fibrin and Chronic-Disease

Chronic inflammatory placental disorders are a group of rare but devastating gestational syndromes associated with adverse pregnancy outcome. This review focuses on three related conditions: villitis of unknown etiology (VUE), chronic histiocytic intervillositis (CHI) and massive perivillous fibrin deposition (MPFD). The hallmark of these disorders is infiltration of the placental architecture by maternal immune cells and disruption of the intervillous space, where gas exchange between the mother and fetus occurs. Currently, they can only be detected through histopathological examination of the placenta after a pregnancy has ended. All three are associated with a significant risk of recurrence in subsequent pregnancies. Villitis of unknown etiology is characterised by a destructive infiltrate of maternal CD8+ T lymphocytes invading into the chorionic villi, combined with activation of fetal villous macrophages. The diagnosis can only be made when an infectious aetiology has been excluded. VUE becomes more common as pregnancy progresses and is frequently seen with normal pregnancy outcome. However, severe early-onset villitis is usually associated with fetal growth restriction and recurrent pregnancy loss. Chronic histiocytic intervillositis is characterised by excessive accumulation of maternal CD68+ histiocytes in the intervillous space. It is associated with a wide spectrum of adverse pregnancy outcomes including high rates of first-trimester miscarriage, severe fetal growth restriction and late intrauterine fetal death. Intervillous histiocytes can also accumulate due to infection, including SARS-CoV-2, although this infection-induced intervillositis does not appear to recur. As with VUE, the diagnosis of CHI requires exclusion of an infectious cause. Women with recurrent CHI and their families are predisposed to autoimmune diseases, suggesting CHI may have an alloimmune pathology. This observation has driven attempts to prevent CHI with a wide range of maternal immunosuppression. Massive perivillous fibrin deposition is diagnosed when >25% of the intervillous space is occupied by fibrin, and is associated with fetal growth restriction and late intrauterine fetal death. Although not an inflammatory disorder per se, MPFD is frequently seen in association with both VUE and CHI. This review summarises current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology and potential prophylaxis against recurrence in these

Topics: Abortion, Habitual; Chorioamnionitis; Chronic Disease; COVID-19; Female; Fetal Death; Fetal Growth Retardation; Fibrin; Humans; Placenta; Pregnancy; Pregnancy Outcome; SARS-CoV-2; Syndrome

Chronic rhinosinusitis (CRS) is one of the most common chronic diseases worldwide. It is a heterogeneous disease, and geographical or ethnic differences in inflammatory pattern in nasal mucosa are major issues. Tissue eosinophilia in CRS is highly associated with extensive sinus disease, recalcitrance, and a higher nasal polyp (NP) recurrence rate after surgery. The prevalence of eosinophilic CRS (ECRS) is increasing in Asian countries within the last 2 decades, and this trend appears to be occurring across the world. International consensus criteria for ECRS are required for the accurate understanding of disease pathology and precision medicine. In a multicenter large-scale epidemiological survey, the "Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis study," ECRS was definitively defined when the eosinophil count in nasal mucosa is greater than or equal to 70 eosinophils/hpf (magnification, ×400), and this study proposed an algorithm that classifies CRS into 4 groups according to disease severity. The main therapeutic goal with ECRS is to eliminate or diminish the bulk of NP tissue. NPs are unique abnormal lesions that grow from the lining of the nasal and paranasal sinuses, and type 2 inflammation plays a critical role in NP development in patients with ECRS. An imbalance between protease and endogenous protease inhibitors might play a pivotal role in the initiation and exacerbation of type 2 inflammation in ECRS. Intraepithelial mast cells in NPs, showing a tryptase+, chymase- phenotype, may also enhance type 2 inflammation. Intense edema and reduced fibrosis are important histological features of eosinophilic NPs. Mucosal edema mainly consists of exuded plasma protein, and excessive fibrin deposition would be expected to contribute to the retention of proteins from capillaries and thereby perpetuate mucosal edema that may play an etiological role in NPs. Upregulation of the coagulation cascade and downregulation of fibrinolysis strongly induce abnormal fibrin deposition in nasal mucosa, and type 2 inflammation plays a central role in the imbalance of coagulation and fibrinolysis.

Topics: Chronic Disease; Eosinophils; Fibrin; Humans; Immunity, Innate; Inflammation; Nasal Mucosa; Nasal Polyps; Rhinitis; Sinusitis

Chronic intervillositis (CI) is a rare placental condition involving diffuse infiltration of intervillous spaces by CD68- or CD45-positive maternal mononuclear inflammatory cells. Because no validated clinical or biochemical markers are specific to CI, the diagnosis is purely histopathological and is made postpartum.. This report describes a case of recurrent CI associated with adverse complications in two successive pregnancies. Both pregnancies were complicated by intrauterine growth restriction. Coexistent massive perivillous fibrin deposition was present in the first placenta. This case highlights the importance of CI in explaining and predicting adverse perinatal outcomes.. CI is associated with adverse pregnancy outcomes and a high risk of recurrence, and it can coexist with massive perivillous fibrin deposition. Pathologists must ensure that the significance of these diagnoses is adequately conveyed to clinicians, to optimize management of subsequent pregnancies.

Topics: Adult; Chorionic Villi; Chronic Disease; Female; Fetal Growth Retardation; Fibrin; Humans; Placenta Diseases; Pregnancy; Recurrence

Fibrin, a natural hydrogel, is the end product of the physiological blood coagulation cascade and naturally involved in wound healing. Beyond its role in hemostasis, it acts as a local reservoir for growth factors and as a provisional matrix for invading cells that drive the regenerative process. Its unique intrinsic features do not only promote wound healing directly via modulation of cell behavior but it can also be fine-tuned to evolve into a delivery system for sustained release of therapeutic biomolecules, cells and gene vectors. To further augment tissue regeneration potential, current strategies exploit and modify the chemical and physical characteristics of fibrin to employ combined incorporation of several factors and their timed release. In this work we show advanced therapeutic approaches employing fibrin matrices in wound healing and cover the many possibilities fibrin offers to the field of regenerative medicine.

Topics: Acute Disease; Animals; Chronic Disease; Drug Delivery Systems; Fibrin; Humans; Hydrogels; Wound Healing

Monitoring chronic wound [CW] healing is a challenging issue for clinicians across the world. Moreover, the health and cost burden of CW are escalating at a disturbing rate due to a global rise in population of elderly and diabetic cases. The conventional approach includes visual contour, sketches, or more rarely tracings. However, such conventional techniques bring forth infection, pain, allergies. Furthermore, these methods are subjective as well as time-consuming. As such, nowadays, non-touching and non-invasive CW monitoring system based on imaging techniques are gaining importance. They not only reduce patients' discomfort but also provide rapid wound diagnosis and prognosis. This review provides a survey of different types of CW characteristics, their healing mechanism and the multimodal non-invasive imaging methods that have been used for their diagnosis and prognosis. Current clinical practices as well as personal health systems [m-health and e-health] for CW monitoring have been discussed.

Topics: Chronic Disease; Diagnostic Imaging; Fibrin; Fibronectins; Humans; Inflammation Mediators; Microscopy, Confocal; Optical Imaging; Prognosis; Severity of Illness Index; Spectrum Analysis; Tomography, X-Ray Computed; Ultrasonography; Wound Healing; Wounds and Injuries

Strong experimental evidence indicates that components of the hemostatic system, including thrombin, exacerbate diverse features of experimental liver disease. Clinical studies have also begun to address this connection and some studies have suggested that anticoagulants can improve outcome in patients with liver disease. Among the evidence of coagulation cascade activation in models of liver injury and disease is the frequent observation of thrombin-driven hepatic fibrin(ogen) deposition. Indeed, hepatic fibrin(ogen) deposition has long been recognized as a consequence of hepatic injury. Although commonly inferred as pathologic due to protective effects of anticoagulants in mouse models, the role of fibrin(ogen) in acute liver injury and chronic liver disease may not be universally detrimental. The localization of hepatic fibrin(ogen) deposits within the liver is connected to the disease stimulus and in animal models of liver toxicity and chronic disease, fibrin(ogen) deposition may not always be synonymous with large vessel thrombosis. Here, we provide a balanced review of the experimental evidence supporting a direct connection between fibrin(ogen) and liver injury/disease pathogenesis, and suggest a path forward bridging experimental and clinical research to improve our knowledge on the nature and function of fibrin(ogen) in liver disease.

Topics: Acute Disease; Animals; Chronic Disease; Disease Models, Animal; Fibrin; Fibrinogen; Humans; Liver Diseases; Mice

Maternal floor infarction/massive perivillous fibrin deposition (MFI/MFD), chronic histiocytic intervillositis (CHIV) and villitis of unknown etiology (VUE) are lesions of the placenta which are characterized morphologically. The cause is thought to be pathological immunotolerance/rejection reaction at the fetomaternal interface. The risk of recurrence is elevated and the lesions can lead to severe pediatric diseases.. This article provides an overview of the pathological and anatomical characteristics of each of these lesions, including diagnostic criteria, suspected etiology, clinical relevance and suggested therapy options.. A selective search of the literature was carried out and experiences from own diagnostic clientele are presented.. While MFI/MFD and CHIV occur more rarely, VUE is relatively common occurring in up to 15 % of placentas at term. Both MFI/MFD and CHIV can occur in the first and second trimester, while VUE typically manifests in the third trimester. All lesions can lead to intrauterine growth retardation or abortion and have a tendency towards disease recurrence. Furthermore, VUE and MFI/MFD can be associated with an adverse neurodevelopmental outcome in the children. For all these entities potential therapy strategies have been reported, which are mainly based on anticoagulation and immunosuppression in subsequent pregnancies.

Topics: Abortion, Spontaneous; Chorionic Villi; Chronic Disease; Female; Fetal Growth Retardation; Fibrin; Histiocytosis; Humans; Infant, Newborn; Infarction; Placenta; Placenta Diseases; Placental Circulation; Pregnancy; Pregnancy Trimester, Third; Recurrence; Risk Factors

Although mortality rates from coronary heart disease in the western countries have declined in the last few decades, morbidity caused by this disease is increasing and a substantial number of patients still suffer acute coronary syndrome (ACS) and sudden cardiac death. Acute coronary syndrome occurs as a result of myocardial ischaemia and its manifestations include acute myocardial infarction and unstable angina. Culprit plaque morphology in these patients varies from thrombosis with or without coronary occlusion to sudden narrowing of the lumen from intraplaque haemorrhage. The coronary artery plaque morphologies primarily responsible for thrombosis are plaque rupture, and plaque erosion, with plaque rupture being the most common cause of acute myocardial infarction, especially in men. Autopsy data demonstrate that women <50 years of age more frequently have erosion, whereas in older women, the frequency of rupture increases with each decade. Ruptured plaques are associated with positive (expansive) remodelling and characterized by a large necrotic core and a thin fibrous cap that is disrupted and infiltrated by foamy macrophages. Plaque erosion lesions are often negatively remodelled with the plaque itself being rich in smooth muscle cells and proteoglycans with minimal to absence of inflammation. Plaque haemorrhage may expand the plaque rapidly, leading to the development of unstable angina. Plaque haemorrhage may occur from plaque rupture (fissure) or from neovascularization (angiogenesis). Atherosclerosis is now recognized as an inflammatory disease with macrophages and T-lymphocytes playing a dominant role. Recently at least two subtypes of macrophages have been identified. M1 is a pro-inflammatory macrophage while M2 seems to play a role in dampening inflammation and promoting tissue repair. A third type of macrophage, termed by us as haemoglobin associated macrophage or M(Hb) which is observed at site of haemorrhage also can be demonstrated in human atherosclerosis. In order to further our understanding of the specific biological events which trigger plaque instability and as well as to monitor the effects of novel anti-atherosclerotic therapies newer imaging modalities in vivo are needed.

Topics: Acute Coronary Syndrome; Cardiac Imaging Techniques; Chronic Disease; Coronary Artery Disease; Coronary Thrombosis; Female; Fibrin; Hemorrhage; Humans; Macrophages; Male; Necrosis; Plaque, Atherosclerotic; Platelet Aggregation; Risk Factors; Rupture, Spontaneous; Vascular Calcification

Acute inflammatory and chronic interstitial lung diseases are characterized by excessive and persistent fibrin deposition in the lung. Intraalveolar fibrin accumulation, observed under these conditions, arises from a leakage of plasma proteins (including fibrinogen) into the alveolar space in combination with a disbalance of alveolar haemostasis. Tissue factor in association with factor VIIa and inhibition of urokinase by plasminogen activator inhibitor-1 are major factors that are responsible for the procoagulant and antifibrinolytic state. In addition, in acute respiratory distress syndrome (ARDS) patients, factor VII-activating protease and extracellular RNA, which may be released into the extracellular milieu from damaged cells during lung injury, may contribute to fibrin formation as well. Fibrin itself can increase vascular permeability, influence the expression of inflammatory mediators and alter the migration and proliferation of various cell types. Additionally, fibrin may inactivate pulmonary surfactant and provide a matrix on which fibroblasts can migrate and produce collagen. Furthermore, cellular activities of haemostatic proteases may also contribute to proinflammatory and fibrotic processes in the lung. The application of coagulation inhibitors, like tissue factor pathway inhibitor, active site-inactivated factor VIIa, activated protein C, antithrombin, heparin or hirudin turned out to be beneficial in experimental models of acute and chronic lung injury. However, the ability of anticoagulant and profibrinolytic agents to improve clinical outcome remains to be elucidated. In the current article, the role of the alveolar coagulation and fibrinolysis systems in acute inflammatory and chronic interstitial lung diseases is discussed with regard to pathomechanisms and modalities of intervention.

Topics: Acute Disease; Animals; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Chronic Disease; Fibrin; Fibrinolysis; Fibrinolytic Agents; Humans; Lung Diseases, Interstitial; Pneumonia; Pulmonary Alveoli

Venous leg ulcers cause patients much distress. Treating them is expensive, with many hidden costs. As understanding of the causes and development of this condition improves, debate over the best treatments or treatment combinations is growing.

