If a patient with a mechanical mitral valve and subtherapeutic International Normalized Ratio (INR) refuses a heparin (unfractionated heparin) drip, is it acceptable to administer enoxaparin (low molecular weight heparin) with dose adjustment or increase the warfarin (coumarin) dose?

Management of Anticoagulation in Patients with Mechanical Mitral Valve Refusing Heparin Drip

For a patient with a mechanical mitral valve and subtherapeutic INR who refuses a heparin drip, therapeutic-dose enoxaparin with anti-factor Xa monitoring is an acceptable alternative until the INR returns to therapeutic range. 1

Rationale for Recommendation

Standard of Care

• ACC/AHA guidelines recommend that patients with mechanical mitral valves who have subtherapeutic INR should receive intravenous unfractionated heparin (UFH) when INR falls below 2.0 2, 1
• The target INR for mechanical mitral valves is 2.5-3.5 2, 1, 3

Alternative Options

Enoxaparin as a Bridge

• Class IIb recommendation: "In patients at high risk of thrombosis, therapeutic doses of subcutaneous UFH (15,000 U every 12 h) or LMWH (100 U per kg every 12 h) may be considered during the period of a subtherapeutic INR" 2
• A retrospective study of 130 bridging episodes showed no thromboembolic events and similar bleeding rates between mechanical heart valve patients and atrial fibrillation patients when using enoxaparin as bridging therapy 4
• Case reports document successful long-term anticoagulation with enoxaparin in patients with mechanical heart valves who had contraindications to warfarin 5

Dosing and Monitoring for Enoxaparin

• Therapeutic dose: 1 mg/kg subcutaneously every 12 hours 2
• Anti-factor Xa monitoring is crucial with target levels of 0.6-1.0 IU/mL 5
• Dose adjustments should be made based on anti-factor Xa levels to minimize bleeding risk while maintaining efficacy

Approach to Management

1. Initiate therapeutic-dose enoxaparin immediately:

   • 1 mg/kg subcutaneously every 12 hours 2
   • Monitor anti-factor Xa levels 4 hours after the third or fourth dose
   • Target anti-factor Xa level: 0.6-1.0 IU/mL 5

2. Simultaneously increase warfarin dose:

   • Increase warfarin dose to achieve target INR of 2.5-3.5 for mechanical mitral valve 2, 3
   • Monitor INR daily until stable in therapeutic range
   • Once INR is therapeutic for two consecutive days, discontinue enoxaparin

3. Close monitoring:

   • Check INR at least every 2-3 days during dose adjustment
   • Monitor for signs of bleeding or thromboembolism
   • Continue aspirin 75-100 mg daily if already prescribed 2

Important Considerations and Pitfalls

Risks of Subtherapeutic Anticoagulation

• Mechanical mitral valves have higher thrombotic risk than aortic valves 2, 1
• Risk of thromboembolism is approximately 10-20% per year when not anticoagulated 2

Potential Complications

• Bleeding risk is higher with therapeutic anticoagulation (9.1% per patient-year in recent studies) 6
• Valve thrombosis risk is approximately 0.5% per patient-year even with therapeutic anticoagulation 6

Contraindications to Enoxaparin

• Severe renal impairment (CrCl <30 mL/min) 2
• History of heparin-induced thrombocytopenia
• Active major bleeding

Factors Affecting INR Control

• Diet high in vitamin K
• Medication interactions
• Tobacco use can cause warfarin resistance and subtherapeutic INR 7
• Genetic polymorphisms affecting warfarin metabolism 3

Follow-up

• Once stable on warfarin with therapeutic INR, monitor INR at least every 2-4 weeks
• Consider home INR monitoring for patients with difficult-to-control INR 6
• Educate patient about importance of strict adherence to anticoagulation regimen

Remember that while enoxaparin is an acceptable alternative when a patient refuses heparin, it is still a second-line option. Every effort should be made to educate the patient about the importance of optimal anticoagulation for their mechanical mitral valve.