The relationship between plasminogen activation inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock

Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 /- 2.4 vs. 6.1 /- 3.3 h; P = 0.4). This interval correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene

Age-related differences in outcome and severity of DIC in children with septic shock and purpura

We studied the influence of age on mortality and severity of clotting abnormalities in 79 children (median age: 3.1 years) with meningococcal sepsis. Parameters of coagulation and fibrinolysis and plasma levels of cytokines were prospectively measured on admission. The mortality rate was 27%. The age of survivors was significantly different from that of non-survivors (p = 0.013). With the exception of FVII, vWF and t-PA, parameters of coagulation and fibrinolysis, as well as plasma cytokine levels were related to outcome. Patients were divided in two groups: younger and older than median age. The mortality in children ≤ 3.1 years was 40% versus 13% in children > 3.1 years (p = 0.006). In contrast to cytokine levels, which were not different between the two age groups, fibrinogen, prothrombin, factors V, VII, VIII, vWF, protein C, antithrombin, FDP, and the ratio PAI-1/t-PA were related to age, indicating a more severe coagulopathy in children ≤ 3.1 years despite a similar degree of inflammatory response. A relative deficiency of coagulation factors due to an immature state of the clotting system, as well as an inadequate fibrinolytic response, both related to age may have caused this more severe coagulative response in younger children, and may have contributed to the higher mortality rate

The relationship between plasminogen activation inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock

Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 /- 2.4 vs. 6.1 /- 3.3 h; P = 0.4). This interval correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene

The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock

Proinflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 ± 2.4 vs. 6.1 ± 3.3 h; P = .04). This interval correlated strongly with the levels of TNF- α, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-α concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-α concentration. Thus, an increased PAI-1 response to TNF-α may be associated with fatality, probably because of polymorphism of the PAI-1 gene

Profile of blood donors with serologic tests reactive for the presence of syphilis in São Paulo, Brazil

BACKGROUND: Syphilis screening of blood donors is a common practice worldwide, but very little is known about the meaning of a positive serologic test for syphilis in blood donors and the risk profile of these donors. The aim of this study was to determine the demographic characteristics and risk behaviors of blood donors with recent and past syphilis and their implications for blood bank testing and deferral strategies. STUDY DESIGN AND METHODS: Demographic characteristics, category of donation, number of previous donations, sexual behavior, and history of sexually transmitted diseases were reviewed comparing blood donors with recent and past syphilis from January 1, 1999, to December 31, 2003. RESULTS: A total of 2439 interviews were reviewed, including 2161 (88.6%) donors with past and 278 (11.4%) with recent syphilis infection. Factors associated with recent infection included younger age (≤20 years odds ratio [OR], 36.5; 95% confidence interval [CI], 15.8–84.1), two previous donations (OR, 2.7; 95% CI, 1.9–3.9), male-male sex (homosexual OR, 8.2; 95% CI, 3.2–20.8; and bisexual OR, 11.4; 95% CI, 3.6–36.3), two or more partners in the past 12 months (OR, 2.3; 95% CI, 1.3–4.0), symptoms for syphilis (OR, 4.5; 95% CI, 2.8–7.1), and human immunodeficiency virus (HIV) seropositivity (OR, 39.6; 95% CI, 4.6–339.8). Community donors were also associated with recent syphilis infection (OR, 1.5; 95% CI, 1.2–1.9) compared to replacement donors. CONCLUSION: Sexual history, including male-male sex and multiple partners, were strongly associated with recent syphilis infection, which in turn was strongly associated with HIV. Continuous and vigilant surveillance that includes assessing sexual history and other factors associated with syphilis are needed to guide blood safety policies