Table 5.
Comparison of anticoagulants. APPC: activated prothrombin complex concentrate; CYP3A4: cytochrome P450 enzyme 3A4; FFP: fresh frozen plasma; HIT: heparin-induced thrombocytopenia; Iv: intravenous; IU: international units; LMWH: low-molecular-weight heparins; PCC: prothrombin complex concentrate; P-gp: P-glycoprotein; rFVIIa: recombinant activated factor VII; Sc: subcutaneous; UFH: unfractioned heparins; *all should be used with caution with other anticoagulants, nonsteroid anti-inflammatory drugs, thrombolytics, or platelet inhibitors because of an increased risk of bleeding. ** Time to reach peak plasma concentrations and half-life elimination may be delayed after surgery; from [196–204].
| Parameter | Dabigatran | Rivaroxaban | LMWH | UFH | Warfarin | |
|---|---|---|---|---|---|---|
| Enoxaparin | Dalteparin | |||||
| Routine coagulation monitoring required | No | No | No | Al inicio | Yes | |
| Use with renal insufficiency | Moderate: dosage adjustment (150 mg daily) | Moderate: use caution | Moderate: use caution | Moderate: yes | Moderate: use caution | |
| Severe: contraindicated | Severe: not recommended | Severe: dosage adjustment | Severe: use caution | Severe: use caution | ||
| Use with hepatic insufficiency | Not recommended | Contraindicated | Use caution | Use caution | Use caution | |
| Potential for HIT | No | No | Low | High | No | |
| Drug interactions* | Quinidine, amiodarone, antacids, potent P-gp inhibitors (e.g., verapamil, clarithromycin) | Potent inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, rifampicin). Strong CYP3A4 inducers (e.g., phenytoin, carbamazepine) |
No clinically significant drug interactions known |
No clinically significant drug interactions known | Multiple drugs | |
| Reversal of anticoagulant effect | rFVIIa, APCC (in rats) [35] | rFVIIa, APCC (in rats and primates) [36, 37] | Protamine sulfate (partial) | Protamine sulfate | Vitamin K, FFP, PPC | |
| Target | Factor Iia (thrombin) direct | Factor Xa direct | Factor Xa and IIa (thrombin) indirect | Antithrombin III | Vitamin K epoxide reductase | |
| Route | Oral | Oral | Sc | Iv or Sc | Oral | |
| Peak plasma levels (healthy volunteers)** | 0.5 to 2 hours. After surgery: 7 to 9 hours | 2 to 4 hours | 3 to 5 hours | 4 hours | 1 to 3 hours | 4 hours |
| Therapeutic effect in 5 to 7 days | ||||||
| Half-life elimination∗∗ | 11 | 5 to 9 | 4 to 7 | 3 to 4 | 1 to 2 | 20 to 60 |
| after surgery: 14 to 17 | after surgery: 7 to 11 | |||||
| Dosing for thromboprophylaxis after orthopedic surgery | Initial: 110 mg | Initial: 10 mg | 30 mg twice daily | 5,000 IU daily | 5,000 units every 8 to 12 hours | Individualized once daily based on target INR 2.5 |
| Maintenance: 220 mg once daily | Maintenance:10 mg once daily | |||||