title: Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact.
abstract: Sugammadex prolongs activated partial thromboplastin time (aPTT) and prothrombin time (PT) suggestive of anticoagulant effects. To pinpoint its presumed anticoagulant site of action, the authors assessed Sugammadex's impact on a panel of coagulation assays.
  
  
  
  Sugammadex, Rocuronium, Sugammadex and Rocuronium combined, or saline were added to blood samples from healthy volunteers and analyzed using plasmatic (i.e., aPTT, thrombin time, and fibrinogen concentration) (n = 8 each), PT (quick), activities of plasmatic coagulation factors, and whole blood (extrinsically and intrinsically activated thromboelastometry) assays (n = 18 each). Furthermore, dose-dependent effects of Sugammadex were also assessed (n = 18 each) in diluted Russel viper venom time (DRVVT) assays with low (DRVVT1) and high (DRVVT2) phospholipid concentrations and in a highly phospholipid-sensitive aPTT assay.
  
  
  
  Sugammadex increased PT (+9.1%; P < 0.0001), aPTT (+13.1%; P = 0.0002), and clotting time in extrinsically (+33.1%; P = 0.0021) and intrinsically (+22.4%; P < 0.0001) activated thromboelastometric assays. Furthermore, activities of factors VIII, IX, XI, and XII decreased (-7%, P = 0.009; -7.8%, P < 0.0001; -6.9%, P < 0.0001; and -4.3%, P = 0.011, respectively). Sugammadex dose-dependently prolonged both DRVVT1 and the highly phospholipid-sensitive aPTT assays, but additional phospholipids in the DRVVT2 assay almost abolished these prolongations. Thrombin time, a thromboelastometric thrombin generation assay, clot firmness, clot lysis, fibrinogen concentration, and activities of other coagulation factors were unaltered. Rocuronium, Sugammadex and Rocuronium combined, and saline exerted no effects.
  
  
  
  Sugammadex significantly affects various coagulation assays, but this is explainable by an apparent phospholipid-binding effect, suggesting that Sugammadex`s anticoagulant effects are likely an in vitro artifact.
authors.affiliation: From the Klinik für Anästhesiologie und Intensivmedizin (D.D., M.W.B., H.P., J.W., K.G., J.P.) and Abteilung für Klinische Chemie (L.V.), Universität Duisburg-Essen and Universitätsklinikum Essen, Essen, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Dirkmann
authors.forename: Martin W
authors.initials: MW
authors.lastname: Britten
authors.forename: Henning
authors.initials: H
authors.lastname: Pauling
authors.forename: Juliane
authors.initials: J
authors.lastname: Weidle
authors.forename: Lothar
authors.initials: L
authors.lastname: Volbracht
authors.forename: Klaus
authors.initials: K
authors.lastname: Görlinger
authors.forename: Jürgen
authors.initials: J
authors.lastname: Peters
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D016477:Artifacts; D001780:Blood Coagulation Tests / Q000706:statistics & numerical data; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D012016:Reference Values; D000077122:Sugammadex; D047408:gamma-Cyclodextrins / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D047408:gamma-Cyclodextrins; D000077122:Sugammadex