Anti-factor Xa Assay Research Articles

Heparin-Calibrated Anti-Factor Xa Assay for the Measurement of Direct Anticoagulants such as Apixaban, Rivaroxaban, and Edoxaban.

The first purpose of this study was to determine whether a measurement of the level of direct oral anticoagulants (DOACs) was possible with heparin-calibrated chromogenic anti-factor Xa activity (AXA). The second purpose of this study was to evaluate whether the antidote treatment decision level (30 or 50 ng/mL of DOAC) can be determined by unfractionated heparin (UHF)/low molecular weight heparin (LMWH)-calibrated AXA. AXA was measured by using two reagents and dedicated analyzers (Sysmex CS-5100 analyzer and STA R Max3). Four types of calibrators were used: 1) Stago DOAC (rivaroxaban, edoxaban, and apixaban)-specific calibrator, 2) Stago LMWH calibrator, 3) Sysmex UHF calibrator, and 4) Sysmex LMWH calibrator. Regression analysis was used between assays. Receiver operating characteristic (ROC) curves were performed, and the concordance rate was calculated. The correlation coefficients were in the range of 0.75 - 0.91 for rivaroxaban and 0.81 - 0.94 for apixaban. The correlation coefficient between edoxaban-calibrated AXA and Sysmex LMWH/Sysmex UHF calibrator-calibrated AXA was low (r = 0.47). Overall correlation between DOAC-calibrated AXA and Stago LMWH-calibrated AXA was linear, at only low concentration in all three DOACs. The concordance rate (89.3 - 100%) is good for de-termining the antidote management level by UFH/LMWH-calibrated AXA, compared with those of DOAC-calibrated AXA in rivaroxaban and apixaban. The concordance rate ranged from 63% to 67% between Sysmex UFH/ LMWH-calibrated AXA and edoxaban-calibrated AXA. The findings of our study suggest limitations in calculating accurate concentrations, when using UFH/LMWH-calibrated AXA to measure DOAC. This study demonstrates that UFH/LMWH-calibrated AXA may be useful in determining the presence of DOACs at the cutoff level for the antidote treatment in rivarovaban and apixaban. However, in edoxaban, UFH/LMWH-calibrated AXA could not accurately measure the presence of DOACs at the cutoff for antidote treatment.

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

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). 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). 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. 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.

Anti-Xa Assay Monitoring Improves the Precision of Anticoagulation in Venovenous Extracorporeal Membrane Oxygenation.

Unfractionated heparin (UFH) is the most used anticoagulant in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). Its therapeutic levels are monitored using activated partial thromboplastin time ratio (aPTTr) or antifactor Xa (anti-Xa) assay. This was a retrospective, single-center, cohort study where all adult patients with viral etiology respiratory failure requiring VV-ECMO from January 2, 2015 to January 31, 2022 were included. Anticoagulation was monitored using aPTTr (until November 1, 2019) or anti-Xa assay (after November 1, 2019). We compared the accuracy and precision of anticoagulation monitoring tests using time in therapeutic range (TTR) and variance growth rate (VGR), respectively, and their impact on bleeding and thrombotic events (BTEs). A total of 254 patients, 74 in aPTTr and 180 in anti-Xa monitoring groups, were included with a total of 4,992 ECMO-person days. Accuracy was comparable: mean TTR of 47% in aPTTr and 51% in anti-Xa groups ( p = 0.28). Antifactor Xa monitoring group demonstrated improved precision with a lower variance (median VGR 0.21 vs. 1.61 in aPTTr, p < 0.05). Secondary outcome of less heparin prescription changes (adjusted rate ratio [RR] = 1.01, p = 0.01), fewer blood transfusions (adjusted RR = 0.78, p < 0.05), and ECMO circuit changes (adjusted RR = 0.68, p < 0.05) were seen with anti-Xa monitoring.

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism.

The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

PB1138 The Impact of Switching from Anti-Factor Xa (anti-Xa) Assays to APTT to Monitor Intravenous (IV) Unfractionated Heparin (UFH) at a Quaternary Care Academic Centre

PB1138 The Impact of Switching from Anti-Factor Xa (anti-Xa) Assays to APTT to Monitor Intravenous (IV) Unfractionated Heparin (UFH) at a Quaternary Care Academic Centre

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 0.57L/(h·10kg) and 0.02/h. Comparable to non-ECMO patients, the typical steady-state CL was 0.81L/(h·10kg). Simulations showed that a 75IU/kg UFH bolus dose followed by starting infusions of 25 and 20IU/h/kg for patients aged younger than 6 years and 6years 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 48hours of treatment. The median intensive care unit survival time in patients within and below the target at 24hours was 136 and 66hours, 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.

