Sriskandan S, Kemball-Cook G, Moyes D, Canvin J, Tuddenham E, Cohen J
Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
Crit Care Med. 2000 Nov;28(11):3684-91. doi: 10.1097/00003246-200011000-00025.
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.
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.
University infectious diseases and hemostasis molecular biology laboratories.
CD1 outbred mice.
None.
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.
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.
本研究旨在描述实验性侵袭性A组链球菌感染致小鼠休克时的凝血异常，以解释链球菌中毒性休克综合征患者活化部分凝血活酶时间延长的原因。
对感染化脓性链球菌的小鼠的凝血时间和单一凝血因子进行纵向描述性动物模型研究。随后进行实验研究，以确定链球菌或链球菌产物是否能在体外激活人类接触系统。
大学传染病和止血分子生物学实验室。
CD1远交系小鼠。
无。
在链球菌感染后的不同时间对小鼠血浆进行凝血时间、单一因子检测和缓激肽检测，并与未感染小鼠进行比较。在链球菌产物与人血浆共同孵育的实验中，我们将凝血时间、单一因子检测以及针对一系列发色底物的活性与对照血浆进行了比较。在链球菌坏死性筋膜炎的小鼠模型中，与对照组相比，感染小鼠的活化部分凝血活酶时间显著延长，而凝血酶原时间正常，提示内源性途径存在孤立异常。未观察到出血现象。活化部分凝血活酶时间延长与因子Ⅻ和前激肽释放酶减少有关，而因子Ⅷ、Ⅸ、Ⅺ和高分子量激肽原水平升高。体外研究表明，链球菌上清液除了通过链激酶的作用激活纤溶酶原外，还能激活前激肽释放酶。
链球菌中毒性休克综合征中活化部分凝血活酶时间延长与接触系统激活有关，这可能是导致链球菌中毒性休克综合征严重休克的原因之一。
