-term Prony series was fit to the stress relaxation data. A hyper-viscoelastic modeling framework was then implemented combining the loading and stress-relaxation fits and the results could match the full cyclic loading data for EAs of varying hematocrit and loading frequency. The results of the experimental mechanical characterization and hyper-viscoelastic curve fitting can be incorporated in future modeling efforts to optimize mechanical thrombectomy for AIS patients.

Topics: Animals; Cattle; Elasticity; Embolism; Fibrin; Humans; Ischemic Stroke; Stress, Mechanical; Thromboembolism; Viscosity

Patients with coronary artery disease (CAD) display a prothrombotic fibrin clot phenotype, involving low permeability and resistance to lysis. The determinants of this phenotype remain elusive. Circulating tissue factor (TF) and activated factor XI (FXIa) are linked to arterial thromboembolism. We investigated whether detectable active TF and FXIa influence fibrin clot properties in CAD.. In 118 CAD patients (median age 65 years, 78% men), we assessed Ks, an indicator of clot permeability, and clot lysis time (CLT) in plasma-based assays, along with the presence of active TF and FXIa. We also analysed proteins involved in clotting and thrombolysis, including fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and thrombin activatable thrombolysis inhibitor (TAFI). During a median 106 month (interquartile range 95-119) follow-up, myocardial infarction (MI), stroke, systemic thromboembolism (SE) and cardiovascular (CV) death were recorded.. Circulating TF and FXIa, detected in 20.3% and 39.8% of patients, respectively, were associated with low Ks and prolonged CLT. Solely FXIa remained an independent predictor of low Ks and high CLT on multivariable analysis. Additionally, fibrinogen and PAI-1 were associated with low Ks, while PAI-1 and TAFI-with prolonged CLT. During follow-up low Ks and prolonged CLT increased the risk of MI and the latter also a composite endpoint of MI, stroke/SE or CV death.. To our knowledge, this study is the first to show that circulating FXIa is associated with prothrombotic fibrin clot properties in CAD, suggesting additional mechanisms through which FXIa inhibitors could act as novel antithrombotic agents in CAD.

Topics: Coronary Artery Disease; Factor XIa; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Fibrinolysis; Humans; Plasminogen Activator Inhibitor 1; Stroke; Thromboembolism; Thrombosis

Clot composition, contraction, and mechanical properties are likely determinants of endovascular thrombectomy success. A pre-interventional estimation of these properties is hypothesized to aid in selecting the most suitable treatment for different types of thrombi. Here we determined the association between the aforementioned properties and computed tomography (CT) characteristics using human blood clot analogues.. Clot analogues were prepared from the blood of 4 healthy human donors with 5 red blood cell (RBC) volume suspensions: 0%, 20%, 40%, 60% and 80% RBCs. Contraction was measured as the weight of the contracted clots as a percentage of the original suspension. The clots were imaged using CT with and without contrast to quantify clot density and density increase. Unconfined compression was performed to determine the high strain compressive stiffness. The RBC content was analysed using H&E staining.. The 5 RBC suspensions formed only two groups of clots, fibrin-rich (0% RBCs) and RBC-rich (>90% RBCs), as determined by histology. The density of the fibrin-rich clots was significantly lower (31-38HU) compared to the RBC-rich clots (72-89HU), and the density increase of the fibrin-rich clots was significantly higher (82-127HU) compared to the RBC-rich clots (3-17HU). The compressive stiffness of the fibrin-rich clots was higher (178-1624 kPa) than the stiffness of the RBC-rich clots (6-526 kPa). Additionally, the degree of clot contraction was higher for the fibrin-rich clots (89-96%) compared to the RBC-rich clots (11-77%).. CT imaging clearly reflects clot RBC content and seems to be related to the clot contraction and stiffness. CT imaging might be a useful tool in predicting the thrombus characteristics. However, future studies should confirm these findings by analysing clots with intermediate RBC and platelet content.

Topics: Erythrocytes; Fibrin; Humans; Thrombectomy; Thromboembolism; Thrombosis; Tomography, X-Ray Computed

Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers.. A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity.. ICU at an academic medical center and an academic laboratory.. Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis.. None.. Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3-16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis.. We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition.

Topics: COVID-19; Critical Illness; Cross-Sectional Studies; Fibrin; Fibrinolysis; Humans; Sepsis; Thromboembolism; Thrombosis

Enhanced oxidative stress occurs in atrial fibrillation (AF), however its impact on the efficacy and safety of anticoagulation is unknown. We sought to evaluate whether 8-isoprostaglandin F2 (8-isoprostane) levels are associated with clinical outcomes in anticoagulated AF patients.. In a study involving 243 AF patients (median age 69 years), we measured serum 8-isoprostane, along with prothrombotic markers, including plasma fibrin clot permeability, clot lysis time (CLT), endogenous thrombin potential (ETP), von Willebrand factor (VWF), and fibrinolytic proteins. Ischemic cerebrovascular events, major bleeding, and death were recorded during a median follow-up of 53 months while on anticoagulation, largely on non-vitamin K antagonist oral anticoagulants (NOACs).. Increased 8-isoprostane levels partly through altered fibrin clot structure are associated with thromboembolic events despite anticoagulant therapy in AF patients.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Dinoprost; Female; Fibrin; Hemorrhage; Humans; Risk Factors; Stroke; Thromboembolism; Thrombosis; von Willebrand Factor

Recombinant human tissue plasminogen activator (rh-tPA) is an important thrombolytic agent for treatment of acute ischemic stroke. It requires fibrin binding for plasminogen activation. In contrast, Microlyse, a novel thrombolytic agent, requires von Willebrand factor (VWF) binding for plasminogen activation. We compared rh-tPA with Microlyse, administered 20 minutes after inducing thrombosis, in 2 randomized blinded acute ischemic stroke mouse models. Thrombosis was induced in the middle cerebral artery with different experimental triggers. Where thrombin infusion generates fibrin-rich thrombi, topical FeCl3 application generates platelet-rich thrombi. In the fibrin-rich model, both rh-tPA and Microlyse increased cortical reperfusion (determined by laser speckle imaging) 10 minutes after therapy administration (35.8 ± 17.1%; P = .001 39.3 ± 13.1%; P < .0001; 15.6 ± 7.5%, respectively, vs vehicle). In addition, both thrombolytic agents reduced cerebral lesion volume (determined by magnetic resonance imaging) after 24 hours (18.9 ± 11.2 mm3; P = .033; 16.1 ± 13.9 mm3; P = .018; 26.6 ± 5.6 mm3, respectively, vs vehicle). In the platelet-rich model, neither rh-tPA nor Microlyse increased cortical reperfusion 10 minutes after therapy (7.6 ± 8.8%; P = .216; 16.3 ± 13.9%; P = .151; 10.1 ± 7.9%, respectively, vs vehicle). However, Microlyse, but not rh-tPA, decreased cerebral lesion volumes (13.9 ± 11.4 mm3; P < .001; 23.6 ± 11.1 mm3; P = .188; 30.3 ± 10.9 mm3, respectively, vs vehicle). These findings support broad applicability of Microlyse in ischemic stroke, irrespective of the thrombus composition.

Topics: Animals; Fibrin; Fibrinolytic Agents; Humans; Ischemic Stroke; Mice; Plasminogen; Stroke; Thromboembolism; Thrombolytic Therapy; Thrombosis; Tissue Plasminogen Activator; von Willebrand Factor

In oral and maxillofacial surgery, flap repair is essential to the quality of postoperative life. Still, thrombosis is fatal for the survival of the flaps. Besides, some postoperative thrombotic diseases, such as pulmonary embolism, also intimidate patients' life. The traditional diagnostic methods are still limited by a large amount of hardware and suffer from inconvenience, delay, and subjectivity. Moreover, the treatments mainly rely upon thrombolytics, such as urokinase (UK) plasminogen activator, which may cause bleeding risk, especially intracerebral hemorrhage. Herein, a kind of poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) containing a first near-infrared window (NIR-I) phototheranostic agent Y8 and urokinase plasminogen activator (UK) as the core, and modified with the fibrin-targeting peptide Gly-Pro-Arg-Pro-Pro (GPRPP) were developed for the flap and postoperative thromboembolism treatment (named GPRPP-Y8U@P). The conjugated molecule Y8 endows GPRPP-Y8U@P with the capacity of NIR-II imaging and excellent photothermal/photodynamic therapeutic effects. In vivo experiments demonstrated that GPRPP-Y8U@P could quickly locate thrombus by NIR-II fluorescence imaging, and semi-quantitative analysis of the embolized blood vessels' paraffin section verified its thrombolytic efficiency. Additionally, the urokinase trapped in the NPs would not result in nonspecific bleeding, tremendously improving physical security and curative effects with minimizing side effects. Overall, the advantages of GPRPP-Y8U@P, such as precise localization of the thrombus, thrombus ablation in the site, and mild side effects, demonstrated the attractiveness of this approach for effective clinical monitoring of thrombus therapy.

Topics: Antineoplastic Agents; Fibrin; Humans; Nanoparticles; Optical Imaging; Paraffin; Phototherapy; Thromboembolism; Thrombosis; Urokinase-Type Plasminogen Activator

Topics: Fibrin; Fibrin Clot Lysis Time; Humans; Ischemia; Thromboembolism; Thrombosis

We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients to study the association between histological composition and stroke etiology METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using martius scarlet blue (MSB) staining, and quantification for red blood cells (RBCs), white blood cells (WBCs), fibrin and platelets was performed using Orbit Image Software. A Wilcoxon test was used for continuous variables and χ. 1350 patients were included in this study. The overall rate of Thrombolysis In Cerebral Infarction (TICI) 2c/3 was 68%. 501 patients received tissue plasminogen activator (tPA) (37%). 267 patients (20%) had a large artery atherosclerosis (LAA) source, 662 (49%) a cardioembolic (CE) source, 301 (22%) were cryptogenic, and the remainder had other identifiable sources including hypercoagulable state or dissection. LAA thrombi had a higher mean RBC density (46±23% vs 42±22%, p=0.01) and a lower platelet density (24±18% vs 27±18%, p=0.03) than CE thrombi. Clots from dissection patients had the highest mean RBC density (50±24%) while clots from patients with a hypercoagulable state had the lowest mean RBC density (26±21%).. Our study found statistically significant but clinically insignificant differences between clots of CE and LAA etiologies. Future studies should emphasize molecular, proteomic and immunohistochemical characteristics to determine links between clot composition and etiology.

Topics: Aged; Aged, 80 and over; Erythrocytes; Female; Fibrin; Humans; Male; Middle Aged; Registries; Retrospective Studies; Stroke; Thrombectomy; Thromboembolism; Thrombosis; Tissue Plasminogen Activator

Mechanical thrombectomy can be significantly affected by the mechanical properties of the occluding thrombus. In this study, we provide the first characterisation of the volumetric behaviour of blood clots. We propose a new hyperelastic model for the volumetric and isochoric deformation of clot. We demonstrate that the proposed model provides significant improvements over established models in terms of accurate prediction of nonlinear stress-strain and volumetric behaviours of clots with low and high red blood cell compositions. We perform a rigorous investigation of the factors that govern clot occlusion of a tapered vessel. The motivation for such an analysis is twofold: (i) the role of clot composition on the in vivo occlusion location is an open clinical question that has significant implications for thrombectomy procedures; (ii) in vitro measurement of occlusion location in an engineered tapered tube can be used as a quick and simple methodology to assess the mechanical properties/compositions of clots. Simulations demonstrate that both isochoric and volumetric behaviours of clots are key determinants of clot lodgement location, in addition to clot-vessel friction. The proposed formulation is shown to provide accurate predictions of in vitro measurement of clot occlusion location in a silicone tapered vessel, in addition to accurately predicting the deformed shape of the clot.

Topics: Compressive Strength; Computer Simulation; Elasticity; Erythrocytes; Fibrin; Finite Element Analysis; Friction; Humans; In Vitro Techniques; Ischemic Stroke; Shear Strength; Silicon; Silicones; Stress, Mechanical; Stroke; Thrombectomy; Thromboembolism; Thrombosis

Although arterial and venous thromboembolic disorders are among the most frequent causes of mortality and morbidity, there has been little description of how the composition of thrombi and emboli depends on their vascular origin and age. We quantified the structure and composition of arterial and venous thrombi and pulmonary emboli using high-resolution scanning electron microscopy. Arterial thrombi contained a surprisingly large amount of fibrin, in addition to platelets. The composition of pulmonary emboli mirrored the most distal part of venous thrombi from which they originated, which differed from the structure of the body and head of the same thrombi. All thrombi and emboli contained few biconcave red blood cells but many polyhedrocytes or related forms of compressed red blood cells, demonstrating that these structures are a signature of clot contraction in vivo. Polyhedrocytes and intermediate forms comprised the major constituents of venous thrombi and pulmonary emboli. The structures within all of the thrombi and emboli were very tightly packed, in contrast to clots formed in vitro. There are distinctive, reproducible differences among arterial and venous thrombi and emboli related to their origin, destination and duration, which may have clinical implications for the understanding and treatment of thrombotic disorders.

