Anti factor Xa monitoring for venous thromboprophylaxis in severely burn-injured patients: A systematic review.

INTRODUCTION: Patients with severe burn injuries are at risk of venous thromboembolism (VTE) and associated sequelae. Burn-injured patients may require larger doses of VTE prophylaxis so underdosing may occur with standard regimens. Monitoring anti-factor Xa (AFXa) levels may allow tailoring of dosage but is currently uncommon. The purpose of this systematic review was to methodically review the available literature with respect to AFXa in severe burn-injured patients, and thereby assess its efficacy. METHODS: Using PRISMA guidelines, "Xa" and "burns" were used to systematically review MEDLINE (1946 - present) and EMBASE (1974 - present) databases for publications regarding the monitoring of AFXa levels for thromboprophylaxis in burn-injured patients. RESULTS: Eight studies (432 patients) met inclusion. Peak AFXa level at initial measurement was reported in all studies and was within the range for prophylaxis in 184 of 432 cases (42.6%), below range in 246 of 432 cases (56.9%) and above range for 2/432 (0.5%). Complications were reported in 7 studies (412 patients), with a total of 30 (7.3%) complications, comprising of 16 (53.3%) VTE events and 14 (46.7%) mortalities. Three studies comprising 270 patients compared complications between patients who were within the reference range with patients who were below the range. There were 164 patients from the 'within the reference range' groups that had a total of 6 (3.7%) complications, comprised of 4 (66.7%) VTE events and 2 (33.3%) mortalities. There were 106 patients from the 'below reference range group' that had a total of 11 (10.4%) complications, comprised of 9 (81.8%) VTE events and 2 (18.2%) mortalities. CONCLUSION: Our findings suggest standard prophylactic anticoagulation dosing risks underdosing and therefore, an increased risk in the development of VTE. AFXa monitoring allows individually tailored dose adjustment to reach therapeutic levels, which may be efficacious in reducing VTE events and is therefore recommended where possible.

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

AIMS: 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. METHODS AND RESULTS: 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 60-100 s and 0.3-0.7 IU/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; 23 001 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. CONCLUSIONS: 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.

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

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.

Comparison of enoxaparin 40 mg versus 60 mg dosage for venous thromboprophylaxis in patients undergoing bariatric surgery: A randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common cause of morbidity and mortality after bariatric surgery. Morbid obesity is an independent risk factor for VTE, with goals of prophylactic anti-factor Xa levels within 0.2-0.5 IU/mL. The recommended dosing regimen of enoxaparin for VTE prophylaxis in patients with morbid obesity is lacking in available guidelines. OBJECTIVES: To evaluate the achieving prophylactic anti-factor Xa levels with different dosages of enoxaparin for morbid obesity patients. SETTING: We conducted a study at Chulalongkorn Bariatric and Metabolic Institute, King Chulalongkorn Memorial Hospital. METHODS: We conducted a randomized controlled trial comparing anti-factor Xa levels 4 h after the administration of enoxaparin. All recruited patients randomly received 40 mg or 60 mg of enoxaparin 12 h before the operation. Blood specimens were collected 4 h after the administration of enoxaparin. RESULTS: In total, 56 patients who presented between April 2019 and March 2020 at King Chulalongkorn Memorial Hospital were recruited. Of these patients, 28 received 40 mg and 28 received 60 mg of enoxaparin. In both groups, the rates of achieving target levels were 53.57% and 78.57%, respectively (p-value = 0.048). The mean anti-factor Xa levels were 0.19 IU/mL ± 0.06 IU/mL and 0.28 and 0.28 ± 0.10 IU/mL, respectively (p < 0.001). No significant difference was found in the estimated blood loss between the groups. No patient obtained anti-factor Xa levels exceeding 0.5 IU/mL. In both groups, no symptomatic VTE occurred. CONCLUSIONS: A 60 mg of enoxaparin regimen achieved more prophylactic anti-factor Xa levels than 40 mg in obese patients undergoing bariatric surgery without any adverse events.

Pilot study examining anti-factor Xa levels for heparin monitoring and outcomes in patients with cerebral venous thrombosis.

