scholarly journals Analysis of Inter-Observer Agreement of Adjudication of Colors of Pad Colors of Doac Dipstick to Determine Presence or Absence of Direct Oral Anticoagulants in Outpatients' Urine Samples

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3213-3213
Author(s):  
Loula Papageorgiou ◽  
Job Harenberg ◽  
Ismail Elalamy ◽  
Grigoris Gerotziafas
Keyword(s):  
Interim Analysis ◽  
Assessment Tool ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thromboembolic Disease ◽  
Observer Agreement ◽  
Urine Samples ◽  
Thrombin Inhibitors ◽  
Kappa Index

Abstract Background: The efficacy and safety of direct oral anticoagulants (DOACs) in patients with thromboembolic disease is closely related to patient's adherence to therapy. Objective documentation of drug intake is a useful tool for patients' education and improvement of adherence to treatment but may be improved by accurate point-of-care (POCT) testing. Results of DOAC Dipstick may be one of these methods but may depend on interpretation variability. Aim: We aim to analyze the inter-observer agreement of DOAC Dipstick near-patient device in outpatients on stable anticoagulation with rivaroxaban (R), apixaban (A) and dabigatran (D). Methods: A prospective observational cohort study was performed including patients on active treatment with R, A, and D for secondary VTE prevention. All participants were routinely assessed for DOACs' plasma concentration using STA ® Liquid anti-Xa and STA ® Liquid anti-IIa chromogenic assays , and creatinine clearance (Cockroft -Gault equation). DOAC Dipstick test was performed in patients' urine samples were performed by trained staff according the instructions for use. The assessment was based on pads'colors which are specific for indicating the presence and absence of factor -Xa (FXA) and thrombin inhibitors (THI). In order to assess inter-observer agreement, the study nurse performing the test and the medication-prescribing physician were in charge of evaluating independently each test strip. THI pad and FXA pad served as negative control for patients treated with R and A, and D, respectively. Inter-observer agreement was calculated by Cohen's kappa coefficient (kappa index). Results: A new interim analysis shortly before study termination was performed after enrolment of 79 patients (female/ male 44/35, age 56 ± 18 years, mean and standard deviation). Of those, 20% (n=17) were treated for deep vein thrombosis, 13% (n=10) for pulmonary embolism (PE), 40% (n=32) for recurrent thromboembolic disease, 18.3% (n=13), for cancer-associated thrombosis, 6 for antiphospholipid syndrome (n= 5), 2 % (n=2) for AF. 60 % (n=48 ) were treated with R, 37% (n=29) with A and 3% (n=2) with D. All patients had normal renal function. Anti-factor Xa levels were determined with a median value of 156.6±129.2 ng/ml and anti-factor IIa levels with 191.66±110.34 ng/mL. The inter- observer agreement of colors of FXA and THI pads of urine samples was 0.99 for positivity for R, A, and D. Pads that served as negative controls were assessed correctly as negative by both observers in all cases (kappa index 1.0). Conclusion: Given the encouraging results, the ongoing study should allow the device's validation as an accurate, easy-to-use assessment tool for determination of the presence or absence of DOACs in patients' urine samples also based on a very low inter-observer variability. The aforementioned data confirm the results of the first interim analysis presented in the ISTH 2021 congress. Disclosures Harenberg: DOACSENCE: Other: Founder and managing director.

scholarly journals Performance Characteristics of DOAC Dipstick in Determining Direct Oral Anticoagulants in Urine

2021 ◽  
Vol 27 ◽  
pp. 107602962199355
Author(s):  
Job Harenberg ◽  
Andrea Martini ◽  
Shanshan Du ◽  
Sandra Krämer ◽  
Christel Weiss ◽  
...  
Keyword(s):  
Interobserver Variability ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Urine Samples ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Visual Interpretation ◽  
Dipstick Test ◽  
Urine Color

