Weight-based Enoxaparin Dosing Research Articles

Comparison of postpartum anti-Xa levels following enoxaparin administration to prevent venous thromboembolism using 2 weight-based protocols: a randomized controlled trial

During the postpartum period, enoxaparin is given to high-risk women to prevent venous thromboembolism, a leading cause of maternal mortality. Enoxaparin activity is measured by peak plasma anti-Xa levels. The prophylactic range of anti-Xa is 0.2 to 0.6 IU/mL. Values above and below this range represent subprophylactic and supraprophylactic levels, respectively. Weight-based enoxaparin administration was superior to fixed-dose enoxaparin administration in achieving an anti-Xa prophylactic range. However, it is unknown which weight-based enoxaparin administration is superior (once daily weight categories vs 1 mg/kg body weight). This study aimed to compare the efficacy in reaching prophylactic anti-Xa levels and adverse effects profile of the 2 weight-based enoxaparin dosing protocols. A randomized open-label controlled trial was conducted. Women after delivery, who were intended to receive enoxaparin, were randomized to receive either enoxaparin treatment according to 1 mg/kg (up to 100 mg) or weight categories (≤90 kg, 40 mg; 91-130 kg, 60 mg; 131-170 kg, 80 mg; >170 kg, 100 mg). Plasma anti-Xa levels were obtained 4 hours after the second enoxaparin administration (day 2 of enoxaparin treatment). If the woman was still hospitalized, anti-Xa levels were also obtained on day 4. The primary endpoint was the proportion of women with anti-Xa levels within the prophylactic range at day 2. In addition, data regarding anti-Xa levels in different weight groups and rates of venous thromboembolism and adverse effects were evaluated. Of note, 60 and 64 women received enoxaparin according to 1 mg/kg and weight categories, respectively; moreover, 55 (92%) and 27 (42%) women reached the prophylactic range of anti-Xa at day 2, respectively (P<.0001). The mean anti-Xa levels on day 2 were 0.34±0.09 and 0.19±0.06 IU/mL, respectively (P<.0001). The anti-Xa levels were higher in the 1 mg/kg group than in the weight categories group in the subanalysis of different weight categories (51-70, 71-90, and 91-130 kg). There was no difference in anti-Xa levels on day 4 compared with day 2 in both cohorts (n=25). There was no case of supraprophylactic anti-Xa levels, venous thromboembolism events, or serious hemorrhage. Postpartum enoxaparin administration at 1 mg/kg was superior to weight categories in reaching anti-Xa prophylactic levels without leading to serious adverse effects. Given the high efficacy and safety profile, enoxaparin at 1 mg/kg once daily should be considered the preferred protocol for postpartum venous thromboembolism prophylaxis.

Anti-Factor Xa Level Monitoring for Enoxaparin Prophylaxis and Treatment in High-Risk Patient Groups.

Description Monitoring anti-factor Xa levels is a controversial topic in the inpatient setting due to resource utilization and unclear conditional guideline recommendations regarding this practice. Enoxaparin dosing in certain high-risk patient populations such as those with low body weight, obesity, renal insufficiency, and pregnancy has not been determined. The objective of this review was to assess the safety and efficacy of enoxaparin monitoring via anti-factor Xa levels in high-risk patient populations. The PubMed database was searched for articles related to low-molecular-weight heparin monitoring. Randomized controlled trials and meta-analyses that evaluated the safety and efficacy of enoxaparin prophylaxis and treatment in patients with extremes of weight, renal insufficiency, and pregnancy were selected. Fourteen studies representing four high-risk population patient groups were included. Patients with extremes of weight or who were pregnant were found to have subtherapeutic anti-factor Xa levels due to the weight-based dosing of enoxaparin. Those with renal insufficiency were found to be accumulating enoxaparin, indicating the need for a lower dose. Studies have shown that monitoring may be required in specific high-risk patient groups. Dose adjustments based on anti-factor Xa levels can prevent adverse events associated with enoxaparin. Further research involving larger patient populations would be necessary to determine the clinical efficacy of enoxaparin monitoring with anti-factor Xa levels.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

The efficacy of weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients: A systematic review and meta-analysis.

