What are the management options for a patient on Eliquis (apixaban) with elevated hemoglobin and hematocrit levels?

Elevated Hemoglobin and Hematocrit on Eliquis

Elevated hemoglobin and hematocrit in a patient on apixaban (Eliquis) is not a contraindication to continuing therapy and does not require dose adjustment, but warrants investigation for the underlying cause of polycythemia and assessment for bleeding risk versus thrombotic risk.

Initial Assessment

The presence of elevated hemoglobin/hematocrit while on apixaban requires determining whether this represents:

• Primary polycythemia (polycythemia vera or other myeloproliferative disorder)
• Secondary polycythemia (chronic hypoxia, smoking, sleep apnea, renal pathology)
• Relative polycythemia (dehydration, diuretic use)
• Hemoconcentration from occult bleeding with volume depletion 1

Critical distinction: Anemia (not elevated hemoglobin) is the hematologic abnormality associated with increased bleeding risk and mortality in anticoagulated patients with atrial fibrillation 1. Patients with anemia on apixaban have a 1.92-fold increased risk of major bleeding and 1.68-fold increased mortality risk, though apixaban remains safer than warfarin in this population 1.

Management Algorithm

Step 1: Rule Out Measurement Error and Hemoconcentration

• Repeat complete blood count with manual differential to confirm elevated values
• Assess volume status clinically and check BUN/creatinine ratio to exclude dehydration 1
• Review medications that may cause hemoconcentration (diuretics, testosterone)

Step 2: Evaluate for Occult Bleeding

• Check stool for occult blood and review for any signs of gastrointestinal, genitourinary, or other bleeding 2
• Monitor serial hemoglobin/hematocrit every 2-3 days if bleeding suspected, as recommended for heparin monitoring protocols 3
• Paradoxically, patients may present with elevated hematocrit due to volume contraction from chronic blood loss 1

Step 3: Assess Thrombotic Risk

• Calculate CHA₂DS₂-VASc score if apixaban is for atrial fibrillation, or assess VTE recurrence risk if for venous thromboembolism 4
• Patients with high thrombotic risk (CHA₂DS₂-VASc ≥2 or recent VTE within 3 months) should not have apixaban interrupted for workup 4

Step 4: Perform Hypercoagulable Workup While Continuing Apixaban

Do not stop apixaban for testing - most thrombophilia tests can be performed on therapy 4:

• Genetic testing (Factor V Leiden, Prothrombin G20210A) - unaffected by apixaban 4
• Antiphospholipid antibodies (anti-cardiolipin, anti-beta-2-glycoprotein I) - can be checked on therapy, though lupus anticoagulant may be affected 4
• JAK2 mutation and erythropoietin level if polycythemia vera suspected
• Platelet count to evaluate for myeloproliferative disorders 4

Step 5: Renal Function Assessment

• Calculate creatinine clearance - apixaban clearance is prolonged in renal dysfunction with half-life up to 17 hours 4
• Severe renal impairment (CrCl <15 mL/min) is a relative contraindication to apixaban 4
• Dose adjustment may be needed if CrCl 15-29 mL/min or if patient meets two of three criteria: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL

Continuation of Apixaban

Continue apixaban without interruption in the following scenarios:

• High thrombotic risk (recent VTE, high CHA₂DS₂-VASc score) 4
• No evidence of active major bleeding 5, 2
• Hemoglobin stable on serial monitoring 1

Hold apixaban immediately only if:

• Major bleeding occurs (hemodynamically unstable, hemoglobin drop ≥2 g/dL, or requiring ≥2 units transfusion) 5, 2
• Consider andexanet alfa for life-threatening bleeding 5, 2
• Activated charcoal if last dose within 2 hours 5

Common Pitfalls

• Do not use PT/aPTT to assess apixaban levels - normal values do not exclude therapeutic or supratherapeutic levels 4
• If quantitation needed, use anti-Factor Xa assay calibrated specifically for apixaban 4
• Do not assume elevated hemoglobin means lower bleeding risk - the relationship is complex and anemia (not polycythemia) is the established bleeding risk factor 1
• Do not stop anticoagulation for workup unless active major bleeding present - stopping poses significant thrombotic risk 4

Monitoring Strategy

• Serial CBC monitoring every 2-3 days initially if bleeding suspected, then every 2 weeks 3
• Restrictive transfusion thresholds if bleeding occurs: hemoglobin trigger 70 g/L (80 g/L if cardiovascular disease) 2
• Reassess indication for anticoagulation if bleeding controlled, weighing thrombotic versus bleeding risk 5, 2