A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s Syndrome

Khan, Emon; Ambrose, Nicola; Ahnström, Josefin; Kiprianos, Allan; Stanford, Miles; Eleftheriou, D; Brogan, Paul A.; Mason, Justin C.; Johns, Michael; Laffan, Michael; Haskard, Dorian O.

doi:10.1038/srep38104

Cited by 20 publications

(18 citation statements)

References 56 publications

(59 reference statements)

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“…The expression of Tissue Factor (TF) by microparticles was experimentally shown to contribute to the development of thrombosis (157). Using flow cytometry, it has been demonstrated that the total number of plasma microparticles was elevated in BD patients compared to healthy controls, as were microparticles characterized by TF and Tissue Factor Pathway Inhibitor (TFPI) (157).…”

Section: Small Vessel Vasculitismentioning

confidence: 99%

Biomarkers in Vasculitides of the Nervous System

et al. 2019

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Besides being affected by the rare and severe primary angiitis of the central nervous system (PACNS) the nervous system is also affected by primary systemic vasculitides (PSV). In contrast to PACNS, PSV affect not only the central but also the peripheral nervous system, resulting in a large array of potential symptoms. Given the high burden of disease, difficulties in distinguishing between differential diagnoses, and incomplete pathophysiological insights, there is an urgent need for additional precise diagnostic tools to enable an earlier diagnosis and initiation of effective treatments. Methods available to date, such as inflammatory markers, antibodies, cerebrospinal fluid (CSF) analysis, imaging, and biopsy, turn out to be insufficient to meet all current challenges. We highlight the use of biomarkers as an approach to extend current knowledge and, ultimately, improve patient management. Biomarkers are considered to be useful for disease diagnosis and monitoring, for predicting response to treatment, and for prognosis in clinical practice, as well as for establishing outcome parameters in clinical trials. In this article, we review the recent literature on biomarkers which have been applied in the context of different types of nervous system vasculitides including PACNS, giant-cell arteritis, Takayasu's arteritis, polyarteritis nodosa, ANCA (anti-neutrophil cytoplasm antibody)-associated vasculitides, cryoglobulinemic vasculitis, IgA vasculitis, and Behçet's disease. Overall, the majority of biomarkers is not specific for vasculitides of the nervous system.

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Section: Small Vessel Vasculitismentioning

confidence: 99%

Biomarkers in Vasculitides of the Nervous System

et al. 2019

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“…The TF pathway plays a significant role in several bleeding and clotting disorders. 9,10 Tissue factor pathway inhibitor (TFPI) is the primary inhibitor of TF-induced coagulation in vivo. And TFPI cannot only inhibit activated factor Xa directly, but also inhibit VIIa/TF activity.…”

Section: Tissue Factor and Tissue Factor Pathway Inhibitormentioning

confidence: 99%

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Zhang

Pang

et al. 2019

Pulm. circ.

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Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition characterized with chronic organized thrombi that obstruct the pulmonary vessels, leading to pulmonary hypertension (PH) and ultimately right heart failure. Although CTEPH is the only form of PH that can be cured with surgical intervention, not all patients with CTEPH will be deemed operable. Some CTEPH patients still have a poor prognosis. Therefore, the determination of diagnostic and prognostic biomarkers of CTEPH is of great importance for the early intervention to improve prognosis of patients with CTEPH. Several markers related to multiple mechanisms of CTEPH have been recently identified as circulating diagnostic and prognostic biomarkers in these patients. However, the existing literature review of biomarkers of CTEPH is relatively sparse. In this article, we review recent advances in circulating biomarkers of CTEPH and describe future applications of these biomarkers in the management of CTEPH.

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“…Indeed, three main mechanisms have been described so far by which neutrophils can contribute to thrombo-inflammation in either inflammatory or neoplastic conditions: (1) by the release of neutrophil extracellular traps (NETs); (2) by the formation of neutrophil-derived microparticles; and (3) via the hyperactivation of inflammasome. Interestingly, in BS the contribution of microparticles and inflammasome has been already suggested (9, 10), while the role of NETs is still under investigation.…”

Section: Introductionmentioning

confidence: 99%

Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

et al. 2019

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Behçet's syndrome (BS) is a systemic vasculitis, clinically characterized by different organ involvement and often complicated by thrombosis which occurs in vessels of all sizes. Thrombosis is more frequent in male patients with active disease and represents an important cause of morbidity and mortality. Neutrophil involvement in BS has been repeatedly suggested in the last few years. Indeed, neutrophils have been shown to be hyperactivated in BS patients, probably with a HLAB51 related contribution, and represent the main cells infiltrating not only oral and genital ulcers or erythema nodosum, but also other sites. Besides being deputed to host defense against micro-organisms, neutrophils display fundamental roles both in inflammation and tissue damage becoming inappropriately activated by cytokines, chemokines and autoantibodies and subsequently producing large amounts of superoxide anion ( ) via NADPH oxidase (NOX2). The strict relationship between inflammation and hemostasis has been already demonstrated. Indeed, inflammation and immune-mediated disorders increase the risk of thrombosis, but the pathways that link these processes have not been completely elucidated. In this regard, we recently demonstrated, in a large population of BS patients, a new neutrophil-dependent pathogenetic mechanism of thrombosis. In particular, it was shown that neutrophils, mainly through NADPH oxidase, produce excessive amounts of reactive oxygen species (ROS), which are able to markedly modify the secondary structure of fibrinogen and hence the overall architecture of the fibrin clot that becomes less susceptible to plasmin-induced lysis. These data point out that BS represents “ per se ” a model of inflammation-induced thrombosis and suggest that neutrophils specifically contribute to thrombo-inflammation in this rare disease. In particular, it is suggested that an alteration in fibrinogen structure and function are associated with enhanced ROS production via neutrophil NADPH oxidase. Altogether, these findings improve our understanding of the intricate pathogenetic mechanisms of thrombo-inflammation and may indicate potential new therapeutic targets.

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A low balance between microparticles expressing tissue factor pathway inhibitor and tissue factor is associated with thrombosis in Behçet’s Syndrome

Cited by 20 publications

References 56 publications

Biomarkers in Vasculitides of the Nervous System

Biomarkers in Vasculitides of the Nervous System

Circulating biomarkers in chronic thromboembolic pulmonary hypertension

Behçet's Syndrome as a Model of Thrombo-Inflammation: The Role of Neutrophils

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