fibrin and Vascular-Diseases

Fibrin clot formation is a key event in the development of thrombotic disease and is the final step in a multifactor coagulation cascade. Fibrinogen is a large glycoprotein that forms the basis of a fibrin clot. Each fibrinogen molecule is comprised of two sets of Aα, Bβ, and γ polypeptide chains that form a protein containing two distal D regions connected to a central E region by a coiled-coil segment. Fibrin is produced upon cleavage of the fibrinopeptides by thrombin, which can then form double-stranded half staggered oligomers that lengthen into protofibrils. The protofibrils then aggregate and branch, yielding a three-dimensional clot network. Factor XIII, a transglutaminase, cross-links the fibrin stabilizing the clot protecting it from mechanical stress and proteolytic attack. The mechanical properties of the fibrin clot are essential for its function as it must prevent bleeding but still allow the penetration of cells. This viscoelastic property is generated at the level of each individual fiber up to the complete clot. Fibrinolysis is the mechanism of clot removal, and involves a cascade of interacting zymogens and enzymes that act in concert with clot formation to maintain blood flow. Clots vary significantly in structure between individuals due to both genetic and environmental factors and this has an effect on clot stability and susceptibility to lysis. There is increasing evidence that clot structure is a determinant for the development of disease and this review will discuss the determinants for clot structure and the association with thrombosis and vascular disease.

Topics: Animals; Fibrin; Humans; Thrombosis; Vascular Diseases

The formation of a fibrin clot is a pivotal event in atherothrombotic vascular disease and there is mounting evidence that the structure of clots is of importance in the development of disease. This review describes the crucial events in the formation and dissolution of a clot, with particular focus on genetic and environmental factors that have been identified as determinants of fibrin structure in vivo, and discusses the substantiation of the relationship between fibrin structure and disease in conjunction with a review of the current literature.

Topics: Blood Coagulation; Factor XIIIa; Fibrin; Fibrinogen; Humans; Structure-Activity Relationship; Thrombosis; Vascular Diseases

A review of 117 research publications describes a deficiency in fatty acid transport into intracellular oxidative energy metabolism which causes increased fibrinogen synthesis and turnover into fibrin. The increased production of fibrin, coupled with depressed activation of plasminogen, increases the fibrin/plasmin ratio causing thrombosis-induced atherogenesis. This discovery unifies the two schools of atherogenesis based on blood lipid or fibrin deposition theories.

Topics: Animals; Arteriosclerosis; Energy Metabolism; Fatty Acids, Nonesterified; Fibrin; Fibrinogen; Fibrinolysin; Humans; Models, Biological; Vascular Diseases

Our current hypothesis is that mechanical damage in the spine such as a disc prolapse can lead directly to pain. However, pain arising for this reason is usually of short duration. In many subjects, however, the mechanical problems lead to vascular damage and, in particular, venous obstruction and dilatation with endothelial damage, fibrin deposition, and intravascular thromboses. In turn, this is associated with perineural and intraneural fibrosis. There is a defect in the fibrinolytic system in the peripheral blood that may be the result of vascular damage but in turn may contribute to the persistence of this problem. Therefore, it seems likely that in many patients with chronic mechanical back pain there are important vascular, fibrotic, and inflammatory components to the problem. Treatment in the future should be directed specifically at these aspects of the disorder and hopefully can lead to better control of symptoms.

Topics: Arachnoiditis; Back Pain; Biomechanical Phenomena; Fibrin; Fibrosis; Humans; Lumbar Vertebrae; Spinal Osteophytosis; Vascular Diseases

Topics: Animals; Basement Membrane; Endothelium, Vascular; Fibrin; Fibrinogen; Vascular Diseases

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

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

The effects of phenformin and ethyloestrenol and phenformin and stanozolol on the clinical state, plasma fibrinolytic activity, and fibrinogen-fibrin-related antigen (F.R.-antigen) were compared with placebo in 13 patients with cutaneous vasculitis. Eight patients showed considerable clinical improvement when taking phenformin and an anabolic steroid; an impaired fibrinolytic activity before treatment favoured clinical improvement.

Topics: Adolescent; Adult; Aged; Antigens; Blood Coagulation Tests; Clinical Trials as Topic; Ethylestrenol; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Middle Aged; Phenformin; Skin Diseases; Stanozolol; Vascular Diseases

Topics: Adult; Aged; Arteriosclerosis; Arthritis, Rheumatoid; Blood Coagulation; Clinical Trials as Topic; Ethylestrenol; Female; Fibrin; Fibrinogen; Fibrinolysis; Humans; Male; Middle Aged; Phenformin; Placebos; Time Factors; Vascular Diseases

Primary hemostasis (platelet plug formation) and secondary hemostasis (fibrin clot formation) are intertwined processes that occur upon vascular injury. Researchers have sought to target wounds by leveraging cues specific to these processes, such as using peptides that bind activated platelets or fibrin. While these materials have shown success in various injury models, they are commonly designed for the purpose of treating solely primary or secondary hemostasis. In this work, a two-component system consisting of a targeting component (azide/GRGDS PEG-PLGA nanoparticles) and a crosslinking component (multifunctional DBCO) is developed to treat internal bleeding. The system leverages increased injury accumulation to achieve crosslinking above a critical concentration, addressing both primary and secondary hemostasis by amplifying platelet recruitment and mitigating plasminolysis for greater clot stability. Nanoparticle aggregation is measured to validate concentration-dependent crosslinking, while a 1:3 azide/GRGDS ratio is found to increase platelet recruitment, decrease clot degradation in hemodiluted environments, and decrease complement activation. Finally, this approach significantly increases survival relative to the particle-only control in a liver resection model. In light of prior successes with the particle-only system, these results emphasize the potential of this technology in aiding hemostasis and the importance of a holistic approach in engineering new treatments for hemorrhage.

