Severe chronic urticaria is associated with elevated plasma levels of D‐dimer

BACKGROUND: Patients with chronic urticaria (CU) frequently show signs of thrombin generation as a result of the activation of the extrinsic pathway of coagulation and signs of fibrinolysis as shown by slightly increased mean D-dimer plasma levels. Here, we studied patients with severe CU to see whether the activation of coagulation and fibrinolysis parallels the severity of the disease. METHODS: Eight consecutive patients with severe exacerbations of CU and 13 with slight CU were studied. Plasma prothrombin fragment F(1+2) as well as D-dimer were measured by ELISA. Serum histamine-releasing activity was assessed by basophil histamine release assay. Seventy-four normal subjects were used as controls. RESULTS: In patients with severe CU, median levels of both D-dimer (11.20 nmol/l) and F(1+2) (592 pmol/l) largely exceeded those found in patients with slight CU D-dimer: 2.66 nmol/l (P = 0.001) and F(1+2): 228 pmol/l (P = 0.003) and in normal subjects D-dimer: 1.41 nmol/l (P = 0.0001) and F(1+2): 159 pmol/l (P = 0.0001). Sera from 25% of patients with severe CU and 31% of those with slight CU, but from none of normal subjects, showed in vitro histamine-releasing activity. D-dimer and F(1+2) levels were significantly correlated each other (r = 0.64, P = 0.002) and with CU severity score (r = 0.80-0.90, P = 0.0001), but no correlation was observed between serum histamine-releasing activity and coagulation parameters or severity score. CONCLUSIONS: Severe exacerbations of CU are associated with a strong activation of coagulation cascade and fibrinolysis. Whether this activation is the cause of CU or acts as an amplification system is still a matter of debate.