How do you manage bleeding with Eliquis (apixaban)?

Managing Bleeding with Eliquis (Apixaban)

For life-threatening or critical site bleeding on apixaban, immediately stop the drug and administer andexanet alfa as the specific reversal agent, with 4-factor prothrombin complex concentrate (4F-PCC) as an alternative if andexanet alfa is unavailable. 1

Initial Assessment: Classify Bleeding Severity

Determine if the bleed is major based on whether ≥1 of the following applies: 1

• Bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, intra-articular, intramuscular with compartment syndrome, or retroperitoneal)
• Hemodynamic instability
• Clinically overt bleeding with hemoglobin decrease ≥2 g/dL or transfusion of ≥2 units RBCs

If none of these criteria are met, the bleed is classified as non-major. 1

Management of Life-Threatening or Critical Site Major Bleeding

Immediate Actions: 1

• Stop apixaban immediately and discontinue any concomitant antiplatelet agents
• Secure airway and establish large-bore IV access
• Provide local therapy/manual compression at bleeding site
• Initiate supportive care and volume resuscitation
• Assess and manage comorbidities contributing to bleeding (thrombocytopenia, uremia, liver disease)
• Consider surgical/procedural management of the bleeding source

Reversal Strategy for Apixaban: 1

The American College of Cardiology recommends andexanet alfa as the specific reversal agent for apixaban, dosed as follows: 1

• Low-dose regimen (400 mg IV bolus followed by 4 mg/min infusion for 120 minutes [480 mg total]): Use if the last apixaban dose ≤5 mg was taken <8 hours prior, OR if any dose was taken ≥8 hours prior, OR timing unknown
• High-dose regimen (800 mg IV bolus followed by 8 mg/min infusion for 120 minutes [960 mg total]): Use if the last apixaban dose >5 mg was taken <8 hours prior, OR unknown dose taken <8 hours prior

If andexanet alfa is unavailable: Administer 4-factor prothrombin complex concentrate (4F-PCC) or activated PCC (aPCC) as an alternative. 1 Clinical data demonstrate that 4F-PCC achieves effective hemostasis in 72.4% of patients with major bleeding on apixaban. 2

Additional measure: Consider activated charcoal if apixaban was ingested within 2-4 hours, as it can reduce drug absorption by 50% when given 2 hours post-ingestion. 1, 3

Management of Non-Life-Threatening Major Bleeding

For major bleeding that is NOT at a critical site or life-threatening: 1

• Stop apixaban
• Provide local therapy/manual compression
• Provide supportive care and volume resuscitation
• Stop antiplatelet agents if applicable
• Assess and manage comorbidities contributing to bleeding
• Consider surgical/procedural management of bleeding site
• Do NOT administer reversal/hemostatic agents for non-critical major bleeds 1

Management of Non-Major Bleeding

For non-major bleeding: 1

• Consider continuing apixaban if there is an appropriate indication for anticoagulation
• Provide local therapy/manual compression
• If on concomitant antiplatelet therapy, assess risks and benefits of stopping
• Assess and manage comorbidities contributing to bleeding
• Verify that apixaban dosing is appropriate for the patient's renal function and other factors

Laboratory Assessment

Standard coagulation tests (PT, aPTT) are insensitive to apixaban levels. 1 A prolonged PT suggests clinically important apixaban levels, but a normal PT and aPTT do NOT exclude on-therapy or even above-therapy levels. 1

For quantitation of apixaban levels (if needed): 1

• Preferred: Anti-FXa assay calibrated specifically with apixaban
• Alternative: Liquid chromatography-tandem mass spectrometry
• Unfractionated heparin or LMWH anti-FXa assay below lower limit of quantitation probably excludes clinically relevant levels

Restarting Anticoagulation After Bleeding Control

Once the patient is stable, assess whether to restart anticoagulation: 1

Delay or discontinue anticoagulation if ≥1 of the following applies: 1

• Bleed occurred at a critical site
• Patient is at high risk of rebleeding or of death/disability with rebleeding
• Source of bleed has not been identified
• Surgical or invasive procedures are planned
• Patient does not wish to restart anticoagulation

Restart anticoagulation if: 1

• Clinical indication for continued anticoagulation exists
• Bleeding source has been controlled
• None of the above contraindications apply

Timing of resumption: For low bleeding risk with adequate hemostasis, apixaban can be resumed at least 6 hours after hemostasis is achieved. 4, 5 For high bleeding risk or incomplete hemostasis, delay resumption for 48-72 hours. 5

Critical Pitfalls to Avoid

Do not use vitamin K for apixaban reversal—it is ineffective for direct oral anticoagulants and only works for warfarin. 1

Do not delay resuscitation and local hemostatic measures while obtaining reversal agents. 1 Supportive care and bleeding control should proceed immediately.

Recognize high-risk situations for bleeding: 6, 7 Even mild renal failure, advanced age, extremes in body weight, and drug-drug interactions (particularly with antiplatelet agents, NSAIDs, and cardiovascular drugs) significantly increase bleeding risk.

Avoid unnecessary bridging with heparin products when restarting anticoagulation, as this increases bleeding risk without reducing thrombotic risk. 4, 5

Be aware of thrombotic complications: One case of multiple brain infarctions after 4F-PCC administration has been reported, highlighting the prothrombotic risk of reversal agents. 2

Monitor for rebleeding: In one study, 27.6% of patients with intracranial hemorrhage who received 4F-PCC did not achieve hemostasis, and most died during hospitalization. 2 Patients with ICH require particularly close monitoring.