Biology and Pathogenesis of Thrombosis and Procoagulant Activity in Invasive Infections Caused by Group A Streptococci andClostridium perfringens

Abstract

Group A streptococcal necrotizing fasciitis/myonecrosis and Clostridium perfringens gas gangrene are two of the most fulminant gram-positive infections in humans. Tissue destruction associated with these infections progresses rapidly to involve an entire extremity. Multiple-organ failure is common, and morbidity and mortality remain high. Systemic activation of coagulation and dysregulation of the anticoagulation pathways contribute to the pathogenesis of many diverse disease entities of infectious etiology, and it has been our hypothesis that microvascular thrombosis contributes to reduced tissue perfusion, hypoxia, and subsequent regional tissue necrosis and organ failure in these invasive gram-positive infections. This article reviews the coagulation, anticoagulation, and fibrinolytic systems from cellular players to cytokines to novel antithrombotic therapies and discusses the mechanisms contributing to occlusive microvascular thrombosis and tissue destruction in invasive group A streptococcal and C. perfringens infections. A thorough understanding of these mechanisms may suggest novel therapeutic targets for patients with these devastating infections

Ventilator-associated lung injury: a search for better therapeutic targets

“…The recent literature on sepsis [77][78][79][80][81][82] speculates about improved outcomes in patients receiving anticoagulant therapy, regardless of whether it is in the form of heparin, activated protein C, hirudin or leperudin. For example, mice with naturally reduced factor VII production have an attenuated inflammatory response and enhanced survival when exposed to endotoxin [83].…”

Analysis of Core Housekeeping and Virulence Genes Reveals Cryptic Lineages ofClostridium perfringensThat Are Associated With Distinct Disease Presentations

“…However, if left untreated, severe dehydration or death may occur in infants, the elderly, the debilitated, or the immune compromised. Gas gangrene (also known as clostridial myonecrosis) is an extremely serious disease, requiring both antibiotic and surgical treatment (Present et al 1990;Bryant and Stevens 1997;Bryant 2003). It is usually acquired when wounds become exposed to soil or other environmental material.…”

“…It is usually acquired when wounds become exposed to soil or other environmental material. If left untreated, the disease results in extensive tissue necrosis requiring surgical intervention that often involves limb amputation; unsuccessful treatment results in systemic shock and death (Present et al 1990;Bryant and Stevens 1997;Bryant 2003).…”

A Role of Arginine Deiminase From Streptococcus Pyogenes M49-16 in Promoting Infection and Inhibition of Endothelial Cell Proliferation

“…Это выражается в нарушении процесса коагуляции, снижении адгезивности эндотели-альных клеток и повышении проницаемости эн-дотелиального барьера [1]. Описанные эффекты связывают с индукцией экспрессии на эндотели-альных клетках тканевого фактора и активацией матриксных металлопротеаз [4,5,19]. Эндоте-лиальные клетки экспрессирует еNOS и аргина-зу -ферменты, субстратом для которых является аргинин, поэтому метаболиты аргинина играют важную роль в регуляции функций эндотелия сосудов.…”