anti-Xa Levels Research Articles

An Evaluation of the Appropriateness of Initial Enoxaparin Dosing Among Pediatric Patients.

Background Enoxaparin is a low molecular weight heparin that irreversibly inactivates factor Xa leading to the inhibition of clot formation. Despite the non-FDA approval in pediatrics, enoxaparin is recommended with an initial dose of 1.5mg/kg/q12hrs for patients aged ≤ 2 months and 1mg/kg/q12hrs for patients > 2 months, targeting therapeutic anti-Xa with a range of 0.5 to 1 units/mL. Due to more rapid clearance in pediatrics, our study aims to assess the need for initial higher doses than recommended by the guideline to reach the target anti-Xa level. Methods A retrospective chart review of all pediatric patients under all specialties who were treated with enoxaparin either in inpatient or outpatient settings between February 2021 and June 2022 at children's specialized hospital and meet the inclusion criteria, including age ≤ 15 years old and treated with enoxaparin with initial dose according to the American College of Chest Physicians (CHEST) guideline, while patients who received prophylaxis dosesdid not have anti-Xa levels or creatinine clearance < 30 mL/min/1.73m2 were excluded. Demographic data, laboratory data, and enoxaparin dosing were all collected to assess whether the initial enoxaparin dose will result in a therapeutic level as a primary endpoint and secondary endpoints including the average enoxaparin dose required to achieve the therapeutic level and to report any side effects. All data were entered and analyzed using the Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 25, Armonk, NY), and all categorical variables were reported as frequency and percentage while continuous variables expressed as mean ± SD and the study was approved by our research center institutional review board (IRB). Results Thirty patients were included in the study (17 males), 10 patients were aged ≤ 2 months, four were between 3 and 12 months and 16 were > 12 months, most of the patients received enoxaparin for deep vein thrombosis. In the majority of patients (76.7%), the initial dose failed to achieve the target anti-Xa while a mean dose of 2 mg/kg/q12hrs in patients ≤ 2 months, 1.7mg/kg/q12hrs in patients 3-12 months and 1.3 mg/kg/q12hrs in patients > 12 months was sufficient to reach the target level. After achieving a therapeutic anti-Xa level, only one patient experienced major bleeding while four patients experienced minor bleeding, no edema or thrombocytopenia were reported. Conclusion In conclusion, initiating enoxaparin according to the recommended dose by the guideline failed to achieve target anti-Xa in the majority of patients which necessitates starting enoxaparin with initial higher doses according to the patient's age to provide more prompt achievement of target anti-Xa.

Abstract 14891: Time to Therapeutic Range for Patients With Acute Pulmonary Embolism Undergoing Mechanical Thrombectomy

Introduction: Anticoagulation therapy is the mainstay for the management of patients with acute pulmonary embolism (PE) and achieving a timely time to therapeutic range (TTR) is important. We sought to determine the TTR in patients with acute PE referred for mechanical thrombectomy (MT) and the proportion of patients with therapeutic activated clotting time (ACT) at the time of MT. Methods: This single center retrospective study included all patients who underwent percutaneous MT at a large academic public hospital from January 2020 through April 2023. Therapeutic anticoagulation was defined as an ACT &gt;200 seconds or if the patient received enoxaparin within 6 hours prior to MT. Results: A total of 63 patients (average age 58 years, 43% female) with intermediate or high-risk PE were included in the analysis. The median time from the diagnosis of PE or clot-in-transit (CIT) to MT was 15 (IQR 6.1-23.2) hours. Fifteen patients (23.8%) were initiated on enoxaparin at the diagnosis of acute PE or CIT. Among these patients, 5 (7.9%) were on enoxaparin only and 10 (15.9%) patients were initiated on enoxaparin and then transitioned to a heparin infusion prior to MT. One patient was initiated on argatroban, while the remaining 47 patients were initiated on a heparin infusion at time of diagnosis (77.6% received heparin bolus). In patients who received a heparin infusion, the median ACT in the cath lab was 134 (IQR 118-159) seconds. Only a total of 9/63 (14.3%) were therapeutic by ACT at the time of MT or received therapeutic enoxaparin within 6 hours of MT. Excluding patients who received enoxaparin initially, 34/48 (70.8%) patients reached a therapeutic anti-Xa or partial thromboplastin time (PTT) levels. The median time to reach a therapeutic anti-Xa or aPTT was 5.6 (IQR 3.3-8.2) hours (Figure). Conclusion: In patients with acute PE referred for MT, only a minority of patients had therapeutic ACT prior to mechanical thrombectomy.

