Introduction Elevated levels of tissue factor positive (TF+) microparticles (MPs) are observed in plasma from a variety of patients with an increased risk of thrombosis. We and others have described the measurement of TF activity in MPs isolated from plasma. The aim of this study was to investigate the effects of pre-analytical and analytical variables on TF activity of MPs isolated from blood of healthy volunteers treated ex vivo with or without bacterial lipopolysaccharide. Materials and Methods We evaluated the following parameters: use of different centrifugation speeds to isolate the MPs; comparison of TF activity of MPs isolated from platelet poor plasma versus platelet free plasma; effect of freeze/thaw on MP TF activity; and comparison of the MP TF activity assay with the measurement of TF protein by ELISA or flow cytometry. Results MPs prepared from platelet poor plasma by centrifugation at 20,000 × g or 100,000 × g for 15 minutes had similar levels of TF activity. However, significantly less TF activity was found in MPs isolated from platelet free plasma compared with platelet poor plasma. Interestingly, freeze/thawing of the plasma showed donor to donor variation in MP TF activity, with a moderate increase in some individuals. Conclusion TF+ MPs can be quantitatively isolated from platelet poor or platelet free plasma by centrifugation at 20,000 × g for 15 minutes. Measurement of MP TF activity in plasma can be used to detect a prothrombotic state in patients with various diseases.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. However, the mechanisms by which clots are formed in the deep veins have not been determined. Tissue factor (TF) is the primary initiator of the coagulation cascade and is essential for hemostasis. Under pathological conditions, TF is released into the circulation on small-membrane vesicles termed microparticles (MPs). Recent studies suggest that elevated levels of MPTF may trigger thrombosis. This review provides an overview of the role of TF in VTE.

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The combination of RIG + GEM failed to demonstrate an improvement in survival or response compared with GEM in patients with metastatic pancreatic adenocarcinoma. Rigosertib showed a similar safety profile to that seen in previous trials using the IV formulation.

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. KeywordsTissue factor; tissue factor pathway inhibitor; thrombosis; thromboelastography Significant progress has been made over the last decade in understanding the many complex interactions involved in the process of blood coagulation. The care ofpatientswithdisordersofthrombosisisalsoentering a new era with many new treatment modalities in varying stages of development, including new oral anticoagulants, aptamers targeted against coagulation factors and the use of natural anticoagulants. 1,2 In addition, hemophilia patients with inhibitors can be treated with recombinant factor (F)VIIa, and possibly in the future with drugs that interfere with the activity of anticoagulant proteins, such as tissue factor pathway inhibitor (TFPI). In keeping with these advances, ongoing efforts are aimed at improving our ability to identify at-risk patients, such as those at risk for bleeding or those at risk for venous thromboembolism (VTE). Successful risk stratification has the advantage of both improving outcomes and decreasing the number of patients exposed to unnecessary interventions. This review briefly discusses the role of tissue factor (TF) and TFPI in hemostasis and the measurement of endogenous levels of these proteins in whole blood and plasma. TF is constitutively expressed by perivascular cells, which ensures rapid activation of coagulation at sites of vascular damage. TF is also constitutively expressed in the brain, heart, lung, kidney, and placenta, where it provides additional tissue-specific hemostatic protection to these vital organs. The importance of TF in these organs is underscored by the development of hemorrhages in the brain, lung, and heart in mice expressing low levels of TF or FVIIa. A genetic deficiency of TF has not been described in humans, and a complete absence of TF is embryonically lethal in mice. 4 TF expression can also be induced in a variety of cells, such as monocyt...