How should I manage a patient with a hemoglobin of 6.4 g/dL who is taking apixaban (Eliquis)?

Management of Severe Anemia (Hemoglobin 6.4 g/dL) in a Patient on Apixaban

Immediately hold apixaban and initiate urgent evaluation for occult bleeding, as a hemoglobin of 6.4 g/dL represents severe anemia with significantly increased mortality risk, particularly in patients on anticoagulation. 1, 2

Immediate Actions

Stop apixaban immediately until the bleeding source is identified and controlled. 2, 3, 4 The FDA label for apixaban explicitly states to discontinue the drug in patients with active pathological hemorrhage. 4

Establish hemodynamic stability:

• Obtain large-bore IV access for volume resuscitation if needed 3
• Monitor vital signs closely for hemodynamic instability (hypotension, tachycardia) 1
• Patients with cardiovascular disease have significantly higher mortality risk from hemoglobin drops while anticoagulated 1, 2, 5

Urgent Diagnostic Workup

Identify the bleeding source immediately, as the absence of overt bleeding does not exclude significant hemorrhage. 2

Laboratory evaluation:

• Serial hemoglobin measurements every 4-6 hours to assess ongoing blood loss 2, 6
• PT/aPTT and coagulation studies to evaluate anticoagulant activity 1, 2
• Complete blood count with platelets 1
• Assess for comorbidities: thrombocytopenia, uremia, liver disease, renal insufficiency 2, 6

Imaging studies to locate occult bleeding:

• CT abdomen/pelvis with IV contrast to evaluate for retroperitoneal hemorrhage, intra-abdominal bleeding, or GI sources 2, 6
• CT head without contrast if any neurological symptoms or concern for intracranial hemorrhage, especially given severe baseline anemia 2
• CT angiography if active bleeding is suspected to identify extravasation or pseudoaneurysm 6

Critical pitfall: Do not assume the absence of melena or hematemesis rules out GI bleeding—occult GI bleeding is common in anticoagulated patients. 2

Transfusion Strategy

Transfuse packed red blood cells to maintain hemoglobin ≥7 g/dL (or ≥8 g/dL if coronary artery disease is present). 1, 3 With a hemoglobin of 6.4 g/dL, this patient requires immediate transfusion.

• Each unit of packed RBCs should increase hemoglobin by approximately 1 g/dL 1
• Transfuse 2-3 units initially to achieve target hemoglobin 1
• Avoid over-transfusion to prevent volume overload complications 1

Reversal Agent Considerations

Do not routinely administer andexanet alfa for non-major bleeding without hemodynamic instability. 2, 3

Consider reversal only if:

• Hemodynamic instability develops 3
• Critical site bleeding is identified (intracranial, spinal, pericardial, airway) 1, 3
• Urgent surgery is required 7

If reversal is needed, andexanet alfa is the specific reversal agent for apixaban. 3, 4 Alternatively, 4-factor prothrombin complex concentrate (PCC) may be considered, though it has not been evaluated in clinical studies for apixaban reversal. 4, 7

Note: The pharmacodynamic effect of apixaban persists for at least 24 hours after the last dose (approximately two half-lives). 4, 8

Specialty Consultation

Involve appropriate specialists early once the bleeding source is identified:

• Gastroenterology for GI bleeding 2
• Interventional radiology for angiographic embolization if active bleeding on imaging 6
• Surgery if surgical intervention is required 2

Monitoring and Follow-up

• Continue serial hemoglobin checks every 4-6 hours initially 6
• Repeat imaging if clinical deterioration occurs 6
• Monitor for signs of ongoing bleeding: hypotension, tachycardia, decreasing hemoglobin 1

Restarting Anticoagulation

Delay restarting apixaban until:

• The bleeding source is definitively identified and treated 2, 6
• Hemoglobin is stable without ongoing transfusion requirements 6
• The risk-benefit ratio favors resumption based on thrombotic risk versus bleeding risk 3, 6

Do not restart if:

• Bleeding occurred at a critical site with high rebleeding risk 6
• The bleeding source was not definitively treated 6

Critical consideration: Assess whether apixaban dosing was appropriate initially. A hemoglobin drop on correctly dosed apixaban may indicate need for dose adjustment or permanent discontinuation. 2