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Aberrant activation of the coagulation cascade, abnormal excess of TF on the endothelial wall and high plasma levels of different coagulation factors drive increased thrombin and fibrin production leading to further inflammation and risk of VOC (Sundd et al., 2019)

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It is crucial to note that in most CVOTs the primary endpoint was a composite endpoint of major adverse cardiovascular events (MACE), with HF hospitalisation typically a prespecified secondary or exploratory outcome