Protocol for the Management of Warfarin Reversal

8/7/2019 Protocol for the Management of Warfarin Reversal

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1Authors: Helen Maria, Transfusion Practitioner & Dr. Sarah Wexler, Consultant HaematologistDate written: December 2006For review: December 2008

Guidelines for the management of warfarin reversal

This provides a protocol for best clinical practice when managing warfarin reversal therapy. It applies toadult in-patients who need warfarin reversal to lower their INR, or who are on warfarin and bleeding, orwho are on warfarin and require immediate surgery.Refer to flowchart for summary p5.

1. The Bleeding Patient

Bleeding while on oral anticoagulants increases significantly with INR levels >5.0. Therapeutic decisionsare dependent on the INR and whether there is minor or major bleeding. The dose of vitamin K used toreverse over-anticoagulation depends on the INR.

Recommendations for management are given in Table 1 overleaf:

1.1. Major/life threatening bleeding

This relates to patients with intracranial or rapid onset neurological signs, intra-ocular(not conjunctival) bleeds, compartment syndrome, pericardial bleeds or those withactive bleeding and shock. These patients need an urgent clotting screen

Patients on warfarin may be bleeding for other reasons than the effect of theanticoagulant such as disseminated intravascular coagulation (DIC). A full bloodcount, INR, APTT and Fibrinogen should be determined (also D-Dimers if DIC is apossibility)

Contact a haematologist at this stage

Stop warfarin and reverse anticoagulation with Vitamin K and Prothrombin ComplexConcentrate (PCC), or FFP if PCC not available (PCC may be contraindicated inthe presence of DIC, discuss with haematologist)

Anticoagulation can be effectively reversed with 30 units/kg PCC and Vitamin K 5mg(Konakion MM injection) by slow intravenous injection

However, patients receiving warfarin may have an underlying hypercoagulable state,and infusion of PCC may exacerbate this - discuss with haematologist

In the absence of available concentrate licensed for this use, emergency treatmentwith 15ml/kg of FFP and Vitamin K 5mg (Konakion MM injection) by slow intravenousinjection will partially reverse anticoagulation, though the levels of individual factorswill typically remain


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Retest if necessary and seek haematological advice

Bleeding may occur when patients are not over-anticoagulated. In these circumstances it may still benecessary to reverse anticoagulation and identify the cause of bleeding.

1.3. Minor bleeding

Relevant to patients with INR >8.0, no bleeding or minor bleeding

Stop warfarin

If no other risk factors for haemorrhage, stop treatment until INR 70 years, previousbleeding complications, epistaxis) consider giving Vitamin K 2mg Oral (Konakion MMinjection used orally) or 1mg slow intravenous injection (Konakion MM injection)

Recheck clotting at 24 hours or sooner if there is clinical deterioration

2. INR too high but not bleeding

2.1. INR >3.0 and 4.0 and


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3. Rapid reversal of warfarin prior to urgent surgical procedure

Urgent means clinically essential, not administratively convenient, to do immediate surgery.

For reversal in 4 to 24 hours: Vitamin K 2mg Oral (Konakion MM injection used orally) or 1mg slow intravenous

injection (Konakion MM injection)

For reversal within 1 hour:

Prothrombin Complex Concentrate (PCC) 30 units/kg using a slow IV bolus over 10-15 minutes

Do not use FFP for rapid reversal unless PCC is not available. Always consult a Haematologist.

4. Reintroduction of oral anticoagulants

Timing of reintroduction of oral anticoagulants will depend on the risk of post-operative haemorrhage generally warfarin can be restarted once haemostasis isachieved

Warfarin will take 48-72 hours to reach full effect this could influence the decisionwhen to restart

In many instances oral anticoagulants can be started again as soon as the patienthas an oral intake

5. References

BCSH Guidelines on oral anticoagulation, British Journal of Haematology, 1998, 101, 374-387

BCSH Guidelines for the use of fresh frozen plasma, cryoprecipitate and cryosupernatant, British Journalof Haematology, 2004, 126, 11-28

Management of warfarin reversal, Leeds Teaching Hospitals NHS Trust August 2004

Warfarin reversal, Hanley, J.P. Journal of Clinical Pathology 2004;57;1132-1139

Beriplex P/N reverses severe warfarin induced overanticoagulation immediately and completely inpatients presenting with major bleeding. Evans G., Luddington R., Baglin T; British Journal ofHaematology, 2001;115;998-1001

6. Appendix

Administration of Prothrombin Complex Concentrate (PCC)

The brands of PCC used in the RUH are Octaplex

and Beriplex

. They contain aconcentrate of human coagulation factors II, VII, IX and X and are available via theBlood Bank laboratory x4735 bleep 7555

PCCs can only be used after authorisation by a haematologist

For prompt reversal of warfarin anticoagulation in the presence of haemorrhage dueto over-warfarinisation, a dose of 30 units/kg is recommended

The product must be reconstituted from a dried powder using a supplied diluent inaseptic conditions over not more than 10 minutes. It should then be administered asan IV slow bolus over 10-15 minutes


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Refer to monograph in IV drugs folder

Regular monitoring of the coagulation status is indicated during the treatment as theuse of high doses of PCC has been associated with instances of myocardialinfarction, DIC, venous thrombosis and pulmonary embolism

The on-call Haematologist can be contacted via switchboard

Octaplex

costs 210 for a vial containing 500u (currently 0.42 per unit) and islicensed

Beriplex

costs 175 for a vial containing 500u (currently 0.35 per unit) and isunlicensed

Vitamin K (phytomenadione)

Oral vitamin K is almost completely absorbed, making it as effective as intravenousvitamin K with the delay in action hardly influenced by the absorption time

Only 500 micrograms is required to reduce the INR from >5.0 to a target level of 2.0 3.0

Vitamin K tablets contain 10 mg phytomenadione which will completely reverse

anticoagulation. Therefore, when partial correction is required is may be necessary togive intravenous vitamin K or alternatively give the intravenous preparation orally

Allergic reactions following intravenous administration are rare with new preparationsof vitamin K. If the INR is still too high at 24 hours the dose of vitamin K can berepeated

Subcutaneous absorption of vitamin K is erratic and not recommended


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The bleeding patient INR too high, but not bleeding

Major/life threatening bleeding

IntracranialIntraocularCompartment syndromePericardialActive bleeding and shock

Urgent clinical assessmentCheck clotting screenContact Haematologist

Stop warfarinVitamin K 5mg (Konakion MM injection) byslow IV injection

PCC 30 units/kg

Check clotting screen 20 minutes postadministrationAdequate correction recheck in 4 hoursInadequate correction consider other causes,seek haematologist advice

INR >3.0 and 4.0 and

Protocol for the Management of Warfarin Reversal

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