***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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    ***EXAMPLES*** 
    Input: The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospect i ve r and omised trial . 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial ; 2076 of these were in the control group and 2045 patients received heparin .  The two groups were well matched for age , sex , weight , blood-group , and other factors which could predispose to the development of venous thromboembolism . 180 ( 4 - 4 % ) patients died during the postoperative period , 100 in the control and 80 in the heparin group : 72 % of deaths in the control and 66 % in the heparin group had necropsy examination . 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism ( P smaller than 0 - 005 ) . In addition , emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes . Taking all pulmonary emboli together , the findings were again significant ( P smaller than 0 - 005 ) . Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis ( D.V.T. ) 667 were in the control group and 625 in the heparin group . The frequency of isotopic D.V.T. was reduced from 24 - 6 % in the control group 7 - 7 % in the heparin group ( P smaller 0 - 005 ) . In 30 patients D.V.T. was detected at necropsy ; 24 in the control and 6 in the heparin group ( P smaller 0 - 005 ) . 32 patients in the control group and 11 in the heparin group developed clinical ly diagnosed D.V.T. which was confirmed by venography ( P smaller than 0 - 005 ) . In addition , 24 patients in the control and 8 in the heparin group were treated for clinical ly suspected pulmonary emoblism . The difference in the number of patients requiring treatment for D.V.T. and /or pulmonary embolism in the two groups was again significant ( P smaller than 0 - 005 ) . 9 patients were found at necropsy to have died from haemorrhage ; 5 were in the control and 4 in the heparin group . A careful objective analysis of operative and postoperative bleeding in 1475 patients showed no statistically significant difference in the blood-transfusion requirements or in the fall in the postoperative haemoglobin level either in the individual operative groups or in the group as a whole . However , the difference in the number of patients who developed wound haematoma in the heparin and control groups was significant ( P smaller 0 - 01 ) . The results of the trial indicate that this form of prophylaxis can now be recommended for use on a large scale in " high-risk " patients undergoing major surgery 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 a r and omized , prospect i ve trial of 100 patients , we have studied the safety and efficacy of warfarin sodium in comparison with that of dextran 40 in the prevention of  venous thrombosis in patients at high risk for deep vein thrombosis after elective total hip or knee replacement .  Warfarin was given in a new two-step regimen design ed to avoid bleeding complications while still preventing venous thrombosis . A low dose of warfarin was started ten to 14 days preoperatively , and the prothrombin time was regulated to between 1.5 and 3 seconds longer than control at the time of surgery ; immediately after surgery , the dose was increased to prolong the prothrombin time to 1.5 times control . The overall incidence of venous thrombosis as documented by venography was less in the 53 patients treated with warfarin than in the 37 treated with dextran ( 21 % v 51 % ) , as was the incidence of thrombi in the femoral or popliteal veins ( 2 % v 16 % ) . Objective measures of blood loss showed no difference between patients treated with warfarin or dextran , and excessive postoperative bleeding was infrequent and similar in both treatment groups . This study demonstrates that two-step warfarin therapy provides highly effective prophylaxis of postoperative venous thrombosis after elective hip or knee prosthetic surgery without excessive risk of perioperative bleeding The effect of low-dose heparin prophylaxis on  venous thrombosis and bleeding after major elective surgery was studied in a prospect i ve controlled study of 820 patients . The total incidence of venous thrombosis detected with leg-scanning using fibrinogen labeled with radioactive iodine ( 125I ) was reduced from 16.0 % in the control group to 4.2 % in treated patients . More important , the incidence of popliteal or femoral vein thrombosis was reduced from 2.9 % to 