Switching from Apixaban to Heparin Drip: Timing Recommendations
You should NOT start the heparin drip immediately when switching from apixaban 5mg BID; instead, wait approximately 12 hours after the last apixaban dose before initiating the heparin infusion to avoid excessive anticoagulation overlap.
Pharmacokinetic Rationale
The timing of this transition is based on apixaban's pharmacokinetic profile:
- Apixaban has a terminal plasma half-life of 8 to 14 hours, with peak plasma levels occurring approximately 3 hours after oral administration 1
- The drug is eliminated via multiple pathways including oxidative metabolism and renal/intestinal routes, meaning residual anticoagulant effect persists for several hours after the last dose 1
- Waiting 12 hours allows for significant clearance of apixaban before introducing heparin, reducing the risk of excessive anticoagulation 2
Recommended Transition Protocol
Timing Algorithm:
- Stop apixaban at the regularly scheduled time (do not give an extra dose)
- Wait 12 hours from the last apixaban dose before starting the heparin drip 2
- Initiate heparin using weight-based dosing: 80 U/kg bolus followed by 18 U/kg per hour infusion 1
- Monitor aPTT according to your institution's heparin protocol to achieve therapeutic anticoagulation
Special Considerations for Modified Timing:
Renal impairment (CrCl <30 mL/min):
- Extend the waiting period to 24 hours before starting heparin, as apixaban clearance is significantly delayed 2
Elderly patients (age >80 years):
- Consider extending to 18-24 hours due to altered pharmacokinetics 2
Patients on P-glycoprotein or CYP3A4 inhibitors:
- Extend waiting period to 18-24 hours as these medications increase apixaban plasma concentrations 1, 2
Critical Pitfalls to Avoid
Never overlap full-dose anticoagulants immediately, as this significantly increases major bleeding risk without reducing thrombotic complications 3, 2. The evidence from perioperative management studies demonstrates that overlapping anticoagulants creates excessive anticoagulation 3.
Do not use bridging anticoagulation principles here - this is a direct transition, not a perioperative bridge. Bridging with heparin while on therapeutic apixaban increases hemorrhagic risk 4, 2.
Avoid starting heparin based on coagulation parameters alone - apixaban's anticoagulant effect is not reliably measured by standard coagulation tests, so you cannot use aPTT or PT/INR to determine when it's "safe" to start heparin 5.
Clinical Context
Research demonstrates that residual apixaban significantly affects heparin response. In a prospective study of patients undergoing procedures after interrupted apixaban, standard heparin protocols resulted in delayed and lower levels of anticoagulation, requiring significantly higher heparin doses (51.3 vs 27.8 units/kg/h) to achieve therapeutic ACT levels 5. This confirms that apixaban's anticoagulant effect persists and interacts with heparin dosing requirements.