Is clinical outcome of dengue-virus infections influenced by coagulation and fibrinolysis? A critical review of the evidence

Despite efforts to elucidate the pathogenesis of dengue fever, the progression into severe disease remains poorly understood. In-vitro findings suggest that coagulopathy and disturbances in fibrinolysis have a pivotal role in the pathophysiology. If disturbances in these processes are predictive of clinical outcome in this disease, there could be important consequences for both diagnosis and treatment. We have critically reviewed publications on this topic to assess whether there is an association between activation of coagulation and fibrinolysis and clinical outcome of denguevirus infections. In general, the selected studies showed activation of both the coagulation and fibrinolytic systems in this infection. The activation was more pronounced in severe infections and in cases with a poor clinical outcome. However, the findings were not consistent, and owing to a lack of detailed information on characteristics of patients, disease, and study design, we could not ascertain whether inconsistencies were caused by differences in these characteristics, selection bias, or confounding factors. We conclude that an association between activation of coagulation and fibrinolysis and clinical outcome of denguevirus infections is conceivable but has been inadequately assessed and that methodologically sound studies, complemented with complete and reliable reporting, are needed to show whether there is a true association.