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

Background

In patients with chronic urticaria (CU), plasma shows signs of thrombin generation and autologous plasma skin tests score positive in as many as 95% of cases.

Objective

To evaluate the initiators of blood coagulation that lead to thrombin generation and fibrinolysis in CU.

Methods

Activated factor VII, activated factor XII, fragment F₁₊₂, and D-dimer plasma levels were measured in 37 patients with CU and 37 controls. Skin specimens from 10 patients with CU and 10 controls were tested for tissue factor immunohistochemically.

Results

Mean F₁₊₂ levels were higher in patients than controls (2.54 [SD 2.57] nmol/L vs 0.87 [0.26] nmol/L; P < .001); disease activity was moderate or severe in 9 of 11 (82%) and 9 of 26 (35%) patients showing high or normal F₁₊₂ levels, respectively (P < .025). Mean D-dimer plasma levels were higher in patients than controls (329 [188] ng/mL vs 236 [81] ng/mL; P < .01); disease activity was moderate or severe in 6 of 8 (75%) and 11 of 29 (38%) showing elevated or normal plasma D-dimer levels (P = NS). Factor VIIa levels were higher in patients than controls (2.86 ng/mL [0.66] vs 1.97 ng/mL [0.65]; P < .001). Activated factor VII and F₁₊₂ levels were correlated (r = 0.529; P = .008). Tissue factor reactivity was observed only in CU skin specimens.

Conclusion

The extrinsic pathway of clotting cascade is activated in CU. Disease severity is associated with the activation of the coagulation cascade.

Clinical implications

The involvement of the coagulation pathway in CU opens new perspectives for a better understanding of the pathogenesis and, possibly, for the treatment of this disease.

Key words: Chronic urticaria, coagulation, thrombin, D-dimer, factor VII

Abbreviations used: ASST, Autologous serum skin test, CU, Chronic urticaria, FVIIa, Activated factor VII, FXIIa, Activated factor XII