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The Role of Leukocytes in Disseminated Intravascular Coagulation Associated with Sepsis

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Sepsis

Abstract

Leukocytes play a pivotal role in the pathogenesis of disseminated intravascular coagulation (DIC) and multiple organ failure associated with sepsis. Cytokines such as tumor necrosis factor-a (TNF-α) and interleukin-1β (IL-1β) activate monocytes, neutrophils and endothelial cells. TNF-α increases the expression of tissue factor on surfaces of both monocytes and endothelial cells and decreases the anticoagulant potential of endothelial cells, thereby inducing intravascular coagulation. These cytokines also inhibit the fibrinolytic activity by increasing the endothelial production of plasminogen activator inhibitor-1. These cytokines activate neutrophils to release the various inflammatory mediators such as neutrophil elastase and oxygen free radicals, both of which are capable of damaging endothelial cells. Activated neutrophils damage endothelial cells by adhering to endothelial cells through interaction with E-selectin or ICAM-1, endothelial leukocyte adhesion molecules, expression of which are increased by the actions of these cytokines. Both microthrombus formation and the endothelial cell damage could lead to multiple organ failure by inducing microcirculatory disturbances.

Among physiological anticoagulants, antithrombin, activated protein C and tissue factor pathway inhibitor exert anti-inflammatory activity by inhibiting leukocyte activation. Gabexate mesilate and nafamostat mesilaste, synthetic anticoagulants, also inhibit leukocyte activation. The reduction of both coagulation abnormalities and inflammatory responses by using these therapeutic agents could be useful in the treatment of DIC associated with sepsis.

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  1. Department of Laboratory Medicine, Kumamoto University School of Medicine, Kumamoto

    Kenji Okajima

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Okajima, K. The Role of Leukocytes in Disseminated Intravascular Coagulation Associated with Sepsis. Sepsis 3, 135–142 (1999). https://doi.org/10.1023/A:1009899400421

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