**6. Possible relation between blood transfusions and thrombosis**

The inflammatory response and pro-inflammatory cytokines also lead to activation of the coagulation system and down-regulate the anticoagulant systems (Levi et al., 2003) Activation of the coagulation factors can in turn activate inflammation. This may enhance the development of infections and microvascular thrombi. Both thrombi and infection play a central role in the development and worse outcome of MODS (Gando, 2010). This could occur by increasing the circulating RBC mass and vascular rheologic deformations by RBC transfusions. Activated platelets (during storage) may contribute to thrombosis in patients at risk. It has recently been shown that leukocyte-containing RBCs and platelets contain prothrombotic soluble mediators, which interact with leukocytes preceding the apoptosis and death of leukocytes, subsequently producing microparticles with procoagulant activity (Keating et al., 2010). Leukocyte-containing RBCs contain prothrombotic soluble mediators, such as CD40L, which induce the synthesis of proinflammatory mediators that can further activate the coagulation system (Blumberg et al., 2006). Observational studies showed an association between allogeneic blood transfusions and the development of venous thromboembolism (Nilsson et al, 2007 and Khorana et al., 2008). The possible association between allogeneic blood transfusions and the formation of thrombosis, as a factor aggravating MODS and having a role in increased mortality due to MODS, is a new subject and should be investigated further. Recently one study found that not only inflammatory mediators were increased in bronchoalveolar lavage fluid after cardiac surgery, also coagulation was activated (Tuinman et al, 2011). This study supports that allogeneic blood transfusions could result in both activation of the inflammatory and coagulation systems.