Reassessment of dextran sulfate in anti-Xa assay for unfractionated heparin laboratory monitoring

BackgroundAnti-Xa assays are used for unfractionated heparin (UFH) monitoring. Dextran sulfate (DS) is used in some assays to overcome the artifactual preanalytical release of platelet factor 4. However, the practical implications of this test modification have not been studied extensively. ObjectivesTo investigate the impact of the presence of DS in the anti-Xa assay for UFH laboratory monitoring. MethodsWe studied factor Xa inhibition, using an assay without DS (Stago Liquid Anti-Xa), in normal pool plasma spiked with various concentrations of UFH (up to 1 IU/mL) in the presence of increasing concentrations of DS (up to 2560 μg/mL). We also investigated the effect of DS on FXa inhibition measured after the addition of UFH and heparin antagonists (protamine and Polybrene; Sigma Aldrich). Eventually, we compared the anti-Xa levels measured using the assay without DS to those measured with an assay containing DS (BIOPHEN Heparin LRT, Hyphen BioMed). ResultsDS per se had a detectable anti-Xa effect. FXa inhibition in UFH-spiked plasma linearly increased with increasing concentrations of added DS, with a plateau at approximately 160 μg/mL DS, at which the apparent anti-Xa level had almost doubled. In the presence of heparin antagonists, the addition of DS increased anti-Xa levels, corresponding to the dissociation of the UFH-antagonists complexes in vitro. With the anti-Xa assay containing DS, UFH inhibition was not detected. ConclusionIn the presence of high concentrations of DS, FXa inhibition was much higher than that predicted from added UFH amounts, presumably related to the greater availability of UFH for interaction with antithrombin. While the relevance of measuring this “masked” heparin has not been demonstrated, the presence of DS renders the result inaccurate in the presence of protamine or Polybrene.

When Apixaban and Rivaroxaban Interfere With Anti-Xa Assays: A Cohort Study

Background: The use of direct factor Xa inhibitors, such as apixaban and rivaroxaban, has improved medication adherence. However, in certain situations during hospital admission, patients on these medications may need to be transitioned to unfractionated heparin (UFH) infusions. This transition can skew results of anticoagulation monitoring, such as the anti-Xa assay, due to residual factor-Xa inhibitor activity. Methods: We conducted this retrospective chart among admitted patients to St. Vincent’s Medical Center in Bridgeport, CT between December 2020 till June 2022. Patients who were maintained on Apixaban or Rivaroxaban, factor-Xa inhibitors, and were transitioned to unfractionated intravenous drip were included. A baseline plasma anti-Xa level was noted. Assessment for thrombotic or bleeding events during hospitalization was performed. Results: A total of 48 patients were included in this study. The majority of patients were bridged to UFH for NSTEMI (31%) or pre-procedure (23%). The mean baseline anti-Xa for all patients was 0.92 U/mL. Twelve patients (25%) and one patient (2%) of patients had bleeding and thrombotic events, respectively. Although the mean baseline anti-Xa level was higher for patients who had an adverse event compared to no event, the difference was non-statistically significant. Fifty seven percent of patients who had an adverse event had a supratherapeutic plasma anti-Xa baseline level. A gastrointestinal bleed was the most common type of bleeding event. Conclusions: To prevent thrombotic or bleeding events, we suggest adopting a standard practice of obtaining a baseline anti-Xa level in patients with recent exposure to factor Xa inhibitors in order to guide the timing of UFH initiation, the dosing of heparin, and determine the need for alternative assays, such as the activated partial thromboplastin clotting time.

The effect of renal impairment and obesity on anti-Xa peak and trough levels in patients receiving therapeutic doses of nadroparin: a comparison with control patients.

