***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    Input: Background Recently , a number of studies using intra-articular application of tranexamic acid ( IA-TXA ) , with different dosage and techniques , successfully reduced postoperative blood loss in total knee replacement ( TKR ) . However , best of our knowledge , the very low dose of IA-TXA with drain clamping technique in conventional TKR has not been yet studied . This study aim ed to evaluate the effectiveness and dose-response effect of two low-dose IA-TXA regimens in conventional TKR on blood loss and blood transfusion reduction . Methods Between 2010 and 2011 , a triple-blinded r and omized controlled study was conducted in 135 patients undergoing conventional TKR . The patients were allocated into three groups according to intra-articular solution received : Control group ( physiologic saline ) , TXA-250 group ( TXA 250 mg ) , and TXA-500 group ( TXA 500 mg ) . The solution was injected after wound closure followed by drain clamping for 2 hours . Blood loss and transfusion were recorded .  Duplex ultrasound  was performed . Functional outcome and complication were followed for one year . Results There were forty-five patients per groups . The mean total hemoglobin loss was 2.9 g/dL in control group compared with 2.2 g/dL in both TXA groups ( p > 0.001 ) . Ten patients ( 22 % , control ) , six patients ( 13 % , TXA-250 ) and none ( TXA-500 ) required transfusion ( p = 0.005 ) . Thromboembolic events were detected in 7 patients ( 4 controls , 1 TXA-250 , and 2 TXA-500 ) . Functional outcome was non-significant difference between groups . Conclusions Combined low-dose IA-TXA , as 500 mg , with 2-hour clamp drain is effective for reducing postoperative blood loss and transfusion in conventional TKR without significant difference in postoperative knee function or complication . Trial registration Clinical Trials.gov NCT01850394 Abstract Purpose To compare the blood loss and the blood transfusion between a control group and a group of patients following either a local administration of tranexamic acid or a mechanical post-operative knee flexion , a controlled r and omized study was performed . Methods Sixty patients affected by primary knee osteoarthritis and c and i date s to receive a primary unilateral total knee arthroplasty were enrolled in a prospect i ve , r and omized , controlled study . Exclusion criteria were the following : tranexamic acid allergy , the use of pharmacological anticoagulant therapy , previous knee surgery and renal failure . For each patient , the following parameters were investigated : the blood loss volume , the haemoglobin and haematocrit concentrations and the blood transfusion needs . Results Compared to the control group , the administration of systemic tranexamic acid significantly reduces ( p < 0.05 ) both the blood loss ( average reduction 39.8 % ) and the blood transfusion needs ( 64 % ) . Furthermore , the tranexamic acid group shows a significant reduction ( p < 0.05 ) compared to the knee flexion group of the blood loss ( average reduction 31.8 % ) and the transfusion needs ( 65 % ) . However , even if the knee flexion technique slightly reduces the blood loss ( average reduction 11.6 % ) compared to the control group , this difference is not statistically significant ( n.s . ) . Moreover , this treatment did not reduce the transfusion needs compared to the control group ( n.s . ) . Incidence of complications was not influenced by any of the treatments . Conclusions The use of tranexamic acid compared to knee flexion and to control group significantly reduces blood loss and transfusion needs , without wound complications or symptomatic deep vein thrombosis . Level of evidence Prospect i ve therapeutic study , Level The aim of the present study was to investigate aspects of coagulation and fibrinolysis during knee arthroplasties in order to find out . 1 . whether an increased fibrinolysis is correlated to an increased blood loss 2 . whether there is a difference in markers for coagulation and fibrinolysis in peripheral venous blood compared to those in blood from the wounds 3 . whether the administration of tranexamic acid modifies the fibrinolytic response .  