What laboratory tests should be obtained and monitored for a patient started on apixaban (Eliquis)?

Laboratory Monitoring for Patients on Apixaban (Eliquis)

Routine laboratory monitoring of anticoagulant effect is not required for patients on apixaban, but baseline and periodic laboratory testing should be performed to assess organ function and bleeding risk. 1

Baseline Laboratory Testing (Before Starting Apixaban)

Before initiating apixaban therapy, obtain the following baseline tests 1:

• Complete blood count (CBC) with platelet count 1
• Renal function panel including serum creatinine and calculated creatinine clearance (CrCl) 1
• Hepatic function panel including ALT, AST, and total bilirubin 1
• Activated partial thromboplastin time (aPTT) 1
• Prothrombin time (PT)/International Normalized Ratio (INR) 1

Rationale for Baseline Testing

The renal and hepatic function tests are critical because apixaban dosing depends on kidney function, and the drug is contraindicated in severe hepatic impairment. Apixaban has 27% renal clearance and requires dose reduction when CrCl is 15-50 mL/min combined with other risk factors (age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 1. The drug is contraindicated when CrCl is <15 mL/min according to most guidelines, though some evidence suggests potential use in end-stage renal disease with caution 1, 2.

Ongoing Monitoring During Therapy

Hematologic Monitoring

• Hemoglobin, hematocrit, and platelet count: Check at least every 2-3 days for the first 14 days in hospitalized patients, then every 2 weeks thereafter or as clinically indicated 1
• For outpatients, periodic CBC monitoring is reasonable, particularly in high-risk patients or those with bleeding concerns 1

Renal Function Monitoring

• Monitor renal function periodically, especially in patients with baseline renal impairment, elderly patients (≥75 years), or those receiving nephrotoxic chemotherapy 1
• The frequency should be increased in patients with CrCl 30-50 mL/min or those at risk for acute kidney injury 1
• Declining renal function is an independent predictor of stroke risk and may necessitate dose adjustment or drug discontinuation 1

Hepatic Function Monitoring

• Monitor liver function tests in patients with baseline hepatic impairment or those receiving hepatotoxic chemotherapy 1
• Apixaban is contraindicated when ALT/AST >2× upper limit of normal (ULN) with total bilirubin >1.5× ULN 1

When Anticoagulant Effect Assessment Is Needed

Although routine monitoring of anticoagulant effect is unnecessary, specific clinical situations may warrant assessment 1, 3:

Situations Requiring Drug Level Assessment

• Life-threatening bleeding 1
• Need for urgent surgery or invasive procedure 1
• Suspected drug accumulation (e.g., acute renal failure) 4
• Thromboembolic event while on therapy 1
• Suspected overdose 1

Appropriate Tests for Apixaban Quantification

The preferred test is a chromogenic anti-factor Xa assay calibrated specifically with apixaban standards 1, 5, 3. This assay demonstrates excellent correlation (r² = 0.78-1.00) across a wide range of apixaban concentrations 3.

Important Caveats About Standard Coagulation Tests

• PT and aPTT are NOT sensitive enough to reliably detect or quantify apixaban 1, 5, 3
• PT and aPTT are insensitive to apixaban; a normal PT and aPTT do not exclude on-therapy or even above-therapeutic levels 1
• A prolonged PT suggests clinically important apixaban levels, but cannot quantify them 1
• INR is NOT recommended for monitoring apixaban, though apixaban can prolong INR (typically median 1.4-1.7, rarely >20) 6, 3
• If an apixaban-calibrated anti-Xa assay is unavailable, an anti-Xa assay calibrated with unfractionated heparin or low-molecular-weight heparin can exclude clinically relevant drug levels if below the lower limit of quantitation, but cannot accurately quantify apixaban 1

Special Monitoring Considerations

Patients with End-Stage Renal Disease

• Apixaban use in ESRD is controversial; the FDA label provides limited guidance 1, 4, 2
• If used in ESRD patients on hemodialysis, the recommended dose is 5 mg twice daily, reduced to 2.5 mg twice daily if age ≥80 years or weight ≤60 kg 1
• Close monitoring for bleeding is essential, as drug accumulation can occur despite dose reduction 4
• Anti-factor Xa monitoring may be considered, though clinical correlation is uncertain 4

Patients with Hypoalbuminemia

• Apixaban is 87-94% protein-bound to albumin 7
• In patients with nephrotic syndrome or fluctuating albumin levels, free drug concentrations may vary unpredictably even when total drug levels remain stable 7
• Until pharmacokinetic studies are performed in hypoalbuminemia, warfarin with INR monitoring may be preferable 7

Transitioning from Apixaban to Unfractionated Heparin

• If transitioning from apixaban to UFH within 1 week of last apixaban dose, obtain a baseline UFH-calibrated anti-Xa activity test before starting UFH to detect residual apixaban interference 1
• Residual anti-Xa activity can persist for 48-72 hours after the last apixaban dose in 73% and 33% of patients, respectively 1
• Consider using aPTT for UFH monitoring instead of anti-Xa assay when recent apixaban exposure is present, though this assumes baseline aPTT is normal 1