Anti-factor Xa Activity Research Articles

Abstract 13192: Anti-Factor Xa Activity in Patients With Chronic Thromboembolic Pulmonary Disease With or Without Pulmonary Hypertension Treated With Factor Xa Inhibitors

Introduction and Hypothesis: Data on the efficacy and safety of factor Xa (FXa) inhibitors in chronic thromboembolic pulmonary disease (CTEPD) patients, especially in chronic thromboembolic pulmonary hypertension (CTEPH) patients, remain limited. Here, we aimed to evaluate the effect of FXa inhibitors by measuring anti-factor Xa activity (AXA) in both patients with CTEPD without pulmonary hypertension (PH) and CTEPH. Methods: Twenty-five CTEPD patients without PH and 52 CTEPH patients, treated with either of the FXa inhibitors were enrolled. AXA was measured by using HemosIL heparin calibrator. Blood samples were collected two times at the same day: immediately before the drug administration (trough) and 2-3 h after drug administration (peak). Results: In all 77 patients, median age was 66 (Interquartile range [IQR] 51–73) years, and 43% were male. In addition, 47% of the patients received rivaroxaban of 15 mg/day, 27% received apixaban of 10 mg/day, 14% received edoxaban of 60mg/day, and 12% received edoxaban of 30 mg/day. The median peak AXA of all 77 patients was 1.92 IU/mL and was comparable between CTEPD without PH and CTEPH patients. Significant difference of trough and peak AXA was shown among four different prescribed drugs (P < .001 and P = .006, respectively). During the observational period of median 519 (IQR 364–1118) days, major and clinically relevant non-major bleeding occurred in six patients. ROC analysis to predict bleeding events revealed that the sensitivity and specificity of the cutoff point of a peak AXA of 2.1 IU/mL were 67% and 66%, respectively (AUC 0.66). The cumulative rate of major and clinically relevant non-major bleeding tended to be higher in patients with peak AXA ≥ 2.1 IU/mL than in patients with values below this point (p = .092, Figure). Conclusion: Measuring AXA could be a useful method to evaluate the effect of FXa inhibitors in CTEPD with or without PH patients.

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19

BackgroundRandomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19.MethodsA phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45–60 kg, 80 mg for 61–100 kg or 100 mg for > 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4–0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm).ResultsMajor bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8–16) vs 14 (11–21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups.ConclusionsWeight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients.Trial registrationThe study INHIXACOVID19 was registred on ClinicalTrials.gov with the trial registration number (TRN) NCT04427098 on 11/06/2020.

A retrospective multicenter cohort study of the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19

BackgroundPatients with critical COVID-19 have a high risk of thromboembolism, but intensified thromboprophylaxis has not been proven beneficial. The activity of low-molecular-weight heparins can be monitored by measuring anti-Factor Xa. We aimed to study the association between anti-Factor Xa values and death, thromboembolism, and bleeding in patients with critical COVID-19.MethodThis retrospective cohort study included adult patients with critical COVID-19 admitted to an intensive care unit at three Swedish hospitals between March 2020 and May 2021 with at least one valid peak and/or trough anti-Factor Xa value. Within the peak and trough categories, patients’ minimum, median, and maximum values were determined. Logistic regressions with splines were used to assess associations.ResultsIn total, 408 patients had at least one valid peak and/or trough anti-Factor Xa measurement, resulting in 153 patients with peak values and 300 patients with trough values. Lower peak values were associated with thromboembolism for patients’ minimum (p = 0.01), median (p = 0.005) and maximum (p = 0.001) values. No association was seen between peak values and death or bleeding. Higher trough values were associated with death for median (p = 0.03) and maximum (p = 0.002) values and with both bleeding (p = 0.01) and major bleeding (p = 0.02) for maximum values, but there were no associations with thromboembolism.ConclusionsMeasuring anti-Factor Xa activity may be relevant for administrating low-molecular-weight heparin to patients with critical COVID-19. Lower peak values were associated with an increased risk of thromboembolism, and higher trough values were associated with an increased risk of death and bleeding. Prospective studies are needed to confirm the results.Trial registrationThe study was retrospectively registered at Clinicaltrials.gov, NCT05256524, February 24, 2022.

