Pharmacokinetics of Direct Oral Anticoagulants in Emergency Situations: Results of the Prospective Observational RADOA-Registry

• Published in: Thrombosis and haemostasis Vol. 122; no. 4; pp. 552 - 559
• Main Authors: Lindhoff-Last, Edelgard, Birschmann, Ingvild, Kuhn, Joachim, Lindau, Simone, Konstantinides, Stavros, Grottke, Oliver, Nowak-Göttl, Ulrike, Lucks, Jessica, Zydek, Barbara, von Heymann, Christian, Sümnig, Ariane, Beyer-Westendorf, Jan, Schellong, Sebastian, Meybohm, Patrick, Greinacher, Andreas, Herrmann, Eva
• Format: Journal Article
• Language: English
• Published: Rüdigerstraße 14, 70469 Stuttgart, Germany Georg Thieme Verlag KG 01.04.2022
• Subjects: Administration, Oral; Anticoagulants - therapeutic use; Atrial Fibrillation - drug therapy; Dabigatran - adverse effects; Hemorrhage - drug therapy; Humans; New Technologies, Diagnostic Tools and Drugs; Prospective Studies; Pyridones - therapeutic use; Registries; Rivaroxaban - adverse effects; pharmacokinetics; direct oral anticoagulants; emergency; major bleeding; urgent surgery
• DOI: 10.1055/a-1549-6556
• ISSN: 0340-6245

Abstract Background  Direct oral anticoagulants (DOACs) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. Methods  A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In samples collected as part of routine care DOAC drug concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. Anticoagulant intensity at first presentation and drug half-life ( t 1/2 ), tested in repeat samples, were evaluated. Results  A total of 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. Note that 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban-treated patients t ½ was 17.3 hours (95% confidence interval [CI]: 15.4–19.7) without significant difference in both groups (major bleeding: t ½ 16.7 hours, 95% CI: 14.7–19.3; urgent surgery: t ½ 19.7 hours, 95% CI: 15.2–27.9; p  = 0.292). In apixaban-treated patients t ½ was 25.0 hours (95% CI: 22.9–27.6) with a longer t ½ after urgent surgery ( t 1/2 : 30.8 hours; 95% CI: 26.9–36.4) compared with severe bleeding ( t 1/2 : 20.8 hours; 95% CI: 18.8–23.2; p  < 0.001). Conclusion  Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t ½ .