Objective: There are no studies to date that examine the association between anti-factor-Xa (AFXa)-based heparin monitoring and clinical outcomes in the setting of cerebral venous thrombosis (CVT). Methods: This pilot study included adults aged ≥18 admitted with CVT between 1 January 2018 and 1 January 2021, who were treated with unfractionated heparin (UFH) and were monitored via AFXa-based nomogram within 24 h of arrival. Comparisons were made between patients with AFXa levels within the target therapeutic range (0.25-0.5 IU/mL) and patients whose levels were not within the therapeutic range within 24 h of arrival; the time (hours) from arrival to reach the therapeutic range was also examined. Outcomes were length of stay (LOS) in the hospital, major (actionable) bleeding events, and discharge home (vs. higher acuity location). Continuous data are reported in the form of the median (interquartile range). Results: Among 45 patients, treatment with UFH was initiated 2 (1-11) h after arrival, and the majority (84%) of UFH infusions did not need dose adjustment. AFXa assays were conducted every 6 (5.5-7) h. Thirty patients (67%) fell within the therapeutic range. Outcomes were similar for patients with levels within the therapeutic range vs. not: major bleeding events, 10% vs. 0% (p = 0.54); discharge home, 77% vs. 80% (p = 1.0); LOS, 5 days in each group (p = 0.95). There was also no association between outcomes and time to reach the therapeutic range. Conclusion: Our findings demonstrate the practicability of monitoring UFH based on AFXa values in this population of patients with CVT, but reaching target AFXa levels within 24 h of arrival may not necessarily be prognostic.

Pharmacokinetic Modeling Using Real-World Data to Optimize Unfractionated Heparin Dosing in Pediatric Patients on Extracorporeal Membrane Oxygenation and Evaluate Target Achievement-Clinical Outcomes Relationship.

Unfractionated heparin (UFH) is a commonly used anticoagulant for pediatric patients undergoing extracorporeal membrane oxygenation (ECMO), but evidence is lacking on the ideal dosing. We aimed to (1) develop a population pharmacokinetic (PK) model for UFH, measured through anti-factor Xa assay; (2) optimize UFH starting infusions and dose titrations through simulations; and (3) explore UFH exposure-clinical outcomes relationship. Data from 218 patients admitted to Utah's Primary Children's Hospital were retrospectively collected. A 1-compartment PK model with time-varying clearance (CL) adequately described UFH PK. Weight on CL and volume of distribution and ECMO circuit change on CL were significant covariates. The typical estimates for initial CL and first-order rate constant to reach steady-state CL were 0.57 L/(h·10 kg) and 0.02/h. Comparable to non-ECMO patients, the typical steady-state CL was 0.81 L/(h·10 kg). Simulations showed that a 75 IU/kg UFH bolus dose followed by starting infusions of 25 and 20 IU/h/kg for patients aged younger than 6 years and 6 years or older, respectively, achieved the therapeutic target in 56.6% of all patients, whereas only 3.1% exceeded the target. The proposed UFH titration schemes achieved the target in more than 90% of patients while less than 0.63% were above the target after 24 and 48 hours of treatment. The median intensive care unit survival time in patients within and below the target at 24 hours was 136 and 66 hours, respectively. In conclusion, PK model of UFH was developed for pediatric patients on ECMO. The proposed UFH dosing scheme attained the anti-factor Xa target rapidly and safely.

Clinical outcomes associated with anti-Xa-monitored enoxaparin for venous thromboembolism prophylaxis.

STUDY OBJECTIVE: The objective of the study was to assess clinical outcomes (composite of any venous thromboembolism [VTE], any bleeding, and mortality) associated with anti-Xa monitoring in the 30 days following enoxaparin initiation for VTE prophylaxis. DESIGN: Retrospective cohort study. SETTING: Hospital within an academic healthcare system. PATIENTS: Propensity score-matched hospitalized adults receiving enoxaparin for VTE prophylaxis. INTERVENTION: Low-molecular-weight heparin anti-Xa monitoring. MEASUREMENTS AND MAIN RESULTS: During the 13-month study period, a total of 6611 patients received enoxaparin for VTE prophylaxis, 301 in the anti-Xa monitored group and 6310 in the unmonitored group (4.6% received monitoring). The mean age was 52.9 years and 52% of patients were male. The mean body mass index was 31 kg/m2 and the mean creatinine clearance was 109 mL/min. Twenty percent of patients had active cancer. The most common indication for enoxaparin prophylaxis was hospitalization for medical illness (52%) followed by nonorthopedic surgery (37%). The adjusted odds ratio for the primary outcome comparing monitored to unmonitored patients was 1.26 (95% confidence interval, 0.75-2.11). None of the between-group differences in the individual components of the composite outcome were statistically significant. CONCLUSIONS: Thirty-day clinical outcomes in patients receiving enoxaparin for VTE prophylaxis were not improved by anti-Xa monitoring. Our results support current evidence-based guideline recommendations against anti-Xa monitoring for patients receiving enoxaparin for VTE prophylaxis.

