ABC | Volume 114, Nº5, May 2020

Viewpoint Nascimento et al. Anticoagulation in severe COVID-19 Arq Bras Cardiol. 2020; 114(5):829-833 Systemic inflammatory response in patients with infection can result in endothelial damage, with a consequent increase in thrombin generation and a reduction in endogenous fibrinolysis. 25,26 This prothrombotic state is called sepsis- induced coagulopathy (SIC) and precedes DIC. 27,28 The several mechanisms involved in SIC act simultaneously towards a pro-hemostatic state. Apparently, inflammatory cytokines are the most important factors mediating that coagulation system disorder during sepsis. Evidence has shown a bidirectional relationship between inflammation and coagulation, in which inflammation activates coagulation, and coagulation heightens inflammatory activity (Figure 1). 29-32 Platelets play a central role in the development of coagulation abnormalities in sepsis and they can be activated directly by pro-inflammatory mediators, such as platelet activating factors, as well as by the thrombin generated. Platelet activation can also stimulate the formation of fibrin via an alternative mechanism. The expression of P-selectin in platelet membrane not only mediates the adhesion of platelets to leukocytes and endothelial cells, but also increases the tissue factor expression in monocytes. Under normal circumstances, the activation of coagulation is controlled by three important physiological anticoagulant pathways: the antithrombin system, the activated C-protein system, and the tissue-factor pathway inhibitor. In sepsis, all three pathways are dysfunctional. Amidst all this coagulation system imbalance, endogenous fibrinolysis is largely reduced. According to the criteria established by the International Society on Thrombosis and Hemostasis (ISTH), better clinical outcomes can be identified in patients with SIC on anticoagulant therapy. 27,28 The use of anticoagulants, mainly in critically ill patients, is not free from risk and might be related to severe hemorrhagic complications. Thus, the indication of anticoagulants should be personalized, respecting thrombotic and hemorrhagic risk profiles. Hemophagocytic syndrome (HPS) is characterized by a systemic inflammatory response triggered by the inappropriate activation and proliferation of lymphocytes, which activate macrophages and histiocytes, resulting in phagocytosis of hematological cells. The disease is associated with a large Figure 1 – The novel coronavirus, SARS-CoV-2, activates the inflammatory and thrombotic process. The disease it causes is associated with an increase in inflammatory cytokines (cytokine storm) and coagulation disorders, with predisposition to thrombus formation. Mononuclear cells interact with activated platelets and the coagulation cascade, which activate inflammatory cells by binding thrombin and tissue factor with specific protease activated receptors and by binding fibrin to Toll-like receptor 4. The activation of inflammatory cells results in the release of pro-inflammatory cytokines, leading to impairment of the natural coagulation pathways and shut down of fibrinolysis. PAR: protease-activated receptor; TLR4: Toll-like receptor 4; aPTT: activated partial thromboplastin time; PT: prothrombin time; IL: interleukin; TNFα: tumor necrosis factor-α. Figure adapted from Levi M, van der Poll T. 25 830