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.