Twenty-four patients were included . Twelve patients were given tranexamic acid intravenously at the end of the operation . The dose was repeated three hours later . The other 12 patients were given an equivalent amount of placebo . The administration was r and omised and double-blind . Levels of prothrombin fragments 1 + 2 , D-dimers , plasminogen , alpha 2-antiplasmin , tissue plasminogen activator ( tPA ) , and plasminogen activator inhibitor ( PAI-1 ) in venous blood were investigated just before the operation , at the end of the operation and three hours later . At the end of the operation blood for analysis was also drawn from the wound . Coagulation and fibrinolysis was activated during and after surgery . The activation was significantly higher in blood from the wounds than in peripheral venous blood . We found no direct correlation between the degree of fibrinolysis and blood loss . The administration of tranexamic acid  reduced fibrinolysis in the wounds but not in peripheral venous blood . The postoperative blood loss was reduced by half The ideal method of providing tranexamic acid ( TXA ) for decreasing hemoglobin drop after TKA is still controversial . In this clinical trial , 200 patients were r and omly allocated to four groups . In group 1,500 mg TXA was administered intravenously . In group 2 , the joint irrigated with 3 g of TXA in 100 cc of saline . In group 3 , 1.5 g of TXA was injected through the drain . Group 4 did not take TXA . Albeit all methods had a statistical effect on hemoglobin drop , drainage and number of transfused units when compared to controls , but intravenous injection of TXA seems to be much more effective in terms of reducing hemoglobin drop and transfused units ; and what 's more TXA injection by drain is more effective regarding to reducing postoperative drainage BACKGROUND Total knee arthroplasty ( TKA ) is often carried out using a tourniquet and shed blood is collected in drains . Tranexamic acid decreases the external blood loss . Some blood loss may be concealed , and the overall effect of tranexamic acid on the haemoglobin ( Hb ) balance is not known . METHODS Patients with osteoarthrosis had unilateral cemented TKA using spinal anaesthesia . In a double-blind fashion , they received either placebo  ( n=24 ) or tranexamic acid 10 mg kg(-1 ) ( n=27 ) i.v . just before tourniquet release and 3 h later . The decrease in circulating Hb on the fifth day after surgery , after correction for Hb transfused , was used to calculate the loss of Hb in grams . This value was then expressed as ml of blood loss . RESULTS The groups had similar characteristics . The median volume of drainage fluid after placebo was 845 ( interquartile range 523 - 990 ) ml and after tranexamic acid was 385 ( 331 - 586 ) ml ( P<0.001 ) . Placebo patients received 2 ( 0 - 2 ) units and tranexamic acid patients 0 ( 0 - 0 ) units of packed red cells ( P<0.001 ) . The estimated blood loss was 1426 ( 1135 - 1977 ) ml and 1045 ( 792 - 1292 ) ml , respectively ( P<0.001 ) . The hidden loss of blood ( calculated as loss minus drainage volume ) was 618 ( 330 - 1347 ) ml and 524 ( 330 - 9620 ) ml , respectively ( P=0.41 ) . Two patients in each group developed deep vein thrombosis . CONCLUSIONS Tranexamic acid decreased total blood loss by nearly 30 % , drainage volume by approximately 50 % and drastically reduced transfusion . However , concealed loss was only marginally influenced by tranexamic acid and was at least as large as the drainage volume Purpose The surgical stress of total knee arthroplasty ( TKA ) procedure and the application of intra-operative pneumatic thigh tourniquet increases local fibrinolytic activity , which contributes significantly to post-operative blood loss .  Tranexamic acid , an antifibrinolytic drug , is commonly used to control post-operative blood loss . The recommended mode of administration of tranexamic acid is either oral or intravenous . However , the mechanism of action of the tranexamic acid points towards the possible effectiveness it may have following local/intra-articular application . This prospect i ve , double-blinded , r and omized preliminary study evaluated the efficacy of intra-articular tranexamic acid in reducing TKA-associated post-operative blood loss . Methods Fifty consenting patients with osteoarthritis of the knee scheduled for primary unilateral cemented-TKA were r and omly allocated to one of the two groups : Tranexamic Acid ( TA ) group ( n = 25 , 500 mg/5 ml tranexamic acid ) and the control group ( n = 25 , 5 ml 0.9 % saline ) . The drug and control solution were administered intra-articularly