Laboratory Monitoring of Direct Oral Anticoagulants (DOACs)
Abstract
:1. Introduction
2. DOAC Pharmacokinetics and Pharmacodynamics
2.1. Dabigatran
2.2. Rivaroxaban
2.3. Apixaban
2.4. Edoxaban
2.5. Betrixaban
3. DOAC Inter-Patient Variability
3.1. Management of Patients under DOAC Therapy
3.2. Management of Patients under Multi-Drug Therapy
3.3. Pre-Operative Management of Patients under DOAC Therapy
4. DOAC Laboratory Testing
4.1. Liquid Chromatography–Mass Spectrometry (LC-MS/MS)
4.2. Routine Coagulation Screening Assays
4.2.1. Direct Thrombin Inhibitors (DTIs)
4.2.2. Direct Factor Xa Inhibitors (DiXaIs)
4.3. Quantitative Routine Assays
4.3.1. Direct Thrombin Inhibitors (DTIs)
4.3.2. Direct factor Xa Inhibitors (DiXaIs)
5. Conclusions
Funding
Data Availability Statement
Conflicts of Interest
References
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Dabigatran | Rivaroxaban | Apixaban | Edoxaban | Betrixaban | |
---|---|---|---|---|---|
Action | Anti-IIa | Anti-Xa | Anti-Xa | Anti-Xa | Anti-Xa |
Frequency of intake | Twice daily | Once daily | Twice daily | Once daily | Once daily |
Tmax (h) | 1.5–3 | 2–4 | 3–4 | 1–2 | 3–4 |
Ttrough (h) | 12 | 24 | 12 | 24 | 24 |
Half-life (h) | 12–14 | 5–9 | 10–14 | 9–11 | 35–45 |
Bioavailability | 3–7% | 80–100% | 50% | 62% | 34% |
Protein binding | 35% | 92–95% | 87% | 40–59% | 60% |
Renal clearance (%) | 80% | 40% | 27% | 50% | 6–13% |
Dabigatran a | Rivaroxaban b | Apixaban c,d | Edoxaban e | Betrixaban f | ||
---|---|---|---|---|---|---|
Frequency of intake | Twice daily | Once daily | Twice daily | Twice daily | Once daily | Once daily |
Dose | 150 mg | 20 mg | 5 mg | 10 mg | 60 mg | 80 mg |
Cmax (ng/mL) | 175 (117–275) | 249 (184–343) | 171 (91–321) | 251 (111–572) | 170 (125–245) | 46 (5–117) |
Ctrough (ng/mL) | 91 (61–143) | 44 (12–137) | 103 (41–230) | 120 (41–335) | 36 (19–62) | 17 (16–22) |
Dabigatran | Rivaroxaban | Apixaban | Edoxaban | |
---|---|---|---|---|
AF dosage | 150 mg twice daily | 20 mg once daily | 5 mg twice daily | 60 mg once daily |
Criteria for adjustment | CrCL 30–50 mL/min No recommendation: CrCL < 30 mL/min or HD | CrCL 15–50 mL/min No recommendation: CrCL < 15 mL/min or HD | 2 of 3 required: body weight ≤ 60 kg age ≥ 80 years SCr ≥ 1.5 mg/dL | CrCL 15–50 mL/min Avoid use if: CrCL < 15 mL/min CrCL > 95 mL/min No recommendation for HD |
Dose adjustment | 110 mg twice daily | 15 mg once daily | 2.5 mg twice daily | 30 mg once daily |
VTE treatment Recurrent VTE VTE prophylaxis | 150 mg twice daily 150 mg twice daily 150 mg twice daily | 15 mg (21 days) then 20 mg once daily 10 or 20 mg once daily 10 mg once daily | 10 mg (7 days) then 5 mg twice daily 2.5 mg twice daily 2.5 mg twice daily | 60 mg once daily |
Criteria for adjustment | CrCL 30–50 mL/min No recommendation: CrCL < 30 mL/min | Avoid use if: CrCL < 30 mL/min or HD | No recommendation: CrCL < 25 mL/min | CrCL: 15–50 mL/min or body weight ≤ 60 kg Avoid use if: CrCL < 15 mL/min |
Dose adjustment | 110 mg twice daily | 30 mg once daily |
Dabigatran | Rivaroxaban | Apixaban | Edoxaban | Betrixaban | |
---|---|---|---|---|---|
Drug interaction (inhibitors) | P-gp | Strong CYP3A4+P-gp | Strong CYP3A4+P-gp | P-gp | P-gp |
Plasma concentration | ↑ | ↑ | ↑ | ↑ | ↑ |
Dose adjustment | Reduce or avoid | Avoid | Reduce or avoid | Reduce (VTE) | Avoid: CrCL < 30 mL/min |
Drug interaction (inducers) | P-gp | Strong CYP3A4 or P-gp | Strong CYP3A4 or P-gp | P-gp | P-gp |
Plasma concentration | ↓ | ↓ | ↓ | ↓ | ↓ |
Dose adjustment | Avoid | Avoid | Avoid | Avoid with Rifampin | No recommendation |
Dabigatran | Rivaroxaban | Apixaban | Edoxaban | Betrixaban | |
---|---|---|---|---|---|
PT/INR a,b | ↑ at Cmax | ↑ | Slight or no change | ↑ | ↑ |
APTT a,b | ↑ | ↑at Cmax | Slight or no change | ↑ at Cmax | ↑ at Cmax |
TT | ↑at Cthrough | No change | No change | No change | No change |
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Dunois, C. Laboratory Monitoring of Direct Oral Anticoagulants (DOACs). Biomedicines 2021, 9, 445. https://doi.org/10.3390/biomedicines9050445
Dunois C. Laboratory Monitoring of Direct Oral Anticoagulants (DOACs). Biomedicines. 2021; 9(5):445. https://doi.org/10.3390/biomedicines9050445
Chicago/Turabian StyleDunois, Claire. 2021. "Laboratory Monitoring of Direct Oral Anticoagulants (DOACs)" Biomedicines 9, no. 5: 445. https://doi.org/10.3390/biomedicines9050445