The Mast Cell, Contact, and Coagulation System Connection in Anaphylaxis

Area of Science:

• Immunology
• Hematology
• Allergy

Background:

• Anaphylaxis is a severe allergic reaction involving mast cells and basophils.
• IgE-mediated pathways are well-established, but other mechanisms contribute to anaphylaxis.

Purpose of the Study:

• To explore non-IgE-mediated pathways in anaphylaxis.
• To investigate the role of contact and coagulation systems in anaphylaxis pathogenesis.

Main Methods:

• Analysis of plasma from anaphylactic patients and experimental models.
• Measurement of heparin, factor XII (FXII) activation, and bradykinin (BK) formation.
• Assessment of fibrinolysis and mast cell mediator effects.

Main Results:

• Mast cell heparin facilitates FXII auto-activation, initiating contact and coagulation cascades.
• FXII activation leads to bradykinin formation, correlated with anaphylaxis severity.
• Mast cell tryptase contributes to fibrinolysis, impacting fibrinogen.
• Coagulation and contact system activation by mast cell mediators explain anaphylaxis manifestations like angioedema and hypotension.

Conclusions:

• Anaphylaxis pathogenesis involves significant activation of the contact and coagulation systems.
• These pathways, driven by mast cell mediators, contribute to the clinical severity and symptoms of anaphylaxis.