***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: BACKGROUND The risk of deep-vein thrombosis ( DVT ) and pulmonary embolism after total hip replacement ( THR ) surgery may persist after hospital discharge , but the extent of the risk is not known . We carried out a single-centre , prospect i ve , r and omised , double-blind trial with the aims of quantifying this risk and assessing the efficacy of continued prophylactic treatment . METHODS At hospital discharge 13 - 15 days after surgery , we recruited 179 consecutive THR patients who had no DVT visible on bilateral ascending venography of the legs . The patients were r and omly assigned subcutaneous enoxaparin ( 40 mg , once daily ; n = 90 ) or placebo ( n = 89 ) for 21 ( 19 - 23 ) days . The primary endpoint was the occurrence of DVT or pulmonary embolism . Venography was repeated at the end of 21 days ' treatment or earlier if necessary . FINDINGS There were no deaths and no symptomatic pulmonary embolisms during the study or follow-up periods . Of 173 patients with evaluable venograms , intention-to-treat analysis of efficacy showed that the rate of DVT at day 21 after discharge was significantly lower in the enoxaparin group than in the placebo group ( 6 [ 7.1 % ] vs 17 [ 19.3 % ] , p = 0.018 ) . Distal DVT was detected in one ( 1.2 % ) patient in the enoxaparin group and in ten ( 11.4 % ) patients in the placebo group ( p = 0.006 ) . Proximal DVT was observed in five ( 5.9 % ) patients in the enoxaparin group and in seven ( 7.9 % ) patients in the placebo group ( p = 0.592 ) . A per protocol analysis of efficacy in 155 patients confirmed these findings . Safety was good ; three minor bleeding episodes occurred in the enoxaparin group and one in the placebo group , but none of these episodes necessitated withdrawal from the study . INTERPRETATION In patients who have undergone THR surgery , are without venogram-proven DVT at hospital discharge , and do not receive antithrombotic prophylaxis after discharge , the risk of late-occurring DVT remains high at least until day 35 after surgery . Continued prophylaxis with enoxaparin is effective and safe in reducing this risk In previous r and omised clinical trials of thromboprophylaxis after total hip replacement , low-molecular-weight heparin has been given for an arbitrary 7 to 14 days . The risk factors are mainly perioperative and it is possible that a shorter course may be adequate . We assessed the safety and effectiveness of a three-day course . We assessed 156 primary THR patients after r and omisation to either a control group or to receive enoxaparin at 12 hours preoperatively and 12 and 36 hours postoperatively .  Thrombosis was diagnosed by routine venography . Haemorrhagic side-effects were assessed by measurement of blood loss , and soft-tissue side-effects by descriptive scores for wound discharge and bruising of the leg . The prevalence of calf thrombosis was 15.4 % in the enoxaparin group and 32.1 % in the control group ( p = 0.01 ) ; the prevalence of proximal thrombosis was 15.4 % and 17.9 % respectively ( not significant ) . There was no difference in haemorrhagic side-effects or wound discharge , but there was more bruising in the enoxaparin group Seventy-eight patients having elective total hip replacement were r and omised into 3 groups A ) control ; B ) low molecular weight heparin : ( enoxaparin 40 mg once daily ) and C ) enoxaparin ( 40 mg once daily ) plus graduated elastic compression ( TEDR stockings ) for 8 - 12 days . All patients had a preoperative perfusion lung scan and chest X-Ray and a postoperative perfusion/ventilation scan together with bilateral ascending venography on days 8 - 12 . A blood sample was taken preoperatively , on the 1st , 3rd and 5th postoperative day and at the end of the study . The control group received placebo injections . The venograms and V/Q scans were reported blindly by an independent panel of three and one radiologists respectively . An independent panel of assessors stopped entry in the control group when a total of 45 patients were admitted according to Ethics Committee directives . The study continued with groups B and C. The incidence of DVT ( including