Role of TF-Triggered Activation of the Coagulation Cascade in the Pathogenesis of Chronic Spontaneous Urticaria
Purpose of Review
To overview recent understanding of the relationship between the blood coagulation cascade and chronic spontaneous urticaria (CSU).
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.
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.
KeywordsChronic spontaneous urticaria (CSU) Tissue factor (TF) Extrinsic coagulation cascade eosinophils Endothelial cells Mast cells Eosinophils
Chronic spontaneous urticarial
Chronic idiopathic urticarial
High-affinity IgE receptor
Human umbilical vein endothelial cells
Human dermal microvascular endothelial cells
MAS-related G protein-coupled receptor member X2
Major basic protein
The study was funded by grants to Y.Y from Takeda Science Foundation 2018 and Grant-in-Aid for Scientific Research (C).
Compliance with Ethical Standards
Conflict of Interest
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.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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