anti-Xa Levels Research Articles

Pregnant Woman in Outcomes with Prosthetic Heart Valves

We here sought to assess thrombotic and hemorrhagic complications and associated risk factors during pregnancy, delivery, and postpartum in women with prosthetic heart valves (PHV). Methods: The retrospective cohort study covered January 2011 to December 2022. The objective of the study was to assess the risk factors and frequency of thrombotic and hemorrhagic complications during pregnancy, delivery, and the postpartum period in women with PHV based on the experience of one perinatal center. We included 88 pregnancies with 77 prosthetic heart valves (PHV), which were divided into two groups, mechanical valve prostheses (MVP) (n = 64) and biological valve prosthesis (BVP) (n = 24). In the study we analyzed pregnancy outcomes, as well as thrombotic and hemorrhagic complication frequencies. Results: Of 88 pregnancies, 79 resulted in live births. In the MVP group, there were six miscarriages (9.4%) and two medical abortions (3.1%), including one due to Warfarin’s teratogenic effects. No miscarriages were reported in the BVP group, but one fetal mortality case (4.2%) occurred. During pregnancy, 11 MVP cases (17.2%) experienced thrombotic complications. In the BVP group, one patient (4.2%) had transient ischemic attack (TIA). Two MVP cases required surgical valve repair during pregnancy, and one in the post-delivery stage was caused by thrombotic complications. Postpartum, two MVP cases had strokes, and in one MVP patient, pulmonary embolism was registered, while no thrombotic complications occurred in the BVP group. Hemorrhagic complications affected 15 MVP cases (17.9%) in the postpartum period. There were no registered cases of maternal mortality. Conclusions: The effective control of anti-factor Xa activity reduced thrombotic events. However, the persistently high incidence of postpartum hemorrhagic complications suggests a need to reassess anticoagulant therapy regimens, lower target levels of anti-Xa, and reduce INR levels for discontinuing heparin bridge therapy. Despite the heightened mortality risk in MVP patients, our study cohort did not have any mortality cases, which contrasts with findings from other registries.

Dual guided heparin monitoring with anti-Xa and APTT during micro-axial flow pump support for cardiogenic shock

Abstract Background Precise management of unfractionated heparin (UFH) is key to avoid coagulopathic complications in patients on percutaneous mechanical circulatory support (pMCS) for cardiogenic shock (CS). While the activated partial thromboplastin time (APTT) is commonly used for this purpose, it can be affected by various laboratory factors during critical illness. Alternatively, the anti-Xa test directly measures UFH activity. We proposed a parallel anti-Xa/APTT-based protocol for UFH titration during pMCS. (1) Purpose We aimed to investigate the correlation between parallel anti-Xa/APTT measurements in a CS population on pMCS. We also evaluated mortality correlation in samples exhibiting prolonged APTT and in-range anti-Xa levels, based on fibrinogen levels and INR. Methods We assessed all CS patients with isolated left-sided ImpellaTM-support (>24h) and UFH anticoagulation monitoring per protocol at two pMCS-institutions from April-2017 to June-2022. Overall correlation between parallel anti-Xa/APTT samples was assessed by Pearson correlation coefficient (with ≤0.7 considered to confer a weak correlation). Anti-Xa levels were defined as 0.20-0.30IU/mL or 0.31-0.50IU/mL, with corresponding APTT values of 40-55s and 55-80s, respectively. Samples with prolonged APTT as compared to the in-range anti-Xa were stratified based on fibrinogen (<1.5g/dL or ≥ 1.5g/dL) and INR (<1.5 or ≥1.5) on the same day as the index sample. Mortality of patients with normal fibrinogen ànd INR was then compared to those with abnormal fibrinogen and/or INR via a Chi² test. Results Ninety-three ImpellaTM-runs (77 men, 83%) with a median age of 56 years (IQR 46-66) were analyzed. Median support was 6 days (IQR 4-12). In 2447 parallel anti-Xa/APTT samples, the Pearson correlation coefficient was 0.50 (p<0.001). Among the 1914 in-range anti-Xa samples, APPT was shortened in 460 (24%), in-range in 986 (52%) and prolonged in 468 (24%) samples. In the 59 patients with samples with prolonged APTT, two patients (with 80 samples) were excluded due to absence of fibrinogen and/or INR measurements on the same day. The mortality in patients with prolonged APTT but normal fibrinogen levels and normal INR (N=29; APTT prolongation due to FXI/FXII-consumption) was significantly lower compared to the remaining 28 patients who showed samples with reduced fibrinogen levels and/or prolonged INR (suffering from concomitant conditions) (10% vs. 32%; p=0.043). Conclusion We highlight a weak correlation between anti-Xa and APTT in an anti-Xa guided UFH anticoagulated CS population during left-sided ImpellaTM support. Patients with APTT-prolongation due to concomitant conditions with INR prolongation and/or fibrinogen shortage are at highest mortality risk. The APTT/Anti-Xa coefficient can serve as an independent risk factor whilst managing critically CS patients.