Topics: Azides; Blood Platelets; Fibrin; Hemorrhage; Hemostasis; Humans; Thrombosis; Vascular Diseases

Patients with chronic venous disease (CVD) have elevated levels of leucocyte elastase (LE) released from the activation of leucocytes. In acute deep venous thrombosis (DVT), LE can degrade fibrin from the thrombus resulting in cross-linked fibrin degradation products (E-XDP) being released into the bloodstream. In patients with CVD the levels and significance of circulating E-XDP are unknown. We aimed to investigate the association between plasma E-XDP concentration and severity of CVD. Levels of E-XDP were quantified with a specific enzyme-linked immunosorbent assay (ELISA) in plasma from 142 consecutively recruited CVD patients (mean age 64 years, (range 23-89), 81 were females and 61 males). Patients were also divided into three groups based on CVD severity using the C-class of the Clinical-Etiological-Anatomical-Pathophysiological (CEAP) classification, with C 0-1 class as the reference group, C 2-3 as the second group and C 4-6 as the third group with the most severely affected patients. We found significantly elevated levels of E-XDP in patients with C 4-6 compared with patients with C 0-1 (p = 0.007) and increased with increasing disease severity across the groups (p = 0.02). Significant independent association was observed between levels of E-XDP and the classes C 4-6 after adjustment for age and sex (p < 0.05), but the association was no longer significant after further adjustment for use of statins, use of anticoagulants and history of DVT (p = 0.247). This exploratory study shows that E-XDP levels are elevated in patients with CVD, encouraging further studies on the role of E-XDP in CVD.

Topics: Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Humans; Leukocyte Elastase; Male; Middle Aged; Vascular Diseases; Veins; Young Adult

In the setting of preeclampsia (PE), decidual vasculopathy (DV) can be seen along the free membranes.. We describe DV using stains for CD31, CD34, Cd42b, CD68, desmin, fibrin and Masson's trichrome in patients with preeclampsia and fetal growth restriction.. We first examined the "membrane roll" sections from the placentas of six patients with preeclampsia. Affected vessels showed endothelial proliferation with detachment. Remodeling of the media was characterized by smooth muscle loss with variable degrees of fibrin deposition. CD31 and CD34 highlighted the prominent endothelium and showed striking particulate staining throughout the media. All of these findings infer a sequence of endothelial injury, fragmentation and repair with incorporation of endothelial components into the vascular wall. We evaluated the frequency of DV by clinical presentation; in cases with PE with and without small for gestational age (SGA) (N = 15), and SGA with and without Doppler flow abnormalities (N = 15). All groups except the SGA without Doppler abnormalities showed DV. Among placentas with DV, the most severely affected group was PE with SGA; the least affected was PE without SGA.. The association with SGA suggests that the DV is a subacute process of vascular injury that accelerates in the setting of PE. The majority of DV cases were not initially recognized suggesting a role for endothelial markers for DV detection. We also propose that the rampant endothelial injury seems to be a prominent finding in the decidual vessels of subjects with PE complicated by SGA and a similar process in the systemic vasculature may be responsible for the circulating endothelial microparticles reported in such patients.

Topics: Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; Decidua; Desmin; Female; Fetal Growth Retardation; Fibrin; Humans; Neovascularization, Pathologic; Placenta; Platelet Endothelial Cell Adhesion Molecule-1; Platelet Glycoprotein GPIb-IX Complex; Pre-Eclampsia; Pregnancy; Vascular Diseases

This study examined the clinical significance of intra-alveolar fibrin deposition (IAFD) in transbronchial lung biopsy specimens obtained from patients with organizing pneumonia.. Pathological reports of transbronchial lung biopsies performed between 2004 and 2012 were reviewed to identify cases of intra-alveolar organization with or without fibrin deposition. Clinical charts, computed tomography images, and transbronchial lung biopsy specimens from these cases were examined retrospectively. Diagnosis of organizing pneumonia was reevaluated based upon the consensus of a respiratory physician, a radiologist, and a pathologist.. Transbronchial lung biopsy results of the reviewed patients with organizing pneumonia found seven patients who had IAFD, and 34 who did not. Seven patients' conditions were associated with collagen vascular disease (CVD), and 34 were cryptogenic. IAFD was significantly associated with high C-reactive protein (CRP) values (>5 mg/dl) (p = 0.0012) and underlying CVD (p = 0.0099). Multivariate analysis revealed that IAFD was independently associated with high CRP values (p = 0.0184). Three of 31 patients and six of 27 patients experienced a relapse of organizing pneumonia within 6 months and 1 year, respectively. IAFD (p = 0.0044) and high CRP values (p = 0.0207) were significantly related to relapse within 6 months, while only CRP was significantly related to relapse within 1 year (p = 0.0007).. In patients with organizing pneumonia, IAFD was significantly associated with high CRP values. High CRP values and/or IAFD predicted relapse of organizing pneumonia within 6 months to 1 year.

