title: An update on laboratory measurements of Dabigatran: Smart specific and calibrated dedicated assays for measuring anti-IIa activity in plasma.
abstract: Use of Direct Oral Anticoagulants (DOACs) is continuously increasing for clinical application. The first product released was Dabigatran, which was proposed for many preventive and curative applications, especially for prevention of stroke in patients with non-valvular atrial fibrillation. Although measurement of Dabigatran Anti-IIa activity in plasma is not requested on a routine basis, in some situations its measurement is clinically useful. Especially, before an emergency surgery in treated patients, where its presence at high concentrations, which will expose the patient at an increased bleeding risk, has to be excluded. Hence, smart, specific, rapid and accurate quantitative assays are warranted as an essential required. Hemoclot™ Thrombin Inhibitors and Biophen® DTI were specifically designed for these applications, and can be used on all automated instruments with a standard range protocol for measuring concentrations at peak, or with a low range protocol for testing residual concentrations. Both functional assays have a good correlation with the reference LC-MS/MS method, and concentrations measured are similar. Performances of these assays and interferences of various substances or drugs are discussed. Some differences in variations of clotting times are observed between mechanical or optical clot detection instruments, which could be explained by the fibrin clot structure, altered by direct Factor Xa inhibitors, and more especially Rivaroxaban. Both clotting and chromogenic assays offer a safe and accurate quantitative measurement of Dabigatran in plasma in all situations where this determination is requested. In short this manuscript provides an in depth update on current opinions on laboratory aspects of measuring Dabigatran concentrations in plasma, when required.
authors.affiliation: Hyphen BioMed, Neuville sur Oise, Paris, France. Electronic address: jamiral@hyphen-biomed.com.
authors.forename: Jean
authors.initials: J
authors.lastname: Amiral
authors.affiliation: Hyphen BioMed, Neuville sur Oise, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dunois
authors.affiliation: Research and Development, Hyphen BioMed, Neuville sur Oise, Paris, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Amiral
authors.affiliation: International Consultancy in Blood Components Quality/Safety Improvement, Audit/Inspection and DDR Strategies, London, UK. Electronic address: jseghatchian@btopenworld.com.
authors.forename: Jerard
authors.initials: J
authors.lastname: Seghatchian
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069604:Dabigatran / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans
chemical_list: D000925:Anticoagulants; D000069604:Dabigatran
keywords: Bleeding risk; Chromogenic anti-IIa assay; Dabigatran; Diluted thrombin time; Patient management