fibrin and Pleural-Effusion

Pleural and parenchymal lung injury have long been characterized by acute inflammation and pathologic tissue reorganization, when severe. Although transitional matrix deposition is a normal part of the injury response, unresolved fibrin deposition can lead to pleural loculation and scarification of affected areas. Within this review, we present a brief discussion of the fibrinolytic pathway, its components, and their contribution to injury progression. We review how local derangements of fibrinolysis, resulting from increased coagulation and reduced plasminogen activator activity, promote extravascular fibrin deposition. Further, we describe how pleural mesothelial cells contribute to lung scarring via the acquisition of a profibrotic phenotype. We also discuss soluble uPAR, a recently identified biomarker of pleural injury, and its diagnostic value in the grading of pleural effusions. Finally, we provide an in-depth discussion on the clinical importance of single-chain urokinase plasminogen activator (uPA) for the treatment of loculated pleural collections.

Topics: Acute Disease; Animals; Biomarkers; Blood Coagulation; Epithelium; Fibrin; Fibrinolysis; Humans; Inflammation; Lung; Lung Injury; Pleura; Pleural Effusion; Receptors, Urokinase Plasminogen Activator; Thrombolytic Therapy; Urokinase-Type Plasminogen Activator

In recent years, a higher and higher percentage of patients with pleural effusions or pneumothorax are being treated with small-bore (10-14 F) chest tubes rather than large-bore (>20 F). However, there are very few randomized controlled studies comparing the efficacy and complication rates with the small- and large-bore catheters. Moreover, the randomized trials that are available have flaws in their design. The advantages of the small-bore catheters are that they are easier to insert and there is less pain with their insertion while they are in place. The placement of the small-bore catheters is probably more optimal when placement is done with ultrasound guidance. Small-bore chest tubes are recommended when pleurodesis is performed. The success of the small-bore indwelling tunnelled catheters that are left in place for weeks documents that the small-bore tubes do not commonly become obstructed with fibrin. Patients with complicated parapneumonic effusions are probably best managed with small-bore catheters even when the pleural fluid is purulent. Patients with haemothorax are best managed with large-bore catheters because of blood clots and the high volume of pleural fluid. Most patients with pneumothorax can be managed with aspiration or small-bore chest tubes. If these fail, a large-bore chest tube may be necessary. Patients on mechanical ventilation with barotrauma induced pneumothoraces are best managed with large-bore chest tubes.

Topics: Chest Pain; Chest Tubes; Chylothorax; Drainage; Empyema, Pleural; Fibrin; Hemothorax; Humans; Pleural Effusion; Pleurodesis; Pneumothorax; Randomized Controlled Trials as Topic; Respiration, Artificial; Treatment Outcome; Ultrasonography

Topics: Fibrin; Fibrosis; Humans; Pleura; Pleural Effusion; Pleurisy

Topics: Absorption; Amylases; Antineoplastic Agents; Breast Neoplasms; Bronchial Neoplasms; Capillary Permeability; Carcinoembryonic Antigen; Catheterization; Drainage; Dyspnea; Fibrin; Filtration; Humans; Hydrogen-Ion Concentration; Lymphoma; Pain; Pancreatic Neoplasms; Pleural Effusion; Pleural Neoplasms; Pregnancy Proteins; Quinacrine; Talc; Tetracyclines; Tissue Adhesives; Ultrasonography

A 75-year-old man presented to a French hospital with a 4-day fever after returning from a coronavirus disease-19 (COVID-19) cluster region. A reverse-transcription polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using a nasopharyngeal swab sample. After he returned home and a telephone follow-up, he was found deceased 9 days after first showing symptoms. Whole-body, non-enhanced, post-mortem computed tomography (PMCT) and a forensic autopsy were performed approximately 48 h after death, with sanitary precautions. The PMCT showed bilateral and diffuse crazy-paving lung opacities, with bilateral pleural effusions. Post-mortem virology studies detected the presence of SARS-CoV-2 (B.1 lineage) in the nasopharynx, plasma, lung biopsies, pleural effusion and faeces confirming the persistence of viral ribonucleic acid 48 h after death. Microscopic examination showed that severe lung damage was responsible for his death. The main abnormality was diffuse alveolar damage, associated with different stages of inflammation and fibrosis. This case is one of the first to describe complete post-mortem data for a COVID-19 death and highlights the ability of PMCT to detect severe involvement of the lungs before autopsy in an apparently natural death. The present pathology results are concordant with previously reported findings and reinforce the disease pathogenesis hypothesis of combined viral replication with an inappropriate immune response.