Anti-factor Xa level monitoring of low-molecular-weight heparin for prevention of venous thromboembolism in critically ill patients (AXaLPE): protocol of a randomised, open-label controlled clinical trial

IntroductionWhether and when to monitor the amount of anti-factor Xa (aFXa) activity in critically ill patients with complex diseases to prevent venous thromboembolism (VTE) remain unclear. This study is a...

A-329 Preliminary Clinical Method Comparison of a Near-Patient Platform for Low Blood Volume Testing of aFXa in Pediatric Patients on Heparin Therapy

Abstract Background Up to 15% of hospitalized children receive heparin therapy and require frequent monitoring for Anti-Factor Xa activity (aFXa) and activated partial thromboplastin time (aPTT) to achieve hemostatic balance. Current heparin tests require large blood volumes, which can lead to iatrogenic anemia with frequent sample collection. We performed a small clinical method comparison of a rapid, near-patient platform for simultaneous whole blood testing of aFXa from 50 μL of sample against the clinical standard test. The aPTT assay is in development on the same digital microfluidic (DMF) platform. Methods Four DMF instruments were placed in our laboratory. Preliminary precision of the DMF aFXa assay was obtained using commercial controls (n = 19 for aFXa at 0.98 U/mL; n = 20 for aFXa at 0.42 U/mL). We obtained whole blood or plasma from residual aFXa samples from pediatric patients. Venous samples were collected from patients for routine testing in the core laboratory, and 150 μL of whole blood was saved for aFXa method comparison testing. Patients were either on low molecular weight heparin or unfractionated heparin. We performed a method comparison study to determine assay equivalence to in-house clinical standard tests using plasma for aFXa on the Stago STA R MAX to both plasma and whole blood on the DMF platform. Results For precision, we observed an assay coefficient of variation (CV) of 4.68% and 6.6% for aFXa at 0.98 U/mL and 0.42 U/mL, respectively. The aFXa assay correlated well (R2 = 0.94 for whole blood (n = 9) and R2 = 0.97 for plasma (n = 10)); additional studies are needed to demonstrate aPTT assay equivalence. Conclusions We demonstrated good correlation of the DMF aFXa assay to the clinical standard test. The low blood volume requirement make these tests suitable for use in heparin monitoring where frequent testing is necessary. A large scale clinical method comparison is planned to ensure clinical utility.

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.

The Impact of Continuous Veno-Venous Hemodiafiltration on the Efficacy of Administration of Prophylactic Doses of Enoxaparin: A Prospective Observational Study.

Critically ill patients frequently require continuous renal replacement therapy (CRRT). During CRRT, particles up to 10 kDa in size, such as enoxaparin, may be removed. The aim of this study was to determine if patients receiving prophylactic doses of enoxaparin and treated with continuous veno-venous hemodiafiltration (CVVHDF) reach prophylactic values of anti-Xa factor activity. In this observational trial, we compared two groups: 20 patients treated with CVVHDF and 20 patients not treated with CVVHDF. All of them received prophylactic doses of 40 mg of enoxaparin subcutaneously. Anti-Xa factor activity was determined on the third day of receiving a prophylactic dose of enoxaparin. The first blood sample was taken just before the administration of enoxaparin, and other samples were taken 3 h, 6 h, and 9 h after the administration of a prophylactic dose of enoxaparin. At 3 and 6 h after administration of enoxaparin in both groups, we observed a significant increase in anti-Xa factor activity from baseline, with the peak after 3 h of administration. There were no significant differences in the numbers of patients who had anti-Xa factor activity within the prophylactic range between CVVHDF and control groups. CVVHDF has only a mild effect on the enoxaparin prophylactic effect measured by anti-Xa factor activity. Thus, it seems there is no need to increase the dose of enoxaparin for patients requiring CVVHDF.

HTRS2023.P4.14 Using heparin-calibrated assays to estimate anti-factor Xa activity of factor Xa inhibitors: correlation analysis of published data

HTRS2023.P4.14 Using heparin-calibrated assays to estimate anti-factor Xa activity of factor Xa inhibitors: correlation analysis of published data

Reduced anticoagulation strategy is associated with a lower incidence of intracerebral hemorrhage in COVID-19 patients on extracorporeal membrane oxygenation

