Myeloid cell tissue factor does not contribute to venous thrombogenesis in an electrolytic injury model

Abstract

Introduction Tissue factor (TF) is a potent initiator of the extrinsic coagulation cascade. The role and source of TF in venous thrombotic disease is not clearly defined. Our study objective was to identify the contribution of myeloid cell TF to venous thrombogenesis in mice. Materials and Methods The mouse electrolytic inferior vena cava model was used to induce thrombosis. The following groups of mice were used (1) TFflox/floxLysMCre+ mice that have reduced TF expression in myeloid cells, (2) TFflox/floxLysMCre- littermate controls, (3) Wild type mice given a monoclonal anti-mouse TF antibody (1H1) to inhibit TF activity, and (4) Wild type mice given rat IgG. Evaluations at baseline, day 2, and day 6 post thrombosis included thrombus weight, vein wall inflammatory cell migration, vein wall TF mRNA, and plasma D-dimer levels. Results Inhibition of TF significantly decreased thrombus weight 2 days post venous thrombosis. In contrast, TFflox/floxLysMCre+ had no change in thrombus weight when compared to littermate controls. The absence of myeloid cell TF did not affect infiltration of neutrophils or monocytes into the vein wall. TF mRNA expression in the vein wall decreased at 2 days but then returned to baseline levels by 6 days post thrombosis. D-dimer levels peaked at 2 days post thrombosis in mice with or without myeloid cell TF. Conclusions TF is important in the formation of venous thrombi in the macrovasculature. However, TF expression by myeloid cells does not significantly contribute to venous thrombogenesis in this model.

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

“…Studies with healthy mice have shown that leukocyte TF contributes to thrombosis in the inferior vena cava (IVC) stenosis model, whereas vessel wall TF drives thrombosis in the IVC ligation and electrolytic injury models. [34][35][36][37][38] In small vessels, thrombosis has been shown to be dependent on TF expression by neutrophils, hematopoietic cell-derived TF-positive MPs, and vessel wall TF.…”

Model‐dependent contributions of FXII and FXI to venous thrombosis in mice

“…28 Indeed, vessel wall TF, but not myeloid cell TF, has been shown to drive thrombosis in the IVC stasis model, whereas myeloid cell TF contributes to thrombosis in the IVC stenosis model. 17,28,29 It is, therefore, not surprising that a role for FXII and FXI cannot be detected in this model. Moreover, it has previously been shown that the IVC stasis model is insensitive to neutrophil depletion, platelet depletion, or inhibition of platelet activation.…”

“…The cauterization of back branches and the full ligation of the IVC in this model likely exposes significant amounts of subendothelial TF that may trigger thrombosis 28 . Indeed, vessel wall TF, but not myeloid cell TF, has been shown to drive thrombosis in the IVC stasis model, whereas myeloid cell TF contributes to thrombosis in the IVC stenosis model 17,28,29 . It is, therefore, not surprising that a role for FXII and FXI cannot be detected in this model.…”