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A Diagnostic Solution for Lupus Anticoagulant Testing in Patients Taking Direct Oral FXa Inhibitors Using DOAC Filter.

ABSTRACT: Background: Direct oral factor Xa (FXa) inhibitors interfere with lupus anticoagulant (LA) assays challenging antiphospholipid syndrome diagnosis in treated patients. We evaluated a new device, called DOAC Filter, and its usefulness in this setting. It is a single-use filtration cartridge in which FXa inhibitor compounds are trapped by non-covalent binding while plasma is filtered through a solid phase. Patient samples were analyzed before and after filtration: 38 rivaroxaban, 41 apixaban, and 68 none. Anticoagulant plasma concentrations were measured using specific anti-Xa assays and HPLC-MS/MS. LA testing was performed using dilute Russell Viper Venom Time (dRVVT) and Silica Clotting Time (SCT). Baseline median [min-max] concentrations were 64.8 [17.6; 311.4] for rivaroxaban and 92.1 ng/mL [37.1; 390.7] for apixaban (HPLC-MS/MS). They were significantly correlated with anti-Xa assay results (r = 0.98 and r = 0.94, respectively). dRVVT was positive in 92% rivaroxaban and 72% apixaban and SCT in 28 and 41% of samples, respectively. Post-filtration, median % of neutralization was 100% with rivaroxaban and apixaban concentrations of, respectively, <2 [<2-2.4] and <2 ng/mL [<2-9.6] using HPLC-MS/MS. No significant effect of DOAC Filter was observed on LA testing in controls (n = 31) and LA-positive (n = 37) non-anticoagulated samples. dRVVT and SCT remained positive in, respectively, 16 and 8% of rivaroxaban and 41 and 18% of apixaban samples. DOAC Filter would be an easy-to-use device allowing FXa inhibitor removal from plasma samples, limiting their interference with LA testing in treated patients.

SUBMITTER: Farkh C

PROVIDER: S-EPMC8200390 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants.

Project description:BackgroundLupus anticoagulants (LA) are one laboratory criterion for classification of antiphospholipid syndrome, with presence of vascular thrombosis and/or pregnancy/fetal morbidity being clinical criteria. The presence of LA is detected (or excluded) by laboratory testing, with the activated partial thromboplastin time and dilute Russell's viper venom time the most commonly used tests. Given the association of thrombosis with LA, it is no surprise that anticoagulants are used to treat or manage such patients.ObjectivesTo review and discuss interferences from anticoagulants on LA testing, and strategies to mitigate these.MethodsThis narrative review assessed interference from commonly used anticoagulants, focusing on LA testing while on direct oral anticoagulants (DOACs), including use of DOAC neutralizers.ResultsThe classical anticoagulants comprise vitamin K antagonists such as warfarin, and heparins, predominantly unfractionated heparin and low molecular weight heparin (LMWH). DOACs have emerged with favorable efficacy and safety. These comprise two classes: direct anti-thrombin (anti-IIa; dabigatran) or direct anti-Xa (rivaroxaban, apixaban, edoxaban) agents. All anticoagulants affect clotting assays, although there are differences in effects according to anticoagulant and assay. Nevertheless, because of such interferences, anticoagulants can lead to false-negative or false-positive LA findings. Several strategies can mitigate such interferences, including avoidance of testing while patients are on such anticoagulants, temporarily switching to an anticoagulant (i.e., LMWH) with less assay interference, testing for LA at nadir levels of anticoagulants, and/or use of anticoagulant neutralizers.ConclusionWhilst the best approach is to avoid LA testing on patients taking anticoagulants; if unavoidable, testing may be facilitated by various mitigating strategies.

| S-EPMC8922544 | biostudies-literature

Direct oral anticoagulants-Remove versus Taipan snake venom time for detection of a lupus anticoagulant in patients taking oral direct factor Xa inhibitors.

