Proteolytic enzyme activity in patients with severe head injury and the effect of a proteinase inhibitor. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Prophylaxis of post-traumatic pulmonary insufficiency by protease-inhibitor therapy with aprotinin: a clinical study.
A study was performed to detect the inhibitory effect of intravenously administered aprotinin (Trasylol) on brain and CSF protease activity in 25 patients with severe head injury. The data presented include measurements of CSF protease activity, alpha-1-antitrypsin, alpha-2-macroglobulin, haptoglobulin, polyacrylamidgel-electrophoresis pattern, total protein and hemoglobin content. The results indicate that increased protease activity is present and that this induces autolytic processes which can be inhibited by aprotinin treatment. The survival rate was higher after aprotinin treatment. Total CSF protein content was significantly higher in nonsurvivors than in survivors. Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients.
                This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919.
                10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077).
                Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.
                UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.
                Copyright 2010 Elsevier Ltd. All rights reserved. nan
Tranexamic acid safely reduces mortality in bleeding trauma patients without increasing the risk of adverse events.  TXA should be given as early as possible and within three hours of injury, as treatment later than this is unlikely to be effective. Further trials are needed to determine the effects of TXA in patients with isolated traumatic brain injury.