How to switch from injection heparin (Heparin) to an oral anticoagulant, such as warfarin (Warfarin) or direct oral anticoagulants (DOACs) like apixaban (Apixaban) or rivaroxaban (Rivaroxaban), in patients with pulmonary thromboembolism?

Switching from Heparin to Oral Anticoagulants for Pulmonary Embolism

For hemodynamically stable patients with pulmonary embolism, transition directly to a DOAC (apixaban or rivaroxaban) without waiting for heparin overlap, or alternatively switch to warfarin with continued heparin until INR reaches 2.0-3.0 for at least 2 consecutive days. 1, 2, 3

Preferred Approach: Direct Transition to DOACs

DOACs are the preferred oral anticoagulant over warfarin for non-high-risk PE, offering superior safety with significantly less major bleeding while maintaining equivalent efficacy. 1, 2

Switching to Apixaban

• Stop heparin infusion immediately when administering the first dose of apixaban 3, 4
• Dosing regimen: 10 mg orally twice daily for 7 days, then 5 mg twice daily thereafter 2, 4
• Timing: Give the first apixaban dose at the time the next heparin dose would have been due (for intermittent IV heparin) or immediately after stopping continuous infusion 3, 4
• No bridging anticoagulation is required during this transition 4

Switching to Rivaroxaban

• Stop heparin infusion immediately when administering the first dose of rivaroxaban 3
• Dosing regimen: 15 mg orally twice daily (with food) for 21 days, then 20 mg once daily thereafter 2, 5
• Timing: Give the first rivaroxaban dose at the scheduled time of the next heparin administration 3
• No overlap period is necessary 5, 6

Alternative Approach: Transition to Warfarin

If warfarin is chosen instead of a DOAC (due to contraindications, cost, or patient preference), a different protocol applies. 1, 2

Warfarin Transition Protocol

• Continue full-dose heparin for several days while initiating warfarin simultaneously 3
• Start warfarin while maintaining therapeutic heparin anticoagulation 3, 7
• Overlap duration: Continue heparin for 4-5 days minimum, ensuring INR reaches 2.0-3.0 for at least 2 consecutive days before discontinuing heparin 1, 3, 7
• Target INR: Maintain INR between 2.0-3.0 (not 1.5-2.0, which is inferior) 1
• Total heparin duration: Typically 7-10 days with 4-5 days of warfarin overlap 7, 8
• No tapering of heparin is required—discontinue abruptly once INR is therapeutic 3

Critical Contraindications to DOACs

Do not use DOACs in the following situations—warfarin with heparin bridging is mandatory: 1, 2

• Severe renal impairment (creatinine clearance <30 mL/min) 1, 5
• Antiphospholipid antibody syndrome (requires lifelong warfarin, not DOACs) 1, 2, 9
• Pregnancy or breastfeeding (use LMWH throughout pregnancy) 1, 10
• Mechanical heart valves or moderate-to-severe mitral stenosis 1

Special Populations Requiring Modified Approach

Cancer-Associated PE

• Prefer LMWH over DOACs for at least 3-6 months as monotherapy 1, 2, 9
• After initial LMWH period, may consider transition to oral anticoagulants on case-by-case basis 2
• Continue anticoagulation indefinitely while cancer remains active 1, 2

High Bleeding Risk Patients

• Consider dose-adjusted IV unfractionated heparin (aPTT 1.5-2.5 times baseline) as initial therapy for easier reversibility 2
• Transition to oral anticoagulation only after bleeding risk stabilizes 1
• If using DOACs with combined P-gp and strong CYP3A4 inhibitors, reduce DOAC dose by 50% 4

Monitoring During Transition

For DOAC Transitions

• No coagulation monitoring required for the transition itself 5, 6
• Confirm adequate hemostasis before initiating oral anticoagulant 1, 4
• Assess renal function, hepatic function, and medication interactions before prescribing 2, 5

For Warfarin Transitions

• Monitor INR daily during overlap period until stable therapeutic range achieved 3
• Do not stop heparin until INR ≥2.0 for at least 2 consecutive measurements 1, 3
• Continue monitoring INR regularly (goal >70% time in therapeutic range) 1

Common Pitfalls to Avoid

• Never use heparin as a "bridge" when switching to DOACs—this increases bleeding risk unnecessarily, as DOACs have rapid onset of action 4, 5
• Never stop heparin prematurely when transitioning to warfarin—warfarin takes 4-5 days to achieve therapeutic effect and initially creates a prothrombotic state 3, 7
• Never use low-intensity warfarin (INR 1.5-2.0)—this is inferior to standard intensity (INR 2.0-3.0) for VTE treatment 1
• Never prescribe DOACs in pregnancy—this is an absolute contraindication; use LMWH instead 1, 10
• Never assume all DOACs have identical transition protocols—apixaban and rivaroxaban allow single-drug approaches with higher initial doses, while edoxaban and dabigatran require at least 5 days of parenteral anticoagulation first 5

Duration of Anticoagulation After Transition

• Minimum 3 months for all patients with PE 1, 2
• Discontinue after 3 months if provoked by major transient/reversible risk factor 1, 2
• Continue indefinitely for unprovoked PE or recurrent VTE 1, 2, 9
• Extended therapy with reduced-dose DOACs may be considered after completing initial treatment: rivaroxaban 10 mg daily or apixaban 2.5 mg twice daily 1