isolated asymptomatic calf thrombi ) was as follows : Group A ( n = 14 ) 93 % ; Group B ( n = 32 ) 38 % ; Group C ( n = 32 ) 25 % ( chi 2 ; p < 0.001 for group A versus B or C ) . The incidence of proximal DVT was : Group A 57 % ; group B 28 % ; group C 13 % ( chi 2 ; p = 0.057 for group A versus B and p < 0.005 for group A versus C ) . The incidence of silent pulmonary embolism ( PE ) ( new defect on V/Q scan ) was 28 % ( 8 out of 29 ) in patients with and 5 % ( 2 out of 43 ) in patients without DVT ( chi 2 ; p < 0.02 ) . The combination of high TAT and low anti-Xa activity on the 1st postoperative day identified a high risk group of patients who had a 56 % incidence of proximal DVT on the 8th to 12th postoperative day . Further studies are needed to confirm the suggested increased efficacy in prophylaxis by the combination of LMWH and GEC as compared with LMWH alone Discontinuation of thromboprophylaxis a few days after surgery may unmask delayed hypercoagulability and contribute to late formation of  deep venous thrombosis ( DVT ) . To investigate whether thromboprophylaxis should be prolonged beyond the hospital stay , a prospect i ve , double-blind r and omised study was conducted in 308 patients . All patients received initial thromboprophylaxis with dalteparin , dextran and grade d elastic stockings . On day 7 , patients were r and omised to receive dalteparin ( Fragmin ) 5000 i.u . once daily , or placebo , for 4 weeks . All patients were subjected to bilateral venography , perfusion ventilation scintigraphy and chest X-ray on days 7 and 35 . Patients with venographically verified proximal DVT on day 7 were withdrawn from the r and omised study to receive anticoagulant treatment . The overall prevalence of DVT on day 7 was 15.9 % . On day 35 , the prevalence of DVT was 31.7 % in placebo-treated patients compared with 19.3 % in dalteparin-treated patients ( p = 0.034 ) . The incidence of DVT from day 7 to day 35 was 25.8 % in the placebo-treated group versus 11.8 % in the dalteparin-treated group ( p = 0.017 ) . The incidence of symptomatic pulmonary embolism ( PE ) from day 7 to day 35 was 2.8 % in the placebo-treated group compared with zero in the dalteparin-treated group . This included one patient who died from PE . No patients experienced serious complications related to the injections of dalteparin or placebo . This study shows that prolonged thromboprophylaxis with dalteparin . 5000 IU , once daily for 35 days significantly reduces the frequency of DVT and should be recommended for 5 weeks after hip replacement surgery The main results of three successive prospect i ve clinical trials which represent the successive steps in the definition of once-daily dosing of enoxaparin in elective hip surgery are demonstrated . In the first trial , a dose of 40 mg/day ( 4000 anti-Factor Xa IU ) , in one or two subcutaneous injections , was preferred to a dose of 60 mg because it gave the same efficacy with a better tolerance . In a second , r and omized double-blind trial , the two modes of administration of a dose of 40 mg , in one or two injections daily , were found to be equivalent with regard to tolerance and efficacy . In a third prospect i ve , controlled , r and omized , double-blind multicentre trial , once-daily dosing of enoxaparin at the dose of 40 mg was found superior to 5000 IU of unfractionated heparin tds with regard to tolerance and efficacy . It is concluded that the dose of 40 mg/day , begun 12 h pre-operatively , gives the best benefit : risk ratio in elective hip surgery In a prospect i ve , r and omized , double-blind study , the efficacy and safety of a low-molecular-weight heparin were compared with those of unfractionated sodium heparin ( st and ard heparin ) in 136 patients who had elective total hip replacement . The patients received subcutaneous injection of either 5000 international units of low-molecular-weight heparin once daily or 5000 international units of st and ard heparin three times a day . Treatment with low-molecular-weight heparin began twelve hours before the operation , and treatment with st and ard heparin began two hours preoperatively ; both regimens were continued for ten days . Twelve days postoperatively , bilateral ascending phlebography was performed in 122 patients , sixty-three in the treatment group that received low-molecular-weight heparin and fifty-nine in the treatment group that received st and ard heparin .  