Trauma patients are at high risk of developing venous thromboembolism (VTE), and standard dosing enoxaparin regimens may be inadequate for prophylaxis. This meta-analysis was performed to clarify the efficacy of alternative dosing regimens for VTE prophylaxis in this high-risk group. The objective of this systematic review was to review the evidence regarding weight-based dosing of enoxaparin for VTE prophylaxis in trauma patients. A systematic database search was undertaken for studies comparing standard versus weight-based dosing of enoxaparin for VTE prophylaxis in adult trauma patients, 18 years or older. The primary outcome was the achievement of anti-factor Xa (AFXa) levels within the prophylactic range. Secondary outcomes included subprophylactic AFXa levels, supraprophylactic AFXa levels, VTE incidence, and bleeding events. Meta-analysis was conducted using both fixed- and random-effects models, and presented as odds ratios, risk ratios (RRs), and risk differences (RDs) with 95% confidence intervals (CIs). Four cohort studies were eligible for inclusion. Compared with standard dosing, weight-based enoxaparin prophylaxis dosing was associated with increased odds of prophylactic AFXa levels (odds ratio, 5.85; 95% CI, 3.02-11.30; p < 0.00001) and reduced risk of subprophylactic AFXa levels (RR, 3.97; 95% CI, 3.02-5.22; p < 0.00001). Standard dosing was associated with a reduced risk of supratherapeutic AFXa levels (RR, 0.23; 95% CI, 0.11-0.50; p = 0.0002), but this was not associated with a difference in risk of bleeding events (RD, -0.00; 95% CI, -0.02 to 0.01; p = 0.55). There was no statistical difference in incidence VTE between the two groups (RD, 0.01; 95% CI, -0.02 to 0.03; p = 0.64). Compared with standard dosing, weight-based enoxaparin dosing regimens are associated with increased odds of prophylactic range AFXa levels. Further investigation is required to determine if this translates into improved VTE prophylaxis and reduced VTE incidence. Systematic Review and Meta-Analysis; Level III.

Outcomes of Prophylactic Enoxaparin Against Venous Thromboembolism in Hospitalized Children

To assess the biochemical and clinical outcomes of hospitalized children who received prophylactic enoxaparin. We conducted a retrospective observational study of hospitalized children aged <18 years who received prophylactic enoxaparin against hospital-acquired venous thromboembolism (HA-VTE). Weight-based enoxaparin dosing was administered using a pharmacy-driven protocol, which later included a low molecular weight, anti-Xa level directed-dose adjustment strategy. Primary biochemical and clinical outcomes were achievement of goal anti-Xa range of 0.2 to 0.5 IU/mL and development of HA-VTE, respectively. Secondary clinical outcome was development of clinically relevant bleed. We analyzed 194 children with 13 (6.7%) infants aged <1 year and 181 (93.3%) older children aged ≥1 year. After the initial dose, only 1 (11.1%) infant, but 62 (57.9%) older children, achieved goal. Median number of anti-Xa levels until goal was 2 (interquartile range: 2-3) in infants and 1 (interquartile range: 1-2) in older children (P = .01). HA-VTE developed in 2 (15.4%) infants and 9 (5.0%) older children. Among children with anti-Xa level, HA-VTE developed less frequently in children who achieved (2.1%) than in those who did not achieve (13.6%) goal (P = .046). A total of 4 (2.1%) older children and no infants developed clinically relevant bleed. Among children with anti-Xa level, frequency of bleeding was comparable between children who did (3.2%) and did not achieve (0%) goal (P >.99). Our findings suggest the effectiveness and safety of an anti-Xa level directed strategy of prophylactic enoxaparin. However, this strategy should be investigated in prospective controlled studies.

Complications Associated with Administration of Post-operative Weight-Based Enoxaparin in Orthopaedic Trauma Patients.