Is There a Role for Anti-factor Xa Activity Assay in Venous Thromboembolism Prophylaxis Management Among Orthopaedic Trauma Patients? Systematic Review and Meta-analysis.

To determine the effect of anti-factor Xa assay dosing of low-molecular-weight heparin (LMWH) on rates of venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), bleeding, and mortality among orthopaedic trauma patients. PubMed/MEDLINE, Embase, Ovid, Cochrane Central Register of Controlled Trials (CENTRAL), clinicaltrials.gov , and Scopus were systematically searched from inception of the database to 2021. Prospective, retrospective, and randomized controlled trial studies were included if they compared rates of VTE, DVT, PE, bleeding, and/or mortality between orthopaedic trauma patients receiving anti-factor Xa-based LMWH dosing and those receiving standard dosing. Two independent reviewers screened titles and abstracts for eligibility. Study characteristics including study design, inclusion criteria, and intervention were extracted. Meta-analysis was performed using pooled proportion of events (effect size) with 95% confidence intervals. A random-effects model was used. Heterogeneity was quantified by Higgins I 2 . Heterogeneity and variability between subgroups indicated differences in the pooled estimate represented by a P -value. Six hundred eighty-five studies were identified, and 10 studies including 2870 patients were included. In total, 30.3% and 69.7% received an adjusted and nonadjusted dose of LMWH, respectively. The rate of VTE and DVT were significantly lower in the anti-factor Xa-adjusted cohort, whereas there was no statistically significant difference in rates of PE, bleeding, or mortality between the cohorts. This systematic review and meta-analysis demonstrates that anti-factor Xa activity assay dosing of LMWH among orthopaedic trauma patients leads to a reduction in overall DVT rates, although not PE rates, without an increased risk of bleeding events. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

No Association Between Outcomes And Anti-Factor Xa Levels For Heparin Monitoring In Patients With Cerebral Venous Thrombosis (P14-5.012)

<h3>Objective:</h3> We sought to determine whether Anti-factor-Xa (AFXa) values are associated with outcomes in cerebral venous thrombosis (CVT). <h3>Background:</h3> Intravenous unfractionated heparin (UFH) is a cornerstone of anticoagulant therapy for patients with CVT, but frequent monitoring is needed because of dose-response variability. The AFXa assay is used to monitor UFH treatment. <h3>Design/Methods:</h3> This pilot study included adults (≥18y) admitted to a comprehensive stroke center from 2018 through 2020 who were initially treated for CVT with low-intensity UFH drip and had at least one AFXa assay. AFXa therapeutic values were defined as 0.25 – 0.5 IU/mL. We examined percent of patients who became therapeutic within 24h of arrival, and time (hours, h) to reach therapeutic range. Outcomes included hospital LOS, bleeding event, and discharge disposition. Continuous data are presented as median (interquartile range). <h3>Results:</h3> There were 51 CVT patients included. The time to start UFH was 2h (1–6) from arrival and the time to the first AFXa assay was 8h (4–11) from arrival. AFXa were drawn 4 (2–8) times per patient. AFXa assays were performed within 24h for 45 (88%) patients and 30(67%) patients were in the therapeutic range. There was no association between study outcomes and AFXa being therapeutic or not: bleeding events were 17.2% and 13.3%, respectively (p=1.0), discharge to home was 77% vs. 80% (p=1.0), and hospital LOS was 5 days for each group (p=0.95). There was also no association between study outcomes and the time (h) to reach therapeutic range: discharge home vs. other location (11h vs. 14h, p=0.49), development of a bleed vs. no bleed (9h vs. 12h, p=0.44), and no correlation with hospital LOS (p=0.55). <h3>Conclusions:</h3> The time to achieve therapeutic AFXa was not associated with outcomes, although most patients were within the target AFXa range within 24h of arrival and had favorable outcomes. <b>Disclosure:</b> Dr. Pirahanchi has nothing to disclose. Ms. Salottolo has nothing to disclose. Dr. Burrell has nothing to disclose. Dr. Tang has nothing to disclose. Dr. DiSalvo has nothing to disclose. David Bar-Or has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Ampio Pharmaceuticals. David Bar-Or has stock in Ampio Pharmaceuticals. Dr. Bartt has nothing to disclose.

