fibrin and Thrombophlebitis

Venous thromboembolism, comprising deep vein thrombosis (DVT) and pulmonary embolism, is common in Australia and is associated with high morbidity.. This article provides a summary of the risk factors for DVT of the lower limb and discusses the diagnosis of the condition using a diagnostic algorithm incorporating clinical assessment, D-dimer testing and imaging studies. It also briefly reviews the clinical significance of isolated distal lower limb DVT and superficial vein thrombosis.. Many conditions in the lower limb mimic DVT. Diagnosing DVT on clinical grounds without objective testing is unreliable. Patients incorrectly diagnosed as having DVT may be subjected to unnecessary anticoagulation and its associated risks of bleeding. In contrast, there is a risk of thrombus extension and embolisation when DVT is missed or inappropriately treated.

Topics: Agglutination Tests; Algorithms; Anticoagulants; Australia; Enzyme-Linked Immunosorbent Assay; Fibrin; Fibrin Fibrinogen Degradation Products; Health Status Indicators; Humans; Prevalence; Prognosis; Risk Factors; Thrombophlebitis; Ultrasonography; Whole Blood Coagulation Time

There is considerable evidence that the hemostatic system is involved in the growth and spread of malignant disease. There is an increased incidence of thromboembolic disease in patients with cancers and hemostatic abnormalities are extremely common in such patients. Antihemostatic agents have been successfully used to treat a variety of experimental tumors, and several clinical trials in humans have been initiated. Although metastasis is undoubtedly multifactorial, intravascular coagulation activation and peritumor fibrin deposition seem to be important. The mechanisms by which hemostatic activation facilitates the malignant process remain to be completely elucidated. Of central importance may be the presence on malignant cells of tissue factor and urokinase receptor. Recent studies have suggested that these proteins, and others, may be involved at several stages of metastasis, including the key event of neovascularization. Tissue factor, the principal initiator of coagulation, may have additional roles, outside of fibrin formation, that are central to the biology of some solid tumors.

Topics: Animals; Anticoagulants; Antineoplastic Agents; Biomarkers; Blood Coagulation Tests; Cell Adhesion; Cysteine Endopeptidases; Disseminated Intravascular Coagulation; Factor Xa; Fibrin; Fibrinolysis; Hemostasis; Heparin; Humans; Monocytes; Neoplasm Metastasis; Neoplasm Proteins; Neoplasms; Neoplasms, Experimental; Neoplastic Cells, Circulating; Neovascularization, Pathologic; Platelet Activation; Platelet Aggregation Inhibitors; Receptors, Thrombin; Thrombophilia; Thrombophlebitis; Thromboplastin; Vitamin K

The reliability of D-dimer (NycoCard D-dimer) and CRP (C-reactive protein) tests to exclude suspected deep venous thrombosis (DVT) and pulmonary embolism (PE) was investigated in 116 patients. Venography, ultrasonography or ventilation-perfusion lung scanning was used as the control method in 95, 5, and 14 patients, respectively, and pulmonary angiography in two patients, one of whom also underwent lung scanning, the other venography. Of the 116 patients, 52 had thromboembolism (46 DVT and 6 PE). The respective sensitivity, specificity, and negative and positive predictive values (NPV, PPV) were 94%, 27%, 85% and 51% for the D-dimer test, and 80%, 53% 76% and 60% for the CRP test. As venous thromboembolism is a life-threatening condition, the NPV of an exclusion test must lie very close to 100 per cent, and thus the study showed neither the D-dimer nor the CRP test to be a satisfactory exclusion test for use in cases of suspected DVT or PE.

Topics: C-Reactive Protein; Evaluation Studies as Topic; Fibrin; Humans; Predictive Value of Tests; Pulmonary Embolism; Radiography; Sensitivity and Specificity; Thrombophlebitis

Venous valves are more frequent in distal veins and venulae, providing a protecting action against blood skin reflux. Structurally simple, collagen and endothelium, they allow a cavity to be formed by distension, when occlusion occurs. Venous angioscopy can distinguish bicuspid floating valves, reinforced, reinforcing valves with free edges and seat valves as well as the presence of apertures of small collateral vessels in the sinus, of which they play a role in the filling up. Valves are inefficient in supine and in standing among 20% of the adult population. Sinuses allow vortices to be created, low recirculating zones, where blood flow move slowly in niches, at a low shear rate, independently from the main stream. A deep vortex is located in sinus, usually empty, but likely to receive red cell aggregates and leukocytes in the condition of stasis and hyperviscosity. Such a vortex is hypoxic, cause of endothelial activation. In such areas fibrin-leucocytic nidus are created, histologically recognized, of which sub-endothelium has become thick and thrombogenic. Two stages characterized its progression: stage I: a few alteration in the valves, little thrombin generation, taken over by the coagulation inhibitors: AT III, APC and TFPI. Stage II: damaged valves, local consumption of the inhibitors and extended generation of thrombin over the platelets, through factor IXa. Hereditary inhibitor deficits increase the risk (frequent factor Leyden V). When the coagulation cascade is considered, VIIa-tissue factor complex appears to be the thrombotic pathway, leading first to wall linked thrombin, uneasily reached by AT III and facteur IXa non inhibited by TFPI, therefore explaining the platelet extension. Monocytes, which can bear tissue factor, may be "lodged" inside the niches. Besides this important role in deep venous thrombosis, incompetent venous valves are responsible for the skin venous hypertension, a subsequent ground for ulcers. Their role in chronic venous insufficiency is uncertain. In the near future, venous angioscopy will bring about new findings about the pathophysiology of venous valves.

Topics: Fibrin; Hemodynamics; Humans; Leg; Leukocytes; Thrombophlebitis; Veins

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

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

Topics: Antibodies, Monoclonal; Blood Platelets; Fibrin; Humans; Radionuclide Imaging; Thrombophlebitis

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

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

The existence of a system in the human body capable of inducing the dissolution of endogenous pathologically formed thrombi was appreciated in ancient times. Considered in detail in this article are the data that have elucidated the physiologic regulation of which plasmin formation is dependent on, the plasma concentration of plasminogen, availability of activators of plasminogen in the plasma and surrounding tissue environment, the concentration of naturally present inhibitors, and the existence of fibrin in the circulation. Important in this rapidly progressive scientific discipline is consideration of the factors which control the synthesis of the components of this proteolytic enzyme system. Recently abundant information has indicated that this plasminogen-plasmin proteolytic enzyme system can be utilized therapeutically. Knowledge of the mechanisms of this system has permitted identification of agents that can be exogenously administered to releave thrombotic obstruction to blood flow in the venous (pulmonary emboli, deep vein thrombosis) and arterial (peripheral and central vessels) circulatory systems. Particularly important is the demonstration that thrombolytic agents can directly attack and alleviate the immediate cause of acute myocardial infarction. As a result of the innovations in the present decade, it is evident that the plasminogen system can be advantageously employed to reverse the pathologic effects of all thrombotic diseases.

Topics: alpha 1-Antitrypsin; alpha-2-Antiplasmin; alpha-Macroglobulins; Antifibrinolytic Agents; Antithrombin III; Arterial Occlusive Diseases; Arteriosclerosis; Complement C1 Inactivator Proteins; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Kidney Diseases; Liver Diseases; Myocardial Infarction; Neoplasms; Plasminogen; Pulmonary Embolism; Thrombophlebitis

Topics: Anticoagulants; Blood Coagulation Disorders; Blood Platelets; Disseminated Intravascular Coagulation; Factor X; Fibrin; Fibrinolysis; Humans; Neoplasms; Neovascularization, Pathologic; Thrombophlebitis; Thromboplastin

Topics: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Platelets; Blood Vessels; Cardiopulmonary Bypass; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Infant, Newborn; Kidney Diseases; Myocardial Infarction; Neoplasms; Pregnancy; Pulmonary Embolism; Syndrome; Thrombin; Thrombophlebitis; Thrombosis

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: Antigens; Body Weight; Fibrin; Humans; Postoperative Complications; Prognosis; Risk; Serum Globulins; Thrombophlebitis; Time Factors; Varicose Veins

Fibrinogen plays a pivotal role in both the humoral and cellular mechanisms involved in hemostasis. In performing its hemostatic function, fibrinogen in turn is acted on by several independent enzyme systems that either modify its structure or cleave specific fragments of the molecule into the surrounding milieu. Measurements of enzymatically modified fibrinogen or its proteolysis products represent a means whereby the action of these specific enzymes can be quantitated both in vitro and in vivo. Advances in such techniques as protein purification, affinity chromatography, peptide synthesis, and radioimmunoassay technology permit the translation of recently acquired primary structural data on this important protein into sensitive and specific assays for its circulating derivatives. These assay systems are important tools for probing mechanisms of hemostasis and thrombosis.

Topics: Ancrod; Blood Coagulation Tests; Chemical Phenomena; Chemistry, Physical; Chromatography, Gel; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Humans; Kinetics; Leukocytes; Peptide Hydrolases; Pulmonary Embolism; Thrombin; Thrombophlebitis

Topics: Ancrod; Animals; Arteriosclerosis; Blood Viscosity; Disease Models, Animal; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Intermittent Claudication; Thrombophlebitis; Vascular Diseases

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: Adolescent; Adult; Antithrombin III; Blood Coagulation; Blood Coagulation Disorders; Child; Factor IX; Factor V; Factor VIII; Fibrin; Fibrinogen; Humans; Pulmonary Embolism; Thrombophlebitis

Topics: Animals; Blood Platelets; Bromine; Dogs; Fibrin; Fibrinogen; Indium; Iodine Radioisotopes; Isotope Labeling; Leukocytes; Plasminogen; Radionuclide Imaging; Streptokinase; Technetium; Thrombophlebitis; Urokinase-Type Plasminogen Activator

Topics: Administration, Topical; Adolescent; Adult; Aged; Anabolic Agents; Animals; Child; Child, Preschool; Chronic Disease; Endothelium; Ethylestrenol; Female; Fibrin; Fibrinolysin; Fibrinolysis; Follow-Up Studies; Histocytochemistry; Humans; Inflammation; Leg Ulcer; Male; Middle Aged; Phenformin; Purpura; Rats; Skin Diseases; Thrombophlebitis; Vascular Diseases; Wound Healing

Topics: Blood Coagulation Tests; Blood Platelets; Femoral Vein; Fibrin; Fibrinogen; Humans; Iliac Vein; Iodine Radioisotopes; Methods; Phlebography; Plethysmography, Impedance; Thrombophlebitis; Ultrasonics

Topics: Airway Obstruction; Angiography; Animals; Anticoagulants; Dyspnea; Electrocardiography; Fibrin; Fibrinogen; Fibrinolytic Agents; Heart Auscultation; Heparin; Humans; Ligation; Pulmonary Artery; Pulmonary Embolism; Radionuclide Imaging; Thrombophlebitis; Vena Cava, Inferior

Topics: Adenosine Diphosphate; Arteriosclerosis; Basement Membrane; Blood Coagulation; Blood Coagulation Factors; Blood Flow Velocity; Blood Platelets; Collagen; Fibrin; Fibrinolysis; Humans; Platelet Adhesiveness; Thrombophlebitis; Thrombosis

Topics: Adenine Nucleotides; Animals; Anti-Inflammatory Agents; Anticholesteremic Agents; Anticoagulants; Aspirin; Blood Platelets; Butyrates; Dextrans; Dietary Fats; Dipyridamole; Ethylestrenol; Fibrin; Fibrinolytic Agents; Histamine H1 Antagonists; Humans; Phenformin; Phenylbutazone; Platelet Adhesiveness; Povidone; Prostaglandins; Pulmonary Embolism; Rabbits; Streptodornase and Streptokinase; Thrombophlebitis; Thrombosis; Vasodilator Agents; Venoms

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

Topics: Abruptio Placentae; Amniotic Fluid; Embolism, Air; Embolism, Fat; Female; Fetal Death; Fibrin; Humans; Inhalation; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Circulation; Pulmonary Embolism; Pulmonary Heart Disease; Thrombophlebitis

Topics: Adult; Aged; Antibodies, Monoclonal; Female; Fibrin; Humans; Indium Radioisotopes; Male; Middle Aged; Multicenter Studies as Topic; Radionuclide Imaging; Thrombophlebitis

A technique of quantitative venography has been developed in which values are assigned to the deep veins of the calf, knee, thigh, and pelvis, based upon the calculated volume and degree of occlusion of these venous segments. A maximum score of 40 units reflects complete thrombosis of all segments. This technique has been applied to a randomized, single-blind study of streptokinase versus heparin treatment. Each group of 12 patients had similar mean inital venographic scores; follow-up venograms were performed 5 days after the start of therapy. Streptokinase patients with high initial scores (larger than 20) showed a mean improvement of 12.1 units, while those with low initial scores(less than 20) were essentially unchanged. Heparin patients with high scores had a minimal mean improvement of 1.1 units, but those with low scores had a significant mean extension of thrombosis of 8.6 units. Patients with symptoms for less than 7 days showed greated mean improvement (12.7 units) with streptokinase that those with a longer duration of symptoms (2.0 units); heparin patients in these subgroups showed a mean worsening of 7.5 units and no change, respectively. Extrinsic venous obstruction by tumor did not prevent an excellent response to streptokinase. No single test of coagulation of fibriolysis was a reliable indicator of the degree of venographic response to lytic therapy. Pyrexia and hemorrhagic complications occurred in over one-half of the streptokinase patients; one had an anaphylactic reaction, and one died of intracerebral hemorrhage during therapy. The data suggest that lytic therapy is best restricted to the patient with acute extensive thrombosis. Also, continuous infusions of heparin according to current guidelines may be inadequate to prevent thrombus growth in some patients.

Topics: Adolescent; Adult; Blood Coagulation; Clinical Trials as Topic; Drug Evaluation; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Heparin; Humans; Infusions, Parenteral; Injections, Intravenous; Male; Middle Aged; Phlebography; Prothrombin Time; Streptokinase; Thrombophlebitis; Time Factors

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

Topics: Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Clinical Trials as Topic; Dextrans; Factor V; Factor VIII; Female; Fibrin; Fibrinogen; Humans; Hysterectomy; Iodine Radioisotopes; Middle Aged; Pelvic Exenteration; Thrombophlebitis; Thrombosis; Uterine Neoplasms

Fibrin monomer (FM) is a highly sensitive marker of venous thromboembolism and can be used to rule out deep venous thrombosis (DVT) and/or pulmonary embolism in symptomatic outpatients. The aim of the study was to investigate the usefulness of serial fibrin monomer determinations to predict or rule out DVT after total knee arthroplasty in asymptomatic patients. One hundred and thirty consecutive patients underwent total knee replacement. Blood samples were obtained in 104 of them the day before, at days 1, 3, 6 after surgery and at the day of phlebography. Phlebography was performed in all these patients between days 8 and 12 after surgery. There were 44 DVT (44/104, 42%). As compared with the patients without DVT, FM mean levels were 2 and 1.5 times higher in the DVT group at day 3 (P < 0.001) and day 6 (P < 0.01), respectively. However, no useful cut-off values for DVT prediction or exclusion could be determined due to the scattering of the values. Therefore, despite differences between patients with or without DVT, serial FM determinations are of no value for predicting or ruling out DVT in individual patients undergoing total knee arthroplasty.

