***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: BACKGROUND The role and dose of anticoagulants in thromboprophylaxis for patients with cancer receiving chemotherapy through central venous catheters ( CVCs ) is controversial . We therefore assessed whether warfarin reduces catheter-related thrombosis compared with no warfarin and whether the dose of warfarin determines the thromboprophylactic effect . METHODS In 68 clinical centres in the UK , we r and omly assigned 1590 patients aged at least 16 years with cancer who were receiving chemotherapy through CVCs to no warfarin , fixed-dose warfarin 1 mg per day , or dose-adjusted warfarin per day to maintain an international normalised ratio between 1.5 and 2.0 . Clinicians who were certain of the benefit of warfarin r and omly assigned patients to fixed-dose or dose-adjusted warfarin groups . The primary outcome was the rate of radiologically proven , symptomatic catheter-related thrombosis . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N 50312145 . FINDINGS Compared with no warfarin ( n=404 ) , warfarin ( n=408 ; 324 [ 79 % ] on fixed-dose and 84 [ 21 % ] on dose-adjusted ) did not reduce the rate of catheter-related thromboses ( 24 [ 6 % ] vs 24 [ 6 % ] ; relative risk 0.99 , 95 % CI 0.57 - 1.72 , p=0.98 ) . However , compared with fixed-dose warfarin ( n=471 ) , dose-adjusted warfarin ( n=473 ) was superior in the prevention of catheter-related thromboses ( 13 [ 3 % ] vs 34 [ 7 % ] ; 0.38 , 0.20 - 0.71 , p=0.002 ) . Major bleeding events were rare ; an excess was noted with warfarin compared with no warfarin ( 7 vs 1 , p=0.07 ) and with dose-adjusted warfarin compared with fixed-dose warfarin ( 16 vs 7 , p=0.09 ) . A combined endpoint of thromboses and major bleeding showed no difference between comparisons . We did not note a survival benefit in either comparison . INTERPRETATION The findings show that prophylactic warfarin compared with no warfarin is not associated with a reduction in symptomatic catheter-related or other thromboses in patients with cancer and therefore we should consider newer treatments . FUNDING Medical Research Council and Cancer Research UK Lenalidomide plus dexamethasone is effective in the treatment of multiple myeloma ( MM ) but is associated with an increased risk of venous thromboembolism ( VTE ) . This prospect i ve , open-label , r and omized sub study of a phase 3 trial compared the efficacy and safety of thromboprophylaxis with low-dose aspirin ( ASA ) or low-molecular-weight heparin ( LMWH ) in patients with newly diagnosed MM , treated with lenalidomide and low-dose dexamethasone induction and melphalan-prednisone-lenalidomide consolidation . Overall , 342 patients who did not have clinical indications or contraindications to antiplatelet or anticoagulant therapy were r and omly assigned to receive ASA 100 mg/d ( n = 176 ) or LMWH enoxaparin 40 mg/d ( n = 166 ) . The incidence of VTE was 2.27 % in the ASA group and 1.20 % in the LMWH group . Compared with LMWH , the absolute difference in the proportion of VTE was 1.07 % ( 95 % confidence interval , -1.69 - 3.83 ; P = .452 ) in the ASA group . Pulmonary embolism was observed in 1.70 % of patients in the ASA group and none in the LMWH group . No arterial thrombosis , acute cardiovascular events , or sudden deaths were reported . No major hemorrhagic complications were reported . In previously untreated patients with MM receiving lenalidomide with a low thromboembolic risk , ASA could be an effective and less-expensive alternative to LMWH thromboprophylaxis Purpose Whether an anticoagulant prophylaxis is needed for patients with cancer with a central venous catheter is a highly controversial subject . We design ed a study to compare different prophylactic strategies over 3 months of treatment . Methods We performed a phase III prospect i ve , open-label r and omized trial . After the insertion of a central venous access device , consecutive patients with planned chemotherapy for cancer were r and omized to no anticoagulant prophylaxis , low molecular weight heparin [ low molecular weight heparin ( LMWH ) ; with isocoagulation doses ] , or warfarin 1 mg/day . Treatments were given over the first 3 months . Doppler ultrasound and venographies were performed on days 1 and 90 , respectively , or sooner in case of clinical presumption of thrombosis . Results A total of 420 patients were r and omized , and 407 were evaluable . Forty-two catheter-related deep vein thrombosis ( DVT ) occurred ( 10.3 % ) , 20 in those with no anticoagulation , 8 in those receiving warfarin , and 14 in those receiving LMWH . Nine additional non-related catheter deep vein thrombosis ( CDVT ) occurred . Anticoagulation significantly reduced the incidence of catheter-related DVT ( p = 0.035 ) and catheter non-related DVT ( p = 0.007 ) , with no difference between warfarin and LMWH .  Safety was good ( 3.4 % of attributable events ) but compliance with r and omized prophylaxis was lower than expected . Conclusions Prophylaxis showed a benefit regarding catheter-related and non-catheter-related DVT with no increase in serious side effects Summary : A r and omized controlled trial was undertaken comparing the efficacy and safety of low molecular weight ( LMW ) heparin ( Fragmin ) with sodium heparin for prophylaxis against postoperative thromboembolic disease after major gynaecological surgery . Women were r and omized to receive subcutaneous injections of 5,000 U of either once daily LMW heparin or twice daily sodium heparin . A total of 566 women were recruited , of whom 552 completed the study . Most women ( 461 ) had malignant disease and 430 of these underwent radical surgery . The remainder underwent major , but not radical surgery . There were 5 thromboembolic events in the LMW heparin group and 2 in the sodium heparin group , with no significant difference between these groups . No significant difference was found in the incidence of intraoperative or postoperative transfusion in the 2 groups . The decision of which heparin to use in routine practice can not be made on clinical grounds Central vein thrombosis is the major Hickman catheter complication in our patient population . After noting clots attached to the disposable infusion plug of these catheters , we prospect ively determined whether the presence of clots indicated a high-risk group for thrombosis . Forty-three patients ( 41 with solid tumor , two with acute leukemia ) were studied .  