Topics: Arteries; Blood Coagulation; Blood Platelets; Erythrocytes; Fibrin; Humans; Microscopy, Electron, Scanning; Pulmonary Embolism; Thromboembolism; Veins; Venous Thrombosis

Although it is common practice to wait for an 'embedding time' during mechanical thrombectomy (MT) to allow strut integration of a stentriever device into an occluding thromboembolic clot, there is a scarcity of evidence demonstrating the value or optimal timing for the wide range of thrombus compositions. This work characterizes the behavior of clot analogs of varying fibrin and cellular compositions subject to indentation forces and embedding times representative of those imparted by a stentriever during MT. The purpose of this study is to quantify the effect of thrombus composition on device strut embedding, and to examine the precise nature of clot integration into a stentriever device at a microstructural level.. Clot analogs with 0% (varying densities), 5%, 40%, and 80% red blood cell (RBC) content were created using ovine blood. Clot indentation behavior during an initial load application (loading phase) followed by a 5-min embedding time (creep phase) was analyzed using a mechanical tester under physiologically relevant conditions. The mechanism of strut integration was examined using micro-computed tomography (µCT) with an EmboTrap MT device (Cerenovus, Galway, Ireland) deployed in each clot type. Microstructural clot characteristics were identified using scanning electron microscopy (SEM).. Compressive clot stiffness measured during the initial loading phase was shown to be lowest in RBC-rich clots, with a corresponding greatest maximum indentation depth. Meanwhile, additional depth achieved during the simulated embedding time was most pronounced in fibrin-rich clots. SEM imaging identified variations in microstructural mechanisms (fibrin stretching vs rupturing) which was dependent on fibrin:cellular content, while µCT analysis demonstrated the mechanism of strut integration was predominantly the formation of surface undulations rather than clot penetration.. Disparities in indentation behavior between clot analogs were attributed to varying microstructural features induced by the cellular:fibrin content. Greater indentation was identified in clots with higher RBC content, but with an increased level of fibrin rupture, suggesting an increased propensity for fragmentation. Additional embedding time improves strut integration, especially in fibrin-rich clots, through the mechanism of fibrin stretching with the majority of additional integration occurring after 3 mins. The level of thrombus incorporation into the EmboTrap MT device (Cerenovus, Galway, Ireland) was primarily influenced by the stentriever design, with increased integration in regions of open architecture.

Topics: Animals; Brain Ischemia; Erythrocytes; Female; Fibrin; Ireland; Male; Microscopy, Electron, Scanning; Prostheses and Implants; Sheep; Stroke; Thrombectomy; Thromboembolism; Thrombosis; X-Ray Microtomography

Topics: Arthritis, Rheumatoid; Fibrin; Humans; Thromboembolism; Thrombosis

Topics: Arthritis, Rheumatoid; Fibrin; Humans; Thromboembolism; Thrombosis

APS is associated with arterial and venous thrombosis. The unfavourable fibrin clot phenotype, including formation of dense and poorly lysable clots, has been reported in thrombotic APS. We investigated whether abnormal plasma clot properties are predictive of recurrent thromboembolism in APS.. We followed 126 consecutive patients with thrombotic APS and 105 control subjects, without APS, matched for thrombotic events. Plasma fibrin clot permeability (Ks), turbidity measurements and clot lysis time were evaluated ⩾5 months after a thrombotic event. The primary composite end point was symptomatic recurrent venous thromboembolism, ischaemic stroke and/or myocardial infarction.. During follow-up (median, 62 months; range 46-74 months; 1183.2 patient-years), the primary outcome was observed in 33 (26.2%) APS patients and 16 (15.2%) controls, including 25 (19.8%) and 14 (13.3%) subjects with recurrent venous thromboembolism, respectively. Reduced Ks and prolonged clot lysis time predicted recurrent thromboembolic events in APS patients [per 1 × 10-9 cm2: hazard ratio (HR) = 0.37; 95% CI: 0.24, 0.56; and per 10 min: HR = 1.20; 95% CI: 1.01, 1.40, respectively] and in controls (per 1×10-9 cm2: HR = 0.23; 95% CI: 0.11, 0.42; and per 10 min: HR = 1.51; 95% CI: 1.08, 2.16, respectively). A multivariate analysis showed that positive IgG and IgM anti-β2 glycoprotein I antibodies, withdrawal of anticoagulation, lower platelet count and reduced Ks predicted thromboembolic events in APS patients.. Formation of denser fibrin networks could be a novel risk factor for recurrent thromboembolism in APS, which highlights the importance of fibrin phenotype in thrombotic disorders.

Topics: Adult; Antiphospholipid Syndrome; Blood Coagulation; Female; Fibrin; Fibrin Clot Lysis Time; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Permeability; Poland; Prospective Studies; Recurrence; Thromboembolism; Time Factors

Unsuccessful recanalization attempts in stroke patients have been associated with fibrin-rich thromboemboli linking retrieval mechanism performance and clot composition. To continue development of stroke retrieval mechanisms, the material properties of cerebral thromboemboli must be replicated; however, current methods for emboli analog formation lack quantitative measurements for both material stiffness and composition of cerebral thromboemboli. This study investigates emboli analog (EA) formation to mimic the material stiffness and composition of cerebral thromboemboli to develop new retrieval mechanisms.. To induce static and dynamic environments for clot replication, a 9:1 ratio of porcine whole blood and 2.45% calcium chloride remained stationary or rotated at 34, 50 and 80 RPM. Histology and a custom MATLAB code provided composition analysis results. Likewise, quantitative results from biomechanical testing were obtained for direct comparison of the material stiffness of cerebral thromboemboli.. Fibrin/platelet content as well as material stiffness increased due to increasing rotational speed. Approximately 11% of the biomechanical testing results exhibited nonlinearity after an initial yield point, of which 60% were from statically formed EAs. Those formed at 50 RPM were most similar in material stiffness to thromboemboli extracted from carotid endarterectomy (CEA) procedures (p = 0.97).. The dynamically formed EAs may be altered to obtain a range of fibrin/platelet to erythrocyte ratios. The proposed methodology for EA formation offers a platform for continued development of retrieval mechanism prototypes.

Topics: Animals; Blood Platelets; Erythrocytes; Fibrin; Stroke; Swine; Thromboembolism

γ' fibrinogen has been associated with thrombosis. Here the interactions between γ'γ' or γAγA fibrinogen and red blood cells (RBCs), and their role on fibrin clot properties were studied.. Atomic Force microscopy (AFM)-based force spectroscopy, rheological, electron and confocal microscopy, and computational approaches were conducted for both fibrinogen variants.. AFM shows that the recombinant human (rh)γ'γ' fibrinogen increases the binding force and the frequency of the binding to RBCs compared with rhγAγA, promoting cell aggregation. Structural changes in rhγ'γ' fibrin clots, displaying a nonuniform fibrin network were shown by microscopy approaches. The presence of RBCs decreases the fibrinolysis rate and increases viscosity of rhγ'γ' fibrin clots. The full length of the γ' chain structure, revealed by computational analysis, occupies a much wider surface and is more flexible, allowing an increase of the binding between γ' fibers, and eventually with RBCs.

Topics: Blood Coagulation; Cell Aggregation; Erythrocytes; Fibrin; Fibrinogens, Abnormal; Fibrinolysis; Humans; Microscopy, Atomic Force; Microscopy, Electron, Scanning; Protein Conformation; Rheology; Thromboembolism; Thrombosis; Viscosity

The present study evaluates the in vitro, in vivo, and ex vivo antithrombotic and anticoagulant effect of two flavonoids: quercetin and quercetin-3-O-β-d-glucoside (isoquercetin). The present results have shown that quercetin and isoquercetin inhibit the enzymatic activity of thrombin and FXa and suppress fibrin clot formation and blood clotting. The prolongation effect of quercetin and isoquercetin against epinephrine and collagen-induced platelet activation may have been caused by intervention in intracellular signaling pathways including coagulation cascade and aggregation response on platelets and blood. The in vivo and ex vivo anticoagulant efficacy of quercetin and isoquercetin was evaluated in thrombin-induced acute thromboembolism model and in ICR mice. Our findings showed that in vitro and in vivo inhibitory effects of quercetin were slightly higher than that of quercetin glucoside, whereas in vitro and ex vivo anticoagulant effects of quercetin were weaker than that of quercetin glucoside because of their structural characteristics.

Topics: Acute Disease; Animals; Blood Coagulation; Blood Platelets; Collagen; Disease Models, Animal; Epinephrine; Factor Xa; Fibrin; Fibrinolytic Agents; Flavonoids; Glucosides; Male; Mice; Mice, Inbred ICR; Platelet Activation; Primary Cell Culture; Quercetin; Rats, Sprague-Dawley; Signal Transduction; Thrombin; Thromboembolism

Thromboembolic complications are a common cause of death in breast cancer patients. The in vivo relationship between coagulation factors and circulating tumours is a multifaceted one, with tumour cells implicated in thrombocytosis and platelets associated with coagulation-mediated metastasis. Platelets and fibrin networks are known to be morphologically altered in patients with cancer, and their relationship with breast cancer cells themselves may increase thrombosis susceptibility. This was investigated in vitro, assessing such morphological alterations through the establishment of a MCF-7 breast cancer cell co-culture system with blood plasma. Co-culture duration ranged from zero to thirty minutes, with five-minute intervals, in order to assess the time-dependent ultrastructural conformations of platelet and fibrin networks, using scanning electron microscopy. It was found that enhanced coagulability was related to co-culture duration. Changes in platelet and fibrin network morphology from normal were visible as early as five minutes in co-culture with MCF-7 cells. With longer co-culture duration thrombosis-linked variation in structural configuration was intensified, including advanced platelet aggregation and adherence characteristics, compression of fibrin networks into plaques of increased density, and upsurge of microparticulate extrusion implicated in amplifying procoagulant events during the metastatic process. These results confirm that cancer cells are stimulators of coagulation even in an in vitro system and breast cancer patients may become increasingly susceptible to thrombotic-related consequences with increased exposure to tumour cells, especially during metastasis.

Topics: Blood Coagulation; Blood Platelets; Breast Neoplasms; Coculture Techniques; Female; Fibrin; Humans; MCF-7 Cells; Microscopy, Electron, Scanning; Thromboembolism; Thrombosis; Time Factors

Dendropanax morbifera H. Lev. is well known in Korean traditional medicine for improvement of blood circulation. In this study, rutin, a bioflavonoid having anti-thrombotic and anticoagulant activities was isolated from a traditional medicinal plant, D. morbifera H. Lev. The chemical characteristics of rutin was studied to be quercetin 3-O-α-l-rhamnopyranosyl-(1-6)-β-d-glucopyranoside using high performance liquid chromatography mass spectrometry (HPLC-MS), proton nuclear magnetic resonance ((1)H NMR) and carbon-13 nuclear magnetic resonance ((13)C NMR). Turbidity and fibrin clotting studies revealed that rutin reduces fibrin clot in concentration dependent manner. Rutin was found to prolong activated partial thromboplastin time (aPTT), prothrombin time (PT) and closure time (CT). Furthermore, it decreased the activity of pro-coagulant protein, thrombin. In vivo study showed that rutin exerted a significant protective effect against collagen and epinephrine (or thrombin) induced acute thromboembolism in mice. These results suggest that rutin has a potent to be an anti-thrombotic agent for cardiovascular diseases.

Topics: Animals; Anticoagulants; Antithrombins; Araliaceae; Blood Coagulation; Blood Platelets; Collagen; Epinephrine; Fibrin; Male; Medicine, Korean Traditional; Mice; Partial Thromboplastin Time; Plants, Medicinal; Prothrombin Time; Rutin; Thrombin; Thromboembolism

Formation of compact and poorly lysable fibrin clots have been demonstrated in patients following ischemic stroke. Recently, it has been shown that denser fibrin networks and impaired fibrinolysis occurs in subjects with permanent atrial fibrillation (AF). Fibrin clot phenotype in other types of AF remains to be established. We evaluated fibrin clot properties in paroxysmal (PAF) and persistent AF (PsAF).. We studied 88 non-anticoagulated patients with AF on sinus rhythm and free of stroke (41 with PAF, 47 with PsAF) versus 50 controls. Ex-vivo plasma fibrin clot permeability (Ks) and clot lysis time (CLT) were evaluated along with von Willebrand factor (vWF), peak thrombin generation (TG), platelet factor 4 (PF4) and fibrinolytic proteins.. Compared with control subjects, clots obtained from plasma of patients with PAF and PsAF had similarly lower Ks (-7.7%, P=0.01; -8.6%, P=0.005, respectively) and prolonged CLT (+10.8%, P=0.006; +7.8% P=0.04, respectively). No associations of Ks and CLT with CHA2DS2-VASc and HAS-BLED score were observed. Patients with AF had higher TG, vWF, PF4 and plasminogen activator inhibitor-1 (PAI-1) antigen compared with controls. Multiple linear regression adjusted for age, gender, body mass index and fibrinogen showed that TG (β=-0.41), vWF (β=-0.29) and PF4 (β=-0.28) are the independent predictors of Ks (R(2)=0.78), while CLT was independently predicted by TG (β=0.37), PAI-1 antigen (β=0.29) and vWF (β=0.26) in the AF group (R(2)=0.39).. Patients with PAF and PsAF while on sinus rhythm display unfavorably altered fibrin clot properties, which might contribute to thromboembolic complications.

Topics: Atrial Fibrillation; Blood Coagulation; Chronic Disease; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Platelet Activation; Thrombin; Thromboembolism; Ventricular Dysfunction, Left

The objectives of the present study were to investigate whether kaempferol affects pro-coagulant proteinase activity, fibrin clot formation, blood clot and thrombin (or collagen/epinephrine)-stimulated platelet activation, thrombosis, and coagulation in ICR (Imprinting Control Region) mice and SD (Sprague-Dawley) rats. Kaempferol significantly inhibited the enzymatic activities of thrombin and FXa by 68 ± 1.6% and 52 ± 2.4%, respectively. Kaempferol also inhibited fibrin polymer formation in turbidity. Microscopic analysis was performed using a fluorescent conjugate. Kaempferol completely attenuated phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) 1/2, and phosphoinositide 3-kinase (PI3K)/PKB (AKT) in thrombin-stimulated platelets and delayed aggregation time (clotting) by 34.6% in an assay of collagen/epinephrine-stimulated platelet activation. Moreover, kaempferol protected against thrombosis development in 3 animal models, including collagen/epinephrine- and thrombin-induced acute thromboembolism models and an FeCl3-induced carotid arterial thrombus model. The ex vivo anticoagulant effect of kaempferol was further confirmed in ICR mice. This study demonstrated that kaempferol may be clinically useful due to its ability to reduce or prevent thrombotic challenge.

