An array of mast cell mediators can be active in hemostasis such as histamine, heparin, vasoactive intestinal polypeptide, prostanoids, the proteases tryptase and chymase, tissue-type plasminogen activator and factor VIII. Since high levels of these mediators can be achieved after mast cell degranulation in areas of dense mast cell infiltration, clinically significant bleeding can occur in mast cell activation disease (MCAD;[1–7]; for details with respect to definition of MCAD see Suppl. material available online at www. thrombosis-on line. com). However, bleeding diathesis in patients with MCAD has not been systematically investigated so far. Therefore, the first aim of the present study was to determine the prevalence of bleeding diathesis in patients with MCAD. Secondly, we investigated which mediators were involved in bleeding diathesis in those patients. Thirdly, mast cell mediator-related changes in hemostasis are analyzed in terms of frequency and its diagnostic impact for MCAD.