What oral anticoagulant can a patient with a history of thromboembolic events, currently on heparin (unfractionated heparin) three times a day, be switched to?

Oral Anticoagulation Options After Heparin Three Times Daily

For patients currently on unfractionated heparin (UFH) three times daily with a history of thromboembolic events, the preferred oral anticoagulant is warfarin, with direct oral anticoagulants (DOACs) such as rivaroxaban or apixaban as acceptable alternatives.

Transitioning from UFH to Oral Anticoagulation

Warfarin Transition (Traditional Approach)

The standard approach is to initiate warfarin on day 1 or 2 of heparin therapy and continue both medications with at least 5 days of overlap until the INR reaches therapeutic range (2.0-3.0) for two consecutive days. 1, 2, 3

• Start warfarin while continuing UFH, maintaining the activated partial thromboplastin time (aPTT) at 1.5-2.0 times control throughout the overlap period 3, 4
• Continue UFH for a minimum of 5-7 days total, ensuring adequate overlap with warfarin 1, 2
• Discontinue UFH only after the INR is therapeutic (2.0-3.0) for at least 2 consecutive days 1
• The total duration of anticoagulation should be at least 6 weeks for acute thromboembolism without predisposing conditions, or 3-6 months for venous thromboembolism with risk factors 2, 1

DOAC Transition (Modern Alternative)

Direct oral anticoagulants offer a simpler transition without the need for INR monitoring and can be started immediately after discontinuing heparin. 5, 6, 7

Rivaroxaban Protocol

• Discontinue UFH and start rivaroxaban 15 mg orally twice daily for 21 days, then reduce to 20 mg once daily for long-term therapy 5, 8
• This is the most extensively studied DOAC for transitioning from parenteral anticoagulation, with excellent safety data 5

Apixaban Protocol

• Discontinue UFH and start apixaban 10 mg orally twice daily for 7 days, then reduce to 5 mg twice daily 8
• Dose reduction to 2.5 mg twice daily is required if the patient has at least two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 8

Special Considerations and Contraindications

When to Avoid Warfarin

• Do not start warfarin if heparin-induced thrombocytopenia (HIT) is suspected or confirmed until platelet count recovers to >150,000/μL, as warfarin can cause venous limb gangrene in acute HIT 5, 6, 7
• In patients with severe hepatic impairment, warfarin requires careful dose adjustment and frequent monitoring 1

When to Prefer Warfarin Over DOACs

• Mechanical heart valves (DOACs are contraindicated) 1
• Severe renal impairment with creatinine clearance <30 mL/min (most DOACs require dose adjustment or are contraindicated) 8
• Patients requiring frequent invasive procedures (warfarin's reversibility with vitamin K is advantageous) 1

When to Prefer DOACs Over Warfarin

• Cancer patients may benefit from continued LMWH rather than transitioning to oral agents, as LMWH has shown superior efficacy in cancer-associated thrombosis 1
• Patients unable to maintain reliable INR monitoring 5, 6
• Patients with contraindications to frequent blood draws 5

Critical Pitfalls to Avoid

Never discontinue heparin before achieving adequate anticoagulation with the oral agent. The most dangerous error is creating a gap in anticoagulation, which dramatically increases the risk of recurrent thromboembolism (up to 25% if adequate anticoagulation is not maintained) 4

• Do not stop UFH until warfarin has been therapeutic for at least 2 consecutive days 1, 2
• Do not use prophylactic doses during the transition—maintain therapeutic anticoagulation throughout 5, 6, 7
• Avoid abrupt discontinuation of heparin without immediate initiation of the oral agent 3, 4

Monitoring Requirements

For Warfarin Transition

• Check INR daily during the overlap period until stable in therapeutic range 1, 3
• Maintain aPTT at 1.5-2.0 times control while on UFH (check every 6 hours initially, then every 24 hours when stable) 1, 3
• Continue monitoring INR regularly after heparin discontinuation (initially every few days, then weekly to monthly when stable) 2, 3

For DOAC Transition

• No routine coagulation monitoring required 5, 6
• Assess renal function before initiation and periodically thereafter, as DOACs require dose adjustment in renal impairment 8
• Monitor for bleeding complications clinically 5

Duration of Oral Anticoagulation

• Minimum 3 months for provoked venous thromboembolism 1, 5
• Extended therapy (potentially indefinite) for unprovoked events or recurrent thromboembolism 1, 5
• At least 6 weeks for first episode with clear precipitating factor that has resolved 2