BackgroundIn orthopedic-specific patients, limited evidence exists in regard to prophylactic weight-based enoxaparin dosing in the obese population. We examined the clinical outcomes of administering weight-based enoxaparin to obese orthopedic trauma patients.MethodsThis retrospective study involved 679 patients who underwent orthopedic trauma surgery and were admitted from 1/2016 to 6/2020 at a single institution. Of those patients, 156 patients met our inclusion criteria. Inclusion criteria included BMI>35 kg/m2 and received weight-based enoxaparin post-operatively (defined as any singular dose >40 mg at any time). Blood transfusion, documented hematoma, deep vein thrombosis (DVT), and return visits to the OR after the administration of weight-based enoxaparin were the primary endpoints assessed. Age, BMI, weight, injury severity score (ISS), sex, post-operative time to the first dose of enoxaparin, the total daily dose of enoxaparin, operating room (OR) blood loss, OR time, patient co-morbidities, and pre/post-operative hemoglobin were evaluated for a potential relationship with the primary endpoints.ResultsOne hundred and eighty-five surgeries were performed on a total of 156 patients. Thirty-six of the 185 (19%) surgeries required post-operative blood transfusion after weight-based enoxaparin was given. Higher ISS score, lower pre-operative hemoglobin, and lower post-operative hemoglobin were significant predictors of blood transfusion. Only increased post-operative time to the first dose of enoxaparin was significantly associated with DVT formation. Thirteen of the 156 patients (8.3%) had a post-operative hematoma after administration of enoxaparin, and four of the 13 patients required return to the OR for bleeding complications. ISS was the only significant predictor of post-operative hematoma formation.ConclusionPatients with a higher injury severity score are at an increased risk of adverse bleeding and may benefit from lower doses of enoxaparin administered earlier post-operatively.

An Inpatient COVID-19 Prophylaxis Protocol and Its Outcomes: Adherence and Efficacy

Introduction: Patients with coronavirus disease 2019 (COVID-19) have an increased risk for venous thromboembolic events. Thrombotic events contribute to the morbidity and mortality associated with COVID-19 infection, and have prompted investigation into strategies for mitigating thrombosis risk in patients hospitalized with COVID-19 infection. Our team reviewed the charts of patients hospitalized with COVID-19 pneumonia at a tertiary hospital in metropolitan Phoenix Arizona between 2020-2021, to assess frequency and efficacy of utilizing a VTE prophylaxis algorithm designed to prevent thrombosis in patients infected with COVID-19.Methods: A total of 846 patients were retrospectively evaluated to determine if they were treated with guideline-appropriate anticoagulation while hospitalized with COVID-19, as well as if they developed venous or arterial thrombotic events, or major or minor bleeds. 317 patients were excluded for taking therapeutic anticoagulation prior to admission, or for having a COVID-19 diagnosis >7 days after admission. Appropriate anticoagulation was determined by an institutionally designed COVID-19 thromboprophylaxis algorithm, based on platelet count, d-dimer, bleeding risk, and level of medical care required. Regimen options included: no anticoagulation, prophylactic enoxaparin (40 mg SQ daily) or heparin in the setting of kidney dysfunction, weight-based dosing of enoxaparin (40 mg SQ BID if BMI>40), intermediate intensity enoxaparin without thrombus (30 mg BID if BMI<40, or 40 mg BID if BMI>40), and therapeutic anticoagulation (for example enoxaparin 1 mg/kg BID) with thrombus.Demographics: Demographic data and clinical characteristics were collected for 529 patients. Average age was 59 years old, and the majority were men (58.4%). Most patients were White (58.3%), followed by Hispanic (17.8%), or Native American (15.7%). Fewer patients had a normal BMI (21.3%; BMI 18.5 - 24.9) compared to those who were overweight (31.2%; BMI 25-29.9) or obese (43.1% BMI > 30). Other comorbidities included Type 1 or Type 2 diabetes mellitus (N= 172, 32.5%), hypertension (N = 271, 51.2%), and hyperlipidemia (N = 176, 33.3%).Results: A total of 42 patients (8%), were diagnosed with a venous thrombosis during hospitalization. Patients admitted to the ICU were significantly more likely to have a thrombotic event of any type compared to non-ICU patients (21.6% to 5.7%; p < 0.001). Specifically, critically ill patients had higher incidences of deep vein thrombosis (9.5% to 0.7%), pulmonary emboli (8.1% to 4.8%), and superficial thrombi (2.7% to 0.2%). Only 1.1% of patients (6/529) experienced any bleeding, of which 3 were classified as a major bleed.Discussion: Among patients hospitalized at our institution with COVID-19, the majority were anticoagulated appropriately according to the COVID-19 thromboprophylaxis algorithm. Overall incidence of thrombosis in the study population was 8%. A significantly higher percent of critically ill patients had thrombi, supporting reports of correlation between severity of illness and thrombosis risk. The two regimens of anticoagulation least adhered to were weight-based and intermediate-based dosing, likely reflecting a departure from the hospital's thromboprophylaxis regimens prior to COVID-19 pandemic. Further studies are needed to characterize whether identifiable risk factors correlate with the incidence of thrombosis, and whether treatment with lower than recommended doses of anticoagulation, based on the COVID-19 thromboprophylaxis algorithm, were associated with thrombosis. DisclosuresNo relevant conflicts of interest to declare.