Topics: Bandages; Causality; Chronic Disease; Clinical Trials as Topic; Disease Progression; Fibrin; Humans; Leukocytes; Nitric Oxide; Skin Care; Treatment Outcome; Varicose Ulcer; Vascular Surgical Procedures; Wound Healing

Soluble fibrin detected in clinical plasma samples includes a variety of complexes consisting of fibrin monomer units, fibrinogen, and various proteolytic derivatives of fibrinogen and fibrin. The advantage of measuring soluble fibrin over fibrinopeptide A to detect thrombin action on fibrinogen is the considerably longer half-life of soluble fibrin in the circulation. Soluble fibrin can be detected by a variety of methods, including paracoagulation and precipitation assays, adsorption of fibrin monomer to insolubilized fibrinogen, functional assays based on the cofactor activity of some soluble fibrin compounds in t-PA-induced plasminogen activation, and by using fibrin-specific antibodies. Fibrin-specific antibodies may react with epitopes generated directly by fibrinopeptide A or B release or with epitopes generated by fibrin polymerization. Epitopes dependent on fibrinopeptide A release are often not accessible in native fibrin complexes and require the disaggregation of fibrin compounds to be reactive, whereas epitopes dependent on fibrinopeptide B release or fibrin polymerization are accessible to the monoclonal antibodies in nondenatured fibrin. Since soluble fibrin assays detect different structural or functional properties of soluble fibrin, no common calibrator for all soluble fibrin assays and, often, little correlation between different assay systems in clinical evaluations exist. Clinical applications of soluble fibrin assays include diagnosis and treatment monitoring of intravascular coagulation processes and prethrombotic states, monitoring anticoagulant treatment, and biocompatibility investigations. Some soluble fibrin assays have been demonstrated to be extremely sensitive indicators of acute fibrin formation. For the exclusion of venous thrombosis, D-dimer assays appear to be more sensitive than current soluble fibrin assays, since D-dimer assays detect freshly formed fibrin and proteolytic fragments of particulate clots. Further clinical studies are needed to establish the clinical utility of specific, soluble fibrin assays. The development of rapid, quantitative soluble fibrin assays for clinical routine use should be encouraged.

Topics: Acute Disease; Animals; Blood Coagulation; Chronic Disease; Disseminated Intravascular Coagulation; Epitopes; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Plasminogen; Thrombophilia; Venous Thrombosis

The etiology of venous ulceration is far more complex than Homans' theory of stagnation and hypo-oxygenation. Indeed, studies have shown that flow in lipodermatosclerotic limbs is actually faster than normal. We suggest, therefore, that the terms "stasis dermatitis" and "stasis ulcer" be dropped from medical parlance. The term "lipodermatosclerosis with ulceration" as used by the British, or simply "venous ulcer," would seem more appropriate. Venous hypertension, produced by incompetence of deep and communicating vein valves and thrombosis of segments of the deep system, is closely correlated with the development of venous ulcers. Precisely how this venous hypertension translates into ulceration is unclear. Burnand et al showed that fibrin cuffs are deposited around the capillaries in lipodermatosclerotic limbs. These cuffs may serve as barriers to the diffusion of oxygen, leading to local ischemia and epidermal necrosis. Others suggest that trapped leukocytes in the microcirculation alter capillary permeability by releasing various inflammatory mediators that hasten the flow of fibrinogen across the capillary membrane and promote the formation of fibrin cuffs. Proof of this hypothesis is still lacking, but may eventually come from using radioactive WBC tagging procedures. A synthesis of these two theories may in fact explain the etiology of venous ulceration.

Topics: Capillary Permeability; Cell Hypoxia; Chronic Disease; Fibrin; Fibrinogen; Humans; Hypertension; Leg Ulcer; Leukocytes; Microcirculation; Necrosis; Terminology as Topic; Thrombosis; Venous Insufficiency; Venous Pressure

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: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Chronic Disease; Female; Fibrin; Fibrinogen; Glomerulonephritis; Hemolytic-Uremic Syndrome; Humans; Immune Complex Diseases; Immunoglobulin A; Immunoglobulin G; Kidney Diseases; Lupus Erythematosus, Systemic; Male; Middle Aged; Nephritis; Nephrosis; Nephrotic Syndrome; Purpura; Streptococcal Infections

Topics: Blood Coagulation; Burns; Chronic Disease; Disseminated Intravascular Coagulation; Factor V; Factor VIII; Fibrin; Fibrinogen; Fibrinolysis; Hemagglutination Tests; Hemostasis; Humans; Leukemia; Purpura, Thrombotic Thrombocytopenic; Thrombin

Topics: Blood Coagulation; Bone Marrow; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Fibrinogen; Humans; Liver; Lung Neoplasms; Male; Prostatic Neoplasms; Surgical Procedures, Operative

Topics: Arthritis; Blood Coagulation Factors; Blood Platelets; Chronic Disease; Complement System Proteins; Connective Tissue; Disseminated Intravascular Coagulation; Endotoxins; Factor XII; Fibrin; Fibrinogen; Fibrinolysin; Glomerulonephritis; Humans; Inflammation; Kinins; Leukocytes; Nephritis; Shwartzman Phenomenon

Topics: Blood Protein Electrophoresis; Chronic Disease; Fibrin; Heterozygote; Homozygote; Humans; Leukocytes; Lysosomes; Metabolism, Inborn Errors; Methods; Protease Inhibitors; Protein Deficiency; Pulmonary Emphysema; Trypsin; Trypsin Inhibitors

Topics: Acute Disease; Blood Coagulation Disorders; Blood Coagulation Tests; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Graft Rejection; Humans; Kidney; Kidney Transplantation; Male; Pregnancy; Time Factors; Transplantation, Homologous

Topics: Age Factors; Bronchitis; Chronic Disease; Collagen; Fibrin; Heterozygote; Humans; Kinins; Leukocytes; Lung; Microbial Collagenase; Phenotype; Plasminogen; Pulmonary Emphysema; Trypsin Inhibitors

Objectives Compare the efficacy and safety of fibrin gel to 8% papain gel for wound dressing of venous ulcers. Method Patients with chronic venous ulcers were randomly assigned to one in three groups: Group 1-fibrin gel; Group 2-8% papain gel; Group 3-carbopol gel (control). Patients were seen every 15 days during 2 months, verifying reduction of the ulcer area, local infection, exudation, and epithelization. All serious or nonserious adverse events were recorded. Results Fifty-five patients (total of 63 ulcers) were randomly distributed in three groups (G1 = 21; G2 = 19; G3 = 23). No patient was excluded or discontinued treatment throughout the study. The areas of the ulcers were similarly reduced in all groups (14.3%, 21.1%, and 30.4% in groups 1, 2, and 3, respectively), and all had significant reduction in exudation and contamination. Conclusion The data demonstrate that neither fibrin gel nor papain gel were able to improve the process of ulcer-healing, as compared to control.

Topics: Adult; Aged; Aged, 80 and over; Bandages; Chronic Disease; Double-Blind Method; Elasticity; Female; Fibrin; Gels; Humans; Male; Middle Aged; Papain; Prospective Studies; Treatment Outcome; Varicose Ulcer; Wound Healing

We hypothesized that arthroscopic rotator cuff repairs using leukocyte- and platelet-rich fibrin (L-PRF) in a standardized, modified protocol is technically feasible and results in a higher vascularization response and watertight healing rate during early healing.. Twenty patients with chronic rotator cuff tears were randomly assigned to 2 treatment groups. In the test group (N = 10), L-PRF was added in between the tendon and the bone during arthroscopic rotator cuff repair. The second group served as control (N = 10). They received the same arthroscopic treatment without the use of L-PRF. We used a double-row tension band technique. Clinical examinations including subjective shoulder value, visual analog scale, Constant, and Simple Shoulder Test scores and measurement of the vascularization with power Doppler ultrasonography were made at 6 and 12 weeks.. There have been no postoperative complications. At 6 and 12 weeks, there was no significant difference in the clinical scores between the test and the control groups. The mean vascularization index of the surgical tendon-to-bone insertions was always significantly higher in the L-PRF group than in the contralateral healthy shoulders at 6 and 12 weeks (P = .0001). Whereas the L-PRF group showed a higher vascularization compared with the control group at 6 weeks (P = .001), there was no difference after 12 weeks of follow-up (P = .889). Watertight healing was obtained in 89% of the repaired cuffs.. Arthroscopic rotator cuff repair with the application of L-PRF is technically feasible and yields higher early vascularization. Increased vascularization may potentially predispose to an increased and earlier cellular response and an increased healing rate.

Topics: Aged; Arthroscopy; Blood Platelets; Blood Transfusion, Autologous; Chronic Disease; Female; Fibrin; Humans; Leukocyte Transfusion; Male; Middle Aged; Neovascularization, Physiologic; Pilot Projects; Prospective Studies; Rotator Cuff; Rotator Cuff Injuries; Treatment Outcome; Ultrasonography; Wound Healing

Imaging with the 99mTc-T2G1s monoclonal antifibrin antibody fragment (Fab') has demonstrated promise in the noninvasive detection of venous thrombi in humans. The purpose of this study was to determine whether chronic arterial thrombi can also be detected by antifibrin antibody imaging.. Eighteen subjects with chronic arterial thrombi were studied with planar and tomographic imaging at 0 to 24 hr postinjection of 99mTc-labeled T2G1s monoclonal antifibrin antibody fragment. Imaging with 111In-labeled platelets was also performed. Images were visually graded by two observers as 0, 1, 2 or 3 (no, faint, moderate or marked) uptake, and quantitative analysis of tomographic images was done in 13 subjects.. On visual analysis of planar images, 44% (8 of 18) of antifibrin patient studies were 1.0 or more and 66% (10 of 18) were judged negative compared with 94% (15 of 16) of platelet patient studies judged 1.0 or more and 6% (1 of 16) judged as negative (p < 0.01). Visual analysis of tomographic images was similar, with 61% (11 of 18) of antifibrin studies graded 1.0 or more compared with 100% (17 of 17) of platelet studies (p < 0.01). The tomographic target-to-background ratio was higher with platelets than with antifibrin antibody (2.5 +/- 1.4 versus 1.8 +/- 1.0, p < 0.05).. In the large-vessel chronic arterial thrombi studied, the results of 99mTc-labeled monoclonal T2G1s antifibrin Fab' imaging were positive in only one-half of the patients studied, significantly less than the findings with platelet imaging, which were positive in all subjects. The higher rate of positive images with labeled platelets than with labeled antifibrin antibodies may be largely due to thrombus age, with continued platelet deposition but little active fibrin deposition.

Topics: Aged; Aortic Aneurysm, Abdominal; Blood Platelets; Chronic Disease; Fibrin; Graft Occlusion, Vascular; Heart Diseases; Humans; Image Processing, Computer-Assisted; Indium Radioisotopes; Male; Radioimmunodetection; Technetium; Thrombosis

Nasal polyps (NPs) are multifactorial soft growths inside the nasal passages and are associated with chronic inflammation that originate from the nasal and paranasal sinus mucosae. This study focused on the role of microRNA (miR)-125b and the molecules associated with NP development. Differentially expressed miRNAs between nasal tissues from patients with chronic rhinosinusitis (CRS) with NP (CRSwNP) and CRS without NP (CRSsNP) were screened using microarray analysis. A murine model of CRSwNP was established. The expression of miR-125b in murine tissues was examined using reverse transcription quantitative polymerase chain reaction. Candidate upstream regulators of miR-125b were predicted using bioinformatics tools, and the binding relationship between specificity protein 1 (Sp1) and miR-125b was validated using luciferase and chromatin immunoprecipitation assays. Altered expression of Sp1 and miR-125b was induced to evaluate their relevance to the progression of NPs. miR-125b expression was significantly upregulated in NP tissues from patients with CRSwNP. Sp1 was confirmed as an upstream regulator that promotes miR-125b transcription in NPs. Overexpression of Sp1 reduced levels of d-dimer (an indicator of fibrinogen degradation products) and tissue-type plasminogen activator (t-PA) but increased eosinophil cationic protein and peroxidase levels, as well as the levels of inflammatory factors interleukin-5 (IL-5) and IL-8 in murine NP tissues. However, these trends were reversed after miR-125b downregulation. Sp1 and miR-125b were found to activate the Wnt/β-catenin signaling pathway in NPs. This study demonstrated that Sp1, an upstream transcription factor of miR-125b, accumulates on the miR-125b promoter to activate its transcription, which induces inflammation and fibrin deposition in NP by activating the Wnt/β-catenin axis.

Topics: Animals; Chronic Disease; Fibrin; Humans; Inflammation; Mice; MicroRNAs; Nasal Polyps; Rhinitis; Sinusitis; Sp1 Transcription Factor; Wnt Signaling Pathway

Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP.. We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS.. Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting.. Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue.. The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.

Topics: Blood Coagulation; Chronic Disease; Fibrin; Humans; Nasal Polyps; Rhinitis; Sinusitis; Thromboplastin

Patients with aspirin-exacerbated respiratory disease (AERD) regularly exhibit severe nasal polyposis. Studies suggest that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition associated with a profound decrease in epithelial tissue plasminogen activator (tPA). Retinoids, including vitamin A and its active metabolite retinoic acid (RA), are necessary for maintaining epithelial function and well-known inducers of tPA in endothelial cells.. This study sought to determine whether endogenous retinoids are involved in NP pathophysiology and disease severity in patients with CRSwNP and AERD.. NP tissue was collected from patients with AERD or CRSwNP, and concentrations of retinoids and fibrinolysis markers were measured using ELISA. Normal human bronchial epithelial cells were stimulated alone or in combination with RA and IL-13 for 24 hours.. This study observed lower retinoid levels in nasal polyps of patients with AERD than those with CRSwNP or healthy controls (P < .01). Levels of the fibrin-breakdown product d-dimer were the lowest in AERD polyps (P < .01), which is consistent with lower tPA expression (P < .01). In vitro, all-trans RA upregulated tPA levels in normal human bronchial epithelial cells by 15-fold and reversed the IL-13-induced attenuation of tPA expression in cultured cells (P < .01).. RA, a potent inducer of epithelial tPA in vitro, is reduced in tissue from patients with AERD, a finding that may potentially contribute to decreased levels of tPA and fibrinolysis in AERD. RA can induce tPA in epithelial cells and can reverse IL-13-induced tPA suppression in vitro, suggesting the potential utility of RA in treating patients with CRSwNP and/or AERD.

