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Haemorrhage is a life threating condition. Approximately 5 million people die every year around the world from accidental and non-accidental trauma[i]. After a traumatic injury, hemorrhage is responsible for over 35% of pre-hospital deaths and over 40% of deaths within the first 24 hours, second only to the rates of death due to severe central nervous system injury[ii]. In addition to trauma, there are many other cases and conditions where excessive blood loss can occur: surgeries (i.e. liver transplantation); childbirth (postpartum hemorrhage); disseminated intravascular coagulation (DIC); brain hemorrhage, stomach ulcers, gastro intestinal bleeding and cancer among others.
There are limited effective treatments to halt massive bleeding and to prevent additional complications.
Today´s standard procedures to treat excessive bleeding consist mainly of treatments that promote blood clotting like recombinant Factor VIIa (rFVIIa). However, despite successfully inducing the generation of more clots, the use of rVIIa increases the risk of thromboembolism due to the detachment of blood clots. An alternative is represented by the transfusion of blood/plasma-derived products like fresh frozen plasma (FFP). FFP is largely used to treat excessive bleeding however it has quite low efficacy and in some cases, does not succeed In stopping the bleeding.[iii] This is so, because these treatments increase the presence of plasminogen which triggers hyper activation of the fibrinolytic system (hyperfibrinolysis). The fibrinolytic system is responsible for removing blood clots that can be caused by acquired (severe trauma and surgical procedures) or congenital (deficiency of plasminogen inhibitor) reasons. Therefore, hyperfibrinolysis represents a coagulation abnormality condition where the patient presents an enhanced tendency to bleed upon injury. Standard procedures to treat this condition are based in Tranexamic Acid (TXA), a potent inhibitor of the fibrinolytic protein. However, a number of studies have demonstrated that TXA is effective only in the first three hours post injury[iv] and that its use may cause dangerous side-effects, such as thrombotic events.
[iv] Medcalf, R. L. (2015). The traumatic side of fibrinolysis. Blood, 125(16), 2457-2458. Accessed June 01, 2018. https://doi.org/10.1182/blood-2015-02-629808.