Bleeding outcomes in critically ill patients on heparin with discordant aPTT and anti-Xa activity.

Activated partial thromboplastin time (aPTT) and unfractionated heparin (UFH) level via the anti-factor Xa activity assay (anti-Xa) are commonly used assays for UFH monitoring. While discordance between the two assays is common, its impact on critically ill patient outcomes is unclear. This study aimed to compare the incidence of major bleeding events among critically ill patients with discordant aPTT and anti-Xa activity while on UFH, to patients with no discordance. This was a single-center, retrospective cohort study of critically ill adult patients who had simultaneous anti-Xa and aPTT levels while receiving continuous UFH infusion. The primary outcome was the incidence of a major bleeding event up to 24h after UFH discontinuation. Secondary outcomes included incidence of 30-day thrombosis and hospital length of stay (LOS). Among 264 included patients, 156 patients (59%) had at least one discordant paired level. Patients with discordance had an increased risk of major bleeding events (14% versus 5%; unadjusted risk ratio, 3.0; 95% CI 1.2-7.8; p = 0.01), and increased risk of thrombotic events (4% versus 0%; p = 0.04). Hospital LOS was similar between the two groups (13.8 days versus 11.4 days; p = 0.08). In this cohort of critically ill patients receiving continuous UFH, discordance in aPTT and anti-Xa activity was frequently observed and was associated with an increased risk of major bleeding events. While both assays remain viable monitoring options, evaluating simultaneous levels may aid in the management of critically ill patients. In patients with discordance, an individualized approach balancing bleeding and thrombotic risks should be considered.

Retrospective study evaluating safety, clinical effect, and dosing of dalteparin for the treatment of venous thromboembolism in term neonates.

There is an increased risk of venous thromboembolism (VTE) among neonates due to their unique hemostatic system. However, there is lack of approved treatment options for VTE in neonatal population. Importantly, dalteparin, a low molecular weight heparin approved for pediatric VTE in children ≥1month of age, has also been used for the treatment of neonatal VTE. Based on the request from the Food and Drug Administration, this retrospective study aimed to characterize the safety, clinical effects, and dosing of dalteparin for treatment of VTE among neonates. Data from electronic medical records for neonates (born ≥35weeks of gestation) treated with dalteparin for VTE between January 2010 and December 2021 were collected. The data assessed included bleeding and deterioration in hematological biomarkers among other adverse events, changes in relevant factor antifactor Xa (anti-Xa) levels and VTE status, and dosing of dalteparin and corresponding anti-Xa assay levels. Sixteen neonates from five participating sites in the United Kingdom were included. There were no bleeding events or deaths. Only one serious adverse event of hypoglycemic brain injury (unrelated to dalteparin) was documented in a patient with a history of hyperinsulinism. Median (range) daily dose of dalteparin at initiation was 309 (297-314)IU/kg. Eight of 16 neonates achieved therapeutic anti-Xa level, including two patients who did so after the first dose. Dalteparin treatment in neonates raised no major safety concerns. Larger cohort studies may help provide further insights on clinical effects of dalteparin for neonatal VTE.

Pharmacokinetic model-guided enoxaparin dosing in the Neonatal ICU: Retrospective cohort study to plan for prospective feasibility trial.

Traditional milligram per kilogram (mg/kg) dosing of enoxaparin in neonates frequently fails to achieve target anti-Xa levels promptly, necessitating repeated laboratory monitoring and dose adjustments. This study investigated whether a personalized dosing strategy based on predicted individual clearance and volume of distribution could improve outcomes, comparing standard-of-care (SOC) mg/kg dosing to pharmacokinetic (PK) model-informed precision dosing (MIPD). A retrospective analysis was conducted on hospitalized neonates treated with enoxaparin at less than 44 weeks postmenstrual age from 2019 to 2022. Data on demographics, drug dosing, PK model covariates, and clinical outcomes were extracted from electronic health records and analyzed using the Pumas-AI Lyv dosing tool. The primary focus was on comparing the initial SOC dose to the MIPD-recommended dose. The secondary outcome measured was the time required to achieve therapeutic anti-Xa levels. The study included 168 neonates with a median postnatal age of 15 days (range 1-149) and a median dosing weight of 3.1 kg (range: 0.82-5.2). MIPD-recommended initial doses were 20%-60% higher than SOC doses in 32% of the cases and over 60% higher in 11% of cases. Neonates who received SOC doses that were much lower than the MIPD recommendation showed the longest delays in reaching therapeutic anti-Xa levels. The results indicate that PK model-informed of enoxaparin dosing leads to higher initial dosages than SOC in neonates, potentially reducing the time to therapeutic anti-Xa levels. These findings are being utilized to define dosing limits for a prospective trial of MIPD in neonatal intensive care settings.

