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

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.

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.

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.

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.