Three questions come up again and again on call: which dose, how long to interrupt treatment before a procedure, and how to reverse in bleeding.
Doses in atrial fibrillation
| Drug | Standard dose | Reduced dose and criterion |
|---|---|---|
| Apixaban | 5 mg twice daily | 2.5 mg twice daily if at least two of: age ≥80 years, weight ≤60 kg, creatinine ≥133 µmol/L |
| Rivaroxaban | 20 mg once daily with food | 15 mg once daily at eGFR 15-49 mL/min |
| Edoxaban | 60 mg once daily | 30 mg once daily at eGFR 15-50 mL/min, weight ≤60 kg or concomitant P-gp inhibitor |
| Dabigatran | 150 mg twice daily | 110 mg twice daily if age ≥80 years, concomitant verapamil or increased bleeding risk |
| Warfarin | Individual, target INR 2.0-3.0 | A mechanical valve may require a higher target |
Doses in venous thromboembolism
Treatment doses in deep vein thrombosis and pulmonary embolism differ from the atrial fibrillation doses and include an initial high-dose phase. Follow FASS (the Swedish medicines compendium) and the local protocol. See the pulmonary embolism quick reference for risk stratification.
Renal function
| eGFR (mL/min) | Management |
|---|---|
| >50 | Standard dose, creatinine checked at least annually |
| 30-50 | Dose reduction as in the table above for rivaroxaban and edoxaban. Check every 6 months |
| 15-30 | Dabigatran contraindicated. The other DOACs are possible according to FASS, but the documentation is insufficient; check more frequently. Warfarin is often preferable |
| <15 or dialysis | DOACs are not recommended. Warfarin after individual assessment |
Rule of thumb for the monitoring interval: eGFR divided by 10 gives the number of months until the next check.
Interruption before an elective procedure
The duration of interruption is governed by the bleeding risk of the procedure and by renal function. In markedly reduced renal function (dabigatran at eGFR <30 mL/min, the other DOACs at eGFR <15 mL/min) at least 96 hours should have elapsed since the last dose before an invasive procedure. Exact intervals according to the local protocol or the on-call coagulation service. Bridging with low-molecular-weight heparin is rarely needed with DOACs.
Reversal in major bleeding
| Drug | Reversal |
|---|---|
| Warfarin | Prothrombin complex concentrate (dose by INR and weight) plus vitamin K 10 mg IV |
| Dabigatran | Idarucizumab (Praxbind) |
| Apixaban, rivaroxaban, edoxaban | Prothrombin complex concentrate, consider within 15 hours of the last dose. Andexanet alfa where available |
| Low-molecular-weight heparin | Protamine has only a partial effect |
| Unfractionated heparin | Protamine |
| Antiplatelet agents | Platelet transfusion has weak evidence; discuss with the on-call coagulation service |
Always in parallel: mechanical control of bleeding, tranexamic acid where it is not contraindicated, and contact with the on-call coagulation service. Send samples for INR, APTT, platelet count, fibrinogen and creatinine. With DOACs, drug concentration measurement is available at some laboratories.
Red flags and pitfalls
- Failing to ask when the last dose was taken. It matters more than the laboratory value.
- A normal INR and a normal APTT do not exclude DOAC effect.
- Duplicate therapy. Check that the patient is not simultaneously on a DOAC, low-molecular-weight heparin and an antiplatelet agent without an indication.
- Interactions: strong P-gp or CYP3A4 inhibitors and inducers (azole antifungals, HIV protease inhibitors, rifampicin, carbamazepine, St John's wort) alter DOAC exposure substantially.
- Thrombolysis in stroke has its own thresholds in the patient on anticoagulants; see the acute stroke quick reference.
- Stopping the drug and forgetting to restart it after the procedure. Document the restart date in the medical record.
Sources
- ESC Guidelines for the management of atrial fibrillation.
- Internetmedicin, DOACs, measures in bleeding and medical procedures.
- Svenska Sällskapet för Trombos och Hemostas (SSTH, the Swedish Society for Thrombosis and Haemostasis), clinical advice.