Topics: Aged; Biopsy; C-Reactive Protein; Collagen Diseases; Female; Fibrin; Humans; Male; Pneumonia; Pulmonary Alveoli; Radiography; Recurrence; Retrospective Studies; Vascular Diseases

Topics: Calcinosis; Catheter-Related Infections; Catheters, Indwelling; Diagnosis, Differential; Fibrin; Humans; Jugular Veins; Male; Middle Aged; Radiography; Vascular Diseases

The incorporation of virus- and host-derived procoagulant factors initiates clotting directly on the surface of herpesviruses, which is an explanation for their correlation to vascular disease. The virus exploits the resulting thrombin to enhance infection by modulating the host cell through protease activated receptor (PAR) 1 signalling. Prior reports demonstrated that at least one herpesvirus expresses surface annexin A2 (A2), a cofactor for tissue plasminogen activator (tPA)-dependent activation of plasminogen to plasmin. Since plasmin is both a fibrinolytic protease and PAR agonist, we investigated whether herpesviruses enhance fibrinolysis and the effect of plasmin on cell infection. Herpes simplex virus types 1 (HSV1) and 2, and cytomegalovirus (CMV) purified from various cell lines each accelerated the proteolytic activation of plasminogen to plasmin by tPA. Ligand blots identified A2 as one of several plasminogen binding partners associated with the virus when compared to an A2-deficient virus. This was confirmed with inhibitory A2-antibodies. However, A2 was not required for virus-enhanced plasmin generation. HSV1, HSV2 and CMV accelerated tPA-dependent fibrin clot lysis by up to 2.8-fold. Modest plasmin generation and fibrinolysis was detected independent of exogenous tPA, which was inhibited by plasminogen activator inhibitor type-1 and ε-aminocaproic acid; however, the molecular basis remains speculative. Up to a ~6-fold enhancement of infection was provided by plasmin-mediated cell infection. Inhibitory antibodies revealed that plasmin increased HSV1 infection through a mechanism involving PAR2. Thus, virus-enhanced fibrinolysis may help explain the paradox of the highly procoagulant in vitro herpesvirus surface eliciting only relatively weak independent vascular disease risk.

Topics: Annexin A2; Cytomegalovirus; Fibrin; Fibrinolysin; Fibrinolysis; Herpesviridae; Human Umbilical Vein Endothelial Cells; Humans; Ligands; Plasmids; Plasminogen; Recombinant Proteins; Thrombin; Tissue Plasminogen Activator; Vascular Diseases

Spotting clots: Vascularly constrained colloidal gold nanobeacons (GNBs; see picture) can be used as exogenous photoacoustic contrast agents for the targeted detection of fibrin, a major biochemical feature of thrombus. Fibrin-targeted GNBs provide a more than tenfold signal enhancement in photoacoustic tomography in the near-IR wavelength window, indicating their potential for diagnostic imaging.

Topics: Colloids; Contrast Media; Fibrin; Gold; Humans; Metal Nanoparticles; Tomography, Optical; Ultrasonography; Vascular Diseases

To evaluate the influence of impaired masseter function during growth on the development of temporomandibular synovitis.. Sixteen 3-week-old male Wistar rats were classified into four groups. The first group served as control; and in the second group, jaw opening was forced for 3 hours when the rats were 9 weeks old. In the third and fourth groups, the masseter muscles were bilaterally resected at 3 weeks of age, and the rats in the fourth group were additionally forced to open their jaw at 9 weeks of age. All rats were sacrificed at 9 weeks. Temporomandibular joint (TMJ) tissue samples were processed for histology, and evaluated for cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions by immunohistochemistry to examine the inflammatory changes in the synovial membrane.. The control group showed noninflammatory changes. In the jaw-opening group, vascular dilation and weak COX-2 immunoreactivity were induced by jaw opening in the synovium. In the masseter-resection group, the masseter-resected rats exhibited moderate synovial changes while in the resection with opening group, the masseter-resected rats revealed more significant inflammatory changes including synovial hyperplasia, dilated vasculature, fibrin deposits, and intense immunoreactivity for COX-2 and iNOS, all caused by jaw opening.. These results suggest that masseter activity in the growth period is an important factor in the induction of temporomandibular synovitis.

Topics: Animals; Cyclooxygenase 2; Dilatation, Pathologic; Fibrin; Hyperplasia; Immunohistochemistry; Male; Masseter Muscle; Muscle Weakness; Nitric Oxide Synthase Type II; Range of Motion, Articular; Rats; Rats, Wistar; Stress, Mechanical; Synovial Membrane; Synovitis; Temporomandibular Joint; Temporomandibular Joint Disorders; Vascular Diseases

Topics: Collagen Diseases; Fibrin; Humans; Lung; Lung Diseases, Interstitial; Male; Middle Aged; Pneumonia; Pulmonary Alveoli; Vascular Diseases

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Topics: Animals; Biomarkers; Cerebral Cortex; Dysferlin; Encephalomyelitis, Autoimmune, Experimental; Female; Fibrin; Humans; Immunohistochemistry; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Multiple Sclerosis; Muscle Proteins; Nerve Tissue Proteins; Rats; Rats, Inbred Lew; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vascular Diseases

Fibrinogen and fibrin are molecules with overlapping roles in blood clotting, fibrinolysis, wound healing, inflammation, matrix and cellular interactions and neoplasia. There is currently much interest in the possible use of fibrinolytic agents in human therapeutics. In this study, we report the presence of fibrinolytic activities in shark cartilage extract (SCE). In vitro, SCE at 100 microg/ml completely degraded fibrin gel in an aprotinin-insensitive manner, suggesting a non-plasmin molecular nature. SCE was able to cleave all chains of fibrinogen and fibrin and the cleavage was completely inhibited by 1,10-phenanthroline, suggesting an essential role for metalloprotease(s) in this process. Using fibrinogen zymography, we show that SCE contains two plasmin-independent fibrinolytic activities and that these activities are correlated with the presence of 58 and 62 kDa proteases in the extract. SCE-fibrinolytic activities are inhibited by dithiothreitol, suggesting that disulfide bonds are necessary for the protease structure. Finally, using thromboelastography, SCE markedly induced retraction of human platelet-rich plasma (PRP) clot, this process being completely abolished by 1,10-phenanthroline. These data suggest the presence of novel non-plasmin fibrinolytic activities within SCE. This extract may thus represent a potential source of new therapeutic molecules to prevent and treat vaso-occlusive and thromboembolic disorders.