Topics: Arthroplasty, Replacement, Knee; Biomarkers; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Predictive Value of Tests; Thrombophlebitis

A new diagnostic test has recently become available which is highly specific for plasma soluble fibrin polymers, the thrombus precursor protein (TpP) enzyme immunoassay. In order to evaluate the diagnostic accuracy of this test and that of a new rapid and automated test for the determination of D-dimers, the BC D-dimer test, in patients with clinically suspected deep vein thrombosis (DVT), 70 consecutive symptomatic patients underwent laboratory analysis with both tests and with the classic enzyme-linked immunosorbent assay (ELISA) D-dimer test, followed by the execution of a compression ultrasound (CUS) test of the affected limb. Patients with a positive CUS test were considered to have DVT (20 of 70), whereas those with a serially negative test and an uneventful 3-month follow-up test were regarded as not having DVT (50 of 70). The sensitivity of the TpP test (45.0%) was significantly lower than that of both the BC D-dimer test (80.0%; P = 0.02) and the classic ELISA test (90.0%; P = 0.002). The specificity of the TpP test (66.0%) did not differ from that of either D-dimer test (60.0 and 64.0%, respectively). The negative predictive value of the TpP test (75.0%) was significantly lower than that of the classic ELISA D-dimer test (94.1%; P = 0.02), which in turn did not differ from that of the BC D-dimer test (88.2%). The positive predictive value was similarly low for each investigated test (34.6, 44.4, and 50.0%, respectively). In conclusion, the TpP test can neither be used to detect a DVT nor to exclude its development in patients with the clinical suspicion of this disease. By contrast, the BC D-dimer might safely replace the classic ELISA test for excluding DVT in symptomatic patients.

Topics: Adult; Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Sensitivity and Specificity; Thrombophlebitis

Accurate non-invasive diagnosis of deep venous thrombosis and pulmonary embolism remains an elusive goal. Radiolabeled antibodies specific for the epitope exposed on the beta-chain of fibrin after fibrino-peptide B release (anti-beta) enabled in situ imaging of thrombi in experimental subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi. We postulated that the neoepitope on the beta-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-beta monoclonal antibody to fibrin in various stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fibrin beta-chains. The percentage of beta-chains exposed to the antibodies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium.. The beta-chain amino terminus of fibrin is exposed transiently as subunits are added to the enlarging fibrin network. Anti-beta antibodies bind preferentially to actively enlarging fibrin polymers.

Topics: Antibodies, Monoclonal; Antigen-Antibody Reactions; Biopolymers; Fibrin; Fibrinolytic Agents; Heparin; Humans; Peptide Fragments; Pulmonary Embolism; Thrombophlebitis

NF-6505, a bi-O-Tyr-sulfated decapeptide, which specifically interacts with the anion-binding exosite of the thrombin molecule, was chemically synthesized and assessed for its antithrombotic effects in vitro and in vivo. The IC50 value of this peptide on fibrin-clot formation in vitro was about 0.05 microgram/ml, which indicated a potency similar to that of a recombinant hirudin. NF-6505 caused a 2-fold prolongation of activated partial thromboplastin time when intravenously administered at 1 mg/kg in rats. In a rat venous thrombosis model, a bolus intravenous administration of this peptide dose-dependently inhibited the thrombus formation with an ED50 value of 0.03 mg/kg, a value smaller than that of recombinant hirudin (ED50 = 0.1 mg/kg) or of argatroban (ED50 = 0.2 mg/kg). These results suggest that NF-6505 is a highly potent and safe agent for the clinical treatment of venous thrombosis diseases.

Topics: Amino Acid Sequence; Animals; Anions; Binding Sites; Blood Coagulation; Disease Models, Animal; Fibrin; Hirudins; Humans; In Vitro Techniques; Injections, Intravenous; Male; Oligopeptides; Partial Thromboplastin Time; Rats; Rats, Sprague-Dawley; Thrombin; Thrombophlebitis

This study was performed to determine whether antibodies against the amino-terminus of the beta-chain of fibrin (anti-beta) could noninvasively distinguish actively enlarging thrombi from thrombi stabilized with anticoagulants.. Dogs with unilateral femoral vein thrombi were allocated into three groups: (1) no anticoagulation, (2) intravenous heparin maintained in the "therapeutic" range (0.2 to 0.5 U/mL plasma), and (3) "excess" heparin, maintained at >1.0 U/mL plasma. Thrombolysis was suppressed with tranexamic acid. (111)In-labeled anti-beta was infused, and gamma scans of the legs were performed at regular intervals for 24 hours. Scans were interpreted in a blinded fashion. In addition, for each scan, the number of gamma counts from the femoral area on the thrombosed side was compared with the contralateral side. Clot/blood isotope density was determined postmortem. Leg thrombi in the no-anticoagulation group were 100% detectable, mean (+/-SD) relative count in the thrombosed femoral area was 186% (+/-30%) of the contralateral side, and clot/blood ratio was 14.7 (+/-2.0). Thrombi in the therapeutic heparin group were only 75% detectable, relative counts in the thrombosed femoral areas decreased to 125% (+/-20%), and clot/blood ratio declined to 11.3 (+/-3.5). In the "excess heparin" group, leg thrombi were only 50% detectable, the thrombosed femoral area had relative counts of 118%+/-17%, and the clot/blood ratio fell to 7.8+/-1.9.. Radiolabeled anti-beta noninvasively distinguishes propagating thrombi from those stabilized by anticoagulants. They may be useful for detecting thrombosis clinically as well as for monitoring the efficacy of anticoagulation.

Topics: Animals; Antibodies, Monoclonal; Dogs; Fibrin; Heparin; Indium Radioisotopes; Radioimmunodetection; Thrombophlebitis

The objectives of the study were to determine whether the combination of a negative SimpliRED D-dimer assay and a low soluble fibrin result reliably excludes venous thromboembolism, and whether patients with proven venous thromboembolism and a normal SimpliRED D-dimer have evidence of impaired fibrinolysis. The study was a retrospective analysis of a cohort of 262 consecutive patients, 94 patients presenting with suspected deep venous thrombosis and 168 with suspected pulmonary embolism. Fifty-nine patients (22.5%) were classified as venous thromboembolism-positive, 27 with pulmonary embolism, and 32 with deep venous thrombosis. One hundred and fourteen patients (43.5%) had SimpliRED D-dimer and a soluble fibrin result of less than or equal to 2.0 microg/ml; the negative predictive value was 98.2% (95% confidence interval: 93.8-99.8%), and the likelihood ratio was 0.06. Eight patients with proven venous thromboembolism had a negative SimpliRED D-dimer; all had elevated ELISA D-dimer levels and six had elevated soluble fibrin levels. This suggests that patients with venous thromboembolism and a normal SimpliRED result do not have impaired fibrinolysis as a cause of their false-negative result. This study suggests that the combination of SimpliRED and soluble fibrin can be used to exclude venous thromboembolism in over 40% of patients who present with a clinical suspicion of deep venous thrombosis or pulmonary embolism and that the small group of patients with venous thromboembolism and a normal SimpliRED do not have impaired fibrinolysis.

Topics: Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Point-of-Care Systems; Predictive Value of Tests; Thrombophlebitis

Diagnostic and therapeutic procedures utilizing the high affinity streptavidin (SA)/biotin system are being investigated for in vivo use. We are developing a rapid two-step imaging technique for the diagnosis of deep venous thrombosis and pulmonary embolism. The optimal SA-bound targeting moiety would circulate adequately for sufficient lesion accumulation, but nonbound reagent would clear in a reasonably short time before the injection of radiolabeled biotin. The objective of this study was to cross-link SA and galactose-modified SA to GC4 antifibrin monoclonal antibody and to study the pharmacokinetics and biodistribution of the radiolabeled GC4-SA conjugates after injection into rabbits. A cross-linking method was developed for the synthesis of the GC4-SA conjugates via the addition reaction of sulfhydryl containing SA derivatives with maleimide-GC4. In vivo, radiolabeled trigalactose modified SA-GC4 exhibited a much faster blood clearance compared to mono-galactose modified GC4-SA or GC4-SA containing no galactose.

Topics: Animals; Antibodies, Monoclonal; Bacterial Proteins; Fibrin; Galactose; Iodine Radioisotopes; Pulmonary Embolism; Rabbits; Radioimmunodetection; Streptavidin; Thrombophlebitis

Evidence of activation of coagulation was sought in serial plasma samples from 25 ABMT candidates with malignant lymphoma admitted for bone marrow harvesting: 10 females and 15 males, median age 41 years (range 27-58 years). Nineteen patients had non-Hodgkin's lymphoma (NHL) and six had Hodgkin's disease. Of those with NHL, 14 had high-grade and five low- grade disease. The plasma levels of markers of activation (prothrombin fragment 1 + 2, thrombin-antithrombin complexes, fibrinopeptide A and fibrinmonomers) increased significantly (P < 0.001) in association with harvesting. Except for fibrinopeptide A, the indicators of activation were still significantly elevated 24 h after marrow aspiration. Beta-thromboglobulin, a marker of the platelet release reaction, also increased significantly (P < 0.01). Four out of nine patients in whom a long-term central venous catheter was inserted just after marrow aspiration, developed catheter-related deep vein thrombosis, verified venographically, shortly after harvesting. These results suggest that patient with malignant lymphoma undergoing marrow harvesting develop a hypercoagulable state, and that insertion of a central intravenous catheter immediately after marrow harvesting should be avoided to prevent the development of symptomatic deep vein thrombosis.

Topics: Adult; Anticoagulants; Antithrombin III; beta-Thromboglobulin; Biomarkers; Blood Coagulation; Bone Marrow Transplantation; Catheterization, Central Venous; Circadian Rhythm; Female; Fibrin; Fibrinolysis; Fibrinopeptide A; Heparin; Hodgkin Disease; Humans; Ilium; Lymphoma; Lymphoma, Non-Hodgkin; Male; Middle Aged; Peptide Fragments; Peptide Hydrolases; Plasminogen Activator Inhibitor 1; Platelet Count; Premedication; Prothrombin; Sternum; Subclavian Vein; Thrombophlebitis; Transplantation, Autologous; Wounds and Injuries

Five cases of spontaneous thrombosis of a palmar digital vein are presented. The patients, all female, complained of a tender and unsightly lump over the digital palmar surface at the proximal interphalangeal joint level. Two fingers were affected in one patient. None could recall any history of trauma. In four cases a surgical excision was carried out. Histology confirmed the intraoperative findings of thrombosis of a superficial digital vein in every case. All patients are free from recurrence at a mean follow-up of 2.5 years.

Topics: Adult; Aged; Diagnosis, Differential; Erythrocytes; Female; Fibrin; Finger Joint; Fingers; Follow-Up Studies; Humans; Middle Aged; Recurrence; Synovial Cyst; Thrombophlebitis; Veins

In a prospective study, plasma levels of soluble fibrin (SF) were assessed in 97 patients with colorectal cancer immediately before and 1, 2, 7, and 90 days after surgery, 18 patients undergoing surgery for benign colorectal disease serving as controls. Age distribution, routine blood analysis, duration of surgery, perioperative blood loss and anaesthesia was similar in the two groups. SF was quantitated using a commercial enzyme-linked immunosorbent assay. The preoperative plasma level of SF was normal in cancer patients as a whole. However, patients with disseminated colorectal cancer had higher levels of SF preoperatively compared to patients with localized colorectal cancer (p < 0.01) and controls (p < 0.005). On days 1, 2, and 7 days postoperatively, a rather pronounced increase in plasma SF was observed in cancer patients as well as in the controls. Three months after surgery, plasma SF had normalized in controls and in patients undergoing curative cancer treatment. Postoperative deep venous thrombosis (DVT) was detected in 23% of the cancer patients by means of phlebography. The preoperative values of SF in these patients were higher compared to patients not developing DVT (p < 0.05). Patients with colon cancer displayed higher SF in plasma than patients with rectal cancer (p < 0.05).

Topics: Adult; Age Distribution; Aged; Aged, 80 and over; Case-Control Studies; Colonic Diseases; Colorectal Neoplasms; Female; Fibrin; Humans; Male; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies; Rectal Diseases; Solubility; Thrombophlebitis

This study was designed to test the hypothesis that the detection of non-blood-pool localization due to deep venous thrombosis uptake can be enhanced by computer processing.. Immediate blood-pool and 90-min delay images from 25 patient studies obtained with 99mTc T2G1s antifibrin were paired into 125 image sets (5/pt, including A, P knees, A, P calves and A thighs). After spatially aligning the image pairs, the blood-pool activity obtained from the immediate image was removed from the delayed image to produce a "clot only" image. Unprocessed data (UnP) and computer processed images (CmP) were presented to novice readers as part of a receiver operator characteristic (ROC) comparison study. The image interpreters were asked to provide independent diagnostic assessment at 250 limb sites using both datasets. Image intensity and color scale mappings were freely adjustable. Three readers were presented with images adjusted with optimal image contrast as judged by an observer with knowledge of the correct response.. The area under the ROC curve (Az), a measure of the method's accuracy, for these readers was 88.5% (UnP) and 88.8% (CmP) (p = ns). Four readers whose images were not optimized showed Az of 79.1% (UnP) and 90.7% (CmP) (p < 0.05). Average diagnostic decision time for all readers, per limb site, was 18.2 +/- 7.8 sec, m +/- s.e.m., (UnP) and 7.6 +/- 4.6 sec (CmP).. Novice reader accuracy is improved with computer processed images when image intensity and contrast factors are important. Computer processing can provide "clot" images that minimize nonspecific blood background activity and allow greater interpreter decision speed/confidence.