Anti-Xa peak level monitoring is recommended during LMWH treatment in renal impairment or obesity. The trough level has been proposed as marker for bleeding. We studied the influence of renal impairment and obesity on anti-Xa levels. Peak and trough levels were collected during therapeutic nadroparin treatment in patients with renal impairment, obese patients, and controls. 27 patients (n = 68 samples) were evaluated and combined with published data (n = 319 samples from 35 patients) using population pharmacokinetic (popPK) modelling. Median peak level was 0.44 and 0.95IU/mL in renal impairment with and without dose reduction and 0.60 and 0.43IU/mL in obesity and controls, respectively. Trough levels were < 0.5IU/mL in all patients with renal impairment with dose reduction and in 5/6 control patients. In the popPK model, total body weight and eGFR were covariates for clearance and lean body weight for distribution volume. Model-based evaluations demonstrated peak levels below the therapeutic window in controls and increased levels in renal impairment. Dose reductions resulted in a different effect on peak and trough levels. Obese patients (BMI up to 32kg/m2) had similar levels upon weight-based dosing. In renal impairment, anti-Xa peak levels after dose reduction are comparable to those in controls. Weight-based dosing is suitable for obese patients. Aiming for peak levels between 0.6 and 1.0IU/mL in these patients would result in overexposure compared to controls. Considering the association of trough levels and bleeding risk and our findings, trough monitoring seems to be a suitable parameter to identify nadroparin accumulation.

Performance Assessment of Anti-Xa Assay-Based Heparin Dosing Protocol in Pediatric Patients on Extracorporeal Membrane Oxygenation.

The use of extracorporeal membrane oxygenation (ECMO) in the postoperative cardiac critical care setting is evolving. Anticoagulation monitoring is among the most challenging aspects of pediatrics. However, there is no consensus on the optimal dosing and monitoring of unfractionated heparin in this setting. To address this, we developed an anti-Xa assay-based protocol derived from the best available clinical and anecdotal evidence of ECMO use and assessed its effectiveness in achieving the anti-Xa assay therapeutic target. This prospective single-arm study was conducted in the pediatric carcardiac-surgery intensive care unit of a large tertiary hospital. We used two different anti-Xa assay intensity levels based on the patients' bleeding status. The median patient age was 7 (interquartile range [IQR]: 5-11.25) months, and the median weight was 5.7 (IQR: 3.8-13.82) kg. The median ECMO duration was 6 (IQR: 4.5-7.5) days. The bleeding protocol was used for most patients. Seventy percent achieved the anti-Xa assay therapeutic target during the study period (median: 75.5 h, IQR: 60.5-117.5 h). Hemorrhagic complications were reported in 40% of the patients, and thrombotic complications were reported in 25%. The median length of stay was 37 (IQR: 22-43) days, with a survival-to-discharge rate of 75%. Despite a failure to achieve the anti-Xa assay target within the first ECMO days, most patients achieved the target by the median ECMO duration. Moreover, using two different anti-Xa assay levels reduced thrombotic complications.

Effects of anti-Xa activity monitoring on the outcome of high-risk pregnancies treated with a prophylactic dose of low-molecular-weight heparin.

To evaluate if anti-Xa level monitoring and dose adjustment in women using a prophylactic dose of enoxaparin can decrease placenta-mediated pregnancy complications. This retrospective observational cohort study included pregnant women receiving enoxaparin prophylaxis, who were followed at the Thrombosis and Hemostasis Outpatient clinic between 2010 and 2017. The dose was adjusted according to enoxaparin anti-Xa levels in the study group or the weight of individuals in the control group. Of 585 women surveyed, 110 met the inclusion criteria; 63 of them were included in the study group and 47 in the control group. Mean starting dose was 46 versus 43 mg (p = .25), mean final dose was 52 mg versus 45 mg (p = .03) and dose adjustment was required in 37% versus 11% (p = .002) in the study and control groups, respectively. Twenty-eight percent of anti-Xa measurements in the second trimester were beneath the prophylactic threshold, compared to 11% and 16% in the first and third trimesters, respectively (p = .02). Labors ended with live birth in 91% versus 94% of cases (p = .5), 85% versus 68% of pregnancies were term (p = .05), 11% versus 23% of newborns were low birth weight (p = .1) and placenta-mediated pregnancy complications were documented in 9% versus 19%, (p = .17) in the study group relative to controls, respectively. The most prominent decrease in anti-Xa levels was observed in the second trimester. Monitored women had significantly more term deliveries and demonstrated a trend toward higher birth weight and fewer placenta-mediated pregnancy complications. Larger studies are needed to confirm improved pregnancy outcome in monitored women.

Risk Stratification for Supratherapeutic Peak Anti-Xa Levels in Adult Patients on Therapeutic Enoxaparin.