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 doses did 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.

Anti-Factor-Xa and Activated Partial Thromboplastin Time Concordance and Outcomes in Adults Undergoing Extracorporeal Membrane Oxygenation: A Secondary Analysis of the Pilot Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation Randomized Trial.

OBJECTIVES: To determine the concordance between activated partial thromboplastin time (aPTT) and anti-factor-Xa (anti-Xa) in adults undergoing extracorporeal membrane oxygenation (ECMO) and to identify the factors associated with discordant paired aPTT/anti-Xa. DESIGN: Pre-planned secondary analysis of the Low-Dose Heparin in Critically Ill Patients Undergoing Extracorporeal Membrane Oxygenation pilot randomized unblinded, parallel-group controlled trial. SETTING: Two ICUs in two university hospitals. PATIENTS: Thirty-two critically ill patients who underwent ECMO and who had at least one paired aPTT and anti-Xa assay performed at the same time. INTERVENTIONS: We analyzed the concordance between aPTT and anti-Xa and identified factors associated with discordant paired aPTT/anti-Xa based on their respective therapeutic ranges. We also compared biological parameters between heparin resistance episode and no heparin resistance. MEASUREMENTS AND MAIN RESULTS: Of the 32 patients who were included in this study, 24 (75%) had at least one discordant paired aPTT/anti-Xa. Of the 581 paired aPTT/anti-Xa that were analyzed, 202 were discordant. The aPTT was relatively lower than anti-Xa in 66 cases (32.7%) or relatively higher than anti-Xa in 136 cases (67.3%). Thirty-three heparin resistance episodes were identified in six patients (19%). CONCLUSIONS: In these critically ill patients undergoing ECMO, one third of paired aPTT/anti-Xa measures was discordant. Coagulopathy and heparin resistance might be the reasons for discordance. Our results support the potential importance of routinely monitoring both tests in this setting.

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.

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.

Concordance Between Active Partial Thromboplastin Time and Anti-Factor Xa Assays in Neurocritically Ill Patients Receiving Subcutaneous Heparin Prophylaxis.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

The Role of Anti-Factor Xa Activity in the Management of Ecchymosis in Patients Receiving Rivaroxaban after Total Knee Arthroplasty.

This study aims to evaluate the efficacy of anti-factor Xa activity (aFXa) in predicting ecchymosis after total knee arthroplasty (TKA). One hundred and two unilateral primary TKA patients were recruited consecutively in this prospective observational study. Participants received rivaroxaban (10 mg p.o. qd) from postoperative day 1 (POD1) to POD35 and were divided into a non-ecchymosis group (group A) and an ecchymosis group (group B). AFXa was assessed as the primary outcome on POD1 and POD3. Prothrombin time (PT), activated partial thromboplastin time (APTT) and thromboelastography (TEG) were recorded both preoperatively and postoperatively (on POD1 and POD3). Other outcomes, including venous thromboembolism (VTE), blood loss and wound complications were also collected and compared. As a result, 27.5% of the participants (n = 28) were allocated into group B. Demographic data were comparable between the two groups. The aFXa levels in group B were significantly higher than those in group A on POD1 and POD3, and the aFXa level was assessed as an independent risk factor for ecchymosis. The cut-off value of aFXa was determined to be 121.38 ng/mL at maximal Youden index, associated with area under the receiver operating characteristics curve of 0.67. Group B experienced significantly more blood loss and wound complications than group A. No statistical difference was detected regarding PT, APTT and TEG parameters. AFXa is a promising parameter to predict ecchymosis after TKA. Patients with aFXa > 121.38 ng/mL should be considered as high-risk population for postoperative ecchymosis and may require intense monitoring or dosage modification of anticoagulants.