Topics: Algorithms; Antibodies, Monoclonal; Fibrin; Humans; Image Processing, Computer-Assisted; Leg; Radiography; Radioimmunodetection; ROC Curve; Technetium; Thrombophlebitis

The objective of this study was to determine the clinical utility of an enzyme immunoassay (EIA) for soluble fibrin in patients with clinically suspected deep vein thrombosis (DVT).. 101 unselected patients with clinically suspected DVT underwent blood sampling for measurement of plasma levels of soluble fibrin, and objective testing for DVT. According to results of the objective tests, patients were classified as DVT-positive (n = 34) or DVT-negative (n = 67). Using different cut-points of soluble fibrin results, the sensitivities, specificities, positive and negative predictive values of the soluble fibrin assay were calculated. A soluble fibrin result of < or = 0.75 mg/ml showed a sensitivity and negative predictive value of 100%, and a specificity of 17.9% for DVT, a soluble fibrin result of < or = 1.40 mg/ml showed a sensitivity of 91.2% and a negative predictive value of 93.6%, and a specificity of 65.7% for DVT, whereas a soluble fibrin result of < or = 8.0 mg/ml showed a specificity and positive predictive value of 100% for DVT.. This study demonstrates that the soluble fibrin assay used in the study has potential clinical utility as a diagnostic test in patients with clinically suspected DVT and supports further evaluation of this assay.

Topics: Evaluation Studies as Topic; Female; Fibrin; Humans; Immunoenzyme Techniques; Likelihood Functions; Male; Predictive Value of Tests; Retrospective Studies; Sensitivity and Specificity; Solubility; Thrombophlebitis

Various assays have been developed for quantitation of soluble fibrin or fibrin monomer in clinical plasma samples, since this parameter directly reflects in vivo thrombin action on fibrinogen. Using plasma samples from healthy blood donors, patients with cerebral ischemic insult, patients with septicemia, and patients with venous thrombosis, we compared two immunologic tests using monoclonal antibodies against fibrin-specific neo-epitopes, and two functional tests based on the cofactor activity of soluble fibrin complexes in tPA-induced plasminogen activation. Test A (Enzymun-Test FM) showed the best discriminating power among normal range and pathological samples. Test B (Fibrinostika soluble fibrin) clearly separated normal range from pathological samples, but failed to discriminate among samples from patients with low grade coagulation activation in septicemia, and massive activation in venous thrombosis. Functional test C (Fibrin monomer test Behring) displayed good discriminating power between normal and pathological range samples, and correlated with test A (r = 0.61), whereas assay D (Coa-Set Fibrin monomer) showed little discriminating power at values below 10 micrograms/ml and little correlation with other assays. Standardization of assays will require further characterization of analytes detected.

Topics: Antibodies, Monoclonal; Brain Ischemia; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation Studies as Topic; Fibrin; Humans; Plasminogen; Reagent Kits, Diagnostic; Sepsis; Solubility; Spectrophotometry; Thrombophlebitis

Reversible aggregation of red blood cells (RBC) plays an important role in determining blood flow properties, and it is this aggregation which increases blood viscosity at low shear rates. The structure and sites of venous thrombi, as well as the fact that stasis is a major predisposing factor in venous thrombosis, suggest a strong association between vein thrombosis, slow blood flow and increased blood viscosity. RBC aggregation and disaggregation were measured (SEFAM erythroaggregameter, France) in 54 patients with a history of unexplained leg vein thrombosis. Results were compared to those of controls classified according to age. Increased RBC aggregability was observed in 41% of the patients, and the mean values indicated a significant elevation of RBC aggregability in patients when compared with controls (P < 0.05). Subgroups were compared to study the influence of thrombus recurrence and thrombosis type (deep versus superficial vein thrombosis) on the aggregation parameters. No significant difference was found between these subgroups. The use of compression stockings and veinotropic drugs tended to reduce the abnormalities in RBC aggregability (P < 0.05). An increase in RBC aggregability and in the shear resistance of RBC aggregates, by predisposing to circulatory stasis, is likely to contribute to the evolution and complications of leg vein thrombosis.

Topics: Adult; Bandages; Blood Viscosity; Cardiovascular Agents; Chronic Disease; Erythrocyte Aggregation; Female; Fibrin; Hematocrit; Humans; Leg; Male; Middle Aged; Thrombophlebitis; Venous Insufficiency

Patients with peripheral arterial disease have a high risk of death from cardiovascular events. As defective fibrinolysis associated with leg atherosclerosis has been suggested as a predisposing factor, we sought a relation among decreased fibrinolysis, the presence of leg atherosclerosis and the incidence of thrombotic events in a case-control study nested in the PLAT. Fifty-eight patients with coronary and/or cerebral atherothrombotic disease, free of leg atherosclerosis at Doppler examination, were compared with 50 atherosclerotic patients with leg involvement. High D-dimer (153.0 vs 81.3 ng/ml, p < 0.001) and tPA antigen before venous stasis (14.4 vs 11.8 ng/ml, p < 0.03), and low tPA antigen (6.7 vs 15.6 ng/ml, p < 0.01) and fibrinolytic activity released after venous stasis (fibrinolytic capacity: 113.2 vs 281.4 mm2, p < 0.001) were found in patients with leg atherosclerosis. D-dimer and fibrinolytic capacity, in addition to age, were selected by stepwise discriminant analysis as characterizing patients with leg atherosclerosis. Moreover, higher D-dimer and tPA inhibitor characterized patients with leg atherosclerosis who subsequently experienced thrombotic events. These findings constitute evidence of high fibrin turnover and impaired fibrinolytic potential in patients with leg atherosclerosis. Thus impaired fibrinolysis may contribute to the prothrombotic state in these patients.

Topics: Aged; Arteriosclerosis; Blood Glucose; Blood Pressure; Blood Proteins; Case-Control Studies; Disease Susceptibility; Fibrin; Fibrinolysis; Humans; Leg; Lipids; Male; Middle Aged; Peripheral Vascular Diseases; Prospective Studies; Risk Factors; Smoking; Thrombophlebitis

We evaluated the interpretation, reliability and usefulness of 99m technetium labelled antifibrin immunoscintigraphy for the diagnosis of deep vein thrombosis in the lower limbs.. The diagnostic value of 99m technetium labelled antifibrin immunoscintigraphy was assessed in 44 patients with suspected venous thrombosis. The reference examination was bilateral ascending phlebography; 40 patients had doppler ultrasonography of the veins; 0.5 mg of antibody labelled by 17.5 mCi on average of 99m technetium were injected intravenously, and serial scintigraphic images were collected 1 min, 90 min and 18 hours after injection.. The best results were obtained by comparison between the 90 min and the immediate post-injection images, with 86 percent sensitivity, 73 percent specificity and 81 percent accuracy. Heparin therapy and past history of phlebitis had no influence on the results. The doppler ultrasonography/immunoscintigraphy combination had a 100 percent specificity. 99m Technetium labelled antifibrin immunoscintigraphy had about the same diagnostic value as 111 indium labelled antifibrin immunoscintigraphy.. The introduction of 99m technetium as isotopic marker will make immunoscintigraphy easier and available in numerous nuclear medicine centres. Antifibrin immunoscintigraphy can be an additional diagnostic tool for the difficult diagnosis of deep vein thrombosis.

Topics: Adult; Aged; Antibodies; Female; Fibrin; Humans; Male; Middle Aged; Organotechnetium Compounds; Phlebography; Radionuclide Imaging; Thrombophlebitis; Ultrasonography

Topics: Aged; Ancrod; Blood Coagulation; Cardiopulmonary Bypass; Fibrin; Heparin; Humans; Male; Thrombocytopenia; Thrombophlebitis; Time Factors; Whole Blood Coagulation Time

The aim of this study was to investigate the interactions of t-PA and plasminogen with fibrin derived from an abnormal fibrinogen detected in a 40-year-old male patient who had had an episode of thrombophlebitis with pulmonary embolism. An abnormal fibrinogen was diagnosed on the basis of prolonged thrombin and reptilase times also detected in two other family members. Fibrinogen purified from plasma, in the presence of protease inhibitors, by glycine precipitations, gel filtration and affinity chromatography, was devoid of plasminogen, fibronectin, and vWf. SDS-PAGE analysis according to Laemmli under reducing conditions, showed an abnormal gamma chain (approximately 50% of the total) migrating in a more anodic position (M(r) 48 kDa). By PCR amplification and DNA sequencing, the abnormality was identified as an Asn308-->Lys mutation of the gamma chain. Since such a mutation constitutes a new plasmin cleavage site as first reported for fibrinogen Kyoto I, it may modify interactions of plasminogen and t-PA with carboxy-terminal lysine residues. Ligand-binding studies were therefore performed using intact and plasmin-degraded fibrin surfaces obtained from the abnormal fibrinogen. The plasminogen and t-PA binding isotherms obtained with the abnormal fibrinogen were similar to the control. Moreover, the stimulation by fibrin of plasminogen activation by t-PA was not different from the control. These results suggest (i) that the lysine 308 residue may not be exposed to plasmin cleavage in fibrin, and (ii) that the thrombotic accident of the propositus cannot be explained by an abnormality of the plasminogen/t-PA binding to fibrin.

Topics: Adult; Base Sequence; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogens, Abnormal; Hemostasis; Humans; Male; Molecular Sequence Data; Mutation; Pedigree; Plasminogen; Polymerase Chain Reaction; Pulmonary Embolism; Sequence Analysis, DNA; Thrombin Time; Thrombophlebitis; Tissue Plasminogen Activator

Eighteen patients with suspicion of deep venous thrombosis (DVT) in the lower extremities were imaged both with autologous 99mTc-HMPAO-labeled platelets (Tc-PLT) and 111In-labeled monoclonal antifibrin antibodies (In-MoAbs) on the same day. Presence or absence of thrombosis was verified by venography. Tc-PLT was given i.v. followed after 30 min by In-MoAbs. Anterior and posterior projections of the lower extremities were obtained with a large field-of-view gamma camera at 5 to 25 min, 2 h, 4 to 6 h, and 20 h after administration of the marker. Both Tc-PLT and In-MoAbs detected DVT well but less frequently than venography. Thrombi were visualized at 2 to 4 h after injection. The quality of images was better with Tc-PLT than with In-MoAbs. In the patients treated during the study, heparin significantly (p < 0.01) inhibited the uptake of Tc-PLT but not of In-MoAbs. We conclude that both Tc-PLT and In-MoAbs are suitable agents for the detection of DVT especially in patients without anticoagulation.

Topics: Adult; Aged; Antibodies, Monoclonal; Blood Platelets; Female; Fibrin; Humans; Indium Radioisotopes; Male; Middle Aged; Organotechnetium Compounds; Oximes; Phlebography; Radionuclide Imaging; Technetium Tc 99m Exametazime; Thrombophlebitis

To study blood compatibility of venous prosthesis made of textile or non-textile material, the inferior vena cava of 37 rabbits was partly replaced by 3 mm internal diameter synthetic tube graft made of textile material (T: woven tetron) or non-textile material (P: polytetrafluoroethylene). At designated time intervals after the replacement (5 hours to 4 weeks), graft patency was examined and the dry weight of intraluminal deposits was measured. The harvested grafts were then subjected to light and scanning electron microscopy. All the T-grafts were occluded as early as 5 hours after grafting but when ticlopidine was administered prior to the grafting, all the grafts were patent. All the P-grafts were patent up to 4 weeks after grafting, though the amount of intraluminal deposits was increased in a time related manner, narrowing the lumen of the grafts. The luminal surface of the P-grafts harvested at 5 hours after grafting was covered by piles of fibrin networks entrapping erythrocytes without an association of platelet aggregates, which resembles the finding in the T-grafts harvested from the ticlopidine treated rabbits. In the P-grafts, both the proximal and distal luminal surfaces near the anastomosis were fully covered with endothelial cells by 2 weeks and the entire luminal surface was covered with these cells by 4 weeks. From these results, the following conclusions were obtained; (1) P-graft was superior to T-graft for venous prosthesis, which is mainly due to the inertness of P against platelet activation. (2) Though the luminal surface of the P-grafts was completely covered with endothelial cells by 4 weeks after grafting, the lumen was markedly narrowed by intimal hyperplasia.

Topics: Animals; Biocompatible Materials; Blood Vessel Prosthesis; Endothelium, Vascular; Erythrocytes; Fibrin; Graft Occlusion, Vascular; Male; Microscopy, Electron, Scanning; Platelet Activation; Polyethylene Terephthalates; Polytetrafluoroethylene; Rabbits; Thrombophlebitis; Ticlopidine; Vena Cava, Inferior

Levels of plasma crosslinked fibrin derivatives, a sensitive and direct marker of the lysis of intravascular crosslinked fibrin, were measured serially in 135 patients undergoing major abdominal surgery to determine their behavior and their use as a screening test for postoperative venous thrombosis. Preoperative levels and levels on the first postoperative day were significantly higher by both enzyme immunoassay and latex assay in 31 patients who developed venous thrombosis (positive venography) than in 104 patients who did not (negative 125I fibrinogen leg scan). Preoperative XLFDP levels 400 ng/ml (enzyme immunoassay) had a sensitivity to the diagnosis of postoperative venous thrombosis of 58%, specificity 74%, positive predictive value 41% and negative predictive value of 85%. The sensitivity of XLFDP levels over 1200 ng/ml on the first postoperative day was 65%, specificity 73%, positive predictive value 38% and negative predictive value 89%. These cutoff values were chosen (high negative predictive value) to allow identification of patients who were unlikely to have venous thrombosis. Measurement of plasma XLFDP, a simple inexpensive test, could be used as a screen to select patients for surveillance procedures (IPG or duplex ultrasonography). A substantial increase in XLFDP levels (greater than 500 ng/ml) occurred in virtually all patients, suggesting that fibrinolysis is not 'shutdown' postoperatively and that these assays reflect lytic activity at the fibrin surface more accurately than do measurements of plasminogen activators and their inhibitors.

Topics: Abdomen; Adult; Female; Fibrin; Heparin; Humans; Macromolecular Substances; Male; Mass Screening; Postoperative Complications; Predictive Value of Tests; Sensitivity and Specificity; Sex Characteristics; Thrombophlebitis

Topics: Adolescent; Adult; Antithrombin III; Antithrombin III Deficiency; Female; Fibrin; Humans; Male; Peptide Hydrolases; Thrombin; Thrombophlebitis; Time Factors

The incidence of pericapillary fibrin cuffs was investigated in 49 biopsies of venous leg ulcers and 67 biopsies of leg ulcers of non-venous etiology. Pericapillary fibrin cuffs were seen in 28 biopsies (57.1%) of venous leg ulcers, but only in 11 biopsies (16.4%) of non-venous leg ulcers. In the venous leg ulcers pericapillary fibrin cuffs occurred predominantly near the ulcer surface and around dilated capillaries. Dilation of the capillaries and inflammation probably contribute more to the pathogenesis of pericapillary fibrin cuffs than venous hypertension.