The American Society of Hematology Guidelines for the management of venous thromboembolism recommend against the use of anti-Xa monitoring for assessing enoxaparin dosing based on a low level of evidence associating supratherapeutic levels with an increased risk of bleeding. However, institutions still utilize anti-Xa levels in select patient populations with altered volume of distribution and/or excretion to monitor and adjust therapy. The primary objective of this study was to identify risk factors associated with supratherapeutic peak anti-Xa levels (≥1.10 IU/mL) for patients receiving therapeutic enoxaparin. This was a retrospective single-center study performed at an academic tertiary care hospital. Patients who received enoxaparin at 1 mg/kg twice daily and peak anti-Xa monitoring were separated into supratherapeutic and therapeutic/subtherapeutic cohorts. A total of 436 patients were screened, and 215 were included, with a mean age of 62 years. There were 108 in the therapeutic/subtherapeutic cohort and 107 in the supratherapeutic cohort. Acute kidney injury (AKI), body mass index (BMI), weight, female sex, intensive care unit (ICU) service, Sequential Organ Failure Assessment (SOFA) score ≥4, and creatinine clearance at the time of peak anti-Xa level collection were associated with supratherapeutic anti-Xa levels in univariate models. Adjusted logistic regression models were created and identified BMI in the 30 to 34.9 kg/m2 (odds ratio [OR] 4.35; 95% confidence interval [CI] 1.70-11.13, P < 0.005) and ≥35 kg/m2 (OR 6.75; 95% CI 3.05-14.94, P < 0.005) and AKI (OR 2.62; 95% CI 1.04-6.62, P = 0.042) as significant risk factors for supratherapeutic anti-Xa levels. Our study identified BMI ≥ 30 kg/m2, AKI, female sex, ICU service, SOFA score ≥4, and creatinine clearance as risk factors for supratherapeutic anti-Xa levels in patients receiving 1 mg/kg twice daily dosing of enoxaparin. Further research should be done to provide evidence for the association between anti-Xa levels and bleeding risk.

Early administration of high dose enoxaparin after traumatic brain injury.

Early enoxaparin 30mg BID administration at 24h post-injury has been demonstrated in patients with traumatic brain injury (TBI). However this dose can also yield subtherapeutic anti-Xa levels in 30-50% of trauma patients, suggesting that larger doses may be required for adequate prophylaxis against venous thromboembolism (VTE). The safety of enoxaparin 40mg BID in trauma patients has previously been shown - however, these studies have largely excluded TBI patients. Therefore, we sought to demonstrate the safety of early enoxaparin 40mg BID in a low-risk group of TBI patients. A retrospective review of TBI patients at a Level 1 trauma center was performed. Patients with stable computed tomography (CT) of the head at 6 to 24h post-injury who received enoxaparin 40mg BID were included and serial GCS evaluations to identify possible clinical complications. To evaluate the safety of this dosing regimen, data was then compared to patients from our institution with similar TBI profiles who had received 5,000 units (U) of subcutaneous heparin (SQH) prophylaxis. 199 TBI patients were identified over a nine month period, 40/199 (19.7%) received DVT prophylaxis after traumatic injury. Of these 40, 19 (47.5%) received enoxaparin 40mg BID and 21 (52.5%) received 5,000U of SQH. Low risk TBI patients who were either given enoxaparin (n = 7) or SQH (n = 4), demonstrated no clinical decline in mental status during their inpatient stay. Prior studies have demonstrated that enoxaparin 40mg BID dosing is superior to traditional VTE prophylaxis in trauma patients. However, TBI patients are often excluded from this dosing due to concern for progression. Our study showed no clinical decline in mental status in a small cohort of low-risk TBI patients who received enoxaparin 40mg BID.

Anti-Xa level monitoring of low-molecular-weight heparin during intermittent venovenous hemofiltration

Low-molecular-weight heparin (LMWH) is an anticoagulant used to prevent clotting during blood purification treatments. This study aimed to evaluate the clinical use of the anti-factor Xa level (anti-Xa) for monitoring LMWH anticoagulant levels during intermittent venovenous hemofiltration (IVVHF). This prospective observational study enrolled patients who required IVVHF for renal failure in Beijing Hospital between May 2019 and February 2021. The LMWH anticoagulation was assessed by the coagulation grade of the filter and line. One hundred and ten participants were included. There were 90 patients with a filter and line coagulation grade of ≤ 1 and 20 patients with grade > 1. The anti-Xa level of 0.2 IU/mL was a critical value. The multivariable logistic regression analysis showed that anti-Xa level > 0.2 IU/mL (odd ratio [OR] = 2.263; 95% CI: 1.290–4.871, P = 0.034) and cardiovascular disease (OR = 10.028; 95% CI: 1.204–83.488; P = 0.033) were independently associated with the coagulation grade of the filter and line. Anti-Xa level could monitor LMWH anticoagulation during IVVHF.