Topics: Aged; Alveolar Epithelial Cells; Autopsy; Betacoronavirus; Coronavirus Infections; COVID-19; Fibrin; Humans; Hyperplasia; Lung; Male; Pandemics; Pleural Effusion; Pneumonia, Viral; Pulmonary Alveoli; SARS-CoV-2; Tomography, X-Ray Computed

Topics: Diagnosis, Differential; Fibrin; Humans; Pleural Effusion; Pneumothorax; Tomography, X-Ray Computed

Different macromolecules were administered intraperitoneally to stimulate formation of protein-rich ascitic fluid in rodents. Stimulatory effect of plant lectins depended on the attachment to cell surface carbohydrates, Canavalia ensiformis (ConA) lectin was used in the majority of experiments. The time course of ConA-induced ascites was divided into an early (up to 4 h) and a late (from 6 h on) phase, with a transitional period between the two. Water and protein accumulation showed parallel time courses: volume of the ascitic fluid peaked at around 3 h, and fibrin threads appeared after 6 h. Viscosity of the ascitic fluid and its supernatant increased with time, reaching maximal fibrinogen concentration at around 16 h. Peritoneal permeability, followed by pleural and pericardial effusions, was elicited only by lectins that form soluble complexes with serum glycoproteins, whereas the effect of serum-precipitating lectins was restricted to the peritoneum. Macromolecules with serial positive charges (e.g., polylysine or polyethyleneimine) enhanced peritoneal permeability by ionic interactions with cell surface molecules. Viscosity of the polycation-induced ascitic fluid did not tend to increase with time and corresponded to the early phase of the ConA-induced ascites. Polyglutamate, a polyanionic macromolecule, inhibited the effect of polycations, but not that of ConA. The most efficient stimulatory macromolecules appear to induce ascites by noncovalent cross-linking of cell surface glycoproteins or glycosaminoglycans or both. A similar mechanism may operate in the maintenance of basal secretion to prevent eventual desiccation. Noncovalent cross-linking appears to be a common denominator of both basal and enhanced permeability.

Topics: Animals; Ascites; Ascitic Fluid; Female; Fibrin; Injections, Intraperitoneal; Mice; Pericardial Effusion; Peritonitis; Permeability; Plant Lectins; Pleural Effusion; Polymers; Rats; Rats, Wistar; Serum Albumin; Time Factors; Viscosity

In children, pleural empyema is a recognized complication of severe pneumonia and is characterized by loculated effusions with fibrin septations. The aim of this study was to evaluate the relationship between proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6], intrapleural fibrinolytic system enzymes [tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor type 1 (PAI-1)], and common biochemical indices during pleural infection.. Children with pneumonia complicated by para-pneumonic effusions were enrolled into our study and underwent real-time chest sonography. The patients were divided into 3 groups by ultrasound using a recognized staging system of pleural effusions. Staging of progressive pleural infection was used to correlate with the characteristics of pleural effusions. The correlation of various pleural variables with the formation of complicated para-pneumonic effusions (CPE) was performed and pleural variables for predicting subsequent intervention procedures were also analyzed.. A total of 57 patients were enrolled in the present study. Univariate analysis revealed that the amounts of biochemical indices (pH, glucose, lactate dehydrogenase), proinflammatory cytokines (TNF-alpha, IL-1beta, IL-6), and fibrinolytic system enzymes (tPA, PAI-1) were significantly different with the progressive stages of para-pneumonic effusions (Ptrend < 0.05). For all proinflammatory cytokines, a positive correlation was found with lactate dehydrogenase and PAI-1, whereas a negative correlation was found with pH, glucose, and tPA. Moreover, these cytokines were also significantly correlated with PAI-1 in both non-CPE and CPE. The pleural fluid findings of IL-1beta (> or =50 pg/mL), PAI-1 (> or =1252 ng/mL), and pH (< or =7.30) were the most significant predictive factors for subsequent intervention procedures (P < 0.001).. The increased release of proinflammatory cytokines in pleural fluid caused by bacteria may result in an imbalance of the fibrinolytic system, which can subsequently lead to fibrin deposition and intervention procedures.

