How to manage a new Deep Vein Thrombosis (DVT) in a patient already on Eliquis (Apixaban) for an old DVT?

Management of New DVT While on Eliquis for Old DVT

For patients who develop a breakthrough DVT while on therapeutic apixaban (Eliquis), switching to low molecular weight heparin (LMWH) therapy is recommended over continuing or adjusting the DOAC regimen. 1

Assessment of Breakthrough DVT

When a patient on apixaban develops a new DVT, initial evaluation should focus on:

• Confirmation of therapeutic compliance with apixaban
• Verification that the dosing regimen was appropriate (10 mg twice daily for 7 days followed by 5 mg twice daily for treatment phase)
• Evaluation for underlying conditions that may contribute to anticoagulation failure:
  • Cancer
  • Antiphospholipid syndrome
  • Vasculitis
  • Drug-drug interactions affecting apixaban metabolism

Management Algorithm

Step 1: Confirm Breakthrough Event

• Verify the diagnosis with appropriate imaging
• Assess the extent and location of the new thrombosis

Step 2: Evaluate Potential Causes

• Check patient adherence to apixaban therapy
• Review for potential drug interactions (particularly CYP3A4 and P-glycoprotein inhibitors/inducers)
• Consider underlying hypercoagulable conditions

Step 3: Initiate Treatment

1. Primary Recommendation: Switch to LMWH

   • The ASH 2020 guidelines specifically recommend using LMWH over DOAC therapy for breakthrough VTE during anticoagulant treatment (conditional recommendation) 1
   • LMWH dosing:
     • Enoxaparin: 1 mg/kg twice daily or 1.5 mg/kg once daily
     • Dalteparin: 200 U/kg once daily for the first month, then 150 U/kg once daily
     • Tinzaparin: 175 U/kg once daily 2

2. Alternative Approaches (if LMWH contraindicated):

   • Consider unfractionated heparin (UFH) for patients with severe renal impairment (CrCl <30 mL/min)
   • Initial bolus of 80 U/kg followed by 18 U/kg per hour infusion, adjusted to maintain aPTT at 1.5-2.5 times baseline 1

Step 4: Duration of Therapy

• Continue anticoagulation for at least 3 months from the new DVT event 2
• For patients with unprovoked DVT or ongoing risk factors, extended therapy is recommended 1
• For patients at low-to-moderate bleeding risk, extended therapy is recommended (grade 2B) 1
• For those with high bleeding risk, treatment may be discontinued after 3 months (grade 1B) 1

Special Considerations

Cancer Patients

• LMWH is strongly preferred over DOACs for cancer patients with breakthrough VTE 1, 2
• For cancer-associated thrombosis, use 75-80% of the initial LMWH dose (approximately 150 U/kg once daily) for long-term therapy 2

Monitoring Requirements

• Baseline testing should include complete blood count, renal and hepatic function panel, aPTT, and PT/INR
• Follow-up monitoring of hemoglobin, hematocrit, and platelet count every 2-3 days for the first 14 days, then every 2 weeks 2

Common Pitfalls to Avoid

1. Continuing the same DOAC regimen - Breakthrough VTE while on therapeutic anticoagulation suggests the current regimen is ineffective and requires a change in approach

2. Increasing DOAC dose without evidence - Simply increasing the apixaban dose beyond FDA-approved dosing is not recommended and lacks evidence

3. Failing to investigate underlying causes - Always evaluate for cancer, antiphospholipid syndrome, or other hypercoagulable conditions when breakthrough thrombosis occurs

4. Inadequate duration of therapy - Ensure appropriate duration of anticoagulation based on risk factors and bleeding risk

5. Overlooking drug interactions - Medications affecting CYP3A4 and P-glycoprotein can alter apixaban levels and efficacy

By following this evidence-based approach, clinicians can effectively manage patients who develop breakthrough DVT while on apixaban therapy, reducing the risk of recurrent thrombotic events while minimizing bleeding complications.