Extracellular vesicles in disorders of hemostasis following traumatic brain injury.

Traumatic brain injury (TBI) is a global health priority. In addition to being the leading cause of trauma related death, TBI can result in long-term disability and loss of health. Disorders of haemostasis are common despite the absence of some of the traditional risk factors for coagulopathy following trauma. Similar to trauma induced coagulopathy, this manifests with a biphasic response consisting of an early hypocoagulable phase and delayed hypercoagulable state. This coagulopathy is clinically significant and associated with increased rates of haemorrhagic expansion, disability and death. The pathophysiology of TBI-induced coagulopathy is complex but there is biologic plausibility and emerging evidence to suggest that extracellular vesicles (EVs) have a role to play. TBI and damage to the blood brain barrier result in release of brain-derived EVs that contain tissue factor and phosphatidylserine on their surface. This provides a platform on which coagulation can occur. Preclinical animal models have shown that an early rapid release of EVs results in overwhelming activation of coagulation resulting in a consumptive coagulopathy. This phenomenon can be attenuated with administration of substances to promote EV clearance and block their effects. Small clinical studies have demonstrated elevated levels of procoagulant EVs in patients with TBI correlating with clinical outcome. EVs represent a promising opportunity for use as minimally invasive biomarkers and potential therapeutic targets for TBI patients. However, additional research is necessary to bridge the gap between their potential and practical application in clinical settings.

The pharmacological management of severe influenza infection - 'existing and emerging therapies'.

INTRODUCTION: Over the last century several influenza outbreaks have traversed the globe, most recently the influenza A(H1N1) 2009 pandemic. On each occasion, a highly contagious, virulent pathogen has emerged, leading to significant morbidity and mortality amongst those affected. Areas covered: Early antiviral therapy and supportive care is the mainstay of treatment. Treatment should be started as soon as possible and not delayed for the results of diagnostic testing. Whilst oseltamivir is still the first choice, in case of treatment failure, oseltamivir resistance should be considered, particularly in immunosuppressed patients. Here we review the antivirals currently used for management of influenza and explore a number of investigational agents that may emerge as effective antivirals including parenteral agents, combination antiviral therapy and novel agents in order to adequately target influenza virulence. Expert Commentary: New tools for rapid diagnosis and susceptible strains will help if a patient is not improving because of a resistant strain or an inadequate immune response. Further randomized control trials will be conducted to investigate the use of new antivirals and co-adjuvant therapies that will help to elucidate the process of immune modulation, particularly in immunocompetent patients.