How to manage warfarin bleeds — updated recommendations

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Warfarin and current practice in Australia | How to manage bleeding in patients on warfarin | Patients on warfarin with a high INR and no bleeding | Warfarin best practice — ways you can help | Balance benefits and harms according to clinical setting | References

Summary

Warfarin remains the most commonly prescribed anticoagulant in Australia but like all anticoagulants its use is associated with an increased risk of bleeding.

The Australasian Society of Thrombosis and Haemostasis recently updated consensus guidelines for warfarin reversal to reflect latest evidence and the clinical experience of a panel of author-practitioners.

These guidelines offer advice on strategies to prevent over-anticoagulation. They also address the principles of warfarin reversal in acute care and provide recommendations on bridging (substituting) anticoagulation therapy in different clinical settings.

These strategies are especially important:

  • when warfarin therapy is complicated by bleeding
  • when the INR is above target but with no evidence of bleeding
  • in patients on warfarin therapy who require invasive procedures.

Warfarin and current practice in Australia

Warfarin remains the most commonly prescribed anticoagulant in Australia,1 and like all anticoagulants its use increases the risk of bleeding.2 It is most effective in terms of benefits and harms when the INR is within the therapeutic range (2–3 for most indications),1,3 to balance the risks of both thromboembolism and bleeding.4

In Australian practice it is estimated that people treated with warfarin are maintained within therapeutic range 50–68% of the time.5 Time in therapeutic range can be optimised by addressing correctable causes of poor INR control and avoiding frequent warfarin dose adjustments.1 Correctable causes of poor INR control include:

  • non-adherence
  • concurrent medications
  • alcohol consumption
  • dietary factors such as unstable vitamin K intake or gastrointestinal illness.3

The updated Australasian Society of Thrombosis and Haemostasis (ASTH) consensus guidelines provide strategies to prevent over-anticoagulation and minimise bleeding risk for people taking warfarin, including perioperative patient risk stratification and guidance for reversing warfarin activity in acute care.1

These updated guidelines are timely, with anticoagulation currently indicated for most people with non-valvular AF, i.e. those with a CHADS2 score ≥ 1, and people with VTE, unless contraindicated.6

Refer to the 2013 ASTH guidelines for recommendations related to anticoagulant bridging and perioperative care.1

How to manage bleeding in patients on warfarin

Unlike the 2004 ASTH guidelines and current Therapeutic Guidelines, the 2013 ASTH guidelines recommend different approaches to management of life-threatening compared with clinically significant but non-life-threatening bleeding (Table 1).1,6,7

Review the use of warfarin in light of the bleeding, and stop warfarin permanently if clinically appropriate.1 The revised guidelines also stratify the recommended dose of Prothrombinex-VF for people with clinically significant bleeding, according to their initial and target INR.1

Table 1. ASTH recommendations for patients on warfarin experiencing bleeding1

Clinical setting Recommendations
INR ≥ 1.5 with life-threatening (critical organ) bleeding, including intracranial bleeding Stop warfarin and administer:
  • vitamin K1 5.0–10 mg IV
  • and Prothrombinex-VF 50.0 IU/kg 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 and administer:
  • vitamin K1 5.0–10 mg IV
  • and Prothrombinex-VF 35.0–50.0 IU/kg IV, according to INR
  • if prothrombinex-VF is unavailable, administer fresh frozen plasma 15 mL/kg
Any INR with minor bleeding

Omit warfarin. Repeat the INR measurement the following day and adjust the warfarin dose to maintain a therapeutic INR

Consider vitamin K1 1.0–2.0 mg orally or 0.5–1.0 mg IV if bleeding risk is high or INR is > 4.5 

* Consider administering a Prothrombinex-VF dose < 50.0 IU/kg when INR is 1.5–1.9
Major bleed within the previous 4 weeks, major surgery within the previous 2 weeks,
  thrombocytopenia (platelet count < 50 x 109/L), known liver disease or concurrent
  antiplatelet therapy1
 

Patients on warfarin with a high INR and no bleeding

The new ASTH recommendations are similar to the 2004 recommendations for patients on warfarin with a high INR and no bleeding, although the INR boundaries for stratifying treatment have shifted slightly.

 The clinical setting of:

  • ‘INR higher than the therapeutic range but < 5 and no bleeding’
    has shifted to
    ‘INR higher than the therapeutic range but < 4.5 and no bleeding’

    and
  • ‘INR 5 to 9 and no bleeding’
    has been replaced with
    ‘INR 4.5–10 and no bleeding’. (Table 2). 1,7

Vitamin K is not recommended routinely for patients with an INR up to 10 with no bleeding or risk factors for major bleeding. It does not reduce the risk of bleeding in these people compared with placebo.1,8

Table 2. ASTH recommendations for patients on warfarin with a high INR but no bleeding1

Clinical setting Recommendations
INR higher than the therapeutic range but < 4.5 and no bleeding
  • Reduce or omit the next warfarin dose
  • Resume treatment at a lower warfarin dose when the INR approaches the therapeutic range
  • If the INR is only minimally above the therapeutic range (up to 10%), dose reduction is generally not necessary
INR 4.5–10.0 and no bleeding
  • Stop warfarin treatment: consider reasons for elevated INR and patient-specific factors. Vitamin K1 is usually not necessary

If bleeding risk is high:

