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  • Title: Compound 48/80 suppresses monocytic tissue factor-initiated extrinsic blood coagulation induced by bacterial endotoxin.
    Author: Chu AJ, Raphael UO, Prasad JK, Beydoun S, Ramos N.
    Journal: J Surg Res; 1999 Dec; 87(2):252-7. PubMed ID: 10600357.
    Abstract:
    BACKGROUND: Hypercoagulability is one of the commonly exhibited endotoxemia septic symptoms; it could contribute to the manifestation of disseminated intravascular coagulation presenting threats to cardiovascular functions. The underlying mechanism, however, remains largely complex and unknown. OBJECTIVES: We herein determine whether bacterial endotoxin (LPS) upregulates the activities of clotting factors in plasma, contributing to extrinsic hypercoagulation. Compound 48/80 (48/80) is also tested for its ability to suppress hypercoagulation. METHODS: In an in vitro infection model, we exposed whole blood to LPS (Escherichia coli 0111:B04; 100 ng/ml) for 2 h. Thrombin time (TT), prothrombin time (PT), and the activities of clotting factors ( FVII, FIX, FX ) in plasma contributing to the extrinsic coagulation were determined. Peripheral blood monocytes were isolated from Histoplaque 1077 gradient centrifugation, and the procoagulant activity was determined by a single-stage clotting assay on a Fibrometer. RESULTS: LPS drastically activated monocytic procoagulant activity which was defined as tissue factor (TF) activity, whereas LPS had no effect on TT, PT, and the activities of clotting factors in plasma. 48/80 not only instantaneously offset LPS-induced monocytic TF activation, but also significantly inhibited PT including the activities of clotting factors (FVII, FIX, and FX) in plasma, whereas TT remained unaffected. CONCLUSIONS: Monocytic TF activation was solely responsible for the extrinsic hypercoagulation in response to LPS. 48/80 effectively suppressed LPS-induced monocyticTF-initiated extrinsic coagulation at multiple sites, possibly presenting a new therapy for an instantaneous relief of hypercoagulation under septic conditions.
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