Initiation
Give warfarin on day one of heparin or enoxaparin for long-term anticoagulation. Titrate as follows:
|
Day |
INR |
Dosage |
|---|---|---|
|
1 |
5mg (In patients who are elderly, heart failure, kidney disease, liver disease, dose reduce to 2.5mg) If BMI >40, increase dose of 7.5mg |
|
|
2 |
<1.5 |
Continue dose |
|
≥1.5 |
Decrease or hold dose* |
|
|
3 |
≤1.2 |
Increase dose* |
|
>1.2 and <1.7 |
Continue dose* |
|
|
≥1.7 |
Decrease dose* |
|
|
4 (or until therapeutic) |
Daily increase is <0.2 units |
Increase dose* |
|
Daily increase is 0.2-0.3 units |
Continue dose* |
|
|
Daily increase is 0.4-0.6 units |
Decrease dose* |
|
|
Daily increase is ≥0.7 units |
Hold dose |
*In general, with increased dosage do not exceed 2.5 mg or 50% of the previous daily dose
UCSF Comprehensive Hemostasis and Antithrombotic Service 2011.
- Dosing
- Increase in the INR of >0.3-0.4 units per day should result in a dose reduction (otherwise an INR overshoot is likely).
- Goal INR: 2-3 or 2.5-3.5 for mechanical mitral valves or recurrent systemic thromboembolism.
- Information about the patient's past warfarin dosing history will help you titrate appropriately. Congestive heart failure, liver disease, vitamin K deficiency and certain medications influence warfarin response.
- Considerations:
- Patients with cancer: LMWH is superior to warfarin in this population. Rivaroxaban and apixaban are now alternative agents for patients with non-GI cancers who have VTE.
- Anti-phospholipid syndrome: warfarin is superior to DOACs.
- Valvular atrial fibrillation: warfarin likely superior to DOACs.
Reversal
Supratherapeutic INR without bleeding—hold warfarin and proceed as follows:
|
INR |
Reversal Steps |
|---|---|
|
Above therapeutic, <4.5 |
When INR falls to within therapeutic range, resume warfarin at lower dose |
|
4.5-10 |
Do NOT use vitamin K unless particularly high bleed risk May consider 2.5 to 5 mg vitamin K PO x1 to reduce INR Check INR in 24-48 hours Resume warfarin when INR within therapeutic range |
|
>10 |
Give 2.5 to 5 mg vitamin K PO x1 or IV (may repeat in 24 hours if INR not reduced) Check INR in 24 hours |
UCSF Comprehensive Hemostasis and Antithrombotic Service 2013.
Emergent reversal of warfarin-associated intracranial hemorrhage or life threatening hemorrhage:
- Discontinue warfarin and order INR STAT.
- Assess for contraindications to 4-factor PCC (prothrombin compelx concentrate, eg. Kcentra®): DIC, HIT, previous anaphylaxis to KCentra®.
- Calculate Kcentra® dose:
|
INR |
Kcentra Dose |
Maximum Dose |
|---|---|---|
|
1.5-3.9 |
25 units factor IX/kg |
2500 units factor IX |
|
4.0-6.0 |
35 units factor IX/kg |
3500 units factor IX |
|
>6 |
50 units factor IX/kg |
5000 units factor IX |
|
Unknown INR |
25 units factor IX/kg |
2500 units factor IX |
UCSF Comprehensive Hemostasis and Antithrombotic Service 2013.
- Give vitamin K 10 mg IV (not to exceed 1 mg/min) after PCC infusion.
- Repeat INR 30 minutes after PCC infusion; if >1.5, consider administering 2 units FFP.
- Once INR <1.5, check INR Q4H x 24 hours; if >1.5, at 24 hours, give additional 10 mg vitamin K IV.
- If patient is on concurrent antiplatelet therapy, infuse platelets STAT (for ASA or dipyridamole, infuse one unit; for all others infuse 2 units).
Key Points
- Don’t administer plasma or prothrombin complex concentrates for non-emergent reversal of vitamin K antagonists (outside the setting of major bleeding, intracranial hemorrhage, or anticipated major surgery).
- In non-emergent settings, elevations are best addressed by holding the vitamin K antagonist and/or administering vitamin K.
Eikelboom JW, Connolly SJ, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. N Engl J Med. 2013;369(13):1206‐1214. doi:10.1056/NEJMoa1300615
Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(2 Suppl):e152S‐e184S. doi:10.1378/chest.11-2295
Hirsh J, Dalen J, Anderson DR, et al. Oral anticoagulants: mechanism of action, clinical effectiveness, and optimal therapeutic range. Chest 2001;119:8S-21S.
Lee AY, Levine MN, Baker RI, et al. Low-molecular weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 2003;349:146-153.
Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132(13):1365‐1371. doi:10.1182/blood-2018-04-848333
Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018;378(7):615‐624. doi:10.1056/NEJMoa171194