Abstract TP12: No Association Between Outcomes And Anti-Factor Xa Levels For Heparin Monitoring In Patients With Cerebral Venous Thrombosis

Introduction: For patients with cerebral venous thrombosis (CVT), intravenous unfractionated heparin (UFH) is a cornerstone of anticoagulant therapy. Drawbacks of UFH include difficulty in reaching an optimal dose. Anti-factor-Xa (AFXa) assay is used to monitor UFH treatment. We sought to determine whether AFXa values are associated with outcomes in CVT. Methods: This pilot study included adults (≥18y) admitted to a CSC between 1/1/2018-12/31/2020 who were initially treated for CVT with low-intensity UFH drip and had at least one AFXa assay. AFXa therapeutic values were defined as 0.25 - 0.5 IU/mL. We examined percent of patients who became therapeutic within 24h of arrival, and time (hours) to reach therapeutic range. Outcomes included hospital LOS, bleeding event, and discharge disposition. Continuous data are presented as median (interquartile range). Significance was p&lt;0.20. Results: 51 CVT patients were included. The hospital LOS was 5 (4-9) days, 40 (78%) patients were discharged home, and 7 (14%) developed a bleed; 4 bleeds required no action. The time to start UFH was 2h (1-6) from arrival and the time to the first AFXa assay was 8h (4-11) from arrival. AFXa were drawn 4 (2-8) times per patient. AFXa assays were performed within 24h for 45 (88%) patients and 30 (67%) patients were in the therapeutic range. There was no association between study outcomes and therapeutic AFXa ( Table 1 ). There was also no association between study outcomes and the time (h) to reach therapeutic range: discharge home vs. other location (11h vs. 14h, p=0.49), development of a bleed vs. no bleed (9h vs. 12h, p=0.44), and no correlation with hospital LOS (p=0.55). Conclusions: Most CVT patients were within the target AFXa range within 24h of arrival. The time to achieve therapeutic AFXa was not associated with better outcomes, although most patients had a favorable disposition and bleeding complications were infrequent.

Optical Detection of Heparin in Whole Blood Samples Using Nanosensors Embedded in an Agarose Hydrogel.

Point-of-care quantification of the anticoagulant heparin still remains a significant clinical challenge as the reference method (colorimetric anti-factor Xa assay) cannot be performed in whole blood. Our group recently put forth the novel optical nanosensing principle using an ionic solvatochromic dye as a signal transducer. These nanosensors demonstrated significantly improved selectivity and sensitivity compared to ion-exchange-type polyion nanosensors and enabled protamine/heparin quantification in blood plasma samples. However, because the readout is absorbance-based, they are still not suitable for whole blood measurements. To overcome the background absorbance of blood, the nanosensors were here embedded in an agarose hydrogel capable of filtering out red blood cells while allowing plasma components to diffuse into the gel. Calibration curves for both protamine and heparin were successfully obtained in buffer, undiluted plasma, and undiluted whole blood using different colorimetric image analysis methods and a simple experimental setup.

Anticoagulant management for transition from failed thrombolysis to extra-corporeal membrane oxygenation in patients with high-risk pulmonary embolism: A thoughtful approach

Acute venous thromboembolism represents a spectrum of clinical syndromes of which high-risk pulmonary embolism (PE) with consecutive right ventricular failure and cardiogenic shock (CS) is the most severe presentation. First-line treatment options are surgical pulmonary embolectomy, systemic thrombolysis or catheter-based therapies. The role of mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation (V-A-ECMO) is multifarious in this setting and can be considered as either a bridge to pulmonary artery reperfusion by any of the aforementioned options or as salvage bridge intervention for patients in refractory CS after failure of another treatment. In the subpopulation of patients that are placed on V-A-ECMO after failed thrombolysis, the mortality rates are among the highest, partially due to the high rates of bleeding events. The challenges in the interpretation of anticoagulant monitoring and, consequently, the titration of anticoagulation at least contribute to this high mortality. Here, we discuss the strengths and limitations of different anticoagulant parameters in this setting and propose an approach based on monitoring of Heparin anti-factor Xa (anti-Xa) assay and activated partial thromboplastin time (APTT) in parallel to drive unfractionated heparin (UFH) titration in patients with high-risk PE after fibrinolysis during the first 24 h on V-A-ECMO.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24h of an invasive procedure. This single-center, observational, retrospective study included patients who received andexanet alfa within 24h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre- and postreversal. Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n=20 [45.5%]) or extracranial (n=24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short- or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre- versus postreversal. Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.

