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February 9, 1994

The Pathogenesis of Disseminated Intravascular Coagulation in Sepsis-Reply

Author Affiliations

Academic Medical Center Amsterdam, the Netherlands

JAMA. 1994;271(6):428. doi:10.1001/jama.1994.03510300027023

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In Reply.  —The observation of Logan et al supports the notion that the induction of fibrinolysis and coagulation by cytokines follows different pathways. Endotoxin as well as TNF causes t-PA release in vivo, before thrombin generation can be detected, and neutralization of TNF in endotoxemia inhibits t-PA release, but not thrombin formation. The temporal relationship between neutropenia and t-PA release that occurs in TNF-infused cancer patients was also observed in healthy volunteers who received a bolus TNF injection and may indicate a causal role of activated adhering neutrophils for t-PA release by endothelial cells.This observation merits further investigation, in particular because TNF does not cause the rapid release of t-PA from endothelial cells in vitro, even in the presence of plasma or serum, which suggests that other cells may be involved in TNF-induced activation of the fibrinolytic system in vivo.

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