Effective use of weight-based enoxaparin for deep vein thrombosis chemoprophylaxis in patients with traumatic brain injury

BackgroundEnoxaparin is the recommended agent for deep vein thrombosis (DVT) chemoprophylaxis in trauma patients. Current literature suggests weight-based dosing is superior to standard dosing for adequate chemoprophylaxis. Literature regarding the use of weight-based enoxaparin in the setting of traumatic brain injury (TBI) however is limited. MethodsA retrospective analysis of adult trauma patients admitted between January 1, 2018 to February 28, 2019 was performed. Sixty-six patients with TBI receiving weight-based enoxaparin met inclusion criteria. Incidence of intracranial hemorrhage (ICH) expansion was the primary endpoint. Newly diagnosed venous thromboembolism (VTE) and death were secondary endpoints. ResultsTwo patients, out of sixty-six, had progression of their TBI requiring surgical intervention. Newly diagnosed VTE occurred in one patient. No deaths were due to ICH expansion or VTE. ConclusionsUse of weight-based enoxaparin dosing in the setting of TBI shows promise without an increased incidence of ICH expansion when compared to other studies.Level of Evidence and Study Type: Level IV, Therapeutic.

Achievement of goal anti-Xa activity with weight-based enoxaparin dosing for venous thromboembolism prophylaxis in trauma patients.

The purpose of this study was to evaluate the utility of routine anti-Xa peak monitoring for trauma patients initiated on weight-based enoxaparin for venous thromboembolism (VTE) prophylaxis and identify patient populations where monitoring is necessary. Retrospective study. Augusta University (AU) Medical Center in Augusta, Georgia, a level 1 trauma center. Adult patients admitted to the trauma surgery service requiring chemical VTE prophylaxis. At least three consecutive doses of enoxaparin 0.5 mg/kg subcutaneously every 12 hour for VTE prophylaxis prior to an anti-Xa peak as the initial chemical VTE prophylaxis strategy. The primary end point was the percentage of patients who achieved goal anti-Xa peak of 0.2-0.6 unit/ml. The incidence of newly diagnosed VTE and clinically significant bleeding were assessed as secondary end points. From January 1, 2018, through February 28, 2019, 300 patients met inclusion criteria. Anti-Xa peaks were within goal in 91% of all patients, 7.7% were below goal, and 1.3% were above goal. For patients who did not meet the goal, dose adjustments were made in 70.4% of patients. New levels were obtained in 73.7% of those patients, and all repeat levels was within goal. Clinically significant bleeding occurred in 5.3% of patients. Newly diagnosed VTE occurred in 1.7% of patients. The use of initial weight-based enoxaparin dosing in trauma patients routinely achieved the prespecified target anti-Xa goal. In conclusion, anti-Xa levels are not necessary for routine monitoring of weight-based enoxaparin for VTE prophylaxis in trauma patients. Incidence of clinically significant bleeding and newly diagnosed VTE were similar to previous studies.

Is Weight-Based Enoxaparin Dosing Safe to Use in the Setting of Traumatic Brain Injury?

Journal of the American College of Surgeons 231(4):p e239, October 2020. | DOI: 10.1016/j.jamcollsurg.2020.08.640

Weight-Based Enoxaparin for Venous Thromboembolism in Obesity Gives Similar Anti-Xa Levels to Patients

