Circulating tissue factor and microparticles are not increased in patients with deep vein thrombosis

Steppich, Birgit; Hassenpflug, Matthias; Braun, S; Schömig, Kathrin; Beckerath, Olga von; Beckerath, Nicolas von; Eckstein, H.‐H.; Ott, I.

doi:10.1024/0301-1526/a000081

Cited by 16 publications

(12 citation statements)

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“…Several cross sectional studies have reported increased MP procoagulant functional activity [98, 99], while others have shown increased MPs by FCM [90, 99–102]. Still other studies failed to demonstrate an increase in MPs, either using functional assays [103–105] or FCM [106, 107]. Again, these contradictory results are most likely attributable to differences in methodologies and techniques.…”

Section: Phenotypic Vs Functional Assays For Microparticle Analysismentioning

confidence: 99%

Microparticle analysis in disorders of hemostasis and thrombosis

2015

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Microparticles (MPs) are submicron vesicles released from the plasma membrane of eukaryotic cells in response to activation or apoptosis. MPs are known to be involved in numerous biologic processes, including inflammation, the immune response, cancer metastasis, and angiogenesis. Their earliest recognized and most widely accepted role, however, is the ability to promote and support the process of blood coagulation. Consequently, there is ongoing interest in studying MPs in disorders of hemostasis and thrombosis. Both phosphatidylserine (PS) exposure and the presence of tissue factor (TF) in the MP membrane may account for their procoagulant properties, and elevated numbers of MPs in plasma have been reported in numerous prothrombotic conditions. To date, however, there are few data on true causality linking MPs to the genesis of thrombosis. A variety of methodologies have been employed to characterize and quantify MPs, although detection is challenging due to their submicron size. Flow cytometry (FCM) remains the most frequently utilized strategy for MP detection; however, it is associated with significant technological limitations. Additionally, pre-analytical and analytical variables can influence the detection of MPs by FCM, rendering data interpretation difficult. Lack of methodologic standardization in MP analysis by FCM confounds the issue further, although efforts are currently underway to address this limitation. Moving forward, it will be important to address these technical challenges as a scientific community if we are to better understand the role that MPs play in disorders of hemostasis and thrombosis.

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Section: Phenotypic Vs Functional Assays For Microparticle Analysismentioning

confidence: 99%

Microparticle analysis in disorders of hemostasis and thrombosis

2015

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“…42,43 Several, but not all studies, found that either plasma TF-MP concentration or TF-MP procoagulant activity positively correlates with the risk of VTE. 41,[43][44][45][46] An explanation for these inconsistent findings may be that detection of MPs is often inaccurate because of their small size. With regard to the recurrence of VTE, a clearer picture emerges.…”