Topics: Animals; Blood Coagulation; Collagen; Enzyme Activation; Epinephrine; Factor Xa; Factor Xa Inhibitors; Fibrin; Humans; Kaempferols; Male; Mice; Mitogen-Activated Protein Kinases; Platelet Activation; Protein Multimerization; Protein Structure, Quaternary; Proto-Oncogene Proteins c-akt; Rats; Thrombin; Thromboembolism; Thrombosis

One of the main disadvantages of current t-PA thrombolytic treatment is the increased bleeding risk. Upon activation, thrombin activatable fibrinolysis inhibitor (TAFI) is a very powerful antifibrinolytic enzyme. Therefore, co-administration of a TAFI inhibitor during thrombolysis could reduce the required t-PA dose without compromising the thrombolytic efficacy. In this study we generated and characterised a nanobody that is inhibitory towards rat TAFI and evaluated its profibrinolytic property in vitro and in vivo. Nanobody VHH-rTAFI-i81 inhibits (at a 16-fold molar ratio nanobody over TAFI) the thrombin/thrombomodulin (T/TM)-mediated activation of rat TAFI (rTAFI) by 83 ± 1.8% with an IC50 of 0.46 (molar ratio nanobody over TAFI). The affinity (KA) of VHH-rTAFI-i81 for rTAFI, as determined by surface plasmon resonance (Biacore®), is 2.5 ± 0.2 x 10(10) M(-1) and illustrates a very strong binding. In an in vitro clot lysis assay, administration of VHH-rTAFI-i81 strongly enhances the degree of lysis and reduces time to reach full lysis of t-PA-mediated clot lysis. Epitope mapping discloses that Lys392 is of primary importance for the nanobody/rTAFI interaction besides minor contributions of Tyr175 and Glu183. In vivo application of VHH-rTAFI-i81 in a tissue factor-induced mouse thromboembolism model significantly decreases fibrin deposition in the lungs in the absence of exogenous administered t-PA. Nanobody VHH-rTAFI-i81 is a very potent inhibitor of T/TM-mediated TAFI activation. Co-administration of this nanobody and t-PA enhances the fibrinolytic efficacy. In an in vivo mouse thromboembolism model, VHH-rTAFI-i81 reduces fibrin deposition in the lungs.

Topics: Animals; Antibodies, Blocking; Carboxypeptidase B2; Disease Models, Animal; Drug Therapy, Combination; Epitope Mapping; Female; Fibrin; Fibrinolytic Agents; Humans; In Vitro Techniques; Lung; Mice; Protein Binding; Rats; Single-Domain Antibodies; Surface Plasmon Resonance; Thrombin; Thromboembolism; Thrombomodulin; Tissue Plasminogen Activator

Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure.. The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fisher's exact test. Statistical significance was set at P < .05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves.. Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P < .001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%).. Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Area Under Curve; Chronic Disease; Diabetes Complications; Female; Fibrin; Follow-Up Studies; Heart Valve Prosthesis; Hematoma; Hemostatics; Heparin; Humans; International Normalized Ratio; Liver Diseases; Male; Middle Aged; Oral Hemorrhage; Postoperative Hemorrhage; Prospective Studies; Renal Insufficiency; ROC Curve; Thromboembolism; Tooth Extraction; Tooth Socket; Treatment Outcome; Young Adult

Thrombus and secondary thrombosis plays a key role in stroke. Recent molecular imaging provides in vivo imaging of activated factor XIII (FXIIIa), an important mediator of thrombosis or fibrinolytic resistance. The present study was to investigate the fibrin deposition in a thromboembolic stroke mice model by FXIIIa-targeted near-infrared fluorescence (NIRF) imaging.. The experimental protocol was approved by our institutional animal use committee. Seventy-six C57B/6J mice were subjected to thromboembolic middle cerebral artery occlusion or sham operation. Mice were either intravenously injected with the FXIIIa-targeted probe or control probe. In vivo and ex vivo NIRF imaging were performed thereafter. Probe distribution was assessed with fluorescence microscopy by spectral imaging and quantification system. MR scans were performed to measure lesion volumes in vivo, which were correlated with histology after animal euthanasia.. In vivo significant higher fluorescence intensity over the ischemia-affected hemisphere, compared to the contralateral side, was detected in mice that received FXIIIa-targeted probe, but not in the controlled mice. Significantly NIRF signals showed time-dependent processes from 8 to 96 hours after injection of FXIIIa-targeted probes. Ex vivo NIRF image showed an intense fluorescence within the ischemic territory only in mice injected with FXIIIa-targeted probe. The fluorescence microscopy demonstrated distribution of FXIIIa-targeted probe in the ischemic region and nearby micro-vessels, and FXIIIa-targeted probe signals showed good overlap with immune-fluorescent fibrin staining images. There was a significant correlation between total targeted signal from in vivo or ex vivo NIRF images and lesion volume.. Non-invasive detection of fibrin deposition in ischemic mouse brain using NIRF imaging is feasible and this technique may provide an in vivo experimental tool in studying the role of fibrin in stroke.

Topics: alpha-2-Antiplasmin; Animals; Brain; Factor XIIIa; Feasibility Studies; Fibrin; Fluorescent Dyes; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Peptide Fragments; Reproducibility of Results; Spectroscopy, Near-Infrared; Stroke; Thromboembolism; Time Factors

Mechanical behavior of the thromboembolus is one of the key factors that determine the efficacy of thrombectomy devices for revascularization in AIS. We characterized the mechanical properties and composition of thromboemboli from clinical cases and compared them with commonly used EAs.. Thromboemboli were obtained from patients with AIS by using aspiration devices and from carotid atherosclerotic plaques harvested during endarterectomy. In the laboratory, common EAs were created by varying blood donor species (human, porcine, and bovine), thrombin concentration, and presence of barium sulfate. Stiffness and elasticity of the specimens were measured with DMA. Scanning electron microscopy and histology were used to investigate the ultrastructure and composition of all specimens.. Red thromboemboli from patients composed mainly of fibrin and erythrocytes were much softer than the calcified and cholesterol-rich material. Of the EAs created in the laboratory, those made from bovine blood presented the highest stiffness that was independent of thrombin concentration. Addition of thrombin increased the stiffness and elasticity of human and porcine EAs (P < .05). The presence of barium sulfate significantly reduced the elasticity of all EAs (P < .05).. Endovascular device testing and development requires realistic EAs. The stiffness and elasticity of the cerebral thromboemboli analyzed in this study were closely matched by recalcified porcine EAs and thrombin-induced human EAs. Stiffness of the thrombus extracted from carotid endarterectomy specimens was similar with that of the thrombin-induced bovine and porcine EAs.

Topics: Acute Disease; Aged; Animals; Barium Sulfate; Biomechanical Phenomena; Brain Ischemia; Cattle; Elasticity; Erythrocytes; Fibrin; Humans; Infarction, Middle Cerebral Artery; Male; Species Specificity; Stress, Mechanical; Swine; Thrombectomy; Thrombin; Thromboembolism

Proneness to the formation of tight and rigid fibrin networks has been shown to be independently associated with thrombotic disease. These changes may be visible long before the actual event. Previous research has shown that there is a fundamental difference between fibrin network architecture of controls compared to fibrin networks of patients 48?h post-thrombo-embolic ischemic stroke. This conclusion was made using a high-tech scanning electron microscope (SEM). Here the authors investigate whether ultrastructure of these networks can be successfully analyzed when using a smaller, desktop SEM. Such a screening procedure would not only be inexpensive, but could potentially warn patients of a possible thrombotic event long before any symptoms are prevalent. Platelet-rich plasma, obtained from healthy volunteers and thrombo-embolic ischemic stroke patients (48 h poststroke), was activated by the addition of thrombin. Fibrin networks were compared using a Zeiss ULTRA plus FEG-SEM with InLens and a desktop portable ZEOL SEM (ZEOLNeoScope). This desktop version produces micrographs that may easily be analyzed, and the information gained by studying the micrographs was comparable to that of the Zeiss ULTRA plus FEG-SEM. Such a desktop machine might be used as a screening tool or to identify individuals with risk, before the actual event. In addition, it may provide valuable information in recovering stroke patients.

Topics: Brain Ischemia; Case-Control Studies; Equipment Design; Fibrin; Humans; Microscopy, Electron, Scanning; Platelet-Rich Plasma; Predictive Value of Tests; South Africa; Stroke; Thrombin; Thromboembolism

Cerebrovascular disease is one of the leading causes of death and the cause of long-term adult disability. An important characteristic of thromboembolic ischemic stroke is a prothrombotic or hypercoagulable state and altered fibrin clot structure, whereas a resistance to fibrinolysis is also present. An expansive fibrin network is created when adding thrombin, and in stroke, the network appears thickened, netted and matted, compared with that of healthy individuals. Although this is clearly visible in micrographs of patients, there is a need to quantify the changes. The current study, therefore, investigates fibrin fiber diameters in stroke patients and compares it to healthy individuals. The fiber diameters were measured in nanometres, with University of Texas Health Science Center at San Antonio (UTHSCSA) Image Tool. A total of 100 measurements were done for each of the 12 patients in the healthy control group, and the same number of measurements was done for 12 stroke patients. These measurements were statistically analysed with NCSS 2007, using a significance level of 0.05. Normality was assessed with the Shapiro-Wilk W test and the thickest and thinnest fiber of each individual in the two groups was quantified and differences between groups were assessed with the Student's t-test. Results showed that there is a statistical difference in fibrin fiber thickness during thromboembolic ischemic stroke. We conclude that the changed coagulation and hemostasis, typically associated with stroke, causes a statistically relevant change in fibrin thickness, and that this netted and matted network is more resistant to lyses.

Topics: Case-Control Studies; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Microscopy, Electron, Scanning; South Africa; Stroke; Thromboembolism

Atrial fibrillation (AF) is associated with a prothrombotic state.. We evaluated associations of previous thromboembolic events with fibrinolytic parameters in patients with AF.. We studied 62 consecutive patients with permanent AF (27 men, 35 women, aged 46-89 years [median, 78 years]). Patients receiving warfarin or acenocoumarol on a long-term basis were eligible. We determined plasma fibrin clot lysis time (CLT), plasminogen activator inhibitor-1 (PAI-1) antigen, thrombin-activatable fibrinolysis inhibitor (TAFI) activity and antigen, plasminogen, α2-antiplasmin (α2AP), and soluble thrombomodulin (sTM).. There were 19 subjects (30.6%) with a history of thrombotic events (stroke in 11, myocardial infarction in 8, and pulmonary embolism in 3 patients). They had longer CLT (P = 0.0035 for patients with previous stroke and P = 0.001 for patients with any previous thrombotic event), together with higher PAI-1 (P = 0.025 and P = 0.016, respectively), TAFI activity (P = 0.002 and P = 0.011, respectively), sTM (P = 0.0023 and P = 0.012, respectively), and α2AP (P = 0.007 and P = 0.0006, respectively) than the remaining subjects. AF patients with previous stroke had also higher TAFI antigen than the remainder (P = 0.04). CLT (P = 0.024), PAI-1 (P = 0.022), TAFI activity (P = 0.048), and sTM (P = 0.032, all P for trend) increased with higher CHA2DS2-VASc scores. CLT was not associated with time from thrombotic event to enrollment. Patients taking oral anticoagulants (n = 46) had only slightly higher sTM levels (3.6 [2.9-6.3] vs. 2.9 [2.2-4.1] ng/ml, P = 0.049) than the remaining subjects.. Stroke or other thromboembolic event in AF patients is associated with impaired lysability of fibrin clots combined with elevated PAI-1, TAFI, sTM, and α2AP.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Carboxypeptidase B2; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator; Warfarin

To increase the survival rate of patients with acute superior mesenteric artery thromboembolism (ASMAT) treated by catheter thrombolysis, we examined the effects of delivering edaravone and asialoerythropoietin, agents with tissue-protective activities, using a rabbit autologous fibrin clot ASMAT model. Japanese white rabbits (n=32) were randomly separated into four equal groups. 45 min after introducing autologous fibrin clot, Group U received urokinase and heparin; Group E received urokinase and heparin plus edaravone; Group A received urokinase and heparin plus asialoerythropoietin; and Group EA received urokinase, heparin and edaravone plus asialoerythropoietin via a catheter. The intestines were removed 6 h later and intestinal mucosal damage was scored using the Park's injury score. Survival time was assessed. Average mucosal injury was 5.78+/-1.52 (Group U), 2.88+/-0.72 (Group E), 1.90+/-1.23 (Group A) and 1.18+/-1.25 (Group EA). The degree of mucosal injury was significantly lower in Group EA than in Groups U and E (p<0.05). Conversely, there was no significant difference between Group A and Group EA, or between Group A and Group E. The survival times were 31.50+/-13.30 h (Group U), 51.00+/-24.74 h (Group E), 48.00+/-16.97 h (Group A) and 82+/-51.07 h (Group EA); the difference among the four groups was not significant. In conclusion, the concomitant administration of asialoerythropoietin and edaravone reduced mucosal membrane injury significantly compared with edaravone alone. However, to improve the survival of ASMAT rabbit models, the delivery of an appropriate dose of asialoerythropoietin is required, together with the development of methods to assess peripheral recanalisation.

