Reversing anticoagulation



Bleeding while on oral anticoagulants increases significantly with INR (International Normalised Ratio) level > 5.0, particularly in patients with risk factors for bleeding.

Risk factors for bleeding include:

  • Age ( > 70) years
  • Previous bleeding complications
  • GI haemorrhage/ulcers
  • Hx CVA
  • Recent surgery
  • Uncontrolled BP
  • Recent initiation of anticoagulants

The majority of over-anticoagulated patients will return to their target therapeutic range within 3 days of discontinuing warfarin therapy.


Vitamin K

Vitamin K1 (C31H46O2) and K2(C41H56O2)are two naturally occurring fat-soluble vitamins. Vitamin K is essential in the production of prothrombin.

  • Vitamin K is the first drug of choice to be administered for the reversal of excessive anti-coagulation if the patient has evidence of bleeding.
  • Vitamin K is dispensed in ampoules of 1ml/10mgs known as Konakion® or 0.2mls/2mgs known as paediatric Konakion®. This can be administered sub-lingually using a 1ml syringe and a filter needle to draw up and administer the solution. Vitamin K is also available in 10mg tablets for oral administration.
  • When partial correction is required to achieve a target therapeutic INR, the Intravenous preparation of Vitamin K can be administered in low doses of 1-2mgs sub-lingually.
  • 5mgs of Vitamin K will completely reverse anticoagulation, which is only indicated if the patient is presenting with bleeding as a result of a high INR.
  • Particular caution is advised for patients with prosthetic heart valves, where the use of vitamin K may increase the risk of thrombosis due to overcorrection of the INR. Therefore, if indicated, small doses of vitamin K only (e.g. 1 – 2 mg) are recommended.
  • Prothrombin Complex Concentrate (PCC) is not routinely administered to reverse excessive anticoagulation in the absence of bleeding but should be administered in life threatening major haemorrhage.
  • PCC is more effective than Fresh Frozen Plasma (FFP) for reversal of bleeding associated with excessive anticoagulation; therefore FFP is not indicated or recommended when PCC is available.

Please discuss cardiac valve patients with cardiology BEFORE reversing warfarin.


Procedure

INR Action
3 < INR < 5
  1. ↓ Warfarin dose or stop (for 1 -2 days).
  2. Restart Warfarin ( reduced dose) when INR < 5.
5 < INR < 8
No bleeding
  1. Stop Warfarin.
  2. Recheck INR after 1-2 days.
  3. If there are risk factors for bleeding recheck INR level within 24hrs.
  4. Restart warfarin at reduced dose when INR < 5.0
  5. Determine if there are any causative or contributing factors for the increase in the INR level and adjust dose accordingly.
5 < INR < 8
minor bleeding
  1. Stop warfarin for 1-2 days.
  2. Consider administration of low dose Vitamin K 1-2mgs sub-lingually. depending on extent of bleeding and risk factors for further bleeding. A low dose of vitamin K e.g.1-2mgs of the paediatric intravenous preparation, can be administered sub-lingually. For patients with prosthetic heart valves caution should be taken to avoid over correction of the INR below therapeutic range.
  3. Restart warfarin at reduced dose when INR < 5.0
  4. Determine if there are any causative or contributing factors for the increase in the INR level and adjust dose accordingly
  5. If INR over corrected contact Haematology for dosing instructions and advise.
INR > 8.0
  1. Stop Warfarin
  2. Identify additional risk factors for bleeding: increasing age (e.g. > 70 yr), previous bleeding event/complications (ulcers, wounds, post surgery)
  3. Check for evidence of minor bleeding: epistaxis, bleeding gums, haematuria, oozing wounds, haemoptysis, PR bleeding.
  4. Administer 1-2mgs of Vitamin K sub-lingually. A low dose of vitamin K, e.g.1-2mgs of the paediatric intravenous preparation, can be administered sub-lingually. For patients with prosthetic heart valves caution should be taken to avoid over correction of the INR below therapeutic range.
  5. Recheck INR within 24hrs and restart warfarin at a reduced dose once INR < 5.0.
  6. If there are no risk factors identified or there is no evidence of minor bleeding recheck INR within 24hrs.
  7. Determine if there are any causative or contributing factors for the increase in the INR level and adjust dose accordingly.
  8. If INR remains > 8.0 after 24hours the dose of Vitamin K can be repeated.
  9. If INR over corrected contact Haematology for dosing instructions and advise.

