The presence and release of tissue factor from human platelets

Abstract

Tissue factor (TF) is a transmembrane receptor for FVII that triggers blood coagulation. It is not normally exposed to circulating blood, but may be produced by endothelium and monocytes under pathological conditions. Platelets take up TF-positive microparticles from leukocytes and TF appears on platelets adhering to leukocytes following collagen stimulation of blood. However, the presence of TF in circulating platelets has not been directly demonstrated. In this study, flow cytometric analysis of washed platelets from five healthy adult volunteers demonstrated TF-antigen on both resting platelets and platelets activated by thrombin (0.1 U/ml), collagen (5 microg/ml) or ADP (5 microM). TF released by platelets was demonstrated in the supernatants of non-activated and activated washed platelets by dot-immunoblotting and Western blotting. The amount of TF released from non-activated and activated platelets was quantitated using an enzyme-linked immunosorbent assay (ELISA). Washed non-activated and platelets activated by thrombin, collagen or ADP released 27-35 pg TF per mg protein. TF associated with the platelet surface was biologically inactive, although released TF was functionally active as determined by a two-stage factor X activation assay. We conclude that platelets contain an inactive form of TF that may develop functional activity following its release. However, the role of platelet TF in health and disease remains to be determined.

Non-overt disseminated intravascular coagulation in patients during treatment with antithymocyte globulin for unrelated allogeneic hematopoietic stem cell transplantation

“…Potential sources of active tissue factor in this pathological condition could be cytokine-activated peripheral blood monocytes, 26,27 endothelial cells [28][29][30] or platelets. 31 Our finding of increased levels of sTM as a marker of endothelial activity and inury 30 indicates a cytokinetriggered disturbance of the endothelium, which may be an important factor in the induction of nonovert DIC because of ATG treatment. The generation and presence of microparticles resulting from the interaction of monocytes and platelets seems to be another important mediator of procoagulant activity.…”

No evidence for tissue factor on platelets

“…This paradigm has been challenged by studies suggesting that platelets express active TF after de novo synthesis, 2,3 transfer from monocytes, 4 or release from ␣-granules. 5 In other studies, 6,7 however, the existence of platelet TF could not be demonstrated.…”

“…5 The availability of vast sequence information on BCPs makes it ideal to explore data mining tools to identify their conserved residues. Consensus sequence represents the result of a multiple sequence…”

Tissue Factor and Cardiovascular Disease: Quo Vadis?

“…MPs need to be distinguished from exosomes, which originate from intracellular compartments, are smaller (<0.1 μm), and differ in their composition. The main source of circulating MPs 63,64 are monocytes and platelets, but other vascular cells like ECs, 65 VSMCs, 66 and eosinophils 50 also release TF containing MPs. Levels of TF-containing MP are elevated in patients with cardiovascular risk factors such as diabetes, hypertension, obesity, and dyslipidemia, but their specific role is still debated.…”