Creatinine clearance predicts the goal enoxaparin dose in traumatic brain injury.

Patients with traumatic brain injury (TBI) are at high risk of venous thromboembolism (VTE). Recent guidelines recommend starting TBI patients on enoxaparin 30 mg twice daily and then considering weight-based dosing. Creatinine clearance may be better than weight for patients when considering high and low enoxaparin dose requirements. We hypothesize that creatinine clearance (CrCl) predicts goal enoxaparin dose better than weight-based dosing. A retrospective review was conducted on patients admitted to an urban, academic Level I trauma center from August 2017 to February 2020. Patients were included if greater than 18 years, admitted longer than 48 hours, and head and neck AIS ≥ 3. Patients were excluded if they did not have TBI, if they received deep vein thrombosis prophylaxis other than enoxaparin 12-hour dosing, if no anti-Xa levels were drawn, or if the goal anti-Xa level was not reached. Patients were grouped into dosing cohorts based on dose of enoxaparin required to reach goal. Pearson's correlation was used to compare mean CrCl and mean weight across dosing cohorts. A total of 120 patients met inclusion and exclusion criteria, mean age was 47 years and 68% of patients were male. The mean hospital length of stay was 24 days. There were 5 (4.2%) deep vein thrombosis, no pulmonary embolism, and 5 (4.2%) patients died. Mean CrCl increased significantly with increased dosing of enoxaparin, Pearson's correlation coefficient of 0.484 ( p < 0.001). Weight on admission also increased with increasing enoxaparin dose requirements, with Pearson's correlation coefficient of 0.411 ( p < 0.001). Creatine clearance predicts goal enoxaparin dose in TBI better than a weight-based dosing strategy. Further research with a larger patient population is required to validate CrCl values to guide enoxaparin dosing. Prognostic and Epidemiological; Level IV.

Evaluating residual anti-Xa levels following discontinuation of treatment-dose enoxaparin in patients presenting for elective surgery: a prospective observational trial

IntroductionPrior studies have demonstrated that patients presenting for elective surgery may have higher-than-expected residual anti-Xa level activity at or beyond 24 hours following their last treatment dose of enoxaparin. Given...

Evaluation of a novel blood volume-based enoxaparin dosing guideline for venous thromboembolism prophylaxis in trauma patients.

Fixed-dose and body mass index (BMI)-based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)-based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients. This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti-factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL). A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups. Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels.

The optimized anticoagulation strategy in prolonged hemodialysis.

During extended (nocturnal) hemodialysis (ENHD), the dose of low-molecular-weight heparin (LMWH) can be administered as a single injection or as a divided dose over different time points. Our hypothesis was that a single injection might be sufficient to maintain dialyzer fiber patency. In addition, we investigated whether the biochemical clotting parameter anti-Xa accurately predicts fiber blocking. Our hypothesis was tested in 20 stable patients on ENHD in a random cross-over setting during two consecutive midweek sessions. The regular total dose of LMWH (i.e. enoxaparin, Clexane® 40-100 mg, Sanofi, Belgium) was either given (i) in a single injection at the dialysis start or (ii) divided over two injections, at the start and halfway the dialysis session. Blood samples were taken from the arterial blood line at different time points to determine plasma anti-Xa activity levels. Post-dialysis, the rinsed and dried hemodialyzers were scanned with a reference micro-computed tomography (µCT) scanning technique, and non-blocked fibers were counted in a central cross-section of the dialyzer outlet potting (ImageJ, NIH, USA). The percentage of open fibers in the dialyzers after a single injection of LMWH [91 (61-96)%] versus divided administration [94 (79-98)%] was not different. Time averaged anti-Xa activity levels were clinically not significantly different between both sessions. Anti-Xa activity levels correlated with the administered anticoagulation doses normalized for body weight, but not with the percentages open fibers in the dialyzers. Our results indicate that there is no need to administer enoxaparin over two injections for ENHD up to 8 h. The usefulness of monitoring anti-Xa levels to predict fiber patency, assessed by µCT, can be questioned, but further clinical trials are needed.