Topics: Capillaries; Fibrin; Humans; Leg Ulcer; Skin; Thrombophlebitis; Varicose Ulcer

The recent development of monoclonal antibodies against components of coagulated blood may provide new approaches to the diagnosis of venous thrombosis. Scanning with an indium-111-labeled Fab fragment of a murine monoclonal antifibrin antibody (59D8) and ascending contrast venography were performed in 33 patients. Images of the calves, popliteal fossae, thighs, and pelvis were obtained immediately, 4-6 hours, and 24 hours after injection of 2 mCi (74 MBq) of the antibody. All images were read in a blinded manner. Findings in both studies were positive in 28 patients and negative in three. In 19 patients not undergoing heparin therapy, 19 specific anatomic sites were positive on venograms and 29 were positive on antibody images (19 sites matched). In 14 patients undergoing heparin therapy, 34 sites were positive on venograms and 27 were positive on antibody images (22 sites matched). In most patients, positive results were noted within 1 hour of antibody injection. No adverse effects were noted with the antibody preparation. Preliminary data suggest that antifibrin antibody imaging is sensitive in detecting clots, is safe to use, and may have a role in diagnosing and managing venous thrombosis.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Fibrin; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Indium Radioisotopes; Male; Middle Aged; Radionuclide Imaging; Thrombophlebitis

Deep venous thrombosis remains a major medical problem, affecting a large segment of the population and resulting in significant mortality and morbidity. Current techniques available for detecting deep venous thrombosis present limitations that may mitigate their potential benefit to the patient. Invasive techniques, such as ascending contrast venography, carry risks to the patient with regard to complications such as an allergic reaction to an iodine dye, adverse effects to renal functions, and clot formation in a normal vein. Noninvasive techniques, such as Doppler ultrasound and impedance plethysmography, evaluate only a limited segment of the venous bed. The need remains for a diagnostic technique that is safe, accurate, and widely accessible. A readily available noninvasive scintigraphic technique utilizing radiolabeled monoclonal anti-fibrin antibody may overcome some of these shortcomings. This imaging examination is quite effective in detecting clots in the lower extremities. Compared to contrast venography, 111In-labeled anti-fibrin antibody imaging appears to be as sensitive in identifying acute venous thrombosis. In addition, the preliminary data indicate that anticoagulation with heparin may interfere with adequate visualization of the clots with this technique.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Female; Fibrin; Humans; Iodine Radioisotopes; Magnetic Resonance Imaging; Male; Middle Aged; Plethysmography, Impedance; Radionuclide Imaging; Thrombophlebitis; Ultrasonography

The influence of an acute phase reaction on the size, weight, and fibrin content of experimental venous thrombi was examined in 10 pairs of rabbits. Jugular vein thrombosis was provoked by venous stasis plus mechanical injury 36 hours after one member of each pair received 0.5 ml/kg sterile turpentine in olive oil by subcutaneous injection. Fibrinogen level, factor VIII activity, and antithrombin III activity were significantly higher at the time of thrombus formation in turpentine treated rabbits, as were thrombus size (assessed by visual scoring), dry weight of thrombi, and their fibrin content (derived by measuring 125I-fibrinogen incorporation). In addition, the fibrinogen concentration correlated significantly with size, weight, and fibrin content of thrombi when results from turpentine treated and control animals were pooled, suggesting that plasma fibrinogen concentration at the time of thrombus formation may strongly influence the extent of thrombosis. This effect could help explain observations of a "hypercoagulable state" after injury.

Topics: Acute-Phase Reaction; Animals; Antithrombin III; Factor VIII; Fibrin; Fibrinogen; Inflammation; Rabbits; Thrombophlebitis; Turpentine

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

Topics: Aged; Antibodies, Monoclonal; Fibrin; Humans; Male; Technetium; Thrombophlebitis

For many years intensive efforts to reliably image thrombi by radionuclide techniques have been unrewarding. Recently, however, monoclonal antibodies to platelet cell-surface antigens and to fibrin polymer have emerged as potent thrombus imaging agents in experimental animals. In Britain antiplatelet antibody has been successful in clinical trials, as has antifibrin in the United States. It is to be hoped that radiolabeled antibody technology will evolve to the point where it can detect thrombi anywhere, including the lungs and brain. The relative efficacy of radionuclide thrombus detection and Doppler ultrasonography is currently undefined.

Topics: Animals; Antibodies, Monoclonal; Blood Platelets; Dogs; Fibrin; Humans; Radionuclide Imaging; Thrombophlebitis

A new monoclonal antibody specific for the beta-chain of human fibrin (C22A) and labeled with 111In has been obtained and successfully used in rabbits and dogs for the in vivo detection of venous thrombosis. Studies in humans are currently ongoing. In order to assess the diagnostic value of 111In-antifibrin for the detection of venous thrombosis of the lower extremities, the authors investigated 25 consecutive patients. Ten patients had clinical and instrumental (contrast phlebography and duplex scanning) evidence of acute deep venous thrombosis (DVT), 3 had a long-standing DVT with relapsing episodes of swelling and pain, 5 had superficial venous thrombosis, and the remaining 7 had no signs of thrombosis at all. Twenty patients were being treated with heparin. All patients received 111In-antifibrin at the dose of 74 MBq IV and were scanned with a large field of view gamma camera coupled with a high-energy, parallel-hole collimator at 30 minutes and three, six, and twenty-four hours postinjection. Only the persistence of an abnormal uptake at twenty-four hours confirmed by two observers at visual inspection was considered as positive. A positive result was obtained in 9 of 10 DVT patients (90% sensitivity) and in all SVT patients. The single DVT patient with a negative 111In-antifibrin test had the longest interval between scintigraphy and onset of symptoms (fifty-five days). Thus, the age of thrombi represented a substantial limitation for the test. A false-positive result was obtained in a single SVT patient, in whom also a deep involvement, unconfirmed by phlebography, was suspected (91.6% specificity).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antibodies, Monoclonal; Female; Fibrin; Humans; Indium Radioisotopes; Male; Middle Aged; Phlebography; Radionuclide Imaging; Sensitivity and Specificity; Thrombophlebitis

Fifty-two patients suspected of having deep vein thrombosis under-went scintigraphy with an indium-111-labeled monoclonal antifibrin antibody. Venography disclosed deep vein thrombosis in 31 patients. With the whole limb considered an anatomic entity, antifibrin antibody scintigrams obtained 2 hours after injection had a specificity and sensitivity of 81% and 84%, respectively. A higher sensitivity (92%) was found for a subgroup of patients (n = 44) with symptoms for less than 10 days. Regional sensitivities for all patients and for the subgroup, respectively, were 92% and 100% in the calf, 82% and 94% in the popliteal region, 63% and 71% in the thigh, and only 18% and 13% in the pelvis. Additional imaging performed 6 hours and 21 hours after injection in 12 patients and quantitative analysis done from scintigrams with and without blood-pool (technetium-99m human serum albumin) correction did not improve sensitivity. In-111-antifibrin antibody scintigraphy is an accurate method for diagnosis of acute established deep vein thrombosis of the calf and popliteal region; its sensitivity in the thigh is lower, and it is not feasible for diagnosis in the pelvic area.

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Female; Fibrin; Humans; Indium Radioisotopes; Leg; Male; Middle Aged; Phlebography; Radionuclide Imaging; Sensitivity and Specificity; Thrombophlebitis

The effects of dermatan sulfate and heparin on inhibition of fibrin accretion onto existing thrombi as related to their ex vivo anticoagulant activity and abilities to inhibit increased prothrombin clearance induced by thrombi were investigated. Our results indicate that for equivalent anti-thrombin activities, dermatan sulfate is a more effective inhibitor of fibrin accretion onto existing thrombi than is heparin. These observations raise the possibility that in some clinical conditions dermatan sulfate, rather than heparin, may be a better antithrombotic agent of choice. This beneficial effect of dermatan sulfate appears to be unrelated to anti-factor Xa activity either endogenous to dermatan sulfate itself (which is unlikely since it does not catalyze factor Xa inhibition) or to anti-factor Xa activity associated with other glycosaminoglycans released into the circulation following dermatan sulfate administration since this activity is less than that associated with heparin treatment. It is more likely that dermatan sulfate mediates this beneficial effect by more effectively inhibiting thrombin within a thrombus than can heparin. This possibility is supported by the ability of dermatan sulfate to normalize prothrombin consumption in animals with existing thrombi.

Topics: Animals; Chondroitin; Dermatan Sulfate; Factor Xa; Female; Fibrin; Heparin; Kinetics; Male; Prothrombin; Rabbits; Serine Proteinase Inhibitors; Thrombin; Thrombophlebitis

An antifibrin antibody (T2G1s) Fab' fragment labeled with technetium-99m was tested for its ability to produce images of fresh thrombi in dogs. In gamma camera images, all thrombi were evident by 2-4 hours after injection. Mean thrombus-to-blood and thrombus-to-muscle ratios averaged 4.0 and 69 at four hours after injection and increased to 24 and 270, respectively, by 24 hours after injection. When compared with I-125 fibrinogen injected into the same dogs, Tc-99m-antifibrin Fab' had lower absolute uptake in thrombus but higher thrombus-to-blood ratios due to a faster rate of disappearance from the blood. The primary route of excretion was through the kidneys. Tc-99m-antifibrin Fab' was highly stable in vivo, with an average of 82% of the circulating radioactivity able to bind to fibrin at 4 hours after injection. When compared with an In-111-labeled Fab fragment of antifibrin antibody 59D8, thrombus-to-blood and thrombus-to-muscle ratios were slightly higher for the Tc-99m-labeled antibody, and the blood disappearance rate was slightly faster. The absolute uptake in thrombus, however, was not significantly different, and the thrombus was visualized at about the same time after injection. These studies suggest that Tc-99m T2G1s Fab' is a potential agent for detecting thrombi in a clinical setting.

Topics: Animals; Antibodies; Dogs; Evaluation Studies as Topic; Fibrin; Fibrinogen; Immunoglobulin Fab Fragments; In Vitro Techniques; Indium Radioisotopes; Iodine Radioisotopes; Radionuclide Imaging; Technetium; Thrombophlebitis; Tissue Distribution

Having previously established the specificity of a newly developed radiolabeled polyclonal anti fibrin antibody (AFA) for tagging fibrin depositions, clinical experiments for validation of this agent for imaging deep vein thromboses (DVT) were carried out in comparison with labeled human serum albumin (HSA) and labeled platelets. Patients with DVT were studied with dual tracers on a computerized scintillation camera, four with simultaneous application of 131I-AFA and 99mTc-HSA, and eight with 131I-AFA and 111In-platelets. The results showed that: a) Labeled AFA predominantly delineated thrombi while labeled HSA prevailingly delineated blood pool within a particular vein. b) Labeled AFA was found to be superior in both ways to labeled platelets for DVT imaging, i.e. by imaging effect and by semiquantitative "thrombus:blood pool" (obtained in counts/pixel) ratio index (RI). Average RI with SD obtained with labeled AFA (9 patients) was 2.44 +/- 0.48 and 1.55 +/- 0.27 with labeled platelets (7 patients). The results indicate that a monoclonal AFA, if labeled with 99mTc, 111In or 123I, might have potential for an optimum agent for DVT imaging.

Topics: Adult; Antibodies; Blood Platelets; Female; Fibrin; Humans; Indium Radioisotopes; Iodine Radioisotopes; Male; Middle Aged; Radionuclide Imaging; Technetium Tc 99m Aggregated Albumin; Thrombophlebitis

We have previously reported successful imaging of fresh (2-4 hr old) and aged (1-5 days old) canine thrombi with 131I-labeled intact monoclonal antibody (MAb) specific for fibrin. We now report thrombus imaging with 131I-labeled F(ab')2 and Fab and 111In-labeled intact MAb, F(ab')2, and Fab. Indium-111-labeled F(ab')2 proved to be the best imaging agent due to less nonspecific binding in the liver than whole IgG. Image quality was improved by the higher administered dose permissible with 111In and its better physical characteristics for imaging, compared to 131I. Immunofluorescence of fresh human histologic sections showed intact MAb and F(ab')2 binding to thrombi, pulmonary emboli, and atherosclerotic plaques, strengthening the feasibility of clinical thrombus imaging.

Topics: Animals; Antibodies, Monoclonal; Dogs; Fibrin; Humans; Immunoglobulin Fab Fragments; In Vitro Techniques; Indium Radioisotopes; Iodine Radioisotopes; Radionuclide Imaging; Thrombophlebitis

In organizing thrombi angiogenesis is not dependent on invasion of vasa vasora from the vascular wall. Mononuclear cells of the monohistiocytic system are always present within the clotted blood and are capable of differentiation into various types of mesenchymal cells, including endothelial cells. At first autolytic slits and clefts appear in the fibrinous superficial areas of the thrombus. They are gradually lined by spindle-shaped "pre-endothelial" cells that already possess immunohistological properties of endothelial cells but still resemble primitive mesenchymal cells ultrastructurally. Later these cells gain connection with each other by pseudopodia, overlapping and interdigitation until the channels in the fibrinous matrix are covered by an uninterrupted layer of cells. These cells are now characterized ultrastructurally by the appearance of specific endothelial organelles (Weibel-Palade bodies). Circulation within these channels begins from the blood stream. In addition, angiogenesis by sprouting of vasa vasora from the vascular wall occurs in those areas of the thrombus in contact with the vessel wall. In blood vessels with on unimpaired intimal layer, angiogenesis by invasion of capillaries occurs at an earlier date than capillary formation by mononuclear cells.

Topics: Adolescent; Adult; Aged; Cell Nucleus; Cytoplasm; Endothelium; Female; Fibrin; Granulocytes; Histiocytes; Histocytochemistry; Humans; Immunoenzyme Techniques; Male; Microscopy, Electron; Middle Aged; Monocytes; Neovascularization, Pathologic; Thrombophlebitis; Vacuoles

Fibrinolytic activity in response to venous occlusion (fibrin plate assay and tissue plasmogen activator antigen) was measured in 19 hypogonadic men (group 1), 23 non-hypogonadic men with deep venous thrombosis (DVT) antecedents and 20 healthy men (control group). Four hypogonadic men had DVT antecedents. Two of 20 controls were low responders against 6/19 and 6/23 in groups 1 and 2, respectively, (non-significant difference). The four hypogonadic men with DVT antecedent had abnormal response to venous occlusion. Whether defective fibrinolysis is causally related to hypogonadism cannot be established from these results but this study indicates that the combination of defective fibrinolysis, hypogonadism and DVT in man is relatively common.

