What workup or treatment should be considered for a patient with a history of deep vein thrombosis (DVT) on Eliquis (apixaban) with consistently elevated hemoglobin and hematocrit levels?

Workup and Management for Recurrent DVT with Elevated Hemoglobin/Hematocrit

This patient with recurrent unprovoked DVT and persistently elevated hemoglobin/hematocrit requires immediate evaluation for polycythemia vera (PV) and should continue extended anticoagulation given the second unprovoked VTE event.

Immediate Diagnostic Workup

Polycythemia Vera Evaluation

• The elevated hemoglobin (15.9-16.0 g/dL) and hematocrit (47.0-47.2%) meet diagnostic thresholds for PV in women (Hgb >16.0 g/dL, Hct >48%) 1, 2
• The JAK2 mutation testing already collected is critical, as >95% of PV patients harbor a JAK2 gene variant, which distinguishes PV from secondary erythrocytosis 1, 2
• Bone marrow examination should be performed for morphologic confirmation if JAK2 is positive, though not mandated for diagnosis 2
• The EPO level already collected will help differentiate PV (low EPO) from secondary causes (elevated EPO) 1
• Screen for additional mutations including TET2, ASXL1, SRSF2, IDH2, RUNX1, and U2AF1, as these have prognostic implications 2

Thrombophilia Assessment

• The elevated DRVVT screen (55) suggests possible antiphospholipid antibody syndrome, which requires confirmation with repeat testing at 12 weeks 3
• The protein C activity of 197 is elevated, likely due to acute phase reaction or current anticoagulation with Eliquis 3
• Thrombophilia testing should ideally be performed off anticoagulation, but given recurrent unprovoked VTE, this patient requires extended anticoagulation regardless of results 4, 3

Occult Malignancy Screening

• Screen for occult malignancy in patients with unprovoked VTE, as cancer-associated thrombosis requires different management 3
• Age-appropriate cancer screening including CT chest/abdomen/pelvis should be considered 4

Anticoagulation Management

Duration of Therapy

• For a second unprovoked VTE with low bleeding risk, extended anticoagulation is strongly recommended (Grade 1B) 4, 3
• If moderate bleeding risk exists, extended anticoagulation is still suggested (Grade 2B) 4, 3
• The patient is appropriately on Eliquis (apixaban), which is acceptable for extended therapy 5

Dosing Considerations

• After completing initial treatment phase (typically 6 months), consider reduced-dose apixaban 2.5 mg twice daily for extended-phase therapy 4
• Reduced-dose apixaban (2.5 mg BID) is suggested over full-dose (5 mg BID) for extended therapy, with similar efficacy and potentially lower bleeding risk 4, 5
• Reassess the need for continued anticoagulation at least annually 4, 3

Special Considerations if PV Confirmed

• If PV is diagnosed, all patients should receive therapeutic phlebotomy with hematocrit target <45% in addition to anticoagulation 1, 2
• Low-dose aspirin (81 mg daily) should be added if no contraindications exist, though this must be carefully weighed against bleeding risk while on therapeutic anticoagulation 1, 2
• Patients aged >60 years or with prior thrombosis are high-risk and may benefit from cytoreductive therapy with hydroxyurea or pegylated interferon-α 1, 2

Additional Management

Monitoring Strategy

• Monitor hemoglobin and hematocrit at least every 2-3 days for the first 14 days after any treatment change, then every 2 weeks 4
• Assess for PV-related symptoms including pruritus, erythromelalgia, transient visual changes, and splenomegaly 1
• Monitor for post-thrombotic syndrome development 3, 6

Bleeding Risk Assessment

• The American College of Chest Physicians assesses bleeding risk using criteria such as age, prior bleeding episodes, and concomitant antiplatelet therapy 3
• Current hemoglobin/hematocrit levels are not in the extreme thrombocytosis range (platelet count ≥1000 × 10⁹/L) that would increase bleeding risk from acquired von Willebrand disease 1

Critical Pitfalls to Avoid

• Do not discontinue anticoagulation based solely on identifying a "cause" for the elevated hemoglobin/hematocrit - recurrent unprovoked VTE mandates extended therapy regardless 4, 3
• Do not perform thrombophilia testing to determine anticoagulation duration - the decision for extended therapy is already made based on recurrent unprovoked VTE 4, 3
• If PV is confirmed, do not rely solely on anticoagulation - phlebotomy to maintain hematocrit <45% is essential to reduce thrombosis risk 1, 2
• Avoid adding aspirin to therapeutic anticoagulation without careful bleeding risk assessment, as this significantly increases hemorrhagic complications 1