How do you reverse anticoagulation with Eliquis (apixaban) in a patient with a recent gastrointestinal bleed and normal renal function?

Reversing Eliquis (Apixaban) in Gastrointestinal Bleeding

For life-threatening gastrointestinal bleeding on Eliquis with normal renal function, immediately discontinue the drug and administer andexanet alfa as the specific reversal agent, using a low-dose regimen (400 mg IV bolus followed by 4 mg/min infusion for 120 minutes) if the last dose ≤5 mg was taken <8 hours prior, or high-dose regimen (800 mg IV bolus followed by 8 mg/min infusion for 120 minutes) if the last dose >5 mg was taken <8 hours prior. 1, 2, 3

Initial Assessment and Stratification

Determine bleeding severity immediately:

• Life-threatening bleeding includes hemodynamic instability requiring vasopressors, hemoglobin drop ≥2 g/dL, transfusion requirement ≥2 units RBCs, or bleeding at critical sites (intracranial, intraspinal, intraocular, retroperitoneal, pericardial, or intramuscular with compartment syndrome) 1, 2, 3
• Major but non-life-threatening bleeding meets bleeding criteria but without critical site involvement or severe hemodynamic compromise 3

Assess timing of last Eliquis dose and renal function:

• With normal renal function (CrCl >50 mL/min), apixaban has a half-life of approximately 12 hours, and anticoagulant effects dissipate within 24 hours after the last dose 1
• The drug reaches peak concentration 3-4 hours after oral administration 4

Reversal Strategy Based on Bleeding Severity

For Life-Threatening or Critical Site Bleeding

Administer andexanet alfa immediately as the American College of Cardiology-recommended specific reversal agent 1, 2, 3:

Dosing algorithm:

• Low-dose regimen: 400 mg IV bolus over 15 minutes, followed by 4 mg/min continuous infusion for 120 minutes (total 480 mg infusion) if:

  • Last apixaban dose was ≤5 mg AND taken <8 hours prior 1, 3

• High-dose regimen: 800 mg IV bolus over 15 minutes, followed by 8 mg/min continuous infusion for 120 minutes (total 960 mg infusion) if:

  • Last apixaban dose was >5 mg AND taken <8 hours prior 1, 3

If andexanet alfa is unavailable:

• Administer four-factor prothrombin complex concentrate (4F-PCC) as the alternative, which demonstrates effective hemostasis in 72.4% of patients with major bleeding on apixaban 1, 2, 3
• Note that the FDA label states there is no clinical experience reversing apixaban bleeding with 4F-PCC, though pharmacodynamic studies show endogenous thrombin potential returns to pre-apixaban levels 4 hours after PCC infusion 4

Critical pitfall: Vitamin K, fresh frozen plasma, and protamine sulfate are completely ineffective for reversing Eliquis and should never be used 1, 3

For Major Non-Life-Threatening GI Bleeding

In most cases of lower GI bleeding, simply withholding Eliquis is sufficient 1:

• Discontinue apixaban immediately 1
• Provide aggressive resuscitation with crystalloids and restrictive RBC transfusion (trigger 70 g/L, target 70-90 g/L; or trigger 80 g/L with target 100 g/L if cardiovascular disease present) 1
• Apply local hemostatic measures and manual compression where applicable 1, 3
• Wait for anticoagulant effects to dissipate naturally over 24 hours with normal renal function 1

Do not routinely use reversal agents for non-life-threatening bleeding, as the British Society of Gastroenterology states reversal with andexanet should be reserved for life-threatening hemorrhage only 1

Supportive Management

Discontinue concomitant antiplatelet agents if safely possible 1, 3:

• Aspirin and clopidogrel have irreversible effects lasting 5-7 days, so temporary discontinuation may not provide immediate benefit 1
• However, stopping these agents reduces ongoing bleeding risk 1

Consider activated charcoal if recent ingestion:

• If apixaban was taken within 2-4 hours, activated charcoal reduces absorption by 50% at 2 hours and 27% at 6 hours 1, 4

Seek hematology consultation for severe bleeding 1

Laboratory Monitoring Pitfalls

Standard coagulation tests are unreliable for apixaban:

• PT, aPTT, and INR are insensitive to apixaban levels and should not guide management 3, 4
• A normal PT/aPTT does NOT exclude therapeutic or supratherapeutic apixaban levels 3
• A prolonged PT suggests clinically important levels, but normal values are not reassuring 3

If quantitation is needed:

• Use anti-Factor Xa assay calibrated specifically for apixaban, or liquid chromatography-tandem mass spectrometry 3, 4

Restarting Anticoagulation After Bleeding Control

Resume apixaban at a maximum of 7 days after hemorrhage in patients with ongoing anticoagulation indication 1:

• Patients with atrial fibrillation have relatively low thrombotic risk during temporary discontinuation 1
• Higher thrombotic risk exists in patients with recent stroke, prosthetic metal heart valves, or recent venous thromboembolism (<3 months) 1

Delay or permanently discontinue anticoagulation if:

• Bleeding occurred at a critical site 2
• Patient is at high risk of rebleeding or death/disability with rebleeding 2
• Source of bleeding has not been identified 2
• Surgical or invasive procedures are planned 2

For high thrombotic risk patients (prosthetic metal mitral valve, atrial fibrillation with prosthetic valve or mitral stenosis, <3 months after VTE):

• Consider bridging with low molecular weight heparin starting at 48 hours after hemostasis is achieved 1

Critical consideration: The 30-day risk of thromboembolic complications after reversal is approximately 4.8-7.4%, with most events occurring in patients whose anticoagulation was not restarted 2

Special Considerations for This Patient

With normal renal function:

• Apixaban clearance is not prolonged, so the standard 24-hour dissipation timeline applies 1
• No dose adjustments or extended monitoring periods are needed 4

Endoscopic intervention timing:

• Proceed with urgent colonoscopy or upper endoscopy as clinically indicated once hemodynamic stability is achieved 1
• Access to 7-day on-site colonoscopy with therapeutic capability should be available 1