TFPI fractions in plasma from patients with systemic meningococcal disease

Abstract

Disseminated intravascular coagulation (DIC) is a major complication of meningococcal sepsis and closely associated with the development of multiple organ failure and death [1,2]. Fulminant meningococcal sepsis is characterized by exceptionally high plasma levels of endotoxin, i.e., bacterial lipopolysaccharides, which upregulate tissue factor (TF) on the surface of circulating blood monocytes and possibly on the surface of endothelial cells [1–3]. Fragments of disintegrated monocytes with documented procoagulant activity are present in plasma collected from patients with meningococcal sepsis [4]. TF forms complex with factor VII (FVII), which activates factors IX and X. TF induced coagulation is modulated by tissue factor pathway inhibitor (TFPI), which inhibits coagulation in a two-step fashion. It the first step, TFPI builds an inhibitory complex with activated factor X (FXa). In the second step, the FXa/TFPI complex builds a quaternary inhibitory complex with FVIIa/TF. Numerous experimental studies including gene knock-out [5], immunodepletion of TFPI [6], and supplementation of exogenous TFPI [7] have demonstrated the key role of TFPI in the regulation of TF induced coagulation.