fibrin and Lung-Diseases--Interstitial

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

Topics: Animals; Blood Coagulation; Bronchi; Fibrin; Fibrinogen; Fibrinolysis; Humans; Lung Diseases, Interstitial; Urokinase-Type Plasminogen Activator

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

Topics: Anti-Bacterial Agents; Biopsy; Community-Acquired Infections; Cryptogenic Organizing Pneumonia; Diagnosis, Differential; Female; Fever; Fibrin; Glucocorticoids; Humans; Legionella pneumophila; Legionnaires' Disease; Levofloxacin; Lung; Lung Diseases, Interstitial; Middle Aged; Pneumonia; Prednisolone; Radiography; Rare Diseases; Tomography, X-Ray Computed; Treatment Outcome

Topics: Blood; Chest Tubes; Fibrin; Glucose Solution, Hypertonic; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Pleurodesis; Pneumothorax; Radiography

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

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Topics: Adolescent; Adult; Aged; Alveolitis, Extrinsic Allergic; Antifibrinolytic Agents; Blood Coagulation Factors; Bronchoalveolar Lavage Fluid; CD4-CD8 Ratio; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Hemostatics; Humans; Lung Compliance; Lung Diseases, Interstitial; Lymphocyte Count; Male; Middle Aged; Neutrophils; Pulmonary Fibrosis; Sarcoidosis; Thromboplastin

Idiopathic organizing pneumonia (OP) was classified pathologically into two types, and the clinical profiles were compared. Cases in which fibrin in Masson bodies, alpha-sm-actin and m-actin antibodies were negative were regarded as type I (14 cases), and those in which they were positive as type II (7 cases). No significant differences in age and sex were observed between the two groups. As to clinical symptoms and laboratory findings, dyspnea and CRP positivity were observed more frequently and inflammatory reactions were stronger, in type II than in type I. The two groups could not be distinguished by chest X-ray findings. With regard to treatments and outcome, chest X-ray shadows disappeared completely after steroid therapy in type I, and no deaths occurred despite recurrence in some cases. In type II, chest X-ray shadows partially remained in all cases even after steroid therapy, recurrence was rare, and death occurred in some cases due to exacerbations of the initial episode. These observations suggest that there are two pathological types of OP and that the differences in clinical symptoms, laboratory findings, treatments, and prognosis between the two types must be taken into consideration in treating OP.

Topics: Actins; Adult; Aged; Aged, 80 and over; Autoantibodies; Bronchiolitis Obliterans; Female; Fibrin; Humans; Immunohistochemistry; Lung Diseases, Interstitial; Male; Middle Aged; Prognosis