Contact activation in shock caused by invasive group A Streptococcus pyogenes

Citation
S. Sriskandan et al., Contact activation in shock caused by invasive group A Streptococcus pyogenes, CRIT CARE M, 28(11), 2000, pp. 3684-3691
Citations number
30
Categorie Soggetti
Aneshtesia & Intensive Care
Journal title
CRITICAL CARE MEDICINE
ISSN journal
00903493 → ACNP
Volume
28
Issue
11
Year of publication
2000
Pages
3684 - 3691
Database
ISI
SICI code
0090-3493(200011)28:11<3684:CAISCB>2.0.ZU;2-E
Abstract
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.