BackgroundOptimal anticoagulation strategies for COVID-19 patients with the acute respiratory distress syndrome (ARDS) on venovenous extracorporeal membrane oxygenation (VV ECMO) remain uncertain. A higher incidence of intracerebral hemorrhage (ICH) during VV ECMO support compared to non-COVID-19 viral ARDS patients has been reported, with increased bleeding rates in COVID-19 attributed to both intensified anticoagulation and a disease-specific endotheliopathy. We hypothesized that lower intensity of anticoagulation during VV ECMO would be associated with a lower risk of ICH. In a retrospective, multicenter study from three academic tertiary intensive care units, we included patients with confirmed COVID-19 ARDS requiring VV ECMO support from March 2020 to January 2022. Patients were grouped by anticoagulation exposure into higher intensity, targeting anti-factor Xa activity (anti-Xa) of 0.3–0.4 U/mL, versus lower intensity, targeting anti-Xa 0.15–0.3 U/mL, cohorts. Mean daily doses of unfractionated heparin (UFH) per kg bodyweight and effectively measured daily anti-factor Xa activities were compared between the groups over the first 7 days on ECMO support. The primary outcome was the rate of ICH during VV ECMO support.Results141 critically ill COVID-19 patients were included in the study. Patients with lower anticoagulation targets had consistently lower anti-Xa activity values over the first 7 ECMO days (p < 0.001). ICH incidence was lower in patients in the lower anti-Xa group: 4 (8%) vs 32 (34%) events. Accounting for death as a competing event, the adjusted subhazard ratio for the occurrence of ICH was 0.295 (97.5% CI 0.1–0.9, p = 0.044) for the lower anti-Xa compared to the higher anti-Xa group. 90-day ICU survival was higher in patients in the lower anti-Xa group, and ICH was the strongest risk factor associated with mortality (odds ratio [OR] 6.8 [CI 2.1–22.1], p = 0.001).ConclusionsFor COVID-19 patients on VV ECMO support anticoagulated with heparin, a lower anticoagulation target was associated with a significant reduction in ICH incidence and increased survival.

Massive Apixaban Overdose Confirmed with Blood Concentrations and Managed Without Bleeding: A Single Case Report

Background: Acute overdoses of apixaban, and other direct oral anticoagulants are relatively uncommon. The number of direct oral anticoagulants prescriptions in the United States is increasing, however reports on patient outcomes after documented overdose are sparse. Case report: A 76-year-old man with a past medical history of atrial fibrillation and taking apixaban 5 mg twice daily presented to the emergency department 10 hours after reportedly ingesting 60-70 of his pills. He was alert and had a normal physical examination. Blood tests demonstrated an INR of 12, platelets of 161 000 cells/mm3, hemoglobin 9.7 g/dL, and creatinine 1.81 mg/dL. He received 60 g of activated charcoal and 4 units of fresh frozen plasma prophylactically. Initial blood apixaban concentration was 4 000 ng/mL. Repeat blood apixaban concentrations were 3 000 ng/mL and 2 200 ng/mL at 7 and 14 hours, respectively (thrapeutic range 91-321 ng/mL for a 5 mg twice daily dose). The hybrid anti-factor Xa activity did not correlate with blood apixaban concentrations. Apixaban elimination followed first-order kinetics with an apparent elimination half-life of 14 hours in the presence of impaired renal function. He did not have any minor or major bleeding events.

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants.

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection (ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher (around 5%-8%) than that for esophagus, duodenum and colon cancer (around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-, lesion-, physician- and patient-related factors, use of antithrombotic drugs, especially anticoagulants [direct oral anticoagulants (DOACs) and warfarin], is thought to be the biggest risk factor for post-ESD bleeding. In fact, the post-ESD bleeding rate in patients receiving DOACs is 8.7%-20.8%, which is higher than that in patients not receiving anticoagulants. However, because clinical guidelines for management of ESD in patients receiving DOACs differ among countries, it is necessary for endoscopists to identify ways to prevent post-ESD delayed bleeding in clinical practice. Given that the pharmacokinetics (e.g., plasma DOAC level at both trough and Tmax) and pharmacodynamics (e.g., anti-factor Xa activity) of DOACs are related to risk of major bleeding, plasma DOAC level and anti-FXa activity may be useful parameters for monitoring the anti-coagulate effect and identifying DOAC patients at higher risk of post-ESD bleeding.

Comparison of Time Within Therapeutic Range Using Anti-Factor Xa Versus Activated Partial Thromboplastin Time Monitoring of Unfractionated Heparin in Children.

