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Tissue factor (TF) is an integral membrane protein that is essential to life. It is a component of the factor VIIa-TF complex enzyme and plays a primary role in both normal hemostasis and thrombosis. With a vascular injury, TF becomes exposed to blood and binds plasma factor VIIa, and the resulting complex initiates a series of enzymatic reactions leading to clot formation and vascular sealing. Many cells, both healthy, and tumor cells, produce detectable amounts of TF, especially when they are stimulated by various agents. Despite the relative simplicity and small size of TF, there are numerous contradictory reports about the synthesis and presentation of TF on blood cells and circulation in normal blood either on microparticles or as a soluble protein. Another subject of controversy is related to the structure/function of TF. It has been almost commonly accepted that cell-surface-associated TF has low (if any) activity, that is, is "encrypted" and requires specific conditions/reagents to become active, that is, "decrypted." However there is a lack of agreement related to the mechanism and processes leading to alterations in TF function. In this paper TF structure, presentation, and function, and controversies concerning these features are discussed. [ABSTRACT FROM AUTHOR]

Abstract: Tissue factor (TF) is the major physiological initiator of blood coagulation. It exists as an integral membrane protein that upon injury to the blood vessel becomes exposed to the blood stream and initiates a series of enzymatic reactions that cause blood to clot. TF is also found within circulating blood cells, requiring specific signaling events to promote its expression. In this review we will discuss current controversies concerning the structure–activity relationships of TF and contributions of TF to the hemostatic process, the potential roles of intravascular TF, including non-cell-bound TF and cell-expressed TF and the overall relationship between TF function and hemorrhage control. [Copyright &y& Elsevier]

Introduction: An elevated procoagulant activity observed in trauma patients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of trauma patient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients.Methods: Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa.Results: Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals.Conclusions: For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range. [ABSTRACT FROM AUTHOR]