Hematopoietic cell-derived microparticle tissue factor contributes to fibrin formation during thrombus propagation

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  • Janet Chou
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.
  • Nigel Mackman
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.
  • Glenn Merrill-Skoloff
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.
  • Brian Pedersen
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.
  • Barbara C. Furie
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.
  • Bruce Furie
    From the Center for Hemostasis and Thrombosis Research, Vascular Biology Center, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston MA; and Departments of Immunology and Cell Biology, Scripps Research Institute, La Jolla CA.

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Description

<jats:title>Abstract</jats:title><jats:p>Tissue factor (TF) is expressed on nonvascular cells and cells within the vessel wall and circulates in blood associated with microparticles. Although blood-borne TF accumulates into the developing thrombus during thrombus formation, the contribution of blood-borne TF and vessel wall TF to thrombin generation in vivo following vessel injury is unknown. To determine the source and role of blood-borne microparticle TF, we studied arterial thrombus formation in a living mouse using intravital microscopy. Platelet, TF, and fibrin accumulation in the developing thrombus was compared in wild-type and low TF mice. Compared to wild-type mice, low TF mice formed very small platelet thrombi lacking TF or fibrin. Wild-type and low TF mice received transplants of bone marrow from wild-type and low TF mice. Arterial thrombi in low TF bone marrow/wild-type chimeric mice had decreased size and decreased TF and fibrin levels. Arterial thrombi in wild-type bone marrow/low TF chimeric mice showed decreased platelet thrombus size but normal TF and fibrin levels. This demonstrates that blood-borne TF associated with hematopoietic cell-derived microparticles contributes to thrombus propagation.</jats:p>

Journal

  • Blood

    Blood 104 (10), 3190-3197, 2004-11-15

    American Society of Hematology

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