Topics: Animals; Cartilage; Cell Extracts; Clot Retraction; Disulfides; Enzymes; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolytic Agents; Humans; Metalloproteases; Molecular Weight; Sharks; Vascular Diseases

Hemostatic parameters were examined in 39 patients who underwent allogeneic bone marrow transplantation (BMT). Twenty-six patients survived and 13 patients died within 6 months after BMT. The main causes of death were acute graft-versus-host disease (GVHD: n=6), veno-occlusive disease (VOD: n=2), and thrombotic microangiopathy (TMA: n=2). Plasma levels of D-dimer and thrombomodulin (TM) were significantly elevated in the non-survivor group. Plasma levels of soluble fibrin (SF) and Fas were significantly elevated in the non-survivor group at 1 to 4 weeks after BMT. Plasma levels of thrombin-antithrombin complex (TAT), D-dimer, and tissue plasminogen activator-plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex) were significantly elevated in patients with complications after BMT. Plasma levels of TAT, D-dimer, and tPA-PAI-1 complex were significantly elevated in patients with GVHD. These results suggest that abnormalities of hemostatic parameters might predict poor outcomes or complications in patients with BMT.

Topics: Adolescent; Adult; Biomarkers; Blood Coagulation Factors; Bone Marrow Transplantation; Cause of Death; fas Receptor; Female; Fibrin; Follow-Up Studies; Graft vs Host Disease; Hematologic Neoplasms; Hemostasis; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Transplantation, Homologous; Vascular Diseases

Echogenic immunoliposomes (ELIP) for enhancement of vasoactive and pathologic components of endothelium and atherosclerosis have been developed. A physiologic flow chamber model has been developed to define intravascular ultrasound enhancement of a fibrin interface.. A IgG ELIP was used, which nonspecifically associated with fibrin, to demonstrate the suitability of this model. With varying doses of IgG ELIP, the fibrin wells were imaged at 1, 2, 4, 6, and 9 minutes.. IgG ELIP enhanced fibrin versus saline (P < 0.005) was visible at 1 minute, lasted at least 9 minutes, and at 6 minutes the interface enhanced 27% +/- 6.1%. Enhancement was caused by increases in interface thickness and brightness. Enhancement increased with dose up to 8 mg lipid (n = 4 per time point).. This model can quantitate the components of IVUS enhancement of an interface produced by ELIP. This model may allow for further development and understanding of ELIP and other targeted ultrasound contrast agents.

Topics: Analysis of Variance; Animals; Equipment Design; Fibrin; Humans; Image Enhancement; Immunoglobulin E; Liposomes; Rabbits; Rheology; Ultrasonography; Vascular Diseases

Abnormal plasminogen activation has been implicated in vascular and rheumatic diseases. The development of an autoimmune response to neoepitopes of plasminogen and its activator (tissue-type plasminogen activator, t-PA) was explored in sera from patients with rheumatoid arthritis (RA, n = 30), Behcet's disease (n = 20), primary antiphospholipid syndrome (APS, n = 23), and idiopathic arterial (n = 33) or venous thrombosis (n = 16).. Sera diluted 1/50 were incubated with either plasminogen or t-PA bound to their natural receptors (immobilized fibrin or monocytic cells), and bound immunoglobulins were detected using a sheep peroxidase labeled anti-human Fab IgG. Controls included plates coated with fibrin or cells alone or plasminogen passively adsorbed to the plastic. Sera were considered positive when the absorbance at 405/490 nm was above the mean + 2 SD of normal sera.. Reactivity of sera against plasminogen bound to cells (28%) or to fibrin (22%) was a predominant feature in patients with RA compared with other patient groups and controls. However, some patients with primary APS had reactivity against cell and fibrin bound plasminogen (9 and 13%, respectively). Autoantibodies against fibrin bound t-PA were detected in only 8% of patients with arterial or venous thrombosis.. Conformational changes induced by molecular assembly of plasminogen on cell or fibrin surfaces result in the expression of neoepitopes recognized by autoantibodies. These autoantibodies could be markers of the proteolytic events associated with plasminogen activation in autoimmune diseases.

Topics: Adult; Antigen-Antibody Complex; Antigens; Autoantibodies; Binding Sites, Antibody; Cell Line; Epitopes; Fibrin; Humans; Middle Aged; Plasminogen; Receptors, Cell Surface; Rheumatic Diseases; Tissue Plasminogen Activator; Vascular Diseases

To examine the vascular changes occurring in three archival cases of acute multiple sclerosis, and to provide immunohistochemical evidence of early endothelial cell activation and vascular occlusion in this condition.. Central nervous system tissues from three cases of acute active multiple sclerosis and six non-inflammatory controls were stained using the following methods: haematoxylin and eosin, Luxol fast blue, cresyl violet, Bielschowsky's silver, and reticulin. Tissues were also immunostained with specific antibodies against collagen type IV, factor XIIIa, class II antigens, glial fibrillary acidic protein, and fibrinogen.. Early vascular endothelial cell activation which may progress to vasculitis and vascular occlusion including class II antigen expression and fibrin deposition were identified. The vascular changes were seen prior to cerebral parenchymal reaction and demyelination, and were not seen in control cerebral tissues.. It is proposed that vascular endothelial cell activation may be an early and pivotal event in the evolution of multiple sclerosis, and that demyelination may have an ischaemic basis in this condition. The vascular endothelium may contain an early element in the evolution of multiple sclerosis.