Topics: Asthma, Aspirin-Induced; Chronic Disease; Endothelial Cells; Fibrin; Fibrinolysis; Humans; Interleukin-13; Nasal Polyps; Rhinitis; Sinusitis; Tissue Plasminogen Activator; Tretinoin

Transglutaminase (TGM) isoform catalyze the cross-linking reaction of identical or different substrate proteins. Eosinophil has been recognized in chronic rhinosinusitis with nasal polyps (CRSwNP) forming tissue eosinophil in nasal polyp (NP), and TGM isoforms are suggested to be associated with a critical role in asthma and other allergic conditions. The aim of this study was to reveal the association of specific TGM isoform with both the tissue eosinophil infiltration deeply concerning with the intractable severity of CRSwNP and the fibrin polymerization ability of TGM isoform associated with the tissue eosinophil infiltration, which lead to NP formation and/or maintenance in CRSwNP. NP tissues (CRSwNP group) and uncinate process (UP) (control group) were collected from patients with CRSwNP and control subjects. We examined: (1) the expression level of TGM isoforms by using a real-time polymerase chain reaction (PCR) and the comparison to the issue eosinophil count in the CRSwNP group, (2) the location of specific TGM isoform in the mucosal tissue using immunohistochemistry, (3) the inflammatory cell showing the colocalization of specific TGM isoform in Laser Scanning Confocal Microscopy (LSCM) imaging, and (4) the fibrin polymerase activity of specific TGM isoform using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A certain level of TGM 1, 2, 3, 5 expression was present in both the CRSwNP group and the control group. Only TGM 1 expression showed a positive significant correlation with the tissue eosinophil count in the CRSwNP group. The localization of TGM 1 in NP (CRSwNP) laid mainly in a submucosal layer as inflammatory cells and was at the cytoplasm in the tissue eosinophil. Fibrin polymerase activity of TGM 1 showed the same polymerase ability of factor XIIIA. TGM 1 might influence the NP formation and/or maintenance in CRSwNP related to the tissue eosinophil infiltration, which formed fibrin mesh composing NP stroma.

Topics: Chronic Disease; Eosinophils; Fibrin; Humans; Nasal Polyps; Polymerization; Rhinitis; Sinusitis; Transglutaminases

Acute fibrinous and organising pneumonia (AFOP) is a rare form of interstitial lung disease. It is a pathological diagnosis sharing similarities to organising pneumonia, diffuse alveolar damage and eosinophilic pneumonia, however, is histologically distinct, characterised by intra-alveolar fibrin deposition ('fibrin balls') and associated organising pneumonia. AFOP was first described in 2002, only 150 cases have been reported since. While it has been described in association with infection, autoimmune disorders, connective tissue diseases, drugs, environmental exposures and organ transplant, it can also be idiopathic in nature. AFOP follows an acute course with potential rapid fulminant respiratory failure, or a subacute trajectory with a more favourable prognosis. Corticosteroids are commonly prescribed to induce remission. While cases of relapse of AFOP during weaning or cessation of steroids have been described, there are no published cases of remote relapse of AFOP. We describe a case of idiopathic AFOP, which recurred after 12 years of good health.

Topics: Adrenal Cortex Hormones; Chronic Disease; Fibrin; Humans; Lung Diseases, Interstitial; Pneumonia; Recurrence

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

The chronic wound in legs due to vascular abnormalities occurs in 1% to 2% of the adult population. The current treatments are unsatisfactory, and new approaches should be studied. We report in this article a case of a 52-year-old man with a chronic venous wound at the tibia, which has been conventionally treated for nine years. With six weeks of treatment with the autologous fibrin membrane, we were able to identify scar tissue and vascularization, which are characteristic of a healing process.

Topics: Chronic Disease; Cicatrix; Fibrin; Humans; Male; Middle Aged; Pilot Projects; Wound Healing

Chronic massive rotator cuff tears heal poorly and often retear. This study investigated the effect of adipose-derived stem cells (ADSCs) and transforming growth factor-β3 (TGF-β3) delivered in 1 of 2 hydrogels (fibrin or gelatin methacrylate [GelMA]) on enthesis healing after repair of acute or chronic massive rotator cuff tears in rats.. Adult male Lewis rats underwent bilateral transection of the supraspinatus and infraspinatus tendons with intramuscular injection of botulinum toxin A (n = 48 rats). After 8 weeks, animals received 1 of 8 interventions (n = 12 shoulders/group): (1) no repair, (2) repair only, or repair augmented with (3) fibrin, (4) GelMA, (5) fibrin + ADSCs, (6) GelMA + ADSCs, (7) fibrin + ADSCs + TGF-β3, or (8) GelMA + ADSCs + TGF-β3. An equal number of animals underwent acute tendon transection and immediate application of 1 of 8 interventions. Enthesis healing was evaluated 4 weeks after the repair by microcomputed tomography, histology, and mechanical testing.. Increased bone loss and reduced structural properties were seen in chronic compared with acute tears. Bone mineral density of the proximal humerus was higher in repairs of chronic tears augmented with fibrin + ADSCs and GelMA + ADSCs than in unrepaired chronic tears. Similar improvement was not seen in acute tears. No intervention enhanced histologic appearance or structural properties in acute or chronic tears.. Surgical repair augmented with ADSCs may provide more benefit in chronic tears compared with acute tears, although there was no added benefit to supplementing ADSCs with TGF-β3.

Topics: Acute Disease; Adipose Tissue; Animals; Bone Density; Chronic Disease; Fibrin; Humerus; Hydrogels; Male; Methacrylates; Orthopedic Procedures; Rats; Rats, Inbred Lew; Rotator Cuff Injuries; Stem Cell Transplantation; Transforming Growth Factor beta3; Wound Healing; X-Ray Microtomography

In recent years microinvasive glaucoma surgery has risen in popularity. Among microinvasive glaucoma surgery options is the XEN gel stent (Allergan Plc, Dublin, Ireland), a 45 μm wide ab-interno microstent. It has proven effective in lowering intraocular pressure (IOP) with low complication rates. However, XEN gel stents can become obstructed and cause postoperative rise in IOP. The causes and predicting factors for such obstructions still requires further research.. We describe the case of a 69-year-old male patient, with traumatic glaucoma and chronic intraocular inflammation showed by laser flare photometry, following childhood trauma and anterior segment surgery. Uncontrollable IOP despite maximal antiglaucomatous therapy was managed with XEN-augmented Baerveldt surgery. Despite good initial filtration and IOP control, the XEN stent became obstructed and was surgically replaced. After a month, the new stent became obstructed and was replaced by a thicker-lumened Baerveldt tube. This restored good filtration, and adequate IOP was maintained postoperatively. Microscopic examination of the obstructed XEN stent showed a dense fibrin plug.. This case report shows that fibrin formation could be an important factor in XEN gel stent obstruction, even in initially successfully filtering stents. The association of fibrinogenesis and intraocular inflammation could add a note of caution to the use of XEN gel stents in complicated cataract surgery, or advocate for aggressive anti-inflammatory treatments postoperatively. This could lead to a refinement in success predictors and better patient selection for XEN surgery. Finally, this could open the way to new management options for persistent obstructions, including pharmaceutical fibrinolysis.

Topics: Aged; Chronic Disease; Device Removal; Fibrin; Fibrinolysis; Glaucoma; Glaucoma Drainage Implants; Humans; Inflammation; Intraocular Pressure; Male; Ophthalmologic Surgical Procedures; Prosthesis Failure; Prosthesis Implantation; Risk Factors; Stents; Tonometry, Ocular; Treatment Outcome

Chronic rhinosinusitis with nasal polyps (CRSwNP) is often comorbid with asthma and resistant to therapeutic interventions. We recently reported that excessive fibrin deposition caused by impairment of fibrinolysis might play pivotal role in forming nasal polyp. Nattokinase (NK), a serine protease produced by Bacillus subtilis, has been reported to be a strong fibrinolytic enzyme. NK could be a promising drug candidate for use in the treatment of both CRSwNP and asthma. The objective of this study was to investigate the effects of NK on nasal polyp tissues from patients with CRSwNP. The nasal discharge from patients with CRSwNP and sputum from subjects with asthma were also used to investigate whether NK influences the viscosity of mucus.. To examine the effects on NK on nasal polyp tissues, pieces of nasal polyps were incubated either with saline or NK (10-1000 FU/ml) at 37 °C for 24 h. We assessed the presence of fibrin in nasal polyp tissue incubated with NK by means of immunohistochemistry. To examine the effects of NK on nasal discharge and sputum from patients with CRSwNP and asthma, respectively, were incubated with NK solution at 37 °C for 1 h.. NK effectively shrinks the nasal polyp tissue through fibrin degradation. We also found that the viscosity of the nasal discharge and sputum from patients with CRSwNP and asthma, respectively, was significantly reduced by incubation with NK solution.. NK may be an effective alternative therapeutic option in patients with CRSwNP and comorbid asthma by causing fibrin degradation.

Topics: Adult; Aged; Animals; Asthma; Chronic Disease; Disease Models, Animal; Eosinophils; Female; Fibrin; Humans; Immunoglobulin E; Leukocyte Count; Male; Mice; Middle Aged; Mucus; Nasal Mucosa; Nasal Polyps; Proteolysis; Rhinitis; Sinusitis; Subtilisins; Viscosity

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.

Topics: Adult; Aged; Biomarkers, Tumor; Case-Control Studies; Chronic Disease; Epstein-Barr Virus Infections; Female; Fibrin; Follow-Up Studies; Humans; Immunohistochemistry; Inflammation; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Prognosis

Chronic venous ulceration represents a very common event. Current standard treatment includes local wound care with the application of compression. We report the effects of platelet-rich plasma in patients with chronic venous ulcers, which is able to stimulate fibroblasts, macrophages and mesenchymal cells and growth factors in order to achieve re-epithelialisation and neovascularisation within the microenviroment of the wound. We also documented the efficacy of this method as the sole treatment without surgical procedures.

Topics: Aged; Aged, 80 and over; Antigens, CD34; Chronic Disease; Female; Fibrin; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Platelet-Rich Plasma; Treatment Outcome; Varicose Ulcer; Wound Healing

Multimorbidity is the co-occurrence of chronic diseases associated with low-grade chronic inflammation of connective tissue.. Frequency of occurrence and relative amounts of fibronectin (FN) complexes with fibrin (FN-fibrin) and FN monomer were analyzed in 130 plasma samples of 18 to 94-year-old multimorbid patients in relation to concentrations of FN and extra domain A (EDA)-FN, and C-reactive protein (CRP) as well as to age, number of coexisting chronic diseases and presence of specified diseases.. Immunoblotting revealed, besides FN dimer, the presence of FN monomer, and 750-, 1000-, and 1300-kDa FN-fibrin complexes in the multimorbid plasmas. The FN-fibrin complexes appeared more frequently and in higher relative amounts, but FN monomer less frequently and in a lower relative amount in the groups of elderly multimorbid patients, with a higher number of coexisting diseases and with dominance of cardiovascular diseases and osteoarthrosis, and with CRP concentration of 3-5mg/l. In contrast, the normal plasma contained only the FN-fibrin complex of 750 kDa in a lower relative amount, but with an increasing amount with normal aging. Moreover, FN concentration increased and EDA-FN decreased with the number of co-existing diseases and aging of patients, although both concentration values were lower than in the age-matched normal groups. FN concentration was the lowest in the exacerbation of a chronic disease and EDA-FN in the stable chronic disease groups.. The alterations in plasma FN molecular status were associated with micro-inflammation and micro-coagulation, as well as multimorbidity of subjects and their physiological aging.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aging; C-Reactive Protein; Chronic Disease; Comorbidity; Connective Tissue Diseases; Female; Fibrin; Fibronectins; Humans; Inflammation; Male; Middle Aged; Poland; Young Adult

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

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

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

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

Chronic thromboembolic pulmonary hypertension (CTEPH) is a fatal disease that is distinct from pulmonary arterial hypertension (PAH). Although CTEPH is characterized by obstruction of major pulmonary artery because of chronic thrombus, it remains unclear whether CTEPH is associated with prothrombotic condition.. In addition to conventional markers, GTP-bound levels of Rap1, RhoA, RalA, Rac1, and Ras in platelets, which are implicated for platelet activation, were measured in patients without pulmonary hypertension (non-PH, n=15), patients with PAH (n=19), and patients with CTEPH (n=25). Furthermore, the responsiveness to ex vivo thrombin stimulation was also evaluated. The ratios of the P-selectin positive platelets in the non-PH patients, patients with PAH, and patients with CTEPH were 1.40% (median and interquartile range, 0.83-1.82), 2.40% (1.80-3.39), and 2.63% (1.90-8.22), respectively (non-PH versus CTEPH, P<0.01). The activated GPIIb/IIIa-positive platelets were 6.01% (1.34-7.87), 11.39% (5.69-20.86), and 9.74% (7.83-24.01), respectively (non-PH versus CTEPH, P=0.01). GTP-bound RhoA was 1.79% (0.94-2.83), 4.03% (2.01-5.14), and 2.01% (1.22-2.48), respectively (non-PH versus PAH, P=0.04), and GTP-bound RalA was 1.58% (1.08-2.11), 3.02% (2.03-3.54), and 2.64% (1.42-4.28), respectively (non-PH versus PAH, P=0.023; non-PH versus CTEPH, P=0.048). In contrast, Rac1, Rap1, or Ras was not activated in any groups. The platelets of patients with CTEPH exhibited hyperresponsiveness to ex vivo thrombin stimulation compared with those of non-PH patients when evaluated for the surface markers. Either D-dimer or fibrin degradation product level was not increased in patients with CTEPH.. These results provide the first direct evidence that platelets of patients with CTEPH are highly activated and exhibit hyperresponsiveness to thrombin stimulation.

