fibrin and Hyaline-Membrane-Disease

Extravascular fibrin deposition is characteristic of the acute inflammatory response and is, for example, prominent in the alveolar compartment of patients with the adult respiratory distress syndrome. Fibrin deposition in the injured lung is regulated by a balance of locally expressed pathways of coagulation and fibrin clearance, called fibrinolysis. These pathways comprise part of the interactive network of responses that influence local inflammatory cell traffic, microvascular permeability, and repair mechanisms. In this sense, fibrin turnover in the lung extends beyond traditional hemostasis and may influence the acute inflammatory response and resolution. Within the injured alveolar compartment, fibrin deposition is initiated by increased activity of the extrinsic coagulation pathway-tissue factor associated with factor VII. Activation of the contact and intrinsic coagulation pathways also occurs. Local fibrinolysis is generally impaired, which may potentiate extravascular fibrin deposition. Fibrin turnover in the adult mammalian lung is similarly disrupted in several forms of injury but differs from the injury that occurs in the lungs of premature infants with respiratory distress.

Topics: Animals; Blood Coagulation; Fibrin; Fibrinolysis; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung; Respiratory Distress Syndrome

Topics: Adult; Disseminated Intravascular Coagulation; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Infant, Premature, Diseases; Lung; Organ Size; Pulmonary Atelectasis; Pulmonary Edema; Respiration, Artificial

Topics: Animals; Autopsy; Birth Weight; Blood Coagulation Disorders; Bradykinin; Cardiovascular Diseases; Female; Fibrin; Gestational Age; Humans; Hyaline Membrane Disease; Immune System Diseases; Infant, Newborn; Nervous System Diseases; Neurotransmitter Agents; Oxygen; Pregnancy; Respiratory Tract Diseases; Steroids; Water-Electrolyte Balance

In a double-blind, randomized study, 500 premature infants were treated with plasminogen or placebo intravenously within 60 minutes of birth. There was a substantial decrease in severe clinical respiratory distress, death caused by hyaline membrane disease, and total mortality in the plasminogen-treated infants as compared to the controls.

Topics: Clinical Trials as Topic; Female; Fibrin; Fibrinolysis; Gestational Age; Humans; Hyaline Membrane Disease; Infant, Newborn; Injections, Intravenous; Male; Plasminogen; Pulmonary Alveoli

Topics: Birth Weight; Clinical Trials as Topic; Fibrin; Fibrinolysis; Humans; Hyaline Membrane Disease; Infant, Newborn; Injections, Intravenous; Placebos; Plasminogen; Pulmonary Alveoli; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Umbilical Veins

Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury.

Topics: Amyloid beta-Protein Precursor; Animals; Bronchoalveolar Lavage; Carrier Proteins; Electrophoresis; Fibrin; Fibrinolysis; Histocytochemistry; Humans; Hyaline Membrane Disease; Hyperoxia; Immunohistochemistry; Infant, Newborn; Lung; Lung Injury; Mice; Mice, Inbred Strains; Oxygen; Plasminogen Activator Inhibitor 1; Protease Nexins; Receptors, Cell Surface; RNA Probes; RNA, Messenger; Tissue Plasminogen Activator; Up-Regulation; Urokinase-Type Plasminogen Activator

Lung injury induced by 100% O2 over 6 days is characterized by markedly less alveolar fibrin and rare hyaline membranes in premature versus adult baboons. To determine the mechanism(s) underlying alveolar fibrin deposition in the evolution of hyaline membrane disease (HMD) through diffuse alveolar damage (DAD) and bronchopulmonary dysplasia (BPD), we measured procoagulant and fibrinolytic activities in lung lavage of premature baboons with HMD, those treated with 100% O2 for 6 days (DAD) or for 7 days followed by 14 days 80% O2 (BPD). Lavage procoagulant activity, mainly due to tissue factor associated with Factor VII, was increased by hyperoxia. Plasminogen-dependent fibrinolytic activity, due to both tissue plasminogen activator and urokinase, was stable or increased after hyperoxia. Plasminogen activator inhibitor 1 (PAI-1) was detectable in lavage of animals with HMD but not those with evolving DAD or BPD. Antiplasmin activity was stable or decreased. Although plasminogen was undetectable in lavage, D-dimer was increased in lavage of the groups exposed to hyperoxia versus HMD. The defect in plasminogen activator activity in lavage fluids of adult baboons with DAD induced by O2 does not occur in premature baboons with HMD, evolving DAD, or BPD. Expression of fibrinolytic activity in the lower respiratory tract of premature baboons is dependent on local access to plasminogen, which is present in relatively low concentrations in plasma of these animals.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Factor VII; Fibrin; Fibrinolysis; Humans; Hyaline Membrane Disease; Infant, Newborn; Male; Oxygen; Papio; Plasminogen Activator Inhibitor 1; Respiration, Artificial; Tissue Plasminogen Activator; Urokinase-Type Plasminogen Activator

