thromboplastin and Respiratory-Distress-Syndrome--Newborn

Exchange transfusion, as a form of therapy, was contrasted with the use of fresh frozen plasma or conventional supportive care alone in the management of 19 infants with birth weights of less than 1,000 gm, without severe respiratory distress, and in the management of 82 infants, birth weights less than 2,000 gm, with severe respiratory distress whose disease manifested itself within the first 24 hours of life. Survival for more than five days was similar, regardless of therapy, in infants weighing less than 1,000 gm without severe RDS. In contrast, the use of exchange transfusion significantly decreased the case fatality rate of infants with severe RDS. In the groups receiving exchange transfusion, the mortality rate was 41%, whereas the groups receiving either plasma or supportive care alone the mortality was 80%. Study of coagulation factors and red cell concentrations of fetal hemoglobin and of 2,3-DPG failed to demonstrate any relationship between either improvement in coagulation or oxygen unloading and the improved survival of infants receiving exchange transfusion. Following exchange transfusion there was a significant decrease in the ratio of FIO2 to PaO2, suggesting that pulmonary perfusion and/or ventilation was improved by the procedure.

Topics: Acidosis, Respiratory; Birth Weight; Blood Gas Analysis; Diphosphoglyceric Acids; Erythrocytes; Exchange Transfusion, Whole Blood; Freezing; Humans; Hyaline Membrane Disease; Hypoxia; Infant, Newborn; Infant, Premature, Diseases; Plasma; Positive-Pressure Respiration; Respiratory Distress Syndrome, Newborn; Thromboplastin

In preterm infants, inflammation and intra-alveolar fibrin formation characterize respiratory distress syndrome (RDS). Tissue factor (TF) is a link between inflammation and coagulation pathways. We investigated the relationship between TF and cytokines in preterm infants to gain information of the role of TF in the inflammatory response.. We measured TF in plasma and in tracheal aspirates and analysed TF on monocytes by flow cytometry and 13 cytokines from plasma, in 56 preterm infants (birthweight 600-1500 g) during their first week.. Plasma TF increased and peaked on day 3 and correlated with both RDS and inversely with paO2/FIO2. On day 1, TF in tracheal aspirates was 10-fold higher than in plasma and correlated with plasma TF (4888 vs. 506 pg/mL, R = 0.692, p = 0.013, n = 12). Of main pro-inflammatory cytokines, plasma TF correlated post-natally with IL-8 and IL-6 but not with IL-1 or TNF-α.. Respiratory morbidity associates with high TF in lungs and plasma. In sick newborn infants, upregulation of TF may be mediated by IL-6 and IL-8. High TF and pro-inflammatory cytokines may together participate in the pathogenesis of pulmonary and extrapulmonary injury in preterm infants through pro-inflammatory mechanisms.

Topics: Bronchopulmonary Dysplasia; Cytokines; Female; Humans; Infant, Newborn; Infant, Premature; Inflammation; Lung; Male; Morbidity; Plasma; Respiratory Distress Syndrome, Newborn; Thromboplastin

Neonatal respiratory distress syndrome can progress to bronchopulmonary dysplasia (BPD), a serious pulmonary fibrotic disorder. Given the involvement of the extrinsic coagulation cascade in animal models of lung fibrosis, we examined its role in BPD. We observed a higher number of neutrophils expressing tissue factor (TF) in bronchoalveolar lavage fluid (BALF) from infants with BPD than from those with uncomplicated respiratory distress syndrome together with a parallel decrease in TF and connective tissue growth factor (CTGF) in BALF supernatants during the disease course. The involvement of coagulation in the fibrotic process associated with BPD was further evaluated by treating primary human colonic myofibroblasts with BALF supernatants from infants with BPD. These human colonic myofibroblasts demonstrated an enhanced C5a- and thrombin-dependent migration. Moreover, they expressed TF in an endothelin-1-dependent manner, with subsequent activation of the extrinsic coagulation cascade and CTGF production mediated by protease-activator receptor-1 signaling. These data provide a novel mechanism for the development of BPD and indicate that endothelin-1 signaling contributes to fibrosis by upregulating a TF/thrombin amplification loop responsible for CTGF production, and offer novel and specific therapeutic targets for pulmonary fibrotic disease.