In trials assessing venous thromboembolism (VTE) treatment, obese patients are under-represented or excluded. The main objective of this article is to examine the safety of weight-based enoxaparin dosing in obesity, as assessed by anti-factor Xa (anti-Xa) activity, bleeding, and recurrence. A 5-year retrospective audit of patients with acute VTE, weighing > 100 kg, prescribed enoxaparin 1 mg/kg twice daily, with an anti-Xa level 2 to 6 hours post-dose. The primary outcome was anti-Xa levels, and the secondary outcomes were bleeding and recurrence. Results were compared with patients weighing < 100 kg (n = 64), and obese patients prescribed doses < 1 mg/kg (n = 28). One-hundred sixty-six patients weighing > 100 kg with VTE were identified, with 64 excluded for not fulfilling criteria. The remaining 102 patients had a median weight of 130 kg (range: 105-222 kg). The median peak anti-Xa level was 0.93 U/mL, with 56% of levels being in the proposed therapeutic range (0.5-1.0 U/mL), 40% > 1.0 U/mL, and 4% < 0.5 U/mL. The median anti-Xa levels and distribution were not significantly different between patients > 100 kg and patients < 100 kg, while obese patients prescribed < 1 mg/kg were more frequently subtherapeutic (21%). Regardless of weight, the majority of patients with moderate renal impairment (eGFR 30-59 mL/min) had an anti-Xa level > 1.0 U/mL (61%). In the obese patients, there was no major bleeding or recurrence within 30 days. In comparison, patients weighing < 100 kg, despite similar peak anti-Xa levels, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and cancer. These data support weight-based dosing of enoxaparin in obesity with no maximum dose, ensuring therapeutic drug levels, with anti-Xa levels suggested in obese patients with clinical risk factors for bleeding.

Weight-Based Enoxaparin Dosing for Venous Thromboembolism (VTE) >100kg Gives Similar Anti-Xa Levels to Patients

Background: In clinical trials assessing venous thromboemobolism (VTE) management, patients with obesity are under-represented or specifically excluded. The International Society on Thrombosis and Haemostasis advises against direct-acting oral anticoagulants in patients >120kg(1). Therefore, low-molecular weight heparin and warfarin remain the standard of care in this population.Objective: To assess weight-based enoxaparin dosing in VTE, with no capping of prescribed doses, comparing patients weighing >100kg with those weighing <100kg. The primary outcome was anti-Xa activity levels, as a surrogate marker of bleeding and recurrence risk, with the secondary outcome measures of major bleeding and VTE recurrence at 30 days.Methods: A 5-year retrospective audit of patients with acute VTE who were prescribed enoxaparin at 1mg/kg BD, with an anti-Xa level taken 2-6 hours post-dose. Patients with an eGFR <30 were excluded.Results: 166 patients weighing >100kg with acute VTE were identified, and 63 were excluded for not fulfilling all criteria. 64 patients weighing <100kg were assessed for comparison. Table 1 describes the patient characteristics, anti-Xa levels and clinical outcomes for patient above and below 100kg. Figure 1 demonstrates the anti-Xa levels in group 1 according to weight, and the distribution of anti-Xa levels below, within and above the therapeutic range (0.5-1.0U/mL).Discussion: Patients above and below 100kg dosed with 1mg/kg enoxaparin BD showed no significant difference in either median anti-Xa levels, or distribution of anti-Xa activity. Regardless of weight, the majority of patients with an eGFR of 30-59 mL/min had anti-Xa levels >1.0U/mL. The obese patients did not suffer any major bleeding or VTE recurrence within 30 days. In comparison, the patients weighing <100kg, despite similar levels of anticoagulation, had higher rates of bleeding and recurrence. This was likely due to their older age and comorbidities, particularly renal impairment and concurrent cancer. These findings are consistent with the observation that bleeding risk is primarily determined by clinical characteristics rather than the anti-Xa activity alone.Conclusion: These data support a weight-based dosing strategy for enoxaparin in obese patients with VTE, with no dose-capping, to ensure therapeutic drug levels. Routine anti-Xa levels in patients weighing >100kg, particularly in those with moderate renal impairment, allow tailoring of doses to the therapeutic anti-Xa range.Reference:(1) Martin K et al. Use of the direct oral anticoagulants in obese patients: guidance from the SSC of the ISTH. Journal of thrombosis and haemostasis 2016; 14: 1308-13. DisclosuresNo relevant conflicts of interest to declare.