Effect of endothelium on the anticoagulant activity of a covalent antithrombin-heparin complex.

We developed a covalent antithrombin-heparin complex (ATH) with superior In vivo anticoagulant efficacy compared to non-covalent antithrombin (AT) + unfractionated heparin (H). Previous in vitro studies of ATH, investigating the mechanisms behind its efficacy, were done in the absence of endothelium. Since the endothelial surface modulates hemostasis, we investigated its impact on the in vitro anticoagulant properties of ATH and AT+H. Discontinuous second order rate constant enzyme inhibition assays, fibrin formation, and plasma clot generation were performed in the presence of ATH or AT+H, with and without endothelium present. ATH had an increased rate of direct inhibition of IIa and Xa, and increased inhibition of IIa-induced fibrin formation, compared to AT+H. When compared at equal anti-Xa levels, ATH was less effective than AT+H at catalyzing inhibition of plasma clot generation. These results were found in both the presence and absence of endothelium. Endothelium decreased the rate of IIa inhibition, and reduced clot time in IIa-induced fibrin formation and plasma clot generation assays, for both ATH and AT+H. Endothelium did not impact the activity of ATH differently to AT+H. This supports the growing body of evidence suggesting ATH may be a beneficial anticoagulant for potential clinical use.

A retrospective study of the management and outcomes of pregnancies with inherited antithrombin deficiency.

Antithrombin (AT) deficiency is a rare but highly thrombogenic inherited thrombophilia. Its association with adverse pregnancy outcomes (APO) is undefined. There is limited guidance on managing AT deficiency in pregnancy. Some significant issues remain controversial, including risk assessment for prophylactic anticoagulation, anticoagulant therapy, and monitoring. Our goal was to examine if the antepartum management of patients with AT deficiency affected their pregnancy outcomes. This retrospective, single-center observational study included pregnant women with inherited AT deficiency in Peking Union Medical College Hospital between 2013 and 2024. Seventeen pregnancies in 6 women with AT deficiency were identified. A total of 7 pregnancies received adjusted-dose low-molecular-weight heparin (LMWH) and were monitored by anti-Xa level, AT activity, and D-dimer. There were 5 live births (all received LMWH), 7 second-trimester abortions (1 received LMWH), and 5 early pregnancy losses (1 received LMWH). There were 5 abruptio placentae events (3 received LMWH) and 7 thrombotic events (2 received LMWH). AT deficiency is at least an important partial factor contributing to APO. It is suggested to make a full assessment of AT patients both for venous thrombus embolism and APO risk. We observed a high prevalence of heparin resistance and a positive correlation between adequate anticoagulation and pregnancy outcome based on tight monitoring with anti-Xa level and timely adjustment of the LMWH dosage.

Evaluation of Anti-Xa Target Attainment with Prophylactic Enoxaparin Dosing Regimens for Venous Thromboembolism Prophylaxis in Morbidly Obese Patients.

Subcutaneous enoxaparin has been shown to reduce the risk of venous thromboembolism (VTE) among hospitalized patients. However, alternative enoxaparin dosing strategies may be necessary in morbid obesity. The objective of this study was to assess the rate of target anti-Xa attainment with three enoxaparin dosing regimens for venous thromboembolism (VTE) prophylaxis in morbidly obese patients. In this retrospective study, anti-Xa target attainment was assessed among adult patients with a body mass index (BMI) ≥ 40 kg/m2 receiving enoxaparin 40 mg twice daily (BID), 60 mg BID, or 0.5 mg/kg BID. Univariate and multivariate analyses were conducted. Target anti-Xa levels were defined as a steady-state, peak level of 0.2-0.5 IU/mL. This study included 120 patients with 55 patients receiving 40 mg BID, 44 patients receiving 60 mg BID, and 21 patients receiving 0.5 mg/kg BID. Target anti-Xa levels were achieved in 29.1% of patients in the 40 mg BID arm, 54.5% in the 60 mg BID arm, and 90.5% in the 0.5 mg/kg BID arm. Anti-Xa target attainment was significantly increased in both the 60 mg BID arm (p = 0.01) and the 0.5 mg/kg arm (p < 0.0001), compared to the 40 mg BID arm. In morbidly obese patients, weight-based dosing was associated with a greater attainment of target anti-Xa levels. Further studies are needed to determine the impact of these dosing regimens on clinical outcomes.

