Pharmacokinetics of direct oral anticoagulants in emergency situations - Results of the prospective observational RADOA-registry.

Abstract

Background Direct oral anticoagulants (DOAC) 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 back-up blood samples from routine care DOAC drug concentrations were measured using UPLC-MS/MS. Anticoagulant intensity at first presentation and drug half-life (t1/2), tested in repeat samples, were evaluated. Results 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. 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 t½ was 17.3 hours (95% CI: 15.4 - 19.7) without significant difference in both groups (major bleeding: t½ 16.7 hours, 95% CI: 14.7 - 19.3; urgent surgery: t½ 19.7 hours, 95% CI 15.2 - 27.9; p=0.292). In apixaban treated patients t½ was 25.0 hours (95% CI: 22.9 - 27.6) with a longer t½ after urgent surgery (t1/2: 30.8 hours; 95% CI: 26.9 - 36.4) compared to severe bleeding (t1/2: 20.8 hours; 95% CI: 18.8 - 23.2; p<0.001). Conclusions 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 t½.