***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The efficacy and safety of a low molecular weight heparin ( LMWH ) given as a single predialysis bolus injection was compared to st and ard heparin ( SH ) administered with a continuous infusion in a r and omized , 6 month , open follow-up study in 70 patients undergoing hemodialysis . No major bleeding or adverse events were encountered during a total of 4,000 dialysis procedures ( 2,000 with LMWH ) . Clot formation in the extracorporeal circuit was minimal and comparable between the groups at 4 , 13 , and 26 weeks after the start of the study . No accumulation of LMWH anticoagulant activity was noted . It is concluded that the use of LMWH is a safe , effective , and less complex alternative to SH STUDY OBJECTIVE To evaluate the relationship between impaired renal function and antifactor Xa activity in patients receiving dalteparin .  DESIGN Open-label prospect i ve study . SETTING Inpatient and outpatient units of a large teaching hospital . SUBJECTS Eleven patients with renal impairment and 11 control subjects with normal renal function . INTERVENTION Subjects were administered dalteparin at a dosage of approximately 100 U/kg subcutaneously every 12 hours . MEASUREMENTS AND MAIN RESULTS Peak steady-state antifactor Xa levels were compared between the groups . Mean + /- SD levels were similar for patients with and without renal impairment : 0.47 + /- 0.25 and 0.55 + /- 0.20 U/ml , respectively . A test of equivalency showed statistical significance ( p=0.0001 ) . CONCLUSION No meaningful difference in peak antifactor Xa activity was found between patients with renal impairment and control subjects . To the extent that peak antifactor Xa levels can be used as markers for adjusting doses of dalteparin , these data suggest that such adjustments are not necessary for patients with renal impairment who are not receiving dialysis BACKGROUND Use of low-molecular-weight heparins is avoided in patients with renal insufficiency because of concerns about an excessive anticoagulant effect and increased bleeding risk . To challenge this premise , we evaluated if deep vein thrombosis ( DVT ) prophylaxis with dalteparin sodium confers an excessive anticoagulant effect in critically ill patients with severe renal insufficiency . METHODS We conducted a multicenter , single-arm clinical trial of DVT prophylaxis with dalteparin sodium , 5000 IU once daily in critically ill patients with a creatinine clearance lower than 30 mL/min ( to convert to milliliters per second , multiply by 0.0167 ) . Bioaccumulation was defined by a trough anti-Xa level higher than 0.40 IU/mL , measured twice weekly . The pharmacodynamic properties of dalteparin were assessed by serial anti-Xa levels measured on days 3 , 10 , and 17 . RESULTS We enrolled 156 patients with a mean ( SD ) creatinine clearance of 18.9 ( 6.5 ) mL/min ; 18 were excluded because they died or were discharged before testing ( n = 3 ) or had prevalent DVT ( n = 15 ) . Of 138 patients included , the median ( interquartile range [ IQR ] ) duration of dalteparin exposure was 7 ( 4 - 12 ) days . In 120 patients who had at least 1 trough anti-Xa level ( 427 total measurements ) , no patient had bioaccumulation ( 0 % ; 95 % confidence interval [ CI ] : 0%-3.0 % ) ; the median ( IQR ) trough anti-Xa level was undetectable ( < 0.10 IU/mL [ < 0.10 to < 0.10 IU/mL ] ) . Based on serial measurements , peak anti-Xa levels were 0.29 to 0.34 IU/mL and trough levels were lower than 0.06 IU/mL. Deep vein thrombosis occurred in 7 of 138 patients ( 5.1 % ; 95 % CI , 2.5%-10.1 % ) ; major bleeding occurred in 10 patients ( 7.2 % ; 95 % CI , 4.0%-12.8 % ) , all with trough anti-Xa levels of 0.18 IU/mL or lower . CONCLUSION In critically ill patients with severe renal insufficiency , DVT prophylaxis with dalteparin sodium , 5000 IU once daily , is not associated with an excessive anticoagulant effect due to drug bioaccumulation and is unlikely to contribute to bleeding . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00138099 BACKGROUND Enoxaparin dosage for obese patients and patients with renal impairment remains controversial . OBJECTIVE To compare anti-factor Xa activity ( anti-Xa ) among obese and renal impairment patients to patients with healthy weight and adequate renal function . DESIGN Open , prospect i ve , nonr and omized clinical trial . SETTING A major community teaching hospital . PATIENTS A total of 233 patients with prescription of enoxaparin . INTERVENTIONS Enoxaparin 1.5 mg/kg once daily or 1 mg/kg twice daily except those on dialysis , who received 75 % of the dose . MEASUREMENTS Anti-Xa was measured 4 h post-injection on day 2 or 3 . RESULTS Mean ( 95 % confidence interval ( 95 % CI ) ) anti-Xa was equal to 1.14 IU/mL ( 1.07 - 1.21 ) and 1.14 IU/mL ( 1.08 - 1.20 ) among patients who received one ( n=92 ) and two injections ( n=122 ) per day , respectively . Anti-Xa increases with body mass index ( BMI ) ( 0.01 IU/mL for each kg/m2 ; 95 % CI : 0.002 - 0.017 ) , but the increase is insufficient to reach supratherapeutic anti-Xa . Anti-Xa decreases with higher creatinine clearance ( CrCl ) ( -0.003 IU/mL for each mL/min ; 95 % CI : -0.006 to -0.001 ) . On the twice-daily regimen , this is sufficient to reach supratherapeutic anti-Xa . The odd ratio ( OR ) ( 95 % CI ) of having a nontherapeutic anti-Xa is equal to 2.28 ( 1.25 - 4.16 ) when enoxaparin is administered twice daily and to 3.03 ( 1.16 - 7.86 ) among severe renal impairment patients ( < or = 30 mL/min ) . CONCLUSIONS Based on Anti-Xa , no dosage adjustments are required in obese patients . In renally impaired patients , adjustments may be necessary when enoxaparin is administered twice daily Enoxaparin is a low molecular weight heparin ( LMWH ) that has been shown to be effective in deep vein thrombosis , pulmonary embolism , and unstable angina . Because renal function plays an important role in the clearance of LMWH , the authors sought to investigate the effect of renal function on enoxaparin . This prospect i ve multiple-dose study evaluated 18 patients with varying degrees of renal function initiated on enoxaparin 1 mg/kg subcutaneously every 12 hours .  Peak blood levels of anti-Xa concentrations were obtained 4 + /- 0.5 hours postdose after receiving at least three doses of enoxaparin . The median antifactor Xa levels were higher in patients with creatinine clearance ( CLCr ) < or = 30 mL/min compared to CLCr > or = 31 mL/min ( 1.34 IU/mL vs. 0.91 IU/mL , respectively , p < 0.05 ) . A linear correlation was established between creatinine clearance and anti-Xa concentrations ( p < 0.0005 ) . On the basis of the data , the authors believe that a dose adjustment is necessary in patients receiving repeated doses of enoxaparin with CLCr < or = 30 mL/min Abstract Objectives : Too few very elderly patients with an age-related renal impairment are included in clinical trials . We conducted a study in order to evaluate the safety profile of tinzaparin , a low molecular weight heparin ( LMWH ) , given at a curative dose ( 175 IU/kg once daily ) in very elderly patients treated for up to 30 days . Setting : An 800-bed geriatric hospital . Design : A 1-year prescribing study . Patients : Consecutive in- patients older than age 70 , whose creatinine clearance was above 20 ml/min , and requiring full anticoagulation with LMWH were included . Measurements : Safety parameters ( major bleeding/heparin-induced thrombocytopenia/death ) were recorded . Plasma anti-Xa activity levels were regularly measured throughout the treatment period . Results : Two-hundred in- patients , mean age 85.2 ± 6.9 years ( 70 to 102 ) , mean creatinine clearance 51.2 ± 22.9 ml/min , were given tinzaparin . Six patients died during the treatment period : only one could be related to the anticoagulation treatment . Three major bleeding episodes ( 1.5 % ) were reported . Antithrombotic drug interactions likely contributed to the bleeding event in two of them . Heparin-induced thrombocytopenia was confirmed in two patients ( 1 % ) . No correlation was found between anti-Xa activity and creatinine clearance or age . Conclusions : Tinzaparin can be used safely at a curative dose in very elderly patients as long as ( i ) the accurate bodyweight-adjusted dose is given ; ( ii ) platelet counts and anti-Xa levels are regularly monitored and ; ( iii ) the interaction with other antithrombotic drugs is correctly managed Low-molecular-weight heparins ( LMWHs ) accumulate in patients with impaired renal function . As this accumulation depends on heparin chain length and subsequent reticulo-endothelial/renal elimination , LMWHs might have different pharmacodynamic profiles . The primary objective was to examine if any accumulation effect of two LMWHs , enoxaparin and tinzaparin , occurred after repeated administration of a prophylactic dose over eight days in elderly patients ( age > 75 years ) with creatinine clearance between 20 and 50 ml/min and body weight < 65Kg . Patients were openly r and omized to two groups ( enoxaparin 4,000 IU or tinzaparin 4,500 IU once daily ) . Anti-Xa was measured on day 1 and day 8 . Blood sample s were taken at 0 , 2 , 4 , 5 , 6 , 9 , 12 , 16 and 24 hours . The primary end point was the accumulation factor calculated as a ratio between the maximal anti-Xa activity on day 1 and day 8 . Fifty-five patients were included ( mean age 87.9 + /- 5.5 ) . The creatinine clearance was 34.7 + /- 11.4 ml/min ; the body weight was 52.3 + /- 8.6 kg . The accumulation factor defined was not significant for tinzaparin ( 1.05 , p = 0.29 ) while it was significantly enhanced for enoxaparin ( 1.22 , p < 0.0001 ) . In this pharmacodynamic study performed in elderly patients with impaired renal function , a statistically significant accumulation effect was observed after eight days of prophylactic treatment with enoxaparin but not with tinzaparin , which are two LMWHs with different chain lengths . Trials based on clinical end points should be conducted to evaluate the clinical relevance of these observations Background The safety and optimal use of prophylactic treatment with low-molecular-weight heparins in elderly patients with impaired renal function remain undefined . Methods The primary aim of this study was to analyse , in ‘ real life ’ , the influence of renal function , as assessed by Creatinine clearance ( CLcr ) , on the level of anti-Xa activity in medical hospitalised elderly patients receiving prophylactic dosages of enoxaparin . Consecutive hospitalised acutely ill medical patients aged ≥75 years receiving daily dosages of enoxaparin 4000IU for up to 10 days were prospect ively enrolled in two centres . Peak anti-Xa activity was measured at the beginning and during the course of therapy . Results One hundred and twenty-five patients ( 31 men , 94 women ) , mean age 87.5 ± 6.3 years , mean bodyweight 56.4±11.9 kg and mean CLcr 39.8 ± 16.1 mL/min , were enrolled in the study . The mean maximum anti-Xa activity ( day 1 to day 10 ) [ anti-Xamaxl – l0 ] was 0.64 ± 0.23 IU/mL ( range 0.24–1.50 IU/mL ) . Weak negative correlations were found between CLcr and anti-Xamax and between bodyweight and anti-Xamax . Mean anti-Xamax was slightly but significantly higher in patients with CLcr of 20–30 mL/min compared with patients with CLcr of 31–40,41–50 or 51–80 mL/min ( 0.72 versus 0.61 , 0.61 and 0.60 IU/ m 
    Output:
    
Results For dalteparin and tinzaparin , no accumulation was observed .
Enoxaparin , on the other h and , did lead to accumulation in patients with renal insufficiency , although not in patients undergoing renal replacement therapy .
Bemiparin and certoparin also did show accumulation .
Conclusions In this systematic review , we show that prophylactic dosages of tinzaparin and dalteparin are likely to be safe in patients with renal insufficiency and do not need dose reduction based on the absence of accumulation .
However , prophylactic dosages of enoxaparin , bemiparin , and certoparin did show accumulation in patients with a creatinine clearance ( CrCl ) below 30 ml/min , and therefore , dose reduction is required .
The differences in occurrence of accumulation seem to depend on the mean molecular weight of LMWHs