Anticoagulant Effect of Sugammadex: Just an In Vitro Artifact

Anesthesiology. 2016 Jun;124(6):1277-85. doi: 10.1097/ALN.0000000000001076.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adult
  • Anticoagulants / pharmacology*
  • Artifacts*
  • Blood Coagulation Tests / statistics & numerical data
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Reference Values
  • Sugammadex
  • gamma-Cyclodextrins / pharmacology*

Substances

  • Anticoagulants
  • gamma-Cyclodextrins
  • Sugammadex