  • consider vitamin K1 1.0–2.0 mg orally or 0.5–1.0 mg IV
  • measure INR within 24 hours
  • resume warfarin at a lower dose when the INR approaches the therapeutic range
INR > 10 and no bleeding
  • Stop warfarin treatment
  • Administer 3.0–5.0 mg vitamin K1 orally or IV
  • Measure INR in 12–24 hours, monitor INR daily or every second day over the next week
  • Resume warfarin at a lower dose when the INR approaches the therapeutic range

If bleeding risk is high:

  • consider Prothrombinex-VF, 15–30 IU/kg
  • measure INR in 12–24 hours and monitor closely over the next week
  • resume warfarin at a lower dose when the INR approaches the therapeutic range

Warfarin best practice — ways you can help 

Minimise bleeding risk in patients starting warfarin

Avoid high initial warfarin loading doses; a 5 mg starting dose is generally preferable and an even lower starting dose may be appropriate for older people, who are generally more sensitive to warfarin.1 A slow loading course is safe for people with AF and achieves an INR of 2–3 in 3–4 weeks for most.9

Identify and address correctable risk factors for bleeding

  • Use bleeding risk prediction scores such as HAS-BLED in people with AF to identify correctable risk factors that can be modified to reduce the risk of warfarin-induced bleeding.1,3 These include hypertension and poorly controlled INR.3 For people with non-valvular AF and one or more CHADS2 risk factors for stroke, the benefits of anticoagulation, (unless contraindicated) outweigh the increased risk of intracranial haemorrhage regardless of HAS-BLED score.10
  • Use bleeding risk tools to identify and correct risk factors but not to withhold anticoagulant treatment — people at high risk of bleeding are also at high risk of stroke.
  • Continue to assess risk factors for bleeding in all patients taking warfarin; this may influence clinical monitoring intervals.

Replace medicines that interact with warfarin when possible

  • Avoid concomitant use of NSAIDs and certain antibiotics with warfarin.1
  • Avoid concomitant antiplatelet therapy except when clinical benefit is known, such as with mechanical heart valves, acute coronary syndrome or recent coronary stents.1

Discuss the key points of warfarin management with the patient

Ensure patients understand the importance of dosing and monitoring; provide educational materials on dietary, alcohol and drug (including complementary, alternative and over-the-counter medicines) interactions that influence INR.12

Balance benefits and harms according to clinical setting

Warfarin is highly effective in preventing conditions such as stroke or VTE1 but has a narrow therapeutic window when the risk of both thromboembolism and bleeding is minimised.12

It is more likely to be used safely by patients who are aware of the importance of dosing and monitoring, the drugs and foods that can affect their INR and the signs and symptoms of over-anticoagulation.12

Recent updates to national and international guidelines offer advice on warfarin best practice, including strategies to prevent and manage warfarin over-anticoagulation.1,13

References
  1. Tran HA, Chunilal SD, Harper PL, et al. An update of consensus guidelines for warfarin reversal. Med J Aust 2013;198:198–9. [PubMed]
  2. Australian Medicines Handbook, 2013. Adelaide.
  3. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: An update of the 2010 ESC Guidelines for the management of atrial fibrillation * Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012;33:2719–47. [PubMed]
  4. Oake N, Jennings A, Forster AJ, et al. Anticoagulation intensity and outcomes among patients prescribed oral anticoagulant therapy: a systematic review and meta-analysis. CMAJ 2008;179:235–44. []PubMed]
  5. Australian Government Department of Health and Ageing. Public Summary Document: Dabigatran etexilate, capsules, 110 mg and 150 mg (as mesilate), Pradaxa. March 2011 PBAC. 2011. http://www.health.gov.au/internet/main/publishing.nsf/Content/1863CE366CA53443CA2578BE001241DB/$File/Dabigatran%20PRADAXA%20Boehringer%20Ingelheim%206-3%202011-03%20PSD%20FINAL.pdf (accessed 26 March 2013).
  6. eTG complete online. Therapeutic Guidelines Cardiovascular. Version 6. Melbourne, 2012.(accessed 26 March 2013).
  7. Baker RI, Coughlin PB, Gallus AS, et al. Warfarin reversal: consensus guidelines, on behalf of the Australasian Society of Thrombosis and Haemostasis. Med J Aust 2004;181:492–7. [PubMed]
  8. Crowther MA, Ageno W, Garcia D, et al. Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: a randomized trial. Ann Intern Med 2009;150:293–300. [PubMed]
  9. Prodigy 2009. Anticoagulation – oral, Management. Newcastle UK: [http://www.cks.nhs.uk/anticoagulation_oral/management/scenario_anticoagulation_oral/view_full_scenario#-373892 (accessed 16 October).
  10. Olesen JB, Lip GY, Lindhardsen J, et al. Risks of thromboembolism and bleeding with thromboprophylaxis in patients with atrial fibrillation: A net clinical benefit analysis using a 'real world' nationwide cohort study. Thromb Haemost 2011;106:739–49. [PubMed]
  11. Scottish Interecollegiate Guidelines Network (SIGN). Antithrombotics: indications and management: NHS Quality Improvement Scotland, 2012. http://www.sign.ac.uk/pdf/SIGN129.pdf
  12. Guidelines & protocols advisary committee. Warfarin therapy management. British Columbia: British Columbia Medical Association, 2010. http://www.bcguidelines.ca/pdf/warfarin_management.pdf
  13. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th edn. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e326S–50S. [PubMed]