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IMPACT OF TISSUE FACTOR-BEARING MICROPARTICLES DERIVED FROM TUMOR CELLS ON COAGULATION ACTIVATION

Abstract number: P-S-010

Davila1 M., Amirkhosravi1 A., Coll1 E., Robles1 L., Baker2 C.H., Abdelrahim2 M., Colon2 J., Francis1 J.

11Institute of Translational Research, Florida Hospital 22M. D. Anderson Cancer Center Orlando, Orlando Regional Health System, Orlando, United States

How-to-cite Davila M, Amirkhosravi A, Coll E, Robles L, Baker CH, Abdelrahim M, Colon J, Francis J. IMPACT OF TISSUE FACTOR-BEARING MICROPARTICLES DERIVED FROM TUMOR CELLS ON COAGULATION ACTIVATION. J Thromb Haemost 2007; 5 Supplement 2: P-S-010

Abstract

Introduction: Tissue factor (TF)-bearing microparticles (MPs) from different origins are thought to be involved in the pathogenesis of cancer-associated thrombosis. However, the role of circulating tumor cell-derived MPs is not clearly understood. Here we demonstrate TF-dependent procoagulant activity (PCA) associated with certain tumor cell-derived MPs.

Methods: MPs from human TF-expressing cancer cells were generated in vitro and enumerated by flow cytometry. TF antigen and MP-associated PCA were measured by ELISA and clotting or fluorogenic thrombin generation assays, respectively. In vivo, human TF antigen and PCA were measured in cell-free plasmas of mice previously injected with in vitro-generated MPs or cell-free plasmas from nude mice bearing orthotopically-implanted human tumors.

Results: MPs generated in vitro from as few as 200 cells exhibited high PCA. This activity was exclusively dependent on MP-associated TF. Appreciable levels of human TF antigen and activity were detected in mouse cell-free plasmas no longer than 30 minutes after MP injection, suggesting a rapid clearance of circulating MPs in vivo. Injection of MPs was associated with acute thrombocytopenia and clear signs of thrombosis, which were inhibited by pre-heparinization. Interestingly, low levels of inactive human TF were detected in cell-free plasmas from mice bearing orthotopically-implanted tumors, and not in those from non-tumor bearing controls.

Conclusions: MP-associated TF is released readily from tumor cells in vitro and can significantly activate coagulation, in vitro and in vivo. However, the prothrombotic activity of circulating MPs derived from tumors in vivo requires further investigation.

To cite this abstract use the following format:

Journal of Thrombosis and Haemostasis 2007; Volume 5, Supplement 2: abstract number

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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