Discordant High Activated Partial Thromboplastin Time Relative to Anti-Xa Values in Hospitalized Patients is an Independent Risk Factor for Increased 30-day Mortality.

The activated partial thromboplastin time (aPTT) and anti-factor-Xa levels (anti-Xa) are both used to monitor patients on unfractionated heparin. Our previous study demonstrated that patients with discordant high aPTT relative to anti-Xa had higher rates of mortality and bleeding events. To determine if underlying patient characteristics drive both discordance and adverse outcomes or if discordance is an independent risk factor to adverse outcomes. We analyzed all patients hospitalized at the Stanford Hospital between January 2011 and December 2019 who had simultaneous aPTT and anti-Xa levels performed. From the electronic medical record, we extracted and analyzed 51 patient features including baseline coagulation laboratory results, demographics, values of other common laboratories (basic metabolic panel, complete blood count, etc.), diagnostic procedures, medications, and death. A total of 17,728 patients had 78,701 paired aPTT and anti-Xa levels. Patients with discordant aPTT and anti-Xa where aPTT (seconds) was elevated beyond the expected therapeutic range had a higher 30-day mortality (odds ratio [OR]: 2.16, 95% confidence interval [CI]: 1.78-2.63, p < 0.001). Sectioning the patients based on the degree of discordance and whether aPTT or anti-Xa were signaling excess anticoagulation, we found those with an elevated aPTT discordant to their anti-Xa level had the highest odds of death (OR: 2.46, 95% CI: 1.99-3.10) compared with the concordant group. This finding was still present after controlling for patient comorbidity and other laboratory results at hospital admission. After controlling for patient features strongly associated with increased mortality in heparinized patients, we identified that the discordant pattern of high aPTT to anti-Xa served as an independent predictor of 30-day all-cause mortality, with a higher degree of discordance associated with increased odds of 30-day mortality.

#2147 Enoxaparin dosing in advanced chronic kidney disease: importance of monitoring with anti-Xa levels

Abstract Background and Aims Enoxaparin is a low-molecular-weight heparin (LMWH) that is commonly used in the prevention of deep venous thrombosis (DVT) and the treatment of acute thomboembolic diseases. Current literature indicates that in advanced chronic kidney disease (CKD), there is a reduced clearance and increased half-life of LMWH and therefore, a dose adjustment is recommended. The prescription label recommends a dose adjustment of enoxaparin to 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation when eGFR &amp;lt;30 ml/min. The aim of this study was to examine the accuracy of this dosing strategy to achieve the desired target of anticoagulation in advanced CKD. Method We conducted a prospective study in patients admitted from May 2019 to April 2023 in the Nephrology ward at our centre, who started anticoagulant treatment with enoxaparin during their in-hospital stay for prophylactic or therapeutic indications. We excluded patients with eGFR &amp;gt;30 ml/min at the onset of anticoagulation with enoxaparin. The dosing strategy was 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation in all patients. Blood samples were drawn 4 hours after the third dose of enoxaparin to monitor anti-Xa levels in all cases. Results The study included 153 patients; 70 patients with stage 4-5 CKD and 83 patients on renal replacement therapy. 132 patients (86.3%) received enoxaparin for a therapeutic indication, while 21 patients (13.7%) received it as prophylaxis of DVT. In patients receiving enoxaparin for a therapeutic indication, 73 patients (55.3%) reached the therapeutic target anti-Xa levels (0.6-1), while 32.6% of patients had peak anti-Xa levels below the therapeutic target (&amp;lt;0.6) and 12.1% were over-anticoagulated (&amp;gt;1). There was an inverse relationship between the proportion of patients who were adequately anticoagulated and CKD stage; 66.7%, 58.6% and 48.6% of patients reached the target peak anti-Xa levels in CKD stage 4, 5 and 5D respectively. There was no significant association between anti-Xa levels and obesity or liver disease. In patients receiving enoxaparin for prophylaxis of DVT, 42.9% reached the target anti-Xa levels for prophylaxis (0.3-0.6), while 38.1% had anti-Xa levels below this range and 19% were over-anticoagulated. Conclusion The enoxaparin dosing recommendations indicated by its label entails a high proportion of patients with advanced CKD who do not achieve the target therapeutic levels of antiXa, especially in patients on renal replacement therapy. To ensure adequate anticoagulation in these patients, we recommend using individualized dosing adjustments based on monitoring of anti-Xa levels for the prevention of thromboembolic events and reducing the risk of hemorrhagic events.

