What is the recommended timing for transitioning a patient with normal renal function from Eliquis (apixaban) to heparin (unfractionated heparin or low molecular weight heparin)?

Transitioning from Apixaban to Heparin

Direct Answer

When transitioning from apixaban to heparin in patients with normal renal function, discontinue apixaban and start heparin (either unfractionated heparin or low-molecular-weight heparin) at the time the next dose of apixaban would have been due—no overlap or gap is needed. 1

Timing Protocol

For Unfractionated Heparin (UFH)

• Stop apixaban and initiate UFH infusion immediately when the next apixaban dose would be scheduled 1
• No bridging or overlap period is required due to UFH's rapid onset of action 1
• Standard UFH dosing: 80 units/kg IV bolus, then 18 units/kg/hour infusion, targeting aPTT 1.5-2.5 times control 2

For Low-Molecular-Weight Heparin (LMWH)

• Administer the first LMWH dose at the exact time the next scheduled apixaban dose would be due 1
• No overlap therapy is necessary 1
• Standard LMWH dosing options include:
  • Enoxaparin 1 mg/kg subcutaneously every 12 hours, or 1.5 mg/kg once daily 2
  • Dalteparin 200 IU/kg subcutaneously once daily 2

Key Pharmacologic Considerations

Why No Overlap is Needed

• Apixaban has a relatively short half-life of 7-8 hours in patients with normal renal function 2
• Apixaban is 25% renally cleared, meaning most is eliminated through non-renal pathways 2, 1
• By the time the next apixaban dose would be due (12 hours after the last dose), anticoagulant effect is significantly diminished 2
• Both UFH and LMWH provide immediate anticoagulation upon administration 2

Monitoring Considerations

• For UFH: Monitor aPTT every 6 hours initially until therapeutic range achieved, then daily 2
• For LMWH: Routine monitoring not required in most patients; consider anti-Xa levels (target 0.3-0.7 IU/mL) only in special populations (obesity, renal impairment, pregnancy) 2
• Baseline heparin anti-Xa activity may help identify residual apixaban concentrations if measured immediately before starting heparin, allowing better individualization of initial heparin dosing 3

Special Clinical Scenarios

High Thrombotic Risk Patients

• Ensure absolutely no gap in anticoagulation coverage by starting heparin at the precise time the next apixaban dose would be due 4
• Consider mechanical heart valves, recent large PE, or active arterial thrombosis as high-risk situations requiring meticulous timing 2

Renal Impairment

• For patients with creatinine clearance <30 mL/min, apixaban clearance is prolonged 2, 1
• Consider extending the interval before starting heparin to 18-24 hours after the last apixaban dose in severe renal impairment to avoid excessive anticoagulation 2
• UFH is preferred over LMWH when CrCl <30 mL/min due to LMWH accumulation risk 2

Perioperative Transitions

• If transitioning for urgent surgery with high bleeding risk, apixaban should be held for 48 hours (approximately 6 half-lives) before starting heparin 2
• For emergent procedures, heparin can be started immediately after apixaban discontinuation, but bleeding risk is elevated 2

Common Pitfalls to Avoid

Critical Errors

• Do not overlap apixaban and heparin therapy—this significantly increases bleeding risk without additional antithrombotic benefit 1, 4
• Do not delay heparin initiation beyond the next scheduled apixaban dose—this creates a dangerous gap in anticoagulation coverage 1
• Do not use aPTT to monitor UFH in the first 6-12 hours after apixaban discontinuation—residual apixaban may artificially prolong aPTT; consider using anti-Xa assay instead 3

Dosing Mistakes

• Avoid starting UFH at subtherapeutic doses—use weight-based protocols with adequate bolus dosing 2, 5
• Do not use once-daily LMWH dosing for acute VTE treatment unless using the full anticoagulant dose (enoxaparin 2 mg/kg or dalteparin 200 IU/kg) 2

Monitoring Errors

• Expect more frequent heparin infusion rate adjustments in the first 36 hours after transitioning from apixaban, as residual anti-Xa activity may affect initial dosing requirements 3
• Do not assume therapeutic anticoagulation is maintained—only 29% of patients remain in therapeutic aPTT range for consecutive measurements even after initial achievement 5

Preference for Heparin Type

• LMWH is preferred over UFH for most patients due to lower risk of heparin-induced thrombocytopenia (HIT), more predictable pharmacokinetics, and no need for continuous infusion 2
• UFH is preferred when:
  • Primary reperfusion therapy (thrombolysis, thrombectomy) is being considered 2
  • Severe renal impairment (CrCl <30 mL/min) is present 2
  • Rapid reversibility with protamine may be needed 2
  • Severe obesity complicates LMWH dosing 2