Since the first description in the 1960 [1], a number of studies have documented that ABO blood group has a profound influence on hemostasis, as it is a major determinant of plasma levels of von Willebrand factor (VWF) and consequently, since VWF acts as a specific carrier of factor VIII (FVIII) and protects it from proteolytic degradation, of FVIII [2–5]. It is therefore not surprising that many investigators have studied the possible clinical implications of this biological interaction, i.e. whether the ABO blood group could influence the risk of developing bleeding or thrombotic events [2]. However, while a number of studies have analysed the relationship between ABO blood group and vascular thrombosis [6], especially venous thromboembolism (VTE) [7], only few data have been published on the association between ABO blood group and haemorrhagic disorders [8]. However, as plasma VWF levels are 25–35 % lower in subjects with type-O blood group than in non-O individuals [9], the question of whether the former subjects have an increased bleeding tendency is reasonable. The results available from the literature analysis on such association are quite inconclusive [8], but some studies seem to suggest that O blood group could play a role as a risk factor for the development of more severe hemorrhages. For instance, a Dutch study conducted on patients under vitamin K antagonist (VKA) treatment showed that the risk for non-fatal major bleeding in non-O blood group carriers was 30 % lower than that of O blood group carriers, although the difference was not statistically significant (OR 0.7; 95 % CI: 0.4–1.1) [10]. In keeping with these findings, a recent case–control study conducted by our group in VKA anticoagulated subjects found a higher prevalence, albeit not statistically significant, of O blood group among the patients with grade 2 bleeding complications than among the patients with grade 1 complications (45.4 vs. 35.3 %), suggesting that O blood group may be involved at least in the degree of severity of bleeding complications [11]. Thus, with the aim of clarifying this still controversial issue, we have conducted a retrospective case–control analysis of all the major hemorrhagic events (i.e., cerebral hemorrhage and non-cerebral bleeding events necessitating transfusions with at least three red blood cell (RBC) units) recorded at the Emergency Department of the city hospital of Mantova during the last 3 years (2009–2011). One hundred and ninety-eight major bleeding cases (125 cerebral and 73 non-cerebral) were observed during the study period. The characteristics of the patients, the sites of bleeding and the ABO blood group prevalence are reported in Table 1. The ABO blood group distribution in these two cohorts of patients was then compared with that in the general healthy population of blood donors of Mantova (16, 911 individuals) (Table 2). Overall, no statistically significance difference was observed in the prevalence of O blood group among the three cohorts of individuals evaluated (41.6 % in the group with cerebral hemorrhage, 42.5 % in the group with non-cerebral major bleeding and 43.6 % in the population of blood donors; Pearson’s Chi square test (2 degrees of freedom) = 0.2418, M. Franchini (&) S. Crestani C. Rossi F. Frattini C. Bonfanti Department of Transfusion Medicine and Hematology, Carlo Poma Hospital, Mantua, Italy e-mail: massimo.franchini@aopoma.it