Catheterization of the umbilical artery has been a useful aid in the management of sick neonates for the past few decades. However, it is associated with various complications. Reported studies strongly suggest a significant role of intravascular catheterization in the development of aortic thrombi. Increase in thrombosis of large vessels is believed to be related to mechanical injury in the catheterized vessels, which provide direct exposure of blood to tissue factor (TF), the primary cellular initiator of the extrinsic coagulation pathway. This study was conducted to determine the levels of plasma TF, tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in infants with umbilical arterial catheter (UAC)-associated thrombosis. Quantification of TF was carried out using an in-house sandwich ELISA, whereas TFPI and DD levels were measured with commercial immunoassay kits. Infants with UAC inserted were found to have significantly higher levels of plasma TF (p < 0.001) than baseline levels. However, there were no significantly elevated levels of TFPI or DD. Infants with UAC-associated thrombosis demonstrated a greater increase of TF level (median: 414.5 pg/mL; range: -76.0, 6667.0) than infants without UAC-associated thrombosis (105.0 pg/mL; -976.0, 9480.0; p = 0.009) following UAC insertion. Our findings indicate that quantification and monitoring of TF levels could predict thrombus formation in infants with indwelling UAC. Following umbilical arterial catheterisation, infants with an approximately 3-fold rise in plasma TF levels were most at risk of developing abdominal aorta thrombosis as confirmed by real-time abdominal ultrasonography.
The investigation of many hemostatic defects in newborns is restricted by the lack of normal reference values. The coagulation system of the neonate differs in many ways from that of the adult. The present study was designed to compare the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in the umbilical cord blood of healthy newborns and in adult plasma. TF antigen was quantified using an in-house enzyme-linked immunosorbent assay, whereas TFPI and DD levels were measured with commercial kits. The mean TF level in cord blood (mean standard deviation, 183.94 103.63 pg/ml) was significantly higher ( = 0.008) than that in adults (136.64 65.09 pg/ml). Cord blood exhibited enhanced fibrinolysis, as was reflected by a significantly higher level of DD (924.57 733.87 ng/ml, 0.001) than that in adults (45.57 17.21 ng/ml). Conversely, cord blood (30.88 10.16 ng/ml) demonstrated significantly lower ( 0.001) TFPI levels than that in adults (55.77 21.16 ng/ml). However, no significant differences of these three hemostatic markers were noted between both gender groups in newborns and adults. Our findings indicate that an active and dynamic state of hemostasis exists in cord blood, as the fluidity of cord blood remains preserved in the presence of birth injury.
Dengue virus (DENV) is considered to be the most important arthropod-borne viral disease and causes more than 100 million human infections annually. To further characterize primary DENV infection in vivo, rhesus macaques were infected with DENV-1, DENV-2, DENV-3, or DENV-4 and clinical parameters, as well as specificity and longevity of serologic responses, were assessed. Overt clinical symptoms were not present after infection. However, abnormalities in blood biochemical parameters consistent with heart, kidney, and liver damage were observed, and changes in plasma fibrinogen, D-dimers, and protein C indicated systemic activation of the blood coagulation pathway. Significant homotypic and heterotypic serum immunoglobulins were present in all animals, and IgG persisted for at least 390 days. Serum neutralizing antibody responses were highly serotype specific by day 120. However, some heterotypic neutralizing activity was noted in infected animals. Identification of serotype-specific host responses may help elucidate mechanisms that mediate severe DENV disease after reinfection.