Topics: Animals; Antipyrine; Asialoglycoproteins; Catheterization; Disease Models, Animal; Drug Combinations; Edaravone; Erythropoietin; Fibrin; Fibrinolytic Agents; Free Radical Scavengers; Heparin; Injections, Intra-Arterial; Intestinal Mucosa; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Rabbits; Random Allocation; Reperfusion Injury; Survival Rate; Thromboembolism; Urokinase-Type Plasminogen Activator

Thromboembolic complications occur more frequently in patients with chronic heart failure (CHF) than in the general population. Formation of a compact fibrin clot resistant to lysis has been shown in arterial and venous thrombosis.. To investigate fibrin clot properties in patients with CHF.. Plasma clot permeability, compaction, turbidity and fibrinolysis were assessed in 36 consecutive patients with stable CHF (30M, 6F; aged 64+/-10 years, left ventricular ejection fraction (LVEF) 34.9+/-6.7%) and 36 controls matched for age, sex, cardiovascular risk factors and medication. Exclusion criteria were LVEF >40%, anticoagulant therapy, previous thromboembolic events, atrial fibrillation.. Clots obtained from plasma of patients with CHF had 23% lower clot permeability (p<0.0001), 13% less clot compaction (p<0.001), 15% faster fibrin polymerisation (p<0.0001) and tended to have prolonged fibrinolysis time (p=0.1) compared with controls. C-reactive protein and fibrinogen were associated inversely with clot permeability (R(2)=0.84, p<0.0001 and R(2)=0.79, p<0.0001, respectively) and positively with fibrinolysis time (R(2)=0.88, p<0.0001 and R(2)=0.80, p<0.0001, respectively) in patients with CHF. Plasma thrombin-antithrombin complex concentrations were inversely correlated with clot permeability (R(2)=0.88, p<0.0001) and positively with fibrinolysis time (R(2)=0.91, p<0.0001). Left atrium diameter, but not LVEF, correlated with fibrinolysis time (R(2)=0.61, p=0.027).. Patients with CHF with sinus rhythm are characterised by faster formation of compact plasma fibrin clots, which might predispose to thromboembolic complications.

Topics: Aged; Aged, 80 and over; Blood Coagulation; Blood Coagulation Tests; Case-Control Studies; Female; Fibrin; Fibrinolysis; Heart Failure; Heart Rate; Hemorheology; Humans; Male; Middle Aged; Thromboembolism; Ultrasonography

Topics: Animals; Brain; Cerebrovascular Circulation; Fibrin; Humans; Mice; Microvessels; Thrombin; Thromboembolism

The aim of this study was to evaluate the effects of intra-arterial administration of edaravone after superior mesenteric artery (SMA) thromboembolism in a rabbit model. 24 Japanese white rabbits were randomly allocated to a urokinase group (group U) and a urokinase with edaravone group (group E). A further three rabbits, which were administered an autologous blood clot alone, served as a control group (group C). A 4-Fr sheath was inserted into an SMA. An autologous blood clot was administered to an SMA (group C). After 45 min, urokinase (6000 IU) and heparin (250 IU) were administered through the catheter, either alone (group U) or in conjuction with edaravone (0.5 mg kg(-1)) (group E). In eight rabbits from each of groups U and E, 6 h after reperfusion, the small intestine was harvested and divided into five equal parts. The degree of intestinal tissue injury in each part was rated on a scale of 0-8. After 1 week, survival times and blood biochemistry data were compared among rabbits in group U (four rabbits), group E (four rabbits) and group C (three rabbits), and significant differences (p<0.05) were recorded. Intestinal mucosal damage was significantly greater in group U (5.8 +/- 1.5) than in group E (2.9 +/- 0.7). Survival time tended to be longer in group E (p>0.4, not significant compared with group U). Liver and kidney function showed signs of deterioration over time whether or not edaravone was administered, but administration of edaravone reduced intestinal mucosal damage. An increase in survival rate requires improvements in evaluation methods to enable identification of ischaemic areas.

Topics: Animals; Anticoagulants; Antipyrine; Case-Control Studies; Disease Models, Animal; Edaravone; Fibrin; Free Radical Scavengers; Heparin; Intestine, Small; Mesenteric Artery, Superior; Mesenteric Vascular Occlusion; Rabbits; Random Allocation; Reperfusion Injury; Thromboembolism; Urokinase-Type Plasminogen Activator

Routinely available coagulation assays are not capable of detecting clinically defined hypercoagulable states. A number of global coagulation assays have been developed with the potential to evaluate hypercoagulability, which predisposes to the common clinical events of arterial and venous thromboembolism (VTE).. We hypothesized that the overall hemostatic potential (OHP) assay would show abnormal fibrin generation and lysis in patients with clinically defined hypercoagulable states.. We used the OHP assay as described by Blombäck and colleagues [1,2] in 161 clinically hypercoagulable patients with arterial or VTE, pregnancy complications or autoimmune disease. Eighty patients had associated antiphospholipid antibodies (APLA). Ninety-eight normal plasma donors were tested for comparison.. We derived three new assay parameters for correlation with hypercoagulable states: the maximum optical density, maximum slope, and delay in onset of fibrin generation. We found significantly different assay results for all patients' parameters examined when compared with controls, indicating both increased fibrin generation and reduced fibrinolysis in hypercoagulable patients. The findings were similar whether samples were collected in association with an acute thrombotic event or not. Estimated assay sensitivity for detection of a clinically defined hypercoagulable state was 96%.. The OHP assay is a simple, inexpensive global test that is useful for assessing patients with hypercoagulable states including APLA. OHP results are significantly abnormal in hypercoagulable groups compared with controls, indicating that both increased fibrin generation and reduced fibrinolysis contribute to hypercoagulable states. The assay may ultimately assist in tailoring clinical management to patients' individual requirements.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiphospholipid Syndrome; Blood Coagulation Tests; Case-Control Studies; Female; Fibrin; Fibrinolysis; Hemostasis; Humans; Male; Middle Aged; Pilot Projects; Predictive Value of Tests; Pregnancy; Pregnancy Complications, Hematologic; Reproducibility of Results; Sensitivity and Specificity; Thromboembolism; Thrombophilia; Time Factors; Venous Thrombosis

Topics: Anticoagulants; Drug Administration Schedule; Factor Xa Inhibitors; Female; Fibrin; Fondaparinux; Humans; Middle Aged; Perioperative Care; Phenprocoumon; Polysaccharides; Postoperative Hemorrhage; Surgical Procedures, Operative; Thromboembolism; Thrombophilia; Venous Thrombosis; Vitamin K

Inherited thrombophilias are associated with an increased risk of maternal thromboembolism and certain adverse pregnancy outcomes, including second- and third-trimester fetal loss, placental abruption, severe intrauterine growth restriction, and early-onset, severe preeclampsia. Pregnant patients with severe thrombophilias, especially antithrombinopathies are at very high risk for both thromboembolism and adverse pregnancy outcomes. A case of a patient with antithrombin deficiency is reported, who had two successful pregnancies after eight miscarriages. Our case shows that a combined treatment with antithrombin substitution and a prophylactic, body-weight-adjusted dose of low-molecular-weight heparin may be successful in preventing pregnancy loss and thromboembolism in antithrombin deficiency during pregnancy, although other complications, such as preeclampsia and intrauterine growth restriction cannot always be prevented.

Topics: Abortion, Habitual; Adult; Anticoagulants; Female; Fibrin; Heparin; Humans; Infertility, Female; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism; Thrombophilia; Treatment Outcome

To observe the changes in fibrin of microemboli in micro-embolism soon after thrombolysis, in order to provide a theoretical basis for micro-thrombolytic therapy.. Thirty adult male SD rats weighing (180+/-10)g were randomized into five groups: 5, 30, 60 and 90 minutes groups after micro-thromboembolization and the control group. Rat cremasteric artery was embolized with photochemical method, and micro-thrombi were produced after thrombolysis by staphylokinase. The levels of tissue plasminogen activator (t-PA) and tissue plasminogen activator inhibitor (PAI) were immunohistochemically determined, and taken as the markers of fibrin dissolution.. Fibrin was observed in pathologic sections as well as fibrinolytic markers t-PA and PAI in immunohistochemical sections. The levels of t-PA were found to be reduced while that of PAI increased gradually with passage of time.. Fibrin is one of the main constituents of microthrombi soon after thrombolysis. The content of fibrous emboli increases after microembolization with the passage of time. Thrombolysis plays an important role in the treatment of "no reflow phenomenon".

Topics: Animals; Disease Models, Animal; Fibrin; Fibrinolysis; Fibrinolytic Agents; Male; Plasminogen Inactivators; Random Allocation; Rats; Rats, Sprague-Dawley; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator

This study compared the antithrombotic effect of plasma angiotensin converting enzyme inhibitors (ACE-Is): captopril (CAP), enalapril (ENA) and tissue ACE-Is: perindopril (PER), quinapril (QUIN) in experimental venous and arterial thrombosis. Normotensive Wistar rats were treated p.o. with CAP (75 mg/kg), ENA (20 mg/kg), PER (2 mg/kg) and QUIN (3 mg/kg) for 10 days. The influence of ACE-Is on coagulation and fibrinolytic systems as well as platelet function was evaluated. The hypotensive effect of ACE-Is was equal in all groups. QUIN maintained the final carotid blood flow at the highest value in comparison to PER and plasma ACE-Is. The arterial thrombus weight was reduced in PER and QUIN groups while venous thrombus weight was also reduced after CAP. Tissue and plasma ACE-Is caused the inhibition of platelet adhesion and aggregation. A reduction of fibrin generation, prolongation of prothrombin time (PT), activated partial thromboplastin time (APTT) and shortening of euglobulin clot lysis time (ECLT) were observed after PER and QUIN treatment. In conclusion, given in equipotent hypotensive doses, tissue ACE-Is exerted more pronounced antithrombotic effect than plasma ACE-Is in experimental thrombosis. The differences between tissue and plasma ACE-Is in terms of their more pronounced inhibition of experimental thrombosis may be related to the intensified activation of fibrinolysis and inhibition of coagulation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Captopril; Carotid Arteries; Disease Models, Animal; Enalapril; Fibrillar Collagens; Fibrin; Hemostasis; Male; Perindopril; Platelet Adhesiveness; Platelet Aggregation; Quinapril; Rats; Rats, Wistar; Regional Blood Flow; Tetrahydroisoquinolines; Thromboembolism

Thromboembolic adverse reactions reported after transfusion of SD-plasma in the United States (US) prompted us to perform a comparative study with SD-plasma from the US and the European (EU) market. In SD-plasma from US, residual tri-N-butyl phosphate was found, and citrate concentrations were lower than in EU-plasma. Except for substantial losses of FV, FVIII and antiplasmin found for all SD-plasmas, clotting factor activities were mainly retained. However, for SD-plasma from US, markedly elevated concentrations of lipoprotein (a) [Lp(a)], fibrin monomer and a particularly high degree of complement activation (C3a des-Arg) were observed. Furthermore, pronounced differences were found for protein S. Although SD-plasma pools from US contained nearly normal concentrations of free and bound protein S antigen, protein S activities were almost completely absent. In contrast to this, SD-plasma from EU showed a moderate loss of both protein S activity and free antigen. Antitrypsin inhibitor activities were much more diminished in SD-plasma from US than from EU. In view of a possible thrombogenicity of SD-plasma from US, the loss of protein S and elevated Lp(a) concentrations could be of significance. The very high levels of C3a des-Arg in US plasma could possibly have an additional effect, through priming platelet activation after transfusion.

Topics: Blood Coagulation Factors; Complement C3a; Europe; Fibrin; Humans; Lipoprotein(a); Plasma; Plasma Exchange; Protein S; Thromboembolism; United States

Thromboembolism secondary to atrial fibrillation accounts for approximately one-fourth of all strokes. Although considerable resources have been targeted to pharmacologic prophylaxis, neither the cellular nor the biochemical composition of atrial thrombi is known. Quantitative immunohistochemistry was undertaken to define the composition of atrial thrombi and to explore morphological differences between atrial appendage thrombi and those that embolize.. Serial sections of thrombi obtained during valve replacement surgery or embolectomy from 22 patients with atrial fibrillation were stained with antibodies against fibrin, integrin beta3, or tissue factor and analyzed with NIH-image.. Thrombi showed distinct regions staining for either fibrin or platelets and on average, the fibrin-rich regions predominated (P < 0.0001). The platelet content of embolized thrombi was nearly twice that of atrial thrombi (P = 0.02). Non-staining amorphous material comprised nearly half of atrial thrombi in situ, but was rare in embolized thrombi (P < 0.001). Tissue factor colocalized to areas rich in platelets and granulocytes.. The abundance of fibrin relative to platelets underscores the enhanced efficacy of warfarin prophylaxis in clinical trials. The finding of tissue factor localized to platelet-leukocyte clusters suggests its blood-borne origin. Compositional differences between in situ and embolized thrombi suggest directions for investigating propensity for embolization.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Blood Platelets; Female; Fibrin; Heart Valve Prosthesis; Humans; Immunohistochemistry; Integrin beta3; Male; Thromboembolism; Thromboplastin; Thrombosis; Warfarin

Elevated circulatory levels of many blood coagulation factors are known to be a risk factor for deep vein thrombosis in humans. Here we report the first direct demonstration of a close association between elevated circulatory factor IX levels in mice with thrombosis as well as myocardial fibrosis. Transgenic mice overexpressing human factor IX at persistently high levels died at much younger ages than their cohorts expressing lower levels, or nontransgenic control animals. The median survival age of animals was inversely related to the circulatory levels of human factor IX. Prematurely dying animals had focal fibrotic lesions predominantly present in the left ventricular myocardium, and vasculatures in these lesions showed fibrin deposition. Thromboemboli were also present in other organs, including lung and brain. These observations support the hypothesis that persistently high circulatory levels of factor IX are a risk factor not only for thrombosis and/or thromboembolism, but also for myocardial fibrosis mimicking human myocardial infarction.

