Warfarin maintenance: management of high and low INRs

Use the following guides to adjust maintenance doses for patients already stabilised on warfarin to achieve a target INR (international normalised ratio) of 2.5 ± 0.5.

Practice tips

  • Consider recent INR trends - avoid adjusting warfarin doses based on an asymptomatic, single, unexplained out-of-range INR, unless clinically significant
  • Use the MedicineWise Anticoagulant Safety Checklist to identify causes for INR instability and guide maintenance dose adjustments
  • Dose adjustments should be based on the total weekly dose of warfarin
  • When changing the warfarin dose, check INR every 7–14 days until the INR is stable
  • Consider available tablet strengths and the patient’s ability to break scored tablets when prescribing future doses.
  • Older people may take longer to respond to dose changes
  • Missed doses will be reflected in the INR in 2–5 days
  • For warfarin dose initiation, refer to MedicineWise News

Dose adjustments should be based on the total weekly dose of warfarin.

Table 1: Warfarin dose adjustment algorithm for target INR 2.5 ± 0.5 and no bleeding[1,2] [A]

INR
≤ 1.5 1.6– 1.9 2–3
3.1–3.9 4.0–4.4 ≥ 4.5
Dose adjustment
Increase weekly dose by 15%[B]

Continue current dose

If repeat INR falling or low for 2 consecutive INRs, increase weekly dose by 10%

Continue current dose
Continue current dose

If repeat INR rising or high for 2 consecutive INRs, reduce weekly dose by 10%
Omit warfarin dose for 1 day, reduce weekly dose by 10%
See Table 2 for patients on warfarin with high INR and no bleeding and Table 3 for patients on warfarin with bleeding
Next INR test
7–14 days[C] 7–14 days[C] Continue current INR testing interval
7–14 days[C] 7–14 days[C]

Abrreviations: INR = international normalised ratio.

[A] Clinical judgment may allow variation in the application of the algorithm.[1]

[B] Consider bridging with a low molecular weight heparin (LMWH) if the INR is low and the patient is at high risk of thromboembolism.

[C] A repeat INR in the next 1–2 days days may be useful in the following situations:

  • to avoid missing an INR that has been rising since the last INR level, particularly when the INR ≥ 4
  • if a cause for a change in INR cannot be identified
  • if there has been a dramatic change from the previous INR, e.g. from 3.0 to 1.6.

 

 


The advice in Tables 2 and 3 is taken from an ‘Update of Consensus Guidelines for Warfarin Reversal’ on behalf of the Australasian Society of Thrombosis and Haemostasis.[2]

If the patient is bleeding consider urgent hospital referral is recommended. Prothrombinex-VF and fresh frozen plasma provide immediate reversal. Vitamin K1 is essential for sustaining the reversal achieved.


Table 2: Management of patients on warfarin with high INR and no bleeding[2]

Clinical setting Recommendations
INR 4.5–10.0 and no bleeding
If bleeding risk is high[D]:
  • consider vitamin K1 1–2 mg orally or 0.5–1 mg IV
  • measure INR within 24 hours
  • resume warfarin at a reduced dose once INR approaches therapeutic range
INR >10.0 and no bleeding
  • Stop warfarin
  • Administer 3–5 mg vitamin K1 orally or IV[E]
  • Measure INR in 12–24 hours then daily to second daily over the following week
  • Resume warfarin at a reduced dose once INR approaches therapeutic range
If bleeding risk is high[D]:
  • consider Prothrombinex-VF, 15–30 IU/kg
  • measure INR in 12–24 hours and monitor closely over the following week
  • resume warfarin at a reduced dose once INR approaches therapeutic range
 Abrreviations: INR = international normalised ratio; IV = intravenously.

[D] Recent major bleed (within previous 4 weeks) or major surgery (within previous 2 weeks), thrombocytopenia (platelet count < 50 x 109/L), known liver disease or concurrent antiplatelet therapy.[2]

[E] Extrapolated from oral vitamin K data in absence of IV data.[2]

Table 3: Management of patients on warfarin with bleeding[2][F]

Clinical setting Recommendations
INR ≥1.5 with life-threatening[G] (critical organ) bleeding
Stop warfarin therapy and administer:
  • vitamin K1 5–10 mg IV
  • and Prothrombinex-VF 50 IU/kg[H] IV
  • and fresh frozen plasma 150–300 mL
If Prothrombinex-VF is unavailable, administer fresh frozen plasma 15 mL/kg
INR ≥ 2.0 with clinically significant bleeding (not life threatening)
Stop warfarin therapy and administer:
  • vitamin K1 5–10 mg IV
  • and Prothrombinex-VF 35–50 IU/kg IV according to INR
If Prothrombinex-VF is unavailable, administer fresh frozen plasma 15 mL/kg
Any INR with minor bleeding

Stop warfarin

Repeat INR the following day and adjust warfarin dose to maintain INR in the target therapeutic range

If bleeding risk is high[I] or INR > 4.5, consider vitamin K1 1–2 mg orally or 0.5–1 mg IV

 Abbreviations: INR= international normalised ratio; IV  = intravenously.

[F] Indication for warfarin therapy should be reviewed; if clinically appropriate, consider permanent cessation.[2]

[G] Includes intracranial bleeding.[2]

[H] Consider administering a Prothrombinex-VF dose less than 50 IU/kg when INR 1.5–1.9.[2]

[I] Recent major bleed (in the previous 4 weeks) or major surgery (in the previous 2 weeks), thrombocytopenia (platelet count < 50 x 109/L), known liver disease or on current antiplatelet therapy.[2]

References

  1. Kim YK, Nieuwlaat R, Connolly SJ, et al. Effect of a simple two-step warfarin dosing algorithm on anticoagulant control as measured by time in therapeutic range: a pilot study. J Thromb Haemost 2010;8:101–6.
  2. Tran HA, Chunilal SD, Harper PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust 2013;198:doi:10.5694/mja12.10614. https://www.mja.com.au/journal/2013/198/4/update-consensus-guidelines-warfarin-reversal (accessed 25 June 2013).