The role of fibrinolysis in the pathogenesis of hyaline membrane disease was studied in newborn rabbits at 28- or 29-day gestation. Hyaline membrane was recognized in the lungs of rabbits that were exposed to intrauterine hypoxia and received trans-4-aminomethylcyclohexane carboxylic acid (t-AMCHA), a plasmin inhibitor found to cause a marked decrease in the fibrinolytic activity of lung extracts. In the newborn rabbits subjected to intrauterine hypoxia alone, surface activity of lung extracts was reduced, but hyaline membrane was not seen. By immunofluorescent examination the hyaline membrane was found to be rich in fibrinogen and its derivatives. Electron microscopic examination revealed that they contained various amounts of cellular debris, bundles of fibrils and electron-dense, finely granular deposits and polymerized fibrin with 230 A periodicity. Disintegration of pulmonary epithelial cells was also seen. These findings indicate that diminished fibrinolytic activity of lung tissue contributes to intra-alveolar accumulation of fibrinogen, fibrin and their degradation products, thereby bringing about morphological and physiological disintegration of the terminal airways.

Topics: Animals; Fibrin; Fibrinogen; Fibrinolysis; Humans; Hyaline Membrane Disease; Hypoxia; Infant, Newborn; Lung; Rabbits; Tranexamic Acid

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Disease Progression; Factor V; Factor VII; Fibrin; Fibrin Fibrinogen Degradation Products; France; Humans; Hyaline Membrane Disease; Infant, Newborn; Intensive Care Units, Neonatal; Plasminogen; Prothrombin; Respiratory Distress Syndrome, Newborn; Retrospective Studies; Risk Factors; Severity of Illness Index; Time Factors

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

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

Topics: Apgar Score; Asphyxia Neonatorum; Blood; Cerebral Hemorrhage; Female; Fibrin; Fibrinogen; Fibrinolysis; Gestational Age; Humans; Hyaline Membrane Disease; Hydrogen-Ion Concentration; Infant, Newborn; Obstetric Labor Complications; Oxygen; Partial Pressure; Pregnancy; Pregnancy Complications; Prognosis; Respiratory Distress Syndrome, Newborn; Time Factors

Topics: Child; Child, Preschool; Fibrin; Humans; Hyalin; Hyaline Membrane Disease; Infant; Infant, Newborn

Topics: Adenosine Triphosphatases; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Macrophages; Methylation; Microsomes; Mitochondria; Palmitic Acids; Phosphatidylcholines; Phosphatidylethanolamines; Phospholipids; Pulmonary Alveoli; Pulmonary Atelectasis; Pulmonary Emphysema; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Surface Tension; Surface-Active Agents

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

Topics: Epithelium; Fibrin; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung; Microscopy, Electron

Topics: Blood Proteins; Chromatography; Chromatography, Gel; Erythroblastosis, Fetal; Female; Fibrin; Humans; Hyalin; Hyaline Membrane Disease; In Vitro Techniques; Infant, Newborn; Pregnancy

Topics: Animals; Arginine; Autopsy; Fibrin; Glycoproteins; Guinea Pigs; Histocytochemistry; Humans; Hyaline Membrane Disease; Indicators and Reagents; Infant, Newborn; Lipoproteins; Lung; Oxygen; Tyrosine; Vagotomy

Topics: Animals; Calcium; Cattle; Culture Techniques; Enzymes; Fibrin; Fibrinolysis; Humans; Hyaline Membrane Disease; Infant, Newborn; Lung; Plasminogen; Rabbits; Species Specificity; Thiocyanates

Topics: Animals; Fetus; Fibrin; Fibrinolysin; Guinea Pigs; Histocytochemistry; Humans; Hyaline Membrane Disease; Infant; Infant, Newborn; Infant, Premature; Physiology; Plasminogen; Research; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn

Topics: Chemistry Techniques, Analytical; Deoxyribonuclease I; Enzyme Precursors; Fibrin; Fibrinolysin; Humans; Hyalin; Hyaline Membrane Disease; Infant, Newborn; Plasminogen; Streptodornase and Streptokinase; Streptokinase

An investigation of the pulmonary fibrinolytic enzyme system in 31 infants who died with hyaline membrane formation was reviewed. There was complete lack of plasminogen activator activity in the lungs of 84 per cent of these infants. This phenomenon was shown to result from an abnormal inhibitor. A comparable inhibitor was found in normal placental tissue, and it is postulated that this inhibitor is released into the circulating blood as the result of placental infarction. Fibrin, a basic component of the hyaline membrane, is probably precipitated from a physiological capillary transudate associated with the formation of amniotic fluid by the lungs. The presence of an inhibitor of fibrinolysis would then result in the accumulation of intrapulmonary fibrin and the formation of hyaline membranes.

Topics: Amniotic Fluid; Blood Coagulation Disorders; Female; Fibrin; Fibrinolysis; Humans; Hyalin; Hyaline Membrane Disease; Infant; Infant, Newborn; Lung; Placenta; Plasminogen; Pregnancy; Thrombolytic Therapy