Testing for direct oral anticoagulants (DOACs) in patient urine may facilitate medical treatment decisions. The aim of this study was to investigate interobserver variability by 2 independent observers compared to laboratory staff in the visual interpretation of factor Xa (DXI) and thrombin inhibitors (DTI) using the DOAC Dipstick test. We also examined whether test pads reacted to other anticoagulants and abnormal urine colors. The colors of the DOAC Dipstick direct factor Xa inhibitor and thrombin inhibitor pads were interpreted with 100% accuracy (95% confidence interval 0.862 to 1.000) for urine samples from persons treated with apixaban (n = 26), rivaroxaban (n = 24), and dabigatran (n = 29) and without anticoagulant therapy (n = 29). The factor Xa and thrombin inhibitor pads did not interact with heparin, nadroparin, fondaparinux, or coumadin. One µg/mL r-Hirudin and 6 µg/mL argatroban interacted with the DTI pad; however, this is unlikely to cause clinical problems because dabigatran is unlikely to be administered together with r-Hirudin and argatroban in clinical circumstances. Abnormal urine color was reliably detected by the urine color pad, so can prevent false interpretation of the DOAC Dipstick pad colors. In conclusion, we have demonstrated that interobserver variability when interpreting the DOAC Dipstick test strip is low and that factor Xa and thrombin inhibitor pads do not react to other anticoagulants such as heparins and coumadin. R-Hirudin and argatroban can be detected by the thrombin inhibitor pad and abnormal urine colors can be detected by the urine color pad to prevent false interpretation of the results in patient urine samples.

Heparin induced thrombocytopenia

2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Factor Xa ◽  
Additional Treatment ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Clinical Aspects ◽  
Heparin Induced Thrombocytopenia

SummaryHeparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

scholarly journals Direct oral anticoagulant (DOAC) interference in hemostasis assays

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 129-133
Author(s):  
Karen A. Moser ◽  
Kristi J. Smock
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Sample Collection ◽  
Educational Materials ◽  
Direct Factor Xa Inhibitors ◽  
Testing Algorithms

Abstract Direct oral anticoagulants (DOACs) are a group of direct coagulation factor inhibitors including both direct thrombin inhibitors and direct factor Xa inhibitors. These medications may cause hemostasis assay interference by falsely increasing or decreasing measured values, depending on the analyte. Considering the potential for DOAC interference in a variety of hemostasis assays is essential to avoid erroneous interpretation of results. Preanalytic strategies to avoid DOAC interference include selecting alternatives to clot-based hemostasis assays in patients taking DOACs when possible and sample collection timed when the patient is off anticoagulant therapy or at the expected drug trough. Clinical laboratories may also provide educational materials that clearly describe possible interferences from DOAC, develop testing algorithms to aid in detection of DOAC in submitted samples, use DOAC-neutralizing agents to remove DOACs before continuing with testing, and write interpretive comments that explain the effects of DOAC interference in hemostasis tests. Using a combination of the described strategies will aid physicians and laboratorians in correctly interpreting hemostasis and thrombosis laboratory tests in the presence of DOACs.

scholarly journals Direct oral anticoagulants; a review for the non-specialist

2021 ◽  
Vol 13 (4) ◽  
Author(s):  
Thilina Gunawardena
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Onset Of Action ◽  
Novel Anticoagulants ◽  
Number Of Patients ◽  
Direct Factor Xa Inhibitors ◽  
Pharmacokinetic Properties ◽  
Clinical Overview

Thrombin inhibitors and direct factor Xa inhibitors represent a major breakthrough in the field of anticoagulation pharmacotherapy. These novel agents have replaced warfarin as the oral anticoagulant of choice in certain indications, as they possess equal or superior efficacy and better safety profiles. They have a quick onset of action, predictable pharmacokinetic properties and minimal drug and food interactions. So they do not require frequent blood monitoring and dose adjustments as with warfarin. Considering all the advantages, there seems to be a rapid increase in the number of patients who are started on these novel anticoagulants. In this review, we highlight the pharmacology of these direct oral anticoagulants and the evidence-based indications for their use. We aim to provide a clinical overview for the non-specialist who may be called upon to manage a patient who is currently on one of these novel anticoagulants.

scholarly journals Direct oral anticoagulants and venous thromboembolism

2016 ◽  
Vol 25 (141) ◽  
pp. 295-302 ◽  
Author(s):  
Massimo Franchini ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Direct Anticoagulants ◽  
Deep Vein

Venous thromboembolism (VTE), consisting of deep vein thrombosis and pulmonary embolism, is a major clinical concern associated with significant morbidity and mortality. The cornerstone of management of VTE is anticoagulation, and traditional anticoagulants include parenteral heparins and oral vitamin K antagonists. Recently, new oral anticoagulant drugs have been developed and licensed, including direct factor Xa inhibitors (e.g. rivaroxaban, apixaban and edoxaban) and thrombin inhibitors (e.g. dabigatran etexilate). This narrative review focusses on the characteristics of these direct anticoagulants and the main results of published clinical studies on their use in the prevention and treatment of VTE.