Optimal dosing of enoxaparin in overweight and obese children.

Current enoxaparin dosing guidelines in children are based on total body weight. This is potentially inappropriate in obese children as it may overestimate the drug clearance. Current evidence suggests that obese children may require lower initial doses of enoxaparin, therefore the aim of this work was to characterise the pharmacokinetics of enoxaparin in obese children and to propose a more appropriate dosing regimen. Data from 196 unique encounters of 160 children who received enoxaparin treatment doses were analysed. Enoxaparin concentration was quantified using the chromogenic anti factor Xa (anti-Xa) assay. Patients provided a total of 552 anti-Xa samples. Existing published pharmacokinetic (PK) models were fitted and evaluated against our dataset using prediction-corrected visual predictive check plots (pcVPCs). A PK model was fitted using a nonlinear mixed-effects modelling approach. The fitted model was used to evaluate the current standard dosing and identify an optimal dosing regimen for obese children. Published models of enoxaparin pharmacokinetics in children did not capture the pharmacokinetics of enoxaparin in obese children as shown by pcVPCs. A one-compartment model with linear elimination best described the pharmacokinetics of enoxaparin. Allometrically scaled fat-free mass with an estimated exponent of 0.712 (CI 0.66-0.76) was the most influential covariate on clearance while linear fat-free mass was selected as the covariate on volume. Simulations from the model showed that fat-free mass-based dosing could achieve the target anti-Xa activity at steady state in 77.5% and 78.2% of obese and normal-weight children, respectively, compared to 65.2% and 75.5% for standard total body weight-based dosing. A population PK model that describes the time course of anti-Xa activity of enoxaparin was developed in a paediatric population. Based on this model, a unified dosing regimen was proposed that will potentially improve the success rate of target attainment in overweight/obese patients without the need for patient body size categorisation. Therefore, prospective validation of the proposed approach is warranted.

Anticoagulation on Extracorporeal Support: An Alternative Strategy.

To the Editor, We read with extreme interest the updated Extracorporeal Life Support (ELSO) guidelines for anticoagulation during extracorporeal membrane anticoagulation (ECMO)1 and would like to integrate this valuable document with a potential alternative therapeutic anticoagulation strategy for patients requiring veno-venous ECMO. This approach is based on subcutaneous administration of low-molecular-weight heparin (LMWH) 3 times a day, paired with antifactor Xa (anti-Xa) assay monitoring, 3 times a day, each sample equidistant between two administrations of LMWH. Anticoagulation monitoring is integrated on a regular schedule with additional blood tests, including hemoglobin and hematocrit, platelets count, Fibrinogen, D-dimers, haptoglobin levels, and with full coagulation tests and point-of-care viscoelastic testing on an as needed basis. We designed and started implementing an algorithmic protocol (detailed in Figure, Supplemental Digital Content 1, https://links.lww.com/ASAIO/A838) to standardize dosage adjustment based on anti-Xa value, potential evidence of clinically significant bleeding or prothrombotic states, and eventual need for surgical interventions or other invasive procedures. Despite paucity of literature related to anticoagulation management based on LMWH only during ECMO support,2–4 we decided to introduce this approach since the second wave of Coronavirus disease 2019 (COVID-19) pandemic, to simplify and standardize anticoagulation management, reducing the strain on the team members, particularly on most recently recruited, and less experienced ones, involved to expand ECMO capacity. The rationale for the off-label three-daily dosing (despite the commonly recommended once/twice daily dosing) is to achieve and constantly maintain a therapeutic level of anticoagulation, avoiding excessive peaks and minimizing peak-to-trough variability, with the aim of effective prevention of thrombosis without increasing bleeding risk.5 The rationale for anti-Xa assessment 4 hours after LMWH administration is to thoroughly evaluate its effect, including peak, occurring 3–5 hours after subcutaneous administration, being able to properly adapt subsequent dosing. During the run, the protocol anticipates some conditions which demand to modify LMWH administration (dose or timing): need for invasive elective or emergent procedures; we do not consider percutaneuos central venous catheter, pulmonary artery catheter and arterial line placement, nor percutaneous tracheostomy among procedures requiring dosing adjustment; evidence of clinically significant bleeding defined (as per ELSO Registry definition); evidence of thrombotic complications (both intracircuit or patient complications). Since the implementation of this protocol, we did not notice increased ratio of thrombotic events; no patient required the circuit to be replaced more than once during the run (mean duration 19 days [6–52]). No cannula thrombosis, nor thrombosis involving the cannula or cannulated vessels have been observed, despite the high risk profile of this patient population. No brain hemorrhages, nor GI or cannulation site bleedings requiring more than medical approach were observed; and increased incidence of pulmonary hemorrhages was noticed: clinical evidence suggested these as presumably disease, rather than anticoagulation, related. We recognize that such an algorithm significantly deviates from conventional clinical practice and from guidelines, but in our limited, single center experience, its application in a population of COVID-19 patients requiring V-V ECMO was feasible and safe (unpublished data, manuscript in preparation), and easy to be implemented at bedside, in selected settings.