To compare unfractionated heparin (UFH) monitoring using time in therapeutic range of activated partial thromboplastin time (aPTT) versus anti-factor Xa activity (anti-Xa) in children. This retrospective chart review, with data between October 2015 and October 2019, included pediatric patients younger than 18 years on therapeutic UFH infusion with aPTT or anti-Xa monitoring. Patients receiving extracorporeal membrane oxygenation, dialysis, concomitant anticoagulants, prophylactic UFH, no stated goal, and UFH administered for less than 12 hours were excluded. The primary outcome compared the percentage of time in therapeutic range between aPTT and anti-Xa. Secondary outcomes included time to first therapeutic value, UFH infusion rates, mean rate adjustments, and adverse events. A total of 65 patients were included, with 33 aPTT patients and 32 anti-Xa patients, representing 39 UFH orders in each group. Baseline characteristics were similar between groups, with an overall mean age of 1.4 years and mean weight of 6.7 kg. The anti-Xa cohort demonstrated a statistically significantly higher percentage of time in therapeutic range compared with the aPTT group (50.3% vs 26.9%, p = 0.002). The anti-Xa group also demonstrated a trend toward decreased time to first therapeutic value compared with aPTT (14 vs 23.2 hours, p = 0.12). Two patients in each group experienced new or worsening thrombosis. Six patients in the aPTT cohort experienced bleeding. This study demonstrated greater time was spent within therapeutic range for children receiving UFH monitored with anti-Xa compared with aPTT. Future studies should assess clinical outcomes in a larger population.

Clinical outcomes of ultrasound-assisted coagulation monitoring-adjusted catheter-directed thrombolysis for acute pulmonary embolism

BackgroundUltrasound-assisted catheter-directed thrombolysis (USAT) may reverse right ventricular dysfunction due to acute pulmonary embolism (PE) with a favorable safety profile. MethodsWe studied intermediate-high- and high-risk acute PE patients who underwent USAT at the University Hospital Zurich, 2018–2022. The USAT regimen included alteplase 10 mg per catheter over 15 h, therapeutic-dosed heparin, and dosage adaptations based on routinely monitored coagulation parameters, notably anti-factor Xa activity and fibrinogen. We focused on the mean pulmonary arterial pressure (mPAP) and the National Early Warning Score (NEWS) before and after USAT, and reported the incidence of hemodynamic decompensation, PE recurrence, major bleeding, and death over 30 days. ResultsWe included 161 patients: 96 (59.6 %) were men and the mean age was 67.8 (SD 14.6) years. Mean PAP decreased from a mean of 35.6 (SD 9.8) to 25.6 (SD 8.2) mmHg, whereas the NEWS decreased from a median of 5 (Q1-Q3 4–6) to 3 (Q1-Q3 2–4) points. No cases of hemodynamic decompensation occurred. One (0.6 %) patient had an episode of recurrent PE. Two (1.2 %) major bleeding events occurred, including one (0.6 %) intracranial, fatal hemorrhage in a patient with high-risk PE, severe heparin overdosing, and a recent head trauma (with negative CT scan of the brain performed at baseline). No other deaths occurred. ConclusionsUSAT resulted in a rapid improvement of hemodynamic parameters among patients with intermediate-high risk acute PE and selected ones with high-risk acute PE, without any recorded deaths related to PE itself. A strategy including USAT, therapeutic-dosed heparin, and routinely monitored coagulation parameters may partly explain the overall very low rate of major bleeding.

Heparin in Acid and Alkaline Environments—A Study of the Correlations between Hydrodynamic Properties and Desulphation

This work evaluated the hydrodynamic properties of heparin hydrolysed at temperatures ranging from 40 °C to 80 °C in buffered acid and alkaline environments. The correlation between hydrodynamic parameters led to the conclusion that polymer conformational changes appeared to be minimal until chain depolymerisation, initiated at pH 1 and 80 °C. However, the synergy of conformational changes, even if minimal, and sulphate loss observed at pH 1, pH 3 and pH 12 (various temperatures) resulted in a loss of the antifactor Xa activity. Therefore, the ‘contribution’ of conformational changes should be added to the generally recognized effect of desulphation towards the activity of heparin. This is of significance as the processing of medical heparin is complex, and requires adjustment of several physical and chemical factors, including pH and temperature.