Topics: Adolescent; Child; Child, Preschool; Cytokines; Female; Fibrin; Glucose; Humans; Hydrogen-Ion Concentration; Infant; Inflammation; L-Lactate Dehydrogenase; Male; Plasminogen Activator Inhibitor 1; Pleural Effusion; Pneumonia, Bacterial; Pneumonia, Pneumococcal; Tissue Plasminogen Activator; Ultrasonography

Repeated thoracenteses is indicated in patients with refractory, symptomatic transudative effusions. However, their effect on cytokines and fibrinolytic activity in pleural transudates remains unclear.. Twenty-one patients with symptomatic, large amount of free-flowing transudative effusions caused by heart failure were studied. Thoracentesis with drainage of 500 mL of pleural fluid per day was done for 3 consecutive days (days 1 to 3). Pleural fluid characteristics, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-8, vascular endothelial growth factor (VEGF), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1) were measured during each tap. Chest ultrasonography was done on day 6 to detect the fibrin strands in pleural effusion and the outcome of effusion was evaluated within 7 days after repeated thoracenteses.. Effusion levels of lactate dehydrogenase, neutrophils, TNF-alpha, IL-1 beta, IL-8, VEGF, and PAI-1 increased significantly during repeated thoracenteses. Furthermore, the values of PAI-1 and PAI-1/tPA obtained on days 2 and 3 were highly correlated with those of TNF-alpha, IL-1 beta, IL-8, and VEGF. On day 6, pleural fibrins were observed on chest ultrasonography in 6 patients (29%, fibrinous group) but were absent in the remaining 15 patients (nonfibrinous group). Compared with the nonfibrinous group, the effusion levels of TNF-alpha, IL-1 beta, VEGF, and PAI-1 on day 2 and day 3, and recurrence of symptomatic effusion after repeated thoracenteses were significantly higher in fibrinous group.. Repeated thoracenteses may induce local release of proinflammatory cytokines, VEGF and PAI-1, which may result in fibrin deposition and impair resolution of pleural transudates.

Topics: Aged; Aged, 80 and over; Cell Count; Cytokines; Erythrocytes; Female; Fibrin; Fibrinolysis; Glucose; Heart Failure; Humans; Hydrogen-Ion Concentration; Interleukin-1beta; L-Lactate Dehydrogenase; Leukocytes; Lung; Male; Paracentesis; Plasminogen Activator Inhibitor 1; Pleural Effusion; Retreatment; Tissue Plasminogen Activator; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Intrapleural loculation can increase morbidity in hemothoraces or parapneumonic effusions. Intrapleural fibrin precedes visceral-parietal pleural adhesions. We speculated that single-chain urokinase plasminogen activator alone or bound to its receptor could prevent these adhesions by their relative resistance to local inhibition by plasminogen activator inhibitors. We found that recombinant human single-chain urokinase-bound rabbit pleural mesothelial cells or lung fibroblasts with kinetics similar to that reported for human cells (kD of approximately 5 nM). The receptor-bound fibrinolysin maintained in vitro fibrinolytic activity in the presence of pleural fluids from rabbits with tetracycline-induced pleural injury over 24 hours. In rabbits given intrapleural single-chain urokinase 24 and 48 hours after intrapleural tetracycline (n = 10 animals), adhesions were prevented, whereas the receptor-complexed form (n = 12) attenuated adhesions versus vehicle/tetracycline-treated rabbits (n = 22, p

Topics: Animals; Anti-Bacterial Agents; Biomarkers; Body Fluids; Cell Count; Disease Models, Animal; Epithelium; Female; Fibrin; Fibroblasts; Pleura; Pleural Effusion; Pleurisy; Rabbits; Receptors, Cell Surface; Receptors, Urokinase Plasminogen Activator; Tetracycline; Tissue Adhesions; Urokinase-Type Plasminogen Activator

Topics: Exudates and Transudates; Fibrin; Humans; Patient Selection; Pleural Effusion; Pleurisy; Reproducibility of Results; Sensitivity and Specificity; Thoracoscopy; Time Factors

The mesothelium contains both procoagulant and fibrinolytic activities. An imbalance between these activities could account for the abnormal fibrin turnover and pleural fibrin deposition that is characteristic of pleural inflammation. Procoagulant activity of human pleural mesothelial cells (HPMC) is in part due to tissue factor, and the prothrombinase complex can also assemble at the HPMC surface. HPMC express tissue plasminogen activator (tPA) but no detectable fibrinolytic activity in a fibrin plate assay. Inhibition of HPMC fibrinolytic activity is due, in part, to elaboration of plasminogen activator inhibitors-1 and -2 (PAI-1 and PAI-2) as well as antiplasmins. Synthesis of PAI-1 and PAI-2 is inhibited by actinomycin D and cyclohexamide. HPMC PAI-1 is increased by transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha), as is tPA release, while PAI-1 mRNA is unchanged and tPA mRNA is increased. PAI-2 release is induced by TNF-alpha and TGF-beta. Because they are a rich source of PAI-1 and PAI-2, HPMC may contribute to the high levels of these inhibitors in pleural exudates. Stimulation of HPMC by TNF-alpha or TGF-beta in vitro did not alter HPMC procoagulant activity nor the balance of elevated PAI and antiplasmins relative to PA, changes that collectively favor formation and persistence of pericellular fibrin.