Pulmonary scintigraphy was performed in 127 patients . Deep-vein thrombosis was diagnosed in forty-four patients : nineteen ( 30 per cent ) of the sixty-three who received low-molecular-weight heparin and twenty-five ( 42 per cent ) of the fifty-nine who received st and ard heparin . All but four patients , two from each treatment group , were asymptomatic . The difference in the total rate of thrombosis in the two groups was not significant ( p = 0.189 ) . However , thrombosis occurred in the thigh in only six ( 10 per cent ) of the patients who received low-molecular-weight heparin but in eighteen ( 31 per cent ) of those who received st and ard heparin , a significant difference ( p = 0.011 ) . Pulmonary embolism was detected in twenty-seven patients : eight ( 12.3 per cent ) of those who received low-molecular-weight heparin and nineteen ( 30.6 per cent ) of those who received st and ard heparin . Only three patients had clinical signs of embolism . Pulmonary embolism was significantly more frequent in the group that received st and ard heparin ( p = 0.016 ) . Total loss of blood and the total amount of blood that was transfused were significantly reduced in the patients who received low-molecular-weight heparin compared with those who received st and ard heparin . Prophylaxis was not discontinued because of hemorrhage in any patient . The efficacy of low-molecular-weight heparin was superior to that of st and ard heparin in the prevention of femoral thrombosis and pulmonary embolism , although the over-all incidence of deep-vein thrombosis was not statistically different . ( ABSTRACT TRUNCATED AT 400 WORDS Consecutive patients undergoing total hip replacement in 43 centres were r and omly assigned to receive blindly either enoxaparin ( 40 mg ) or tinzaparin ( 4,500 anti-Factor IU Xa ) , as once daily subcutaneous injections . The first injection was administered 12 h preoperatively . Efficacy was assessed by bilateral venography performed 12 - 14 days postoperatively . Efficacy and safety were blindly and central ly adjudicated . Among the 499 patients included , 440 had a venogram . The total incidence of DVTs was 44 ( 20.1 % ) of the 219 patients of the enoxaparin group and 48 ( 21.7 % ) of the 221 patients of the tinzaparin group . The upper limit of the 80 % confidence interval of the difference between the two treatment groups was less than 5.0 % . Therefore according to the protocol 's specifications equivalence was shown . Proximal DVTs occurred in 10.5 % of the enoxaparin group ( 23 patients ) and in 9.5 % ( 21 patients ) of the tinzaparin group . No overt major bleeding was observed . One patient in the enoxaparin group developed severe thrombocytopenia and died . The LMWH tinzaparin appears clinical ly to be as effective and safe as enoxaparin in the prophylaxis of deep vein thrombosis after total hip replacement , at the doses used and under the conditions of this study There is experimental evidence that low-molecular-weight fractions of heparin are as effective as the st and ard form but cause less bleeding . We therefore performed a double-blind , r and omized trial comparing PK10169 low-molecular-weight heparin with placebo for the prevention of venous thrombosis in patients undergoing elective hip surgery .  Prophylactic treatment with a fixed dose was begun postoperatively and continued for 14 days . Fifty patients in each treatment group underwent surveillance with [125I]fibrinogen leg scanning and impedance plethysmography . In the first 24 patients ,  venography  was performed only if either surveillance test was 
    Output:
    
We find no convincing evidence that starting prophylaxis preoperatively is associated with a lower incidence of venous thromboembolism than starting postoperatively .
Perioperative regimens may lower the risk of postoperative thrombosis , but if so , this positive effect is offset by an increase in postoperative major bleeding