Topics: Adult; Aged; Blood Platelets; Case-Control Studies; Chronic Disease; Female; Fibrin; Hemodynamics; Humans; Hypertension, Pulmonary; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Glycoprotein GPIIb-IIIa Complex; Pulmonary Embolism; ral GTP-Binding Proteins; Regression Analysis; rhoA GTP-Binding Protein; Thrombin

Emerging evidence indicates that various haemostatic components can regulate the progression of liver disease. Thrombin-activatable fibrinolysis inhibitor (TAFI) possesses anti-inflammatory properties besides its anti-fibrinolytic function. Here, we investigated the contribution of TAFI to the progression of disease in murine models of chronic and acute liver failure. Chronic carbon tetrachloride (CCL4) administration induced liver damage and fibrosis both in TAFI knockout (TAFI-/-) mice and wild-type controls. Smooth muscle actin-α (α-SMA) content of liver tissue was significantly increased after 1 and 3 weeks, and pro-collagen α1 expression was significantly increased after 3 and 6 weeks in TAFI-/- mice. TAFI-/- mice showed significantly elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 3 weeks of CCL4. Neutrophil influx was significantly increased in TAFI-/- mice after 6 weeks of CCL4. No difference in hepatic fibrin deposition between TAFI-/- and wild-types was observed. After acetaminophen intoxication, necrosis was significantly increased in TAFI-/- mice at 24 hours (h) after injection. AST and ALT levels were decreased at 2 and 6 h after acetaminophen injection in TAFI-/- mice, but were significantly higher in the TAFI-/- mice at 24 h. Similarly, hepatic fibrin deposition was decreased at 6 h in TAFI-/- mice, but was comparable to wild-types at 24 h after injection. In conclusion, TAFI deficiency results in accelerated fibrogenesis and increased liver damage in murine models of chronic and acute liver disease, which may be related to increased inflammation.

Topics: Acetaminophen; Actins; Acute Disease; Alanine Transaminase; Animals; Aspartate Aminotransferases; Carbon Tetrachloride; Carboxypeptidase B2; Chemical and Drug Induced Liver Injury; Chronic Disease; Collagen Type I; Collagen Type I, alpha 1 Chain; Fibrin; Gene Expression Regulation; Liver; Liver Cirrhosis, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Necrosis; Neutrophil Infiltration; RNA, Messenger; Time Factors

Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary thromboembolism (PTE), but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated.. Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP). Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls).. Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037) and 95% confidence interval (95% CI, 1.262-3.289) showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G) genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype.. Fibrinogen Aα Thr312Ala (A/G) polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chronic Disease; Female; Fibrin; Fibrinogen; Fibrinolysis; Gene Frequency; Genotype; Humans; Hypertension, Pulmonary; Male; Middle Aged; Polymorphism, Single Nucleotide; Pulmonary Embolism; Young Adult

Chronic cholestatic liver injury induced by cholestasis in rodents is associated with hepatic fibrin deposition, and we found evidence of fibrin deposition in livers of patients with cholestasis. Key components of the fibrinolytic pathway modulate cholestatic liver injury by regulating activation of hepatocyte growth factor. However, the exact role of hepatic fibrin deposition in chronic cholestasis is not known. We tested the hypothesis that fibrinogen (Fbg) deficiency worsens liver injury induced by cholestasis. Fbg-deficient mice (Fbgα(-/-) mice) and heterozygous control mice (Fbgα(+/-) mice) were fed either the control diet or a diet containing 0.025% α-naphthylisothiocyanate (ANIT), which selectively injures bile duct epithelial cells in the liver, for 2 weeks. Hepatic fibrin and collagen deposits were evident in livers of heterozygous control mice fed the ANIT diet. Complete Fbg deficiency was associated with elevated serum bile acids, periportal necrosis, and increased serum alanine aminotransferase activity in mice fed the ANIT diet. Fbg deficiency was associated with enhanced hepatic expression of the transcription factor early growth response-1 (Egr-1) and enhanced induction of genes encoding the Egr-1-regulated proinflammatory chemokines monocyte chemotactic protein-1, KC growth-regulated protein, and macrophage inflammatory protein-2. Interestingly, peribiliary collagen deposition was not evident near necrotic areas in Fbg-deficient mice. The results suggest that in this model of chronic cholestasis, fibrin constrains the release of bile constituents from injured intrahepatic bile ducts, thereby limiting the progression of hepatic inflammation and hepatocellular injury.

Topics: 1-Naphthylisothiocyanate; Afibrinogenemia; Aged; Animals; Bile Ducts; Cholestasis; Chronic Disease; Collagen; Diet; Disease Models, Animal; Early Growth Response Protein 1; Feeding Behavior; Female; Fibrin; Fibrinogen; Gene Expression Regulation; Humans; Hyperplasia; Inflammation; Liver; Liver Cirrhosis; Male; Mice; Middle Aged; Neutrophils; Xenobiotics

This prospective, uncontrolled pilot study evaluated the safety and clinical performance of Leucopatch an additive-free, autologous platelet-rich fibrin in the treatment of recalcitrant chronic wounds. Fifteen patients, with 16 lower extremity chronic wounds of varying etiologies were treated weekly with Leucopatch, prepared at the point of care from a donation of the patients' blood, for 6 weeks, or until healing was complete. The wounds had been present for 2 to 108 months (median 24 months) and ranged in size from 0.4 to 15.7 cm(2) (median 2.3 cm(2)) and had not responded to previous treatments. Of the 13 wounds (12 patients) included in the per-protocol efficacy analysis, 4 healed completely (31%). Mean wound area decreased significantly by 65% (95% confidence interval = 45.6% to 83.8%) resulting in a median wound size of 0.9 cm(2) (range = 0-9.6cm(2)). There were no serious adverse events. Two adverse events, one of noncompliance and one infection, were observed; neither was considered to be related to treatment. The results indicate that Leucopatch is easy to prepare and apply in the clinic, is safe, and may be a clinically effective treatment of recalcitrant chronic wounds.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Blood Platelets; Chronic Disease; Confidence Intervals; Female; Fibrin; Humans; Male; Middle Aged; Pilot Projects; Platelet-Rich Plasma; Prospective Studies; Regression Analysis; Secondary Prevention; Statistics as Topic; Transplantation, Autologous; Treatment Failure; United States; Wound Healing; Wounds and Injuries; Young Adult

Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.. Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.. Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.

Topics: Animals; Arterioles; Biomarkers; Cell Proliferation; Chronic Disease; Complement C3; Complement C3a; Complement C5a; Endothelium, Vascular; Fibrin; Gene Deletion; Humans; Hypertension, Pulmonary; Hypoxia; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Platelet Activation; Pulmonary Artery; Thromboplastin; Up-Regulation

The purpose of this study was to evaluate the effectiveness of phacoemulsification and viscogoniosynechialysis in the management of patients with chronic angle-closure glaucoma (CACG). Fifty-six eyes of 45 recruited patients were classified into two groups: group 1 had medically controlled CACG (IOP 21 mmHg with maximum tolerated medications) including 21 eyes. All of the patients had at least one quadrant without peripheral anterior synechia in gonioscopy. After phacoemulsification, a viscoelastic agent was used for viscogoniasynecialysis. Success was defined as IOP

Topics: Aged; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bevacizumab; Chronic Disease; Female; Fibrin; Follow-Up Studies; Glaucoma, Angle-Closure; Gonioscopy; Humans; Iris; Macular Edema; Male; Middle Aged; Ophthalmologic Surgical Procedures; Phacoemulsification; Postoperative Complications; Prospective Studies; Tomography, Optical Coherence; Treatment Outcome; Viscoelastic Substances

Preterm infants exposed to oxygen and mechanical ventilation are at risk for bronchopulmonary dysplasia (BPD), a multifactorial chronic lung disorder characterized by arrested alveolar development and nonsprouting, dysmorphic microvascular angiogenesis. The molecular regulation of this BPD-associated pathological angiogenesis remains incompletely understood. In this study, the authors used focused microarray technology to characterize the angiogenic gene expression profile in postmortem lung samples from short-term ventilated preterm infants (born at 24 to 27 weeks' gestation) and age-matched control infants. Microarray analysis identified differential expression of 13 of 112 angiogenesis-related genes. Genes significantly up-regulated in ventilated lungs included the antiangiogenic genes thrombospondin-1, collagen XVIII alpha-1, and tissue inhibitor of metalloproteinase-1 (TIMP1), as well as endoglin, transforming growth factor-alpha, and monocyte chemoattractant protein-1 (CCL2). Increased expression of thrombospondin-1 in ventilated lungs was verified by real-time polymerase chain reaction (PCR) and immunolocalized primarily to intravascular platelets and fibrin aggregates. Down-regulated genes included proangiogenic angiogenin and midkine, as well as vascular endothelial growth factor (VEGF)-B, VEGF receptor-2, and the angiopoietin receptor TEK/Tie-2. In conclusion, short-term ventilated lungs show a shift from traditional angiogenic growth factors to alternative, often antisprouting regulators. This angiogenic shift may be implicated in the regulation of dysmorphic angiogenesis and, consequently, deficient alveolarization characteristic of infants with BPD.

Topics: Antigens, CD; Blood Platelets; Bronchopulmonary Dysplasia; Chemokine CCL2; Chronic Disease; Collagen Type XVIII; Down-Regulation; Endoglin; Female; Fibrin; Gene Expression Profiling; Humans; Infant, Newborn; Infant, Premature; Lung; Male; Neovascularization, Physiologic; Receptor, TIE-2; Receptors, Cell Surface; Respiration, Artificial; Retrospective Studies; Thrombospondin 1; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor alpha; Up-Regulation; Vascular Endothelial Growth Factor B

To develop an in-vitro model to evaluate the efficiency of wound-rinsing solutions in removing adherent, hydrophobic, denatured proteins. We hypothesised that saline solutions would be less effective than surfactant-containing solutions in removing denatured proteins.. Prepared slides containing dried blood plasma or fibrin were incubated for up to one hour in histological troughs filled with one of four test solutions: physiological saline solution, Ringer's solution, a surfactant-containing solution and an antiseptic. The concentration of dissolved proteins was measured using a modified Biuret test. Results were analysed by plotting protein concentration against the incubation time.. During the incubation period, the protein concentration increased in all of the test solutions, with the lowest concentration reported in the two saline-based solutions. These stayed clear, while the surfactant-containing solution become opaque, indicating that the surfactant had encased hydrophic substances, such as denatured proteins.. Ringer's solution and saline are inappropriate solvents for adhering wound coatings. A sterile, surfactant-containing wound rinsing solution contains the essential properties for thorough and gentle cleansing of chronic wounds.. None.

Topics: Anti-Infective Agents, Local; Chronic Disease; Drug Evaluation, Preclinical; Fibrin; Humans; Isotonic Solutions; Plasma; Protein Denaturation; Ringer's Solution; Skin Care; Sodium Chloride; Surface-Active Agents; Therapeutic Irrigation; Wound Healing; Wounds and Injuries

Topics: Aged; Biopsy; Chronic Disease; Colonic Polyps; Colonoscopy; Colorectal Neoplasms; Diagnosis, Differential; Diarrhea; Fibrin; Granulation Tissue; Humans; Hyperplasia; Inflammatory Bowel Diseases; Intestinal Mucosa; Male

Chronic wounds are a growing challenge for physicians and health insurance agencies. The burden of affected patients is enormous, because of pain but also because of long-lasting therapies and dependence on nursing services. In other areas of medicine, computer-based diagnostics is established, yet, accurate wound documentation is rarely conducted and is often limited to size measurement with a ruler and a rough photo documentation. Objective assessment of lesions by evaluation of granulation tissue, fibrin coverage and necrosis is not performed. The aim of this study was to investigate the spread and variety in judgement of a chronic wound. A diabetic ulcer was described by 16 wound therapists (eight physicians and eight nurses). Granulation tissue, fibrin coverage, necrosis, size and depth of the lesion, wound exudate and wound edges were judged, and the therapeutical consequences were determined. Study data show an extensive inhomogeneity and a wide spread of the results, like in no other field of medical diagnostics. This could be shown in the group of physicians, as well as in the group of nursing personnel. As the choice of treatment by a specialist is based upon the assessment of the wound, it is possible that in practice it can lead to suboptimal therapy. This is a consequence of varying treating physicians and subsequent changes in treatment regimens. This results in a prolongation of treatment and burden for the patient. Circumstances like this contribute to rising of costs in this area of the health care system. The goal is to apply objective wound diagnostic technologies in the field of chronic wounds to catch up with other diagnostic procedures.

Topics: Chronic Disease; Clinical Competence; Diabetic Foot; Fibrin; Granulation Tissue; Humans; Necrosis; Nurses; Observer Variation; Physicians; Reproducibility of Results; Wound Healing

Deep venous thrombosis and pulmonary thromboembolism are common within weeks of spinal cord injury (SCI) but clinically uncommon in the chronically paralyzed. Fibrinogen half-life (FHL) and fibrin uptake of the legs (FUT), as indicators of an active thrombotic process, have been used to test this clinical impression.. Data from the use of autologous preparations of radioiodinated fibrinogen to determine FHL and FUT in 17 men paralyzed at cervical (6), thoracic (10), and lumbar levels (1), at ASIA grades A (15) and C (2) in 1974 to 1976 were reviewed. Group A consisted of 12 subjects 29 +/- 8 years of age and paralyzed 1 week to 5 months (median, 1 month). Group B consisted of 5 subjects 46 +/- 17 years of age and paralyzed 24 to 96 months (median, 36 months). Group B subjects were older and paralyzed longer than Group A. Group C consisted of 4 able-bodied control subjects enrolled at the same time for FHL studies, and these subjects were 34 to 38 years of age.. FHL was 61 +/- 14 hours for all SCI subjects and 95 +/- 23 hours for Group C (P = 0.001). Group A FHL was 59 +/- 16 hours, and FUT was positive in 8 of 12 subjects. Group B FHL was 66 +/- 7 hours, and FUT was positive in 3 of 4 subjects (1 FUT not done; P = 0.30 and 1.0, respectively).. Fibrinogen metabolism was abnormal in patients with acute SCI at high risk for pulmonary thromboembolism (PE) but continued to be abnormal beyond the high risk period for PE, possibly because of the greater age of the patients in the long-term paralysis group.