A073 Analyzing the adequacy of BMI-tiered enoxaparin dosing for venous thromboembolism prophylaxis in the bariatric surgery population based on anti-factor Xa assay data

A073 Analyzing the adequacy of BMI-tiered enoxaparin dosing for venous thromboembolism prophylaxis in the bariatric surgery population based on anti-factor Xa assay data

Case Report: Extended Duration Andexanet Alfa Infusion in a Surgical Trauma Patient

Background: Andexanet alfa (andexanet) is the only FDA-approved medication for reversal of apixaban and rivaroxaban anticoagulation for life-threatening or uncontrolled bleeding. Infusion modifications may be required in surgical patients undergoing prolonged operative intervention but have not previously been described. Case Report: A 78-year-old woman on rivaroxaban for atrial fibrillation was admitted to the trauma service for a mechanical fall, sustaining a T4 burst fracture with severe canal stenosis and spinal cord edema resulting in loss of strength and sensation in her legs. Clinically relevant rivaroxaban activity was verified with an elevated low molecular weight heparin anti-factor Xa assay, and laboratory confirmed coagulopathy was demonstrated by a prolonged prothrombin time, thromboelastography (TEG) R-time, and activated clotting time (ACT). The patient required urgent surgical intervention for spinal fixation. Given the expected prolonged duration of the procedure, standard dose andexanet was initiated with a prolonged infusion at half the standard rate during the operation. The procedure was successful and intraoperative TEGs demonstrated normalization of R-time and ACT throughout the procedure. The patient did not experience any complications postoperatively and successfully discharged to inpatient rehabilitation. Conclusion: Modifications to the andexanet infusion may be required in surgical patients requiring rivaroxaban reversal for a prolonged procedure. Further data are needed to determine the optimal approach to infusion modification.

Reassessing the Pediatric Dosing Recommendations for Unfractionated Heparin Using Real-World Data: A Pharmacokinetic-Pharmacodynamic Modeling Approach.

Optimal pediatric dosing of unfractionated heparin (UFH) is challenging because of the paucity of clinical outcome and pharmacokinetic-pharmacodynamic (PK/PD) studies in pediatrics. This study aimed to: (i) develop a PK/PD model for UFH, quantified by anti-factor Xa assay, and the UFH effect, measured by activated partial thromboplastin time (aPTT); and (ii) use simulations to evaluate pediatric UFH infusions for achieving the anti-factor Xa (0.3-0.7IU/mL) therapeutic target. Electronic health record data were retrospectively collected from 633 patients aged <19years admitted to Texas Children's Hospital. The PK/PD model was developed using a 70% (training)/30% (testing) split-sample approach. A 1-compartment PK model with linear elimination adequately described the UFH PK. An allometrically scaled body weight on clearance (CL) and volume of distribution (Vd) with an age-dependent maturation function of extracellular water on Vd were the covariates identified. Comparable with literature, the typical values for CL and Vd were 3.28L/(h·50kg) and 8.83L/50kg, respectively. A linear model adequately described the UFH-aPTT relationship with an estimated slope of 150 seconds/(IU/mL). Simulations of the currently recommended starting infusions (28IU/h/kg for pediatrics <1yearold or 20IU/h/kg for pediatrics >1yearold) showed that the anti-factor Xa therapeutic target was achieved only in 15.3%, 14.6%, 36.9%, and 45.11% of subjects in the age groups of <1year, 1-6years, 6-12years, and 12-19years, respectively. In conclusion, the UFH anti-factor Xa target is not achieved initially, especially in young pediatrics, suggesting the need to optimize UFH dosing to achieve higher therapeutic success.