mentioning

confidence: 99%

Mechanistic View of Risk Factors for Venous Thromboembolism

Reitsma

Versteeg²,

Middeldorp³

2012

ATVB

176

138

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Abstract-Venous thromboembolism is an episodic disease with an annual incidence of 2 to 3/1000 per year that is associated with a high morbidity and mortality. Risk factors for venous thromboembolism come in many guises. They fit into an extended version of Virchow's triad and they tilt the hemostatic balance toward clot formation. This can be achieved by decreasing blood flow and lowering oxygen tension, by activating the endothelium, by activating innate or acquired immune responses, by activating blood platelets, or by increasing the number of platelets and red blood cells or modifying the concentrations of pro-and anticoagulant proteins in the blood. In this narrative review we will discuss the known common risk factors within this pathophysiological framework. (Arterioscler Thromb Vasc Biol. 2012;32:563-568.)Key Words: endothelium Ⅲ platelets Ⅲ pulmonary embolism Ⅲ risk factors Ⅲ Venous thrombosis V enous thromboembolism (VTE) is the third most common vascular disease after myocardial infarction and ischemic stroke. The annual incidence of symptomatic and objectively confirmed VTE, the collective term generally used for deep venous thrombosis, pulmonary embolism or both, is 2 to 3 per thousand inhabitants. 1 The incidence varies strongly with age from 0.1 in adolescence to 8 per 1000 in those above the age of 80 years. 1 The mechanistic framework that helps to understand and group the causes of VTE is an extension of the triad of Virchow, which postulates that thrombosis is caused by changes in (1) blood flow, (2) the state of the vessel wall, and/or (3) the composition of blood. 2 In a more current reductionist's view, stasis and low oxygen tension, activation of the endothelium, activation of innate (involving monocytes and granulocytes) and acquired immunity, activation of blood platelets, the concentration and nature of microparticles (MPs), and the individual concentrations of pro-and anticoagulant proteins all claim a role (see the Figure). In addition, red blood cells are present in venous clots. We will use this reductionist's framework to group and discuss the known common risk factors for VTE that are summarized in Table. Blood Flow, Oxygen Tension, and Endothelial Activation Prolonged stasis in a vein, in particular in deepest parts of the pocket of a venous valve, causes lowered oxygen tension. 3 This oxidative stress will lead to the upregulation of multiple stress-response genes including hypoxia inducible factor 1-alpha, P-selectin (CD62), and other adhesion receptors. 4,5 The resulting proinflammatory state of the endothelium supports the local recruitment of monocytes, granulocytes, platelets, and MPs. The recruitment of these actors and their activation may lead to the local exposure of tissue factor (TF), 6 thus initiating the extrinsic pathway of coagulation. When damaged granulocytes start releasing neutrophil extracellular traps, DNA, and RNA, factor XII may become activated thus triggering the intrinsic pathway of coagulation and further facilitating the formation of a thrombus. 7,8 T...

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“…Studies evaluating the role of MP-TF in the pathophysiology of VTE in the general (non-cancer) population are scarce and so far no study specifically addressed its association with recurrent VTE. Two previous studies reported that MP-TF activity was not increased in patients with a first manifestation of acute VTE compared to control patients [ 13 , 32 ]. In contrast, Ye et al did observe higher monocyte-derived MP-TF levels and MP-TF activity in patients with an acute episode of first or recurrent DVT compared with healthy controls although this study comprised only 50 patients [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Association between micro particle-tissue factor activity, factor VIII activity and recurrent VTE in patients with acute pulmonary embolism

Kooiman

Exter

Kilicsoy

et al. 2015

J Thromb Thrombolysis

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Studies on the association between microparticle expressing tissue factor (MP-TF) activity, FVIII activity (FVIII:C) and recurrent VTE yielded inconclusive results. We studied these associations in patients diagnosed with acute pulmonary embolism. Plasma levels of MP-TF and FVIII activity were measured in 277 patients with a first and 72 patients with a recurrent VTE. All patients were categorized based on the quintiles of MP-TF and FVIII activity in those with a single VTE. For both markers, odds ratios (ORs) for recurrent VTE were computed using patients in the lowest quintile as a reference group. No association was observed between MP-TF activity and recurrent VTE, with an OR of 1.4 (95 % CI 0.7–2.9) in the highest quintile of MP-TF activity. Compared with the reference group, patients in the highest quintile of FVIII:C were at increased risk of recurrent VTE, OR 4.2 (95 % CI 1.4–12.2). MP-TF activity was not associated with recurrent VTE whereas high FVIII:C levels were associated with a 4-fold increased risk of VTE recurrence. Future prospective studies are necessary to explore the potential of FVIII:C as a tool for risk stratification, either by itself or in combination with other pro-thrombotic markers.

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Circulating tissue factor and microparticles are not increased in patients with deep vein thrombosis

Abstract: Circulating TF and microparticles are not elevated in deep venous thrombosis. The increase in IL-6, IL-8 and F1 + 2 during thrombosis was not proportional to the extent or predisposing risk factors.

Cited by 16 publications

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Microparticle analysis in disorders of hemostasis and thrombosis

Microparticle analysis in disorders of hemostasis and thrombosis

Mechanistic View of Risk Factors for Venous Thromboembolism

Association between micro particle-tissue factor activity, factor VIII activity and recurrent VTE in patients with acute pulmonary embolism

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