Topics: Acute Disease; Adolescent; Adult; Brain; Endothelium, Vascular; Female; Fibrin; HLA-D Antigens; Humans; Immunoenzyme Techniques; Male; Microcirculation; Multiple Sclerosis; Thrombosis; Vascular Diseases; Vasculitis

Vascular or tissue-type plasminogen activator (plasma t-PA) is the circulating physiological fibrinolytic enzyme of endothelial cell origin which function is regulated by fibrin and a specific inhibitor (PAI). To study the pattern of release of t-PA and the behavior of t-PA-PAI complexes in plasma we determined t-PA activity in 44 healthy subjects before and after 10 min of forearm venous occlusion using a new spectrophotometric solid-phase fibrin-tPA activity assay. The assay is based on 1) the high affinity binding of t-PA to fibrin, and 2) the detection of fibrin-bound t-PA by measuring the release of pNA from a chromogenic substrate in the presence of plasminogen. Values at rest were rather undetectable in plasma (0.05 +/- 0.03 IU/ml, in 23 out of 44 samples) but were positively detected in all the euglobulins: 0.88 +/- 0.68 IU/ml. After venous occlusion the majority of plasmas (36 out of 44) showed a slight increase in t-PA activity (0.65 +/- 0.63 IU/ml) as compared to the important level observed in all the euglobulins (9.78 +/- 9.58 IU/ml). So, the ratio plasma/euglobulin t-PA activity was very low (0.06) and remained identical in both pre- and postocclusion samples. However, when diluted plasmas were tested the inhibitory effect disappeared and t-PA activity increased indicating that although t-PA circulates in a neutralized state it can be available for fibrinolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Fibrin; Glycoproteins; Humans; In Vitro Techniques; Kinetics; Plasminogen Inactivators; Spectrophotometry; Tissue Plasminogen Activator; Vascular Diseases

Pericapillary fibrin deposition is thought to contribute to the pathogenesis of venous ulceration. To our knowledge, however, there is no previous evidence that pericapillary fibrin is deposited in the tissue adjacent to venous ulcers. We prospectively studied patients with ulcers of the lower extremities for the presence of dermal pericapillary fibrin in the skin adjacent tot he ulcers. On direct immunofluorescence, pericapillary fibrin was found in 14 (93%) of the 15 patients with venous ulceration but in only one (7%) of the 14 subjects with ulcers due to other causes. We also confirmed the presence of dermal pericapillary fibrin in legs with venous disease without ulcerations. We conclude that the pericapillary fibrin is easily demonstrable in the dermis adjacent to venous ulcers. In the evaluation of ulcers due to uncertain causes, the presence of dermal pericapillary fibrin may provide additional diagnostic help.

Topics: Biopsy; Blood Gas Monitoring, Transcutaneous; Capillaries; Fibrin; Fluorescent Antibody Technique; Humans; Leg; Skin; Ulcer; Vascular Diseases; Veins; Wound Healing

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

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

29 autogenous vein grafts, from 26 patients with peripheral arterial disease, were studied. 4 grafts of Group I (less than 3 months duration) were patent and removed for reasons other than graft failure. These showed 'arterialisation' only; 4 grafts of Group II (duration 5-18 months) showed thrombotic occlusion; 21 grafts of Group III (duration greater than 2 years) showed impaired graft patency and lipid identifiable as apolipoprotein B-containing-lipoproteins (LpB), and fibrinogen-related antigens (FRA) were seen as intramural deposits in the thickened grafts. LpB was also seen in a perifibrous distribution on the collagen of organised thrombi. Complicated lesions in some Group III grafts showed stenosis or occlusion, ulceration, calcification or aneurysm formation. These features suggest that a process indistinguishable from 'true' atherosclerosis affects vein grafts of long duration. The ways in which such changes may: contribute to graft failure; and improve our understanding of the basic processes involved in atherogenesis, are discussed.

Topics: Adult; Aged; Apolipoproteins B; Arteries; Arteriosclerosis; Endothelium; Female; Fibrin; Graft Occlusion, Vascular; Histocytochemistry; Humans; Lipid Metabolism; Male; Middle Aged; Time Factors; Vascular Diseases; Veins

Until recently, fibrin deposition has been generally viewed as a ubiquitous, but passive, characteristic of both acute and chronic inflammatory processes. An increasing number of studies, however, suggest that fibrin deposition and fibrin degradation products may play an active role in these reactions, especially in the development of tissue edema. As the intravascular-to-extravascular "gateway" for movement of fluids, solutes, and cells must pass, the vascular endothelial cells may play a crucial regulatory role in this process. Recent evidence suggests that the interaction of whole fibrin with endothelial cells may lead to endothelial cell injury. This work examines the role of fibrin and fibrinogen-associated factors (FAF) in the injury of cultured vascular endothelial cells (VEC). It was demonstrated that endothelial cell injury, evidenced by retraction of the cells, was induced not only by whole fibrin, but also by soluble thrombin-cleaved products of fibrinogen. This reaction was shown to be specific for endothelial cells, nontoxic, and completely reversible. The general biological importance of this reaction was further underscored in that active factors could be generated from fibrinogen obtained from a number of species. Reproducible, quantitative assays of cultured endothelial cell retraction were developed to aid in the characterization of the endothelial cell-specific FAFs.