Topics: Acute Disease; Adult; Case-Control Studies; Chronic Disease; Disease Progression; Fibrin; Fibrinogen; Half-Life; Humans; Iodine Radioisotopes; Male; Middle Aged; Paralysis; Pulmonary Embolism; Risk Factors; Spinal Cord Injuries; Time Factors; Venous Thrombosis

Considerable confusion exists regarding the proper classification of idiopathic eosinophilic pneumonia (IEP). Furthermore, there are no reports describing the clinicopathological differences between the various forms of eosinophilic pneumonias.. The histological findings in acute eosinophilic pneumonia (AEP) and chronic eosinophilic pneumonia (CEP) were examined and the clinical and radiological features were contrasted with them.. Radiologically, ground glass opacity and interlobular septal thickening were characteristic of the AEP cases, while air space consolidation was seen in all CEP cases. Histologically, interstitial oedema and fibrin deposition were prominent in the AEP cases. Type II cells were detached from the alveolar walls, although the basal lamina was predominantly intact. In CEP, in addition to cellular infiltration, there was prominent intraluminal fibrosis. Disruption of the basal lamina was observed and nests of intraluminal fibrosis were directly adjacent and connected to the alveolar walls.. An essential histological difference between AEP and CEP is the severity of basal lamina damage and the amount of subsequent intraluminal fibrosis. In AEP particularly, these findings explain the radiographical findings, as well as the rapid and complete improvement noted in such cases.

Topics: Acute Disease; Adolescent; Adult; Aged; Basement Membrane; Biopsy; Bronchoalveolar Lavage; Chronic Disease; Female; Fibrin; Humans; Lung; Male; Middle Aged; Pulmonary Alveoli; Pulmonary Edema; Pulmonary Eosinophilia; Pulmonary Fibrosis; Radiography, Thoracic; Retrospective Studies; Tomography, X-Ray Computed

We sought to investigate the benefit, predictors of procedural success, and safety of pre-procedural intra-coronary fibrin-specific lytic infusion (ICL) in patients with failed prior percutaneous coronary intervention (PCI) for chronic total occlusions (CTO).. Percutaneous coronary intervention for CTO remains a challenge with a high incidence of procedural failure secondary to inability to cross the occlusion with the guidewire.. Eighty-five patients who underwent unsuccessful PCI procedures of CTO (more than three months' duration) had a repeat attempt of recanalization with the use of pre-procedural ICL. Patients received a weight-adjusted dose of either alteplase (tPA) (2 to 5 mg/h) or tenecteplase (TNK) (0.5 mg/h) for a total of 8 h. The total dose of ICL therapy was infused split between the guiding catheter and an intracoronary infusion catheter. A step-down multivariate logistic regression analysis was completed to determine the best predictors of procedural success. In-hospital major adverse cardiac events (MACE) including myocardial infarction, acute reocclusion, stroke, and death, as well as bleeding complications, were also examined.. The procedure was successful in 46 of 85 cases (54%). Four of 85 (5%) contained dissections that did not result in perforations, tamponade, or MACE. The incidence of groin complications was 7 of 85 (8%) and of bleeding complications requiring transfusions was 3 of 85 (3.5%). On multivariate analysis, predictors of success were tapering morphology (odds ratio, 15.5; 95% confidence interval, 3.73 to 63; p = 0.0002) and lack of bridging collaterals (odds ratio, 5.08; 95% confidence interval, 1.53 to 17; p = 0.008).. Intracoronary infusion of fibrin-specific thrombolytic therapy may provide a valuable and safe option for facilitating percutaneous revascularization of CTO.

Topics: Angioplasty, Balloon, Coronary; Cardiac Catheterization; Chronic Disease; Coronary Angiography; Coronary Stenosis; Female; Fibrin; Fibrinolytic Agents; Humans; Male; Middle Aged; Preoperative Care; Reoperation; Treatment Failure

Our objective was to compare the efficacy of adjunctive intrapleural fibrinolytic agents (IPFA) (streptokinase, urokinase) on fibrinopurulent stage empyema and chronic stage empyema in children. IPFA were used in 78 pediatric patients with empyema (36 fibrinopurulent stage empyemas, 42 chronic stage empyemas) between December 1994 and September 2002. Pleural biopsy was done for staging in all cases. Streptokinase 250,000 units in 100 ml normal saline (62 patients) or 100,000 units urokinase in 100 ml normal saline (16 patients) was instilled daily into the patient's chest tube, and the tube was clamped for 4 h, followed by suction. This treatment was continued daily for 2-8 days until resolution was demonstrated by chest radiographs and/or computed chest tomography. Success of treatment was 97.2% (complete response 24/36, partial response 11/36) in the fibrinopurulent stage and 9.4% (complete response 2/42, partial response 2/42) in chronic empyema cases. In one patient with fibrinopurulent empyema, the treatment was stopped due to allergic reaction and pleural hemorrhage; this patient died 1 day later in a septic condition. Although an invasive method, the pleural biopsy technique may be an alternative way of more properly staging thoracic empyema in selected children in whom staging based on radiographic and biochemical findings is doubtful. Intrapleural fibrinolytic treatment is an effective and safe therapy of choice and may have significant benefit in most children with fibrinopurulent phase empyema, except for those with bronchopleural fistula. IPFA do not seem to be effective in children with chronic phase empyema.

Topics: Adolescent; Biopsy; Chest Tubes; Child; Child, Preschool; Chronic Disease; Drug Hypersensitivity; Empyema, Pleural; Female; Fibrin; Fibrinolytic Agents; Hemorrhage; Humans; Infant; Male; Pleural Diseases; Staphylococcal Infections; Streptokinase; Suction; Tomography, X-Ray Computed; Treatment Outcome; Urokinase-Type Plasminogen Activator

Most animal models of venous thrombosis involve acute thrombosis with hypercoagulability in small rodents. To better replicate human disease, we developed two models in the pig, a species similar to humans in size and in vascular and coagulation reactivity. One model involves de-endothelialisation with 50% or 80% stenosis and the other replacement of a venous segment by a Gore-Tex vascular prosthesis. Both models were tested with and without acute induced hypercoagulability (thromboplastin infusion). Thrombi obtained without thromboplastin infusion were composed of a multilayered platelet and a fibrin meshwork structure similar to that usually found in humans. With thromboplastin infusion, the thrombi were homogeneous fibrin structures imprisoning red blood cells. The high incidence of thrombosis obtained with the 80% stenosis model would be useful for studying anticoagulant treatments, whereas the low incidence with 50% stenosis would be useful for evaluating procoagulant effects of conditions or treatments. These new models shed further light on the development of venous thrombi under conditions similar to those seen in humans and may prove useful for investigating anticoagulant and procoagulant effects.

Topics: Animals; Blood Vessel Prosthesis; Chronic Disease; Constriction, Pathologic; Disease Progression; Endothelium, Vascular; Fibrin; Hemorheology; Jugular Veins; Models, Animal; Swine; Thrombophilia; Thromboplastin; Venous Thrombosis

A particular Lewis rat substrain (LEW/Maa) develops chronic glomerulonephritis in the anti-Thy 1 model (aThy 1-GN) characterized by increased microaneurysm formation, chronic glomerular sclerosis and persistent albuminuria. This phenotype is accompanied by increased and prolonged glomerular induction of inducible nitric oxide synthase (iNOS) when compared to the LEW/Moe substrain, in which aThy 1-GN resolves quickly. We investigated the effect of selective iNOS inhibition by l-N6-(1-iminoethyl)-lysine (L-NIL) administration on aThy 1-GN in LEW/Maa rats.. Nephritic rats were studied over a period of 7 days. L-NIL-treated animals received 20 mg/day L-NIL in the drinking water starting two days prior to disease induction. iNOS activity was determined in cultured glomeruli and in urine samples, respectively. Severity of aThy 1-GN was determined by scoring glomerular matrix expansion and microaneurysm formation, and by albuminuria measurements (ELISA). Immunohistochemical evaluation was performed including staining for macrophages (ED-1), platelets (PL-1) and fibrin deposition.. L-NIL treated rats (+NIL) showed a significant decrease in peak nitrate production by ex vivo cultured glomeruli, and in urinary nitrate excretion versus untreated nephritic rats (-NIL). Mean arterial pressure remained unchanged in both +NIL and -NIL rats. +NIL rats developed significantly increased albuminuria (+44%) associated with a significant increase in glomerular platelet (+45%) and fibrin deposition (+48%).. Selective inhibition of iNOS aggravated albuminuria in chronic aThy 1-GN in LEW/Maa rats. Induction of iNOS during the inflammatory phase of this model may be a partially protective mechanism by interfering with intraglomerular coagulation processes.

Topics: Albuminuria; Animals; Blood Platelets; Blood Pressure; Chronic Disease; Enzyme Inhibitors; Fibrin; Isoantibodies; Kidney Glomerulus; Lysine; Nephritis; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; Rats, Inbred Lew; Thrombosis

Chronic allograft nephropathy (CAN), the major cause of renal graft failure, frequently displays extensive interstitial fibrin deposition. Little is known in regard to the cause of the altered coagulation/fibrinolysis balance and its relevance in the pathogenesis of CAN. Thrombin, present within the fibrin clots, can interact with a specific receptor, protease-activated receptor 1 (PAR-1), and modulate a variety of cell functions. On the other hand, the derangement of the fibrinolytic system may directly affect extracellular matrix (ECM) degradation.. In the present study, we investigated, by in situ hybridization, PAR-1 gene expression and the mRNA levels for tissue factor and plasminogen activator inhibitor 1 (PAI-1), two key regulatory molecules of coagulation and fibrinolysis, in 16 CAN biopsies and in 10 normal human kidney grafts. The thrombin-induced transforming growth factor beta (TGF-beta) gene and protein expression in proximal tubular cells (PTC) was investigated by Northern blotting and ELISA, respectively.. Fibrin deposits, absent in normal grafts, were observed in the interstitial space and arterial wall of CAN. Tissue factor gene expression was not increased either at the vascular or at the interstitial level in CAN. On the contrary, PAI-1 gene expression, barely detectable in control tissue, was strikingly increased in CAN, with a distribution resembling the pattern of fibrin deposition. Note that PAI-1 gene expression was directly correlated with the degree of interstitial fibrosis. In addition, fibrin deposits were strictly associated with a marked increase of PAR-1 gene expression in endothelial cells and PTC. The tubular expression of PAR-1 was significantly higher in Banff grade II-III than in grade I. In vitro, incubation of PTC with thrombin caused a significant up-regulation of TGF-beta gene expression, followed by an increased TGF-beta release into the supernatant. Interestingly, urine from CAN patients contained significantly higher levels of TGF-beta.. Fibrin deposits in CAN may result from the increased expression of PAI-1 and the subsequent inhibition of fibrinolysis. The reduced fibrinolysis may cause, in turn, a decreased ECM turnover. Finally, thrombin, preserved in the active form within the fibrin clots, may interact with PAR-1 highly expressed on PTC and induce an up-regulation of ECM deposition in a TGF-beta-dependent manner.

Topics: Chronic Disease; Extracellular Matrix; Fibrin; Fibrinolysis; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Plasminogen Activator Inhibitor 1; Receptor, PAR-1; Receptors, Thrombin; RNA, Messenger; Transforming Growth Factor beta; Transplantation, Homologous

To determine the regulatory role of plasminogen in hepatic repair following a chronic liver injury, we injected carbon tetrachloride (CCl(4)) biweekly into mice lacking plasminogen (Plg(0)) and plasminogen-sufficient littermates (Plg(+)). On gross examination, we found that Plg(0) livers became enlarged and pale with foci of red nodules as early as 4 weeks after CCl(4) injection, while Plg(+) livers appeared minimally affected by 6 weeks. Microscopically, Plg(0) livers had a pronounced pericentral linking, with accumulation of centrilobular eosinophilic material in injured areas, which resulted in a significant increase in liver mass and total protein. Immunohistochemistry revealed that fibrin accumulated progressively in injured regions. However, the combined genetic loss of plasminogen and fibrinogen did not correct the abnormal phenotype. Mason's trichrome staining revealed intense signal in centrilobular regions and electron microscopy showed a marked increase in fibrillary material demonstrating an excessive accumulation of extracellular matrix in Plg(0) mice. The zone-specific increase in matrix components was associated with an increase in the number of activated hepatic stellate cells within injured sites of Plg(0) livers. Taken together, these data suggest that the progressive accumulation of fibrin-unrelated matrix substrates in Plg(0) livers after a chronic injury results from the combined effects of impaired proteolysis and increased matrix production.

Topics: Afibrinogenemia; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chronic Disease; Extracellular Matrix; Fibrin; Liver; Liver Diseases; Matrix Metalloproteinase 9; Mice; Mice, Knockout; Microscopy, Electron; Plasminogen; Time Factors

To evaluate the efficacy and safety of a new hydrodynamic catheter for removal of chronic iliac vein thrombus.. Unilateral iliac vein thrombosis was induced in seven pigs by combining permanent coil and temporary balloon occlusion. Thrombectomy was performed with a new hydrodynamic catheter (10 F S.E.T.) 3 days after thrombus induction. After thrombectomy, the animals were killed and the iliac veins were examined histologically.. Complete thrombectomy (100% thrombus removal) was achieved in three of seven animals, 75% removal in three of seven animals, and only 30% removal in one animal. The average thrombus removal was 75%. Successful re-establishment of flow was achieved in five of seven cases. Histologically, the thrombi were partially organized, meeting the histologic criteria for early chronic venous thrombosis. Minor venous wall damage caused by the thrombectomy procedure without acute hemodynamic consequences was observed in four of seven cases.. The 10-F S.E.T. catheter was reasonably effective in removing chronic iliac vein thrombus with no hemodynamically significant complications.