Glass bead-activated clotting time (gb-ACT) for monitoring the anticoagulation effects in elderly patients with high risk of venous thromboembolism (VTE)

ABSTRACT Background To find a new bedside method to monitor the anticoagulation effects of low-molecular-weight heparins (LMWHs) in patients with a high risk of venous thromboembolism (VTE). Research design and methods A total of 32 hospitalized patients (aged ≥60 years) who were at high risk of VTE were assigned to receive subcutaneous LMWH for 5 to 14 days. Plasma anti-factor Xa (anti-Xa) activity was conducted by a chromogenic method, and the glass bead-activated whole blood clotting time (gb-ACT) value was obtained by a Sonoclot Analyzer. Results A correlation between the gb-ACT values and the anti-Xa levels was suggested (R = 0.447, p = 0.002), and it was stronger in the older group aged 80 years above (R = 0.467, p = 0.008) and in the group of patients with an eGFR of 30 ~ 60 mL/min (R = 0.565, p = 0.005). The area under the curve (AUC) for gb-ACT by receiver operating characteristic (ROC) curve evaluation was 0.725 (p = 0.011), and the gb-ACT >282.5s provided a sensitivity of 60% and specificity of 74% for anti-Xa >0.800 IU/ml. Conclusions The gb-ACT values detected by a Sonoclot Analyzer could act as a novel bedside method in the monitoring of LMWH anticoagulation.

Prophylactic Unfractionated Heparin in Antepartum Hospitalizations: A Randomized Controlled Trial.

To assess the effect of gestational age-based dosing of unfractionated heparin (UFH) compared with standard dosing of UFH for thromboprophylaxis on an elevated serum activated partial thromboplastin time (aPTT) during prolonged antepartum hospitalizations. This was a randomized trial of pregnant persons who were admitted in the antepartum period for at least 72 hours. Participants were randomly allocated to the standard dose of UFH (5,000 units subcutaneously every 12 hours) or the gestational age-based dose of UFH (first trimester [less than 14 weeks]: 5,000 units subcutaneously every 12 hours; second trimester [14-27 6/7 weeks]: 7,500 units subcutaneously every 12 hours; third trimester (28 weeks or more): 10,000 units subcutaneously every 12 hours). The primary outcome was the proportion of antepartum patients who had an elevated serum aPTT value above the normal range (more than 36.2 seconds) 6 hours after an UFH dose. Secondary outcomes included the development of venous thromboembolism (VTE) and reported side effects of heparin administration. Between December 15, 2020, and April 1, 2022, 97 patients with antepartum hospitalizations were screened and 46 were randomized: 22 allocated to standard dosing and 24 allocated to gestational age-based dosing of UFH. A significantly greater proportion of antepartum patients who received gestational age-based dosing had an abnormal elevation in aPTT compared with those who received standard dosing (33.3% vs 4.8%, P =.02). Gestational age-based dosing resulted in higher maximum [interquartile range] aPTT (30.4 [27.4, 37.5] vs 26.6 [23.0, 29.6], P =.01) and anti-Xa levels (0.09 [0.09, 0.11] vs 0.09 [0.09, 0.09], P =.04). There was no significant difference in VTE between groups ( P =.47). Gestational age-based dosing of UFH for thromboprophylaxis of antepartum hospitalizations was associated with significantly increased rates of elevated coagulation parameters compared with standard fixed dosing. This study suggests a need for close monitoring if higher doses of UFH during pregnancy are used later in gestation. The efficacy of gestational age-based dosing compared with standard dosing for UFH to prevent thromboembolic events remains an area for future investigation. ClinicalTrials.gov , NCT04635839.

Pharmacologic Venous Thromboembolism Prophylaxis in Patients with Nontraumatic Subarachnoid Hemorrhage Requiring an External Ventricular Drain.

Optimal pharmacologic thromboprophylaxis dosing is not well described in patients with subarachnoid hemorrhage (SAH) with an external ventricular drain (EVD). Our patients with SAH with an EVD who receive prophylactic enoxaparin are routinely monitored using timed anti-Xa levels. Our primary study goal was to determine the frequency of venous thromboembolism (VTE) and secondary intracranial hemorrhage (ICH) for this population of patients who received pharmacologic prophylaxis with enoxaparin or unfractionated heparin (UFH). A retrospective chart review was performed for all patients with SAH admitted to the neurocritical care unit at Emory University Hospital between 2012 and 2017. All patients with SAH who required an EVD were included. Of 1,351 patients screened, 868 required an EVD. Of these 868 patients, 627 received enoxaparin, 114 received UFH, and 127 did not receive pharmacologic prophylaxis. VTE occurred in 7.5% of patients in the enoxaparin group, 4.4% in the UFH group (p = 0.32), and 3.2% in the no VTE prophylaxis group (p = 0.08). Secondary ICH occurred in 3.83% of patients in the enoxaparin group, 3.51% in the UFH group (p = 1), and 3.94% in the no VTE prophylaxis group (p = 0.53). As steady-state anti-Xa levels increased from 0.1 units/mL to > 0.3 units/mL, there was a trend toward a lower incidence of VTE. However, no correlation was noted between rising anti-Xa levels and an increased incidence of secondary ICH. When compared, neither enoxaparin nor UFH use was associated with a significantly reduced incidence of VTE or an increased incidence of ICH. In this retrospective study of patients with nontraumatic SAH with an EVD who received enoxaparin or UFH VTE prophylaxis or no VTE prophylaxis, there was no statistically significant difference in the incidence of VTE or secondary ICH. For patients receiving prophylactic enoxaparin, achieving higher steady-state target anti-Xa levels may be associated with a lower incidence of VTE without increasing the risk of secondary ICH.