Topics: Animals; Blood; Cattle; Cell Survival; Cells, Cultured; Culture Media; Endothelium, Vascular; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Peptides; Pulmonary Artery; Thrombin; Vascular Diseases

The author's theory of the endoendothelial fibrin lining (EEFL), first advanced in 1953 and developed by him ever since, localizes the homeostasis between steady fibrin formation and deposition, or 'fibrination', and continuous fibrinolysis in the more or less immobile portion of the plasmatic zone next to the vessel wall. In 1971, the author advanced, in relation to the EEFL, the theory of fibrinogen gel clotting without thrombin action or 'fibrinogenin' formation in vivo. Considerable direct and indirect experimental evidence, secured by the author and by several other investigators, advanced markedly the knowledge of the normal physiology and the pathophysiology of various disease processes involving the vessel wall and blood circulation. The information presented is an extension to that given in the author's recent overview (Clin. Hemorheology 1, 9-72, 1981). It deals both with new data by several investigators including those by the author, as well as with older data from the literature. The author maintained already in 1960 that the blood together with the blood vessels, in which it circulates, constitute 'an entity'. In 1981 he postulated this entity to be a very special organ, named conveniently 'vessel-blood organ', which is ubiquitous and penetrates all other organs and adjacent tissues. The EEFL of the vessel-blood organ is considered by the author as the crucial critical interface between the blood and the vessel wall. It is the primary barrier, followed by the endothelium (comprising the endothelial cells and the interendothelial cement substance which contains or is identical with 'cement fibrin') and the basement membrane for the exchanges between the blood, the vessel wall and its surrounding tissues and spaces. The EEFL acts as anticoagulant, is antithrombogenic, maintains vascular patency and aids cardiac action by decreasing significantly the apparent viscosity of blood, referred to in the literature as the 'Copley-Scott Blair phenomenon'. A new concept of leukocyte emigration traversing the capillary wall is presented, affecting focal fibrinolysis of the EEFL and of fibrin contained in the interendothelial cement substance and in the basement membrane. The physical property of capillary (or vascular) permeability is related to the existence of the EEFL, since, as found by Copley et al, both fibrinopeptides, liberated in the transition of fibrinogen to fibrin, and plasminopeptides, freed in the conversion of plasminogen to plasmin, enha

Topics: Basement Membrane; Blood Vessels; Calcium; Capillaries; Capillary Permeability; Endothelium; Fibrin; Fibrinogen; Fibrinolysis; Gels; Homeostasis; Permeability; Surface Properties; Thrombosis; Vascular Diseases

Neuropathologic examination of an autopsy series of 54 patients of various types of CVD revealed a very high frequency of pathologic changes both in brain parenchyma (in 81%) and vessels (in 78%). A broad but continuous spectrum of primary vascular alterations was observed, ranging from fibrinoid deposits in intact or necrotizing vessel walls to fibrohyalinosis and endothelial proliferations. In acute SLE showing LE cells within brain tissues, immune complex deposits were observed for the first time in brain vessels, in addition to similar deposits in the plexus chorioideus and in hematoxylin bodies. Secondary complications are frequently affecting the brain in CVD; they are mainly sequels of systemic atherosclerosis, hypertension, thromboemboli from SLE endocarditis, cardiac, hepatic or renal dysfunctions, or infections and should be clinically differentiated from primary brain involvement in CVD to ensure the appropriate therapeutic measures.

Topics: Arthritis, Rheumatoid; Brain; Cerebral Arteries; Collagen Diseases; Complement C3; Fibrin; Humans; Immunoglobulin G; Lupus Erythematosus, Systemic; Myositis; Polyarteritis Nodosa; Purpura, Thrombotic Thrombocytopenic; Vascular Diseases; Vasculitis

The incidence of positive ethanol gelation test (EGT) after addition of brinase (a proteolytic enzyme preparation from Aspergillus oryzae) to anticoagulated and non-anticoagulated human plasma was studied. In vitro addition of brinase to plasma causes positive EGT, and the incidence is dose-dependent. In plasma from warfarin-treated patients and/or after addition of heparin to plasma, prior to the addition of brinase, a significantly reduced incidence of positive EGT is observed. The incidence is lowest after heparin. Gels formed in the presence of heparin are easier susceptible to enzymatic degradation than those formed in the absence of heparin.

Topics: Blood Coagulation Tests; Brinolase; Ethanol; Fibrin; Fibrinogen; Gels; Heparin; Humans; Peptide Hydrolases; Time Factors; Vascular Diseases; Warfarin

Topics: Capillary Permeability; Fibrin; Humans; Plasma; Vascular Diseases

Radially oriented acicular crystalline aggregates could be induced by incubating heparinised blood with bacterial endotoxins. These aggregates did not appear in the blood of 37 healthy volunteers but were observed in the blood of 130 patients, predominantly those with vasculitis, psoriasis, and bacterial infections. Study of these asteroid structures, which resemble 'sunbursts', led to the view that they are oriented crystals of fibrin radiating from a central platelet mass undergoing lysis.