Catheters were flushed daily with heparin ( 10 units/ml ) , and urokinase ( 5000 - 10,000 units ) was injected when blood could not be drawn . Clots within the catheter lumen were detected visually after expressing , onto a 4 X 4-inch gauze pad , the first 5 - 10 ml of admixed blood and flush solution or iv infusion fluid drawn from the catheter prior to blood drawing . Clots were detected in 153 of 508 specimens ( 30 % ) . Forty of 43 patients had clots , varying in length from fragments to 5 cm , in at least one specimen . In patients and out patients had a similar percentage of clotted specimens . Eight patients developed clinical ( six ) or autopsy-proven ( two ) thrombosis . There was no difference between patients with and without thrombosis in percent of discards positive for clots . This study indicates that clots are frequently present in the lumina of Hickman catheters . It is likely that these clots embolize to the lungs when catheters are flushed . Consequences of embolization are unknown PURPOSE Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism . There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment . Furthermore , the incidence of such events in these patients is dependent on the achieved International Normalized Ratio ( INR ) . The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR . PATIENTS AND METHODS In a retrospective analysis , the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy . Eligible patients participated in two multicenter , r and omized clinical trials on the initial treatment of venous thromboembolism . Patients were initially treated with heparin ( st and ard or low-molecular weight ) . Treatment with vitamin K antagonists was started within 1 day and continued for 3 months , with a target INR of 2.0 to 3.0 . RESULTS In 1,303 eligible patients ( 264 with malignancy ) , 35  recurrences  and 12  bleeds occurred . Patients with malignancy , compared with nonmalignant patients , had a clinical ly and statistically significantly increased overall incidence of recurrence ( 27.1 v 9.0 , respectively , per 100 patient-years ) as well as bleeding ( 13.3 v 2.1 , respectively , per 100 patient-years ) . In both groups of patients , the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0 . CONCLUSION Although adequately dosed vitamin K antagonists are effective in patients with malignant disease , the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy Background Advanced pancreatic cancer ( APC ) , beside its high mortality , causes the highest rates of venous thromboembolic events ( VTE ) . Enoxaparin , a low molecular weight heparin ( LMWH ) , is effective in prevention and treatment of VTE . Some small studies indicated that this benefit might extend to patients with cancer and probably prolong survival due to independent mechanisms . We initiated this safety investigation to get feasibility information on intensified chemotherapy combined with LMWH in out patients with APC treated in 1st line . Methods The trial was a prospect i ve , open-label , single center investigation in out patients with inoperable pancreatic cancer who were treated with intensified first-line chemotherapy along with concomitant application of subcutaneous LMWH .  The combined chemotherapy consisted of gemcitabine 1 g/m2 ( 30 min ) , 5-FU 750 mg/m2 ( 24 h ) , folinic acid 200 mg/m2 ( 30 min ) , and Cisplatin 30 mg/m2 ( 90 min ) on day 1 and 8 ; q3w for the first 12 weeks ( GFFC ) followed by gemcitabine alone in patients without cancer progression . The simultaneous application of prophylactic enoxaparin started on day 1 of chemotherapy with a fixed dose of 40 mg daily . Statistical analyses were performed using R 3.01 with software package CMPRSK and SPSS software v19.0 . Results The investigation was stopped after recruitment of 19 patients . At this time 15 patients had completed the required 12 weeks of treatment . Based on 71 cycles of GFFC + enoxaparin ( median 4/pt [ range : 2–4 ] ) and 108 cycles of single-agent gemcitabine + enoxaparin ( median 4/pt [ range : 0–18 ] ) the cumulative frequency of NCI-CTC toxicities grade 3/4 was below 10 % . One case ( 5 % ) of a symptomatic non-lethal thromboembolic event was observed while receiving LMWH treatment . No severe bleeding event as defined in the protocol has been observed . The median overall survival was 10.05 [ 95 % CI : 8.67 - 18.14 ] months . Conclusions The addition of enoxaparin to GFFC chemotherapy is feasible , safe and does not appear to affect the efficacy or the toxicity profile of the chemotherapy regimen in patients with advanced pancreatic adenocarcinoma . Based on these findings we have initiated the r and omized CONKO-004 trial to examine whether enoxaparin reduces the incidence of thromboembolic events or increases overall outcome .Trial registration Clinical Trials NCT01945879 Background Advanced pancreatic cancer , in addition to its high mortality , is characterized by one of the highest rates of venous thromboembolic events ( VTE ) as compared to other types of cancer . Enoxaparin , a low molecular weight heparin ( LMWH ) , has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients . Results of some small studies suggest that this benefit might extend to patients with cancer , however , 
    Output:
    
Compared with no anticoagulation , we found a statistically significant reduction of symptomatic DVT with heparin and asymptomatic DVT with VKA .
Heparin was associated with a higher risk of thrombocytopenia and asymptomatic DVT when compared with VKA .
However , the findings did not rule out other clinical ly important benefits and harms .