Discordance between aPTT and anti-Xa in monitoring heparin anticoagulation in mechanical circulatory support.

It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance. aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100s and 0.3-0.7IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning random forest model and a multivariate regression model were applied to patient demographics, device type, and 14 laboratory variables; 23001 pairs of simultaneously measured aPTT/anti-Xa were collected from 699 MCS patients. aPTT and anti-Xa were concordant in 35.5% of paired observations and discordant in 64.5% (aPTT>antiXa 61.5%; aPTT<antiXa 3.0%). Discordance with a high aPTT relative to anti-Xa (aPTT>antiXa) was associated with high INR, eGFR, and total bilirubin, as well as low platelets, haemoglobin, pre-albumin, white blood cell count, and haptoglobin. Total artificial heart and durable ventricular assist devices were more likely to be associated with aPTT>anti-Xa than temporary MCS devices. aPTT and anti-Xa were frequently discordant in MCS patients receiving heparin anticoagulation. Clinical conditions common in MCS patients such as concurrent warfarin use, malnutrition, haemolysis, and thrombocytopenia, as well as durable type of MCS devices were associated with a high aPTT relative to anti-Xa.

Monitoring anti-Xa levels in elderly medical patients undergoing thromboprophylaxis: A prospective cohort study.

Given the rising incidence of venous thromboembolism (VTE) and insufficient thromboprophylaxis dosing evidence in certain patients, the precise monitoring of anti-Xa (aFXa) levels is crucial. The aim of this study is to investigate the achievement of prophylactic aFXa levels in medical inpatients who were receiving parenteral anticoagulant and to evaluate the impact of various factors on aFXa levels. This is a single-center observational cohort study conducted on patients admitted to the Department of Internal Medicine at the University Hospital of Heraklion, Greece, from March to August 2023. These individuals received low-molecular-weight heparins thromboprophylaxis owing to an increased risk of VTE. Data regarding demographics, past medical history, and somatometric and laboratory findings were recorded. The established range for peak prophylactic aFXa levels was defined as 0.2-0.5 IU/mL. In this study, we enrolled 150 individuals [91 (60.7%) women] with a mean age of 80.0 ± 14.1 years. Sixty-two (41.4%) patients exhibited non-prophylactic peak aFXa levels. Supratherapeutic levels were observed in all underweight patients and subtherapeutic levels in 12 of 13 obese patients in class II and III. A multivariate linear regression analysis revealed that body weight, cancer, and the Charlson Comorbidity Index (CCI) were independent factors influencing aFXa levels. Our study reveals a substantial portion of medical elderly inpatients on thromboprophylaxis with non-prophylactic aFXa levels, with a notable prevalence among underweight and severely obese patients. Body weight, cancer, and CCI were identified as independent factors influencing aFXa levels, advocating for tailored thromboprophylaxis strategies. Further research is warranted to validate personalized dosing approaches and to enhance clinical decision-making. Geriatr Gerontol Int 2024; 24: 587-594.

Enoxaparin treatment dosing for venous thromboembolism in pediatric patients with obesity.

The optimal enoxaparin dosing for treatment of venous thromboembolism (VTE) in pediatric patients with obesity remains uncertain. We described the mean enoxaparin dose required to attain anti-factor Xa (anti-Xa) levels of 0.5-1unit/mL in pediatric patients with obesity. Pediatric patients with obesity (body mass index [BMI]≥95th percentile) who received treatment dose of enoxaparin from 2013 to 2022 and had at least one appropriately timed anti-Xa level were retrospectively evaluated. Daily enoxaparin dose required to achieve an anti-Xa level of 0.5-1unit/mL was reviewed and compared by the severity of obesity. The correlation coefficients between enoxaparin dose requirement and BMI, BMI percentile, and weight were measured by Spearman's rank correlation coefficient. Pediatric patients with obesity (n=89) required a mean enoxaparin dose of 0.8±0.18mg/kg twice daily to attain a therapeutic anti-Xa level. Children with BMI 95th-99th percentile and weight ≤100kg achieved the target level on a significantly higher weight-based enoxaparin dose compared to BMI greater than 99th percentile (0.95±0.15 vs. 0.75±0.15mg/kg twice daily; p<.001) and weight greater than 100kg (0.95±0.14 vs. 0.7±0.12mg/kg twice daily; p<.001). BMI, BMI percentile, and weight showed a moderate to strong negative correlation with enoxaparin dose requirement. Pediatric patients with obesity required a lower weight-based dose of enoxaparin to achieve a therapeutic anti-Xa than the recommended starting dose of 1mg/kg twice daily for treatment of VTE. Among obesity indices, weight showed the strongest negative correlation with total daily enoxaparin requirement.

