ROLE OF LEUKOCYTES IN DISSEMINATED INTRAVASCULAR COAGULATION SYNDROME ASSOCIATED WITH SEPSIS

OKAJIMA, Kenji

J Korean Soc Emerg Med > Volume 7(3); 1996 > Article

Original Article

Journal of The Korean Society of Emergency Medicine 1996;7(3): 326-336.

ROLE OF LEUKOCYTES IN DISSEMINATED INTRAVASCULAR COAGULATION SYNDROME ASSOCIATED WITH SEPSIS

Kenji OKAJIMA

Department of Laboratory Medicine, Kumamoto University Medical School Kumamoto, JAPAN

Published online: September 30, 1996.

ABSTRACT

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 appear to be two major mechanisms involved. 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 cytokines as tumor necrosis factor-alpha (TNF- α)or interleukin-1 β or by the inflammatory mediators such as granulocyte proteases 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. ARDS 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- α 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 Ⅲ, 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.