What is the management for a patient on apixaban (eliquis) with hematuria and hematochezia?

Management of Hematuria and Hematochezia in a Patient on Apixaban 5mg BID

Immediately discontinue apixaban (at least temporarily) and assess the severity of bleeding to determine if hospitalization, transfusion, or reversal agents are needed. 1

Initial Assessment and Immediate Management

Determine Bleeding Severity

The first critical step is to classify whether this represents major bleeding requiring aggressive intervention or minor bleeding that can be managed conservatively. 1

Major bleeding criteria include: 1

• Hemoglobin decrease ≥2 g/dL
• Transfusion requirement of ≥2 units of red blood cells
• Bleeding at a critical site (intracranial, intraspinal, intraocular, pericardial, retroperitoneal, intramuscular with compartment syndrome)
• Fatal bleeding

If major bleeding is present:

• Hold apixaban immediately 1
• Provide supportive care including fluid resuscitation and blood product transfusion as needed 1
• Consider reversal agents (see below) 1

If bleeding does NOT meet major criteria and hemostasis can be achieved without hospitalization, procedure, or transfusion:

• Continue apixaban may be reasonable 1
• Close monitoring is essential 1

Reversal Strategy for Major Bleeding

First-Line Reversal Agent: Andexanet Alfa

For apixaban-associated major bleeding, administer andexanet alfa as the specific reversal agent if available at your institution. 1

Dosing based on timing and dose of last apixaban: 1

Low-dose andexanet (400 mg IV bolus followed by 4 mg/min infusion for 120 minutes [480 mg total]):

• Last apixaban dose ≤5 mg taken <8 hours prior, or timing unknown
• Last apixaban dose taken ≥8 hours prior (any dose)

High-dose andexanet (800 mg IV bolus followed by 8 mg/min infusion for 120 minutes [960 mg total]):

• Last apixaban dose >5 mg taken <8 hours prior, or timing unknown
• Unknown dose of apixaban taken <8 hours prior

Clinical evidence: Andexanet alfa reduced anti-FXa activity by 92% for apixaban and achieved excellent or good hemostasis in 12 hours after infusion in the ANNEXA-4 trial. 1 The reversal effect occurs within 2 minutes and is maintained during the infusion. 2

Alternative Reversal Agents if Andexanet Alfa Unavailable

If andexanet alfa is not available, administer prothrombin complex concentrate (PCC) or activated PCC (aPCC). 1, 3

• Dosing: 50 units/kg (maximum 4,000 units) 1
• Note: These agents have not been studied in randomized trials for DOAC reversal but represent reasonable alternatives 1

Adjunctive Measures

Consider activated charcoal (50 g) if apixaban was ingested within the last 2-4 hours. 1 This reduces apixaban absorption and lowers plasma concentration. 4

Important caveat: Hemodialysis does NOT substantially impact apixaban exposure and is not recommended for reversal. 4 Protamine sulfate and vitamin K are not expected to affect apixaban's anticoagulant activity. 4

Source Identification and Treatment

While managing anticoagulation, simultaneously investigate and treat the underlying bleeding source: 1

• Hematuria: Obtain urinalysis, urine culture, renal function tests, imaging (CT urogram or ultrasound), and consider urology consultation
• Hematochezia: Assess hemodynamic stability, perform digital rectal exam, consider colonoscopy or CT angiography depending on severity

Common pitfall: Do not delay source control while waiting for anticoagulation reversal in life-threatening bleeding. Endoscopic, interventional, or surgical hemostasis may be required urgently. 1

Restarting Anticoagulation

Once the patient is stable and the bleeding source is controlled, consider restarting anticoagulation to balance thrombotic risk against recurrent bleeding risk. 1

Key considerations: 1

• Assess the ongoing indication for anticoagulation (e.g., atrial fibrillation with high stroke risk, venous thromboembolism)
• Ensure the bleeding source has been definitively addressed
• Timing depends on bleeding severity and underlying thrombotic risk
• In the ANNEXA-4 trial, 10% of patients had thrombotic events at 30 days, with the majority occurring in those NOT restarted on anticoagulation 1

Monitoring Considerations

Do not use standard coagulation tests (PT, INR, aPTT) or anti-FXa activity to monitor reversal effectiveness when using PCC. 1 These tests are not useful for guiding management in this setting.

Apixaban half-life considerations: 1

• Normal renal function (CrCl ≥80 mL/min): 6-15 hours
• Impaired renal function prolongs half-life (up to 17 hours with CrCl <15 mL/min)
• The pharmacodynamic effect persists for at least 24 hours after the last dose 4

Special Warnings

Concomitant antiplatelet agents: If the patient is also taking aspirin, clopidogrel, or other antiplatelet drugs, weigh the risk-benefit of discontinuing these agents, though it may be reasonable to stop them temporarily during major bleeding. 1 Note that irreversible antiplatelet agents (aspirin, clopidogrel, prasugrel) have prolonged effects lasting several days. 1

Thrombotic risk: Premature discontinuation of apixaban without adequate alternative anticoagulation increases the risk of thrombotic events, particularly stroke in atrial fibrillation patients. 4 This must be balanced against bleeding risk when making decisions about restarting therapy.