Project description:BackgroundThe optimal method of detecting a lupus anticoagulant (LA) for patients taking direct factor Xa inhibitor (DFXaI) direct oral anticoagulants (DOACs) remains controversial. Methods include charcoal adsorption of the DOACs to allow testing with the activated partial thromboplastin time (APTT) and dilute Russell viper venom time (dRVVT), or use of the DFXaI-insensitive Taipan snake venom time (TSVT) and Ecarin time (ET) assays on neat plasma.ObjectivesThe objective was to compare the utility of APTT and dRVVT analysis following DOAC Remove against TSVT/ET on untreated plasma for LA detection in spiked plasmas and routine clinical samples for patients on DFXaIs.Patients/methodsVarious LA-negative and LA-positive samples were assayed by APTT, dRVVT, and TSVT/ET, and then separately spiked with rivaroxaban, apixaban, and edoxaban calibrators to a concentration of ~190 ng/ml and the assays repeated on spiked plasma before and after DOAC Remove treatment. Testing of 284 consecutive samples from DFXaI-anticoagulated patients by APTT/dRVVT and TSVT/ET before and after DOAC Remove treatment was undertaken.ResultsIn the spiking model, we found that both TSVT/ET and DOAC Remove strategies generally distinguished LA-negative and LA-positive samples, but some false-positive LA results occurred. In the investigation of 284 consecutive patient samples on DFXaIs, the percentage agreement for LA detection in neat samples tested by TSVT/ET versus APTT and dRVVT after DOAC Remove treatment was 90% (Cohen kappa 0.12).ConclusionOur data highlight uncertainty and disagreement for testing LA in patients on DFXaI. Further studies are required.

| S-EPMC8784856 | biostudies-literature

Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States.

Project description:INTRODUCTION:While trials have demonstrated non-inferiority of direct oral anticoagulant drugs (DOAC) to low-molecular-weight heparins (LMWH) for the treatment of cancer associated thrombosis (CAT), it is unclear if the newer intervention is cost-effective. METHODS:We performed a cost-utility analysis using a Markov state-transition model over a time horizon of 60?months in a hypothetical cohort of 65-year-old patients with active malignancy and first acute symptomatic CAT who were eligible to receive either rivaroxaban/edoxaban or dalteparin. We obtained transition probability, relative risk, cost, and utility inputs from the literature. We estimated the differential impact on costs and quality-adjusted life years (QALYs) per patient and performed one-way and probabilistic sensitivity analyses to test the robustness of results. RESULTS:Using the base-case analysis over 60?months, DOAC versus dalteparin was associated with an incremental cost reduction of $24,129 with an incremental QALY reduction of 0.04. In the one-way sensitivity analysis, the cost of dalteparin contributed the most to the incremental cost difference; relative risk of death related to underlying cancer contributed the most of the incremental QALY difference. The probabilistic sensitivity analysis confirmed the base-case analysis, with a large reduction in cost but small reduction in QALYs. CONCLUSION:Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.

| S-EPMC6661186 | biostudies-literature

Direct oral anticoagulant (DOAC) versus low-molecular-weight heparin (LMWH) for treatment of cancer associated thrombosis (CAT): A systematic review and meta-analysis.

Project description:INTRODUCTION:It is unclear if direct oral anticoagulants (DOACs) are effective and safe alternatives to low-molecular-weight heparin (LMWHs) for the treatment of cancer-associated venous thromboembolism (VTE). We aim to synthesize existing literature that compared DOACs versus LMWHs in this high-risk population. MATERIALS AND METHODS:We conducted a systematic review using EMBASE, MEDLINE and CENTRAL for all observational studies and randomized controlled trials (RCTs) (PROSPERO: CRD42017080898). Two authors independently reviewed study eligibility, extracted data, and assessed bias. Primary outcomes included 6-month recurrent VTE and major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB) and mortality. RESULTS:We screened 426 articles, reviewed 25 in full-text, and selected 13 and 2 for qualitative and quantitative synthesis, respectively. Based on a meta-analysis of the 2 RCTs, DOACs had lower 6-month recurrent VTE (42/725) when compared to LMWH (64/727) (RR: 0.65 (0.42-1.01)). However, DOACs had higher major bleeding (40/725) when compared to LMWH (23/727) (RR 1.74 (1.05-2.88)). Similarly, CRNMB was higher (RR 2.31 (0.85-6.28)) for patients receiving DOACs. There was no difference in mortality (RR 1.03 (0.85-1.26)). Observational studies were heterogeneous with high risks of bias but showed recurrent VTE rates consistent with the meta-analysis. CONCLUSIONS:DOACs were more effective than LMWHs to prevent recurrent VTE but were associated with a significantly increased risk of major bleeding as well as a trend toward more CRNMB. The absolute risk differences were small (2-3%) for both primary outcomes and may reflect better compliance with DOACs than LMWHs.

| S-EPMC6119655 | biostudies-literature

Indication and outcome of lupus anticoagulant and antiphospholipid antibodies testing in routine clinical practice.