Topics: Fibrin; Fibrinolysin; Hypogonadism; Plasminogen; Thrombophlebitis

Defibrotide is a profibrinolytic agent which has potent stimulatory effects on vascular prostacyclin (PGI2) production and secretion. We have studied the effects of this substance on the morphological organization of venous thrombi by combining ultrastructural evaluation with histometric analysis. Thrombosis was induced by inserting a collagen-coated thread into the femoral vein of rabbits 2 h before sacrifice. The results show that Defibrotide is highly effective in reducing the size of the thrombus. This is due to combined profibrinolytic action and interference with platelet and leukocyte adhesion as indicated by results showing that: (i) large deposits of fibrin-like material are smaller and less abundant; (ii) platelet aggregates are smaller, and (iii) the density of leukocytes in thrombus is strongly decreased. Polymorphism is prominent in platelets which are indistinguishable from control suggesting that the primary site of action of Defibrotide is on adhesion. The inhibitory effect on leukocyte participation to the thrombotic process is probably due to PGI2 release and may be of relevance on maturation and aging of the thrombus.

Topics: Animals; Blood Platelets; Collagen; Femoral Vein; Fibrin; Fibrinolysis; Fibrinolytic Agents; Male; Polydeoxyribonucleotides; Rabbits; Thrombophlebitis

The authors report success in imaging thrombi using labeled monoclonal antibody or antibody fragments. An In-111 labeled antibody fragment appears to be the best imaging agent studied to date.

Topics: Animals; Antibodies, Monoclonal; Dogs; Fibrin; Immunoglobulin Fab Fragments; Indium Radioisotopes; Iodine Radioisotopes; Radionuclide Imaging; Thrombophlebitis

The measurement of crosslinked fibrin derivatives in plasma has received evaluation as a screening test in the diagnosis of venous thrombosis. Plasma samples were taken from 104 patients undergoing venography because of clinical suspicion of lower limb venous thrombosis. The samples were assayed using a monoclonal antibody identifying an epitope on D dimer and larger crosslinked fibrin derivatives in an enzyme immunoassay. 100% of patients with positive venograms had elevated levels of these molecules. While a percentage of patients with negative venograms also had increased levels, alternative clinical explanations were apparent in most. A normal D dimer value excludes the diagnosis of venous thrombosis, while an increased value supports it. The measurement of crosslinked fibrin derivatives in plasma may play a role in the selection of patients for venography.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibody Specificity; Evaluation Studies as Topic; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; Male; Middle Aged; Protein Conformation; Thrombophlebitis

Previous studies with models of deep-vein thrombosis (DVT) have demonstrated that leukocyte (PMN)-mediated vein injury may be an initiating event in DVT (14, 17). Since heparin (H) can prevent DVT, we studied its effect on vascular injury and thrombosis in our model. Three groups of rabbits were treated with H either sc (73 and 147 U/kg) or iv (662 U/kg). Scanning electron microscopy revealed that the 73 U/kg sc dose was ineffective. All veins had PMN accumulation, fibrin deposition and complex thrombus formation. There was no increase in anti-Xa activity; activated partial thromboplastin times (APTT) and whole blood clotting times were normal. The 147 U/kg sc and the intravenous dose did not inhibit PMN-mediated vein injury. The endothelium was sloughed by migrating PMNs, basement membrane was exposed, and platelets adhered to it. Thrombosis was completely absent in the iv dose group. This correlated with increased anti-Xa activity and prolonged APTT and whole blood clotting times. Our results indicate that heparin does not inhibit the PMN adhesion and migration which produces vascular injury. However, the anticoagulant activity of heparin effectively reduces fibrin deposition and complex thrombus formation.

Topics: Animals; Fibrin; Heparin; Injections, Intravenous; Injections, Subcutaneous; Male; Microscopy, Electron, Scanning; Neutrophils; Rabbits; Thrombophlebitis; Veins

Radioimmunoimaging of fresh canine venous thrombi with a murine monoclonal antibody specific for human and dog fibrin has been reported. Successful imaging of canine deep venous thrombi 1, 3, and 5 days old at the time of antibody injection is reported. Images were positive in all dogs, and the uptake of fibrin-specific antibody was equivalent to that of fresh thrombi.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Dogs; Fibrin; Iodine Radioisotopes; Radionuclide Imaging; Thrombophlebitis; Time Factors

Topics: Antibodies, Monoclonal; Epitopes; Fibrin; Fibrinolysis; Humans; Myocardial Infarction; Thrombophlebitis; Tissue Plasminogen Activator

A congenitally abnormal fibrinogen was isolated from blood of a young man with deep-vein thrombosis. Two other affected members of his family had three episodes of severe arterial thrombosis. The fibrinogen showed a delayed clotting by thrombin, but a normal clotting by Arvin, Reptilase, and prothrombin-staphylocoagulase complex. Analysis of the fibrinopeptides A and B by High Performance Liquid Chromatography did not reveal an abnormal peptide structure. The rate of release of A and B peptides by thrombin was strongly delayed, whereas the rate of release of fibrinopeptide A by Arvin appeared to be normal. The fibrin polymerization rate was normal. Interactions between the abnormal fibrinogen, platelets and the fibrinolytic system were also normal. Evidence is presented that the defective interaction between fibrinogen Milano II and thrombin is associated with a defective binding of thrombin to the fibrin moiety of the abnormal fibrinogen.

Topics: Adult; Blood Coagulation Disorders; Fibrin; Fibrinogen; Fibrinogens, Abnormal; Fibrinopeptide A; Fibrinopeptide B; Humans; Male; Pedigree; Platelet Aggregation; Thrombin; Thrombophlebitis; Thrombosis

Fibrinolytic activities of whole blood and plasma were determined by 125I-fibrin radiometric assay in 16 normal subjects, and in 11 patients with systemic lupus erythematosus (SLE), 14 with progressive systemic sclerosis (PSS), 23 with venous thromboembolic disease, and 20 patients awaiting elective surgery. Mean whole blood and plasma activities for patients with PSS, and for those awaiting elective surgery, were similar to normal values, as was the mean plasma activity in patients with SLE. However, mean whole blood activity in SLE was significantly decreased compared with normals (p less than 0.05), with mean plasma activity accounting for 44% of mean whole blood activity (compared with 17% in normal subjects), representing a 67% decrease in mean calculated cellular phase activity in SLE, when compared with normals. Since the numbers of cells (neutrophils, monocytes) possibly involved in cellular activity were not decreased, the findings suggest a functional defect in fibrinolytic activity of one or more blood cell types in SLE. An additional finding was the participation of the cellular phase as well as the well-known plasma phase of blood in the fibrinolytic response to thromboembolism.

Topics: Female; Fibrin; Fibrinolysis; Humans; Iodine Radioisotopes; Leukocyte Count; Lupus Erythematosus, Systemic; Male; Monocytes; Neutrophils; Plasma; Plasma Cells; Scleroderma, Systemic; Thrombophlebitis

The article reports on measurements of D dimer, a terminal plasmic lysis product of crosslinked fibrin, with an enzyme immunoassay (ELISA) employing recently developed specific monoclonal antibodies. Due to its sensitivity the test can be used on plasma samples. The D dimer concentrations in patients with deep vein thrombosis diagnosed by laboratory apparatus were significantly increased compared to a control group; in one patient with additional pulmonary embolism, the level was even higher. Moderately elevated concentrations of D dimer were observed in the hypercoagulable state of pregnancy, puerperium and during the postoperative course. This reduces the specificity of the test with regard to the recognition of thromboembolic episodes under these conditions. Obstetric patients with disseminated intravascular coagulation (DIC) showed excessively increased levels of D dimer. Hence, a marker function with regard to the recognition of thromboembolic disease can be attributed to the D dimer; the diagnosis of DIC can be confirmed if very high concentrations are detected.

Topics: Adult; Antibodies, Monoclonal; Antibody Specificity; Disseminated Intravascular Coagulation; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Ovarian Neoplasms; Pregnancy; Pregnancy Complications; Pregnancy Complications, Cardiovascular; Pregnancy Complications, Hematologic; Pregnancy Complications, Neoplastic; Pulmonary Embolism; Thrombophlebitis

The specific detection of fibrin monomer and fibrin degradation products is of high importance in the laboratory diagnosis of intravascular clotting (disseminated intravascular coagulation, deep vein thrombosis). The methods proposed until now are partly time-consuming, needing special laboratories or insensitive and poorly specific. Applying ristomycin instead of ristocetin (another member of the vancomycin antibiotics) a new simple, specific and sensitive method has been elaborated and recommended for the laboratory diagnosis of intravascular coagulation and its differentiation from primary fibrinogenolysis. The results obtained from in vitro and animal experiments and from human studies are presented.

Topics: Animals; Chemical Precipitation; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Humans; In Vitro Techniques; Male; Rabbits; Ristocetin; Streptokinase; Thrombin; Thrombophlebitis

Fibrinaemia following total hip replacement was evaluated in eighteen patients, grouped according to a negative and a positive fibrinogen uptake test (FUT), after having excluded two patients due to a false negative test, using phlebography as reference. The ethanol gelation test (EGT) was employed for detection of circulating soluble fibrin, and the conversion of fibrinogen to fibrin was evaluated by the level of fibrinopeptide A (FPA). Eight patients were cleared with respect to thrombosis, whereas ten had a positive FUT. All patients developed a positive EGT, irrespective of thrombosis, coinciding with the postoperative increase in fibrinogen. FPA increased to approximately twice its preoperative level in both groups of patients, but reached its maximum earlier in patients with thrombosis. However, this parameter had no discriminative value in this type of postoperative thrombosis, possibly due to massive thromboplastin release in both groups.

Topics: Aged; Aprotinin; Female; Fibrin; Fibrinogen; Fibrinopeptide A; Heparin; Hip Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Reference Values; Thrombophlebitis; Time Factors; Warfarin

Murine monoclonal antibody (Mab) specific for the NH2-terminal region of human fibrin, but not cross-reactive with fibrinogen, was used in radioimmuno-imaging of fresh, induced venous thrombi in three dogs. Iodine-131-labeled Mab was injected intravenously, with iodine 125-labeled polyclonal murine gamma-G globulin (IgG) simultaneously injected as a control. Images were strongly positive at 24 and 48 hours in all three animals, with thrombus-to-blood and thrombus-to-muscle ratios of 8.4 and 228.0, respectively, for I-131-labeled Mab; these ratios for control IgG were 1.2 and 13.0. Radioimmunodetection of thrombi in vivo is feasible in dogs and may have clinical application since Mab is specific to human fibrin.

Topics: Animals; Antibodies, Monoclonal; Antibody Specificity; Cross Reactions; Dogs; Fibrin; Iodine Radioisotopes; Radionuclide Imaging; Thrombophlebitis

Among the serious complications encountered with long-term, indwelling Silastic central venous catheters are catheter-induced intravascular thrombi. These thrombi are usually treated by removal of the catheter to prevent thrombus propagation, embolization, or infection. We treated ten patients with urokinase infusion who had experienced 12 incidents of induced intravascular thrombi. Catheter phlebography and two-dimensional echocardiography were used for diagnosis and follow-up. Eleven of the 12 episodes were treated successfully, with complete dissolution of the thrombus. One patient with a calcific thrombus had only partial clot lysis and required catheter removal. By utilizing urokinase infusion to treat Silastic catheter-induced intravascular thrombi, nine of ten central venous catheters were preserved and the possible need for thrombectomy was averted. No serious complications were encountered. In our experience, urokinase therapy has been an effective and safe method for treating Silastic catheter-induced intravascular thrombi.

Topics: Catheters, Indwelling; Child, Preschool; Echocardiography; Fibrin; Follow-Up Studies; Heart Diseases; Humans; Infant; Infusions, Parenteral; Phlebography; Silicone Elastomers; Thrombophlebitis; Thrombosis; Time Factors; Urokinase-Type Plasminogen Activator

Low molecular weight heparin fractions (LMWH) are less hemorrhagic but are as effective as standard heparin (SH) in preventing experimentally-induced venous thrombosis. The effect of LMWH in preventing extension of established thrombi is unknown. We have compared the effects of two LMWH's (CY, PK), and a low molecular weight heparinoid (a dermatan/heparan/chondroitin mixture, OH) with SH on the prevention of extension of established venous thrombi, by measuring their ability to inhibit the accretion of 125I-fibrin onto venous thrombi pre-formed in rabbit jugular veins. Anticoagulant activity was assayed ex vivo by the APTT and a chromogenic anti-Xa assay, and the antithrombotic effect of these glycosaminoglycans was related to their anticoagulant effects. Autologous thrombi were formed in both jugular veins of each rabbit. The rabbits were then injected with 125I-fibrinogen and treated with a bolus dose of glycosaminoglycan or saline, followed by a continuous infusion for 4 hours. All four glycosaminoglycans significantly inhibited 125I-fibrin accretion (p less than 0.001). SH, CY and PK were equipotent at doses of 42.5-62.5 anti-Xa U/kg/hr in preventing fibrin accretion by 50%. Higher doses had no further effect. OH was significantly more potent than the other three glycosaminoglycans at any given dose (p less than 0.005). There was no correlation between the antithrombotic effect and the anticoagulant effects. We conclude that these LMWH's are as effective as SH in preventing extension of established thrombosis.

Topics: Animals; Anticoagulants; Disease Models, Animal; Female; Fibrin; Fibrinogen; Glycosaminoglycans; Heparin; Infusions, Parenteral; Injections, Intravenous; Male; Rabbits; Structure-Activity Relationship; Thrombophlebitis

The fibrinolytic capacity was assessed in 18 healthy subjects and in 8 patients each with non-idiopathic venous thrombosis, idiopathic venous thrombosis and myocardial infarction after intravenous administration of 1-deamino-8-D-arginine vasopressin (DDAVP) (0.4 microgram/kg) in comparison to venous occlusion. In healthy subjects the results obtained by either stimulus were approximately in agreement. Compared to the control group, in patients with non-idiopathic venous thrombosis the fibrinolytic capacity was not changed either after venous occlusion or after administration of DDAVP. In 5 out of 8 patients with idiopathic venous thrombosis the capacity was significantly reduced both after venous occlusion and after administration of DDAVP. In 4 out of 8 patients with myocardial infarction the capacity was significantly below the limit after administration of DDAVP while it was not after venous occlusion. In determining the fibrinolytic capacity DDAVP proved to be superior to venous occlusion.

