Contact activation in shock caused by invasive group A Streptococcus pyogenes

Area of Science:

• Coagulation and Hemostasis
• Infectious Diseases
• Molecular Biology

Background:

• Streptococcal toxic shock syndrome (STSS) is characterized by profound shock.
• Prolonged activated partial thromboplastin time (aPTT) is observed in STSS patients.
• The underlying hemostatic abnormalities in STSS remain incompletely understood.

Purpose of the Study:

• To investigate coagulation abnormalities in a murine model of invasive Group A Streptococcus infection.
• To elucidate the mechanisms behind the prolonged aPTT seen in STSS.
• To determine if streptococci or their products activate the human contact system.

Main Methods:

• A longitudinal descriptive study of coagulation parameters in CD1 outbred mice infected with Streptococcus pyogenes.
• In vitro experiments co-incubating streptococcal products with human plasma.
• Assays included aPTT, prothrombin time, single factor levels, and bradykinin assays.

Main Results:

• Infected mice showed significantly prolonged aPTT but normal prothrombin times, indicating intrinsic pathway involvement.
• Reduced levels of Factor XII and prekallikrein were observed in infected mice.
• In vitro, streptococcal supernatants activated prekallikrein and plasminogen (via streptokinase).

Conclusions:

• The prolonged aPTT in experimental streptococcal infection is linked to contact system activation.
• This activation, involving Factor XII and prekallikrein, may contribute to the shock observed in STSS.
• Understanding these hemostatic changes offers insights into STSS pathogenesis.