Warfarin administration and monitoring: Difference between revisions

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==Overview==
==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 [[IN]]R monitoring with a target [[INR]] range of 2-3.  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)."<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>  Current recommendations on chronic warfarin management are mainly based on the RE-LY trial<ref name="pmid19717844">{{cite journal| author=Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al.| title=Dabigatran versus warfarin in patients with atrial fibrillation. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 12 | pages= 1139-51 | pmid=19717844 | doi=10.1056/NEJMoa0905561 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19717844  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083817 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2] </ref> which was published in 2009 with modifications due to subsequent practice guidelines by the [[American College of Chest Physicians]] in 2012.<ref name="pmid22315259"/>
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 [[IN]]R monitoring with a target [[INR]] range of 2-3.  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)."<ref name="pmid22315259">{{cite journal| author=Holbrook A, Schulman S, Witt DM, Vandvik PO, Fish J, Kovacs MJ et al.| title=Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. | journal=Chest | year= 2012 | volume= 141 | issue= 2 Suppl | pages= e152S-84S | pmid=22315259 | doi=10.1378/chest.11-2295 | pmc=PMC3278055 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22315259  }} </ref>  Current recommendations on chronic warfarin management are mainly based on the RE-LY trial<ref name="pmid19717844">{{cite journal| author=Connolly SJ, Ezekowitz MD, Yusuf S, Eikelboom J, Oldgren J, Parekh A et al.| title=Dabigatran versus warfarin in patients with atrial fibrillation. | journal=N Engl J Med | year= 2009 | volume= 361 | issue= 12 | pages= 1139-51 | pmid=19717844 | doi=10.1056/NEJMoa0905561 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19717844  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20083817 Review in: Ann Intern Med. 2010 Jan 19;152(2):JC1-2] </ref> which was published in 2009 with modifications due to subsequent practice guidelines by the [[American College of Chest Physicians]] in 2012.<ref name="pmid22315259" />


==Adjustment of Warfarin Dose According to INR==
==Adjustment of Warfarin Dose According to INR==
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{| class="wikitable"
{| class="wikitable"
! INR Value
! INR Value
! Response per RE-LY<ref name="pmid19717844"/>
! Response per RE-LY<ref name="pmid19717844" />
! Alternative by ACCP<ref name="pmid22315259"/>
! Alternative by ACCP<ref name="pmid22315259" />
|-
|-
| ≤ 1.5
| ≤ 1.5
| ↑ weekly dose by 15%<br/>Repeat INR in 7-10 days.
| ↑ weekly dose by 15%<br />Repeat INR in 7-10 days.
| Patients with stable INRs at baseline, now with a single subtherapeutic INR value: no routine bridging with heparin
| Patients with stable INRs at baseline, now with a single subtherapeutic INR value: no routine bridging with heparin
|-
|-
| 1.51-1.99
| 1.51-1.99
| ≤1.5: ↑ weekly dose by 10%<br/>Repeat INR in 7-10 days.
| ≤1.5: ↑ weekly dose by 10%<br />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
| 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
|-
|-
Line 25: Line 25:
|-
|-
| 3.01 - 4
| 3.01 - 4
| weekly dose by 10%<br/>Repeat INR in 7-10 days.
| "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
| 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
| 4.01 - 4.99
| Hold dose for 1 day, then ↓ weekly dose by 10%<br/>Repeat INR in 7-10 days.
| Hold dose for 1 day, then ↓ weekly dose by 10%<br />Repeat INR in 7-10 days.
| rowspan="2" | Patients with INRs 4.5 - 10 and with no evidence of bleeding: ACCP suggests against the routine use of vitamin K
| rowspan="2" | Patients with INRs 4.5 - 10 and with no evidence of bleeding: ACCP suggests against the routine use of vitamin K
|-
|-
| 5 - 8.99
| 5 - 8.99
| Hold dose until INR therapeutic, then ↓ weekly dose by 15%<br/>Repeat INR in 1 day.
| Hold dose until INR therapeutic, then ↓ weekly dose by 15%<br />Repeat INR in 1 day.
|-
|-
| ≥ 9.0
| ≥ 9.0
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| Patients with INRs > 10.0 with no evidence of bleeding: ACCP suggests that oral [[vitamin]] K be administered
| Patients with INRs > 10.0 with no evidence of bleeding: ACCP suggests that oral [[vitamin]] K be administered
|-
|-
| colspan=3|* 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.<ref name="pmid22084331">{{cite journal| author=Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M| title=Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. | journal=Ann Intern Med | year= 2011 | volume= 155 | issue= 10 | pages= 653-9, W201-3 | pmid=22084331 | doi=10.7326/0003-4819-155-10-201111150-00003 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22084331  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22431689 Review in: Ann Intern Med. 2012 Mar 20;156(6):JC3-3] </ref>
| colspan="3" |* 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.<ref name="pmid22084331">{{cite journal| author=Schulman S, Parpia S, Stewart C, Rudd-Scott L, Julian JA, Levine M| title=Warfarin dose assessment every 4 weeks versus every 12 weeks in patients with stable international normalized ratios: a randomized trial. | journal=Ann Intern Med | year= 2011 | volume= 155 | issue= 10 | pages= 653-9, W201-3 | pmid=22084331 | doi=10.7326/0003-4819-155-10-201111150-00003 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22084331  }}  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22431689 Review in: Ann Intern Med. 2012 Mar 20;156(6):JC3-3] </ref>
|}
|}



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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 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)."[1] Current recommendations on chronic warfarin management are mainly based on the RE-LY trial[2] which was published in 2009 with modifications due to subsequent practice guidelines by the American College of Chest Physicians in 2012.[1]

Adjustment of Warfarin Dose According to INR

INR Value Response per RE-LY[2] Alternative by ACCP[1]
≤ 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 ≤1.5: ↑ 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.[3]

Based on the existing medical research and clinical practice guidelines, institutions have algorithms to standardize the chronic administration of warfarin. For instance, the RE-LY and ACCP guidelines have been combined by the Department of Internal Medicine at KUSM-W and is located at Warfarin by Wichita.

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[4]:

  • 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.[5] The importance of choice of pill size is not clear.[6][7]

Management of Warfarin Related Bleeding

The management of bleeding among patients on warfarin includes:[1]

References

  1. 1.0 1.1 1.2 1.3 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.
  2. 2.0 2.1 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
  3. 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
  4. 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.
  5. Ebell MH (2005). "Evidence-based adjustment of warfarin (Coumadin) doses". Am Fam Physician. 71 (10): 1979–82. PMID 15926414.
  6. 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.
  7. 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.