1.0 % . Prophylaxis result ed in a slight increase in bleeding-minor wound hematoma , mean volume of blood transfused , and a post-operative hematocrit fall in treated patients . However , increased bleeding was clinical ly minor , and prophylaxis was well tolerated 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 OBJECTIVE To compare efficacy , safety , and feasibility of adjusted-dose oral anticoagulants ( OAC ) versus fixed-dose subcutaneous low molecular weight heparin ( LMWH ) for the prevention of deep venous thrombosis ( DVT ) in patients who have undergone elective hip or knee replacement . DESIGN Multicentre , single blind r and omised trial . OAC ( acenocoumarol , target International Normalised Ratio , 2.0 - 3.0 ) and LMWH ( nadroparine , 60 aXa IU/kg once daily ) were started preoperatively and continued for 10 days . All outcome measures were adjudicated by an independent committee unaware of treatment allocation . SUBJECTS 672 consecutive patients scheduled for elective hip or knee replacement surgery . All patients wore bilateral graduated compression stockings . MAIN OUTCOME MEASURES The endpoint for the assessment of efficacy was venography confirmed DVT or confirmed symptomatic pulmonary embolism . The endpoint for the assessment of safety was clinical ly important bleeding during study treatment or within 48 h of the end of treatment . RESULTS Among the 517 patients with interpretable venograms , 391 had a hip replacement and 126 had a knee implant . DVT was demonstrated in 50 ( 20 % ) of 257 patients allocated to OAC and 43 ( 17 % ) of 260 patients allocated to nadroparine ( p = 0.45 ) , for an absolute difference in DVT incidence of 2.9 % in favour of nadroparine ( 95 % CI , -3.7 - 9.5 ) . Clinical ly important bleeding occurred in eight ( 2.3 % ) of the 342 oral anticoagulant treated patients and in five ( 1.5 % ) of the 330 nadroparine treated patients ( p = 0.62 ) , for an absolute difference in favour of nadroparine of 0.8 % ( 95 % Cl , -1.3 - 2.9 ) . CONCLUSION Patients who undergo major orthopaedic operations have a high risk of venous thromboembolism . Once daily fixed-dose subcutaneous nadroparine is at least as efficacious and safe as daily adjusted OAC for prophylaxis against DVT after hip or knee implantation but is more simple to administer Abstract The efficacy of small doses of peri-operative subcutaneous heparin in preventing deep venous thrombosis has been studied in a controlled clinical trial involving 251 patients undergoing major operations . The results indicate that the regimen of sodium heparin used was safe . It reduced the frequency of postoperative deep venous thrombosis from 24 % in the control group to 0·8 % in the test group as detected by the 125 I-fibrinogen test . In addition it reduced the frequency of the dangerous extensive thrombi often responsible for pulmonary emboli from 7.4 % to In a prospect i ve study all  positive phlebographies within the well-defined population of the city of Malmö , Sweden , during 1987 were studied in order to determine the incidence of  deep venous thrombosis ( DVT ) .  Epidemiological data were analysed for the detection of patient groups at increased risk of DVT .  The incidence was found to be equal for both sexes , i.e. 1.6 per 1000 inhabitants a year . Risk factors were found to be in accordance with earlier studies . The median age for men was 66 years , compared to 72 years for women . At diagnosis of DVT , 19 % of subjects had a known malignancy and within 1 year 5 % ( 19 cases ) developed a new malignancy . Of the men , 29 % had  postoperative or post-traumatic ( fracture ) DVT  , compared to 46 % of the women . Fewer patients with DVT than expected ( 39 % ) belonged to blood group 0 ( 31 % ) ( P less than 0.005 ) . Pulmonary embolism 
    Output:
    
Low-molecular-weight heparin initiated 12 hours before surgery or 12 to 24 hours postoperatively was not more effective than oral anticoagulants .
Low-molecular-weight heparin initiated postoperatively in close proximity to surgery at half the usual dose was not associated with a clinical ly or statistically significant increase in major bleeding rates ( P = .16 ) .
The timing of initiating low-molecular-weight heparin significantly influences antithrombotic effectiveness .
The practice of delayed initiation of low-molecular-weight heparin prophylaxis results in suboptimal antithrombotic effectiveness without a substantive safety advantage