When to use apixaban (eliquis) in patients with venous thromboembolism (VTE) and positive antiphospholipid (aPL) antibodies?

Apixaban Use in Venous Thromboembolism with Positive Antiphospholipid Antibodies

Apixaban should not be used in patients with venous thromboembolism (VTE) who have positive antiphospholipid antibodies (aPL), particularly those with triple-positive aPL. Instead, warfarin or heparin-containing products should be used for these patients 1.

Rationale for Avoiding Apixaban in aPL-Positive Patients

• Safety and effectiveness concerns have been documented when using apixaban in patients with antiphospholipid syndrome (APS), with evidence of VTE recurrence and bleeding complications 1
• Warfarin remains the best choice to prevent VTE recurrence in patients with APS 1, 2
• For patients with definite APS, prolonged warfarin therapy at a target INR of 2.0-3.0 is recommended for first venous events, and INR >3.0 for recurrent and/or arterial events 2
• The American Society of Hematology specifically suggests using LMWH over DOAC therapy for patients with breakthrough VTE during therapeutic anticoagulation 3

General Apixaban Use in VTE Without aPL

When apixaban is appropriate for VTE patients without aPL, the following guidelines apply:

• Initiate at 10 mg twice daily for the first 7 days, followed by 5 mg twice daily for the remainder of treatment 3, 4
• Apixaban has shown noninferiority to conventional therapy (enoxaparin/warfarin) for VTE treatment with significantly less bleeding 4
• Based on high-quality evidence from large randomized controlled trials, apixaban has a category 1 recommendation for DVT/PE treatment in patients without APS 3

Contraindications and Cautions for Apixaban

• Avoid apixaban in patients with severe hepatic impairment 3
• Use with caution in patients with renal dysfunction, as 27% of the drug is eliminated through renal clearance 3
• Avoid in patients with severe renal impairment (CrCl <15 mL/min) 3, 5
• Patients with gastric and gastroesophageal tumors are at increased risk for hemorrhage with DOACs, and LMWHs are preferred in this setting 3

Special Populations

• For patients with cancer-associated VTE without aPL, apixaban has shown lower or similar rates of recurrent VTE compared with dalteparin 3
• For patients with provoked VTE and enduring risk factors (but without aPL), low-intensity therapy with apixaban (2.5 mg twice daily) for extended treatment has shown lower risk of symptomatic recurrent VTE than placebo, with a low risk of major bleeding 6
• Patients with a history of VTE who have a single positive aPL test should undergo further testing to determine if they have a persistent antibody before determining treatment 2

Algorithm for Decision-Making

1. Test for aPL in patients with unprovoked VTE or those with clinical features suggesting APS 2
2. If positive for aPL (especially triple-positive), use warfarin with target INR 2.0-3.0 for first venous events and >3.0 for recurrent/arterial events 2
3. If negative for aPL, apixaban can be used following standard dosing regimen 3, 4
4. For patients with a single positive aPL test, repeat testing to confirm persistence before making treatment decisions 2

Common Pitfalls

• Using DOACs in APS patients despite lack of evidence supporting their use in this population 1
• Failing to test for aPL in patients with unprovoked VTE or those with clinical features suggesting APS 2
• Not recognizing that patients with triple-positive aPL are at particularly high risk for recurrent thrombosis and require more intensive anticoagulation 1, 2
• Overlooking the need for indefinite anticoagulation in patients with APS 2