Monitoring heparin therapy: stability of two different anti-Xa assays using blood samples collected in citrate-containing and CTAD tubes

BackgroundAnti-factor Xa assays and activated partial thromboplastin time (aPTT) are mainly employed to monitor patients treated with heparins. According to the Clinical and Laboratory Standards Institute and the French Working Group on Haemostasis and Thrombosis, anti-factor Xa activity and aPTT should be tested within 2 h of blood sampling for unfractionated heparin (UFH) monitoring. However, discrepancies exist depending on the used reagents and collecting tubes. The study aim was to determine the stability of aPTT and anti-factor Xa measurements using blood samples collected in citrate-containing or citrate-theophylline-adenosine-dipyridamole (CTAD) tubes and stored for up to 6 h.MethodsPatients receiving UFH or low molecular weight heparin (LMWH) were enrolled; aPTT and anti-factor Xa activity were tested using two different analyser/reagent pairs (Stago and reagent without dextran sulfate; Siemens and reagent with dextran sulfate) after 1, 4 and 6 h of sample storage as whole blood or as plasma.ResultsFor UFH monitoring, comparable anti-factor Xa activity and aPTT results were obtained with both analyser/reagent pairs when samples were stored as whole blood before plasma isolation. With samples stored as plasma, anti-factor Xa activity and aPTT were not affected up to 6 h after sampling when using the Stago/no-dextran sulfate reagent pair. With the Siemens/dextran sulfate-containing reagent, aPTT was significantly altered after 4 h of storage. For LMWH monitoring, anti-factor Xa activity remained stable (whole blood and plasma) for at least 6 h. Results were comparable with citrate-containing and CTAD tubes.ConclusionsAnti-factor Xa activity in samples stored as whole blood or plasma was stable for up to 6 h, regardless of the reagent (with/without dextran sulfate)/collection tube. Conversely, aPTT was more variable because other plasma parameters can influence its measure and complicate the interpretation of its variations after 4 h.

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.

Novel fondaparinux protocol for anticoagulation therapy in adults with renal failure and suspected heparin-induced thrombocytopenia: a retrospective review of institutional protocol

IntroductionThe literature recommends against the use of fondaparinux in patients with kidney failure and dialysis as it may, with repeated dosing, accumulate and put patients at risk of bleeding. The management of patients with thrombosis in the presence of heparin-induced thrombocytopenia HIT requires the introduction of an alternative anticoagulant like bivalirudin or argatroban. When these drugs are not available, fondaparinux, remains the only alternative. In similar scenarios, there are few studies addressing how to administer it. MethodsWe developed a protocol for fondaparinux in patients with renal failure where pharmacokinetic parameters are altered, and levels changed only after hemodialysis or in cases of residual renal activity. Patients received a full first dose except for high risk of bleeding. We targeted a peak anti-factor Xa activity level of 0.6–1.3 units/ml and changed the subsequent dose accordingly. Furthermore, we monitored the patients for signs of bleeding, a drop in hemoglobin level, or clinical signs of thrombosis. DiscussionWe described 10 patients with kidney failure and suspected HIT taking fondaparinux. All the patients achieved therapeutic anti-factor Xa activity levels. However, one developed new-onset venous thromboembolism (VTE) despite therapeutic anti-factor Xa levels. Another patient experienced a bleeding episode. We believe that these two patients developed complications due to their medical conditions rather than the use of fondaparinux.ConclusionFondaparinux can be safely used in kidney failure using our protocol. However, despite its safety profile and relative success, this case series was small. More robust studies need to be conducted prior to drawing conclusions.

Rivaroxaban and apixaban are less effective than enoxaparin for the prevention of catheter-induced clotting in vitro

BackgroundCentral venous catheters are prone to clotting, particularly in patients with cancer. Although low-molecular-weight heparin and direct oral anticoagulants, such as apixaban and rivaroxaban, have been evaluated for the prevention of catheter thrombosis, their efficacy remains uncertain. ObjectivesCompare apixaban and rivaroxaban with enoxaparin for the prevention of catheter-induced clotting in vitro. MethodsTo address this uncertainty, we used a well-established microplate-based assay to compare the effects of enoxaparin, apixaban, and rivaroxaban on catheter-induced thrombosis and thrombin generation in human plasma. ResultsConsistent with our previous findings, catheter segments shortened the clotting time and promoted thrombin generation. When compared at concentrations with similar anti-factor Xa activity as enoxaparin, apixaban and rivaroxaban were >20-fold less potent than enoxaparin for the prevention of catheter-induced clotting and thrombin generation. ConclusionThe prevention of catheter thrombosis in patients with cancer is challenging. Clinical trials are needed to compare the efficacy of low-molecular-weight heparin with that of direct oral anticoagulants both for the prevention and treatment of catheter thrombosis.