Evaluation of a Multimodal Heparin Laboratory Monitoring Protocol in Adult Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: Anticoagulation monitoring practices vary during extracorporeal membrane oxygenation (ECMO). The Extracorporeal Life Support Organization describes that a multimodal approach is needed to overcome assay limitations and minimize complications. OBJECTIVE: Compare activated clotting time (ACT) versus multimodal approach (activated partial thromboplastin time (aPTT)/anti-factor Xa) for unfractionated heparin (UFH) monitoring in adult ECMO patients. METHODS: We conducted a single-center retrospective pre- (ACT) versus post-implementation (multimodal approach) study. The incidence of major bleeding and thrombosis, blood product and antithrombin III (ATIII) administration, and UFH infusion rates were compared. RESULTS: Incidence of major bleeding (69.2% versus 62.2%, p = 0.345) and thrombosis (23% versus 14.9%, p = 0.369) was similar between groups. Median number of ATIII doses was reduced in the multimodal group (1.0 [IQR 0.0-2.0] versus 0.0 [0.0 -1.0], p = 0.007). The median UFH infusion rate was higher in the ACT group, but not significant (16.9 [IQR 9.6-22.4] versus 13 [IQR 9.6-15.4] units/kg/hr, p = 0.063). Fewer UFH infusion rate changes occurred prior to steady state in the multimodal group (0.9 [IQR 0.3 -1.7] versus 0.1 [IQR 0.0-0.2], p < 0.001). CONCLUSION: The incidence of major bleeding and thrombosis was similar between groups. Our multimodal monitoring protocol standardized UFH infusion administration and reduced ATIII administration.

The effect of contrast agents on the anticoagulant properties of oral factor Xa inhibitors.

BACKGROUND: Contrast agents may affect the anticoagulant properties of novel oral anticoagulants. PURPOSE: To evaluate the effect of iohexol as a contrast agent on the anticoagulant activity of oral factor Xa inhibitors. MATERIAL AND METHODS: The study included 65 individuals who underwent contrast computed tomography(CT). Group 1 comprised 20 patients using rivaroxaban, Group 2, 20 patients using apixaban, and Group 3, 20 patients using edoxaban. Group 4 was the control group of five healthy volunteers. Iohexol (60 mL) was used as a contrast agent. Blood samples of 2 mL were withdrawn into two tubes at 4 h after the drug dose and 1 h after the contrast CT (CT was performed 3 h after the drug was taken) from all the patients, and for the control group, at any time before and 1 h after contrast CT. The anticoagulant properties of rivaroxaban, apixaban, and edoxaban were evaluated using anti-factor Xa levels. RESULTS: The anti-factor Xa level was increased after using the contrast agent in the rivaroxaban group (0.66 ± 0.32 U/mL vs. 0.67 ± 0.32 U/mL; P = 0.01) and the edoxaban group (0.74 ± 0.35 U/mL vs. 0.76 ± 0.36 U/mL; P = 0.006). No significant difference was observed in the apixaban group (0.66 ± 0.33 U/mL vs. 0.66 ± 0.32 U/mL; P = 0.21) and control group (0.02 ± 0.01 U/mL vs. 0.03 ± 0.01 U/mL; P = 0.33). CONCLUSION: The anticoagulant properties of rivaroxaban and edoxaban tended to increase significantly, but there was no statistically significant difference in the anticoagulant properties of apixaban after the administration of contrast agent. To determine whether the small laboratory difference has a clinical effect, there is a need for larger clinical trials (NCT04611386).

The Safety of Direct Oral Anticoagulants Compared to Warfarin in Patients Hospitalized With Acute Kidney Injury.

