Abstract 164: Specific Point-of-Care Testing of Coagulation in Patients Treated With Non-Vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Florian Härtig ◽  
Andreas Peter ◽  
Charlotte Spencer ◽  
Matthias Ebner ◽  
Christine S Zürn ◽  
...  
Keyword(s):  
Vitamin K ◽  
Point Of Care ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Rapid Assessment ◽  
Plasma Concentrations ◽  
Vitamin K Antagonist ◽  
Point Of Care Testing ◽  
Blood Samples ◽  
First Time

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF) and venous thrombosis. Ischemic stroke rate in NOAC-treated AF-patients is 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity-POCT accurately predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment will be enrolled (N=40 for each NOAC). Subjects receiving other anticoagulants will be excluded. 6 blood samples will be collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations will be measured by mass spectrometry. Results (preliminary): Until now 138 blood samples of 23 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-371ng/mL. ECT-POCT ranged from 20-219s. Pearson’s correlation coefficient showed strong correlation for ECT-POCT and dabigatran-concentrations (r=0.94, p<0.001). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT (>50s) with 100% sensitivity and 82% specificity. Baseline-samples not containing any dabigatran yielded normal ECT-POCT. Conclusions: This is the first study evaluating NOAC-specific POCT. Preliminary results show excellent correlation for ECT-POCT and dabigatran; relevant dabigatran-concentrations were detected in 100%. More pioneering results on NOAC-specific POCT will be presented.

Abstract 20: Specific Point-of-care Testing of Coagulation in Patients Treated with Non-vitamin K Antagonist Oral Anticoagulants Part I (SPOCT-NOAC I)

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Florian J Härtig ◽  
Andreas Peter ◽  
Charlotte Spencer ◽  
Matthias Ebner ◽  
Christine Meyer-Zuern ◽  
...  
Keyword(s):  
Vitamin K ◽  
Whole Blood ◽  
Point Of Care ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Rapid Assessment ◽  
Plasma Concentrations ◽  
Vitamin K Antagonist ◽  
Point Of Care Testing ◽  
Blood Samples

Introduction: Non-vitamin K antagonist oral anticoagulants (NOAC) are increasingly replacing vitamin K antagonists for prevention of thromboembolism in atrial fibrillation (AF). Despite treatment, stroke rate in NOAC-treated AF-patients remains 1-2% per year. Subsequently, stroke physicians face a growing number of NOAC-treated patients with acute stroke. Rapid assessment of coagulation in NOAC-treated patients is vital prior to thrombolysis or reversal therapy, but existing point-of-care testing (POCT) is suboptimal. For the first time we evaluate NOAC-specific POCT. Hypothesis: Ecarin clotting time (ECT)- and anti-Xa activity (ENOX)-POCT predict plasma concentrations of dabigatran and apixaban/edoxaban/rivaroxaban. Methods: 80 patients receiving first NOAC-dose and 80 already on NOAC-treatment are enrolled in the SPOCT-NOAC I trial (N=40 for each NOAC). Subjects receiving other anticoagulants are excluded. Six blood samples are collected from each patient: before drug intake, 30min, 1, 2, and 8h after intake, and before next dose. NOAC-concentrations are measured by mass spectrometry. Results: 240 blood samples of 40 dabigatran-treated patients were analyzed. Dabigatran-concentrations ranged from 0-274ng/mL. ECT-POCT ranged from 20-196s. Pearson’s correlation coefficient showed strong correlation between ECT-POCT and dabigatran-concentrations (r=0.87). Performance was improved through the use of citrated in place of non-citrated whole blood (r=0.93). Dabigatran-concentrations >50ng/mL (threshold for thrombolysis according to expert recommendation) were detected by ECT-POCT >50s with 98% sensitivity and 79% specificity. Baseline-samples not containing any dabigatran yielded normal ECT values. Conclusions: This is the first study evaluating NOAC-specific POCT. Final results in the dabigatran group of SPOCT-NOAC show excellent correlation between ECT-POCT and dabigatran plasma concentrations; performance of ECT-POCT is even increased through the use of citrated whole blood. Relevant dabigatran-concentrations are detected with excellent sensitivity and specificity. In addition to ECT-POCT, we will present data on ENOX-POCT from apixaban-, edoxaban- and rivaroxaban-treated patients.

scholarly journals Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants including edoxaban

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Florian Härtig ◽  
Ingvild Birschmann ◽  
Andreas Peter ◽  
Sebastian Hörber ◽  
Matthias Ebner ◽  
...  
Keyword(s):  
Blood Sample ◽  
Point Of Care ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Rapid Assessment ◽  
Plasma Concentrations ◽  
Test System ◽  
Systematic Evaluation ◽  
Operating Characteristics ◽  
Blood Samples