Topics: Base Sequence; Blood Coagulation Factors; Cells, Cultured; Cycloheximide; Dactinomycin; Epithelium; Fibrin; Fibrinolysis; Fibroblasts; Humans; Inflammation; Lung; Mesothelioma; Molecular Sequence Data; Oligonucleotide Probes; Plasminogen Activator Inhibitor 1; Plasminogen Activator Inhibitor 2; Pleural Effusion; Prothrombin; RNA, Messenger; Tissue Plasminogen Activator; Transforming Growth Factor beta; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Urokinase-Type Plasminogen Activator

Intrapleural fibrin deposition commonly accompanies pleural injury and may contribute to the organization of exudative pleural effusions, which leads to lung entrapment. Previous investigators have observed an increase in procoagulant proteins in pleural effusions but very little thrombin formation. FVa is the protein cofactor in the prothrombinase complex that dramatically enhances the generation of thrombin from prothrombin by the serine protease fXa. The presence of fVa within the pleural space could influence fibrin formation and pleural scarification. We examined pleural fluids obtained from patients who had lung cancer, CHF, and empyema for the presence of fV/fVa. The fV antigen was increased in exudative pleural fluids, in comparison with transudates. However, the specific activity of fV antigen present in exudates was significantly less than that observed for the lower concentration of antigen present in transudate and could not be activated to the same degree by thrombin. Immunoblots of fV antigen in exudates indicated that fV was partially cleaved and inactivated by unidentified proteases. We conclude that although fV is present in pleural fluid, it may be present in a degraded form, which may partially account for a lack of thrombin-generating capacity in these pleural fluids. The presence of fV does not necessarily correlate with pleural loculation.

Topics: Blood Coagulation Factors; Empyema; Factor V; Fibrin; Fibrinolysin; Glucose; Heart Failure; Humans; Immunoblotting; L-Lactate Dehydrogenase; Lung Neoplasms; Molecular Weight; Pleural Effusion; Thrombin

Turpentine was injected into the right pleural cavity of nude immune-incompetent mice, causing a temporary irritative exudative pleuritis. A transient occurrence of so-called rheumatoid arthritis cells was observed in the pleural fluid together with parallel characteristic biochemical changes. In similar experiments in nude mice, however, immunization followed by intrapleural application of bovine fibrin showed irritative "dry" pleuritis without the presence of rheumatoid arthritis cells. This is in contrast with previous results from similar experiments done using normal mice. The conclusion from the present experiments is that in nude immune-incompetent mice only the non-immunological, turpentine-induced pleuritis will generate cellular and biochemical changes typical of the rheumatoid disease in patients, while the fibrin-induced pleuritis fails to show similar changes. This suggests that the rheumatoid-like pleural changes described in the present experiments in nude mice have a non-immunological basis.

Topics: Animals; Blood Glucose; Blood Proteins; Fibrin; L-Lactate Dehydrogenase; Male; Mice; Mice, Nude; Pleural Effusion; Pleurisy; Proteins; Turpentine

The potential importance of pleural fibrin deposition in the pathogenesis of pleural injury is supported by both clinical and experimental observations. We hypothesized that the local equilibrium between procoagulant and fibrinolytic activities is disrupted to favor fibrin deposition in exudative pleuritis. To test this hypothesis, we characterized procoagulant and fibrinolytic activities in pleural exudates from patients with pneumonia, lung cancer, or empyema and transudates from patients with congestive heart failure. Procoagulant activity was generally increased in exudative processes and was due mainly to tissue factor. All effusions contained antithrombin III and inhibited factor Xa and thrombin, but endogenous prothrombinase or thrombin activities were variably detected. Pleural fluid fibrinolytic activity was increased in congestive heart failure and was due to both tissue plasminogen activator and urokinase. Depressed fibrinolytic activity was found in pleural exudates despite increased concentrations of plasminogen, mainly glu-1-plasminogen, and was due to inhibition of plasminogen activation by plasminogen activator inhibitors 1 and 2 and of plasmin, in part by alpha 2-antiplasmin. Concentrations of PAI-1 in exudative pleural fluids were increased up to 913-fold, compared with normal pooled plasma. Exudative pleural effusions are characterized by increased procoagulant and depressed fibrinolytic activity, favoring fibrin deposition in the pleural space. The balance of these activities is reversed and favors fibrin clearance in congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Blood Coagulation; Blood Coagulation Factors; Empyema; Fibrin; Fibrinolysis; Heart Failure; Humans; Pleura; Pleural Effusion; Pleural Effusion, Malignant; Pneumonia

