fibrinopeptide-a and Pulmonary-Fibrosis

In seven patients with systemic sclerosis (SS), we evaluated the clinical effectiveness of oral administration of saprogrelate hydrochloride (SH: 300 mg/day) for 2 months on Raynaud's phenomenon (RP) and respiratory failure estimated by Hugh-Jones classification.. We evaluated laboratory data (arterial blood gas (pH, PaO2 and PaCO2), pulmonary function tests (%VC, FEV1/FVC and %DL(CO)), mean pulmonary arterial pressure (mPAP), white blood cell count, C-reactive protein and the plasma levels of fibrinopeptide A (FPA), beta-thrombogloblin (beta-TG), platelet factor 4 (PF4) and thrombomodulin (TM)) before and after SH administration.. The frequency and duration of RP, as well as the coldness, numbness and pain of RP were significantly decreased after SH administration (P < 0.05, P < 0.01 and P < 0.001). Respiratory failure estimated by Hugh-Jones classification was also significantly decreased after SH administration (P < 0.05), and the %DL(CO) was significantly increased (P < 0.01). The mPAP decreased significantly after SH administration (P < 0.05). Plasma FPA, beta-TG and PF4 significantly decreased after administration (P < 0.05 and P < 0.01).. SH therapy could prevent RP and respiratory failure in patients with SS.

Topics: Adult; Aged; beta-Thromboglobulin; Blood Pressure; C-Reactive Protein; Female; Fibrinopeptide A; Humans; Leukocyte Count; Male; Middle Aged; Platelet Factor 4; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Ventilation; Raynaud Disease; Respiratory Insufficiency; Scleroderma, Systemic; Serotonin Antagonists; Thrombomodulin

Extravascular coagulation and fibrinolysis is an integral part of inflammatory reactions. Disordered expression of procoagulant and profibrinolytic factors by mononuclear phagocytes of the lung (i.e. lung alveolar macrophages (LAM) and interstitial macrophages) may have important bearings on inflammatory lung tissue destruction and repair. Based on this hypothesis we have measured the presence of trigger molecules and activation products of the coagulation and fibrinolytic system in cell-free bronchoalveolar lavage fluid and in bronchoalveolar cells. Patient groups with chronic obstructive disease (COLD) (n = 76), idiopathic pulmonary fibrosis (IPF) (n = 29), sarcoidosis (n = 22), lung cancer (n = 36), pneumonia (n = 39), acquired immunodeficiency syndrome (AIDS) (n = 17) and a control group (n = 60) were studied by bronchoalveolar lavage (BAL). In all patient groups tissue thromboplastin (TPL) and fibrinopeptide A (FPA) were significantly increased compared to controls. Plasminogen activator (PA) activity was significantly lower in patients than in normals, and usually associated with high levels of antifibrinolytic activity. The level of PA inhibitor (PAI-2) was not significantly higher in any patient group compared to controls. The sensitivity of the method for fibrin degradation products (FDP) analysis was not high enough to detect FDP in BAL fluid of control individuals, whereas such products could be demonstrated in 25-53% of patients in various categories. We conclude that disordered expression of procoagulant and plasminogen activator activities in bronchoalveolar lavage fluid may reflect a milieu that favours accumulation of fibrin in inflammatory lung tissue and form the basis for the development of pulmonary fibrosis.

Topics: Acquired Immunodeficiency Syndrome; Blood Coagulation; Bronchoalveolar Lavage Fluid; Fibrin Fibrinogen Degradation Products; Fibrinolysis; Fibrinopeptide A; Humans; Inflammation; Lung Diseases; Plasminogen Inactivators; Pulmonary Fibrosis; Thromboplastin

Extravascular, primarily, alveolar fibrin deposition is commonly associated with the alveolitis of many interstitial lung diseases including the interstitial lung disease associated with rheumatoid arthritis (RA). We therefore hypothesized that coagulation pathways, which promote fibrin formation, would be activated in the alveolar lining fluids of patients with rheumatoid interstitial lung disease. To test this hypothesis, we studied the bronchoalveolar lavage (BAL) fluids from patients with rheumatoid interstitial lung disease (n = 7) and patients with RA unassociated with interstitial lung disease (n = 10) to characterize and quantitatively compare the BAL procoagulant material and levels of fibrinopeptide A (FPA), which is cleaved from fibrinogen by thrombin. FPA reactive peptide concentrations were significantly greater in rheumatoid interstitial lung disease than RA when normalized per ml of concentrated BAL fluid (p = 0.02), per mg BAL total protein (p = 0.01) or BAL albumin content (p = 0.03) and correlated with BAL antigenic neutrophil elastase concentrations (r = 0.87). Procoagulant activity was present in similar concentration of BAL of patients with RA and rheumatoid interstitial lung disease and was mainly attributable to tissue factor associated with factor VII (or VIIa). Our results demonstrate that tissue factor and factor VII are endogenous in the alveoli of subjects with RA and interstitial lung disease and could interact with distal coagulation substrates which may enter the alveoli in interstitial lung disease to locally promote fibrin deposition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arthritis, Rheumatoid; Blood Coagulation Factors; Bronchoalveolar Lavage Fluid; Factor VII; Factor X; Fibrinogen; Fibrinopeptide A; Humans; Middle Aged; Neutrophils; Peptide Hydrolases; Pulmonary Fibrosis; Thromboplastin