Abstract Background Direct oral anticoagulants (DOAC) including edoxaban are increasingly used for stroke prevention in atrial fibrillation. Despite treatment, annual stroke rate in these patients remains 1–2%. Rapid assessment of coagulation would be useful to guide thrombolysis or reversal therapy in this growing population of DOAC/edoxaban-treated stroke patients. Employing the Hemochron™ Signature Elite point-of-care test system (HC-POCT), clinically relevant plasma concentrations of dabigatran and rivaroxaban can be excluded in a blood sample. However, no data exists on the effect of edoxaban on HC-POCT results. We evaluated whether edoxaban plasma concentrations above the current treatment thresholds for thrombolysis or anticoagulation reversal (i.e., 30 and 50 ng/mL) can be ruled out with the HC-POCT. Methods We prospectively studied patients receiving a first dose of edoxaban. Six blood samples were collected from each patient: before, 0.5, 1, 2, 8, and 24 h after drug intake. HC-POCT-based INR (HC-INR), activated clotting time (HC-ACT+ and HC-ACT-LR), activated partial thromboplastin time (HC-aPTT), and mass spectrometry for edoxaban plasma concentrations were performed at each time-point. We calculated correlations, receiver operating characteristics (ROC) and test-specific cut-offs for ruling out edoxaban concentrations > 30 and > 50 ng/mL in a blood sample. Results One hundred twenty blood samples from 20 edoxaban-treated patients were analyzed. Edoxaban plasma concentrations ranged from 0 to 512 ng/mL. HC-INR/HC-ACT+/HC-ACT-LR/HC-aPTT ranged from 0.7–8.3/78–310 s/65–215 s/19–93 s, and Pearson’s correlation coefficients showed moderate to very strong correlations with edoxaban concentrations (r = 0.95/0.79/0.70/0.60). With areas under the ROC curve of 0.997 (95% confidence interval: 0.991–0.971) and 0.989 (0.975–1.000), HC-INR most reliably ruled out edoxaban concentrations > 30 and > 50 ng/mL, respectively, and HC-INR results ≤1.5 and ≤ 2.1 provided specificity/sensitivity of 98.6% (91.2–99.9)/98.0% (88.0–99.9) and 96.8% (88.0–99.4)/96.5% (86.8–99.4). Conclusions Our study represents the first systematic evaluation of the HC-POCT in edoxaban-treated patients. Applying sufficiently low assay-specific cut-offs, the HC-POCT may not only be used to reliably rule out dabigatran and rivaroxaban, but also very low edoxaban concentrations in a blood sample. Because the assay-specific cut-offs were retrospectively defined, further investigation is warranted. Trial registration ClinicalTrials.gov, registration number: NCT02825394, registered on: 07/07/2016, URL

scholarly journals Point-of-Care Testing of Coagulation in Patients Treated With Non–Vitamin K Antagonist Oral Anticoagulants

Stroke ◽  
2015 ◽  
Vol 46 (10) ◽  
pp. 2741-2747 ◽  
Author(s):  
Matthias Ebner ◽  
Andreas Peter ◽  
Charlotte Spencer ◽  
Florian Härtig ◽  
Ingvild Birschmann ◽  
...  
Keyword(s):  
Vitamin K ◽  
Point Of Care ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Point Of Care Testing

scholarly journals Specific Point-of-Care Testing of Coagulation in Patients Treated with Dabigatran

2021 ◽  
Author(s):  
Florian Härtig ◽  
Ingvild Birschmann ◽  
Andreas Peter ◽  
Matthias Ebner ◽  
Charlotte Spencer ◽  
...  
Keyword(s):  
Point Of Care ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Rapid Assessment ◽  
Plasma Concentrations ◽  
High Sensitivity ◽  
Diagnostic Study ◽  
Blood Samples ◽  
Urgent Surgery ◽  
Coagulation Testing

Abstract Background and Purpose Accurate and rapid assessment of coagulation status is necessary to guide thrombolysis or reversal of anticoagulation in stroke patients, but commercially available point-of-care (POC) assays are not suited for coagulation testing in patients treated with direct oral anticoagulants (DOACs). We aimed to evaluate the direct thrombin monitoring (DTM) test card by Helena Laboratories (Texas, United States) for anti-IIa-specific POC coagulation testing, hypothesizing that its POC-ecarin clotting time (POC-ECT) accurately reflects dabigatran plasma concentrations. Methods A prospective single-center diagnostic study (ClinicalTrials.gov-identifier: NCT02825394) was conducted enrolling patients receiving a first dose of dabigatran and patients already on dabigatran treatment. Blood samples were collected before drug intake and 0.5, 1, 2, 8, and 12 hours after intake. POC-ECT was performed using whole blood (WB), citrated blood (CB), and citrated plasma (CP). Dabigatran plasma concentrations were determined by mass spectrometry. Results In total, 240 blood samples from 40 patients contained 0 to 275 ng/mL of dabigatran. POC-ECT with WB/CB/CP ranged from 20 to 186/184/316 seconds. Pearson's correlation coefficient showed a strong correlation between dabigatran concentrations and POC-ECT with WB/CB/CP (R2  = 0.78/0.90/0.92). Dabigatran concentrations >30 and >50 ng/mL (thresholds for thrombolysis, surgery, and reversal therapy according to clinical guidelines) were detected by POC-ECT with WB/CB/CP (>36/35/45 and >43/45/59 seconds) with 95/97/97 and 96/98/97% sensitivity, and 81/87/94 and 74/60/91% specificity. Conclusion This first study evaluating DOAC-specific POC coagulation testing revealed an excellent correlation of POC-ECT with actual dabigatran concentrations. Detecting clinically relevant dabigatran levels with high sensitivity/specificity, the DTM assay represents a suitable diagnostic tool in acute stroke, hemorrhage, and urgent surgery.