Topics: Adult; Blood Coagulation Tests; Deamino Arginine Vasopressin; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Middle Aged; Myocardial Infarction; Prognosis; Thrombophlebitis; Thrombosis

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

Topics: Dose-Response Relationship, Drug; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Follow-Up Studies; Humans; Streptokinase; Thrombophlebitis; Urokinase-Type Plasminogen Activator

Topics: Aged; Clinical Laboratory Techniques; Factor XIII; Fibrin; Fibrinogen; Humans; Male; Partial Thromboplastin Time; Thrombin; Thrombophlebitis

Thrombus-related uptake of 131 I-fibrin des-AABB has been compared to that of 125 I-fibrinogen in 13 patients with established venous thrombosis. Both tracers originated from a common pool of beta-alanine precipitated fibrinogen. Scan-recordings were performed as a radiofibrin (ogen) uptake test. Uptake characteristics of des-AABB fibrin were similar to those of fibrinogen, when measured as percentage of concomitant radioactivity over the heart. Due to its longer circulation time, fibrinogen was superior to fibrin des-AABB for the detection of venous thrombi. Circulating des-AABB fibrin was cleared biphasically, with an initial rapid decline followed by a gradual exponential decrease. Mean half-lives were 5.5 +/- SD 3.5 hr and 10 +/- SD 3.5 hr, respectively. The elimination rates were uninfluenced by thrombus activity, as judged by the fibrin(ogen) uptake test. Metabolic half-life of fibrinogen in the total material was 62 +/- SD 19 hr. Dissociation of fibrinogen and soluble des-AABB fibrin clearance rates was evident, describing their own, independent elimination patterns, probably reflecting different clearing mechanisms.

Topics: Fibrin; Fibrinogen; Half-Life; Humans; Iodine Radioisotopes; Metabolic Clearance Rate; Radionuclide Imaging; Thrombophlebitis

Fibrin was prepared from purified fibrinogen, plasma, and pathologic arterial thrombi and assayed for thrombin activity. Activity was detected on fibrin from each of these sources when assayed by three techniques: the rate of release of FPA from fibrinogen, a clotting time assay, and the rate of hydrolysis of the chromogenic substrate S-2238. Of the labeled thrombin initially associated with fibrin during clot formation in vitro, all but 10% to 15% could be removed easily by manual compression or by incubation in buffer. Radiolabeled thrombin that remained bound to clots of purified fibrinogen retained full functional activity, whereas that bound to plasma clots expressed only 4% of expected activity. Plasmic lysis of fibrin from clots of purified fibrinogen released bound thrombin quantitatively into solution in active form. The solubilized thrombin retained association with specific macromolecular fibrin derivatives as demonstrated by sedimentation analysis, electrophoretic co-migration, and partitioning in agarose gel. Plasmic lysates of fibrin prepared in vitro from plasma or pathologic arterial clots also expressed thrombin activity, in an amount similar to the fibrin from which they were prepared. Our studies demonstrate the presence of functionally active thrombin on fibrin prepared from in vitro clots and in vivo thrombi as well as in association with soluble plasmic derivatives of these substrates. This activity may constitute a prothrombotic influence and may contribute to the elevated FPA-levels seen in patients with thrombotic disease.

Topics: Blood Coagulation; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Fibrinolysin; Humans; In Vitro Techniques; Plasma; Thrombin; Thrombophlebitis

Determination of the fibrinolytic activity should be performed in patients with recurrent thromboembolic disease. As a screening procedure we suggest the euglobulin clot lysis time test after venous occlusion. This test is sufficiently reliable and easier to perform than the fibrin plate method, especially outside coagulation laboratories.

Topics: Adult; Aged; Blood Coagulation Tests; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Serum Globulins; Thrombophlebitis

Topics: Blood Vessels; Enzyme Activation; Fibrin; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Thrombophlebitis

Fragment E1, a product of plasmic digestion of cross-linked fibrin, binds specifically in vitro to polymerized fibrin but not to fibrinogen. Purified human Fragment E1 was radiolabeled with 125I or 131I by the Iodogen technique. The uptake of radioiodinated Fragment E1 in vitro into forming or preformed clots was demonstrated. Animal biodistribution studies of radioiodinated Fragment E1 showed its rapid removal from the circulation; radioactive catabolites did not reside long in any organ and were excreted in the urine. The uptake in vivo was evaluated in pigs with preexisting venous thrombi of various ages from 1 h up to 5 d at the time of intravenous systemic injection of the tracer. Radioiodinated fibrinogen was also injected into the same animals to compare the uptake of the two tracers. Thrombus-to-blood ratios for Fragment E1 averaged 43:1 (range 10-108) and 29:1 (range 8-107) in thrombi 1-6 h and 1-5 d old, respectively. In contrast, mean thrombus-to-blood ratios for fibrinogen were, in the same time intervals, 26:1 (range 17-41) and 2:1 (range 0.5-3.9), respectively. It is concluded that radioiodinated Fragment E1 is a specific marker of thrombi in vivo: its uptake by fresh thrombi is better than that of labeled fibrinogen and, in contrast to radioiodinated fibrinogen, this fragment is incorporated into old thrombi as well.

Topics: Animals; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; In Vitro Techniques; Iodine Radioisotopes; Isotope Labeling; Swine; Thrombophlebitis

Topics: Adult; Animals; Child; Dogs; Fibrin; Fibrinolytic Agents; Humans; Hypertension; Leg Ulcer; Oxygen Consumption; Stanozolol; Thrombophlebitis; Venous Pressure

To evaluate the effect of ibuprofen on early thrombus formation following inferior vena cava (IVC) replacement, a 4-cm segment of IVC was replaced with a 5-cm (10-mm-i.d.) segment of reinforced polytetrafluoroethylene (PTFE) graft in 12 dogs. Autologous platelets and canine fibrinogen were labeled with 111In and 125I, respectively, and injected into each animal 24 hr prior to vena cava replacement. Six dogs served as controls and six were treated with 12.5 mg/kg ibuprofen intravenously 1 hr preoperatively. All dogs were heparinized with 100 U/kg intravenous heparin prior to crossclamping the IVC: heparin was not reversed at the end of the procedure. Three hours after normal circulation was restored, the grafts were removed and counts of radioactivity made. All grafts were patent. The mean platelet count for the control group was 12.8 X 10(6)/mm2, while in the grafts from the treated group it was 0.960 X 10(6)/mm2. The decreased platelet deposition was significant in all graft segments (P less than 0.01). Fibrin deposition was reduced from 3.38 micrograms/mm2 to 0.25 micrograms/mm2 (P less than 0.01) by ibuprofen. Although fibrin and red blood cells are the major constituents of venous thrombi, platelet aggregation appears to play an important role if prosthetic material is implanted into the venous system. Ibuprofen not only reduced platelet deposition by 13.5-fold, but also reduced fibrin deposition by 13.5-fold. The ratio of platelets to fibrin in control and treated animals was similar (3.84 and 3.79, respectively). These data suggest that antiplatelet medication combined with heparin therapy might decrease early thrombus formation in venous prostheses.

Topics: Animals; Blood Platelets; Blood Vessel Prosthesis; Dogs; Erythrocytes; Fibrin; Ibuprofen; Platelet Aggregation; Polytetrafluoroethylene; Thrombophlebitis; Vena Cava, Inferior

The plasminogen activator (PA) activity in superficial hand and foot veins was determined with a fibrin slide technique in 68 patients (46 with and 22 without thrombosis). The activity in the hand veins was identical to that of the foot veins in 57% of the patients and higher in 38%. There was a correlation between activity in hand and foot veins in patients with and without thrombosis. Thus, biopsy specimens from superficial hand veins can be used for assessing the PA activity in patients with leg thrombosis.

Topics: Adolescent; Adult; Aged; Female; Fibrin; Fibrinolysis; Foot; Hand; Humans; Male; Middle Aged; Plasminogen Activators; Thrombophlebitis; Veins

Topics: Antithrombin III; Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostasis; Humans; Solubility; Thrombophlebitis; Tinea; Venous Insufficiency

The finding of 4 cases of venous thrombosis in patients with raised serum alpha 1-antitrypsin (AAT) levels has focused attention on the role of the inhibitors of leucocyte protease or granulocyte-induced fibrinolysis. A composite fibrin plate assay was devised to determine the fibrinolytic and fibrinolytic-inhibitor potential of viable circulating granulocytes, mononuclear cells and platelet-free plasma. A plasmin-dependent and a plasmin-independent pathway were identified in circulating granulocytes, a biological function which appeared to be completely absent from the mononuclear fraction. In order to explore the effect of AAT on the cellular fibrinolytic pathway, viable granulocyte and plasma fractions were exposed to the inhibitor in a purified system as well as to several aliquots of plasma containing an excess of AAT obtained from a patient with venous thrombo-embolic disease. The unequivocal inhibition of granulocyte fibrinolytic activity by pure AAT solutions as well as by plasma with a raised AAT level would seem to provide further evidence that by counteracting protease liberated by cellular elements, notably the granulocyte, the patient is deprived of a vital component of the fibrinolytic defence mechanism.

Topics: Adult; alpha 1-Antitrypsin; Female; Fibrin; Fibrinolysis; Granulocytes; Humans; Male; Middle Aged; Neutrophils; Thrombophlebitis

Deep vein thrombosis in man presents a considerable clinical challenge. Despite the availability of prophylactic measures, therapeutic thrombolysis is often necessary, but is difficult and hazardous. Treatments have included the administration of plasmin, other less specific proteolytic enzymes, the indirect plasminogen activator, streptokinase, and the direct activators, urokinase and streptokinase-human plasmin complex. All these treatments have been associated with some haemostatic breakdown, which has discouraged their widespread application. The enzyme components of the coagulation and fibrinolytic pathways can, in general, be classed as serine proteases, with a catalytic mechanism which operates via acyl-enzyme intermediates. Chase and Shaw showed that p-nitrophenyl-p'-guanidinobenzoate could specifically acylate the active centre of trypsin-like enzymes, giving rise to a stable p-guanidinobenzoyl enzyme and other stable acyl-enzymes have since been described. We report here the fibrinolytic use of acylated derivatives of plasmin (E.C.3.4.21.7) and streptokinase-plasmin(ogen) complexes.

Topics: Acylation; alpha-2-Antiplasmin; Animals; Binding Sites; Disease Models, Animal; Dogs; Enzyme Activation; Fibrin; Fibrinogen; Plasminogen; Rabbits; Streptokinase; Thrombophlebitis

For the estimation of fibrinolytic activity in euglobulin precipitates after venous stasis, the euglobulin clot lysis time (ECLT) proved to be as reproducible and probably even more sensitive than the fibrin plate method (FP). Furthermore, when euglobulin precipitates from 55 healthy individuals and 36 patients with thromboembolic disease were examined, a good correlation between the two methods was observed. The present observations indicate that the ECLT is suitable for routine screening of fibrinolytic activity after venous stasis.

Topics: Adult; Aged; Blood Coagulation Tests; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Serum Globulins; Thrombophlebitis

Women who were to be operated upon for prolapse of the uterus were treated preoperatively with estrogens for atrophic vaginal mucosa and examined postoperatively by the 125I-fibrinogen uptake test and phlebography. Among 11 women who received 50 micrograms of ethinyl estradiol daily for three weeks, fibrin deposits were found in six. Of eight women receiving 200 micrograms daily for 12 days, such deposits developed in four. Corresponding figures for the control group were 18 of 157, p < 0.001. Estrogens, therefore, should not be given preoperatively, and those patients treated with preparations containing estrogens should have such therapy discontinued preoperatively.. This study determines whether or not fibrin deposits occur more frequently in patients who had gynecologic surgical procedures for prolapse of uterus and treated with estrogens than in those in a control group. 11 women were given 50 ug of ethinyl estradiol daily for 3 weeks while 8 women were given 200 ug ethinyl estradiol daily for 12 days. The remaining 157 women who received no hormonal treatment served as controls. The women were examined postoperatively by the Iodine fibrinogen uptake test and phlebography according to the method of Nylander. The chi-square test with Yate's correction was used for data analysis. Fibrin deposits were found in 6 of the 11 women who received 50 ug ethinyl estradiol for 3 weeks and in 4 of 8 women receiving 200 ug for 12 days. Corresponding figures for the control group were 18 of 157, p 0.001. Estrogens should not prescribed to patients preoperatively. Estrogen therapy should be discontinued in patients who are about to be operated.

Topics: Estradiol; Ethinyl Estradiol; Female; Fibrin; Humans; Iodine Radioisotopes; Middle Aged; Phlebography; Postoperative Complications; Thrombophlebitis; Uterine Prolapse

A prospective study was carried out to confirm the validity of a predictive index for patients at risk of developing deep vein thrombosis. The index, which correctly identified nine out of 10 patients and incorrectly identified seven out of 52 patients as being at risk, is based on five variable--namely, the euglobulin lysis time, serum concentration of fibrin-related antigen, age, percentage overweight for height, and presence of varicose veins. Thus a population of patients at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively by means of this index, so that prophylaxis may be used more rationally.

Topics: Adult; Aged; Antigens; Blood Coagulation Tests; Body Weight; Female; Fibrin; Humans; Postoperative Complications; Risk; Serum Globulins; Thrombophlebitis; Varicose Veins

Administration of prophylactic low-dose subcutaneous heparin to prevent postoperative deep vein thrombosis is expensive, entails treating many patients unnecessarily, and causes some side effects. By using a predictive index a population of patients who are at particularly high risk of developing postoperative deep vein thrombosis may be identified preoperatively. Prophylaxis was given only to these patients, resulting in an incidence of deep vein thrombosis of 3.8% compared with 16.1% in previous studies in which no specific prophylaxis was given. By limiting prophylaxis to the group of patients identified by the predictive index as being at high risk of developing postoperative deep vein thrombosis results may be obtained that are as good as those expected from treating the whole population. Thus many patients are saved from exposure to low-dose subcutaneous heparin.

Topics: Aged; Antigens; Blood Coagulation Tests; Body Weight; Drug Administration Schedule; Female; Fibrin; Heparin; Humans; Middle Aged; Postoperative Complications; Risk; Serum Globulins; Thrombophlebitis; Time Factors

Blood tests for fibrinogen/fibrin degradation products (FDP/fdp) and soluble fibrin complexes (SFC) were performed in 100 patients at high risk for thromboembolism in order to assess the diagnostic value of these determinations in patients suspected to have pulmonary embolism. Tests were positive significantly less often in high-risk patients, and mean values were significantly lower, when compared with patients with established pulmonary embolism (P less than .001). However, no significant differences existed between high-risk patients and patients with deep venous thrombosis of the legs. Positivity rates and mean values were significantly higher in the presence of pulmonary embolism than in patients with deep venous thrombosis alone (P less than .05). Elevated FDP/fdp and SFC values are useful in the diagnosis of pulmonary embolism in high-risk patients; moreover, positive results in a patient with deep venous thrombosis suggests that pulmonary embolism has occurred.

