***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Intraoperatively administered , tranexamic acid ( TA ) does not reduce bleeding in total hip replacement ( THR ) . Therefore , its prophylactic use was attempted in the present study because this has been shown to be more effective in cardiac surgery . We investigated 40 patients undergoing THR in a prospect i ve , r and omized , double-blinded study . Twenty patients received TA given in two bolus doses of 10 mg/kg each , the first just before surgical incision and the second 3 h later . In addition , a continuous infusion of TA , 1.0 mg · kg−1 · h−1 for 10 h , was given after the first bolus dose . The remaining 20 patients formed a control group . Both groups used preoperative autologous blood donation and intraoperative autotransfusion . Intraoperative bleeding was significantly less ( P = 0.001 ) in the TA group compared with the control group ( 630 ± 220 mL vs 850 ± 260 mL ) . Postoperative drainage bleeding was correspondingly less ( P = 0.001 ) ( 520 ± 280 vs 920 ± 410 mL ) . Up to 10 h postoperatively , plasma D-dimer concentration was halved in the TA group compared with the control group . One patient in each group had an ultrasound-verified late deep vein thrombosis . In conclusion , we found TA , administrated before surgical incision , to be efficient in reducing bleeding during THR . Implication s In a prospect i ve , double-blinded study of 40 patients undergoing total hip replacement , the preoperative administration of tranexamic acid  reduced bleeding by 35 % , probably by decreasing induced fibrinolysis . Whether tranexamic acid therapy can replace predonation of autologous blood or intraoperative autotransfusion requires further study The objective of this study was to determine whether topical tranexamic acid ( TXA ) carried similar hemostatic effect compared with intravenous TXA in total hip arthroplasty ( THA ) . Three hundred and three THA patients were enrolled and r and omized into 3 groups : no TXA group , topical and intravenous TXA group . The results showed that the topical and intravenous TXA group had reduced but similar blood transfusion rates ( 5.88 % v. s. 5.94 % , P = 0.816 ) . No significant difference was detected in total blood loss between the two TXA groups [ ( 963.4 ± 421.3 ) ml vs. ( 958.5 ± 422 ) ml P = 0.733 ] . We conclude that topical use of TXA was equally effective and safe compared with intravenous TXA in reducing blood loss and transfusion rate following THA without substantial complications BACKGROUND Total knee arthroplasty ( TKA ) is associated with significant perioperative blood loss and need for transfusion . This study aim ed to evaluate the effectiveness and safety of tranexamic acid ( TXA ) to reduce perioperative blood loss in patients receiving TKA . MATERIAL AND METHODS A total of 92 patients who accepted unilateral TKA from May 2012 to May 2013 r and omly received either 15 mg/kg TXA in 100 mL normal saline solution ( TXA group , n=46 ) or the same amount of normal saline solution ( placebo group , n=46 ) at 15 min before the tourniquet was loosened . The following data were recorded : intraoperative blood loss ; post-operative drainage at 12 h ; total drainage amount ; hidden blood loss ; total blood loss ; transfusion volumes ; number of transfusions ; post-operative hemoglobin at 1 , 3 , and 5 days ; D-dimer ; number of lower limb ecchymoses ; and deep vein thrombosis ( DVT ) . RESULTS A total of 81 patients were available for analysis  ( TXA group , n=41 ; placebo group , n=40 ) . Post-operative12-h drainage , post-operative 24-h D-dimer values , total drainage volume , hidden blood loss , total blood loss , and the rate of postoperative ecchymosis were lower in the TXA group than in the placebo group ( p<0.05 ) . The post-operative 3-day Hgb was higher in the TXA group than in the placebo group ( p=0.000 ) . The rate of transfusion and DVT was similar in both groups ( n.s . ) . CONCLUSIONS Perioperative blood loss could be reduced after TKA by intravenously injecting 15 mg/kg TXA at 15 min before the tourniquet was loosened . The application of TXA is not associated with increased risk of DVT In this study , we evaluated the hemostatic effects of tranexamic acid ( TNA ) , an antifibrinolytic drug , by examining the timing of its administration during total hip arthroplasty . One hundred seven patients being treated for osteoarthritis of the hip joint were r and omly divided into 5 groups based on the timing of TNA administration . The intraoperative blood loss , postoperative blood loss , and hemoglobin of these patients who received TNA at different times during the procedure were monitored . We found that the intraoperative blood loss in the preoperative TNA administration groups was significantly lower than both control and postoperative TNA administration groups . Furthermore , 1 g TNA 10 minutes before surgery and 6 hours after the first administration was most effective for the reduction of blood loss during total hip arthroplasty We performed a r and omized , double-blind study on the effect of tranexamic acid on blood loss and blood transfusions in 40 primary total hip arthroplasties .  Tranexamic acid , 10 mg/kg body weight , or placebo , was given intravenously just before the operation . Blood loss during the operation and postoperatively into the drains was recorded , as also were blood hemoglobin concentrations . Ultrasound examination 1 week postoperatively was done to estimate the blood loss due to remaining hematomas . Total ( operation + drain ) blood loss was 0.76 ( 95 % CI 0.63 - 0.89 ) L in the tranexamic acid group as compared to 1.0 ( CI 0.81 - 1.2 ) L in the placebo group ( p = 0.03 ) . The number of blood transfusions during the day of operation was 2 vs. 10 ( p = 0.07 ) and the total number during the hospital stay was 5 vs. 13 ( p = 0.2 ) . 