Weight-based enoxaparin dosing and deep vein thrombosis in hospitalized trauma patients: A double-blind, randomized, pilot study

BackgroundVenous thromboembolism is a cause of morbidity and mortality in trauma patients. Chemoprophylaxis with low-molecular-weight heparin at a standardized dose is recommended. Conventional chemoprophylaxis may be inadequate. We hypothesized that a weight-adjusted enoxaparin prophylaxis regimen would reduce the frequency of venous thromboembolism in hospitalized trauma patients and at 90-day follow-up. MethodsThis prospective, randomized pilot study enrolled adult patients admitted to a level 1 trauma center between July 2013 and January 2015. Subjects were randomized to receive either standard (30 mg subcutaneously every 12 hours) or weight-based (0.5mg/kg subcutaneously every 12 hours) enoxaparin. Surveillance duplex ultrasound for lower extremity deep vein thrombosis was performed on hospital days 1, 3, and 7, and weekly thereafter. The primary outcome was deep vein thrombosis during hospitalization. Secondary outcomes included venous thromboembolism at 90 days and significant bleeding events. ResultsTwo hundred thirty-four (124 standard, 110 weight-based) subjects were enrolled. There was no difference between standard and weight-based regarding age, body mass index, percentage female gender, injury severity score, or percentage that had surgery. There was a trend toward less in-hospital deep vein thrombosis in weight-based (12 [9.7%] standard vs 4 [3.6%] weight-based, P = .075). At 90 days, there was no difference in venous thromboembolism (12 [9.7%] standard vs 6 [5.5%] weight-based, P =.34). There was 1 bleeding event, which occurred in a standard subject. ConclusionWeight-based enoxaparin dosing for venous thromboembolism chemoprophylaxis in trauma patients may provide better protection against venous thromboembolism than standard. A definitive study is necessary to determine whether weight-based dosing is superior to standard.

Optimizing Weight-based Enoxaparin Dosing for Lung Transplant Recipients

Optimizing Weight-based Enoxaparin Dosing for Lung Transplant Recipients

Review of current evidence available for guiding optimal Enoxaparin prophylactic dosing strategies in obese patients-Actual Weight-based vs Fixed.

The current debate over the optimal Enoxaparin prophylactic dosing strategies in obese patients centre around whether it should be based on the actual weight of the patient (i.e. weight-based), or at an artificially fixed amount, as it is the case in Australia (40mg daily). The vast majority of the evidence available today is laboratory-based, measuring serum Antifactor-Xa activities as a marker for physiological response. The aim of the parent study is to compare the clinical outcomes for obese patients who received fixed doses of enoxaparin compared to those who received weight-based doses within the licensed dosage recommendations. This review was conducted to examine whether a gap in knowledge exists in relation to dosing obese patients with enoxaparin as VTE prophylaxis after hospital admission to aid in development of the parent study concept. Databases such as Medline, EBSCOhost, ProQuest were interrogated using combinations of words such as "enoxaparin", AND "dosing strategy", AND "obese/obesity" AND "prophylaxis". Only eleven out of 14 primary studies which were considered to be sufficiently similar in methodology and anticipated outcomes were reviewed and analysed. Pooled data from the eleven studies suggested that weight-based or higher-than-fixed dosing had a 36.2% higher success rate than fixed dosing, and was more likely to achieve the desired serum Anti-Xa activity levels (52.2% and 16% respectively). The rate of failure to achieve this is significantly lower in the weight-based groups (13.3%) than in fixed-dose groups (18.5%). These eleven studies reviewed included 601 patients in total. There is insufficient evidence to support or negate the current enoxaparin health outcomes in obese and very obese patients due to the lack of post-discharge follow-up from hospitals. Further research is required to compare long-term outcomes after fixed and weight-based dosing of enoxaparin. The optimal dose of enoxaparin per kilogram of body weight for prophylaxis remains to be determined.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients.

BACKGROUND:Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery.METHODS:Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2–0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT).RESULTS:Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding.CONCLUSIONS:Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2–0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.

Increased Enoxaparin Dosing for Venous Thromboembolism Prophylaxis in General Trauma Patients.

