***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: IMPORTANCE Severely injured patients experiencing hemorrhagic shock often require massive transfusion . Earlier transfusion with higher blood product ratios ( plasma , platelets , and red blood cells ) , defined as damage control resuscitation , has been associated with improved outcomes ; however , there have been no large multicenter clinical trials . OBJECTIVE To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma , platelets , and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio . DESIGN , SETTING , AND PARTICIPANTS Pragmatic , phase 3 , multisite , r and omized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013 . INTERVENTIONS Blood product ratios of 1:1:1 ( 338 patients ) vs 1:1:2 ( 342 patients ) during active resuscitation in addition to all local st and ard-of-care interventions ( uncontrolled ) . MAIN OUTCOMES AND MEASURES Primary outcomes were 24-hour and 30-day all-cause mortality . Prespecified ancillary outcomes included time to hemostasis , blood product volumes transfused , complications , incidence of surgical procedures , and functional status . RESULTS No significant differences were detected in mortality at 24 hours ( 12.7 % in 1:1:1 group vs 17.0 % in 1:1:2 group ; difference , -4.2 % [ 95 % CI , -9.6 % to 1.1 % ] ; P = .12 ) or at 30 days ( 22.4 % vs 26.1 % , respectively ; difference , -3.7 % [ 95 % CI , -10.2 % to 2.7 % ] ; P = .26 ) . Exsanguination , which was the predominant cause of death within the first 24 hours , was significantly decreased in the 1:1:1 group ( 9.2 % vs 14.6 % in 1:1:2 group ; difference , -5.4 % [ 95 % CI , -10.4 % to -0.5 % ] ; P = .03 ) . More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group ( 86 % vs 78 % , respectively ; P = .006 ) . Despite the 1:1:1 group receiving more plasma ( median of 7 U vs 5 U , P < .001 ) and platelets ( 12 U vs 6 U , P < .001 ) and similar amounts of red blood cells ( 9 U ) over the first 24 hours , no differences between the 2 groups were found for the 23 prespecified complications , including acute respiratory distress syndrome , multiple organ failure , venous thromboembolism , sepsis , and transfusion-related complications . CONCLUSIONS AND RELEVANCE Among patients with severe trauma and major bleeding , early administration of plasma , platelets , and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days . However , more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours . Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group , no other safety differences were identified between the 2 groups . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01545232 Introduction The California Prehospital Antifibrinolytic Therapy ( Cal-PAT ) study seeks to assess the safety and impact on patient mortality of tranexamic acid ( TXA ) administration in cases of trauma-induced hemorrhagic shock . The current study further aim ed to assess the feasibility of prehospital TXA administration by paramedics within the framework of North American emergency medicine st and ards and protocol s. Methods This is an ongoing multi-centered , prospect i ve , observational cohort study with a retrospective chart- review comparison . Trauma patients identified in the prehospital setting with signs of hemorrhagic shock by first responders were administered one gram of TXA followed by an optional second one-gram dose upon arrival to the hospital , if the patient still met inclusion criteria . Patients administered TXA make up the prehospital intervention group . Control group patients met the same inclusion criteria as TXA c and i date s and were matched with the prehospital intervention patients based on mechanism of injury , injury severity score , and age . The primary outcomes were mortality , measured at 24 hours , 48 hours , and 28 days . Secondary outcomes measured included the total blood products transfused and any known adverse events associated with TXA administration . Results We included 128 patients in the prehospital intervention group and 125 in the control group . Although not statistically significant , the prehospital intervention group trended toward a lower 24-hour mortality rate ( 3.9 % vs 7.2 % for intervention and control , respectively , p=0.25 ) , 48-hour mortality rate ( 6.3 % vs 7.2 % for intervention and control , respectively , p=0.76 ) , and 28-day mortality rate ( 6.3 % vs 10.4 % for intervention and control , respectively , p=0.23 ) . There was no significant difference observed in known adverse events associated with TXA administration in the prehospital intervention group and control group . A reduction in total blood product usage was observed following the administration of TXA ( control : 6.95 units ; intervention : 4.09 units ; p=0.01 ) . Conclusion Preliminary evidence from the Cal-PAT study suggests that TXA administration may be safe in the prehospital setting with no significant change in adverse events observed and an associated decreased use of blood products in cases of trauma-induced hemorrhagic shock . Given the current sample size , a statistically significant decrease in mortality was not observed . Additionally , this study demonstrates that it may be feasible for paramedics to identify and safely administer TXA in the prehospital setting OBJECTIVE To quantify the impact of fibrinogen-containing cryoprecipitate in addition to the