Topics: Bacterial Infections; Blood Platelets; Crystallization; Dermatitis; Endotoxins; Enterobacteriaceae; Fibrin; Hemolysis; Humans; Hypersensitivity; In Vitro Techniques; Pseudomonas aeruginosa; Psoriasis; Streptococcus; Vascular Diseases

Erythema elevatum diutinum consists of chronic, often painful, predominantly acral skin nodules and plaques, associated with an underlying cutaneous vasculitis. A patient with this disorder is described, who had an elevated sedimentation rate, positive antinuclear factor, impaired clot lysis, and dramatic fibrin deposition in skin vessel walls. A variety of treatments were without benefit in this case as in most others, but phenformin produced marked improvement for periods of 11 and 16 months on two occasions. Protection of the lesions from minor trauma is also important.

Topics: Adjustment Disorders; Antibodies, Antinuclear; Blood Coagulation; Blood Sedimentation; Erythema; Female; Fibrin; Humans; Middle Aged; Phenformin; Vascular Diseases

The histotopical distribution of IgD and fibrin was examined in skin lesions of 12 patients with cutaneous vasculitis, by means of the direct IF method. IgD was found in 9 cases mostly in a striking fixation to the PMN-leucocytic inflammation cells. Homogeneous depositions of IgD in cutaneous blood vessel walls were seen twice. In 3 cases with older, lympho-histiocytic infiltrations, IgD was lacking. Fibrin was constantly present in the blood vessel walls of fresh and older vasculitis lesions, and showed up in the regions of "fibrinoid necrosis" in form of distorted vascular rings. Although neither IgD nor fibrin appear in a disease-specific histotopical distribution, their simultaneous in vivo demonstration, connected with the result of vascular bound complement, is a good aid to substantiate the diagnosis of cutaneous vasculitis.

Topics: Fibrin; Fluorescent Antibody Technique; Histocytochemistry; Humans; Immunoglobulin D; Inflammation; Microcirculation; Skin; Skin Diseases; Vascular Diseases

Hyalinizing segmental vasculitis or livedo vasculitis (atrophie blanche) is a clinical entity with a distinctive immunohistopathologic morphology that can be distinguished from other forms of cutaneous vasculitis by histologic and direct immunofluorescent studies. Our studies showed that immunoglobulins and complement components (C-1g, C-3, and properdin) were localized in diseased vessel walls, suggesting an immune pathogenesis.

Topics: Atrophy; Biopsy; Blood Vessels; Complement System Proteins; Extremities; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Properdin; Skin; Vascular Diseases

Topics: Adult; Arteries; Biopsy; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Graft Rejection; Humans; Hypertension, Malignant; Kidney; Kidney Diseases; Kidney Glomerulus; Kidney Tubular Necrosis, Acute; Pre-Eclampsia; Pregnancy; Scleroderma, Systemic; Transplantation, Homologous; Vascular Diseases

Topics: Aneurysm; Arteries; Blood Vessel Prosthesis; Collagen; Elasticity; Endothelium; Fibrin; Fibroblasts; Fistula; Humans; Infections; Intestinal Fistula; Plastics; Polyethylene Terephthalates; Postoperative Complications; Textiles; Thrombosis; Vascular Diseases

Topics: Chromatography, Gel; Fibrin; Fibrinogen; Fibrinolysis; Humans; Molecular Weight; Snake Venoms; Thrombin; Vascular Diseases; Venoms

Topics: Alkaloids; Animals; Autopsy; Blood Platelets; Capillaries; Cardiomegaly; Dilatation; Disease Models, Animal; Endothelium; Fibrin; Haplorhini; Heart Ventricles; Heterocyclic Compounds; Lung; Macaca; Microscopy, Electron; Thrombosis; Vascular Diseases

Hyaline deposits in arterioles and arteries of spleen were studied immunohistochemically. Hyaline lesions in arteriosclerotic heart disease were characterized by significant deposits of IgG, IgM, beta1C-beta 1A-globulins and beta-lipoproteins. These corresponded to histochemically stained deposits of acid mucopolysaccharides and microscopic areas of musculoelastic tissue damage in the hyaline masses. While, in young adults and a few other cases of other diseases, an occasional granular to linear deposit of IgG, IgM, beta1C-beta 1A-globulin and beta-lipoprotein was noted, no localization of IgA, rabbit antihuman fibrin and rabbit antihuman fibrinogen was seen. A variety of other histochemical staining reactions were found to be negative. These findings suggest that: a) hyaline deposits in splenic arterioles and arteries occur with greater severity in patients with hypertensive and arteriosclerotic heart disease; b) a possible abnormality related to filtration defects in arteries and arterioles, resulting in the trapping of plasma proteins, appears likely; c) increased localization of acid mucopolysaccharides and destruction of musculoelastic tissue is not an uncommon feature in hyaline masses; d) fibrin is not a component of these deposits and e) further study of other organs is necesary to observe the composition of hyaline in arterioles and arteries.