Topics: Animals; Coronary Thrombosis; Disease Models, Animal; Factor IX; Female; Fibrin; Fibrosis; Gene Expression Regulation; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myocardial Infarction; Myocardium; Recombinant Fusion Proteins; Risk Factors; Thromboembolism; Thrombophilia

Topics: Agglutination Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Sensitivity and Specificity; Thrombin; Thromboembolism; Ultrasonography; Venous Thrombosis

Paroxysmal nocturnal haemoglobinuria (PNH) is characterized pathophysiologically by intravascular lysis of blood cells and clinically by thromboembolic events, often atypical in localization. In this study, we examined the plasmatic coagulation system of PNH patients to investigate a potential relation between coagulation alterations and disease intensity (PNH clone size). We found evidence for both an increase in procoagulant and in fibrinolytic activity, resulting in increased fibrin generation and turnover. Whereas a positive association of the procoagulant potential with PNH clone size was notable, fibrinolytic activity showed an inverse association with clone size. As a possible cause, a growing impairment of fibrinolytic activation and/or an increasing displacement of fibrinolytic activity is assumed. These mechanisms are most likely caused by the detachment of the glycosyl-phosphatidyl-inositol-anchored urokinase plasminogen activator receptor from cell surfaces, causing a progressive resistance to fibrinolytic stimuli, together with a probable shift of the fibrinolytic potential from cell surfaces to soluble, circulating complexes, resulting in a cellular fibrinolysis-steal phenomenon. Together, these processes are accused of mediating an increased thrombophilic risk in PNH. As hereditary prothrombogenic defects were found more frequently in patients suffering ischaemic complications, genetic thrombophilia seems to confer an additional thromboembolic risk in PNH, and should therefore be screened for.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation; Case-Control Studies; Cell Size; Clone Cells; Female; Fibrin; Fibrinolysis; Hemoglobinuria, Paroxysmal; Humans; Male; Middle Aged; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Risk Factors; Thromboembolism; Thrombophilia

Topics: Alleles; Amino Acid Substitution; Case-Control Studies; Fibrin; Fibrinogen; Humans; Male; Myocardial Infarction; Polymorphism, Genetic; Thromboembolism

Anti-beta 2-glycoprotein I antibodies bind to endothelial cells through beta 2-GPI. The antibodies are present in patients with systemic lupus erythematosus and antiphospholipid syndrome and are associated with the pathogenesis of the disease. Anti-endothelial cell antibodies that react with constitutive antigens on ECs are present in patients with vasculiditis and other diseases. Both types of antibodies can activate ECs. Frequent findings in APLS and vasculitis are fibrin deposits and thromboembolic phenomena. These indicate that the coagulation system is activated. However, the mechanism of activation is not clear. ECs generate tissue factor upon stimulation with various substances. In the present study we report that monoclonal anti-beta 2-GPI antibodies and AECAs, derived from a patient with primary APLS and a patient with Takayasu's arteritis, respectively, induce a potent tissue factor in ECs. The production of TF activity, TF antigen and TF mRNA is dose and time dependent. The TF activity was induced also by F(ab)2 but not by Fc fragments and was abolished completely by pre-incubation with ant-TF antibodies. The TF that is induced in ECs by AECAs with and without beta 2-GPI specificity may activate the coagulation and thereby play a major role in the pathogenesis of fibrin deposition and thrombus formation in diseases that are associated with the presence of these antibodies.

Topics: Antibodies; Antigens; Antiphospholipid Syndrome; Apolipoproteins; beta 2-Glycoprotein I; Binding Sites, Antibody; Cells, Cultured; Endothelium, Vascular; Fibrin; Glycoproteins; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fc Fragments; Lupus Erythematosus, Systemic; Membrane Glycoproteins; RNA, Messenger; Takayasu Arteritis; Thromboembolism; Thromboplastin; Vasculitis

Few data exist by which the anti-thrombotic efficacy of different anticoagulants may be compared. We used a radiolabeled antibody specific for polymerizing fibrin to compare the in vivo anti-thrombotic potencies of different systemic anticoagulants (enoxaparin, dalteparin, and unfractionated heparin).. Deep venous thrombi (DVTs) were induced in dogs' femoral veins. The dogs were then treated with one of the following subcutaneous regimens: enoxaparin 100 units/kg (1.0 mg/kg) every 12 hours (n=4), dalteparin 200 units/kg every 24 hours (n=4), or unfractionated heparin 240 units/kg every 8 hours with dose adjustment via aPTT (n=3). 111Indium-labeled anti-fibrin antibodies, specific for propagating thrombi, were given intravenously and nuclear scans of the legs were taken over the following 24 hours. Thrombus propagation was estimated by the ratio of gamma emissions from the legs containing DVTs divided by the emissions from the contralateral "control" legs. DVTs accumulated labeled anti-fibrin antibodies at the same rates in both the enoxaparin group and the dalteparin group (gamma emissions 171+/-6% and 168+/-36% of control by 24 hours, respectively). DVTs in the adjusted dose unfractionated heparin group tended to accumulate antibodies at a slower rate (129+/-19% of control by 24 hours).. Enoxaparin and dalteparin inhibited propagation of pre-formed thrombi to the same degree. Subcutaneous unfractionated heparin, adjusted every 8 hours by aPTT, tended to suppress ongoing thrombosis more than either LMWH.

Topics: Animals; Antibodies; Anticoagulants; Balloon Occlusion; Dalteparin; Diagnostic Imaging; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Enoxaparin; Factor Xa; Factor Xa Inhibitors; Femur; Fibrin; Gamma Rays; Heparin; Heparin, Low-Molecular-Weight; Indium Radioisotopes; Prothrombin; Thromboembolism; Venous Thrombosis

To assess in a swine model the in vivo thrombogenicity of various microcatheters and guiding catheters as a function of catheter material, catheter coating, and duration of implantation.. Microcatheters (Tracker 18 and Fastracker 18, Target Therapeutics, Fremont, Calif; Magic 1.8, Balt, Montmorency, France; and Transit, Cordis Endovascular Systems, Miami Lakes, Fla) were placed through 6F guiding catheters (Fasguide, Target Therapeutics, and Envoy, Cordis Endovascular Systems) into the common carotid arteries of swine for 30 minutes (short term), 90 minutes (medium term), and 35 days (long term). Guiding catheters were implanted for 5 hours. At the end of the implantation periods the catheters were retracted and fixed for scanning electron microscopy.. The surface of the Fastracker microcatheter was devoid of debris after both short- and medium-term implantation. The Tracker microcatheter had minimal accumulation of cellular elements whereas the Transit microcatheter showed moderate accumulation of nondeformed red blood cells. Neither the Tracker nor the Transit microcatheter showed evidence of increasing debris accumulation after medium-term implantation as compared with short-term implantation. The Magic microcatheter was coated with gross thrombus after both short- and medium-term implantation. The Fasguide guiding catheter was nearly devoid of debris, while the Envoy guiding catheter had moderate thrombus formation. Long-term implantation of the Fastracker microcatheter was well tolerated whereas that of the Transit catheter resulted in vessel occlusion.. Hydrophilic microcatheters and guiding catheters are less thrombogenic than their nonhydrophilic counterparts, but not all hydrophilic coatings are equally hypothrombogenic. Degree of thrombogenicity depends on catheter material rather than surface morphology. Medium-term implantation did not yield increasing thrombus formation relative to short-term implantation.

Topics: Animals; Carotid Artery Thrombosis; Carotid Artery, Common; Catheters, Indwelling; Cerebral Angiography; Equipment Design; Fibrin; Microscopy, Electron, Scanning; Platelet Aggregation; Surface Properties; Swine; Thromboembolism

Homozygous plasminogen-deficient (Plg-/-) mice had a significantly reduced thrombolytic capacity toward intravenously injected 125I-fibrin labeled plasma clots prepared from Plg-/- murine plasma (9% +/- 3% lysis after 8 hours; (mean +/- SEM, n = 6), as compared with 82% +/- 8% in wild-type mice; P < .0001). Bolus injection of 1 mg purified murine plasminogen in 10- to 17-week-old Plg-/- mice increased the plasminogen antigen and activity levels at 8 hours to normal levels (130 +/- 5 micrograms/mL). Plasminogen administration was associated with significant restoration of thrombolytic potential (64% +/- 7% spontaneous clot lysis; P < .0001 versus lysis without plasminogen injection). Bolus injection of 1 mg plasminogen in homozygous tissue-type plasminogen activator-deficient (t-PA-/-) mice doubled the plasminogen antigen and activity levels after 8 hours and increased 125I-fibrin clot lysis at 8 hours from 13% +/- 3% to 34% +/- 5% (P = .008). Fibrinogen, t-PA antigen and alpha 2-antiplasmin activity levels after 8 hours were not significantly different in the groups with or without plasminogen injection. Injection of plasminogen induced a variable increase (on average 7- to 10-fold) of PAI-1, but no correlation with the extent of spontaneous clot lysis was observed. Histopathologic examination at the end of the experiments revealed that fibrin deposition in the liver of Plg-/- mice was slightly reduced 8 hours after bolus plasminogen injection (P = .007) and markedly reduced after 24 hours (P < .0001). Plasminogen antigen levels in liver extracts were comparable with those found in wild-type mice at 8 hours (130 +/- 20 versus 110 +/- 15 ng/mg protein) and decreased to 25 +/- 3.2 ng/mg protein at 24 hours. Thus, restoration of normal plasminogen levels in Plg-/- mice normalized the thrombolytic potential toward experimentally induced pulmonary emboli, and resulted in removal of endogenous fibrin deposits within 24 hours.

Topics: Animals; Female; Fibrin; Fibrinolysis; Liver; Lung; Male; Mice; Mice, Knockout; Plasminogen; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator

The aim of the present study was to correlate the preoperative plasma levels of TDP in patients with colorectal cancer to tumor stage, metastasis, and postoperative thromboembolic complications.. Ninety-one patients with colorectal cancer, 20 patients with colorectal adenoma, and 71 patients without neoplastic lesions in the colon or rectum were included in this prospective study. Before surgery, total fibrin and fibrinogen degradation products (TDP) were measured in plasma of all patients with a specific enzyme-linked immunosorbent assay test. Phlebography was performed postoperatively in 82 of 91 patients with colorectal cancer.. Median TDP in plasma of patients with colorectal cancer (805 (range, 339-5,024) ng fibrinogen equivalents (ngFE)) was significantly higher than TDP in patients with colorectal adenoma (591 (range, 417-1386) ngFE/ml) and TDP in patients without neoplastic lesions in the colon (632.8 (range, 180-2622) ngFE/ml; P < or = 0.003). In patients with colorectal cancer and liver metastasis, TDP in plasma (1085.5 (range, 468-5024) ngFE/ml) was significantly higher than in patients with localized tumor growth (753 (range, (339-2,780) ngFE/ml; P < or = 0.02). Twenty of 82 patients (24 percent) with cancer developed thromboembolic complications. TDP was preoperatively significantly higher in this group of patients (1,101 (range, 468-2,167) ngFE/ml) compared with patients without thromboembolic complications (753 (range, 339-5024) ngFE/ml; P < or = 0.04).. Preoperative plasma levels of TDP were elevated in patients with colorectal cancer, especially in patients with liver metastasis and in patients developing postoperative deep venous thrombosis.

Topics: Adenocarcinoma; Adult; Aged; Case-Control Studies; Colorectal Neoplasms; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Postoperative Complications; Prospective Studies; Thromboembolism

The exact mechanisms for thrombus formation in patients with valvular heart disease have not been clearly defined. Abnormalities in plasma coagulation factors indicative of a prothrombotic state may in part account for the risk of stroke and thromboembolism in such patients. The aim of this study was, therefore, to determine the effects of mitral regurgitation (MR) and aortic stenosis (AS) on plasma fibrinogen or fibrin D-dimer levels as indices of a thrombogenic (or prothrombotic) state. A total of 25 patients with valve disease in sinus rhythm were studied: 12 patients (all women; mean age fifty-five years, sem 3.3) with MR; and 13 patients (7 men, 6 women; mean age fifty-seven years, sem 3.5) with AS were studied. Patients with MR had a median plasma fibrinogen that was significantly elevated when compared with female population values (median difference 0.62 g/L; 95% confidence intervals (CI) 0.27 to 1.05, P = 0.0016). However, these patients had a median plasma fibrin D-dimer that was lower than that for population controls (median difference 21 ng/mL; 95% CI 0 to 38, P = 0.05). Patients with aortic valve disease had a median plasma fibrinogen that was significantly increased when compared with population controls (median difference 0.82 g/L; 95% CI 0.34 to 1.24, P = 0.001). These patients had a plasma fibrin D-dimer level that was similar to population values (median difference 3 ng/mL; 95% CI -25 to 22, P = 0.80). Patients with MR or AS have higher plasma fibrinogen levels when compared with "normal" population values, suggesting possible hemorheologic abnormalities in these patients. Subjects with MR had lower plasma fibrin D-dimer levels, suggesting lesser intravascular clotting, consistent with clinical echocardiographic studies. Subjects with AS had plasma fibrin D-dimer levels similar to the "normal" population values, suggestive of a different pathophysiological mechanism for thromboembolism. These findings add to an improved understanding of the relationship between clinical observations and the significance of plasma fibrinogen and fibrin D-dimer levels in thrombogenesis.

