- Introduction Activation of the coagulation cascade resulting in thrombin production is a prominent feature of exacerbations in chronic spontaneous urticaria (CU). Autologous serum skin test (ASST) causes wheal-and-flare reactions in 30% to 50% of CU cases. Objective The aim of this study was to evaluate the clinical and laboratory data in patients with CU with positive and negative ASST. To understand the role of platelets in CU, we investigated the relation between CU clinical severity, platelet count and their mean platelet volume (MPV). Methods Clinical and laboratory data were prospectively collected from 373 patients with CU who attended our Allergy and Clinical immunology Clinic during the period 2003 to 2007. The laboratory data were compared with 46 healthy subjects. Results There were no significant differences in platelet counts between the groups, nevertheless the platelets in ASST-positive CU patients were characterized by a higher MPV (9.12 ± 1.25 fl), than that in ASST-negative patients (7.95 ± 1.08 fl; P = 0.039) and control group (7.72 ± 1.04 fl; P = 0.007). There was a significant positive correlation between CU severity score and MPV in ASST-positive patients (r = 0.44; P < 0.001) but not in ASST-negative patients. Higher levels of C-reactive protein (5.31 ± 2.74 mg/L) were measured in the ASST-positive CU group compared with the ASST-negative CU group (2.53 ± 1.27; P = 0.029) and the control group (2.34 ± 1.38; P = 0.003). Conclusion CU with positive ASST is characterized with higher clinical severity, increased MPV and C-reactive protein.