through the drain tube immediately after the wound closure . Parameters related to blood loss ( drop in haemoglobin , haematocrit differential ) and the drain output [ volume ( ml ) ] were compared between the two groups . Results On a comparative basis , TA-group obtained significant reduction in the drain output [ 95 % CI : 360.41–539.59 , p < 0.001 ] at 48 h post-operatively . Even though the control group received sixfold more blood transfusion than TA-group , it showed a greater drop in haemoglobin and haematocrit ( p < 0.05 ) . Conclusions Local application of tranexamic acid seems to be effective in reducing post-TKA blood loss as well as blood transfusion requirements . Level of evidence Therapeutic study , Level II Background The antifibrinolytic tranexamic acid reduces surgical blood loss , but studies have not identified an optimal regimen . Questions / purpose sWe studied different dosages , timings , and modes of administration to identify the most effective regimen of tranexamic acid in achieving maximum reduction of blood loss in TKA . Methods We prospect ively studied five regimens ( four intravenous , one local ; 40 patients each ) with a control group ( no tranexamic acid ) . The four intravenous ( 10-mg/kg dose ) regimens included ( 1 ) intraoperative dose ( IO ) given before tourniquet deflation , ( 2 ) additional preoperative dose ( POIO ) , ( 3 ) additional postoperative dose ( IOPO ) , and ( 4 ) all three doses ( POIOPO ) . The fifth regimen was a single local application ( LA ) . Two independent parameters of drain loss and total blood loss , calculated by the hemoglobin balance method , were evaluated statistically . Results Both parameters were reduced in all five regimens as against the control . A significant reduction in drain loss was seen in the POIO , IOPO , and POIOPO groups whereas total blood loss was significantly reduced in the POIO , POIOPO , and LA groups . The POIOPO group had the least drain loss ( 303 mL ) and least total blood loss ( 688 mL ) . The IO group had the greatest drain loss and the IOPO group the greatest total blood loss . Conclusions Single-dose tranexamic acid did not give effective results . The two-dose regimen of POIO was the least amount necessary for effective results . When compared against the control , this regimen produced reduction of drain loss and total blood loss , whereas the IOPO regimen did not . The three-dose regimen of POIOPO produced maximum effective reduction of drain loss and total blood loss . Level of Evidence Level I , therapeutic study . See Guidelines for Authors for a complete description of levels of evidence A high-dose local tranexamic acid has been introduced in total knee arthroplasty for bleeding control . We are not sure about the systemic absorption and side effects . The aim of this study was to evaluate the effect of low dosage of intra-articular tranexamic acid injection combined with 2-hour clamp drain in minimally bleeding computer-assisted surgery total knee replacement ( CAS-TKR ) . A prospect i ve r and omized controlled trial was conducted in a total of 48 patients underwent CAS-TKR . The patients were r and omly assigned to receive either of a mixed intra-articular solution of tranexamic acid 250 mg with physiologic saline ( TXA group ) , or physiologic saline ( control group ) and then followed by clamp drain for 2 hours .  Postoperative blood loss was measured by three different methods as drainage volume , total hemoglobin loss and calculated total blood loss . Transfusion requirement and postoperative complications were recorded . All patients were screened for deep vein thrombosis and the functional outcomes were evaluated at 6 months after surgery . The mean postoperative drainage volume , total hemoglobin loss and calculated total blood loss in TXA group were 308.8 mL , 2.1 g/dL and 206.3 mL compared to 529.0 mL , 3.0 g/dL and 385.1 mL in the control group 
    Output:
    
The authors found a statistically significant reduction in blood loss and transfusion rates when using topical tranexamic acid in primary TKA .
Furthermore , the currently available evidence does not support an increased risk of deep venous thrombosis or pulmonary embolism due to tranexamic acid administration .
Topical tranexamic acid was effective for reducing postoperative blood loss and transfusion requirements without increasing the prevalence of thromboembolic complications