Topics: Adolescent; Adult; Aged; Animals; Arteriosclerosis; Beta-Globulins; Child; Child, Preschool; Complement System Proteins; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Glycosaminoglycans; Histocytochemistry; Humans; Hyalin; Hypertension; Immunoglobulin G; Immunoglobulin M; Infant; Infant, Newborn; Lipoproteins, LDL; Middle Aged; Rabbits; Splenic Artery; Vascular Diseases

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: Arthritis, Rheumatoid; Blood Sedimentation; Exudates and Transudates; Fibrin; Gangrene; Humans; Osteoarthritis; Polyarteritis Nodosa; Synovial Fluid; Vascular Diseases; Wounds and Injuries

Topics: Biopsy; Carbamates; Eclampsia; Female; Fibrin; Gestational Age; Humans; Immunosuppressive Agents; Lymph Nodes; Pre-Eclampsia; Pregnancy; Vascular Diseases

Topics: Animals; Blood Coagulation Disorders; Chemical Precipitation; Fibrin; Fibrinogen; Humans; In Vitro Techniques; Indicator Dilution Techniques; Protamines; Rabbits; Streptokinase; Thrombin; Vascular Diseases

Topics: Complement System Proteins; Cryoglobulins; Fibrin; Fluorescent Antibody Technique; Humans; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Inflammation; Purpura; Skin; Urticaria; Vascular Diseases

Topics: Animals; Blood Vessels; Endothelium; Endotoxins; Fibrin; Heparin; Leukocytes; Microscopy, Electron; Platelet Adhesiveness; Rabbits; Sepsis; Shock, Septic; Vascular Diseases

Topics: Adult; Blood Coagulation Tests; Blood Urea Nitrogen; Child; Disseminated Intravascular Coagulation; Female; Fibrin; Glomerulonephritis; Hematologic Diseases; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Nephritis; Nephrotic Syndrome; Urinary Tract Infections; Vascular Diseases

Topics: Adolescent; Adult; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Pressure; Child, Preschool; Desoxycorticosterone; Erythrocytes; Female; Fibrin; Glomerulonephritis; Humans; Hypertension, Malignant; Kidney Diseases; Male; Middle Aged; Necrosis; Nephrectomy; Urea; Vascular Diseases

Topics: Animals; Arteries; Blood Circulation; Capillary Permeability; Elastic Tissue; Fibrin; Humans; Membranes; Microscopy, Electron; Muscle, Smooth; Necrosis; Staining and Labeling; Vascular Diseases

Topics: Blood Vessels; Diphtheria; Fibrin; Granulomatosis with Polyangiitis; Humans; Hypertension, Malignant; Lupus Erythematosus, Systemic; Necrosis; Polyarteritis Nodosa; Pyelonephritis; Rheumatic Fever; Sepsis; Splenic Artery; Tuberculosis, Meningeal; Vascular Diseases

Topics: Adult; Aged; Animals; Aorta; Blood Vessel Prosthesis; Connective Tissue; Detergents; Dogs; Fibrin; Heparin; Humans; Male; Polymers; Saphenous Vein; Vascular Diseases; Vena Cava, Inferior

Topics: Alkaloids; Animals; Aspartate Aminotransferases; Bilirubin; Blood Platelets; Blood Proteins; Cell Wall; Collagen; Cytoplasmic Granules; Female; Fibrin; Haplorhini; Hepatic Veins; Microscopy; Microscopy, Electron; Muscle, Smooth; Prothrombin Time; Vascular Diseases

Topics: Animals; Arteries; Arteriosclerosis; Electric Stimulation; Erythrocyte Aggregation; Fibrin; Methods; Microscopy, Electron; Rabbits; Thrombosis; Time Factors; Vascular Diseases

Topics: Animals; Aorta, Abdominal; Blood Platelets; Carotid Arteries; Cold Temperature; Disease Models, Animal; Erythrocytes; Fibrin; Inflammation; Microscopy, Electron, Scanning; Rabbits; Vascular Diseases

Topics: Adolescent; Adult; Drug Hypersensitivity; Female; Fibrin; Histocytochemistry; Humans; Male; Middle Aged; Necrosis; Polysaccharides; Skin; Thrombosis; Vascular Diseases

Topics: Animals; Blood Vessels; Dogs; Fibrin; Hydrochloric Acid; Hypertension; Necrosis; Norepinephrine; Rabbits; Vascular Diseases

Topics: Arteriosclerosis; Fibrin; Hyalin; Hypertension; Hypertension, Renal; Kidney; Microscopy; Pathology; Rats; Research; Vascular Diseases

Topics: Animals; Arteriosclerosis; Epinephrine; Fibrin; Fibrinolysis; Humans; Pathology; Pharmacology; Pulmonary Artery; Pulmonary Embolism; Rabbits; Research; Serotonin; Vascular Diseases; Vasoconstriction

Topics: Blood Circulation; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Fibrin; Humans; Plastics; Postoperative Complications; Thrombosis; Vascular Diseases

Topics: Angiography; Arteriosclerosis Obliterans; Fibrin; Humans; Leg; Pathology; Thromboangiitis Obliterans; Vascular Diseases

Topics: Fibrin; Humans; Peripheral Vascular Diseases; Skin; Vascular Diseases; Vasculitis

Topics: Female; Fibrin; Humans; Infant Mortality; Infarction; Placenta; Placenta Diseases; Pregnancy; Vascular Diseases

Topics: Blood Coagulation; Blood Coagulation Disorders; Factor XIII; Fibrin; Hemorrhagic Disorders; Humans; Vascular Diseases

Topics: Fibrin; Hot Temperature; Humans; Liver Diseases; Vascular Diseases

Topics: Fibrin; Fibrinolysis; Hemorrhagic Disorders; Humans; Vascular Diseases

Topics: Bone Plates; Fibrin; Fibrinolysis; Humans; Liver Diseases; Vascular Diseases

Topics: Animals; Arteriovenous Anastomosis; Arteriovenous Fistula; Arteriovenous Shunt, Surgical; Fibrin; Peripheral Vascular Diseases; Rabbits; Renal Dialysis; Vascular Diseases

Topics: Arterial Occlusive Diseases; Fibrin; Fibrinogen; Humans; Peripheral Vascular Diseases; Vascular Diseases