scholarly journals The Risk of Gastrointestinal Bleeding between Non-Vitamin K Antagonist Oral Anticoagulants and Vitamin K Antagonists in the Asian Atrial Fibrillation Patients: A Meta-Analysis

2020 ◽  
Vol 18 (1) ◽  
pp. 137
Author(s):  
Kuang-Tsu Yang ◽  
Wei-Chih Sun ◽  
Tzung-Jiun Tsai ◽  
Feng-Woei Tsay ◽  
Wen-Chi Chen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
Optimal Dosage

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) are more commonly used to prevent atrial fibrillation (AF) patients from thromboembolic events than vitamin K antagonists (VKAs). However, the gastrointestinal bleeding (GIB) risk in the Asian AF patients associated with NOACs in comparison with VKAs remained unaddressed. Materials and Methods: A systematic search of studies on NOACs and VKAs in the Asian AF patients was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov. The primary outcome was the hazard ratio (HR) of any GIB associated with NOACs versus VKAs. The secondary outcome was the GIB risks in different kinds of NOACs compared with VKAs. Results: This meta-analysis included two randomized controlled trials (RCTs) and four retrospective studies, comprising at least 200,000 patients in total. A significantly lower HR of GIB risks was found in all kinds of NOACs than VKAs in the Asian AF patients (HR: 0.633; 95% confidence interval: 0.535–0.748; p < 0.001). Additionally, the GIB risks of different NOACs were apixaban (HR: 0.392), edoxaban (HR: 0.603), dabigatran (HR: 0.685), and rivaroxaban (HR: 0.794), respectively. Conclusions: NOACs significantly reduced the risk of GIB in the Asian AF patients compared with VKAs. In the four NOACs compared with VKAs, apixaban probably had a trend of the least GIB risk. We need further head-to-head studies of different NOACs to confirm which NOAC is the most suitable for Asian AF patients and to know the optimal dosage regimen of different NOACs.

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Reversal Agents ◽  
Limited Availability ◽  
Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

The NOACs: clinical pharmacology

ESC CardioMed ◽  
2018 ◽  
pp. 268-272
Author(s):  
Jeffrey Weitz
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Active Site ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
High Affinity

The limitations of vitamin K antagonists prompted the development of new oral anticoagulants that could be administered in fixed doses without routine coagulation monitoring. Focusing on thrombin and factor Xa because of their prominent roles in coagulation, structure-based design led to the development of small molecules that bind to the active site pockets of these enzymes with high affinity and specificity. Four non-vitamin K antagonist oral anticoagulants are now licensed: dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. In phase III randomized clinical trials that included over 100,000 patients these agents have proven to be at least as effective as vitamin K antagonists for prevention of stroke in patients with non-valvular atrial fibrillation and for treatment of venous thromboembolism, and to produce less bleeding, particularly less intracranial bleeding.

scholarly journals Non-vitamin K antagonist oral anticoagulants vs. vitamin-K antagonists in patients with atrial fibrillation and chronic kidney disease: a nationwide cohort study

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Emma Kirstine Laugesen ◽  
Laila Staerk ◽  
Nicholas Carlson ◽  
Anne-Lise Kamper ◽  
Jonas Bjerring Olesen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
All Cause Mortality ◽  
Comparable Population

Abstract Background We aimed to compare effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin-K antagonists (VKA) in atrial fibrillation (AF) patients with chronic kidney disease (CKD) not receiving dialysis. Methods By using personal identification numbers, we cross-linked individual-level data from Danish administrative registries. We identified every citizen with a prior diagnosis of AF and CKD who initiated NOAC or VKA (2011–2017). An external analysis of 727 AF patients with CKD (no dialysis) was performed to demonstrate level of kidney function in a comparable population. Study outcomes included incidents of stroke/thromboembolisms (TEs), major bleedings, myocardial infarctions (MIs), and all-cause mortality. We used Cox proportional hazards models to determine associations between oral anticoagulant treatment and outcomes. Results Of 1560 patients included, 1008 (64.6%) initiated VKA and 552 (35.4%) initiated NOAC. In a comparable population we found that 95.3% of the patients had an estimated glomerular filtration rate (eGFR) < 59 mL/min. Patients treated with NOAC had a significantly decreased risk of major bleeding (hazard ratio (HR): 0.47, 95% confidence interval (CI): 0.26–0.84) compared to VKA. There was not found a significant association between type of anticoagulant and risk of stroke/TE (HR: 0.83, 95% CI: 0.39–1.78), MI (HR: 0.45, 95% CI: 0.18–1.11), or all-cause mortality (HR: 0.99, 95% CI: 0.77–1.26). Conclusion NOAC was associated with a lower risk of major bleeding in patients with AF and CKD compared to VKA. No difference was found in risk of stroke/TE, MI, and all-cause mortality.

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