BACKGROUND: Direct oral anticoagulants (DOACs) are preferred over warfarin for many indications, though their safety has not been well established in patients with acute renal impairment. OBJECTIVE: The purpose of this study was to evaluate the frequency of bleeding complications associated with DOACs compared with warfarin in patients admitted to the hospital with acute kidney injury (AKI). METHODS: This was a retrospective cohort study evaluating patients admitted to the Penn Medicine Lancaster General Hospital with a diagnosis of AKI from October 2017 through September 2021 and receiving therapy with oral anticoagulants. Comparing DOACs with warfarin, the primary endpoint was the percent frequency of composite major and minor bleeding during the admission and within 30 days of discharge. RESULTS: There were 112 hospitalization encounters included in the study. Of these, 42 (37.5%) patients were receiving warfarin and 70 (62.5%) patients were receiving DOAC therapy before admission. There was a higher frequency of the primary endpoint of bleeding in patients receiving DOACs as compared with warfarin, though this was not statistically significant (18.5% vs. 11.9%, respectively, P = 0.432). There were no differences between groups in the frequency of major bleeding, minor bleeding, or transfusions. Patients receiving DOAC therapy were more likely to experience anticoagulation-related readmissions or emergency department visits compared with patients on warfarin therapy (11.4% vs. 0%, P = 0.024). CONCLUSION AND RELEVANCE: Direct oral anticoagulants and warfarin were associated with statistically similar rates of bleeding in patients presenting with AKI. Further research is necessary to elucidate if DOACs are safer than warfarin in this patient population.

Anti-factor Xa vs aPTT for heparin monitoring in extracorporeal membrane oxygenation.

PURPOSE: The goal of this study was to evaluate the correlation of anti-factor Xa (anti-Xa) and activated partial thromboplastin time (aPTT) measures with heparin dosing in adult patients on extracorporeal membrane oxygenation (ECMO) support. METHODS: This was a retrospective cohort study evaluating adult patients managed on ECMO for at least 24 hours who received unfractionated heparin for systemic anticoagulation and were monitored per protocol using anti-Xa and/or aPTT coagulation assays. The primary outcome was the correlation between aPTT and anti-Xa measures. The secondary outcomes included, but were not limited to, the number of hemorrhagic and thrombotic events. RESULTS: Twenty-seven patients were included in this study. In the 227 events where both laboratory values were collected, a weak correlation was found between anti-Xa and aPTT (Spearman's correlation coefficient = 0.4, P = 0). In the 12 hemorrhagic events that occurred, aPTT was collected for only 10 events. Fifty percent of those events were associated with supratherapeutic aPTT, while none of the hemorrhagic events were associated with a supratherapeutic anti-Xa level. Two thrombotic events occurred, one of which had subtherapeutic anti-Xa and aPTT and the other of which had neither an anti-Xa nor aPTT measure on the day the event occurred. CONCLUSION: In a population of patients on ECMO, many of whom had coronavirus disease 2019 (COVID-19), there was a weak association between aPTT and anti-Xa measures. Hemorrhagic evens were more common than thrombotic events; however, a relationship between these events and aPTT or anti-Xa levels was not determined. The applicability of these findings to an ECMO population without COVID-19 is unknown and will require further study.

Anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time in patients treated with factor Xa inhibitors.

The regimens for factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) vary with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF). The dosage and duration of FXa inhibitor therapy also differ. However, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each FXa inhibitor has not fully been assessed. Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Each FXa inhibitor showed various ranges of AXA values, and twice-daily use resulted in higher absolute AXA values than once-daily use. AXA values and PT for 20 mg apixaban at both trough and peak times were significantly higher than those for 5 mg or 10 mg. AXA values for 60 mg edoxaban at peak time were significantly higher than those for 15 mg or 30 mg. AXA values for 30 mg of rivaroxaban at both trough and peak times were significantly higher than those for 10 mg or 15 mg. In a nonlinear regression model of the relationship between AXA and PT or APTT, PT was positively correlated with AXA values for each FXa inhibitor. This study obtained trough and peak levels of AXA, PT, and APTT in patients with VTE or NVAF who were administered apixaban, edoxaban, and rivaroxaban.

Critically ill patients with edema and ascites may experience subtherapeutic anti-factor Xa levels following abdominal subcutaneous enoxaparin treatment.

Enoxaparin is a low molecular weight heparin that is principally prescribed for the treatment and prevention of thromboembolic disorders. In clinical practice, the abdominal site for subcutaneous enoxaparin administration is most preferable because of its simplicity and safety. However, subcutaneous enoxaparin bioavailability in critically ill patients with ascites is uncertain. According to this case report, the bioavailability and absorption of subcutaneous enoxaparin was potentially impaired in a critically ill patient with ascites and local edema based on the therapeutic drug monitoring of anti-factor Xa levels.