Detection of tissue factor in platelets: why is it so troublesome?

Østerud, Bjarne; Bouchard, Beth A.

doi:10.1080/09537104.2019.1624708

Cited by 17 publications

(24 citation statements)

References 61 publications

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“…Here, we describe that TF-negative platelet-derived EVs enhance FVIIa-dependent FXa production on undamaged fibroblasts despite having virtual no ability to support FXa generation alone. The platelet-EVs and liposomes used in our experiments did not support TF activity [43] but had high levels of externalised PS and PE. The enhanced fibroblast-dependent FX activation was inhibited by annexin V, demonstrating that PS or PE were important for the effect but in this case the PS/PE were from a source that was exogenous to the undamaged fibroblasts.…”

Section: Plos Onementioning

confidence: 85%

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

et al. 2020

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Tissue factor (TF) is critical for the activation of blood coagulation. TF function is regulated by the amount of externalised phosphatidylserine (PS) and phosphatidylethanolamine (PE) on the surface of the cell in which it is expressed. We investigated the role PS and PE in fibroblast TF function. Fibroblasts expressed 6-9 x 10 4 TF molecules/cell but had low specific activity for FXa generation. We confirmed that this was associated with minimal externalized PS and PE and characterised for the first time the molecular species of PS/PE demonstrating that these differed from those found in platelets. Mechanical damage of fibroblasts, used to simulate vascular injury, increased externalized PS/PE and led to a 7-fold increase in FXa generation that was inhibited by annexin V and an anti-TF antibody. Platelet-derived extracellular vesicles (EVs), that did not express TF, supported minimal FVIIadependent FXa generation but substantially increased fibroblast TF activity. This enhancement in fibroblast TF activity could also be achieved using synthetic liposomes comprising 10% PS without TF. In conclusion, despite high levels of surface TF expression, healthy fibroblasts express low levels of external-facing PS and PE limiting their ability to generate FXa. Addition of platelet-derived TF-negative EVs or artificial liposomes enhanced fibroblast TF activity in a PS dependent manner. These findings contribute information about the mechanisms that control TF function in the fibroblast membrane.

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Section: Plos Onementioning

confidence: 85%

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

et al. 2020

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“…However, this assumption is the subject of a controversial discussion, as other, flow cytometric based, investigations indicated that no TF would be expressed on activated platelets ( 117 ). Only recently has the debate whether platelets can release TF by themselves been portrayed elsewhere in detail ( 118 , 119 ). Regardless of this debate, platelet CD40L expression has been reported to induce monocyte expression of tissue factor, which in turn activates the extrinsic coagulation cascade ( 120 ); thus, emphasizing the intimate interaction between platelets, immune cells and the plasmatic coagulation system.…”

Section: Platelet Receptors and Interactions In The Context Of Thrombmentioning

confidence: 99%

Platelets as Mediators of Neuroinflammation and Thrombosis

et al. 2020

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Beyond platelets function in hemostasis, there is emerging evidence to suggest that platelets contribute crucially to inflammation and immune responses. Therefore, considering the detrimental role of inflammatory conditions in severe neurological disorders such as multiple sclerosis or stroke, this review outlines platelets involvement in neuroinflammation. For this, distinct mechanisms of platelet-mediated thrombosis and inflammation are portrayed, focusing on the interaction of platelet receptors with other immune cells as well as brain endothelial cells. Furthermore, we draw attention to the intimate interplay between platelets and the complement system as well as between platelets and plasmatic coagulation factors in the course of neuroinflammation. Following the thorough exposition of preclinical approaches which aim at ameliorating disease severity after inducing experimental autoimmune encephalomyelitis (a counterpart of multiple sclerosis in mice) or brain ischemia-reperfusion injury, the clinical relevance of platelet-mediated neuroinflammation is addressed. Thus, current as well as future propitious translational and clinical strategies for the treatment of neuro-inflammatory diseases by affecting platelet function are illustrated, emphasizing that targeting platelet-mediated neuroinflammation could become an efficient adjunct therapy to mitigate disease severity of multiple sclerosis or stroke associated brain injury.

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“…64 Both the antigen and the procoagulant activity of TF have been detected on platelets, 8,65 although Østerud and Olsen and Bouchard et al contradicted these findings, [66][67][68][69] likely due to methodological differences. 70,71 Platelet granular contents have been shown to influence TG. An illustrating example was found in FV-deficient patients who have no detectable plasma FV and PPP-TG, in which the absence of life-threatening bleedings could be explained by FV contribution from platelets leading to sufficient PRP-TG.…”

Section: Influence Of Platelet Granule Secretion On Prp-tgmentioning

confidence: 99%

Added Value of Blood Cells in Thrombin Generation Testing

et al. 2021

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The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form thrombin, has improved our knowledge of the coagulation system and shows promising utility in coagulation management. Although plasma TG gives comprehensive insights in the function of pro- and anticoagulation drivers, it does not measure the role of blood cells in TG. In this literature review, we discuss currently available continuous TG tests that can reflect the involvement of blood cells in coagulation, in particular the fluorogenic assays that allow continuous measurement in platelet rich plasma and whole blood. We also provide an overview about the influence of blood cells on blood coagulation, with emphasis on the direct influence of blood cells on TG. Platelets accelerate the initiation and velocity of thrombin generation by phosphatidylserine exposure, granule content release and surface receptor interaction with coagulation proteins. Erythrocytes are also major providers of phosphatidylserine and erythrocyte membranes trigger contact activation. Furthermore, leukocytes and cancer cells may be important players in cell-mediated coagulation, because under certain conditions, they express tissue factor, release procoagulant components and can induce platelet activation. We argue that testing TG in the presence of blood cells may be useful to distinguish blood cells-related coagulation disorders. However, it should also be noted that these blood cells-dependent TG assays are not clinically validated. Further standardization and validation studies are needed to explore their clinical usefulness.

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Detection of tissue factor in platelets: why is it so troublesome?

Cited by 17 publications

References 61 publications

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

Platelets as Mediators of Neuroinflammation and Thrombosis

Added Value of Blood Cells in Thrombin Generation Testing

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