In vitro evaluation of anticoagulant therapy management when urgent percutaneous coronary intervention is required in rivaroxaban-treated patients.

We investigated in vitro the management of intraprocedural anticoagulation in patients requiring immediate percutaneous coronary intervention (PCI) while using regular direct oral anticoagulants (DOACs). Twenty-five patients taking 20 mg of rivaroxaban once daily comprised the study group, while five healthy volunteers included the control group. In the study group, a beginning (24 h after the last rivaroxaban dose) examination was performed. Then, the effects of basal and four different anticoagulant doses (50 IU/kg unfractionated heparin (UFH), 100 IU/kg UFH, 0.5 mg/kg enoxaparin, and 1 mg/kg enoxaparin) on coagulation parameters were investigated at the 4th and 12th h following rivaroxaban intake. The effects of four different anticoagulant doses were evaluated in the control group. The anticoagulant activity was assessed mainly by anti-factor Xa (anti-Xa) levels. Beginning anti-Xa levels were significantly higher in the study group than in the control group (0.69 ± 0.77 IU/mL vs. 0.20 ± 0.14 IU/mL; p < 0.05). The study group's 4th and 12th-h anti-Xa levels were significantly higher than the beginning level (1.96 ± 1.35 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.001 and 0.94 ± 1.21 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.05, respectively). Anti-Xa levels increased significantly in the study group with the addition of UFH and enoxaparin doses at the 4th and 12th h than the beginning (p < 0.001 at all doses). The safest anti-Xa level (from 0.94 ± 1.21 to 2.00 ± 1.02 IU/mL) was achieved 12 h after rivaroxaban with 0.5 mg/kg enoxaparin. Anticoagulant activity was sufficient for urgent PCI at the 4th h after rivaroxaban treatment, and additional anticoagulant administration may not be required at this time. Twelve hours after taking rivaroxaban, administering 0.5 mg/kg of enoxaparin may provide adequate and safe anticoagulant activity for immediate PCI. This experimental study result should confirm with clinical trials (NCT05541757).

742 Evaluation of Anti-Xa Levels and Venous Thromboembolism Prophylaxis with Enoxaparin in Burn Patients

Abstract Introduction Previous studies have found that standard dose enoxaparin is inadequate in achieving goal prophylactic anti-Xa levels in burn patients. A new venous thromboembolism (VTE) prophylaxis protocol was implemented at our institution (Table 1). The objective of this study was to assess the efficacy and safety of the updated VTE prophylaxis protocol to determine if goal anti-Xa levels can be achieved earlier compared to the previous enoxaparin dosing protocol. Methods This was a retrospective cohort study evaluating a historic protocol group from 3/1/21 to 5/31/21 and a new protocol group from 10/1/21 to 12/31/21. Revisions were made to the new protocol group and evaluated from 7/1/22 to 8/31/22. Adult patients admitted with cutaneous and/or inhalation burn who received enoxaparin for VTE prophylaxis and had anti-Xa monitoring were included. The primary endpoint was protocol efficacy defined as percentage of initial anti-Xa levels within goal range and time to goal anti-Xa level. Secondary endpoints included protocol adherence, rate of VTE occurrence, number of missed or held doses if VTE occurred, correlation to published enoxaparin dosing equations in burn patients, and bleeding events. Results Results can be found in Table 2. The median (IQR) initial anti-Xa level in the historical (n=29) vs. new protocol group (n=22) was 0.09 (0.04-0.14) units/mL vs. 0.15 (0.10-0.19) units/mL (p=0.036). After adjusting the BMI cutoff in the new protocol from 40 kg/m2 to 35 kg/m2, the median initial anti-Xa was 0.16 (0.12-0.22) units/mL vs. 0.24 (0.19-0.28) units/mL (p=0.018). The mean ± SD time for patients to achieve goal anti-Xa level was 5 ± 3 days in the historical protocol and 5 ± 2 days in the new protocol group (p = 0.456). After protocol modification, the median time to goal anti-Xa level was 4 (3-6) days vs. 2 (1-3) days (p=0.002). No differences were noted in secondary outcomes. Conclusions The new protocol resulted in a higher initial anti-Xa level with more patients within goal anti-Xa range which was reached in less time after modification of the BMI cutoff for weight-based dosing. The maximum anti-Xa level in the modified group was still within the prophylactic range with the new protocol, indicating no increase in supratherapeutic levels compared to previously utilized dosing strategies and there were no differences in major or minor bleeding events which supports its safety. Applicability of Research to Practice This protocol can be replicated and utilized by other burn centers with the potential for a multicenter analysis and provides a framework for developing standardized VTE prophylaxis dosing recommendations with enoxaparin in burn patients.

