Tissue Factor and Tissue Factor Pathway Inhibitor as Key Regulators of Global Hemostasis: Measurement of Their Levels in Coagulation Assays

Raj S Kasthuri; Sam L Glover; Jeremiah Boles; Nigel Mackman

doi:10.1055/s-0030-1265293

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2010; 36(7): 764-771
DOI: 10.1055/s-0030-1265293

Tissue Factor and Tissue Factor Pathway Inhibitor as Key Regulators of Global Hemostasis: Measurement of Their Levels in Coagulation Assays

Raj S. Kasthuri¹ , Sam L. Glover¹ , Jeremiah Boles¹ , Nigel Mackman¹

¹Division of Hematology and Oncology, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Abstract

ABSTRACT

The tissue factor (TF)/factor (F)VIIa complex is the primary initiator of coagulation in vivo. Tissue factor pathway inhibitor (TFPI) is the physiological inhibitor of the TF/FVIIa complex. Deficiencies of either TF or TFPI have not been reported in humans, and a complete absence of either of these two proteins in mice is embryonically lethal. To maintain normal hemostasis, levels of TF and TFPI need to be balanced. Increased levels of TF can overwhelm the inhibitory capacity of TFPI, resulting in thrombosis. Decreased levels of TF are associated with bleeding. Global assays of coagulation are defined as tests capable of evaluating all components of the clotting cascade that are present in plasma. In these tests the thrombogenic surface is either provided by platelets or exogenous phospholipids. Clotting assays currently used in clinical practice are not designed to measure endogenous levels of TF and TFPI. Therefore, there is a need to develop sensitive and specific assays for measuring levels of functional TF and TFPI in whole blood and plasma. These assays could be useful in patient management in many scenarios.

KEYWORDS

Tissue factor - tissue factor pathway inhibitor - thrombosis - thromboelastography

Full Text

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Nigel MackmanPh.D.

UNC Chapel Hill, 917 Mary Ellen Jones Building

CB7035, Chapel Hill, NC 27599

Email: nmackman@med.unc.edu