Project description:ObjectivesLupus anticoagulans (LACs) and aPLs, both further summarized as aPL, are frequently assessed in routine daily clinical practice in diagnostic workups for suspected autoimmune diseases or to test for underlying risk factors in patients with thrombosis or obstetric complications. The aim of this study was to determine the prevalence of aPL positivity in patients with an indication for aPL testing in routine clinical practice.MethodsIn this retrospective single-centre study, indication for aPL testing, aPL test results and clinical data were collected for patients tested between June 2015 and April 2018.ResultsDuring the study period, 16 847 single aPL tests were performed in 2139 patients. In 212 patients one or more positive aPL test was found, confirmed in 43.9% with a second positive test. Indications for aPL testing were diagnostic workup/follow-up of autoimmune diseases (33.6%), thrombosis (21.4%) and obstetric complications (28%). Seventy-four patients (3.5% of all patients) fulfilled the criteria of APS, of whom 51% were newly diagnosed. Second positive aPL titres and titres of APS patients were significantly higher compared with positive aPL titres at the first measurement (P < 0.05). Patients with indications of arterial thrombosis and diagnostic workup/follow-up of autoimmune diseases had significantly higher levels of aCL IgG and anti-β2 glycoprotein I (β2GPI) IgG compared with patients with other indications.ConclusionThe prevalence of one or more positive aPL test was 9.9% and APS was diagnosed in 3.5% of the patients. Patients with arterial thrombosis had significantly higher anti-β2GPI IgG and aCL IgG, which should be confirmed in future studies.

| S-EPMC8669994 | biostudies-literature

Direct oral anticoagulant: Review article.

Project description:Venous thromboembolism (VTE) and atrial fibrillation (AF) is a major burden on the health care system. The average occurrence of venous thromboembolism annually is around 108 per 100,000 person-year. DOACs have transformed treatment of coagulation disorder, and now, it is the leading treatment for stroke prevention in AF and VTE prophylaxis and treatment. For more many years, oral vitamin K antagonists (VKAs) were the drug of choice in managing VTE. VKAs treatment is safe and effective if therapeutic international normalized ratio (INR) maintained on the target. However, achieving a stable, therapeutic international normalized ratio (INR) can be difficult and challenging in the context of drug and food interactions and liver disorder, resulting in undertreatment which increases the risk of thromboembolism or overtreatment which might cause bleeding. Herein, we provide an overview of DOACs indications, use in specific comorbidities, monitoring parameters, perioperative management, and reversal agents.

| S-EPMC9638657 | biostudies-literature

Physician Practice Patterns for Performing Thoracentesis in Patients Taking Anticoagulant Medications.

Project description:BackgroundPatients undergoing thoracentesis often have comorbid conditions or take medications that potentially put them at higher bleeding risk. Direct oral anticoagulant (DOAC) use has also increased significantly. There are no published guidelines or consensus on when to perform thoracentesis in patients on anticoagulants. Recent studies support the safety of a more liberal approach for thoracentesis among patients with coagulopathy.MethodsWe conducted a survey to ascertain the practices of physicians regarding thoracentesis in patients with increased bleeding risk. The survey was administered to the email distribution lists of the American Association of Bronchology and Interventional Pulmonology and of the American Thoracic Society.ResultsThe survey was completed by 256 attending physicians. Most of them were general pulmonologists practicing at academic medical centers. Most of them would perform a thoracentesis in patients receiving acetylsalicylic acid or prophylactic doses of unfractionated heparin or low molecular weight heparin (96%, 89%, and 88%, respectively). Half of the respondents would perform a thoracentesis in patients on antiplatelet medications (clopidogrel and ticagrelor, 51%; ticlopidine, 53%). A minority would perform thoracentesis in patients on direct oral anticoagulants or infused thrombin inhibitors (19% and 12%, respectively). The only subgroup that had a higher proclivity for performing thoracentesis without holding medications were attending physicians practicing for under 10 years. Relative to noninterventional pulmonologists, there were no significant differences in the responses of interventional pulmonologists.ConclusionThere was variation in the practice patterns of attending physicians in performing thoracentesis in patients with elevated bleeding risk. Further data and guidelines regarding the safety of thoracentesis in these patients are needed.

| S-EPMC6923589 | biostudies-literature

Knowledge and medication adherence of oral anticoagulant-taking patients in Vietnam.