To review the evidence regarding increased enoxaparin dosing for venous thromboembolism (VTE) prophylaxis in the general trauma patient population. A search of MEDLINE databases (1946 to October 2016) was conducted using the search terms enoxaparin, thromboembolism prophylaxis, venous thromboembolism, trauma, anti-factor Xa, and weight-based dosing. Additional references were identified from a review of literature citations. Search results were limited to English-language studies conducted in humans. Trials that included only obese patients or nontrauma patients were excluded. A total of 7 trials (958 patients) explored the use of increased dosing of enoxaparin for VTE prophylaxis in trauma patients. Patients were divided by enoxaparin dosing strategies: standard dosing of 30 mg twice daily (BID; n = 509), higher initial dosing regimen (n = 216), or dosing based on anti-FXa level adjustments (n = 233). The majority of the 42 total VTE events (64.3%) occurred in the standard dosing regimen. Within each group, VTE was reported in 5.3% of patients in the standard dosing group, 3.2% in the higher initial dosing group, and 4% in the anti-FXa adjustment group. Initial subtherapeutic anti-FXa levels occurred in 33% to 92% of standard dose patients and 9% to 39% of higher initial dose patients. The average weight-based dose required to achieve a therapeutic level ranged between 0.43 and 0.54 mg/kg/dose BID. The overall rate of bleeding was low, with 3 incidents (0.37%) reported. Standard-dose enoxaparin prophylaxis may not be optimal for the general trauma patient population. Weight-based enoxaparin dosing (0.5 mg/kg/dose BID) is an option in trauma patients considered to be at a lower risk of bleeding complications.

If some is good, more is better: An enoxaparin dosing strategy to improve pharmacologic venous thromboembolism prophylaxis.

Empiric enoxaparin dosing is inadequate for most trauma patients, leading to below target initial anti-Xa levels and requiring dose adjustment for optimal venous thromboembolism prophylaxis. We hypothesize that patient factors affecting initial anti-Xa levels can be identified based on drug pharmacokinetics, allowing creation of a new dosing protocol that will provide a higher percentage of in-target (0.2-0.4 IU/mL) patients at initial anti-Xa level assessment. Records of 318 trauma patients were evaluated, and NONMEM and PSN software were used to analyze 11 variables for their effects on anti-Xa levels. Computer modeling was used to select a new dosing protocol, which was implemented on the trauma service as a quality improvement project. The first 145 patients appropriately enrolled were assessed for response and complications. Only 29.5% of the pre-intervention group had initial anti-Xa levels in the appropriate prophylactic range (). Levels were most strongly influenced by patient weight, outweighing contributions from all other variables. A new regimen for initial dosing was therefore designed with three weight-defined categories for ease of administration. The post-intervention group showed an increase in in-target initial anti-Xa levels to 74.5% (p < 0.001), with a corresponding decrease in subprophylactic patients from 68.0% to 20.7%. There was an increase in supraprophylactic levels to 4.8%, but no supraprophylactic patients had hemorrhagic complications.(Figure is included in full-text article.) CONCLUSIONS: Implementation of a new, categorized, weight-based enoxaparin dosing protocol was safe and significantly improved the percentage of trauma patients with in-target anti-Xa levels on initial assessment. Further studies are needed to determine whether such dosing decreases venous thromboembolism rates. Therapeutic/care management study, level II.

