Guidelines for the management of an elevated international normalized ratio (INR) in adult patients with or without bleeding

Clinical setting

Action

INR higher than the therapeutic range but <5
bleeding absent

• Lower the dose or omit the next dose of warfarin. Resume therapy at a lower dose when the INR approaches therapeutic range.
• If the INR is only minimally above therapeutic range (up to 10%), dose reduction may not be necessary.

INR 5-10(1)
bleeding absent

• Cease warfarin therapy; consider reasons for elevated INR and patient-specific factors.
• If bleeding risk is high, give vitamin K (1-2 mg orally or 0.5-1 mg intravenously).
• Measure INR within 24 hours,(2) resume warfarin at a reduced dose once INR approaches the therapeutic range.

INR >10
bleeding absent

• Where there is a low risk of bleeding, cease warfarin therapy, give 2.5-5 mg vitamin K orally or 1 mg intravenously. Measure INR in 6-12 hours, resume warfarin therapy at a reduced dose once INR approaches the therapeutic range.
• Where there is a high risk of bleeding,(3) cease warfarin therapy, give 2 mg vitamin K intravenously. Consider Prothrombinex-VF (25-50 unit/kg) and fresh frozen plasma (150-300 mL)(5), measure INR in 6-12 hours, resume warfarin therapy at a reduced dose once INR approaches the therapeutic range.

Any clinically significant bleeding where warfarin-induced coagulopathy is considered a contributing factor

For suspected intracerebral haemorrhage while on warfarin, see Stroke section.

• Cease warfarin therapy. Give the following treatment urgently: 10 mg vitamin K intravenously, as well as Prothrombinex-VF (50 unit/kg) and fresh frozen plasma (150-300 mL)(5).
• Monitor the patient continuously until the bleeding stops. For details, see (4)

  OR

• If fresh frozen plasma is unavailable, cease warfarin therapy, give 10 mg vitamin K intravenously, and Prothrombinex-VF (50 unit/kg)(5).
• Monitor the patient continuously until the bleeding stops. For details, see (4)

  OR

• If Prothrombinex-VF is unavailable, cease warfarin therapy, give 10 mg vitamin K intravenously, and 15-30 mL/kg of fresh frozen plasma.
• Monitor the patient continuously until the bleeding stops. For details, see (4)

Any INR with minor bleeding

• Omit warfarin, repeat INR the following day and adjust warfarin dose to maintain INR in the target therapeutic range.
• If bleeding risk is high (3) or INR >5, consider vitamin K₁, 1 - 2 mg orally or 0.5 - 1 mg IV.

1. Bleeding risk increases exponentially from INR 5 to 10; INR ≥6 should be monitored closely.
2. Vitamin K effect on INR can be expected within 6-12 hours.
3. Examples of patients in whom the bleeding risk would be expected to be high include the following: active gastrointestinal disorders (such as peptic ulcer or inflammatory bowel disease); receiving concomitant antiplatelet therapy; major surgical procedure within the preceding two weeks; known liver disease; and those with a low platelet count (<50 x 10⁹/L).
4. Monitoring:
   • INR alone is not useful for monitoring the effectiveness of clotting factor replacement. It is only useful for monitoring warfarin use in steady state situations.
   • Monitoring should be done immediately after treatment using a coagulation screen (INR, APTT, thrombin time and fibrinogen). If still abnormal, more coagulation factors should be given immediately.
   • If normal recheck in 4-6 hours (reflecting shortest half-life of factor VII and vitamin K onset of action).
   • If normal again, then recheck at 24 hours, or sooner if patient clinically unstable.
   • In all situations carefully reassess the need for ongoing warfarin therapy.
5. To arrange Prothrombinex-VF, complete the Blood Product Request QMR22B form with the required dose (50 units/kg). Write "Life-threatening bleed on warfarin" clearly on the form. Send in a Lamson tube to the Blood Bank or fax to Blood Bank (80159), then inform the New Zealand Blood Service doctor on call via phone (80310).