Disseminstaed intravascular coagulation syndrome(DIC) is a potentially lethal disorder in which microthombi form systemically. In the pathogenesis of DIC, tissue injury and endothelial injury appeear to be two major mechanisms invovied Tissue injury refers to the pathologic conditions such as obstetrical complications or multiple taruma In such cases, release of tissue factor, a triggering substance for the extrinsic pathway of coagulation, induces intravascular coagulation. Endothelial injury is induced mainly by such cytoldnes as tumor necrosis factor-alpha (TNF- a) or interleuldn-1(i or by the inflammatory mediators such as granulocyte protpnses or oxygen free radicals that are derived from activated leukocytes in the pathophysiology of sepsis. The activated leukocyte-induced endothelial injury may deeply related to the pathogenesis of DIC and adult respiratory distress syndrome(ARDS) in sepsis. AIRS as well as DIC can influence the outcome of patients with sepsis. Antithrombin III (AT III) and activated protein C (APC) prevent the endotoxin-induced pulmonary vascular injury in animals independent on their anticoagulant properties, but dependent on their inhibitory activities on cytokine production by monocytes. Gabexate mesilate (GM), a synthetic inhibitor for the proteases generated within the coagulation cascade, also prevents the endotoxin-induced pulmonary vascular injury as well as the coagulation abnormalities mainly by inhibiting TNF- a production by monocytes, Although heparin prevents the endotoxin-induced coagulation abnormalities, it does not prevent the pulmonary vascular injury.
These observations strongly suggest that AT 111, APC, and GM, but not heparin, may be useful in treating both the activated leukocyte-induced coagulation abnormalities and endothelial injury in patients with DIC associated with sepsis.
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