antifibrinolytic tranexamic acid on survival in combat injured . DESIGN Retrospective observational study comparing the mortality of 4 groups : tranexamic acid only , cryoprecipitate only , tranexamic acid and cryoprecipitate , and neither tranexamic acid nor cryoprecipitate . To balance comparisons , propensity scores were developed and added as covariates to logistic regression models predicting mortality . SETTING A Role 3 Combat Surgical Hospital in southern Afghanistan . PATIENTS A total of 1332 patients were identified from prospect ively collected U.K. and U.S. trauma registries who required 1 U or more of packed red blood cells and composed the following groups : tranexamic acid  ( n = 148 ) , cryoprecipitate ( n = 168 ) , tranexamic acid/cryoprecipitate ( n = 258 ) , and no tranexamic acid/cryoprecipitate ( n = 758 ) . MAIN OUTCOME MEASURE In-hospital mortality . RESULTS Injury severity scores were highest in the cryoprecipitate ( mean [ SD ] , 28.3 [ 15.7 ] ) and tranexamic acid/cryoprecipitate ( mean [ SD ] , 26 [ 14.9 ] ) groups compared with the tranexamic acid ( mean [ SD ] , 23.0 [ 19.2 ] ) and no tranexamic acid/cryoprecipitate ( mean [ SD ] , 21.2 [ 18.5 ] ) ( P < .001 ) groups . Despite greater Injury Severity Scores and packed red blood cell requirements , mortality was lowest in the tranexamic acid/cryoprecipitate ( 11.6 % ) and tranexamic acid ( 18.2 % ) groups compared with the cryoprecipitate ( 21.4 % ) and no tranexamic acid/cryoprecipitate ( 23.6 % ) groups . Tranexamic acid and cryoprecipitate were independently associated with a similarly reduced mortality ( odds ratio , 0.61 ; 95 % CI , 0.42 - 0.89 ; P = .01 and odds ratio , 0.61 ; 95 % CI , 0.40 - 0.94 ; P = .02 , respectively ) . The combined tranexamic acid and cryoprecipitate effect vs. neither in a synergy model had an odds ratio of 0.34 ( 95 % CI , 0.20 - 0.58 ; P < .001 ) , reflecting nonsignificant interaction ( P = .21 ) . CONCLUSIONS Cryoprecipitate may independently add to the survival benefit of tranexamic acid in the seriously injured requiring transfusion . Additional study is necessary to define the role of fibrinogen in resuscitation from hemorrhagic shock 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 rebleeding in spontaneous intracranial haemorrhage . We aim ed to determine the effectiveness and safety of TXA in preventing progressive intracranial haemorrhage in TBI . Methods This is a double blinded , placebo controlled r and omized trial . We enrolled 238 patients older than 16 years with moderate to severe TBI ( post-resuscitation 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 st and ard treatments . The primary outcome was progressive intracranial haemorrhage ( PIH ) which was defined as an intracranial haemorrhage seen on the second CT scan that was not seen on the first CT scan , or an intracranial haemorrhage seen on the first scan that had exp and ed 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 . The difference was not statistically significant [ RR = 0.65 ( 95 % CI 0.40 to 1.05 ) ] . There were no significant difference in the risk of death from all causes in patients allocated to TXA compared with placebo [ RR = 0.69 ( 95 % CI 0.35 to 1.39 ) ] and the risk of unfavourable outcome on the Glasgow Outcome Scale [ RR = 0.76 ( 95 % CI 0.46 to 1.27 ) ] . There was no evidence of increased risk of thromboembolic events in those patients allocated to TXA . Conclusions TXA may reduce PIH in patients with TBI ; however , the difference was not statistically significant in this trial . Large clinical trials are needed to confirm and to assess the effect of TXA on death or disability after TBI BACKGROUND 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 . METHODS This r and omised controlled trial was undertaken in 274 hospitals in 40 countries . 20 211 adult trauma patients with , or at risk of significant bleeding were r and omly 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 . R and omisation was balanced by centre , with an allocation sequence based on a block size of eight , generated with a computer r and om 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 infa rct ion , stroke and pulmonary embolism ) , multiorgan failure , head injury , and other AL analyses were by intention to treat . This study is registered as IS RCT N86750102 , Clinical trials.gov NCT00375258 , and South African Clinical Trial Register DOH-27 - 0607 - 1919 . RESULTS 10096 patients were allocated to tranexamic acid and 10 115 to placebo , of whom 10060 and 10067 , respectively , were analysed . All-cause mortality was significantly reduced with tranexamic acid ( 1463 [ 14.5 % ] tranexamic acid group vs 1613 [ 160 % ] placebo group ; relative risk 0.91 , 95 % CI 085 - 097 ; p = 00035 ) . The risk of death due to bleeding was significantly reduced ( 489 [ 49 % ] vs 574 [ 5 - 7 % ] ; relative risk 0 - 85 , 95 % CI 0.76 - 0.96 ; 
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Conclusion Compared to the CRASH-2 trial , adult trauma patients receiving TXA identified in our systematic review had a lower incidence of mortality at 28 or 30 days , but a higher incidence of in-hospital thrombotic events .
Our findings neither support nor refute the findings of the CRASH-2 trial but suggest that incidence rates in adults with trauma in setting s outside of the CRASH-2 trial may be different than those observed in the CRASH-2 trial