***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: Introduction Critically ill patients are predisposed to venous thromboembolism . We hypothesized that higher doses of enoxaparin would improve thromboprophylaxis without increasing the risk of bleeding . Peak anti-factor Xa ( anti-Xa ) levels of 0.1 to 0.4 IU/ml reflect adequate thromboprophylaxis for general ward patients . Studies conducted in orthopaedic patients demonstrated a statistically significant relationship between anti-Xa levels and wound haematoma and thrombosis . Corresponding levels for critically ill patients may well be higher , but have never been vali date d in large studies . Methods Eighty critically ill patients weighing 50 to 90 kilograms were r and omised in a double-blinded study to receive subcutaneous ( sc ) enoxaparin : 40 mg once daily ( QD ) , 30 mg twice daily ( BID ) , 40 mg BID , or 1 mg/kg QD , each administered for three days . Anti-Xa activity was measured at baseline , and daily at 4 , 12 , 16 and 24 hours post administration . Antithrombin , fibrinogen , and platelets were measured at baseline and twice daily thereafter . Results Two patients were transferred prior to participation . On day 1 , doses of 40 mg QD ( n = 20 ) and 40 mg BID ( n = 19 ) yielded mean peak anti-Xa of 0.20 IU/ml and 0.17 IU/ml respectively . A dose of 30 mg BID ( n = 20 ) result ed in much lower levels ( 0.08 IU/ml ) . Patients receiving 1 mg/kg QD ( n = 19 ) achieved near steady-state mean peak anti-Xa levels from day 1 ( 0.34 IU/ml ) . At steady state ( day 3 ) , mean peak anti-Xa levels of 0.13 IU/ml and 0.15 IU/ml were achieved with doses of 40 mg QD and 30 mg BID respectively . This increased significantly to 0.33 IU/ml and 0.40 IU/ml for doses of 40 mg BID and 1 mg/kg QD respectively . Thus anti-Xa response profiles differed significantly over the three days between enoxaparin treatment groups ( P < 0.0001 ) . Doses of 40 mg BID and 1 mg/kg QD enoxaparin yielded target anti-Xa levels for over 80 % of the study period . There were no adverse effects . Conclusions Doses of 40 mg QD enoxaparin ( Europe ) or 30 mg BID ( North America ) yield levels of anti-Xa which may be inadequate for critically ill patients . A weight-based dose yielded the best anti-Xa levels without bioaccumulation , and allowed the establishment of near steady-state levels from the first day of enoxaparin administration . Trial registration Current Controlled Trials IS RCT N91570009 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 WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Venous thromboembolism is a frequent complication in critically ill patients that has a negative impact on patient outcomes . Critically ill patients have significantly lower plasma anti-factor-Xa activity levels compared with control patients after administration of subcutaneous heparin . The clinical relevance of the different anti-factor-Xa levels after prophylactic doses of low molecular weight heparin ( LMWH ) in critically ill patients is not completely understood . WHAT THIS STUDY ADDS The st and ard dose of 40 mg enoxaparin led to a significant increase in anti-FXa levels in this selected cohort of ICU patients with normal renal function . This study found only subtle pharmacokinetic differences , but a comparable pharmacodynamic action , after enoxaparin administration in critically ill and normal medical ward patients . Thrombin generation with TGA RC-low and TGARC-high reagents was significantly reduced in ICU and normal ward patients after receiving LMWH . Both readouts appear equally useful for estimating the pharmacodynamics of enoxaparin . The ex vivo model of thrombosis was used for the first time in patients to evaluate the anti-thrombotic activity of LMWH . This method did not show any difference in thrombus formation after administration of enoxaparin in the individual group of patients . AIM In critically ill patients , reduced anti-FXa plasma activity following subcutaneous administration of enoxaparin or nadroparin has been described . In this study , we aim ed to investigate the bioactivity of enoxaparin in critically ill patients and controls . METHODS A prospect i ve , controlled , open label study was performed on a medical intensive care unit ( ICU ) and a general medical ward . Fifteen ICU patients ( male = 12 , median age 52 years [ IQR 40 - 65 ] , with a median Simplified Acute Physiology Score of 30 [ IQR 18 - 52 ] ) and sex- and age-matched medical ward patients were included . The anti-FXa plasma activity was measured after a single subcutaneous dose of40 mg enoxaparin . The thrombus size of a clot formed in an ex vivo perfusion chamber and endogenous thrombin potential ( ETP ) were measured . RESULTS The anti-FXa plasma activity increased significantly after enoxaparin administration , with peak levels at 3 h after treatment , but was comparable between the ICU