Topics: Aortic Valve Stenosis; Cross-Sectional Studies; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Thromboembolism

Fibrinogen Tampere was found in a woman with severe thromboembolic disease. The thrombin induced clotting time of her plasma and purified fibrinogen was slightly prolonged. The activation of fibrinogen Tampere appeared to be normal but subsequent gelation was defective. We studied fibrin gels formed at different ionic strengths and at different fibrinogen and calcium concentrations by liquid permeation, turbidity, and 3D laser microscopy. Crosslinking was studied by SDS-gel electrophoresis. The gels formed from fibrinogen Tampere were at ionic strength above 0.2 much tighter and had lower fiber mass-length ratios than normal gels as judged by permeability and turbidity data. At ionic strength 0.15 and at different calcium concentrations analysis by permeability showed the same results for fibrinogen Tampere as for normal gels. Analysis by turbidity at ionic strength 0.15 suggested swelling of the fibers at low calcium concentrations. 3D microscopy revealed perturbed clot architecture under all conditions. In fibrin gels from fibrinogen Tampere, the gamma-chain crosslinking was normal but the crosslinking of alpha-chains was delayed at ionic strength 0.2 and also at lower ionic strengths on lowering the calcium concentration. The abnormal gelation may be due to a mutation in the fibrinogen molecule. Tendency to form tight fibrin gels and/or insufficient crosslinked fibrin matrix may be pathogenetic in this thrombotic disease.

Topics: Adult; Female; Fibrin; Fibrinogens, Abnormal; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism

With advancing age, an increasing number of healthy individuals have laboratory signs of heightened coagulation enzyme activity. Such biochemical hypercoagulability might be the basis of either the increased thrombotic tendency occurring with age or a harmless manifestation of this process. To see whether these alterations are also present in the very elderly who had aged successfully, 25 healthy centenarians were studied and results of coagulation and fibrinolysis measurements were compared with those obtained in two control groups of healthy adults, 25 ranging in age from 18 to 50 years and 25 from 51 to 69 years. Older controls had, in general, slightly higher values of several coagulation and fibrinolysis measurements than younger controls. Centenarians had striking signs of heightened coagulation enzyme activity, as assessed directly by measuring activated factor VII in plasma (P < .01, compared with either control group) or indirectly by measuring the plasma levels of the activation peptides of prothrombin, factor IX, factor X, and thrombin-antithrombin complexes (all P < .001). Heightened coagulation enzyme activity was accompanied by signs of enhanced formation of fibrin (high fibrinopeptide A, P < .001) and secondary hyperfibrinolysis (high D-dimer and plasmin-antiplasmin complex, P < .001). Plasma concentrations of fibrinogen and factor VIII were higher than in controls, whereas other coagulation factors were not elevated. In conclusion, this study shows the very elderly do not escape the state of hypercoagulability associated with aging, but that this phenomenon is compatible with health and longevity. Hence, high plasma levels of the coagulation activation markers in older populations do not necessarily mirror a high risk of arterial or venous thrombosis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; Blood Coagulation; Blood Coagulation Factors; Disease Susceptibility; Enzyme Activation; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Reference Values; Thromboembolism

Radioactive tracers are used in nuclear medicine imaging studies to detect sites of human disease. Use of animal models helps to establish tracer biodistribution kinetics and, thus, is critical to the early testing of radiopharmaceuticals. We developed a method to characterize the premortem temporal, spatial, and compartmental biodistribution of tracer molecules in the rat and used this method to study three tracers of potential value in detecting thromboembolic disease. Dynamic gamma scintigraphy was used to determine the spatial and temporal distribution of 99mTc-labeled IgG antifibrin antibody, Fab' fragment of antifibrin, and oxidized human serum albumin (OHSA). The blood pool compartment within each tissue was determined from the biodistribution of 131I-labeled bovine serum albumin injected prior to termination. The biodistribution of the blood compartment was maintained by immediately freezing the rat carcass in isotonic saline. Three-dimensional maps of tracer distribution in the tissue and blood compartments were then constructed from cross sections of the frozen tissue. These maps were used to relate necropsy tissue counts to premortem scintigraphic images. Over a 60-min interval after administration of tracer via a tail vein, significant differences in biodistribution were evident. The IgG remained within the blood pool, but there was rapid blood clearance of the OHSA molecules by the kidney and liver. The Fab' molecules were cleared more slowly by the kidney; Fab' molecules were found in the extravascular spaces, whereas IgG and OHSA were not found. The kinetics of OHSA and Fab' in organ regions paralleled changes in the blood compartment.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Fibrin; Gamma Rays; Immunoglobulin Fab Fragments; Immunoglobulin G; Kinetics; Lung; Male; Muscles; Myocardium; Radioactive Tracers; Radionuclide Imaging; Rats; Rats, Sprague-Dawley; Serum Albumin; Technetium; Thromboembolism; Tissue Distribution

Topics: Afibrinogenemia; Arteriosclerosis; Fibrin; Fibrinogens, Abnormal; Gels; Heparin; Humans; Image Processing, Computer-Assisted; Microscopy, Confocal; Thromboembolism; Thrombosis

To assess the activation status of blood coagulation in thrombosis-prone pregnant women receiving a reduced dosage of heparin.. Forty-three women were given subcutaneous heparin treatment during pregnancy; the dosage was monitored so that the heparin (anti-Xa) level was within the stipulated range of 0.08-0.15 anti-Xa units 3 hours after injection. Several coagulation variables were investigated and some routine analyses were performed. The results were compared with those of a control group of 26 healthy pregnant women.. Compared with the control values, hemoglobin (P < .01), fibrinogen (P < .05), and total protein S (P < .01) were increased already before heparin treatment was started and continued to be increased significantly throughout pregnancy. During heparin treatment, protein C levels (P < .01) and the factors measured by prothrombin time (P < .001) were increased compared with the controls. Antithrombin decreased, though not as much as when patients are given therapeutic dosages. The fibrinolytic inhibitors behaved as in normal pregnancy. Three variables measuring thrombin formation or coagulation activation (ie, thrombin-antithrombin complexes, D-dimers, and soluble fibrin) were increased in a high proportion before heparin treatment was started; they normalized somewhat during treatment.. In early pregnancy, women with previous thrombotic episodes have high plasma levels of coagulation variables and of markers of coagulation activation compared with controls. Such changes may be used to predict the need for treatment and, in the future, to control treatment.

Topics: Adult; Antithrombin III; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Heparin; Humans; Partial Thromboplastin Time; Peptide Hydrolases; Platelet Count; Pregnancy; Pregnancy Complications, Hematologic; Protein C; Prothrombin; Puerperal Disorders; Recurrence; Thrombin; Thromboembolism

Thrombolytic therapy is rarely used in venous thromboembolism because of the fear of hemorrhagic complications. Preliminary clinical experiences with recombinant tissue-type plasminogen activator (rt-PA) in patients with deep vein thrombosis have shown that even this fibrin-specific plasminogen activator causes an unacceptable rate of hemorrhagic complications. Theoretical considerations and the available experimental and clinical data suggest that infusion of rt-PA over a short period of time would result in a more favorable risk-benefit ratio. Shortening the period of rt-PA infusion results in higher peak plasma levels, thus allowing a higher concentration of the plasminogen activator on the surface and inside the occluding thrombus. In addition, a bolus infusion can prevent or minimize the interaction between rt-PA and the hemostatic system, reducing the likelihood of a systemic lytic state, of a platelet function defect, and, possibly, of bleeding side effects. In venous thromboembolism animal models, the efficacy of bolus rt-PA can be further increased by the adjunctive administration of an effective antithrombotic treatment. This is because the accretion of new fibrin on the thrombi counteracts the lysis of preformed fibrin and influences negatively the final thrombus size. Effective adjunctive antithrombotic treatment includes either high doses of heparin, producing an unclottable activated partial thromboplastin time (aPTT), or doses of recombinant hirudin, doubling the aPTT. When used as an alternative to rt-PA, bolus doses of a hybrid plasminogen activator with prolonged half-life efficiently reduce thrombus size by lysing preformed and newly formed fibrin. Preliminary clinical experience in patients with pulmonary embolism seems to confirm that rt-PA infused as a bolus is at least as effective as, and probably more effective than, rt-PA infused over a longer period.

Topics: Animals; Blood Coagulation; Drug Therapy, Combination; Fibrin; Fibrinolysis; Heparin; Hirudin Therapy; Hirudins; Rabbits; Recombinant Proteins; Thromboembolism; Thrombolytic Therapy; Tissue Plasminogen Activator

A 49-year-old man had for 30 years suffered from severe recurrent thromboembolism with leg-vein thrombosis, pulmonary emboli, mesenteric infarction, cerebrovascular accident, cerebral vein thrombosis, portal vein thrombosis and femoral artery occlusion requiring leg amputation. In addition to moderately increased clotting activation with single-fold positive demonstration of fibrin monomers and a D-dimer concentration of 1 mg/l platelet aggregation was increased and could not be influenced by aspirin, 300 mg daily. Despite aspirin there were recurrent transitory attacks of cerebral ischaemia. Fibrin monomers were threefold positive and D-dimer concentration was increased to 4 mg/l (elevated clotting activation). Ticlopidine administration (250 mg daily) reduced adenosine diphosphate-induced platelet aggregation by 30% without effect on collagen-induced platelet aggregation. In parallel to these changes the patient's general condition clearly improved: fibrin monomers were no longer demonstrated and the D-dimer level fell to 0.5 mg/l.

Topics: Aspirin; Fibrin; Humans; Male; Middle Aged; Platelet Aggregation; Recurrence; Thromboembolism; Ticlopidine

Low dose heparin therapy has been used routinely for prophylaxis of deep venous thrombosis, yet in vitro data regarding its antithrombotic effects are sparse. The effects of heparin on venous thrombus formation were studied in an in vitro perfusion system. Fresh blood collected from human volunteers was treated with varying heparin doses and perfused at a shear rate of 100 sec-1 over everted, injured porcine vein segments, simulating conditions in the venous circulation. Platelet and fibrin deposition were measured by use of indium 111 and iodine 125 radiolabels, respectively. The effects of heparin on the intrinsic coagulation cascade were monitored by the activated clotting time. Increasing doses of heparin resulted in significant reductions in fibrin and platelet deposition (ANOVA F = 2.67 and 3.17, respectively, p less than 0.05). At a dose of only 0.19 USP units/ml blood, equivalent to a 1000 unit bolus of heparin in a 70 kg man, a noticeable reduction in both fibrin and platelet deposition was observed without an increase in the activated clotting time. These data confirm the antithrombotic effects of heparin at low dose ranges and may explain the clinically observed phenomenon of deep venous prophylaxis without an appreciable alteration in the conventional coagulation assays.

Topics: Animals; Blood Coagulation; Fibrin; Heparin; Humans; In Vitro Techniques; Indium Radioisotopes; Models, Cardiovascular; Platelet Adhesiveness; Swine; Thromboembolism

Topics: Adult; Aged; Aged, 80 and over; Erythrocyte Aggregation; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Methods; Middle Aged; Pulmonary Embolism; Thromboembolism

Because the effects of red blood cell (RBC) concentration on hemostasis and thrombus formation have not been studied experimentally under conditions of whole blood flow without anti-coagulation, normal baboons were bled or transfused to obtain three different groups: a low hematocrit (Ht) group (20% less than Ht less than 25%), a normal Ht group (35% less than Ht less than 40%), and a high Ht group (50% less than Ht less than 55%). Measurements of platelet count, bleeding time, platelet aggregation, fibrinogen level, and coagulation time (APTT) were equivalent to normal values in each group. Thrombus formation was induced using a device composed of collagen-coated tubing followed by two sequentially placed expansion chambers designed to exhibit flow recirculation and stasis. The device was exposed for up to 40 minutes in an arterio-venous shunt system. Wall shear rates in the tubular collagen segment were 100 seconds-1 and 500 to 750 seconds-1. The accumulation of 111In-platelets and 125I-fibrinogen/fibrin was measured radioisotopically; RBC incorporation was determined from measurements of total thrombus hemoglobin. Thrombus that formed on the collagen substrate was rich in platelets and poor in fibrin and RBCs. Under high flow conditions, thrombus composition showed no dependence on Ht. Surprisingly, under low flow conditions, platelet thrombus volume was negatively correlated with Ht (r = -.73, P = .005), and was increased by greater than twofold in the low Ht group as compared with the high Ht group. Thrombus that formed in the disturbed flow regions contained relatively few platelets but was rich in fibrin and RBCs. The predominant finding was a positive correlation between RBC incorporation and Ht at both high and low shear rates (r = .90, P = .00003; and r = .77, P = .002, respectively), with thrombus volume increasing three- to sixfold between the low and high Ht groups. Thus, in vivo variations in Ht ranging between 20% and 55% did not affect hemostasis, but were found either to promote or inhibit the net accumulation of thrombus, depending on local flow conditions.

Topics: Animals; Blood Platelets; Disease Models, Animal; Erythrocyte Count; Erythrocytes; Fibrin; Hematocrit; Hemostasis; Male; Papio; Thromboembolism

Plasmin generation in vivo was assessed by measuring plasma levels of plasmin-a2-plasmin inhibitor complex (PAP) with an ELISA in 42 patients with arterial or venous thromboembolic diseases. Plasma concentration of PAP was markedly elevated in patients with venous thromboembolic diseases during acute illness (3.32 +/- 3.71 ug/ml, mean +/- SD) as compared to healthy subjects (0.24 +/- 0.13 ug/ml, n = 14), while it was nearly normal (0.30 +/- 0.13 ug/ml) in patients with venous thromboembolic diseases in chronic stage. Patients with arterial thromboembolism had modestly elevated PAP; 1.05 +/- 0.77 ug/ml during acute episode, and 0.84 +/- 0.40 ug/ml in chronic stage. These results indicate that excessive activation of fibrinolytic system (plasmin generation in vivo) occurs actually in many patients with thrombotic diseases, especially in venous thromboembolic diseases during acute illness.