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

Topics: Animals; Blood Coagulation; Cattle; Disseminated Intravascular Coagulation; Ellagic Acid; Factor IX; Factor X; Fibrin; Humans; Lung; Male; Rabbits; Thrombin; Thrombophlebitis; Thromboplastin

Topics: Blood Proteins; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Plasminogen; Plasminogen Activators; Streptokinase; Thrombin; Thrombophlebitis

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel-electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.

Topics: Autoradiography; Chemical Precipitation; Disseminated Intravascular Coagulation; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrinogen; Fibrinolytic Agents; Hot Temperature; Humans; Molecular Weight; Peptides; Thrombophlebitis; Urokinase-Type Plasminogen Activator

The authors conducted a series of experiments concerning the condition of hypercoagulability of patients with a history of thrombosis, in view of determining whether or not the risk of thrombosis could be assessed by laboratory tests. To that end they assayed antithrombin iii activity and soluble fibrin complexes in their test subjects. Antithrombin activity was assayed by a chromogenic method; soluble fibrin complexes by the hemoagglutination test. The activity of antithrombon III was significantly reduced in patients with venous thrombosis, not so in arterial thrombosis. Testing for soluble fibrin complexes was invariably unrewarding, probably because the thrombosis episodes under investigation were of too long standing.

Topics: Adolescent; Adult; Antithrombin III; Disease Susceptibility; Female; Fibrin; Humans; Male; Middle Aged; Reference Values; Risk; Solubility; Thrombophlebitis; Thrombosis

Soluble fibrin complexes, fibrin degradation products, and anti-thrombin III levels were determined in the plasma of 20 patients undergoing elective total hip replacement. The presence of deep venous thrombophlebitis was determined by venography at the end of the first postoperative week. Patients who developed thrombosis exhibited impairment of fibrinolysis as de-Patients who developed thrombosis exhibited impairment of fibrinolysis as detected levels of anti-thrombin III and soluble fibrin complexes were not useful in indicating the presence of deep venous thrombosis. However, the preoperative level of soluble fibrin complexes closely correlated with the subsequent development of thrombosis. Elevated soluble fibrin complexes appear to identify a group of patients with activated coagulation systems who are prone to develop thrombosis during total hip replacement.

Topics: Antithrombin III; Blood Coagulation Tests; Fibrin; Fibrin Fibrinogen Degradation Products; Hip Joint; Humans; Joint Prosthesis; Phlebography; Postoperative Complications; Thrombophlebitis

Rabbit anti-human fibrin globulin (A.F.G.) was labelled with iodine (131I) and used as a thrombus-detecting agent. 131I-A.F.G. labelled thrombi were displayed by means of a gamma scintillation camera. Normal subjects and patients with thrombophlebitis of legs, acute fibrin depositions other than thrombi, and chronic varicosities were examined. The 131I-A.F.G. technique detected both formed thrombi and those that were forming and could discriminate between acute thrombosis and chronic varicosities. Thrombophlebitis and extravascular fibrin depositions were best demonstrated between 24 and 27 hours of 131I-A.F.G. injection. Radiolabelled A.F.G. in normal veins and chronic varicosities was best displayed within 6 hours of injection.

Topics: Acute Disease; Animals; Antibodies; Chronic Disease; Diagnosis, Differential; Female; Fibrin; Humans; Immunodiffusion; Iodine Radioisotopes; Isotope Labeling; Middle Aged; Rabbits; Radionuclide Imaging; Thrombophlebitis; Time Factors; Varicose Veins

The passage of a minimal electric charge was used to initiate thrombosis in rabbit femoral veins, and the events occurring during formation of the thrombus were observed using scanning electron microscopy. Thrombosis began to occur within ten minutes after passage of the charge, upon an apparently unaltered endothelium. The first event was the laying down of a fibrin meshwork and this was shortly followed by the appearance of regularly arranged platelet clumps.

Topics: Animals; Blood Platelets; Femoral Vein; Fibrin; Microscopy, Electron, Scanning; Rabbits; Thrombophlebitis; Thrombosis; Time Factors

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 23 high risk patients the change in plasminogen activator activity in response to surgical operation was studied by euglobulin lysis time (ELT) and fibrin plate lysis before, during and for up to 6 days following a major surgical procedure. Fibrin degradation products (FDP) were also measured. The aim was to relate any changes to postoperative deep vein thrombosis (DVT) as diagnosed by the 125I fibrinogen test. Peroperative increase and postoperative inhibition of fibrinolytic activity were seen in all the patients. Changes in fibrinolytic activity as measured by the ELT and during the first 24 hours by the fibrin plate technique were similar. This suggests that during this period the response was independent of plasma fibrinogen changes. There was no significant difference in these parameters between patients who developed DVT and those who did not. The relationship between venous thrombo-embolism and elevation of serum FDP was confirmed.

Topics: Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Humans; Male; Postoperative Complications; Serum Globulins; Thrombophlebitis; Time Factors

A range of clinical data was obtained from 124 patients about to undergo operation and several coagulation tests were performed. No patient received prophylaxis for deep vein thrombosis, and isotopic scanning after operation showed that 20 patients had developed thrombosis. a simiple prognostic index for predicting which patients would develop postoperative deep vein thrombosis was constructed using the clinical and coagulation data obtained before operation. The five variables with the best predictive power-euglobulin lysis time, age, presence of varicose veins, fibrin related antigen, and percentage overweight-produced an equation that identfied 95% of those who developed deep vein thrombosis and misallocated only 28% of those who did not develop thrombosis. In view of the complications that low-dose heparin and dextran can cause, giving prophylaxis to under a third of the patients who will not develop deep vein thrombosis is clearly better than giving it to all.

Topics: Adult; Age Factors; Antigens; Body Weight; Fibrin; Humans; Middle Aged; Postoperative Complications; Prognosis; Serum Globulins; Thrombophlebitis; Varicose Veins

Levels of fibrin(ogen) degradation products (F.D.P.) have been measured by radioimmunoassay for degradation product E (FgE) and by tanned-red-cell haemagglutination-inhibition immunoassay (T.R.C.H.I.I.) in the serum of thirty-three patients undergoing total hip replacement. Levels of F.D.P. did not correlate with thermographic evidence of deep-venous thrombosis. However, in 34 patients with pulmonary embolism, levels of F.D.P. measured by the T.R.C.H.I.I. were transiently raised at the time of embolus, and FgE concentrations were increased for up to 5 days preceding the embolus. Since the measurments of FgE is simple, convenient, and cheap, this estimation might constitute a valuable screening test for major thromboembolic episodes in the postoperative period.

Topics: Aged; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Inhibition Tests; Hip; Humans; Middle Aged; Phlebography; Postoperative Complications; Pulmonary Embolism; Radioimmunoassay; Thermography; Thrombophlebitis

A study of serum levels of fibrinogen-fibrin-related antigen (F.R.-antigen) in outpatients presenting with clinical features suggesting deep vein thrombosis was undertaken. A raised serum level of this antigen (greater than 12 mg/1) is strong evidence in favour of the diagnosis of deep vein thrombosis. It is virtually conclusive evidence if other known causes of a raised level of the antigen are absent. On the other hand, a normal serum level of F.R.-antigen does not exclude even extensive thrombosis, and other objective techniques are required to substantiate the diagnosis.

Topics: Adult; Antigens; Female; Fibrin; Fibrinogen; Humans; Latex Fixation Tests; Leg; Male; Middle Aged; Outpatient Clinics, Hospital; Pulmonary Embolism; Thrombophlebitis

Topics: Anemia, Hemolytic; Breast Diseases; Disseminated Intravascular Coagulation; Female; Fibrin; Gangrene; Humans; Middle Aged; Necrosis; Thrombophlebitis; Warfarin

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

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

Topics: Adult; Age Factors; Aged; Arteries; Blood Flow Velocity; Blood Pressure; Blood Vessels; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diabetic Retinopathy; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Leg; Male; Middle Aged; Obesity; Plasminogen; Plethysmography, Impedance; Regional Blood Flow; Thrombophlebitis

Topics: Blood Coagulation; Endothelium; Femoral Vein; Fibrin; Humans; Leg; Leukocytes; Pelvis; Platelet Aggregation; Thigh; Thrombin; Thrombophlebitis; Veins

Topics: Blood Vessels; Eye; Fibrin; Histocytochemistry; Humans; Plasminogen Activators; Thiocyanates; Thrombophlebitis

Topics: Fibrin; Hemostasis; Humans; Thrombin; Thrombophlebitis

Topics: Agranulocytosis; Animals; Blood Cell Count; Blood Platelets; Female; Fibrin; Fibrinogen; Iodine Radioisotopes; Jugular Veins; Leukocyte Count; Male; Mechlorethamine; Platelet Adhesiveness; Rabbits; Staining and Labeling; Thrombophlebitis

Topics: Acute Disease; Antithrombins; Blood Cell Count; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Liver Cirrhosis; Lymphatic Diseases; Platelet Adhesiveness; Prothrombin Time; Retinal Detachment; Thrombin; Thrombophlebitis

Topics: Adolescent; Adult; Behcet Syndrome; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Thrombophlebitis

The structure of 50 small thrombi in femoral valve pockets and the microscopic contents of 35 apparently empty pockets were studied in an attempt to ascertain the nature of the microscopic nidi from which thrombi form and their manner of growth to visible thrombi. Sixteen thrombi had little or no cellular invasion. Most of these recent structures had two main regions, red areas restricted distally in the pocket by the vein wall, and larger white regions comprising most of the thrombus length and often covering the red areas. Red areas are the early sites of cellular adhesion and invasion and the likely sites of origin of most thrombi. They were usually dominated by red cells and fibrin. White zones, which represent propagation growth, are characterized by many foci of platelets with fibrin borders (platelet-fibrin units). Some red areas also contained platelet-fibrin units but they were few and tiny; platelets were not seen in others and one small wholly red thrombus was devoid of platelets. Degenerative changes in platelet-fibrin units were observed, and it is postulated that many become purely fibrin structures. There was no significant evidence of preceding intimal damage in the vein wall. Therefore nidi are laid down on normal endothelium probably on the vein wall near the apex of the pocket. Some pockets, empty of thrombi, contained condensed foci of red cells or tiny fibrin fragments surfaced by endothelial cells and considered to be the remnants of aborted thrombi; a few contained clumps of platelets or leucocytes. It is postulated that any of these may represent the nidi from which thrombi grow. Several thrombi also incorporated large fat droplets, numerous in two. Fat embolic globules derived from fractures are their likely source.

Topics: Aged; Anticoagulants; Autopsy; Blood Coagulation; Blood Platelets; Erythrocytes; Female; Femoral Fractures; Femoral Vein; Fibrin; Humans; Leukocytes; Male; Middle Aged; Staining and Labeling; Thrombophlebitis; Thrombosis

Thrombi deposited on prosthetic devices in the superior vena cava of the rhesus monkey were studied by morphologic and biochemical technics. Glass or silicone-coated glass (SCG) rings were implanted for 30 minutes to 14 days. Thrombus was deposited on the surface of each prosthetic device, and deposition was much greater and more rapid on glass surfaces than on SCG surfaces. On SCG surfaces, initial deposits consisting of single platelets, small platelet aggregates and erythrocytes were seen by scanning electron microscopy. These were followed by larger platelet aggregates, fibrin and, much later, leukocytes. Transmission electron micrographs revealed disintegration of the platelets forming aggregates and an osmiophilic deposit on the prosthetic surface. Shortened partial thromboplastin times were observed in all test animals but the sham-operated one, and therefore may be predictive of thrombus formation.

Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Disease Models, Animal; Female; Fibrin; Glass; Haplorhini; Leukocytes; Macaca; Male; Microscopy, Electron; Microscopy, Electron, Scanning; Platelet Adhesiveness; Prostheses and Implants; Silicones; Thrombophlebitis; Time Factors; Vena Cava, Superior

Topics: Animals; Chemical Precipitation; Electrophoresis, Polyacrylamide Gel; Factor XIII; Fibrin; Fibrinogen; Humans; Immune Sera; Immunodiffusion; Molecular Weight; Rabbits; Streptokinase; Thrombophlebitis

Topics: Abdominal Muscles; Animals; Blood Sedimentation; Erythrocytes; Fibrin; Fibrinogen; Hematocrit; Heparin; Injections, Intravenous; Postoperative Complications; Rabbits; Thrombophlebitis; Time Factors

Topics: Animals; Blood Coagulation; Disease Models, Animal; Dogs; Electric Injuries; Electrodes; Electrophoresis, Polyacrylamide Gel; Femoral Vein; Fibrin; Ligation; Platelet Aggregation; Pulmonary Embolism; Thrombophlebitis

Topics: Animals; Blood Coagulation; Electrophoresis, Polyacrylamide Gel; Fibrin; In Vitro Techniques; Jugular Veins; Polymers; Rabbits; Thrombophlebitis

Topics: Animals; Blood Platelets; Dextrans; Endothelium; Female; Fibrin; Hemostasis; Male; Rabbits; Thrombophlebitis; Time Factors

Topics: Acenocoumarol; Aged; Fibrin; Fibrinogen; Half-Life; Heart Failure; Heparin; Humans; Injections, Intravenous; Iodine Radioisotopes; Leg; Middle Aged; Radionuclide Imaging; Thrombophlebitis

Topics: Adult; Aged; Animals; Antibodies; Aspartate Aminotransferases; Bronchitis; Bronchopneumonia; Erythrocytes; Female; Fibrin; Fibrinogen; Humans; Injections, Intravenous; Iodine Radioisotopes; Leg; Male; Middle Aged; Myocardial Infarction; Sheep; Thrombophlebitis

Topics: Animals; Blood Cell Count; Blood Platelets; Carotid Artery Thrombosis; Chromium Isotopes; Dogs; Erythrocytes; Female; Fibrin; Fibrinogen; Hematocrit; In Vitro Techniques; Iodine Isotopes; Iron Isotopes; Jugular Veins; Male; Microscopy, Phase-Contrast; Radiometry; Scintillation Counting; Thrombophlebitis; Thrombosis

Topics: Adrenalectomy; Basement Membrane; Blood Platelets; Edema; Endothelium; Epithelial Cells; Fibrin; Humans; Infant; Kidney; Kidney Glomerulus; Male; Microscopy, Electron; Mitochondria; Nephrectomy; Renal Veins; Thrombophlebitis

Topics: Antithrombins; Blood Coagulation; Blood Coagulation Tests; Fibrin; Fibrinogen; Fibrinolysis; Hematocrit; Humans; Iodine Radioisotopes; Macroglobulins; Plasminogen; Postoperative Complications; Thrombophlebitis; Time Factors

Topics: Animals; Blood; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Depression, Chemical; Fibrin; Jugular Veins; Prothrombin Time; Rabbits; Sodium Chloride; Thrombin; Thrombophlebitis; Time Factors