and medical ward groups ( median 0.16 IU ml-1 [ IQR 0 - 0.22 IU ml-1 ] vs. 0.2 IU ml-1 [ IQR 0.15 - 0.27 IU ml-1],respectively , P = 0.13 ) . The area under the anti-FXa activity curve from 0–12 h was similar between the groups ( median 0.97 IU ml-1 h [ IQR0.59 - 2.1 ] and 1.48 IU ml-1 h1 [ IQR 0.83 - 1.62 ] , P = 0.42 for the ICU group compared with the control group , respectively ) . The ETP was lower in the ICU group ( P < 0.05 ) at baseline , but it was comparable at 3 h between the groups . Thrombus size decreased at 3 h compared with pre-dose ( P = 0.029 ) and was not different between the groups . CONCLUSION Similar bioactivity was achieved with a st and ard dose of subcutaneous enoxaparin in this selected cohort of ICU and general ward patients with normal renal function Introduction Intensive care unit ( ICU ) patients often suffer from subcutaneous oedema , due to administration of large fluid volumes and the underlying pathophysiological condition . It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin , a low molecular weight heparin , when it is given by subcutaneous administration for venous thromboembolism prophylaxis . The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema . Methods This non-r and omized open parallel group follow-up pilot study was conducted in two mixed medical-surgical intensive care units at two teaching hospitals . Seven ICU patients with subcutaneous oedema ( index group ) and seven ICU patients without subcutaneous oedema ( reference group ) were studied .  Anti-Xa activity was determined at 0 , 3 , 4 , 6 , 8 , 12 and 24 hours after subcutaneous administration of 2,500 IU dalteparin . Plasma concentrations of factor anti-Xa activity were measured using a chromogenic factor Xa inhibition assay . Results The characteristics of the index group were : age , 58 years ; male/female ratio , 5/2 ; body mass index at admission , 23.4 kg/m2 ( at study day , 30.6 kg/m2 ) . The characteristics of the reference group were : age , 49 years ; male/female ratio , 6/1 ; body mass index at admission , 24.8 kg/m2 ( at study day , 25.0 kg/m2 ) . In the index group , creatinine clearance was lower compared to the reference group ( 71 versus 131 ml/minute , p = 0.003 ) . Sequential organ failure assessment score did not differ between index and reference groups ( 4 versus 5 ) . Mean arterial pressure was comparable between index and reference groups ( 91 versus 95 mmHg ) and within the normal range . The mean Cmax value was not different between ICU patients with and without subcutaneous oedema ( 0.15 ± 0.02 versus 0.14 ± 0.02 IU/ml , p = 0.34 ) . In the index group , the mean AUC(0–24 h ) value was slightly higher compared with the reference group ( 1.50 ± 0.31 versus 1.15 ± 0.25 h·IU/ml , p = 0.31 ) . This difference was not significant . Conclusion In this pilot study , there was no clinical ly relevant difference in anti-Xa activity after subcutaneous administration of 2,500 IU dalteparin for venous thromboembolism prophylaxis between ICU patients with and without subcutaneous oedema . Critically ill patients seem to have lower anti-Xa activity levels than healthy volunteers BACKGROUND Deep venous thromboses ( DVT ) continue to cause significant morbidity in critically ill patients . St and ard prophylaxis for high risk patients includes twice-daily dosing with 30 mg enoxaparin . Despite prophylaxis , DVT rates still exceed 10 % to 15 % . Anti-Xa levels are used to measure the activity of enoxaparin and 12-hour trough levels < or=0.1 IU/mL have been associated with higher rates of DVT in orthopedic patients . We hypothesized that low Anti-Xa levels would be found in critically ill trauma and surgical patients and that low levels would be associated with higher rates of DVT . METHODS All patients on the surgical intensive care unit ( ICU ) service were prospect ively followed . In the absence of contraindications , patients were given prophylactic enoxaparin and anti-Xa levels were drawn after the third dose . Trough levels < or=0.1 IU/mL were considered low .  Screening duplex exams  were obtained within 48 hours of admission and then weekly . Patients were excluded if they did not receive a duplex , if they had a prior DVT , or if they lacked correctly timed anti-Xa levels .  DVT rates and demographic data were compared between patients with low and normal anti-Xa levels . RESULTS Data were complete for 54 patients . Eighty-five percent suffered trauma ( Injury Severity Score of 25 + /- 12 ) and 74 % were male . Overall , 27 patients ( 50 % ) had low anti-Xa levels . Patients with low anti 
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Of note , none of the studies detected any correlation with bleeding events and anti-FXa levels .
Based on the current literature , no definite conclusions can be drawn on targeted anti-FXa level in critically ill patients when using LMWH thromboprophylaxis