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We appreciate the thoughtful questions raised by Drs Sorenson and McCurdy and the support of our article1Kaplan D. Casper T.C. Elliott C.G. et al.VTE incidence and risk factors in patients with severe sepsis and septic shock.Chest. 2015; 148: 1224-1230Abstract Full Text Full Text PDF PubMed Scopus (151) Google Scholar investigating the incidence of VTE in severe sepsis and septic shock. Our finding of a VTE incidence of 37.2% is higher than in prior reports, perhaps owing in part to our study design in which all patients were evaluated with ultrasound imaging. We agree that strategies to reduce VTE risk in sepsis might include weight-based dosing of heparinoids, which may prevent VTE in patients who are obese more effectively compared with fixed-dosing regimens.2Wang T.F. Milligan P.E. Wong C.A. Deal E.N. Thoelke M.S. Gage B.F. Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients.Thromb Haemost. 2014; 111: 88-93Crossref PubMed Scopus (91) Google Scholar, 3Rondina M.T. Wheeler M. Rodgers G.M. Draper L. Pendleton R.C. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients.Thromb Res. 2010; 125: 220-223Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar Although we were unable to detect a significant correlation between BMI and VTE in our study, this may be a result of the markedly prothrombotic state in severe sepsis and septic shock. Critically ill patients who are septic are also at increased risk of bleeding, partly because of sepsis-associated coagulopathy.4Semeraro N. Ammollo C.T. Semeraro F. Colucci M. Coagulopathy of acute sepsis.Semin Thromb Hemost. 2015; 41: 650-658Crossref PubMed Scopus (78) Google Scholar Thus, increased anticoagulant dosing may cause excess bleeding in this population. Prospective, randomized, controlled trials are needed to optimize anticoagulant selection and dosing to prevent VTE severe sepsis and septic shock. The timing of VTE development in sepsis also intrigues us, and we appreciate this insightful comment. Cook et al5Cook D. Crowther M. Meade M. et al.Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors.Crit Care Med. 2005; 33: 1565-1571Crossref PubMed Scopus (309) Google Scholar performed serial ultrasound examinations on 817 critically ill patients (5.4% of whom had sepsis) and found that the median time to VTE diagnosis was 8 days (interquartile range, 4-14 days). Since only a small minority of patients in this cohort had sepsis, however, additional prospective studies are needed to determine the timing of VTE in septic patients. This information would potentially lead to earlier VTE diagnosis and treatment, and more favorable clinical outcomes. Meanwhile, providers should maintain a low threshold for evaluating the possibility of VTE in sepsis. In our opinion, whether VTE is an unavoidable consequence is not yet known. Whereas thromboprophylaxis reduces VTE in hospitalized medically ill and surgical patients, current guideline-supported VTE prevention strategies may be less effective among critically ill patients who have sepsis. Higher-intensity anticoagulation (perhaps regardless of BMI) combining thromboprophylaxis with mechanical devices or using recently approved anticoagulants may reduce VTE risk but requires further investigation. Increased Incidence of VTE in Septic Shock: Is this Preventable?CHESTVol. 149Issue 4PreviewWe read with great interest the article entitled, “VTE Incidence and Risk Factors in Patients With Severe Sepsis and Septic Shock,” published a recent issue of CHEST (November 2015).1 This well-conducted prospective study investigated the incidence of VTE in 113 patients presenting to three academic ICUs with severe sepsis or septic shock. Despite all patients receiving guideline-recommended thromboprophylaxis, the incidence of VTE at ICU discharge was 37.2%, a marked increase in VTE compared with previous studies that did not focus specifically on patients with sepsis. Full-Text PDF VTE Incidence and Risk Factors in Patients With Severe Sepsis and Septic ShockCHESTVol. 148Issue 5PreviewProspective studies on the incidence of VTE during severe sepsis and septic shock remain absent, hindering efficacy assessments regarding VTE prevention strategies in sepsis. Full-Text PDF

Non–weight-based enoxaparin dosing subtherapeutic in trauma patients

BackgroundWe report our experience dosing and monitoring enoxaparin with anti-factor Xa activity (anti-FXaA) levels for venous thromboembolism prophylaxis in trauma patients (TP). Materials and methodsTP receiving standard, non–weight-based dosed enoxaparin administered every 12 h for venous thromboembolism prophylaxis with peak anti-FXaA levels measured were prospectively monitored and evaluated and those whose first anti-FXaA levels ≥ or <0.2 IU/mL were compared. Anti-FXaA levels and enoxaparin dose (mg/kg actual body weight) were evaluated for correlation. ResultsOf the fifty-one TP included, initial anti-FXaA levels were <0.2 IU/mL in 37 (72.5%) whose dose was lower than those within target range (0.38 [0.32–0.42] mg/kg versus 0.45 [0.39–0.48] mg/kg, P = 0.003). Thirty-seven TP achieved anti-FXaA level ≥0.2 IU/mL (23 requiring dose increases) at a dose of 0.49 [0.44–0.54] mg/kg. Correlation between dose and anti-FXaA levels for the initial 51 anti-FXaA levels (r = 0.360, P = 0.009) and for all 103 anti-XaA levels (r = 0.556, P < 0.001) was noted. ConclusionsNon–weight-based enoxaparin dosing did not achieve target anti-FXaA levels in most TP. Higher anti-FXaA levels correlated with larger weight-based enoxaparin doses. Weight-based enoxaparin dosing (i.e., 0.5 mg/kg subcutaneously every 12 h) would better achieve target anti-FXaA levels.