Topics: Animals; Blood Platelets; Catheterization, Peripheral; Chronic Disease; Equipment Design; Erythrocytes; Evaluation Studies as Topic; Female; Fibrin; Iliac Vein; Regional Blood Flow; Rheology; Safety; Surface Properties; Swine; Thrombectomy; Thrombosis; Treatment Outcome; Vascular Patency

Local hyperfibrinolysis plays an important role in the pathogenesis of chronic subdural hematoma (CSH). The purpose of this study is to elucidate the nature of the local hyperfibrinolysis in CSH, by comparing the pattern of fibrin/fibrinogen degradation product (FDP) of hematomas with that of purified fibrin clots digested by plasmin in vitro. Forty-seven hematoma samples were subjected to the analysis. FDPs of CSH and the purified fibrin clots digested by plasmin for different incubation times were identified using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immuno-blotting, and then quantified by densitometry. The effect of alpha-2 plasmin inhibitor (A2-PI) on the degradation process was also studied. The FDP pattern of CSH was similar to those of purified fibrin digested by plasmin for 0.75-2 h. The FDP composition of CSH was closest to that of purified fibrin digested for 1 h. By adding the physiological concentration of A2-PI at the second hour, further degradation of high molecular weight FDPs was inhibited and the early FDP pattern persisted after 24 h. Local hyperfibrinolysis in CSHs is characterized by incomplete fibrinolysis, which occurs only on the solid fibrin clot, and is arrested in the liquid hematoma. As a result, high molecular weight FDPs persist in CSHs for weeks or months in the hematoma. A2-PI seems to play an important role in producing this unique FDP pattern in CSH.

Topics: Chronic Disease; Densitometry; Electrophoresis, Polyacrylamide Gel; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinolysin; Hematoma, Subdural; Humans; Molecular Weight

Topics: Animals; Cat Diseases; Cats; Chronic Disease; Feline Infectious Peritonitis; Fibrin; Male; Necrosis; Orchitis; Testis

The incidence of chronic hydrocephalus was studied in 39 patients with subarachnoid hemorrhage, who underwent perivascular coating with fibrin glue of cerebral arteries after clipping of aneurysm. A use was made of this procedure in order to prevent vasospasm by keeping the main cerebral arteries away from direct contact with subarachnoid clots. Most cases in this series belonged to group 3 of Fisher's CT grade (33/39, 84.6%). As a result, despite the high CT grade, the incidence of chronic hydrocephalus was as low as 17.9% (7/39), almost in agreement with those of the previous literature. In conclusion, (1) coating with fibrin glue did not increase the incidence of chronic hydrocephalus and (2) intrathecal application of fibrin glue is a promising method in the field of clinical neurosurgery.

Topics: Adhesives; Adult; Aged; Aged, 80 and over; Cerebral Arteries; Chronic Disease; Female; Fibrin; Follow-Up Studies; Humans; Hydrocephalus; Intracranial Aneurysm; Ischemic Attack, Transient; Male; Middle Aged; Subarachnoid Hemorrhage; Time Factors; Tissue Adhesives; Tomography, X-Ray Computed

We prepared a composite of fibrin clot and ciprofloxacin for use as a biodegradable antibiotic delivery system with sustained effect for the treatment of chronic osteomyelitis. In vitro, ten experiments were performed in which 10 mg of ciprofloxacin were incorporated into 4 ml of fibrin clot. The clots were preserved in nutrient broth and incubated at 37 degrees C for a total of 60 days. Every 24 h a broth specimen was obtained, and the ciprofloxacin concentration was determined by microbiological assay. The maximum level of antibiotic was noted on the first day (49.9 +/- 5.1 mg/l). The ciprofloxacin-fibrin clot complexes usually disintegrated after 60 days. In vivo, the fibrin-ciprofloxacin clots were made as previously described. The composite was implanted in the medullary canal of rabbit tibiae, and the antibiotic concentration was measured in bone, muscle, skin and serum. In all tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration against the common causative organisms of osteomyelitis for 10 days. The implant caused no systemic side-effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.

Topics: Animals; Anti-Infective Agents; Biodegradation, Environmental; Chronic Disease; Ciprofloxacin; Drug Carriers; Drug Combinations; Drug Delivery Systems; Fibrin; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Tissue Distribution

Massive chronic intervillositis (MCI) is an unusual placental lesion associated with poor fetal growth and adverse pregnancy outcome; it has not previously been associated with spontaneous abortion or recurrent pregnancy loss. This article reports a patient who had 10 spontaneous abortions with repetitious massive chronic intervillositis documented in four of five gestations spanning all three trimesters. Characteristic placental histology induced massive infiltration of the maternal intervillous space by chronic inflammatory cells and fibrin, without associated chronic villitis; the cellular infiltrate was composed predominantly of LCA and CD68 immunoreactive cells with scattered CD45RO positivity, consistent with a monocyte/macrophage population with occasional T lymphocytes. Elevated maternal serum alpha-fetoprotein was documented in two pregnancies. These findings support the concept that this unusual placental lesion may have an immunologic basis, and suggest that MCI may be a histopathologically recognizable cause of recurrent spontaneous abortion.

Topics: Abortion, Habitual; Adult; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Chorionic Villi; Chronic Disease; Female; Fibrin; Humans; Immunohistochemistry; Leukocyte Common Antigens; Macrophages; Male; Monocytes; Placenta Diseases; Pregnancy; Pregnancy Outcome; T-Lymphocytes

The photometric method of Fickenscher et al. for the determination of factor XIII (FXIII) activity has been used in the study of 35 patients with severe chronic hepatopathy, in comparison with 25 normal subjects. The FXIII proteic fractions a and b were determined by quantitative immuno-electrophoresis after Laurell. The plasmatic FXIII activity, as well as the proteic fractions a and b, were significantly reduced in hepatopatic patients, in comparison to controls, and proportional to the prolongation of prothrombin times. Ratios between functional and immunological levels of FXIII in hepatopatics were similar to those observed in controls. These results confirm the involvement of fibrin stabilization deficiency in the coagulation defect of severe chronic hepatopathies. The correlations between functional and antigenic values are in agreement with the hepatic origin of FXIII. The method of Fickenscher has been proved to be rapid and simple, and it may be useful in the routine study of hepatopathies, for a better knowledge of the role of FXIII deficiency in the complex coagulopathy of liver diseases, as well as of other acquired FXIII deficiencies.

Topics: Adult; Aged; Chronic Disease; Evaluation Studies as Topic; Factor XIII; Factor XIII Deficiency; Female; Fibrin; Humans; Immunoelectrophoresis; Liver Diseases; Male; Middle Aged; Photometry; Prothrombin Time

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

Fibrinogen, fibrin monomer, and D dimer were analyzed in 41 cases of chronic subdural hematoma (SDH) to characterize local rebleeding, coagulation, and fibrinolysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Chronic SDH's were divided into five groups according to their appearance on computerized tomography: high-density, isodensity, low-density, mixed-density, and layering types. The concentration of fibrinogen, which indicates rebleeding, was higher in the mixed-density (15.7 +/- 3.4 mg/dl (mean +/- standard error of the mean)) and layering (15.7 +/- 2.6 mg/dl) types of hematoma, and lower in the low-density hematomas (1.4 +/- 0.6 mg/dl) compared with the isodense hematomas (6.9 +/- 1.1 mg/dl). Fibrin monomer, which indicates coagulative activity, had a distribution similar to that of fibrinogen: 87 +/- 22, 18 +/- 8, 175 +/- 40, and 177 +/- 23 micrograms/ml in isodense, low and mixed-density, and layering types of hematomas, respectively. The D dimer, which indicates fibrinolytic activity, was higher in the layering hematoma type (2032 +/- 384 micrograms/ml), and lower in low-density hematomas (301 +/- 164 micrograms/ml) compared to isodense (1310 +/- 256 micrograms/ml) and mixed-density (1039 +/- 207 micrograms/ml) types of hematomas. These observations suggest the following characterization of each type of chronic SDH. The layering type is active, with a high tendency to rebleed and for hyperfibrinolytic activity. The mixed-density type has a high tendency to rebleed with lower hyperfibrinolytic activity than the layering type. The low-density hematoma is stable with a low tendency to rebleed and to fibrinolytic activity.

Topics: Adult; Aged; Aged, 80 and over; Blood Coagulation Disorders; Chronic Disease; Electrophoresis, Polyacrylamide Gel; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hematoma, Subdural; Humans; Immunoblotting; Male; Middle Aged; Recurrence; Sodium Dodecyl Sulfate

Nonoperative therapeutic approaches to chronic venous ulceration, although effective, often require prolonged dressing care and immobilization with leg elevation. Results of skin grafting, perforator ligation, and valve interpositions and reconstructions improve results of ulcer healing but have not uniformly prevented ulcer recurrence. Our hypothesis is that reconstruction of chronic venous ulcers by excision of the diseased tissue bed and replacement with a free flap containing multiple competent microvenous valves and a normal tissue microcirculation will result in long-term cure of these debilitated patients.. Six patients with chronic venous insufficiency and recurrent ulceration (class 3) underwent excision of ulcers and surrounding liposclerotic tissue beds and reconstruction with fasciocutaneous free flaps (two bilateral). Preoperative and postoperative photoplethysmography was used to assess venous refilling times. Duplex scanning was performed to assess deep venous reflux.. There were no flap failures. Photoplethysmographic venous refilling times measured on flaps demonstrated significant immediate and long-term increases from preoperative values (all results +3 by Society of Vascular Surgery outcome grading). Long-term maintenance of tissue integrity is shown by absence of recurrent ulceration and no evidence of recurrent tissue lipodermatosclerosis in all flaps at follow-up (8 months to 7.5 years; mean 24 months). No recurrent lipodermatosclerosis was seen on flap biopsy at 2 and 7 years. Separate cadaveric injection studies, including scanning electron microscopy, revealed numerous microvenous valves directed toward the draining pedicle in the flaps used for reconstruction.. This is the first comprehensive report providing combined laboratory and clinical evaluation, anatomic rationale, and long-term outcome of surgical rehabilitation of patients with chronic venous ulceration who have undergone microsurgical flap reconstruction.

Topics: Adult; Anastomosis, Surgical; Capillaries; Chronic Disease; Female; Fibrin; Humans; Hyperplasia; Male; Microcirculation; Microsurgery; Middle Aged; Photoplethysmography; Popliteal Vein; Scleroderma, Localized; Surgical Flaps; Tibia; Ultrasonography; Varicose Ulcer; Venous Insufficiency; Venules; Wound Healing

Topics: Animals; Antibody Formation; Cell Adhesion Molecules; Chronic Disease; Complement C3; Cytokines; Fibrin; Graft Rejection; Immunoglobulin M; Isoantibodies; Kidney Transplantation; Rats; Rats, Inbred F344; Rats, Inbred Lew; Transplantation, Homologous

Pericapillary fibrin cuffs are probably involved in the pathogenesis of venous leg ulcers. Factor XIII (Fibrin stabilizing factor) is of importance in wound healing. Its activity, which may affect ulceration, was found to be significantly reduced in the blood of venous leg ulcer patients and in post-phlebitic patients, compared with healthy controls.

Topics: Chronic Disease; Factor XIII; Factor XIII Deficiency; Fibrin; Humans; Leg Ulcer; Postphlebitic Syndrome; Varicose Ulcer; Wound Healing

Distribution of fibrinogen/fibrin and fibronectin in regions of experimental myocardial infarction were studied by the immunofluorescence technique. Distinct from normal myocardium 3 and 12 to 24 h after coronary artery ligation infiltration of necrotized cardiomyocytes by fibrinogen/fibrin and plasma fibronectin was detected. Fibrinogen/fibrin and plasma fibronectin constitute "primary matrix" of granulation tissue. On the third day after experimental infarction, synthesis of cellular fibronectin begins. Its content in the extracellular matrix (ECM of granulation tissue significantly increases on days 7 to 15. The amount of fibronectin in the ECM of developing scar tissue dramatically decreases 30 days after infarction, Fibrinogen/fibrin was continually identified in granulation tissue in zones of myocardial infarction. However, its amount in the ECM of developing scar tissue gradually decreased.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Arteries; Chronic Disease; Coronary Aneurysm; Coronary Vessels; Epitopes; Fibrin; Fibrinogen; Fibronectins; Fluorescent Antibody Technique; Granulation Tissue; Ligation; Male; Myocardial Infarction; Myocardium; Rats; Rats, Inbred Strains

Light and electron immunocytochemistry using antibodies recognising a class II major histocompatibility complex antigen, fibrin, fibronectin, albumin and factor VIII related antigen has been used to stain sections of spinal cord from normal guinea pigs and those with chronic relapsing experimental allergic encephalomyelitis (CREAE). It was found that class II MHC antigens, fibrin and fibronectin were present in normal blood vessels and at high levels in lesions from animals at all stages of the disease. The possible immunological roles of these antigens suggest their participation in the initiation and maintenance of disease state.

Topics: Animals; Antibodies, Monoclonal; Blood Vessels; Chronic Disease; Encephalomyelitis, Autoimmune, Experimental; Fibrin; Fibronectins; Guinea Pigs; Histocompatibility Antigens Class II; Immunologic Techniques; Microscopy, Electron; Recurrence; Spinal Cord; Staining and Labeling

Fibrin glue (FG), made with highly concentrated human fibrinogen and clotting factors, was used to achieve parenchymal organ hemostasis in patients with disordered coagulation secondary to massive transfusion, chronic disease, and disseminated intravascular coagulation; it was effective in controlling liver hemorrhage in seven patients and in the performance of a splenorrhaphy in one other patient. The coagulation profile was grossly abnormal in all patients, and the mean +/- SD intraoperative blood loss was 5.1 +/- 4.2 L; patients received 14 +/- 10 U of blood perioperatively. The amount of FG required to achieve hemostasis varied directly with the extent of injury and intraoperative blood loss (r = .84), and all patients with a blood loss greater than 4 L required at least 25 mL of FG to stop bleeding. Two patients died postoperatively secondary to cardiac arrest and adult respiratory distress syndrome. Because FG does not depend on adequate platelet or clotting factor levels to be effective, it is especially useful in patients with parenchymal organ hemorrhage and disordered coagulation.

