**8. References**

160 Perioperative Considerations in Cardiac Surgery

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.

Transfusion of allogeneic blood components is commonly used in cardiac surgery. Several observational and randomized studies found higher morbidity and mortality if patients were transfused with allogeneic blood products. In the last years the clinical effects of transfusion triggers, the storage times and the presence of allogeneic leukocytes in red blood cells were investigated intensively. In cardiac surgery it has been found that allogeneic blood transfusions could increase postoperative complications, which is controversial in the last years. Clinical effects of storage of RBCs are discussed intensively and until now there is no clear evidence that older RBCs are deleterious in cardiac surgery. It has been found that mainly leukocyte-containing blood products play a crucial role in the development of postoperative complications in cardiac surgery. To understand the differences between leukocyte-containing and leukocyte-depleted RBC transfusions we described in this review several possible causal mechanisms. Soluble mediators derived from deteriorating leukocytes during storage of RBC are unlikely to play a role. The complement activation by lectin pathway may be relevant to explore as a causal deleterious effect of plasma transfusions, although does not explain excess death by MODS in association with allogeneic leukocytes. An acute phase reaction represented by procalcitonin could be excluded as a mediator induced by allogeneic leukocytes. A difference in cytokine responses in the recipient was the only significant factor that could be identified as playing a possible causal role. In most countries of the Western World transfusion of leukodepleted blood components is standard practice. Although the final conclusion on this issue is not made yet. Furthermore other factors, such as plasma and platelet transfusions (due to activation or

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

**7. Conclusions** 


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