Topics: Acute Disease; alpha-2-Antiplasmin; Antifibrinolytic Agents; Chronic Disease; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Male; Pancreatitis-Associated Proteins; Thromboembolism; Thrombophlebitis

In order to assess thrombogenicity and liver toxicity of different coagulation factor concentrates, antithrombin III, soluble fibrin, alanine aminotransferase (ALAT) and gamma-glutamyl transpeptidase (GT) were measured in samples taken before, 30 min and 24 h after the infusion. Seventy-six studies were performed in 55 patients with haemophilia A (37), B (11) or von Willebrand's disease, type III (7). A sharp rise of soluble fibrin was observed in 2 patients with haemophilia B, indicating that modern factor IX concentrates may still be thrombogenic. A slight increase was also seen after infusion of factor VIII-von Willebrand factor concentrates of low purity. Antithrombin III, ALAT and GT did not change significantly after any of the factor concentrates. The alterations in those parameters did not correlate with the impairment of liver function.

Topics: Adult; Alanine Transaminase; Antithrombin III; Factor VIII; Fibrin; Fibrinogen; Follow-Up Studies; gamma-Glutamyltransferase; Humans; Injections, Intravenous; Liver; Solubility; Thromboembolism

Monoclonal antibody 59D8 developed by Hui et al., binds to fibrin but not fibrinogen. An 111In-labeled Fab fragment of 59D8 was studied in vitro and in animal models to evaluate its potential for imaging thrombi and emboli in man. Rabbits and dogs were used as models for studying thrombus uptake in vivo. Thrombi and emboli up to 4 days old were successfully visualized at 4-24 hr postinjection in five of eight rabbits. In dogs, 0.5-hr-old and 24-hr-old thrombi were successfully imaged at 24 hr in six of eight animals, and 3/6 of these were positive at 3-4 hr postinjection. Thrombus-to-blood ratios in the dogs averaged 7.1 +/- 1.3. The findings suggest this antibody may be useful for imaging thrombi in man.

Topics: Animals; Antibodies, Monoclonal; Cross Reactions; Dogs; Fibrin; Immunoglobulin Fab Fragments; Immunoglobulin G; In Vitro Techniques; Indium Radioisotopes; Pentetic Acid; Rabbits; Radionuclide Imaging; Thromboembolism; Thrombosis

This article deals with the clinical importance of antithrombin III (AT III) in renal disease. Patients with nephrotic syndrome demonstrates a high risk of thromboembolism. A renal AT III loss is an important pathogenetic factor in these events. Patients with serumalbumin below 2.0 g/dl are mostly endangered. In patients with acute oligoanuric renal failure low AT III-levels due to consumption were often found that lead to diminished protection against intravascular coagulation processes and can therefore contribute to progression of illness. An AT III-substitution may be of some benefit in these patients. Additionally AT III was given in patients with dialysis-dependent renal failure and low levels of AT III leading to a reduced incidence of thrombosis of the extracorporeal system. Unnecessary high doses were also avoided and a minimal heparinization could be performed more efficiently in bleeding risk patients. Furthermore, AT III-levels during renal transplantation and during organ rejection are reported.

Topics: Acute Kidney Injury; Antithrombin III; Antithrombin III Deficiency; Female; Fibrin; Humans; Kidney Diseases; Nephrotic Syndrome; Pregnancy; Puerperal Disorders; Risk; Sepsis; Thromboembolism; Thrombosis

In this short review I have tried to report the literature findings and describe some of our observations on fibrinolysis and atherosclerosis. Although at this time it is difficult to state that diminished FA plays a pathogenic role in atherosclerosis, it certainly seems to represent a risk factor.

Topics: alpha-2-Antiplasmin; Animals; Arteriosclerosis; Blood Coagulation Disorders; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Plasminogen Activators; Thromboembolism; Thrombosis

Soluble crosslinked fibrin derivatives (XDP) in serum were determined by enzyme immunoassay utilizing monoclonal antibodies and compared with serum fibrinogen/fibrin degradation products (FDP) assayed by conventional techniques. In healthy subjects and patients with miscellaneous disorders not usually associated with activation of the haemostasis mechanism, mean XDP levels were 45 and 70 ng/ml respectively. However, elevated levels of XDP occurred in conditions commonly associated with intravascular and possibly extravascular activation of the coagulation system. Markedly raised mean XDP values (677-6900 ng/ml) occurred in treated pulmonary embolism, disseminated neoplasia, severe inflammatory disorders and complicated postoperative states, and lesser but significant elevation (mean 150-400 ng/ml) in treated venous thrombosis, uneventful postsurgical states, localized neoplasia, liver disease and symptomatic arterial disease. Levels during initial streptokinase therapy (mean 24 000 ng/ml) fell tenfold as treatment was continued. The degree of XDP elevation over normal values was significantly higher than that of FDP in conditions with a propensity for venous thrombosis (post-operative states, disseminated neoplasia and inflammatory diseases) than in liver disease, localized neoplasia or patients receiving heparin therapy for venous thromboembolism.

Topics: Adult; Aged; Antibodies, Monoclonal; Blood Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Immunoenzyme Techniques; Inflammation; Liver Diseases; Middle Aged; Neoplasms; Streptokinase; Thromboembolism; Vascular Diseases

Topics: Blood Coagulation Tests; Calcium; Densitometry; Drug Combinations; Fibrin; Fibrinogen; Fibrinolytic Agents; Heparin; Humans; Injections, Subcutaneous; Thrombelastography; Thromboembolism

Topics: Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Fibrinolysis; Glomerulonephritis; Hemostasis; Humans; Liver Cirrhosis; Postoperative Complications; Pulmonary Embolism; Thrombin; Thromboembolism; Thrombophlebitis

In order to evaluate the efficacy of an anticoagulant treatment in neoplasia, we have looked for the existence and the possible role of hemostatic unbalance in patients affected by limited and uncomplicated thyroid and breast cancer by examining hemostasis in 25 patients. Our data allowed us to evidentiate an accelerated and increased fibrinoformation associated with the presence of plasminogen's activation inhibitor which overlaps the increased plasminogen's activators. We evidentiated also an increase of platelet functions in vitro and of their activation in vivo. These findings support the hypothesis of a possible role played by hemostasis alterations in the pathogenesis of thromboembolic complications, cancer growth and/or metastatization, and justify prophylactic and therapeutic anticoagulation.

Topics: Adult; Age Factors; Aged; Anticoagulants; beta-Thromboglobulin; Breast Neoplasms; Female; Fibrin; Fibrinolysis; Hemostasis; Humans; Male; Middle Aged; Platelet Aggregation; Thromboembolism; Thyroid Neoplasms

Congenital dysfibrinogenaemia is described in three members of a family presenting with recurrent thrombosis and in two other young members not yet affected. An abnormality in the polymerization of fibrin monomers was noted. In addition, the pathological fibrin clots were found to be less sensitive to degradation by a post venous occlusion euglobulin solution than normal fibrin. After fibrin clot incubation with lys-plasminogen at different concentrations, the biological activity of plasminogen in patient fibrin clot on S 2251 after SK-addition, was less than that observed with normal fibrin. It is speculated that defective in vivo thrombolysis might explain the recurrent thrombosis observed in this family. This finding represents a new concept in understanding thromboembolic diseases.

Topics: Adolescent; Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Fibrin; Fibrinogen; Humans; Male; Pedigree; Syndrome; Thromboembolism

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: Blood Coagulation; Blood Platelet Disorders; Cerebrovascular Disorders; Fibrin; Fibrinolysis; Humans; Platelet Aggregation; Risk; Thromboembolism

Based on literature reports suggesting the possible incorporation of Tc-99m sulfur colloid (Tc-SC) into fibrin deposits, this study was undertaken to evaluate the potential of this radiopharmaceutical as an imaging agent in thromboembolic disease. Animal models of deep-vein thrombosis and pulmonary embolism were used. The mean thrombus-to-blood (T/B) uptake ratios were comparable for fresh and older thrombi (up to 72 hr). Thrombus uptake was significantly lower in a group of five control dogs that received pertechnetate instead of Tc-SC. Intravenous heparin administration (5,000 IU) 2 hr before injection of Tc-SC caused a depression in T/B ratios but did not totally block Tc-SC uptake. Gamma imaging with Tc-SC allowed demonstration of deep-vein thrombi, but imaging of pulmonary emboli as areas of increased activity was not satisfactory. This study supports the concept of thrombus detection with radiolabeled particles but not the extension of this principle to the imaging of pulmonary emboli.

Topics: Animals; Colloids; Dogs; Evaluation Studies as Topic; Fibrin; Heparin; Lung; Pulmonary Embolism; Radionuclide Imaging; Sulfur; Technetium; Thromboembolism; Thrombosis; Time Factors

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

A qualitatively abnormal fibrinogen was detected in the plasma of a 53 year old woman with severe arterial thrombotic disease. The concentrations of plasma fibrinogen and serum fibrinogen related material were normal. The abnormal fibrinogen was electrophoretically normal. The defects detected were an abnormality of polymerization of fibrin monomers and a decreased rate of release of fibrinopeptide A. The absorption of radiolabelled partially degraded plasminogen on to fibrin prepared from purified fibrinogen Copenhagen was normal.

Topics: Adsorption; Blood Coagulation Tests; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Pedigree; Plasminogen; Polymers; Thromboembolism

Topics: Blood Coagulation Tests; Fibrin; Heparin; Humans; Infusions, Parenteral; Monitoring, Physiologic; Pacemaker, Artificial; Thromboembolism

Coagulation studies in 55 healthy pregnant women indicated that in spite of high coagulation activity, a positive ethanol gelation test for fibrin in plasma is not a normal feature of pregnancy. The four case reports presented stress the value of the ethanol test in monitoring treatment of thromboembolic disease in pregnancy.

Topics: Adult; Blood Coagulation Tests; Ethanol; Female; Fibrin; Fibrinogen; Humans; Pregnancy; Pregnancy Complications, Hematologic; Thromboembolism

Topics: Air; Animals; Anticoagulants; Biocompatible Materials; Blood Physiological Phenomena; Blood Proteins; Chemical Phenomena; Chemistry, Physical; Fibrin; Fibrinogen; Humans; Leukocytes; Models, Biological; Phagocytosis; Platelet Adhesiveness; Platelet Aggregation; Serum Albumin; Surface Properties; Thromboembolism; Tryptophan

Testing for soluble fibrin complexes was performed using a sensitive and reliable haemagglutination assay, with red cells sensitized by fibrin monomers. The principle is based on the fact that the monomers linked to red cells and induce their agglutination. This test, used in clinical trials, has revealed the presence of soluble complexes in every confirmed case of acute DIC, but also in Chronic DIC where diagnosis is difficult to establish (negative ethanol gelation test, normal or sub-normal levels of fibrin breakdown products). In Cirrhosis of the liver, the test gives positive results in a non negligible number of cases. Several hypotheses are made to explain why in certain confirmed cases of DIC, low fibrin breakdown products levels are found.

Topics: Aged; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemagglutination Tests; Humans; Liver Cirrhosis; Male; Prostatic Neoplasms; Solubility; Surgical Procedures, Operative; Thromboembolism

Soluble fibrin monomer complexes (SFMC) were determined in users of different oral contraceptives. Quantitative gel filtration of beta-alanin precipitated plasma samples yielded the relative (per cent of total fibrinogen content) and absolute (mg per 100 ml plasma) amount of SFMC. Increased levels of SFMC were observed in users of oral contraceptives, when compared to age, parity and socioeconomic background matched control groups. This increase was more pronounced in users of Neogynon (0.05 mg ethinyl estradiol, 0.25 mg norgestrel) than in the one using Microgynon (0.03 mg ethinyl estradiol, 0.15 mg norgestrel). Users of Ovulen (0.1 mg mestranol, 1 mg ethynodiol diacetate) in addition to the rise of SFMC levels exhibited elevated fibrinogen levels in plasma. The data presented indicate a limited state of hypercoagulability in users of oral contraceptives.

Topics: Adult; Chromatography, Agarose; Contraceptives, Oral; Female; Fibrin; Fibrinogen; Humans; Thromboembolism

Fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were measured serially in 60 patients heparinized for pulmonary embolism or deep venous thrombosis. Eight patients had recurrent thromboembolism. In patients without recurrence, FDP/fdp and SFC tended to normalize within three to five days. In patients with recurrence, results of both tests were significantly higher on admission, and FDP/fdp values were significantly higher throughout ten days of therapy, than in patients without recurrence. The SFC values were not different between the two groups during the first six days of treatment, but again became significantly higher on the seventh day in patients with recurrence. There were no differences in clotting times, heparin dosage, or any other clinical features between patients with and without recurrence. Measurement of FDP/fdp and SFC can help identify patients at risk of recurrent thromboembolism if performed serially during treatment.

Topics: Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Pulmonary Embolism; Recurrence; Risk; Thromboembolism; Thrombophlebitis

The subunit fibrin composition of thrombi of both venous and arterial origin was examined by sodium dodecyl sulphate gel electrophoresis. The thrombi were recovered by surgical intervention and all had the same fibrin subunit composition. The alpha chains were cross-linked as alpha-chain polymers alpha (p), the gamma chains as gamma-chain dimers (gamma-gamma) while the beta chains were not crosslinked; a further subunit of molecular weight 33 000 was shown to be present in all the fibrins examined and was a degradation fragment of the beta or gamma chains. This data suggests that the crosslinked alpha chains are rate limiting to the lysis of thrombi in vivo. The digestion of pulmonary emboli by plasmin yielded soluble degradation products which were identified as D dimer and E, the latter fragments being the major products obtained by the lysis of in-vitro made plasma clots. The similarity of the composition and lysis of thrombus fibrin to that formed in vitro augurs well for the justification of in-vitro research on mechanisms in thrombolysis.