Topics: Adult; Aged; Aprotinin; Blood Coagulation Disorders; Chronic Disease; Disseminated Intravascular Coagulation; Drug Combinations; Factor XIII; Female; Fibrin; Fibrin Tissue Adhesive; Fibrinogen; Hemostasis, Surgical; Humans; Liver; Male; Spleen; Thrombin; Tissue Adhesives; Transfusion Reaction

The stomach surgically removed from 38 patients because of chronic ulcers are studied. The fibrinoid necrosis zone observed at the bottom of 30 ulcers is formed of two layers out of which the superficial layer only is necrotic while the deep one represent a fibrinoid swelling. The latter consists of the network of collagen fibers and fibrin elements with surviving connective tissue cells. Two processes going into the opposite directions take place on the border between the fibrinoid zone and granulation tissue: the spread of the fibrinoid to the granulation tissue and its organization by the granulation tissue elements. Interrelationship between these processes as well as the intensity of the fibrinoid necrosis rejection from the surface determines the thickness of the zone. Fibrinoid prevents the stomach wall digestion but at the same time inhibits the ulcer healing.

Topics: Adult; Chronic Disease; Fibrin; Gastrectomy; Gastric Mucosa; Histocytochemistry; Humans; Microscopy, Electron; Middle Aged; Necrosis; Staining and Labeling; Stomach; Stomach Ulcer

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

Cross-linked fibrin degradation products (XDP) were measured with a highly sensitive and specific ELISA in 21 patients with essential mixed cryoglobulinemia (EMC) and in 16 controls. Patients had significantly increased levels of XDP, together with abnormalities in routine coagulation tests. Moreover, XDP were higher in patients with more severe disease. These results support the hypothesis that EMC patients have a chronic disseminated intravascular coagulation (DIC), and underline the significance of XDP measurement in the evaluation of these patients.

Topics: Adult; Aged; Chronic Disease; Cryoglobulinemia; Disseminated Intravascular Coagulation; Enzyme-Linked Immunosorbent Assay; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged

Topics: Aged; Cholecystitis; Cholestasis; Chronic Disease; Embolism; Fibrin; Hepatic Duct, Common; Humans; Male; Postoperative Complications

The concentration of urinary fibrin(ogen) degradation products (FDP) was determined by using enzyme immunoassay and radio immunoassay, and their urinary levels were compared with histologically classified types of glomerulonephritis. Urinary FDP levels were higher in the severe type of proliferative glomerulonephritis and at the active phase of systemic lupus erythematosus (SLE). They were also high in the membranous glomerulonephritis. Molecular weight of urinary FDP of a patient with severe proliferative glomerulonephritis was determined to be 150,000 and 68,000, respectively after gel filtration. Urinary FDP levels were higher in patients with glomerular fibrin deposit than in patients without fibrin deposit or normal volunteers. The amounts of excreted protein in urine was not related to the amounts of FDP. Decrease in the reciprocal of serum creatinine levels resulted in high urinary FDP levels, indicating that high urinary FDP levels may represent deterioration of renal function.

Topics: Chromatography, Gel; Chronic Disease; Creatinine; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Humans; Immunoassay; Molecular Weight

Eight of ten patients with chronic or subacute cutaneous lupus erythematosus completed 16 weeks of oral isotretinoin therapy (80 mg/day). All eight patients noted an excellent clinical response without significant side effects. (Two patients did not return to initial two-week follow-up.) Peripheral blood B- and T-cell counts were unaffected by therapy. Therapy was associated with resolution of routine histopathologic abnormalities, conversion of abnormal lesional direct immunofluorescence microscopy to normal, normalization of the epidermis on electron microscopy, and reduction of all T cells near the dermoepidermal junction without change in ratio of T-helper/inducer cells to T-suppressor/cytotoxic cells. Isotretinoin is a clinically effective short-term therapy for chronic or possibly for subacute cutaneous lupus erythematosus. The primary mechanism of action remains unestablished.

Topics: Administration, Oral; Adult; Basement Membrane; Chronic Disease; Complement C3; Drug Evaluation; Female; Fibrin; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Isotretinoin; Lupus Erythematosus, Discoid; Lymphocytes; Male; Middle Aged; Skin; Tretinoin

Various biochemical processes in hematoma fluid arising from chronic subdural bleeding have not yet been clearly explained. We examined the question whether formation of hematoma fluid after onset of bleeding is preceded by complete clotting with fibrin formation and subsequent lysis of the clot. 22 samples of hematoma fluid taken during operation were used. The protein content was 5.7 +/- 9.8 g/l (mean +/- SD), and coagulable fibrinogen could not be demonstrated whereas 0.99 +/- 0.45 mg/ml fibrin(ogen) break-down products were found immunologically. The high levels of crosslinked D-D fibrin derivatives (0.32 +/- 0.26 mg/ml) were conspicuous: there was a correspondingly high degree of crosslinking (86.2% x/- 12.2%) of the fibrin(ogen) break-down products (calculated from the proportion of dimeric to monomeric gamma-chains). Monoclonal antibodies specific for D-D were employed for the first time to answer the question. The characterization of the crosslinked fibrin derivatives together with their submolecular sub-units and the quantification of the D-D content serve to prove that fibrin is both formed and broken down in chronic subdural hematomas.

Topics: Adult; Aged; Blood Protein Electrophoresis; Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysis; Hematoma, Subdural; Humans; Middle Aged; Molecular Weight

Topics: beta-Thromboglobulin; Chronic Disease; Fibrin; Humans; Platelet Aggregation; Respiratory Insufficiency; Thrombosis

We report experimental studies showing the relationship of the reflectivity of blood clot to both the red cell mass and the fibrin mesh. The highest amplitude echoes are returned by the fibrin mesh. These studies are compared with clinical examples of the different types of neonatal intracranial haemorrhage, as demonstrated by ultrasound. We conclude that the typical high-amplitude echoes characteristic of intracerebral haemorrhage are primarily due to the amount of fibrin mesh present, and not to the intact red cell mass, as has been previously suggested.

Topics: Blood Coagulation; Cerebral Hemorrhage; Cerebral Ventricles; Chronic Disease; Erythrocyte Volume; Fibrin; Hematoma, Subdural; Humans; Infant, Newborn; Subarachnoid Hemorrhage; Ultrasonography

Topics: Adult; Antithrombin III; Chronic Disease; Female; Fibrin; Fibrinogen; Humans; Male; Middle Aged; Respiratory Insufficiency

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

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

Topics: Adolescent; Adult; Blood Coagulation Tests; Child; Chronic Disease; Esophageal and Gastric Varices; Female; Fibrin; Humans; Liver Cirrhosis; Liver Diseases; Male; Middle Aged; Polymers; Portacaval Shunt, Surgical; Prognosis

In summary, this series of 48 patients with acute and chronic DIC demonstrates the reliability of laboratory tests in both aiding a diagnosis of DIC and in offering reasonable predictability of efficacy of therapy, as noted by the correction of abnormalities after delivery of antiprocoagulant therapy for this syndrome. It appears that the diagnostic tests most likely to aid in diagnosis and to reliably inform the clinician when the intravascular clotting process has been stopped are those that determine the antithrombin-III level, the presence of soluble fibrin monomer, and the finding of elevated fibrin(ogen) degradation products, thrombocytopenia and a prolonged thrombin time in the face of the appropriate type of bleeding in the appropriate clinical setting. In addition, it would appear that mini-dose heparin therapy is highly effective in controlling the intravascular clotting process in acute DIC, whereas antiplatelet therapy utilizing two agents is effective in chronic DIC. In addition, in this population, patients with acute disease demonstrated a 74 percent survival rate and those with chronic disease had a 100 percent survival rate from the disseminated intravascular clotting process.

Topics: Acute Disease; Afibrinogenemia; Antacids; Antithrombin III; Chronic Disease; Dipyridamole; Disseminated Intravascular Coagulation; Fibrin; Fibrin Fibrinogen Degradation Products; Heparin; Humans; Partial Thromboplastin Time; Platelet Count; Prothrombin Time; Thrombin Time; Thrombocytopenia

Twenty patients with the ascites of chronic liver disease were investigated for in vivo evidence of active coagulation within ascites by detection of fibrin monomer. Increased levels of fibrin monomer, increased fibrin/fibrinogen degradation products, and absent or low levels of fibrinogen in the ascites of all patients tested confirmed the presence of intraperitoneal coagulation when ascites is present.

Topics: Ascites; Ascitic Fluid; Blood Coagulation; Blood Proteins; Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Liver Diseases; Peritoneal Cavity

Data from the literature concerning the frequent lack of correlation between the clinical manifestations of diabetic neuropathy on the one hand and the morphofunctional status of the appropriate nerves, disorders in carbohydrate and lipid metabolism, and the influence of antidiabetic therapy on metabolism and the clinical picture of diabetic neuropathy on the other, are presented. In this connection, abundant evidence of frequent affection of various blood vessels, particularly small and smallest, in diabetic neuropathy is considered. But even these data attest to a non-infrequent lack in diabetic neuropathy of the involvement of the appropriate vessels, particularly the lack of basal membrane thickening which is a most common indication to the diabetic involvement of capillaries. Attention is drawn to the possible role of genetic heterogeneity of people with regard to the development of various forms of diabetic neuropathy.

Topics: Adult; Aged; Basement Membrane; Blood Vessels; Chronic Disease; Diabetic Angiopathies; Diabetic Neuropathies; Diabetic Retinopathy; Endothelium; Fibrin; Gangrene; Humans; Microcirculation; Middle Aged; Nerve Fibers; Nervous System

Topics: Animals; Chronic Disease; Fibrin; Fibrinolysin; Fibrinolysis; Granuloma; Male; Mice; Mice, Inbred BALB C; Plasminogen Activators; Plasminogen Inactivators; Schistosomiasis; Spectrometry, Fluorescence; Time Factors; Urokinase-Type Plasminogen Activator

In order to determine the role of intrarenal vascular coagulation (IVC) in chronic glomerulonephritis, coagulant parameters in renal blood (RVB), urine FDP's and renal histology were examined in 70 patients with chronic glomerulonephritis (CGN). RVB was obtained by Seldinger's technique. A correlation was obtained between an increase of fibrinogen, FDP and soluble fibrin monomer complexes (SFMC) in RVB and the degree of intraglomerular fibrin deposition shown on immunofluorescence. An increase of FDP's, SFMC and a slight decrease of fibrinolytic activity in RVB were observed in patients with CGN with decreased renal function or with the nephrotic syndrome. Daily excretion of FDP in the urine and the extent of intraglomerular fibrin deposition were greater in nephrotics than in non-nephrotics. We conclude that measurement of coagulation parameters in RVB is a reliable and sensitive method of assessing IVC, and that IVC plays an important role in aggravation of chronic glomerulonephritis, particularly when the nephrotic syndrome is present.

Topics: Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Glomerulonephritis; Histocytochemistry; Humans; Kidney Failure, Chronic; Kidney Glomerulus; Nephrotic Syndrome; Renal Veins

The endothelial cells of both eyes of 60 unilateral iridocyclitic patients were photographed with a specular microscope to establish the possible effect of iridocyclitis on corneal endothelial cells. Chronic severe iridocyclitis with mutton-fat keratic precipitates (KP) lowered the central endothelial cell count. Five patients out of the seven with mutton-fat KPs had a distinctly lower central cell density in the affected eye. In the remaining patients, no significant difference in cell densities could be demonstrated between affected and healthy eyes. Neither the inflammatory process itself nor the round white KPs had a deleterious effect on the central corneal endothelial cell densities.

Topics: Adolescent; Adult; Age Factors; Aged; Aqueous Humor; Cell Count; Child; Chronic Disease; Cornea; Endothelium; Female; Fibrin; Humans; Male; Microscopy; Middle Aged; Photography; Recurrence; Time Factors; Uveitis, Anterior

Topics: Acute Disease; Afibrinogenemia; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Hemostatics; Humans; Hypoprothrombinemias; Thrombocytopenia

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

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

Using selectively immunological methods, it was possible, through FSP determination, for plasmin activities and plasminogen concentrations to be occasionally and exclusively detected in inflammatorily altered liquores and in bloody liquores, respectively. Thus, bloody cerebrospinal fluid, in contrast with inflammatorily altered liquor, usually shows free fibrinolytic activity, so that antifibrinolytic therapy of intracranial aneurysmal hemorrhage is pathophysiologically justifiable.

Topics: Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Chronic Disease; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Fibrinolysin; Hemorrhage; Humans; Inflammation; Plasminogen

The frequent occurrence of abnormal fibrin polymerisation in patients with liver disease has recently been reported. To investigate this further, fibrin polymerisation was studied in 68 patients with cirrhosis or chronic active liver disease. Thirty-three of these patients demonstrated impairment of this phase of blood coagulation. When other tests of liver function were compared in patients demonstrating this abnormality and those in whom fibrin polymerisation was normal, it was found that the former group demonstrated significantly reduced albumin concentrations (p less than 0.0002), raised bilirubin and aspartate aminotransferase levels (p less than 0.0006 and less than 0.003 respectively), and greater prolongation of the one-stage prothrombin time (p less than 0.001) with more marked reduction in factor VII levels (p less than 0.002) compared with the latter patients. It is concluded that defective fibrin polymerisation occurring in patients with liver disease indicates the presence of severely impaired hepatocellular function. This might account for the grave prognosis reported in cirrhotic patients with abnormal fibrin polymerisation who also suffer bleeding from gastro-oesophageal varices.