Andexanet Alfa, the Possible Alternative to Protamine for Reversal of Unfractionated Heparin

2020 ◽  
Vol 55 (2) ◽  
pp. 261-264
Author(s):  
John N. Maneno ◽  
Genevieve Lynn Ness
Keyword(s):  
Unfractionated Heparin ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Hospital Setting ◽  
Factor Xa ◽  
Thrombin Inhibitors ◽  
Thrombin Time ◽  
Reversal Agent

The recent shortage of protamine prompted an investigation of alternatives for reversal of unfractionated heparin. Heparin is an anticoagulant utilized in the hospital setting. Available options for anticoagulation include direct oral anticoagulants, vitamin K antagonists, thrombin inhibitors, low-molecular-weight heparins, and heparin. Protamine is the approved reversal agent for heparin with few alternatives under investigation. Although andexanet was designed as an antidote for apixaban and rivaroxaban, in vitro studies show that in a dose-dependent technique, andexanet had near full reversal of heparin, reversed anti–factor Xa activity, and neutralized anticoagulant effects of activated partial thromboplastin time and thrombin time induced by heparin.

scholarly journals Heparin is more effective than apixaban in inhibiting in vitro contact activated coagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Engelen ◽  
C Van Laer ◽  
M Jacquemin ◽  
C Vandenbriele ◽  
K Peerlinck ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Mechanical Heart Valves ◽  
Contact Activation

Abstract Introduction Contact of blood with artificial surfaces such as mechanical support devices, catheters, and mechanical heart valves activates the contact activation (CA) pathway of coagulation. Furthermore, recent animal data and clinical studies suggest a more important contribution of CA in pathological thrombus formation in other cardiovascular diseases. Direct oral anticoagulants (DOACs) are recommended as first-line treatment in most patients who require long-term anticoagulation. However, because DOACs directly inhibit a single downstream coagulation factor (thrombin (fXIIa) or factor Xa (fXa)), it has been suggested that their efficacy could be reduced in the presence of strong activation of the CA pathway as compared to anticoagulants that target multiple, more upstream located coagulation factors. Purpose To compare the efficacy of a DOAC (apixaban) and heparin to suppress thrombin generation in the presence of strong CA pathway activation. Methods Pooled platelet-poor plasma was spiked with either apixaban (dissolved in DMSO and PBS) or unfractionated heparin to achieve therapeutic plasma levels. SynthASil, a commercially available mixture of phospholipids and silica, was used to stimulate the CA pathway in two different dilutions (1–80 and 5–80). Downstream coagulation was accessed by Thrombin Generation Test using Thrombinoscope by Stago and associated Thrombin Calibrator (activity 640 nM). The endogenous thrombin potential (area under the thrombin generation curve; ETP), peak thrombin generation (PTG), time to peak (ttPeak) and time to start (ttStart) were accessed. Results With decreasing concentrations of apixaban, stimulation with the lower dose SynthASil reveals an increasing ETP and PTG. As expected, ttPeak and ttStart decreased. Even supratherapeutic levels of apixaban (i.e. 1120 ng/mL) could not inhibit thrombin from being generated, in striking contrast with UFH where no thrombin was formed. Using a five times higher dose of SynthASil showed comparable ETP for all concentrations of apixaban, allocated around the control value. PTG, however, slightly increased with decreasing concentrations of apixaban. ttPeak and ttStart slightly decreased. Except for the subtherapeutic UFH concentration of 0,114 IU/mL, no thrombin was generated with UFH. Conclusion UFH is more effective in inhibiting downstream thrombin generation compared to apixaban as a response to activation of the CA pathway in vitro. These findings could help explain why direct inhibitors were not able to show non-inferiority in patients with mechanical heart valves and support the development of specific CA pathway inhibitors for patients with conditions that activate the CA pathway. Thrombin generation curves Funding Acknowledgement Type of funding source: None

Influence of Direct Oral Anticoagulants on Anti–Factor Xa Measurements Utilized for Monitoring Heparin

2017 ◽  
Vol 52 (2) ◽  
pp. 154-159 ◽  
Author(s):  
Kelly A. Macedo ◽  
Peter Tatarian ◽  
Kenneth R. Eugenio
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa

scholarly journals Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Alok Dabi ◽  
Aristides P. Koutrouvelis
Keyword(s):  
Side Effects ◽  
Intracranial Hemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Reversal Agents ◽  
United States Food ◽  
Life Threatening

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

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