Topics: Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Humans; Immunoelectrophoresis, Two-Dimensional; Molecular Weight; Peptides; Pulmonary Embolism; Thromboembolism; Thrombophlebitis

In 56 placentas there were fibrin clots in the vessels of the chorionic plate and the stem villi. Fifty infants survived. The fibrin clots in the relatively large placental vessels are considered to be the result of intrauterine shock. A similar pathogenetic concept is postulated as in the well-known diseminated fibrin thromboembolism which is evident in the visceral organs of children who died in the perinatal period. This identification of these fibrin clots in the vessels of the stem villi, especially in cases of so-called risk deliveries, allows the risk for newborn to be determined during their first days of life (hyaline-membrane disease, hemorrhagic diathesis, etc.). One can testify the intrauterine shock by these findings, even in newborn who survive the respiratory distress syndrome.

Topics: Disseminated Intravascular Coagulation; Female; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Hematologic; Respiratory Distress Syndrome, Newborn; Shock; Thromboembolism

Soluble fibrin monomer complexes (SFMC) were determined in 12 patients following delivery, 2, 4, 6 days and 3 months post partum. Quantitative gel filtration (1 per cent agarose) of the beta-alanine-precipitated plasma samples yielded the relative (per cent of the total fibrinogen content) and absolute (milligrams per 100 ml. of plasma) amount of SFMC. During the early puerperium the amount of SFMC remained essentially constant, with average postpartum values of 6.3 +/- 1.2 per cent and 27.6 +/- 9.1 mg. per 100 ml. (mean and standard deviation). Three months after delivery the level of SFMC was significantly (p less than 0.001) decreased (3.3 +/- 1.3 per cent and 8.4 +/- 3.4 mg. per 100 ml.). The quantitative estimation of SFMC in the early puerperium as presented in this study indicates that a state of hypercoagulability can be evaluated by measuring the thrombin-mediated catabolic products of fibrinogen.

Topics: Adult; Female; Fibrin; Fibrinogen; Humans; Postpartum Period; Pregnancy; Puerperal Disorders; Thromboembolism

Topics: Arteriosclerosis; Blood Coagulation; Blood Coagulation Factors; Fibrin; Fibrinolysis; Hemophilia A; Hemostasis; Humans; Thromboembolism; Thrombosis

Soluble fibrin monomer complexes have been determined in approximately 500 obstetric patients by protamine sulfate precipitation, as a test for intravascular coagulation. The incidence of positive fibrin monomer was less than 1% in 139 samples drawn during normal pregnancy. In confirmed abruptio placentae, 84% of samples were positive, but other sources of antepartum bleeding were negative. Positive results were obtained in 24% of samples from patients between 3 and 48 hours after injection of hypertonic saline for second trimester abortion, 33% were positive by only 3% were positive after administration of prostaglandins. The test for intravascular coagulation is simple and rapidly carried out. The results correlated well with the clinical condition of patients with disseminated intravascular coagulation. However, the test is usually negative in patients with thromboembolic phenomena.

Topics: Abruptio Placentae; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Fibrinogen; Humans; Pregnancy; Pregnancy Complications; Pregnancy Complications, Hematologic; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prostaglandins; Protamines; Thromboembolism

Topics: Animals; Fibrin; Fibrinogen; Fibrinolysis; Humans; In Vitro Techniques; Microcirculation; Models, Biological; Plasminogen Activators; Rabbits; Thromboembolism

In a post mortem study of shock-induced changes in the bone marrow, marrow from six different parts of the skeletal system was examined in a total of 109 patients. The comparison of a group of 64 subjects deceased in shock conditions with a control group of 25 deceased without shock showed: In 76,6% of all patients with shock, fibrin networks were found in the sinus and perisinoidal interstice of bone marrow. This can be demonstrated abundantly in every fourth patient with shock. Microthrombi and emboli occluding vessels in the marrow were seen in only 6.3% of the shock cases (controls 0%). The different forms of fibrin precipitates appear most commonly after shock caused by infection. Platelet aggregates in the vessels are seen in 28.2% of all cases with shock (controls 8%). 5% of the cases with shock showed infarction-like necroses of the bone marrow and a further 23% necroses of small cell groups. In every fifth patient with shock, a great number of nucleated blood cells and their precursors were found in the marrow sinus (controls 8%). In a third group of 20 patients with serious illness alledgedly without shock, 45 per cent had a fibrin network when compared with the control group. When several of these findings are present simultaneously, one can apply the term "shock marrow".

Topics: Adult; Aged; Autopsy; Bone Marrow; Bone Marrow Examination; Female; Fibrin; Humans; Male; Middle Aged; Platelet Aggregation; Shock; Shock, Septic; Thromboembolism

Topics: Fibrin; Fibrinolysis; Humans; Protein Conformation; Thromboembolism

Topics: Anticoagulants; Antithrombins; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Cell Aggregation; Ethanol; Fibrin; Fibrinolysis; Gels; Humans; Postoperative Care; Prognosis; Thrombelastography; Thrombin; Thromboembolism; Thrombosis

In 15 out of 35 patients with myelomatosis histological examination showed intravascular fibrin within the glomeruli, and this was associated with proliferation of the mesangial complex in 12. The presence of intravascular fibrin and mesangial proliferation was not associated with any specific immunoglobulin abnormality or with the presence or absence of Bence Jones proteinuria. In addition to fibrin being present within glomerular capillaries it was also shown in intertubular capillaries in three cases of myelomatosis with acute tubular necrosis. It is suggested that intraglomerular coagulation and fibrin deposition may contribute to the genesis of renal failure in myelomatosis.

Topics: Acute Kidney Injury; Autopsy; Bence Jones Protein; Biopsy, Needle; Capillaries; Disseminated Intravascular Coagulation; Female; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin A; Immunoglobulin D; Immunoglobulin G; Kidney; Kidney Glomerulus; Kidney Tubules; Male; Microscopy; Multiple Myeloma; Proteinuria; Retrospective Studies; Thromboembolism; Urea

Topics: Fibrin; Fibrinogen; Humans; Thromboembolism; Thrombophlebitis

Topics: Adolescent; Adult; Buffers; Female; Fibrin; Fibrinogen; Heparin; Humans; Male; Middle Aged; Protamines; Pulmonary Embolism; Sulfates; Thromboembolism; Thrombophlebitis; Thrombosis; Tromethamine

Topics: Disseminated Intravascular Coagulation; Female; Fetal Death; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Liver; Pregnancy; Thromboembolism

Topics: Aminocaproates; Animals; Blood Coagulation; Blood Coagulation Disorders; Chlorides; Densitometry; Disseminated Intravascular Coagulation; Dogs; Endotoxins; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Mercury; Methods; Myocardial Infarction; Protamines; Rabbits; Sulfates; Thromboembolism

Topics: Animals; Blood Platelets; Blood Protein Electrophoresis; Disseminated Intravascular Coagulation; Dogs; Erythrocytes; Escherichia coli Infections; Fibrin; Fibrinolysis; Lipoproteins; Lung; Microcirculation; Neutrophils; Pulmonary Circulation; Sepsis; Thromboembolism; Time Factors; Triglycerides

Topics: Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Humans; Immunoassay; Immunodiffusion; Precipitin Tests; Thromboembolism

Topics: Adult; Aged; Antifibrinolytic Agents; Disseminated Intravascular Coagulation; Factor V; Factor VII; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Middle Aged; Multiple Myeloma; Plasminogen; Thromboembolism

Topics: Afibrinogenemia; Animals; Antibodies; Fibrin; Fibrinogen; Hemorrhage; Humans; Immune Sera; Immunoelectrophoresis; Rabbits; Thromboembolism; Thrombosis

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: Birth Weight; Blood Vessels; Female; Fibrin; Gestational Age; Glycosaminoglycans; Hematoma; Humans; Myofibrils; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications; Rupture, Spontaneous; Thromboembolism; Thrombosis; Umbilical Arteries

Topics: Adrenal Glands; Asphyxia Neonatorum; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Disseminated Intravascular Coagulation; Embryonic and Fetal Development; Fibrin; Fibrinogen; Hemorrhage; Humans; Hypothermia; Infant, Newborn; Liver; Respiration, Artificial; Thromboembolism; Vitamin K Deficiency

Topics: Adolescent; Adult; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Labor, Obstetric; Obstetric Labor Complications; Plasminogen; Postpartum Period; Pregnancy; Stress, Physiological; Surgical Procedures, Operative; Thromboembolism

Topics: Animals; Cattle; Fibrin; Fibrinolysis; Heparin; Plasminogen; Pulmonary Embolism; Thrombin; Thromboembolism

Topics: Animals; Blood Platelets; Fibrin; Fibrinolytic Agents; Humans; In Vitro Techniques; Methods; Microscopy, Electron; Platelet Adhesiveness; Snakes; Thromboembolism; Venoms

Topics: Animals; Antifibrinolytic Agents; Aorta; Arteries; Arteriosclerosis; Capillary Permeability; Cholesterol; Cyclohexanecarboxylic Acids; Fibrin; Fibrinogen; Fibrinolysis; Pulmonary Artery; Rabbits; Thromboembolism

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Coagulation Factors; Cerebral Arterial Diseases; Chromatography; Chromatography, Gel; Diagnosis, Differential; Fibrin; Fibrinogen; Hematoma, Subdural; Humans; Infant; Iodine Radioisotopes; Male; Middle Aged; Molecular Weight; Postoperative Complications; Thromboembolism; Thrombosis

Topics: Animals; Blood Platelets; Cyclohexanecarboxylic Acids; Disseminated Intravascular Coagulation; Dogs; Female; Fibrin; Fibrinolysis; Intestines; Kidney; Liver; Lung; Male; Pancreas; Portal Vein; Shock, Hemorrhagic; Spleen; Thromboembolism; Thrombophlebitis

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

Of 119 neonates dying after 48 hours of life, 19 (16%) showed disseminated fibrin thromboembolism, a histological condition that is very similar to one form of maternal hypofibrinogenaemia. The incidence is nearly five times that among stillbirths and neonates dying within 48 hours of birth. Most of the mothers had a normal pregnancy, labour, and puerperium. One twin may show the condition while the other survives. It is suggested that the affected infants have either no fibrinolytic mechanism, a defective one, or one which for some unaccountable reason was not brought into action. The antecedent plasma fibrinogen level is likely to have been high in some cases, but a fatal outcome can ensue with normal or low levels. The process was considered to be totally responsible for death in six cases (5%) of the series. Renal tubular hyaline droplets apparently rich in haemoglobin were only encountered in one infant (no. 4) who died from massive bilateral adrenal haemorrhage. In the later part of the neonatal period, the process is liable to be indistinguishable clinically from secondary thrombotic processes, which occurred with almost the same incidence in the present series (14(12%) of 119 cases).

Topics: Adrenal Glands; Autopsy; Esophagus; Fibrin; Humans; Infant, Newborn; Infant, Newborn, Diseases; Intestine, Small; Liver; Pituitary Gland; Pulmonary Veins; Renal Veins; Stomach; Thromboembolism; Time Factors

Topics: Animals; Aorta; Blood Cell Count; Blood Platelets; Cyclohexanecarboxylic Acids; Dextrans; Dogs; Fibrin; Fibrinogen; Fibrinolysis; Hematocrit; Heparin; Lung; Methods; Microcirculation; Molecular Weight; Pulmonary Circulation; Thromboembolism

Topics: Animals; Budd-Chiari Syndrome; Dogs; Femoral Artery; Fibrin; Humans; Portal Vein; Pulmonary Embolism; Rabbits; Thrombin; Thromboembolism; Thrombosis; Veins

Topics: Animals; Blood Platelets; Cattle; Fibrin; Heart Valve Prosthesis; Leukocytes; Macrophages; Methods; Postoperative Care; Textiles; Thromboembolism; Tricuspid Valve

Topics: Arteriosclerosis; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Extracorporeal Circulation; Fibrin; Fibrinolysis; Hemorrhage; Heparin; Heparin Antagonists; Humans; Hyperlipidemias; Hypersensitivity; Natriuresis; Osteoporosis; Protamines; Prothrombin Time; Thromboembolism; Thrombophlebitis; Thromboplastin

Topics: Adult; Cardiomegaly; Cardiomyopathies; Electrocardiography; Fibrin; Heart Conduction System; Heart Ventricles; Humans; Male; Radiography, Thoracic; Thromboembolism

Topics: Animals; Blood Coagulation Factors; Cats; Fibrin; Fibrinolysin; Fibrinolysis; Humans; Plasminogen; Prothrombin Time; Streptokinase; Thromboembolism

Topics: Adrenal Gland Diseases; Adult; Afibrinogenemia; Arteries; Cerebral Hemorrhage; Female; Fetal Death; Fetal Diseases; Fibrin; Humans; Infant, Newborn; Liver Diseases; Portal Vein; Pregnancy; Splenic Diseases; Thromboembolism; Umbilical Arteries; Umbilical Cord

Topics: Animals; Blood Coagulation; Blood Platelets; Fatty Acids; Fibrin; Heart; Heart Failure; In Vitro Techniques; Injections, Intravenous; Rabbits; Thromboembolism; Thrombosis

Topics: Angiography; Blood Coagulation Tests; Brachial Artery; Deoxyribonuclease I; Female; Femoral Artery; Fibrin; Fibrinogen; Humans; Injections, Intra-Arterial; Perfusion; Plasminogen; Pregnancy; Puerperal Disorders; Serum Globulins; Streptodornase and Streptokinase; Streptokinase; Subclavian Vein; Thrombin; Thromboembolism; Thrombophlebitis

Topics: Deoxyribonuclease I; Fibrin; Fibrinolysin; Fibrinolysis; Microscopy; Microscopy, Phase-Contrast; Rabbits; Research; Solubility; Streptodornase and Streptokinase; Streptokinase; Thromboembolism

Topics: Fibrin; Humans; Polysaccharides; Pyrogens; Thromboembolism