In mice immunized with bovine fibrin, the same antigen was applied to the pleural cavity. A granulomatous pleuritis appeared affecting both the visceral and the parietal pleura, especially located around the antigen particle. Rheumatoid arthritis (RA) cells were constantly found in the pleural cavity when pleural lesions were present. This immunological, granulomatous pleuritis is the first experimental model for the study of RA cell-positive types of pleurisy in humans.

Topics: Animals; Arthritis, Rheumatoid; Disease Models, Animal; Fibrin; Granulocytes; Inclusion Bodies; Lung; Male; Mice; Mice, Inbred BALB C; Pleura; Pleural Effusion; Pleurisy

Topics: Antigens, Neoplasm; Ascitic Fluid; Female; Fibrin; Genital Neoplasms, Female; Humans; Pleural Effusion

Topics: Fibrin; Fibrinogen; Humans; Lung Neoplasms; Pleural Effusion; Tuberculosis, Pulmonary

In order to measure quantitatively fibrin and fibrinogen in biological material such as thrombi, exudates, or tissues, the following method was developed and tested on model thrombi of different composition. Any fibrin and fibrinogen present is proteolytically degraded by endogenous and/or exogenous plasmin to their common late, soluble fragments D and E. Fragment E is determined by electroimmunoassay using a specific antiserum. From the amounts of fragment E the original fibrin(fibrinogen) antigen and thus of fibrin plus fibrinogen can be calculated on the basis of a molecular weight ratio of 340,000 for fibrinogen to 48,500 for fragment E. Purified fibrinogen degraded to fragments by plasmin resulted in a yield of 89.9% +/- 1.5 of the expected amount of fragment E. Fibrin under identical conditions resulted in a yield of 84.0% +/- 2.4, whereas crosslinked fibrin gave yields of 78.2% +/- 9.2 only after prolonged incubation. Control studies demonstrated that the presence of plasma proteins did not change the yield of fragment E. Measurement of the fibrin(fibrinogen) content of thrombotic material contained in surgically removed human aortic aneurysms demonstrated the validity and applicability of this method to biological material.

Topics: Antigens; Aorta; Blood Coagulation; Cross Reactions; Exudates and Transudates; Fibrin; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Plasma; Pleural Effusion; Time Factors

Topics: Adult; Female; Fibrin; Humans; Pleural Effusion; Postoperative Complications; Radiography; Thoracic Surgery; Tuberculosis, Pulmonary

Topics: Child; Child, Preschool; Fibrin; Humans; Infant; Male; Pleural Effusion; Pleurisy; Tuberculosis, Pleural

Material with leuckocyte migration inhibition (LMI) activity has been demonstrated in various types of nonimmunologically induced acute pleural inflammatory exudates. This activity is present in inflammatory cell-free exudate and appears to involved the deposition of fibrin around the migrating leukocyte, resulting in "cell-trapping." This is supported by the fact that removal or inhibition of fibrin formation leads to loss of exudate LMI activity. Both fibrinogen and complement as well as vitamin K-dependent clotting factors appear to be required for LMI activity. The mechanism involved in the LMI reaction and its significance in nonimmune and cell-mediated immune inflammation are discussed.

Topics: Animals; Cell Migration Inhibition; Fibrin; Heparin; Hot Temperature; Hydroxyapatites; Inflammation; Irritants; Leukocytes; Male; Pleural Effusion; Rats; Thrombin; Warfarin; Zymosan

Topics: Animals; Benzoates; Chromatography, DEAE-Cellulose; Cobalt; Copper; Edetic Acid; Electrophoresis; Electrophoresis, Disc; Esterases; Ethylmaleimide; Fibrin; Hot Temperature; Hydrazines; Iodoacetates; Kinetics; Mast-Cell Sarcoma; Mice; Oximes; Peptide Hydrolases; Phlorhizin; Pleural Effusion; Zinc

Topics: Adult; Female; Fibrin; Humans; Male; Pleural Effusion; Pleurisy; Radiography