Major or life threatening bleeding

  • Intracranial bleed.
  • Retroperitoneal bleed/Intra-ocular bleed.
  • Muscle bleed, with compartment syndrome.
  • Pericardial bleed.
  • Active bleed with hypotension or 3g fall in Hb.

Emergency Reversal

  1. Stop warfarin
  2. Consult with Haematology and Cardio-thoracic consultant/registrar if mechanical valve in-situ.
  3. Administer Prothrombin Complex Concentrate (PCC) Octaplex as per the manufactures instructions, refer to “Policy and Procedure for the Prescribing, Ordering and Administration of Prothrombin Complex Concentrates (PCC) in Cork University Hospital”.
  4. PCC (Octaplex) dose in Major Bleed

    Patients INR Dose PCC
    INR 2 - 3.9 25 IU / Kg
    INR 4 - 6 35 IU / Kg
    INR > 6 50 IU / Kg
  5. Administer 10mgs of Vitamin K intravenously (IV Vitamin K will provide 70% correction of INR within 8 hours). For patients with prosthetic heart valves caution should be taken to avoid over correction of anti-coagulation below therapeutic range. A low dose of IV Vitamin K (1-2mgs) can be administered sub-lingually. Discuss with cardio-thoracic, cardiac or haematology consultant or registrar before administering Vitamin K.
  6. Note: there may be an increased risk of bleeding when obtaining intravenous access due to high INR.
  7. Recheck INR within 30-mins to 1 hour of administration of PCC. There may be an initial correction of the INR shortly after administration of PCC however this may be temporary due to the half-life of factor VII in PCC.
  8. The INR should be repeated 6hrs post administration of PCC and regularly until the patients INR is within their target range.
  9. Further Vitamin K may be required.
  10. Warfarin should be commenced once haemodynamically stable.
  11. If INR over corrected contact Haematology for dosing instructions and advise.

Reversing Dabigatran

Contact haematology SpR - reversal agent available on trial in CUH.

Dabigatran is an oral direct thrombin inhibitor (DTI) licensed for stroke prevention in atrial fibrillation. Unlike warfarin, there is not yet available (on trial) reversal agent and measurement of the anticoagulant effect is not ‘routine’.

The PT/INR response to Dabigatran is inconsistent and should not be measured when assessing a patient who is bleeding or needs emergency surgery.

The activated partial thromboplastin time (APTT) provides a qualitative measurement of the anticoagulant effect of Dabigatran. Knowledge of the time of last dose is important for interpretation of the APTT.

If a patient receiving Dabigatran presents with bleeding:

  • Omit/delay next dose of Dabigatran
  • Measure APTT and PT (consider DTI assay if available).
  • Administer activated charcoal, with sorbitol, if within 2 h of ingestion;.
  • Give Tranexamic acid (TXA) - 1 g intravenously if significant bleeding (TXA infusion guide).
  • Involve haematology team.
  • Maintain renal perfusion and urine output to aid Dabigatran excretion.

Dabigatran exhibits low protein binding and may be removed by dialysis.

Supportive care should form the mainstay of treatment.

If life/limb threatening bleeding, consider another haemostatic agent. There is currently (Jan 2014) no evidence to support the choice of one haemostatic agent (FEIBA, recombinant factor VIIa, prothrombin complex concentrates) over another.


Reversing Rivaroxaban (Xarelto®)

The PT/INR / APTT responses to Rivaroxaban are not reliable indicators of the level of anticoagulation.

If a patient receiving Rivaroxaban presents with significant bleeding:

  • Omit/delay next dose of Rivaroxaban.
  • Administer activated charcoal, with sorbitol, if within 2 h of ingestion.
  • Give PCC at 50 IU / Kg.
  • Involve haematology team.


Content by Dr Íomhar O' Sullivan 29/07/2004. Reviewed by Dr ÍOS 01/12/2004, Dr Chris Luke 27/02/2006, Dr ÍOS 03/03/2007, Dr Chris Luke 23/09/2011. Last review Dr Susan O’Shea, Dr ÍOS 22/11/18.