The reasons for the apparent worse outcome of transfused compared with nontransfused critically ill patients may be found in several detrimental effects of transfused blood, globally referred to under the acronym "Non-Infectious Serious Hazards Of Transfusion" or NISHOT ( Table 2 ) [53] . These include, among others, deleterious effects on the immune system (transfusion-related immunomodulation or "TRIM") or on the cardiopulmonary system, e.g., transfusion-related acute lung injury ("TRALI") [54] or transfusion-associated circulatory overload ("TACO"); the latter is currently the leading reported cause of transfusion-associated mortality [55] . These effects may be enhanced by pathologic conditions (e.g., sepsis) in which the microcirculation is impaired [56] and/or when the RBCs have been stored for some time.