Topics: Blotting, Western; Bronchoalveolar Lavage Fluid; Bronchopulmonary Dysplasia; Cells, Cultured; Colon; Complement C5a; Connective Tissue Growth Factor; Endothelin-1; Female; Fibrosis; Green Fluorescent Proteins; Humans; Immunohistochemistry; Infant, Newborn; Lung; Male; Microscopy, Fluorescence; Myofibroblasts; Receptor, Anaphylatoxin C5a; Receptor, PAR-1; Receptors, Complement; Respiratory Distress Syndrome, Newborn; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Thrombin; Thromboplastin

Respiratory distress syndrome (RDS) is characterized by intrapulmonary fibrin deposition, which can adversely affect surfactant function, and stimulate fibroblast proliferation, which may contribute to the development of bronchopulmonary dysplasia (BPD). We speculated that the premature lung may have impaired regulation of thrombin, thus making preterm infants susceptible to fibrin formation within the lung. Therefore, we studied the effect of stretch, which simulates fetal breathing movements (FBMs), on the generation and inhibition of a key hemostatic enzyme-thrombin-by rat fetal mixed lung cells (FMLCs). Our results showed that stretch induced glycosaminoglycan production with increased antithrombin activity due to an increase in the concentration of active chondroitin sulfate. Stretch downregulated secretion of tissue factor procoagulant activity, which may lead to decreased thrombin generation on the surface of FMLCs. Overall, stretch enhanced the local control of thrombin by FMLCs. These results suggest that premature infants, who will have experienced less FBM, may have impaired thrombin regulation. Impaired thrombin regulation likely contributes to increased fibrin deposition and, potentially, the development of BPD.

Topics: Animals; Cells, Cultured; Chondroitin Sulfates; Fetus; Fibrin; Glycosaminoglycans; Humans; Infant, Newborn; Lung; Pulmonary Stretch Receptors; Rats; Rats, Wistar; Respiration; Respiratory Distress Syndrome, Newborn; RNA, Messenger; Thrombin; Thromboplastin

Based on the fact that both tissue thromboplastin and lung surfactant show lamellar structures under the electron microscope and belong chemically to lipoprotein, the thromboplastic activity of lung surfactant in amniotic fluid was studied by measuring plasma recalcification time. The results obtained were as follows (1) The surfactant fractions isolated from amniotic fluid and rabbit or pig lung showed the thromboplastic activity with dose response. (2) The thromboplastic activity of amniotic fluid increased with advancing gestational age. (3) It was found that the thromboplastic activity determined by plasma recalcification time was parallel with the surfactant concentration of amniotic fluid. (4) The shortening rate of plasma recalcification time in amniotic fluid could estimate well the risk of RDS, and the critical value for RDS was assumed to be about 33%.

Topics: Amniotic Fluid; Animals; Female; Fetal Organ Maturity; Humans; Infant, Newborn; Lung; Pregnancy; Prenatal Diagnosis; Pulmonary Surfactants; Rabbits; Respiratory Distress Syndrome, Newborn; Thromboplastin

Topics: Animals; Animals, Newborn; Cell Membrane; Cesarean Section; Disseminated Intravascular Coagulation; Epithelial Cells; Female; Heparin; Humans; Infant, Newborn; Isotonic Solutions; Microcirculation; Microscopy, Electron; Pregnancy; Pulmonary Alveoli; Pulmonary Surfactants; Rabbits; Respiratory Distress Syndrome, Newborn; Sodium Chloride; Thrombin; Thromboplastin

Topics: Animals; Blood Coagulation Disorders; Cricetinae; Embolism; Female; Fibrinogen; Humans; Infant, Newborn; Placenta; Pregnancy; Respiratory Distress Syndrome, Newborn; Thromboplastin

Topics: Adenine Nucleotides; Adult; Blood Coagulation Tests; Blood Platelets; Clot Retraction; Collagen; Hemorrhagic Disorders; Humans; Infant, Newborn; Infant, Premature; Platelet Adhesiveness; Respiratory Distress Syndrome, Newborn; Thrombelastography; Thrombin; Thromboplastin

Topics: Bicarbonates; Blood Coagulation Factors; Factor IX; Factor V; Factor VII; Factor X; Humans; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Prothrombin; Respiratory Distress Syndrome, Newborn; Sodium; Thromboplastin; Tromethamine