14. Direct Oral Anticoagulants (DOACs)

Can be substituted for warfarin in many instances and do not require bridging prior to becoming therapeutic unless oral intake is precluded (discuss with pharmacy).
NOT approved in the setting of mechanical heart valves—per RE-ALIGN, rates of bleeding and thromboembolism are higher with dabigatran than warfarin.
Do NOT use in patients with antiphospholipid syndrome (less effective than warfarin).
Generally contraindicated in patients with end-stage renal disease.
Rivaroxaban and apixaban now often used in patients with non-GI cancers.
Check with pharmacy about possible drug interactions.

Indication	Renal Function (CrCl mL/min)	Recommended Dose	Transition from parenteral	Reversal
Non-valvular atrial fibrillation	>30	150 mg po twice daily	Start DOAC at least 2 hours before turning off drip OR two hours before next dose	Dialysis Idarucizumab If no contraindication to prothrombin complex concentrates, administer activated PCC (FEIBA)
	15-30	75 mg po twice daily
	<15 or dialysis	Avoid use
Treatment of DVT/PE	>30	150 mg po twice daily after 5-10 days of parenteral therapy with UFH/LMWH
	<30 or dialysis	Avoid use

Indication	Renal Function (CrCl mL/min)	Recommended Dose	Transition from parenteral	Reversal
Non-valvular atrial fibrillation	>30	20 mg po daily with evening meal	Start DOAC within 2 hours prior to next dose of LMWH or immediately after stopping heparin gtt	Not amenable to dialysis Andexanet alfa for life-threatening bleed If Andexanet alfa not available, administer 4-factor PCC (off-label)
	15-30	15 mg po once daily with evening meal
	<15	Avoid use
Treatment of DVT/PE	≥30	15 mg twice daily with food for 21 days, then 20 mg once daily with food
	<30	Avoid use
Knee replacement	≥30	10 mg once daily for 12-14 days
	<30	Avoid use
Hip replacement	≥30	10 mg once daily for 35 days
	<30	Avoid use

Indication	Recommended Dose	Dose Adjustments	Transition from parenteral	Reversal
Non-valvular atrial fibrillation	5 mg twice daily	2.5 mg twice daily if any 2 of the following: Age ≥ 80 years Body weight ≤ 60 kg Serum creatinine ≥ 1.5 mg/dL	Start DOAC at the time of next scheduled dose of LMWH or immediately after stopping heparin gtt	Not amenable to dialysis Andexanet alfa for life-threatening bleed If Andexanet alfa not available, administer 4-factor PCC (off-label)
Treatment DVT/PE	10 mg twice daily x 7 days followed by 5 mg twice daily
Prophylaxis after TKA/THA	2.5 mg twice daily	TKA 12 days, THA 35 days

Indication

Recommended Dose

Dose Adjustments

Transition from parenteral

Reversal

Non-valvular atrial fibrillation

5 mg twice daily

2.5 mg twice daily if any 2 of the following:

Start DOAC at the time of next scheduled dose of LMWH or immediately after stopping heparin gtt

Not amenable to dialysis

Andexanet alfa for life-threatening bleed

If Andexanet alfa not available, administer 4-factor PCC (off-label)

Treatment DVT/PE

10 mg twice daily x 7 days followed by 5 mg twice daily

Prophylaxis after TKA/THA

2.5 mg twice daily

TKA 12 days, THA 35 days

Discontinue drug. DOACs have relatively short half-lives (generally 8-17 hours).
If <2 hours since administration/ingestion, administer activated charcoal.
If dabigatran, and dialysis access is feasible, consider hemodialysis.
If patient is on concurrent antiplatelet therapy, consider STAT platelet transfusion (one unit for aspirin or dipyridamole, two units for more potent agents).
FFP and/or cryoprecipitate are NOT recommended due to unclear efficacy and large volume.
Contraindications to PCCs include DIC and HIT. PCCs raise thrombotic risk and should be used with caution if history of VTE in past 6 weeks. Consider their use only when other measures fail.

UCSF guidelines for the reversal of major bleeding to TSOACs in adults, UCSF Comprehensive Hemostasis and Antithrombotic Service 2013.

Eikelboom JW et al. Dabigatran vs warfarin in patients with mechanical heart valves. N Engl J Med 2013; 369:1206-1214

Hospital Handbook