Review Article

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications

Table 1

Properties of different direct oral anticoagulants (DOACs) [8, 1315].

DabigatranRivaroxabanApixabanEdoxabanBetrixaban

Mechanism of actionDirect thrombin inhibitorFactor Xa inhibitorFactor Xa inhibitorFactor Xa inhibitorFactor Xa inhibitor
Time to peak serum level1 hour, 2 hours with food2–4 hours3-4 hours1-2 hours3-4 hours
Elimination half-life (hours)12–17 (young), 14–17 h (in elderly)5–9 (young), 11–13 (in elderly)12 (8–15)10–1419–27
Elimination80% renal70% liver, 30% renal30% renal50% renal11% renal, 89% fecal
Bioavailability3%–7%66%–100% higher with food50%62%34%
Dose/frequency NVAF150 mg bid (110 mg bid, if age > 80 years)20 mg once daily5 mg bid60 mg once dailyNot licensed
VTE therapy and prophylaxis150 mg bid (after 5 d of LMWH)15 mg bid × 21 d, then 20 mg once daily10 mg bid × 7 d, then 5 mg bid60 mg bid (after 5 d of LMWH)160 mg on day 1, then 80 mg daily
VTE prophylaxis post elective hip/knee surgery150 mg once daily10 mg once daily2.5 mg bidNot licensedNot licensed
P-gp resecretionYesYesYesYesYes
CYP3A4 metabolismNoYesYesMinimalNo
Follow-up monitoringRenal function, CBC periodically, at least annuallyRenal function, CBC periodically, at least annually; hepatic functionRenal function, CBC periodically, at least annuallyRenal function, CBC periodically, at least annuallyRenal function, CBC periodically, at least annually
Quantitative assayDilute thrombin time (dTT), ecarin clotting time (ECT)Specific, calibrated anti-FXa assaysSpecific, calibrated anti-FXa assaysSpecific, calibrated anti-FXa assaysSpecific, calibrated anti-FXa assays

Anti-FXa assay = anti-factor Xa assay, bid = twice daily, CBC = complete blood count, CYP3A4 = cytochrome P450 3A4, d = day, DOACs = direct oral anticoagulants, FXa = factor Xa, INR = international normalized ratio, LMWH = low-molecular weight heparin, mg = milligram, NVAF = nonvalvular atrial fibrillation, P-gp = P-glycoprotein, PTT = partial thromboplastin time, and VTE = venous thromboembolism.