In a patient with suspected deep vein thrombosis who has normal renal function and is not pregnant or breastfeeding, what is the initial apixaban dosing regimen and which imaging study should be obtained?

Initial Apixaban Dosing and Imaging for Suspected DVT

For a patient with suspected DVT and normal renal function, initiate apixaban 10 mg orally twice daily for 7 days, then 5 mg twice daily, and obtain compression ultrasonography of the affected extremity as the first-line imaging study. 1, 2

Apixaban Dosing Regimen

Loading Phase (Days 1-7)

• Administer apixaban 10 mg orally twice daily for the first 7 days without any parenteral anticoagulation lead-in. 1, 2 This distinguishes apixaban from dabigatran and edoxaban, which require 5-10 days of parenteral therapy before initiation. 1, 2

• The 10 mg twice daily loading dose provides immediate therapeutic anticoagulation and eliminates the need for bridging with enoxaparin or unfractionated heparin. 2, 3

Maintenance Phase (Day 8 Onward)

• Switch to apixaban 5 mg orally twice daily beginning on day 8 and continue for a minimum of 3 months. 1, 2 This maintenance dose applies regardless of whether the DVT is provoked or unprovoked during the initial treatment period. 2

Critical Dosing Considerations

• Do not confuse the VTE treatment dose with the atrial fibrillation dose. 2 The age ≥80 years and weight ≤60 kg dose-reduction criteria used for atrial fibrillation do NOT apply when treating VTE. 2, 4 All patients receive the standard 10 mg twice daily loading and 5 mg twice daily maintenance doses regardless of age or weight, unless severe renal impairment is present. 2

• Do not use the 2.5 mg twice daily dose during initial treatment. 5, 2 This reduced dose is only for extended secondary prevention after completing at least 6 months of standard therapy or for prophylaxis in specific surgical settings. 5, 2

Imaging Study Selection

First-Line Imaging

• Compression ultrasonography (duplex ultrasound) of the affected extremity is the initial imaging modality of choice for suspected lower extremity DVT. 1 This non-invasive test has high sensitivity and specificity for proximal DVT and can be performed at the bedside. 1

Alternative Imaging Scenarios

• If compression ultrasonography is negative but clinical suspicion remains high, consider repeat ultrasound in 5-7 days or proceed to venography or MR venography. 1

• For suspected upper extremity DVT or when ultrasound is technically inadequate, consider CT venography or MR venography as alternative imaging modalities. 1

• For suspected pulmonary embolism accompanying DVT, CT pulmonary angiography is the gold standard imaging study. 1

Renal Function Assessment

Pre-Treatment Evaluation

• Check creatinine clearance using the Cockcroft-Gault formula before initiating apixaban therapy. 5, 2 This is mandatory as renal function determines safety and appropriateness of apixaban use. 5

Dosing Based on Renal Function

• For CrCl >50 mL/min: Use standard dosing (10 mg twice daily × 7 days, then 5 mg twice daily). 5, 2

• For CrCl 30-50 mL/min: Use standard dosing with no adjustment needed for treatment. 5, 2 Apixaban has only 27% renal elimination, making it more favorable than other DOACs in mild-to-moderate renal impairment. 5, 6

• For CrCl 15-30 mL/min: Use apixaban with caution at standard initial dosing, but consider switching to enoxaparin or monitoring closely. 2, 6

• For CrCl <15 mL/min: Apixaban is contraindicated. 5, 2, 6 Use enoxaparin 1 mg/kg subcutaneously every 12 hours with anti-Xa monitoring or unfractionated heparin instead. 2

Duration of Anticoagulation

Minimum Treatment Duration

• Continue anticoagulation for at least 3 months for all DVT patients. 1, 2 This applies to both provoked and unprovoked DVT during the initial treatment phase. 2

Extended Therapy Considerations

• For provoked DVT (e.g., surgery, immobilization, long-haul travel): Discontinue anticoagulation after 3 months. 2 Extension beyond 3 months is not indicated unless recurrent DVT occurs. 2

• For unprovoked DVT: Consider indefinite anticoagulation with annual reassessment of bleeding risk versus thrombosis risk. 2 After 6 months of standard-dose therapy, the dose may be reduced to 2.5 mg twice daily for extended secondary prevention. 1, 2

• For recurrent VTE: Indefinite anticoagulation is recommended. 2

Drug Interactions and Contraindications

Absolute Contraindications

• Active bleeding, severe hepatic impairment (Child-Pugh C), and intracranial vascular malformations are contraindications. 1, 6

• Severe renal impairment (CrCl <15 mL/min) is an absolute contraindication. 5, 2, 6

Critical Drug Interactions

• Avoid concurrent use with combined P-glycoprotein and strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, clarithromycin). 5, 2 These can significantly increase apixaban levels and bleeding risk. 5

• Avoid combination with other anticoagulants, antiplatelets (especially dual antiplatelet therapy), NSAIDs, SNRIs, or SSRIs due to increased bleeding risk. 1, 2

Relative Contraindications

• Pregnancy and breastfeeding: Apixaban crosses the placenta. 1 Use LMWH instead. 1

• Neuraxial anesthesia: Do not perform spinal or epidural procedures if insufficient discontinuation time has elapsed (typically 48-72 hours). 5

Monitoring Requirements

Laboratory Monitoring

• Routine laboratory monitoring of anticoagulant effect is not required for apixaban at standard doses. 2 This is a key advantage over warfarin. 2

• Baseline laboratory assessment should include: complete blood count with platelets, renal function (creatinine clearance), hepatic function (AST, ALT, bilirubin), and PT/INR. 2

• If clinically significant bleeding is suspected, repeat hemoglobin/hematocrit testing, but no regular monitoring schedule is needed. 2

Common Pitfalls to Avoid

• Do not apply atrial fibrillation dose-reduction criteria to VTE treatment. 5, 2 The 2.5 mg twice daily dose used in elderly or low-weight AF patients does not apply to acute VTE treatment. 2

• Do not skip the 7-day loading phase. 2, 7 Shortened lead-in therapy (fewer than 7 days at 10 mg twice daily) has been associated with increased bleeding events, particularly in patients with bleeding risk factors. 7

• Do not use apixaban in cancer-associated thrombosis as first-line therapy. 1 LMWH (dalteparin 200 U/kg once daily for 1 month, then 150 U/kg once daily) is preferred for the first 6 months in cancer patients. 1 Apixaban is upgraded to grade 1A as an alternative but remains second-line to LMWH. 1

• Do not forget to assess for gastrointestinal or genitourinary malignancy risk. 1 Patients at high risk of GI or GU bleeding may be better served with LMWH or a different DOAC. 1