Activation of the tissue factor pathway of blood coagulation in patients with chronic urticaria

Asero, Riccardo; Tedeschi, A.; Coppola, R.; Griffini, Samantha; Paparella, Paolo; Riboldi, Piersandro; Marzano, Angelo Valerio; Fanoni, Daniele; Cugno, Massimo

doi:10.1016/j.jaci.2006.08.043

Cited by 166 publications

(180 citation statements)

References 32 publications

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“…In addition to that, thrombin can cause degranulation of MC via PAR-1 and may increase vascular permeability by a direct effect on endothelial cells (34,35,41). The available data support the role of eosinophils as a source of TF and subsequent activation of the coagulation cascade in CU pathogenesis (22,38). Moreover, TF promotes transendothelial migration of eosinophils (Fig.…”

Section: Role Of Eosinophils Tissue Factor and Thrombinmentioning

confidence: 78%

“…In contrast, the activation of coagulation in patients with other skin diseases such as BP is associated with an increased thrombotic risk (9,88). Chronic urticaria is frequently characterized by the presence of elevated levels of plasma markers of thrombin generation and fibrinolysis during severe exacerbations of the disease (37,38,47), which can be due to the expression of TF by activated eosinophils (22). The activation of coagulation and fibrinolysis decreases till complete normalization during remission (47,89).…”

Section: Discussionmentioning

confidence: 99%

“…Asero et al (37) first observed elevated plasma levels of prothrombin fragment F1 + 2 which were related to urticaria severity, suggesting that the severity of the disease is paralleled by the amount of thrombin generated. Thrombin generation was demonstrated to be associated with the activation of the extrinsic (tissue factor) pathway because, in CU patients, increased plasma levels of activated factor VII (FVIIa) were observed, whereas no activation of factor XII was seen (38). These data are in line with the early observations by Bork et al (46), who found a reduction of factor VII associated with an increase of factor XII in ten patients with CU, indicating an activation and subsequent consumption of factor VII but not of factor XII.…”

Section: Coagulation Biomarkers In Chronic Urticariamentioning

confidence: 99%

See 2 more Smart Citations

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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Chronic urticaria (CU) is a widespread skin disease, characterized by the recurrence of transient wheals and itch for more than 6 weeks. Besides autoimmune mechanisms, coagulation factors, in particular tissue factor and thrombin, might also participate in the disease pathophysiology. Tissue factor expressed by eosinophils can induce activation of blood coagulation generating thrombin which in turn can increase vascular permeability both directly, acting on endothelial cells, and indirectly, inducing degranulation of mast cells with release of histamine, as demonstrated in experimental models. D-dimer, a fibrin degradation product, generated following activation of the coagulation cascade and fibrinolysis, has been found to be increased during urticaria exacerbations; moreover, it has been proposed as a biomarker of severity and resistance to H1-antihistamines in CU patients. The possible role of coagulation in CU is also supported by case reports, case series and a small controlled study showing the efficacy of anticoagulant therapy in this disease. The purpose of this review was to summarize the available data on the possible contribution of coagulation to the pathophysiology of CU focusing on clinical aspects and possible future therapeutic developments.Chronic urticaria (CU) is a widespread skin disease characterized by the recurrence of transient wheals and itch for more than 6 weeks. It is believed that over 50% of CU cases are accompanied by a deep subcutaneous and/or submucosal edema, called angioedema (AE; 1).It is well known that the characteristic symptoms of urticaria appear following the activation of mast cells (MCs) and basophils in the skin by various stimuli. These cells release several biologically active substances, the most important of which is histamine. Histamine induces vasodilation, increases vascular permeability and stimulates sensory nerve endings. These effects lead to the appearance of erythema, wheals and itch (2). It is supposed that other biologically active substances may have similar effects. These include serotonin, C3a and C5a anaphylatoxins, platelet-activating factor (PAF), neuropeptides, and arachidonic acid metabolites (prostaglandin D2, leukotrienes C4, D4 and E4; 3).Activation and degranulation of basophils and MCs may occur by immunological (formation of immune complexes, complement activation, IgE cross-linking), nonimmunological (pseudoallergy, infection, or direct effect of agents on MCs), or mixed mechanisms. The mechanism and cause of urticaria remain unclear in many patients with CU.In recent years, attention was paid to several important aspects of the disease pathogenesis. It is believed that about 30-50% of patients have CU symptoms associated with autoimmune reactions and synthesis of autoantibodies against IgE (4) and/or the FceRI a-subunit on MCs and basophils (autoimmune/autoreactive urticaria; 5). Furthermore, these patients show an increased frequency of HLA DRB1*04 (DR4) as it occurs in other autoimmune diseases (6). The role of coagulation casc...

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Section: Role Of Eosinophils Tissue Factor and Thrombinmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Coagulation Biomarkers In Chronic Urticariamentioning

confidence: 99%

See 1 more Smart Citation

Chronic urticaria and coagulation: pathophysiological and clinical aspects

Tedeschi

Kolkhir

Asero³

et al. 2014

Allergy

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“…CSU is characterized by the activation of the coagulation cascade [38,39]. And it is probable that both intrinsic and extrinsic pathways are affected in CSU patients [40].…”

Section: Comorbidities and Possible Triggering Factorsmentioning

confidence: 99%

Comorbidities in Chronic Spontaneous Urticaria

Gönül¹,

Ayvaz²,

Kartal³

2017

A Comprehensive Review of Urticaria and Angioedema

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Chronic spontaneous urticaria (CSU) is a disease that makes people's lives miserable with unknown etiology. In recent years, there have been many studies trying to explain the etiology of CSU, and many of them reported that there are some comorbidities or triggering factors related to CSU. However, it has not been clearly known yet that whether these conditions are true comorbidities associated with CSU or they are coincidentally found at the same time. In this chapter, related comorbidities and conditions have been told.

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“…The first observations in this sense, published in 2006, noted that chronic urticaria is associated with elevated plasma levels of prothrombin fragment F1+2, a marker of thrombin generation, and that such levels parallel the disease severity [9]. Subsequent studies found that thrombin generation is associated with the activation of the extrinsic pathway of coagulation as shown by increased plasma levels of activated factor VII (FVIIa) [10]. In patients with severe urticaria, the activation of the coagulation cascade may be intense enough to lead to fibrinolysis, as shown by an increase in plasma levels of Ddimer paralleling disease severity [11].…”

Section: Introductionmentioning

confidence: 99%