Project description:BackgroundOral anticoagulants for venous thromboembolism are not thoroughly managed in ambulatory settings in low-/middle-income countries, primarily because of patients' neglect of medication knowledge and adherence.ObjectivesThis study was conducted to investigate patient knowledge, adherence, and the associated factors at a Vietnamese tertiary hospital, serving as a reference for educational programs in other local and regional health care facilities.MethodsA randomly recruited cross-sectional study was conducted on patients using vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC). The primary and secondary outcomes were the knowledge score (in percent) and adherence to oral anticoagulants. Student's t-tests or chi-squared tests were used to compare the crude differences in mean or proportion between patients taking VKA and DOAC. Regression models were conducted to adjust the potential confounders and determine factors associated with patient knowledge and adherence.ResultsA total of 199 patients were included. After adjusting for potential confounders, patients receiving a DOAC had similar knowledge scores and levels of adherence compared with those taking VKA, with both groups being suboptimal. Previous counseling was associated with higher knowledge. Better medication knowledge, female sex, and no history of venous thromboembolism were associated with better adherence.ConclusionGood knowledge and adherence of oral anticoagulant-taking patients remain limited in Southeast Asian clinical practice. Further studies in similar settings should examine the associations between these factors and the effectiveness of the regimens. More effective measures targeting patient knowledge and adherence should be implemented to optimize anticoagulation therapy, improve the patients' outcomes, and mitigate the associated adverse effects.

| S-EPMC9932105 | biostudies-literature

Robust diagnostic genetic testing using solution capture enrichment and a novel variant-filtering interface.

Project description:Targeted hybridization enrichment prior to next-generation sequencing is a widespread method for characterizing sequence variation in a research setting, and is being adopted by diagnostic laboratories. However, the number of variants identified can overwhelm clinical laboratories with strict time constraints, the final interpretation of likely pathogenicity being a particular bottleneck. To address this, we have developed an approach in which, after automatic variant calling on a standard unix pipeline, subsequent variant filtering is performed interactively, using AgileExomeFilter and AgilePindelFilter (http://dna.leeds.ac.uk/agile), tools designed for clinical scientists with standard desktop computers. To demonstrate the method's diagnostic efficacy, we tested 128 patients using (1) a targeted capture of 36 cancer-predisposing genes or (2) whole-exome capture for diagnosis of the genetically heterogeneous disorder primary ciliary dyskinesia (PCD). In the cancer cohort, complete concordance with previous diagnostic data was achieved across 793 variant genotypes. A high yield (42%) was also achieved for exome-based PCD diagnosis, underscoring the scalability of our method. Simple adjustments to the variant filtering parameters further allowed the identification of a homozygous truncating mutation in a presumptive new PCD gene, DNAH8. These tools should allow diagnostic laboratories to expand their testing portfolios flexibly, using a standard set of reagents and techniques.

| S-EPMC4285299 | biostudies-literature

Novel reversal agents and laboratory evaluation for direct-acting oral anticoagulants (DOAC): An update.

Project description:Novel oral anticoagulants (NOACs) are no longer "novel" but their reversal agents definitely are. Although NOACs enjoy high clinical efficacy, monitoring and reversal of their effect is a challenge which this review attempts to surmount. Ideally, for NOAC activity measurement, specific anti-Factor IIa levels and anti -Factor Xa levels should be monitored (chromogenic assays), but such tests are not readily available. Modifications of the existing coagulation tests catering to this unmet need for quantification of DOAC activity have been reviewed. The available United States Food and Drug Administration (FDA) approved reversal agents, idarucizumab for dabigatrin and andexanet alfa for anti-Xa direct acting oral anticoagulants have given promising results but are prohibitively priced. Medline, Embase, and Scopus databases were thoroughly searched for clinical trials on laboratory investigations and specific as well as non-specific reversal-agents for DOACs.

| S-EPMC6423941 | biostudies-literature

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