Download PDF
Thromb Haemost 1996; 75(04): 578-584
DOI: 10.1055/s-0038-1650325
Original Article
Schattauer GmbH Stuttgart

Infusion of Phospholipid Vesicles Amplifies the Local Thrombotic Response to TNF and Anti-Protein C into a Consumptive Response

Authors

  • F B Taylor Jr.

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA

  • S E He

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA

  • A C K Chang

    2   University of Oklahoma Health Sciences Center, Oklahoma City, USA

  • J Box

    3   Howard Hughes Medical Institute, Oklahoma City, USA

  • G Ferrell

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA

  • D Lee

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA

  • M Lockhart

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA

  • G Peer

    2   University of Oklahoma Health Sciences Center, Oklahoma City, USA

  • C T Esmon

    1   The Oklahoma Medical Research Foundation, Oklahoma City, USA
    2   University of Oklahoma Health Sciences Center, Oklahoma City, USA
    3   Howard Hughes Medical Institute, Oklahoma City, USA
Further Information

Publication History

Received 19 September 1995

Accepted after resubmission 05 January 1996

Publication Date:
10 July 2018 (online)

 PDF Download  Permissions and Reprints

Summary

Inflammation often is considered a contributing factor to both thrombosis and disseminated intravascular coagulation. The molecular mechanisms that dictate which of these clinical manifestations will result from the inflammatory stimulus remain obscure. Bacterial infection and certain tumors are common initiators of the disseminated intravascular coagulant response. Complement activation resulting from bacterial infection shares with selected tumors the capacity to generate or release membrane particles that lack functional adhesion receptors and hence could circulate to amplify a disseminated intravascular coagulant response. We developed a model of venous thrombosis that resulted in localized thrombus formation without disseminated intravascular coagulation. The model involves infusion of tumor necrosis factor, blockade of protein C and a partial decrease in venous flow caused by ligation of the superficial femoral vein without obstruction of the deep femoral vein. Infusion of phospholipid vesicles into this model resulted in amplification of a localized thrombotic response into a consumptive response.

Seven different groups of animals were studied. The first three groups established the conditions necessary to produce deep vein thrombosis. The second four groups established the conditions necessary to produce disseminated intravascular coagulation. The infusion of phospholipid vesicles plus tumor necrosis factor and anti-protein C antibody resulted in consumption of fibrinogen, the production of thrombin/antithrombin complexes, a fall in platelet count, and venous thrombosis. Without ligation and catheterization phospholipid vesicles failed to produce the consumptive response. We conclude, therefore, that phospholipid vesicles can amplify a local thrombotic response into a consumptive response, and that vesiculation accompanying inflammation is one means by which localized coagulant activity may be amplified to produce disseminated intravascular coagulation.