Topics: Fibrin; Fibrinogen; Humans; Thromboembolism; Thrombophlebitis

Topics: Aged; Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Dysgerminoma; Female; Fibrin; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Prostatic Neoplasms; Stomach Neoplasms; Testicular Neoplasms; Thrombophlebitis

Topics: Adenosine Diphosphate; Adult; Aged; Antithrombins; Blood Cell Count; Blood Coagulation; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Clot Retraction; Collagen; Disseminated Intravascular Coagulation; Epinephrine; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemorrhage; Humans; Male; Middle Aged; Plasminogen; Platelet Adhesiveness; Polycythemia Vera; Prothrombin Time; Thrombin; Thrombophlebitis

Topics: Animals; Dogs; Embolism; False Positive Reactions; Fibrin; Fibrinogen; Fibrinolysis; Iodine Radioisotopes; Models, Biological; Phlebography; Radionuclide Imaging; Thrombin; Thrombophlebitis

Topics: Autopsy; Barium Sulfate; Cell Adhesion; Collagen; Endothelium; Femoral Artery; Femoral Vein; Fibrin; Fibrinolysis; Humans; Leukocytes; Phagocytosis; Radiography; Thrombophlebitis

Topics: Aged; Biopsy; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Iodine Radioisotopes; Male; Middle Aged; Plasminogen; Postoperative Complications; Rectal Neoplasms; Thrombophlebitis; Veins

Topics: Animals; Arteries; Blood Cell Count; Blood Platelets; Dogs; Erythrocytes; Female; Fibrin; Fibrinogen; Immune Sera; Iodine Radioisotopes; Male; Platelet Adhesiveness; Thrombocytopenia; Thrombophlebitis; Thrombosis; Veins

The fibrinolytic system was studied in primary biliary cirrhosis (16 patients) and large bile duct obstruction (10 patients, nine of whom had carcinoma). Plasma fibrinolysis (plasminogen activator activity) was decreased and fibrinogen increased in both groups of patients, particularly in those with large duct obstruction. These changes were related to the degree of cholestasis. Plasminogen activator activity was inversely related to serum triglyceride levels in patients with primary biliary cirrhosis. Urokinase inhibitors were decreased in both groups and antiplasmins increased in patients with large duct obstruction; fibrin/fibrinogen degradation products were normal in primary biliary cirrhosis and moderately increased in large duct obstruction. None of these fibrinolytic indices was related to the degree of cholestasis. Fibrinolytic activity and fibrinogen returned almost to normal levels after palliative surgery in the three patients with large duct obstruction who were studied. The decreased plasma fibrinolysis and increased fibrinogen may be due to altered lipid metabolism in cholestatic jaundice. In patients undergoing surgery for large duct obstruction there may be an increased risk of thrombosis.

Topics: Adult; Aged; Antifibrinolytic Agents; Bile Duct Neoplasms; Cholestasis; Common Bile Duct; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Lipid Metabolism; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Palliative Care; Pancreatic Neoplasms; Plasminogen; Postoperative Complications; Thrombophlebitis; Triglycerides

Topics: Adult; Aged; Blood Platelets; Collagen; Endothelium; Female; Femoral Vein; Fibrin; Fibrinolysis; Hemosiderin; Humans; Ischemia; Leukocytes; Male; Middle Aged; Plasminogen; Popliteal Vein; Staining and Labeling; Thrombophlebitis; Veins

Topics: Adult; Antibodies; Antibodies, Anti-Idiotypic; Blood Cell Count; Blood Coagulation; Blood Coagulation Disorders; Blood Platelet Disorders; Clot Retraction; Erythrocytes; Factor X; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Male; Plasminogen; Platelet Adhesiveness; Pulmonary Embolism; Stimulation, Chemical; Thrombin; Thrombophlebitis; Thrombosis

Topics: Acute Kidney Injury; Animals; Blood Urea Nitrogen; Diagnosis, Differential; Disease Models, Animal; Fibrin; Fibrinogen; Graft Rejection; Hydronephrosis; Iodine Radioisotopes; Kidney Transplantation; Ligation; Protein Binding; Rabbits; Renal Artery Obstruction; Renal Veins; Thrombophlebitis; Thrombosis; Transplantation, Homologous

Topics: alpha 1-Antitrypsin; Blood Coagulation; Clot Retraction; Fibrin; Fibrinolysis; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Leukocytes; Macroglobulins; Plasminogen; Streptokinase; Thrombophlebitis; Thrombosis; Time Factors

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

Topics: Animals; Blood Platelets; Carotid Arteries; Dogs; Embolism; Endothelium; Femoral Artery; Fibrin; Leg; Microscopy, Electron, Scanning; Thrombophlebitis; Thrombosis; Time Factors; Vasa Vasorum

Topics: Catheterization; Collateral Circulation; Fibrin; Forearm; Hand; Heparin; Humans; Methods; Polytetrafluoroethylene; Polyvinyls; Radiography; Subclavian Vein; Thrombophlebitis; Time Factors; Wrist

Topics: Fibrin; Fibrinogen; Half-Life; Humans; Iodine Isotopes; Radiometry; Surface Properties; Thrombophlebitis; Wound Healing

Topics: Acute Disease; Adolescent; Adult; Aged; Blood Coagulation Tests; Diagnosis, Differential; Fibrin; Fibrinogen; Humans; Iodine Radioisotopes; Methods; Middle Aged; Phlebography; Protamines; Pulmonary Embolism; Radionuclide Imaging; Staphylococcus; Thrombophlebitis

Topics: Blood Coagulation Disorders; Blood Platelet Disorders; Blood Platelets; Fibrin; Humans; Phospholipids; Platelet Adhesiveness; Thrombophlebitis; Thrombosis

Topics: Aged; Angiography; Antigens; Female; Femoral Neck Fractures; Fibrin; Fibrinogen; Fibrinolysis; Heart Failure; Humans; Iodine Radioisotopes; Male; Neoplasm Metastasis; Postoperative Complications; Pulmonary Embolism; Radionuclide Imaging; Sepsis; Thrombophlebitis

Topics: Fibrin; Fibrinogen; Humans; Pulmonary Embolism; Thrombophlebitis

Topics: Antigens; Fibrin; Fibrinogen; Humans; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis

Topics: Fibrin; Fibrinogen; Humans; Iodine Isotopes; Postoperative Complications; Radionuclide Imaging; Thrombophlebitis; Time Factors

Topics: Acute Disease; Age Factors; Aged; Fibrin; Fibrinogen; Humans; Middle Aged; Myocardial Infarction; Serologic Tests; Thrombophlebitis

Topics: Ammonia; Blood Cell Count; Blood Coagulation; Blood Platelets; Blood Proteins; Factor XIII; Factor XIII Deficiency; Fibrin; Fibrinolysin; Fibrinolysis; gamma-Globulins; Humans; Hypergammaglobulinemia; Immune Sera; Methods; Putrescine; Solubility; Streptokinase; Thrombocytopenia; Thrombophlebitis; Time Factors

Topics: Blood Vessels; Cornea; Female; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Histocytochemistry; Kidney Glomerulus; Methods; Plasminogen; Regeneration; Thrombophlebitis; Uterus; Wound Healing

The isotopic method described previously for quantification of plasmin- (125)I by disc gel electrophoresis was modified by inclusion of euglobulin precipitation to expand its applicability to plasmas containing low radioactivity of plasmin- (125)I and plasminogen- (125)I. It was found that the euglobulin precipitation method precipitates 72.4+/-2.1 (sd)% of both plasmin- (125)I and plasminogen- (125)I. Using this method and plasminogen- (125)I as a tracer, studies were first made of the effects of heparin and epsilon-aminocaproic acid in dogs on plasmin- (125)I generation in responese to a single injection of urokinase and to venous injury; second, of the effects of venous occlusion and thrombosis on plasmin- (125)I generation; and third, in vitro studies of plasminogen- (125)I affinity to fibrin and its activation in blood clots. The venous injury was produced by the damage of venous endothelium by an injection of 90% phenol and the thrombosis by a thrombin injection into an occluded vein. Heparin and epsilon-aminocaproic acid under the present experimental conditions inhibited about 78 and 100%, respectively of plasmin- (125)I generation by the urokinase injection. Similar inhibitory effects of heparin and epsilon-aminocaproic acid were observed on plasmin- (125)I generation in response to venous injury. The venous occlusion caused a small degree of plasmin- (125)I generation, but thrombin thrombosis did not seem to stimulate the generation of plasmin- (125)I. The in vitro studies showed that plasminogen- (125)I does not have a specific affinity to fibrin and is incorporated into blood clots in approximately equal concentrations as those in serum during clotting processes, and that blood clots per se do not stimulate plasmin- (125)I generation. These results suggest that injured veins release considerable amounts of vascular plasminogen activators into circulation and that these play an important role in thrombus dissolution in vivo.

Topics: Aminocaproates; Animals; Blood Coagulation; Dogs; Electrophoresis, Disc; Fibrin; Fibrinolysin; Fibrinolytic Agents; Heparin; Iodine Isotopes; Kinetics; Methods; Phenols; Plasminogen; Protein Binding; Thrombin; Thrombophlebitis; Vascular Diseases

Topics: Animals; Dogs; Electrophoresis, Disc; Enzyme Activation; Fibrin; Fibrinolysin; Hindlimb; Iodine Isotopes; Ligation; Phenols; Plasminogen; Thrombin; Thrombophlebitis; Tourniquets; Vascular Diseases; Veins; Wounds and Injuries

Topics: Aged; Aminocaproates; Animals; Blood Flow Velocity; Blood Platelets; Dextrans; Electric Stimulation; Fibrin; Fibrinogen; Humans; Iodine Isotopes; Leg; Male; Middle Aged; Phlebography; Platelet Adhesiveness; Postoperative Complications; Prostatectomy; Rabbits; Thrombophlebitis; Time Factors

Topics: Adult; Anticoagulants; Blood Cell Count; Blood Platelets; Ethyl Biscoumacetate; Ethylestrenol; Female; Fibrin; Fibrinogen; Fibrinolysis; Fluorescent Antibody Technique; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Neutrophils; Phagocytosis; Phenformin; Phlebography; Platelet Adhesiveness; Pulmonary Embolism; Pyrazoles; Thrombophlebitis; Time Factors

Topics: Adhesiveness; Blood Platelets; Erythrocytes; Fibrin; Humans; Microscopy, Electron, Scanning; Thrombophlebitis; Varicose Veins

Topics: Adult; Cerebral Hemorrhage; Contraceptives, Oral; Dura Mater; Ethinyl Estradiol; Female; Fibrin; Hematoma; Humans; Intracranial Embolism and Thrombosis; Lynestrenol; Mestranol; Middle Aged; Pia Mater; Sinus Thrombosis, Intracranial; Testosterone; Thrombophlebitis

Topics: Alanine; Blood Coagulation; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Glycine; Heparin; Humans; Male; Methods; Middle Aged; Pancreatic Neoplasms; Thrombin; Thrombophlebitis; Tyrosine; Warfarin

Topics: Adult; Arm; Chronic Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Hemiplegia; Humans; Immobilization; Leg; Macroglobulins; Male; Middle Aged; Plasminogen; Posture; Pre-Eclampsia; Pregnancy; Thrombophlebitis

Topics: Fibrin; Fibrinogen; Humans; Lung; Peptide Hydrolases; Plasminogen; Prothrombin Time; Spleen; Thrombophlebitis

Topics: Aged; Antigens; Fibrin; Fibrinogen; Humans; Iodine Isotopes; Middle Aged; Postoperative Complications; Pulmonary Embolism; Thrombophlebitis; Time Factors

Topics: Blood Coagulation Disorders; Disseminated Intravascular Coagulation; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Premature; Renal Veins; Thrombophlebitis

Topics: Autopsy; Benzalkonium Compounds; Carbon; Catheterization; Cineradiography; Fibrin; Fluorocarbon Polymers; Heparin; Humans; Nylons; Polyethylenes; Rubber; Silicones; Sodium; Subclavian Vein; Thrombophlebitis

Topics: Adolescent; Adult; Aged; Antigens; Antithrombins; Blood Cell Count; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Child; Child, Preschool; Factor V; Factor VIII; Female; Fibrin; Fibrinogen; Hemiplegia; Humans; Immune Sera; Immunodiffusion; Male; Middle Aged; Nephrotic Syndrome; Phlebitis; Pulmonary Artery; Renal Veins; Thrombophlebitis; Thrombosis

A total of 76 "high-risk" surgical patients were studied for evidence of venous thromboembolic disease. Episodes of deep vein thrombosis and of pulmonary embolism were related to changes in blood levels of fibrin degradation products (F.D.P.). When diagnosed either by ordinary clinical means or by venography and isotope scanning significantly raised F.D.P. levels were found in all cases. Serum F.D.P. estimations are unlikely to help in detecting deep vein thrombosis, but may prove valuable in diagnosing pulmonary embolism.

Topics: Adult; Aged; Female; Fibrin; Fibrinogen; Humans; Iodine Radioisotopes; Male; Middle Aged; Phlebography; Postoperative Complications; Pulmonary Embolism; Radionuclide Imaging; Thrombophlebitis

Topics: Fibrin; Fibrinogen; Humans; Immunoassay; Pulmonary Embolism; Thrombophlebitis

Topics: Adult; Age Factors; Aged; Catheterization; Contrast Media; Female; Fibrin; Foreign Bodies; Humans; Jugular Veins; Male; Methods; Phlebography; Subclavian Vein; Thrombophlebitis

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: 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: Blood Coagulation Disorders; Blood Coagulation Factors; Blood Coagulation Tests; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Humans; Middle Aged; Purpura, Thrombocytopenic; Thrombophlebitis; Thromboplastin

Topics: Animals; Carotid Artery Thrombosis; Cattle; Dogs; Electricity; Femoral Vein; Fibrin; Fibrinolysis; Jugular Veins; Thrombin; Thrombophlebitis

Topics: Animals; Blood Coagulation Disorders; Capillaries; Dogs; Fibrin; Gastric Mucosa; Heparin; Humans; Kidney Glomerulus; Lung; Male; Middle Aged; Popliteal Vein; Pulmonary Embolism; Rabbits; Rats; Thrombophlebitis; Thrombosis

Topics: Aged; Antigen-Antibody Reactions; Fibrin; Fibrinogen; gamma-Globulins; Humans; Iodine Isotopes; Leg Injuries; Middle Aged; Radiometry; Thrombophlebitis

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; Humans; Inflammation; Infusions, Intravenous; Streptodornase and Streptokinase; Streptokinase; Thrombophlebitis

Topics: Fibrin; Fibrinogen; Humans; Thrombophlebitis