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Role of TF-Triggered Activation of the Coagulation Cascade in the Pathogenesis of Chronic Spontaneous Urticaria

  • Urticaria and Atopic Dermatitis (M Furue and T Nakahara, Section Editors)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of Review

To overview recent understanding of the relationship between the blood coagulation cascade and chronic spontaneous urticaria (CSU).

Recent Findings

The relationship between severities of CSU and the increase of coagulation markers, and the effectiveness of anti-coagulants, such as warfarin, suggest a causative role of the blood coagulation in the pathogenesis of CSU. However, mechanisms of the initiation of blood coagulation, and the link between blood coagulation and wheal formation in urticaria, remained unclear. In blood vessels, vascular endothelial cells and eosinophils may express tissue factor (TF), which triggers the activation of extrinsic coagulation cascade. We recently revealed that histamine and TLR agonists synergistically induce TF expression by endothelial cells and produce active forms of coagulation factors, such as Xa and IIa, which may induce plasma extravasation. The exposure of skin mast cells to the exuded plasma may then induce degranulation of the skin mast cells via various receptors, releasing a massive amount of histamine, resulting in wheal formation observed in CSU.

Summary

Further elucidation of the mechanism of blood coagulation and the pathway of mast cell activation by activated coagulation factors may be a target for the development of new and more effective treatments for CSU.

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Abbreviations

CSU:

Chronic spontaneous urticarial

CIU:

Chronic idiopathic urticarial

TF:

Tissue factor

PAR:

Protease-activated receptor

FcεRI:

High-affinity IgE receptor

HUVEC:

Human umbilical vein endothelial cells

HMVEC:

Human dermal microvascular endothelial cells

TLR:

Toll-like receptor

LPS:

Lipopolysaccharide

IL:

Interleukin

LPS:

Lipopolysaccharides

SP:

Substance P

MRGX2:

MAS-related G protein-coupled receptor member X2

NMU:

Neuromedin U

MBP:

Major basic protein

EPO:

Eosinophil peroxidase

CRP:

C-reactive protein

PAF:

Platelet-activating factor

References and Recommended Reading

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Funding

The study was funded by grants to Y.Y from Takeda Science Foundation 2018 and Grant-in-Aid for Scientific Research (C).

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Authors and Affiliations

  1. Department of Dermatology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3, Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yuhki Yanase PhD, Shunsuke Takahagi MD,PhD & Michihiro Hide MD,PhD

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  1. Yuhki Yanase PhD
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  2. Shunsuke Takahagi MD,PhD
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  3. Michihiro Hide MD,PhD
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Correspondence to Michihiro Hide MD,PhD.

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Yuhki Yanase declares that he has no conflict of interest. Shunsuke Takahagi declares that he has no conflict of interest. Michihiro Hide declares that he has no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Urticaria and Atopic Dermatitis

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Yanase, Y., Takahagi, S. & Hide, M. Role of TF-Triggered Activation of the Coagulation Cascade in the Pathogenesis of Chronic Spontaneous Urticaria. Curr Treat Options Allergy 5, 383–391 (2018). https://doi.org/10.1007/s40521-018-0183-3

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