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Contact activation in shock caused by invasive group A Streptococcus pyogenes
S Sriskandan1, G Kemball-Cook, D Moyes
1Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, London, UK. s.sriskandan@ic.ac.uk
Objectives:
The aim of this study was to characterize abnormalities of coagulation in mice with experimental, invasive group A, streptococcal shock, in an attempt to explain the prolongation of the activated partial thromboplastin time identified in patients with streptococcal toxic shock syndrome.
Design:
A longitudinal descriptive animal model study of coagulation times and single coagulation factors in mice infected with Streptococcus pyogenes. This was followed by an experimental study to determine whether streptococci or streptococcal products could activate the human contact system in vitro.
Setting:
University infectious diseases and hemostasis molecular biology laboratories.
Subjects:
CD1 outbred mice.
Interventions:
None.
Measurements And Main Results:
Coagulation times, single factor assays, and bradykinin assays were conducted on murine plasma at different times after streptococcal infection and compared with uninfected mice. In experiments in which streptococcal products were co-incubated with human plasma, we compared coagulation times, single factor assays, and activities against a range of chromogenic substrates with control plasma. In a murine model of streptococcal necrotizing fasciitis, the activated partial thromboplastin times were significantly prolonged in infected mice compared with controls, whereas prothrombin times were normal, suggesting an isolated abnormality of the intrinsic pathway. Bleeding was not seen. Prolongation of activated partial thromboplastin time was associated with reduced factor XII and prekallikrein, whereas levels of factors VIII, IX, XI, and high molecular weight kininogen were elevated. In vitro studies suggested that streptococcal supernatants can activate prekallikrein, in addition to causing plasminogen activation through the action of streptokinase.
Conclusions:
Prolongation of activated partial thromboplastin time in streptococcal toxic shock syndrome is associated with activation of the contact system, possibly contributing to the profound shock associated with streptococcal toxic shock syndrome.