Axitinib dengue with warning signs and severe dengue. Criteria for dengue with warning signs diagnosis include clinical fluid accumulation, mucosal bleed, liver enlargement and increased hemoconcentration concurrent with thrombocytopenia, while severe dengue is characterized by severe plasma leakage, hemorrhage and organ impairment. Liver enlargement and increase in the levels of plasma transaminases levels are also among the criteria to diagnose dengue with warning signs and severe dengue. Hemostasis abnormalities, namely thrombocytopenia, increased vascular permeability, coagulopathy and abnormal fibrinolysis, have been frequently observed in dengue patients. DHF patients present decreased plasma levels of fibrinogen and plasminogen, reduced a2-antiplasmin activity and an increase of fibrin degradation products, plasmin-antiplasmin complexes and tissue-type plasminogen activator, indicating that patients with life-threatening forms of dengue develop hyperfibrinolysis. Excessive activation of fibrinolysis increases the tendency for hemorrhage, which is in agreement with the report that DENVinfected rhesus macaques presented hemorrhagic manifestations and elevated fibrinolysis products in plasma. Recently, molecules secreted by DENV-infected cells have been associated with the pathogenesis of clinical manifestations, being an interesting and unexplored field for dengue research. In a previous study of the global effects of DENV infection on protein secretion by a hepatic cell line, our group identified a-enolase among the differentially-secreted proteins. Enolase is found in all living organisms and is highly conserved across species. In humans, three isozymes of enolase exist: a-enolase, b-enolase and c-enolase, which are encoded by three different genes: ENO1, ENO2 and ENO3. a-enolase is expressed in almost all tissues, while b-enolase is found preferentially in muscle and c-enolase is expressed in neurons and neuroendocrine tissues. Aside from its canonical enzymatic role in glycolysis and gluconeogenesis pathways, in which it catalyzes the dehydration of 2-phospho-Dglycerate to phosphoenolpiruvate and the reverse reaction of hydration of PEP to PGA, respectively, several other functions have been attributed to a-enolase. ENO1 mRNA alternative stop codon produces a 37 kDa nuclear protein that binds c-myc P2 promoter and functions as a transcriptional suppressor. a-enolase has also been associated with thermal tolerance and has been described as a heat shock protein in the yeast Saccharomyces cerevisiae and a hypoxic stress protein in endothelial cells. Moreover, a-enolase binds to plasminogen and regulates its activation. Plasminogen activation mediated by a-enolase plays important roles in several physiological and pathophysiological processes, including tissue remodeling, inflammatory response, pathogen invasion and metastasis of tumor cells. Since dengue is an inflammatory disease characterized by haemostatic dysfunction and alterations in vascular permeability, we hypothesize that an increase in a-enolase secretion may contribute to the excessive fibrinolysis observed in dengue. In this work, we investigated the effects of DENV infection on a-enolase expression, secretion and post-translational.