The kinetics of heparin adsorption with Dowex 1x1 ion exchange resin

The recovery of heparin from the porcine intestinal mucosa by using the ion exchange resin was studied. The procedure involved the following steps: alkaline hydrolysis, ion exchange resin adsorption, and elution. The activity of heparin was measured by an antifactor Xa assay. The ammonium chloride/ammonium hydroxide was used as a buffer, and the effect of salt concentration on the adsorption efficiency was evaluated. The results showed that the highest heparin yield (86.17%) was achieved at the lowest concentration of ammonium chloride. The pseudo-first-order model was shown as more adequate to describe heparin adsorption onto the resin.

Comparison of anti-factorXa assay and rotational thromboelastogram in evaluating the efficacy of enoxaparine treatment in patients with acute coronary syndrome without ST- segment elevation

Amaç: Tromboelastogram parametrelerindeki değişiklerin standart olarak önerilen AntiFXa aktivitesi ile karşılaştırılarak bu testin enoksaparin tedavisinin monitörizasyonundaki rolünün incelenmesidir.&#x0D; Gereç ve Yöntem: ST segment yükselmesi olmayan miyokard infarktüsü tanısıyla koroner yoğun bakım ünitesine yatırılan 25 hasta çalışmaya alınmıştır. Hastalara yatış anında iki tüp kan alınmış ve 1mg/kg enoksapirinin üçüncü dozu yapıldıktan 4 saat sonra iki tüp kan daha alınmıştır. Hastalara AntiFXa, tromboelastogram, aktive koagülasyon zamanı bakılmıştır.&#x0D; Bulgular: Enoksoparin uygulaması sonrası aktive koagülasyon zamanı değerinde bir miktar artış izlenmekle birlikte bunun anlamlı olmadığı görüldü (p₌0.094). Enoksoparin sonrası tromboelastogram parametrelerinden maksimum amplitüde(MA) azalmış (MA bazal 65.4±11.9 sonra 63.4±7.8), R zamanı artmış (5±1.7 den 8.4±4.6,), K zamanı artmış (1.89±1.06 dan 2.56±1.4), açı azalmıştır. (66.34±5.6 dan 57.9±11.4). AntiFXa artmıştır (0.122±0.06 dan 0.501±0.359).&#x0D; Sonuç: Tromboelastogram parametreleri değerlendirildiğinde tipik artmış bir prokoagülan aktivite olmamakla birlikte kısmen artmış bir fibrinolitik aktivite saptanmıştır.

Adequate Antithrombin III Level Predicts Survival in Severe COVID-19 Pneumonia.

Critically ill patients with COVID-19 are at an increased thrombotic risk, hence thromboprophylaxis with heparin is considered mandatory. Antithrombin III (ATIII) is the most potent endogenous anticoagulant and is required for the clinical efficacy of heparin. Profound hypercoagulable and inflammatory state associated with COVID-19 can result in decreased ATIII levels and ineffective heparin treatment resulting in increased mortality. The present study evaluated ATIII levels in critically ill patients of COVID-19 and correlated them with other coagulation parameters and disease outcomes. A retrospective review of those critically ill COVID-19 patients was performed who were on a therapeutic dose of low molecular weight heparin (LMWH) and had serial measurements of ATIII, anti-factor Xa (antiFXa) assay and other routine coagulation parameters. A total of 27 critically ill COVID-19 patients were identified, out of these, 12 survived and 15 had disease-induced mortality. ATIII levels were found to be significantly lower in non-survivors on the third day of serial measurement along with worsening of other coagulation parameters. AntiFXa levels were found to be higher in non-survivors as compared to survivors. Further studies are required to establish ATIII as a prognostic marker and to determine the utility of monitoring antiFXa levels in COVID-19 patients on LMWH therapy.