Meningococcemia and purpura fulminans in adults: acute deficiencies of proteins C and S and early treatment with antithrombin III concentrates

Abstract

It has been recently suggested that an acquired deficiency of proteins C and S could contribute to the pathogenesis of meningococcemic purpura fulminans (PF) in children. Our study was designed to measure the levels of antithrombin III (AT III), protein C, and protein S during adult PF and to determine the effects of an early infusion of high doses of AT III concentrates on clinical and biological alterations of PF. We studied five consecutive adult patients with meningococcemia (type B) and PF. The levels of AT III, protein C (antigen and activity), and protein S (total and free) were measured at admission and 24 h and 1 month later. The treatment included in each case: amoxycillin, dobutamine and high doses of AT III concentrates. All patients survived and were discharged without any sequelae. At admission, biological data were consistent with severely depressed protein C and protein S levels and moderately decreased AT III levels, without any discrepancy between protein C antigen and activity. After 24 h, AT III and protein S levels were within normal ranges, whereas protein C levels were still depressed. These data are consistent with the theory of a particular imbalance in the anticoagulant systems during meningococcemic PF, contrasting with the usual findings observed during septic disseminated intravascular coagulation. The possibility must be considered that high doses of one anticoagulant (AT III concentrates) could compensate for the acute decrease in the other (protein C system).

4G/5G promoter polymorphism in the plasminogen-activator-inhibitor-1 gene in children with systemic meningococcaemia

“…Concentrations of protein C, protein S and antithrombin III are low in plasma [11], the endothelial production of prostacyclin is impaired [14], thrombomodulin is down-regulated on the endothelial surface [18], while procoagulant molecules such as tissue factor are increased on monocytes [27]. This leads to deposition of fibrin with histologically demonstrable widespread microthromboses [10].…”

Protein C promoter polymorphisms associate with sepsis in children with systemic meningococcemia

“…In patients with meningococcal sepsis, low PC levels have been correlated with an increased severity of thrombotic lesions and poor outcome (Brandtzaeg et al 1989;Fijnvandraat et al 1995;Fourrier et al 1990;Hesselvik et al 1991;Leclerc et al 1992;Powars et al 1987). On the other hand, inherited PC levels did not show an inXuence on outcome in surviving subjects (Westendorp et al 1996).…”

“…The coagulopathy of meningococcal disease involves a complex dysregulation of procoagulant, anti-coagulant, and Wbrinolytic proteins. Tissue factor expression on monocytes and probably on endothelium is up-regulated (Conkling et al 1988;Gregory et al 1989;Mackman 1995), prostacyclin production by endothelial cells is impaired (Heyderman et al 1991), concentrations of protein S and antithrombin are diminished (Brandtzaeg et al 1989;Fourrier et al 1990), and activation of protein C is impaired (Faust et al 2001a, b). The strong activation of coagulation results in depletion of many hemostatic proteins, particularly protein C (PC) (Leclerc et al 1992).…”

Purpuras

“…12 Des déficits transitoires en protéine S et en protéine C ont été rapportés au cours de l'évolution du purpura fulminans. 13,14 La pathogénie du purpura fulminans est encore imparfaitement connue. L'hypothèse d'une production importante d'interleukine 1 et de Tumor necrosis factor par les kératinocytes et les cellules endothéliales a été évoquée.…”

“…L'incidence du PR est d'environ14 à 18 pour 100 000 enfants par an. Le PR est la cause la plus fréquente de vasculite chez l'enfant (75 % des cas de PR surviennent entre 2 et 11 ans), mais s'observe également, bien que plus rarement, chez l'adulte.…”