Lupus anticoagulant testing for patients on direct oral anticoagulants

Abstract As use of direct factor Xa inhibitor (direct oral anticoagulant; DOAC) therapy increases, a modified lupus anticoagulant (LAC) testing method was studied to remove interfering DOACs, allowing clinicians to evaluate patients for antiphospholipid syndrome (APS) without altering anticoagulation treatment. We evaluated the use of DOAC-StopTM on our LAC testing panel with two assays: dilute Russell viper venom time (dRVVT), a factor X activator, and Silica Clotting Time (SCT), an intrinsic coagulation pathway activator. The plasma specimens were pretreated with DOAC-STOPTM beads by mixing on a rocking platform for 5 minutes and centrifugation at 5000 rpm for 5 minutes. The treated plasma supernatant was used for each step of the assay including the screen, confirm (addition of phospholipid), 50:50 mix (addition of reagent plasma with coagulation factors) and confirm 50:50 mix. The total ratio (ratio between screen and confirm ratios relative to mean of normal ranges) was calculated and used per the package insert in the positive or negative interpretation of each LAC testing panel. The study included patients with one or more of the following characteristics identified during coagulation sign-out and chart review: no evidence of a LAC (NELAC), evidence of a LAC, and whether on apixaban or rivaroxaban therapy. The effectiveness of DOAC removal was characterized with an apixaban spiking experiment for NELAC and LAC patient specimens which showed no change in LAC testing panel interpretation before and after DOAC-STOPTM treatment. A second experiment with apixaban-spiked NELAC samples demonstrated removal of anti-factor Xa activity upon comparison of pre- and post-treatment with DOAC-STOPTM. Of 10 patients taking rivaroxaban, nine had positive dRVVT interpretations; eight of these specimens changed to negative interpretations after DOAC-STOPTM treatment. For SCT, two positive interpretations remained positive, while two of the remaining eight negatives became positive after treatment. Of nine patients taking apixaban, two had positive dRVVT interpretations, one of which became negative post-treatment. Of the seven negative interpretations, one became positive post-treatment. For SCT, three were positive pre-treatment and seven were negative with no change post-treatment. Providing a LAC testing option for patients on DOACs may be of benefit to patients and clinicians in APS assessment, eliminating the risk of suspending anticoagulation therapy. Our study shows DOAC-STOPTM effectively removes DOAC interference in the majority of patient specimens studied, though LAC testing and interpretation in the setting of a high-complexity patient population on DOAC therapy remains challenging with occasional false positives and false negatives.

Abstract 9574: Distribution of Anti-Factor Xa Activity Value, Prothrombin Time, and Activated Partial Thromboplastin Time in Patients Treated With Factor Xa Inhibitors

Introduction: The distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) has not fully been assessed. Purpose: To clarify the distribution of AXA, PT, and APTT in patients taking FXa inhibitors. Methods: 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. Results: At trough time of apixaban, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P &lt; 0.001). PT in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P = 0.006). At peak time, the AXA values in patients administered 20 mg were significantly higher than those administered 5 mg or 10 mg (P &lt; 0.001). PT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P &lt; 0.001). APTT in patients administered 20 mg was significantly higher than those administered 5 mg or 10 mg (P &lt; 0.001). At peak time of edoxaban, the AXA values in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P &lt; 0.001). PT in patients administered 60 mg were significantly higher than those administered 15 mg or 30 mg (P = 0.006). APTT in patients administered 60 mg was significantly higher than those administered 30 mg (P = 0.003). At trough time of rivaroxaban, the AXA values in patients administered 30 mg were significantly higher than those administered 10 mg or 15 mg (P = 0.001). At peak time, AXA values in patients administered 30 mg were significantly higher than those administered 15 mg (P = 0.028). Conclusion: This study determined the distribution of AXA, PT, and APTT in patients administered apixaban, edoxaban, and rivaroxaban.