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.

Population Pharmacokinetics and Probability of Target Attainment Analysis of Nadroparin in Different Stages of COVID-19.

The risk of thrombotic complications in critical patients with COVID-19 remains extremely high, and multicenter trials failed to prove a survival benefit of escalated doses of low-molecular-weight heparins (nadroparin calcium) in this group. The aim of this study was to develop a pharmacokinetic model of nadroparin according to different stages of COVID-19 severity. Blood samples were obtained from 43 patients with COVID-19 who received nadroparin and were treated with conventional oxygen therapy, mechanical ventilation, and extracorporeal membrane oxygenation. We recorded clinical, biochemical, and hemodynamic variables during 72h of treatment. The analyzed data comprised 782 serum nadroparin concentrations and 219 anti-Xa levels. We conducted population nonlinear mixed-effects modeling (NONMEM) and performed Monte Carlo simulations of the probability of target attainment for reaching 0.2-0.5IU/mL anti-Xa levels in study groups. We successfully developed a one-compartment model to describe the population pharmacokinetics of nadroparin in different stages of COVID-19. The absorption rate constant of nadroparin was 3.8 and 3.2 times lower, concentration clearance was 2.22 and 2.93 times higher, and anti-Xa clearance was 0.87 and 1.1 times higher in mechanically ventilated patients and the extracorporeal membrane oxygenation group compared with patients treated with conventional oxygen, respectively. The newly developed model indicated that 5.900IU of nadroparin given subcutaneously twice daily in the mechanically ventilated patients led to a similar probability of target attainment of 90% as 5.900IU of subcutaneous nadroparin given once daily in the group supplemented with conventional oxygen. Different nadroparin dosing is required for patients undergoing mechanical ventilation and extracorporeal membrane oxygenation to achieve the same targets as those for non-critically ill patients. ClinicalTrials.gov identifier no. NCT05621915.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

British Society for Haematology guideline for anticoagulantmanagement of pregnant individuals with mechanical heart valves.

Creatinine Clearance May Predict Goal Enoxaparin Dose in Trauma.

Guidelines for enoxaparin dosing after trauma recommend an initial dose of 40 mg twice daily for most patients and then adjusting by anti-Xa levels. Previous studies indicated higher enoxaparin doses are necessary with higher levels of creatinine clearance (CrCl). We sought to determine if the goal enoxaparin dose correlates with the admission CrCl to reduce the reliance on measuring anti-Xa levels. A retrospective review was conducted of patients admitted to an urban, academic Level 1 trauma center from April 2017 to February 2020. Patients started on enoxaparin who reached goal anti-Xa trough levels were included, and patients were excluded if they did not reach goal anti-Xa levels. Data collection included patient demographics, injury characteristics, admission CrCl, and final enoxaparin dose. CrCl was then correlated with the final enoxaparin dose. Of 421 patients included, the mean age was 46.6 years and 73% were male. The median goal enoxaparin dose was 40 mg twice daily. The mean CrCl significantly increased with increasing twice-daily doses of enoxaparin (20 mg: 69.2 mL/min; 30 mg: 89 mL/min; 40 mg: 112.8 mL/min; 50 mg: 140.5mL/min; 60 mg: 147.4 mL/min; and 70 mg: 140 mL/min; p < 0.01). Admission CrCl may predict the enoxaparin dose required to achieve adequate anti-Xa levels. Our data indicate that CrCls of approximately 70, 90, 110, 140, and 150 mL/min may predict the twice-daily enoxaparin doses of 20, 30, 40, 50, and 60 mg, respectively. CrCl dosing guidance may reduce the time to goal anti-Xa levels and the frequency of anti-Xa measurements. Further research is necessary, and enoxaparin dosing should continue to be monitored by anti-Xa levels.