Purpura fulminans

Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation. Purpura fulminans is an acute, often fatal, thrombotic disorder which manifests as blood spots, bruising and discolouration of the skin resulting from coagulation in small blood vessels within the skin and rapidly leads to skin necrosis and disseminated intravascular coagulation. Purpura fulminans is caused by defects in the protein C anticoagulant pathway. Identification of the cause of purpura fulminans often depends on the patient’s age and circumstances of presentation. Congenital (inherited) defects in protein C activity are autosomal dominant and may be partial or severe loss of function. Hundreds of natural mutations of the protein C gene (PROC) have been identified. Acquired protein C deficiency is caused by either depletion of available protein C in plasma or decreased protein C synthesis (caused by administration of vitamin K antagonists, severe liver failure or complications of prematurity). Purpura fulminans is a presenting feature of severe acute sepsis, such as Neisseria meningitidis, Streptococcus pneumoniae, Group A and B Streptococci, and less commonly with Haemophilus influenzae, Staphylococcus aureus, or Plasmodium falciparum (malaria) infections, particularly in individuals with asplenia. In some cases, a combination of sepsis and a partial congenital defect in the protein C anticoagulant pathway initiates purpura fulminans. In rare instances, purpura fulminans is an autoimmune manifestation against protein C or protein S after normally benign infections, such as chicken pox. Sometimes purpura fulminans has unknown cause. Regardless of the underlying cause of purpura fulminans, the mechanism of disease is similar with deficiency in protein C concentration or decrease in protein C activity which promotes blood clotting (thrombosis). In cases of severe sepsis, there is widespread activation of the acute systemic inflammatory response, including activation of the coagulation and complement pathways, as well as endothelial dysfunction. Activated protein C helps regulate the systemic inflammatory response. During sepsis, signalling by the inflammatory cytokines, interleukin-1 and tumour necrosis factor, mediate altered protein transcription in the systemic inflammatory response, resulting in decreased synthesis of the regulatory proteins antithrombin, protein C and protein S, with increased synthesis of prothrombotic proteins Factor VIII, von Willebrand factor, and fibrinogen. Activated protein C binds to endothelial protein C receptor and subsequently cleaves the endothelial cell protease activated receptor-1, not only altering coagulation profiles but down-regulating pro-inflammatory and pro-apoptotic mediators, up-regulation of anti-inflammatory and anti-apoptotic pathways and stabilization of the endothelial cell barrier functions.