Objectives: The aim of this study was to characterize abnormalities of coag
ulation in mice with experimental, invasive group A, streptococcal shock, i
n an attempt to explain the prolongation of the activated partial thrombopl
astin 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 Streptococus pyogenes.
This was followed by an experimental study to determine whether streptococ
ci or streptococcal products could activate the human contact system in vit
ro.
Setting: University infectious diseases and hemostasias molecular biology l
aboratories.
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 com
pared coagulation times, single factor assays, and activities against a ran
ge of chromogenic substrates with control plasma. In a murine model of stre
ptococcal necrotizing fasciitis, the activated partial thromboplastin times
were significantly prolonged in infected mice compared with controls, wher
eas prothrombin times were normal, suggesting an isolated abnormality of th
e intrinsic pathway. Bleeding was not seen. Prolongation of activated parti
al thromboplastin time was associated with reduced factor XII and prekallik
rein, whereas levels of factors VIII, IX, XI, and high molecular weight kin
inogen were elevated. In vitro studies suggested that streptococcal superna
tants can activate prekallikrein, in addition to causing plasminogen activa
tion through the action of streptokinase.
Conclusions: Prolongation of activated partial thromboplastin time in strep
tococcal toxic shock syndrome is associated with activation of the contact
system, possibly contributing to the profound shock associated with strepto
coccal toxic shock syndrome.