Author's response to reviews Title:Tranexamic acid for patients with traumatic brain injury: a randomized, double-blinded, placebo-controlled trial. Authors:

Background Traumatic brain injury (TBI) is commonly accompanied by intracranial bleeding which can worsen after hospital admission. Tranexamic acid (TXA) has been shown to reduce bleeding in elective surgery and there is evidence that short courses of TXA can reduce re-bleeding in spontaneous intracranial haemorrhage. We aimed to determine the effectiveness and safety of TXA in preventing progressive intracranial haemorrhage in TBI. Methods We enrolled 238 patients older than 16 years with moderate to severe TBI (postresuscitation Glasgow Coma Scale (GCS) 4 to 12) who had a Computerized Tomography (CT) brain scan within eight hours of injury and in whom there was no immediate indication for surgery. We excluded patients if they had a coagulopathy or a serum creatinine over than 2.0 milligrams%. The treatment was a single dose of 2 grams of TXA in addition to other standard treatments. The primary outcome was progressive intracranial hemorrhage (PIH) which was defined as an intracranial hemorrhage seen on the second CT scan that was not seen on the first CT scan, or an intracranial hemorrhage seen on the first scan that had expanded by 25% or more on any dimension (height, length, or width) on the second scan. Results Progressive intracranial haemorrhage was present in 21 (18%) of 120 patients allocated to TXA and in 32 (27%) of 118 patients allocated to placebo [RR=0.65 (95%CI 0.40 to 1.05)]. The relative risk of death from all causes in patients allocated to TXA compared with placebo was 0.69 (95% CI 0.35 to 1.39) and the relative risk for unfavourable outcome on the Glasgow Outcome Scale was 0.76 (95% CI 0.46 to 1.27) respectively. There was no evidence of increased risk of thromboembolic events in those allocated to TXA. Conclusion Finally TXA may reduce PIH in patients with TBI. Large clinical trials are needed to confirm and to assess the effect of TXA on death or disability after TBI.