INFLUENCE OF VARIOUS FACTORS ON ANTI-XA LEVELS IN HOSPITALIZED MEDICAL PATIENTS RECEIVING PARENTERAL THROMBOPROPHYLAXIS

Objective: Venous thromboembolism (VTE) stands as a prevalent vascular disease, intimately linked to increased risk for morbidity and mortality. The aim of this study was to investigate the influence of various factors on anti-Xa levels in hospitalized medical patients receiving parenteral thromboprophylaxis. Design and method: This is a single-center cohort study encompassing patients admitted to the Internal Medicine Department of the University Hospital of Heraklion, from March to August 2023. These patients were placed on thromboprophylaxis due to a heightened risk of developing VTE. Data regarding demographics, past medical history, somatometric and laboratory findings as well as the type and dose of parenteral anticoagulant were recorded. The measurement of anti-Xa levels were conducted 4 hours subsequent to the third subcutaneous administration of anticoagulant. Results: In this study, we enrolled 150 individuals [91 women (60.7%)], with an average age of 80 years. Sixty-two (41.4%) patients exhibited non-therapeutic anti-Xa levels. The levels were subtherapeutic (&lt;0.2units/mL) in 36 patients and supratherapeutic (&gt;0.5units/mL) in 26 patients. Non-therapeutic anti-Xa levels were observed in all underweight patients and in 12 out of 13 obese class II and III patients. It's noteworthy that therapeutic anti-Xa levels were observed in more than half of healthy-weight and overweight patients. A univariate logistic regression analyses was conducted to explore factors (age, sex, past medical history, somatometric and laboratory findings) that had impact on anti-Xa levels. Among these, only body weight emerged as independent factor influencing anti-Xa levels. Conclusions: In our study, we demonstrated that 41.3% of medical patients who were administered parenteral thromboprophylaxis exhibited non-therapeutic anti-Xa levels. This was more profound for underweight or obese class II and III patients. Body weight was emerged as independent factor influencing anti-Xa levels. Further studies on weight-based LMWH thromboprophylaxis dosing in this population are likely to yield new insights improving decisions in daily clinical practice.

599 To Titrate or Not to Titrate, That Is the Burning Question: Enoxaparin and VTE Prophylaxis

Abstract Introduction Patients who sustain burn injury undergo metabolic and physiologic changes that place them at elevated risk of developing venous thromboembolism (VTE). Although the benefit and safety of enoxaparin titration for prevention of VTE in trauma patients is well established, there is a lack of evidence regarding its applicability for burn injured patients. In this study, we sought to determine the safety and applicability of enoxaparin titration for burn injured patients admitted for treatment of their injury. Methods We performed a single center retrospective study of burn injured patients admitted to our American Burn Association verified burn center from June 2022 to June 2023. In May 2022, our burn center adopted the American Association for Surgeons in Trauma (AAST) protocol for enoxaparin dosing. This includes twice daily administration of enoxaparin, followed by measurement of anti-Xa levels prior to administration of the fourth or fifth dose. We previously administered a standard dose of 30mg twice daily. Anti-Xa levels were used to guide enoxaparin dose adjustments to remain within prophylactic range. Patients hospitalized for under 48 hours, with glomerular filtration rate less than 30, and with repeated refusal of enoxaparin were excluded. Results Eighty seven patients met our inclusion criteria. Fifty six patients started at 40mg twice daily dosing; the remainder started at 30mg twice daily dosing. Of these patients, forty two (48%) required dose adjustments by anti-Xa levels. Of those who required dose adjustment, thirty three (78%) required an increase. There was no significant difference in BMI (p=0.25) or inhalation injury (p=0.62) between patients who did and did not require enoxaparin titration. Patients who required titration had a non-significant trend toward larger percent total body surface area affected (p=0.08). There was also a significantly greater change in dosing for patients who required an increase in dose adjustment as opposed to those who required a decrease in dose adjustment (p &amp;lt; 0.0001). Finally, there was no difference in post-operative bleeding between patients who did and did not require dose titration (p=0.57). Conclusions Our results demonstrate that an individual approach to VTE prevention through enoxaparin titration is necessary in order to maintain appropriate prophylactic doses in burn injured patients. Furthermore, adoption of the AAST guidelines is safe and does not result in an increase in post-operative bleeding events. Applicability of Research to Practice This work highlights the safety and benefit of enoxaparin titration in burn injured patients to prevent VTE.

