Role of Tissue Factor in Venous Thrombosis

Manly, David A.; Boles, Jeremiah; Mackman, Nigel

doi:10.1146/annurev-physiol-042210-121137

Cited by 110 publications

(70 citation statements)

References 85 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,12,[25][26][27][28] The most common site for the development of venous thrombi is valve pockets. 26,27,[29][30][31][32] A number of different mouse models have been used to study thrombosis. 33 In general, animal models of thrombosis that do not produce extensive damage to the vessel wall are better models of venous thrombosis than models that expose vessel wall TF.…”

Section: Development Of a Venous Thrombusmentioning

confidence: 99%

Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients

Geddings

Mackman

2013

Blood

Self Cite

284

238

View full text Add to dashboard Cite

Patients with cancer have an increased risk for venous thrombosis. Interestingly, different cancer types have different rates of thrombosis, with pancreatic cancer having one of the highest rates. However, the mechanisms responsible for the increase in venous thrombosis in patients with cancer are not understood. Tissue factor (TF) is a transmembrane receptor and primary initiator of blood coagulation. Tumor cells express TF and spontaneously release TF-positive microparticles (MPs) into the blood. MPs are small membrane vesicles that are highly procoagulant. It has been proposed that these circulating tumor-derived, TF-positive MPs may explain the increased rates of venous thrombosis seen in patients with cancer. In animal models, increased levels of tumor-derived, TF-positive MPs are associated with activation of coagulation. Moreover, these MPs bind to sites of vascular injury and enhance thrombosis. We and others have found that patients with cancer have elevated levels of circulating TF-positive MPs. These MPs are derived from tumors because they express tumor markers and are decreased by tumor resection. Importantly, several studies have shown that increased levels of TF-positive MPs correlate with venous thrombosis in patients with cancer. Taken together, these results suggest that TF-positive MPs may be a useful biomarker to identify patients with cancer who are at high risk for thrombosis.

show abstract

Section: Development Of a Venous Thrombusmentioning

confidence: 99%

Tumor-derived tissue factor–positive microparticles and venous thrombosis in cancer patients

Geddings

Mackman

2013

Blood

Self Cite

284

238

View full text Add to dashboard Cite

show abstract

“…It is a serious cause of mortality and morbidity, especially in older persons. A preponderance of human VT that is not associated with cancer, sepsis, or other systemic challenges is associated with prolonged immobility and occurs in the pockets behind (downstream) of venous valves in the legs or pelvis (1)(2)(3)(4)(5). Venous valves normally make possible the one-way flow of blood toward the heart driven by contractions of leg muscles.…”

Section: Introductionmentioning

confidence: 99%

A Mathematical Model of Venous Thrombosis Initiation

Elizondo

Fogelson

2016

Biophysical Journal

View full text Add to dashboard Cite

We present a mathematical model for the initiation of venous thrombosis (VT) due to slow flow and the consequent activation of the endothelial cells (ECs) lining the vein, in the absence of overt mechanical disruption of the EC layer. It includes all reactions of the tissue factor (TF) pathway of coagulation through fibrin formation, incorporates the accumulation of blood cells on activated ECs, accounts for the flow-mediated delivery and removal of coagulation proteins and blood cells from the locus of the reactions, and accounts for the activity of major inhibitors including heparan-sulfate-accelerated antithrombin and activated protein C. The model reveals that the occurrence of robust thrombin generation (a thrombin burst) depends in a threshold manner on the density of TF on the activated ECs and on the concentration of thrombomodulin and the degree of heparan-sulfate accelerated antithrombin activity on those cells. Small changes in any of these in appropriate narrow ranges switches the response between ''no burst'' and ''burst.'' The model predicts synergies among the inhibitors, both in terms of each inhibitor's multiple targets, and in terms of interactions between the different inhibitors. The model strongly suggests that the rate and extent of accumulation of activated monocytes, platelets, and MPs that can support the coagulation reactions has a powerful influence on whether a thrombin burst occurs and the thrombin response when it does. The slow rate of accumulation of cells supporting coagulation is one reason that the progress of VT is so much slower than that of arterial thrombosis initiated by subendothelial exposure.

show abstract

“…2 TF, therefore, plays a central role in diverse pathologic processes including atherosclerosis, thrombosis, sepsis, and tumor growth. [3][4][5][6][7] Monocytes and macrophages are the predominant source of TF in myeloid cells. [8][9][10] TF expression in these cells is low to undetectable basally, but is induced transcriptionally by inflammatory mediators, such as bacterial lipopolysaccharide (LPS).…”

Section: Introductionmentioning

confidence: 99%