Topics: Aspartate Aminotransferases; Bilirubin; Blood Coagulation Disorders; Chronic Disease; Factor VII; Fibrin; Fibrinogen; Humans; Liver Cirrhosis; Liver Diseases; Prothrombin Time; Serum Albumin; Serum Globulins

Topics: Child; Chronic Disease; Fibrin; Fibrinolysis; Glomerulonephritis; Humans; Kidney; Serum Globulins

Plasma from patients with both acute and chronic liver disease has been examined for evidence of acquired dysfibrinogenaemia, using electrophoretic methods and coagulation tests. An examination of isolated fibrins upon SDS polyacryamide gel electrophoresis failed to demonstrate any molecular or structural defect associated with the polypeptide chains of the patients' fibrinogen or fibrinogen derivatives produced by thrombin or plasmin. However, purified fibrin monomers isolated from plasma using both Reptilase and thrombin exhibited delayed polymerization rates and the occurrence of acquired dysfibrinogenaemia in liver disease is therefore confirmed.

Topics: Acute Disease; Ancrod; Batroxobin; Blood Coagulation Disorders; Blood Coagulation Tests; Chronic Disease; Fibrin; Fibrinogen; Humans; Liver Diseases; Thrombin

Although there have been isolated reports of an acquired abnormal fibrinogen in patients with liver disease, its frequency and clinical significance is not known. In this study 121 consecutive patients with a wide spectrum of hepatic disorders were screened for abnormal fibrin polymerization. A simple colorimetric method using Reptilase was employed. Of 32 patients with proven cirrhosis, 16 (50%) showed abnormal fibrin polymerization. The incidence in decompensated alcoholic cirrhosis was particularly high. The abnormality was also detected in all patients with acute liver failure and seven of 15 with chronic active liver disease. Clinical improvement often correlated with its disappearance. Two patients with primary liver cell tumours demonstrated the abnormal polymerization. In patients with bleeding oesophageal varices the detection of abnormal fibrin polymerization was associated with a poor prognosis. None of the patients with surgical obstructive jaundice (26) or miscellaneous liver disorders (37) had abnormal fibrin polymerization. The occurrence of abnormal fibrin polymerization in liver disease is more frequent than previously suspected and usually signifies severe primary hepatocellular dysfunction. Evidence is presented to support the presence of a primary abnormality of fibrinogen as the cause of impaired fibrin monomer polymerization.

Topics: Batroxobin; Blood Coagulation Tests; Carcinoma, Hepatocellular; Cholestasis; Chronic Disease; Fibrin; Fibrinogen; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Liver Diseases; Liver Neoplasms; Polymers; Thrombin; Time Factors

Our clinical experience with acetic acid solution in the treatment of candida infection of the bladder was confirmed by in vitro experiments. We apply continuous bladder irrigation with increasing concentrations of acetic acid solution up to pH 5.0. The majority of patients had received antibiotics or cytostatic drugs and suffered from chronic and malignant diseases. A case report is given with endoscopic documentation of the influence of acetic acid solution on the bladder.

Topics: Acetates; Aged; Anti-Bacterial Agents; Candida; Candidiasis; Chronic Disease; Cystitis; Cystoscopy; Female; Fibrin; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Long-Term Care; Preoperative Care; Therapeutic Irrigation

Topics: Acute Disease; Adolescent; Adult; Aged; Chronic Disease; Female; Fibrin; Humans; Kidney Diseases; Male; Middle Aged; Nephrotic Syndrome

Topics: Alcoholism; Animals; Aorta; Blood Coagulation; Chronic Disease; Fibrin; Humans; Male; Phosphatidylcholines; Polyenes; Rats; Solubility; Time Factors

Topics: Acute Disease; Adult; Aged; Alcoholism; alpha 1-Antitrypsin; Alpha-Globulins; Chronic Disease; Fatty Liver; Female; Fibrin; Fibrinogen; Fibrinolysis; Hepatitis; Humans; Liver Cirrhosis; Liver Cirrhosis, Biliary; Macroglobulins; Male; Middle Aged; Plasminogen

Topics: Aged; Autopsy; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrosarcoma; Hematoma; Hematuria; Humans; Leiomyosarcoma; Pulmonary Artery; Sarcoma; Thromboplastin

Topics: Adult; Aged; Autopsy; Bronchi; Chronic Disease; Epithelium; Female; Fibrin; Humans; Influenza, Human; Lung; Male; Middle Aged; Orthomyxoviridae; Pneumonia, Viral; Pulmonary Alveoli; Pulmonary Embolism

Topics: Adult; Aged; Chronic Disease; Disseminated Intravascular Coagulation; Factor V; Factor VII; Female; Fibrin; Fibrinogen; Gaucher Disease; Hodgkin Disease; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Middle Aged; Organ Size; Plasminogen; Polycythemia Vera; Prothrombin Time; Spleen; Splenectomy; Splenomegaly

Topics: Adult; Aged; Autoimmune Diseases; Biopsy, Needle; Bronchiectasis; Chronic Disease; Empyema; Female; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Humans; Kidney; Kidney Diseases; Lung; Lung Diseases; Male; Microscopy, Electron; Middle Aged; Phagocytosis; Pleural Diseases; Pneumonia

Indomethacin given to adults with glomerulonephritis usually reduces their urinary excretion of protein and fibrinogen/fibrin-related (F.R.) antigen. Nevertheless, non-responders exist. Platelet aggregation is significantly more strongly inhibited by indomethacin in good responders than in nonresponders. This supports the hypothesis that the reduction of urinary excretion of F.R. antigen during indomethacin administration is related, at least in part, to inhibition of intrarenal platelet aggregation and of the subsequent fibrin deposition.

Topics: Adolescent; Adult; Antigens; Blood Coagulation; Blood Platelets; Chronic Disease; Creatinine; Female; Fibrin; Glomerulonephritis; Humans; Indomethacin; Male; Middle Aged; Platelet Adhesiveness; Proteinuria

Topics: Aged; Blood Coagulation Tests; Blood Platelet Disorders; Chronic Disease; Disseminated Intravascular Coagulation; Fibrin; Gastrointestinal Hemorrhage; Heparin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Prothrombin Time; Thromboplastin

Topics: Blood Cell Count; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Fibrinolysis; Heparin; Humans; Liver Cirrhosis; Pregnancy; Pregnancy Complications, Hematologic; Prothrombin Time; Thrombin; Thromboplastin

Topics: Acute Disease; Adult; Aged; Blood Coagulation Factors; Blood Coagulation Tests; Blood Platelets; Chronic Disease; Disseminated Intravascular Coagulation; Ecchymosis; Ethanol; Female; Fibrin; Fibrinolysis; Hemorrhage; Hemostasis; Humans; Male; Middle Aged; Mucous Membrane; Protamines; Prothrombin Time; Syndrome; Thrombocytopenia

Topics: Adult; Aged; Aneurysm; Aortic Aneurysm; Arteriosclerosis; Blood Cell Count; Blood Coagulation; Blood Platelets; Buttocks; Cell Survival; Chromium Radioisotopes; Chronic Disease; Disseminated Intravascular Coagulation; Female; Fibrin; Fibrinogen; Hemangioma; Humans; Iodine Radioisotopes; Middle Aged; Purpura, Thrombocytopenic; Skin Neoplasms; Syndrome; Thrombosis

Topics: Animals; Brain; Cerebrospinal Fluid; Chronic Disease; Disease Models, Animal; Dogs; Fibrin; Haplorhini; Hematoma, Subdural; Hemiplegia; Macaca

Topics: Arthritis, Juvenile; Child; Child, Preschool; Chronic Disease; Female; Fibrin; Humans; Hydrarthrosis; Hyperplasia; Microscopy, Electron, Scanning; Synovectomy; Synovial Membrane

Topics: Chronic Disease; Factor XIII Deficiency; Fibrin; Humans; Kidney Diseases

Topics: Adolescent; Adult; Angina Pectoris; Chronic Disease; Diabetes Mellitus; Female; Fibrin; Fibrinogen; Hematologic Diseases; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Myocardial Infarction; Neoplasms

Topics: Aged; Airway Obstruction; Bronchitis; Bronchoscopy; Chronic Disease; Diagnosis, Differential; Fibrin; Humans; Male

Topics: Adolescent; Adult; Aged; Anticoagulants; Biopsy; Blood Coagulation; Capillaries; Child; Chronic Disease; Female; Fibrin; Fibrinolytic Agents; Fluorescent Antibody Technique; Glomerulonephritis; Humans; Immunosuppressive Agents; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged

Topics: Acute Disease; Animals; Antigens; Antigens, Viral; Chronic Disease; Coxsackievirus Infections; Endocarditis; Endocardium; Enterovirus; Fibrin; Fluorescent Antibody Technique; Heart Valve Diseases; Injections, Intraperitoneal; Mice; Myocardium; Rheumatic Heart Disease

It appears that in human renal isografts glomerulonephritis in the transplant may be a recurrence of the original disease. In the allograft, nephritis may be either recurrence, an intrinsic part of the rejection process itself, or acquisition de novo of the disease. A number of parallels to both antiglomerular basement membrane disease and circulating antigen-antibody complex disease in the animal model are suggested, but with the possible exception of an occasional demonstration of anti-GBM disease, proof that such mechanisms operate in the glomerulonephritis developing in the human allograft is at present lacking.

Topics: Acute Disease; Adrenal Cortex Hormones; Antigen-Antibody Complex; Antigens, Bacterial; Antilymphocyte Serum; Autoantibodies; Basement Membrane; Chronic Disease; Disease Models, Animal; Fibrin; Glomerulonephritis; Graft Rejection; Humans; Kidney; Kidney Glomerulus; Kidney Transplantation; Recurrence; Streptococcus; Transplantation, Homologous; Transplantation, Isogeneic; Virus Diseases

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

Topics: Acute Disease; Blood Coagulation; Blood Platelets; Chronic Disease; Female; Fibrin; Fibrinolysis; Humans; Male; Myocardial Infarction; Thrombin

Topics: Arthritis, Rheumatoid; Chronic Disease; Fibrin; Humans; Inflammation; Microscopy, Electron; Necrosis; Synovial Membrane; Synovitis

Topics: Acute Disease; Acute Kidney Injury; Antifibrinolytic Agents; Blood Cell Count; Blood Coagulation Factors; Blood Platelets; Blood Urea Nitrogen; Chronic Disease; Creatinine; Fibrin; Fibrinolysis; Humans; Immunoelectrophoresis; Plasminogen; Renal Dialysis; Uremia

We have investigated the formation of fibrin, platelet aggregates, and subendothelial deposits in lipoid nephrosis. Fibrin formation was found in 10 cases of active lipoid nephrosis. Platelet aggregates were found in eight cases and subendothelial deposits in nine. Fibrin and platelets were also found in cases of nephrotic syndrome due to other causes, and in glomerulonephritis. Fibrin was generally absent in lipoid nephrosis in remission and in benign recurrent hematuria. It is suggested that what seems to be a lower incidence in females is more apparent than real and that fibrin or related material may be present in a less easily identifiable form. Steroid therapy apparently had no effect on the presence or absence of fibrin. Most instances were associated with elevated serum cholesterol and alpha(2)-globulin. It is suggested that elevated serum lipids as well as the disease process in the kidney play a role in this phenomenon. It is further suggested that intraglomerular fibrin formation could lead to irreversible renal damage in lipoid nephrosis.

Topics: Adolescent; Adult; Aged; Alpha-Globulins; Biopsy; Blood Platelets; Child; Child, Preschool; Cholesterol; Chronic Disease; Female; Fibrin; Glomerulonephritis; Hematuria; Histocytochemistry; Humans; Kidney Glomerulus; Male; Microscopy, Electron; Middle Aged; Nephrosis, Lipoid; Nephrotic Syndrome; Sex Factors; Steroids

Topics: Animals; Blood Coagulation; Cerebrospinal Fluid; Chronic Disease; Dogs; Fibrin; Haplorhini; Hematoma, Subdural; In Vitro Techniques

The defibrinating agent ancrod (Arvin) was used instead of heparin for intermittent haemodialysis. It was an effective, and apparently safe, anticoagulant and reduced the deposition of fibrin and leucocytes on the Cellophane membrane. Administration was more complicated and urea dialysance was less with ancrod than with heparin.

Topics: Adult; Anticoagulants; Cellophane; Chronic Disease; Fibrin; Fibrinogen; Heparin; Humans; Leukocytes; Male; Membranes, Artificial; Middle Aged; Nephritis; Polycystic Kidney Diseases; Renal Dialysis; Urea; Venoms

Topics: Arteries; Arthritis, Rheumatoid; Chronic Disease; Fibrin; Fibroblasts; Humans; Inflammation; Myocardium; Necrosis; Pericardium; Serous Membrane; Spleen; Tendons

In 81 patients with fibrous intra-abdominal adhesions there was a high incidence of other lesions in which there was a substantial element of fibrosis. These included chronic peptic ulceration, ovarian cysts, fibrous stenotic lesions, and thickened scars. It is suggested that in some patients a generalized fibrotic tendency as well as local factors may play a part in the pathogenesis of adhesions.

Topics: Abdomen; ABO Blood-Group System; Adult; Aged; Chronic Disease; Cicatrix; Constriction; Female; Fibrin; Fibrinolysis; Humans; Male; Middle Aged; Ovarian Cysts; Peptic Ulcer; Tissue Adhesions

Topics: Angiomatosis; Anticoagulants; Arm; Biopsy; Blindness; Blood Coagulation Disorders; Capillaries; Chronic Disease; Factor V; Factor VIII; Female; Fibrin; Fibrinolysin; Humans; Leg Dermatoses; Middle Aged; Pain; Prednisolone; Skin Manifestations; Skin Ulcer; Thrombosis

Topics: Blister; Cantharidin; Chronic Disease; Female; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Male; Prothrombin; Thrombin; Urticaria

Topics: Adjuvants, Immunologic; Animals; Antibodies; Antigens; Arthritis, Rheumatoid; Autoimmune Diseases; Chronic Disease; Fibrin; Gout; Humans; Hypersensitivity, Delayed; Inflammation; Joints; Macrophages; Mycobacterium tuberculosis; Plasma Cells; Polysaccharides; Rabbits; Synovitis; Uric Acid

Topics: Arthritis; Blood Coagulation; Chronic Disease; Fibrin; Fibrinolysis; Humans; Joint Diseases