Warfarin administration and monitoring
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The optimal dose of warfarin among patients on chronic anticoagulation represents a balance between the highest thrombosis prevention and the lowest risk of bleeding. In order to optimize the efficacy to safety ratio, dosing of warfarin requires INR monitoring with a target INR range of 2-3. The quality of management of a group of patients is measured with the time in therapeutic range.[1]
The 2012 American College of Chest Physicians (ACCP) clinical practice guidelines "suggest using validated decision support tools (paper nomograms or computerized dosing programs) rather than no decision support (Grade 2C)."[2] Current recommendations on chronic warfarin management are mainly based on the RE-LY trial[3] which was published in 2009 with modifications due to subsequent practice guidelines by the American College of Chest Physicians in 2012.[2] Randomized controlled trials suggest that non-pharmacist led clinics can achieved good anticoagulation.[4]
Adjustment of Warfarin Dose According to INR
| INR Value | Response per RE-LY[3] | Alternative by ACCP[2] |
|---|---|---|
| ≤ 1.5 | ↑ weekly dose by 15% Repeat INR in 7-10 days. |
Patients with stable INRs at baseline, now with a single subtherapeutic INR value: no routine bridging with heparin |
| 1.51-1.99 | If unexplained, ↑ weekly dose by 10% Repeat INR in 7-10 days. |
Patients with stable INRs at baseline, now with a single out-of-range INR of < 0.5 below or above therapeutic: no change and retest 1-2 weeks |
| 2-3 | No dose adjustment* | |
| 3.01 - 4 | "Do not hold warfarin. If high on 2 consecutive occasions, decrease weekly dose by 10%" | Patients with stable INRs at baseline, now with a single out-of-range INR of < 0.5 below or above therapeutic: no change and retest 1-2 weeks |
| 4.01 - 4.99 | Hold dose for 1 day, then ↓ weekly dose by 10% Repeat INR in 7-10 days. |
Patients with INRs 4.5 - 10 and with no evidence of bleeding: ACCP suggests against the routine use of vitamin K |
| 5 - 8.99 | Hold dose until INR therapeutic, then ↓ weekly dose by 15% Repeat INR in 1 day. | |
| ≥ 9.0 | Hold warfarin and give vitamin K 5.0-10mg PO. Monitor more frequently and repeat vitamin K if necessary | Patients with INRs > 10.0 with no evidence of bleeding: ACCP suggests that oral vitamin K be administered |
| * Per ACCP, "For patients taking VKA therapy with consistently stable INRs, we suggest an INR testing frequency of up to 12 weeks rather than every 4 weeks". One definition of consistent stability is 6 months.[5] | ||
Based on the existing medical research and clinical practice guidelines, institutions have algorithms to standardize the chronic administration of warfarin. Examples are:
- Warfarin by Wichita is a harmonization of the RE-LY and ACCP recommendations
Monitoring
Time in therapeutic range
Time in therapeutic range...
Expected values in various settings are:
- Dedicated anticoagulation clinic
- Primary care
Point of care testing
According to a systematic review, of randomized controlled trials, that compared varioius methods of management to traditional venipuncture with decisions by a health care provider[6]:
- Traditional venipuncture: time in therapeutic range (TTR): 64%
- Patients self-testing and self-management: 4.2% increase in TTR
- Patients self-testing but management by a health care provider: 7.2% increase in TTR
- Point of care testing and management in health care practitioners' offices: 6.1% increase in TTR
Pill selection
Recommendations exist for consistent use of one pill size by anticoagulation clinics.[7] The importance of choice of pill size is not clear.[8][9]
Concomitant vitamin K to reduce erratic control
Daily oral vitamin K may improve control in some patients.[10]
Management of Warfarin Related Bleeding
The management of bleeding among patients on warfarin includes:[2]
- Rapid reversal of anticoagulation with the administration of four-factor prothrombin complex concentrate (PCC), PLUS
- Slow IV injection of 5 to 10 mg vitamin K
References
- ↑ Rosendaal FR, Cannegieter SC, van der Meer FJ, Briët E (1993). "A method to determine the optimal intensity of oral anticoagulant therapy". Thromb Haemost. 69 (3): 236–9. PMID 8470047.
- ↑ 2.0 2.1 2.2 2.3 Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ; et al. (2012). "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. 141 (2 Suppl): e152S–84S. doi:10.1378/chest.11-2295. PMC 3278055. PMID 22315259.
- ↑ 3.0 3.1 Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A; et al. (2009). "Dabigatran versus warfarin in patients with atrial fibrillation". N Engl J Med. 361 (12): 1139–51. doi:10.1056/NEJMoa0905561. PMID 19717844. Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2
- ↑ Entezari-Maleki T, Dousti S, Hamishehkar H, Gholami K (2016). "A systematic review on comparing 2 common models for management of warfarin therapy; pharmacist-led service versus usual medical care". J Clin Pharmacol. 56 (1): 24–38. doi:10.1002/jcph.576. PMID 26100092.
- ↑ Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M (2011). "Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial". Ann Intern Med. 155 (10): 653–9, W201–3. doi:10.7326/0003-4819-155-10-201111150-00003. PMID 22084331. Review in: Ann Intern Med. 2012 Mar 20;156(6):JC3-3
- ↑ Health Quality Ontario (2009). "Point-of-Care International Normalized Ratio (INR) Monitoring Devices for Patients on Long-term Oral Anticoagulation Therapy: An Evidence-Based Analysis". Ont Health Technol Assess Ser. 9 (12): 1–114. PMC 3377545. PMID 23074516.
- ↑ Ebell MH (2005). "Evidence-based adjustment of warfarin (Coumadin) doses". Am Fam Physician. 71 (10): 1979–82. PMID 15926414.
- ↑ Wong W, Wilson Norton J, Wittkowsky AK (1999). "Influence of warfarin regimen type on clinical and monitoring outcomes in stable patients in an anticoagulation management services". Pharmacotherapy. 19 (12): 1385–91. PMID 10600087.
- ↑ Manning DM (2002). "Toward safer warfarin therapy: does precise daily dosing improve international normalized ratio control?". Mayo Clin Proc. 77 (8): 873–5. doi:10.4065/77.8.873-a. PMID 12173723.
- ↑ Boonyawat K, Wang L, Lazo-Langner A, Kovacs MJ, Yeo E, Schnurr T; et al. (2016). "The effect of low-dose oral vitamin K supplementation on INR stability in patients receiving warfarin. A randomised trial". Thromb Haemost. 116 (3). doi:10.1160/TH16-04-0320. PMID 27346552.