114 Burn Specific VTE Prophylaxis: Higher Enoxaparin Dose and Anti-Xa Adjustments Is Safe and Potentially Beneficial

Abstract Introduction Burn and trauma patients are at high risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolus (PE). VTE prophylaxis guidelines for trauma patients recommends a higher standard dose of enoxaparin and anti-Xa level adjustments in select patients; however, no guidelines specific to burn patients exist. We hypothesize that higher standard doses of enoxaparin and anti-Xa level adjustments will be safe and effective at reducing VTE complications in burn patients. Methods This retrospective review included patients admitted to a regional burn center six months prior to and after the initiation of a VTE prophylaxis quality improvement protocol. The protocol doubled the standard dose of enoxaparin, 40 mg daily to 40 mg twice a day, for all burn patients who were &amp;gt; 50 kg and had creatinine clearance &amp;gt; 60mg/dl. Peak anti-Xa level monitoring was indicated if a high-risk factor (TBSA ≥20%, inhalation injury, burn shock, BMI ≥40) was present. Patients on therapeutic anticoagulation or anti-platelet therapy, had a history of chronic kidney disease, decompensated cirrhosis, coagulation disorder, heparin induced thrombocytopenia (HIT), or were admitted for polytrauma were excluded. Efficacy was evaluated by rates of VTE within 31 days of discharge. Safety was evaluated by bleeding complications, including estimated blood loss (EBL), number of transfusions and gastrointestinal (GI) bleeding events. Differences between groups were compared using a two-sample t-test or Wilcoxon rank-sum test. A p-value of &amp;lt; 0.05 signified statistical significance. Results The pre-protocol group included 217 patients and the post-protocol group included 207 patients. There were no significant differences in age (45 vs 44 years), BMI (27 vs 26.4 kg/m2), TBSA (5.9 vs 5.3%), IHI (4.6 vs 7%), number of procedures (3 vs 3), mortality (4.1 vs 3%), or ICU length of stay (1.9 vs 1.6 days) between groups. No significant difference in EBL (50 vs 25 cc), number of transfusions (3.3 vs 2.4 units), or GI bleeding events (1 vs 1) was noted between groups, and no patient developed thrombocytopenia or HIT. There were 5 patients (2.3%) with a VTE within 31 days of discharge in the pre-protocol group compared to 1 patient (0.4%) in the post-protocol group (p=0.19). There was not enough power to determine statistically significant VTE prevention. Conclusions A lack of VTE prophylaxis recommendations for burn patients leads to variability in protocols among burn centers. These protocols are infrequently studied. This protocol, which doubled the standard dose of enoxaparin and adjusted based on anti-Xa levels for high-risk patients, was safe. Efficacy and applicability to other centers needs further elucidation. Applicability of Research to Practice Enoxaparin 40mg twice a day with anti-Xa level adjustments is safe and a promising strategy to reduce the rates of VTE in the burn population without increasing bleeding complications.

Efficacy and Safety of Tinzaparin Thromboprophylaxis in Lung Cancer Patients with High Thromboembolic Risk: A Prospective, Observational, Single-Center Cohort Study.

The aim of this study was to record and assess the efficacy and safety ofthromboprophylaxis with an intermediate dose of Tinzaparin in lung cancer patients with high thrombotic risk. This was a non-interventional, single-arm, prospective cohort study of lung cancer patients who received thromboprophylaxis with Tinzaparin 10.000 Anti-Xa IU in 0.5 mL, OD, used in current clinical practice. Enrolled ambulatory patients signed informed consent. Anti-Xa levels were tested. In total, 140 patients were included in the study, of which 81.4% were males. The histology of the tumor was mainly adenocarcinoma. Lung cancer patients with high thrombotic risk based on tumor, patient, treatment, and laboratory-related factors were enrolled. Only one patient experienced a thrombotic event (0.7%), and 10 patients had bleeding events (7.1%), including only one major event. Anti-Xa levels measured at 10 days and 3 months did not differ significantly between patients who developed hemorrhagic events and those who did not (p = 0.26 and p = 0.32, respectively). Thromboprophylaxis with an intermediate Tinzaparin dose in high thrombotic-risk lung cancer patients is a safe and effective choice for the prevention of VTE.