IM - COMMENTARY Coagulation and infective endocarditis: sooner or later Francesca Santilli 1,2 • Paola Simeone 1,2 • Giovanni Davı ` 1,2 Received: 29 April 2015 / Accepted: 18 May 2015 / Published online: 2 June 2015 Ó SIMI 2015 Infective endocarditis (IE) is one of the best-characterized clinical paradigms, where inflammation, infection and co- agulation are deeply intertwined in a bidirectional crosstalk [1]. Since, in normal circumstances, bacteremia is a daily, harmless event, and the endocardium is non-thrombogenic, a focal endocardial lining damage is believed to occur, leading to activation in situ of the haemostasis system, resulting in a sterile clot, with subsequent bacterial seeding. Thus, the interactions between pathogens, platelets and the coagulation system are critical to vegetation initiation and growth [2]. The triggering prothrombotic abnormality is amplified by ongoing inflammation, sepsis, and organ dysfunction, all contributing to further shifting the haemostatic system towards a thrombophilic state. The extent of the ensuing procoagulant imbalance is likely to be a predictor of a number of diverse outcomes related to IE, including vegetation size, embolic events and surgical complications [2]. Subjects with IE form a heterogeneous group, ranging from those who are successfully treated with no adverse events, to those with severe complications and a high mortality. An early diagnosis, prompt empiric antibiotic treatment and a careful selection of patients at risk of embolic complications remain the cornerstones of IE management [3]. In critically ill patients admitted to general Intensive Care Unit, multiple factors related both to the underlying conditions and to the performed procedures facilitate the occurrence of both infective and non-infective endocardi- tis, whose incidence is largely underestimated [4, 5]. In the manuscript of Durante-Mangoni et al. [6], pub- lished in this issue of IEM, the original choice of inherited thrombophilia as the candidate risk factor evaluated in a large group of IE patients, takes the opportunity to test different hypotheses: first, the role of inherited throm- bophilia, as an underlying substrate favouring IE occur- rence; second, to exploit a model of prothrombotic condition uninfluenced by the disease activity and pre-ex- isting to the onset of endocarditis, in order to dissect out the relative contribution of a prothrombotic state in the ini- tiation of an endocardial bacterial clot, regardless of sub- sequent amplifying loops [6] (Fig. 1). It should be emphasized that the chosen polymorphisms, the factor V Leiden and prothrombin G20201A mutations, are not significantly correlated with myocardial infarction [7], and, although associated with a substantial increase in the relative risk of venous thromboembolism, the absolute risk remains low, in view of the low prevalence of any thrombophilia [8]. Therefore, larger studies are warranted before the hypothesis of an involvement of initial pro- thrombotic abnormalities on the initiation or progression of IE and related outcomes may be ruled out. Nevertheless, the issue raised by the present paper is relevant in terms of the feasibility of testing the efficacy of antithrombotic prophylaxis before IE onset. Although it has been demonstrated that antiplatelet and anticoagulant strategies have an impact on in vitro and animal models of IE [9–11], results from the available clinical studies are conflicting [12, 13]. A post hoc analysis of observational data comparing patients taking long-term aspirin prior to & Francesca Santilli f.santilli@unich.it 1 Center of Excellence on Aging, ‘‘G. D’Annunzio’’ University Foundation, Via Colle dell’Ara, 66013 Chieti, Italy 2 Department of Medicine and Aging, University of Chieti ‘‘G. d’Annunzio’’ School of Medicine, Chieti, Italy 123 Intern Emerg Med (2015) 10:539–541 DOI 10.1007/s11739-015-1258-9