1 patient in each group had a pulmonary embolism BACKGROUND Abundant literature regarding the use of intravenous tranexamic acid ( TXA ) in primary total knee replacement is available . R and omized controlled trials have confirmed the efficacy of topical TXA compared with placebo , but the comparison between topical and intravenous TXA is unclear . The present study was design ed to verify noninferior efficacy and safety of topical intra-articular TXA compared with intravenous TXA in primary total knee replacement with cemented implants . METHODS A Phase-III , single-center , double-blind , r and omized , controlled clinical trial was performed to compare topical intra-articular TXA ( 3 g of TXA in 100 mL of physiological saline solution ) with two intravenous doses of TXA ( 15 mg/kg in 100 mL of physiological saline solution , one dose before tourniquet release and another three hours after surgery ) in a multimodal protocol for blood loss prevention . The primary outcome was the blood transfusion rate , and the secondary outcomes included visible blood loss ( as measured in the drain ) at twenty-four hours postoperatively and invisible blood loss ( as estimated from the Nadler formula ) at forty-eight hours postoperatively . The sample size of seventy-eight patients was calculated to give a statistical power of 99 % for demonstrating noninferiority . Thirty-nine patients each were allocated to receive topical intra-articular TXA ( the experimental group ) and intravenous TXA ( the control group ) ; there were no significant differences in demographics or preoperative laboratory values between the groups . Noninferiority was estimated by comparing the confidence intervals with a delta of 10 % . Student t and Mann-Whitney tests were used to assess the significance of any differences . RESULTS The transfusion rate was zero in both groups ; thus , noninferiority was demonstrated for the primary efficacy end point , suggesting equivalence . Noninferiority was also demonstrated for the secondary efficacy end points . Drain blood loss at twenty-four hours was 315.6 mL ( 95 % confidence interval [ CI ] , 248.5 to 382.7 mL ) in the experimental group and 308.1 mL ( 95 % CI , 247.6 to 368.5 mL ) in the control group ( p = 0.948 , Mann-Whitney ) . Also , estimated blood loss at forty-eight hours was 1259.0 mL ( 95 % CI , 1115.6 to 1402.3 mL ) in the experimental group and 1317.9 mL ( 95 % CI , 1175.4 to 1460.4 mL ) in the control group ( p = 0.837 , Mann-Whitney ) . No significant safety differences were seen between groups . CONCLUSIONS Topical administration of TXA according to the described protocol demonstrated noninferiority compared with intravenous TXA , with no safety concerns . This r and omized controlled trial supports the topical intra-articular administration of TXA in primary total knee replacement with cemented implants . LEVEL OF EVIDENCE Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence Summary Background Post-partum haemorrhage is the leading cause of maternal death worldwide . Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients . We aim ed to assess the effects of early administration of tranexamic acid on death , hysterectomy , and other relevant outcomes in women with post-partum haemorrhage . Methods In this r and omised , double-blind , placebo-controlled trial , we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries . We r and omly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care . If bleeding continued after 30 min , or stopped and restarted within 24 h of the first dose , a second dose of 1 g of tranexamic acid or placebo could be given . Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number . Participants , care givers , and those assessing outcomes were masked to allocation . We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth . However , during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as r and omisation . Although tranexamic acid could influence the risk of death in these cases , it could not affect the risk of hysterectomy . We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage . All analyses were done on an intention-to-treat basis . This trial is registered with IS RCT N76912190 ( Dec 8 , 2008 ) ; Clinical Trials.gov , number NCT00872469 ; and PACTR201007000192283 . Findings Between March , 2010 , and April , 2016 , 20 060 women were enrolled and r and omly assigned to receive tranexamic acid ( n=10 051 ) or placebo ( n=10 009 ) , of whom 10 036 and 9985 , respectively , were included in the analysis . Death due to bleeding was significantly reduced in women given tranexamic acid ( 155 [ 1·5 % ] of 10 036 patients vs 191 [ 1·9 % ] of 9985 in the placebo group , risk ratio [ RR ] 0·81 , 95 % CI 0·65–1·00 ; p=0·045 ) , especially in women given treatment within 3 h of giving birth ( 89 [ 1·2 % ] in the tranexamic acid group vs 127 [ 1·7 % ] in the placebo group , RR 0·69 , 95 % CI 0·52–0·91 ; p=0·008 ) . All other causes of death did not differ significantly by group . Hysterectomy was not reduced with tranexamic acid ( 358 [ 3·6 % ] patients in the tranexamic acid group vs 351 [ 3·5 % ] in the placebo group , RR 1·02 , 95 % CI 0·88–1·07 ; p=0·84 ) . The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid ( 534 [ 5·3 % ] deaths or hysterectomies in the tranexamic acid group vs 546 [ 5·5 % ] in the placebo group , RR 0·97 , 9 
    Output:
    
In conclusion , the results of this systematic review and meta- analysis show that intravenous tranexamic acid is a safe pharmacological treatment to reduce blood loss and transfusion requirements in patients undergoing major orthopaedic surgery