How should I manage a 50‑year‑old woman with menorrhagia due to a small central uterine fibroid, recent extensive proximal left‑leg deep‑vein thrombosis treated with thrombectomy and inferior vena cava filter placement, who now has recurrent proximal deep‑vein thrombosis despite therapeutic apixaban (Eliquis)?

Management of Recurrent DVT Despite Apixaban in a Patient with Menorrhagia and Uterine Fibroid

Switch immediately to therapeutic low-molecular-weight heparin (enoxaparin 1 mg/kg subcutaneously every 12 hours) given documented treatment failure on apixaban, and plan for IVC filter removal once stable on LMWH. 1

Anticoagulation Strategy for Recurrent VTE

Primary anticoagulation approach:

• Transition from apixaban to therapeutic LMWH is the definitive next step for recurrent proximal DVT despite DOAC therapy, as LMWH has superior efficacy in high-risk VTE scenarios 1
• Dose escalation of LMWH by 20–25% should be considered if recurrence occurs even on standard LMWH dosing, with target peak anti-FXa levels of 0.8–1.0 U/mL for twice-daily regimens 1
• Continue anticoagulation for a minimum of 6 months, but extended-duration (indefinite) anticoagulation is strongly indicated given recurrent thrombosis with unclear provocation and persistent risk factors 1

Critical pitfall to avoid:

• Do not simply increase apixaban dose or switch to another DOAC—the evidence for NOACs in recurrent VTE is insufficient, and cancer-associated thrombosis guidelines explicitly recommend LMWH over DOACs for high-risk scenarios 1

IVC Filter Management

The existing IVC filter should be removed as soon as therapeutic anticoagulation is established:

• IVC filters do not reduce mortality and are associated with increased recurrent DVT risk (up to 30% filter-site thrombosis), making removal imperative once anticoagulation is therapeutic 1
• Filters are NOT indicated for recurrent VTE when anticoagulation can be safely administered—their only role is as a temporary bridge during absolute contraindications to anticoagulation 1, 2
• Plan filter removal within 2–4 weeks of achieving stable therapeutic anticoagulation on LMWH, with venography at retrieval to assess for filter-associated thrombus 2, 3

Key evidence:

• The PREPIC trial demonstrated that permanent IVC filters increase DVT without reducing mortality 1
• Multiple guidelines recommend against systematic filter insertion for recurrent VTE in the absence of bleeding contraindications 1

Thrombophilia Workup

Comprehensive hypercoagulable evaluation is mandatory:

• Antiphospholipid antibody syndrome testing (lupus anticoagulant, anticardiolipin IgG/IgM, beta-2 glycoprotein IgG/IgM) is the highest-yield test given recurrent thrombosis 1
• Factor V Leiden and prothrombin G20210A mutation testing should be performed 1
• Protein C, protein S, and antithrombin levels are less reliable during acute thrombosis and while anticoagulated—defer until 2–3 months after completing acute treatment if results will change management 1

Important timing consideration:

• Some assays (particularly lupus anticoagulant) are unreliable on LMWH, but do not delay LMWH initiation—repeat testing after acute phase if initial results are equivocal 1

Anatomic Evaluation for Venous Compression

Vascular imaging is essential to identify correctable mechanical factors:

• CT or MR venography should be obtained to assess for May-Thurner syndrome (iliac vein compression) or extrinsic compression from the fibroid uterus 1, 4
• If significant iliac vein stenosis (>50%) is identified, balloon angioplasty with stenting may be considered after achieving initial clot resolution, as persistent anatomic obstruction predicts recurrent thrombosis 1
• Intravascular ultrasound at the time of venography provides superior assessment of venous compression compared to external imaging alone 1

Clinical context:

• Large uterine fibroids independently increase VTE risk through mass effect and venous compression 5, 4, 6
• The combination of estrogen-containing OCP use (now discontinued) and possible anatomic compression creates a multifactorial thrombotic risk 4, 6

Menorrhagia Management During Anticoagulation

Hormonal therapy is the preferred strategy to control bleeding without interrupting anticoagulation:

• Progestin-only therapy (oral or intrauterine levonorgestrel system) is first-line for menorrhagia control in women requiring long-term anticoagulation 7
• GnRH agonists (leuprolide) can be used as a bridge to definitive therapy if progestins are insufficient 7
• Estrogen-containing contraceptives are absolutely contraindicated given the recent thrombotic event and ongoing high VTE risk 4, 7, 6

Avoid tranexamic acid:

• Tranexamic acid and other procoagulants should NOT be used in women with large fibroids and VTE history, as they further increase thrombotic risk 6

Uterine Artery Embolization Considerations

If UAE is pursued, specific peri-procedural anticoagulation management is required:

• Continue LMWH through the UAE procedure if bleeding risk is acceptable—do not routinely hold anticoagulation for this intervention 1
• If anticoagulation must be held for the procedure, limit interruption to <24 hours and resume therapeutic dosing immediately post-procedure 3
• Do NOT place a new IVC filter for peri-procedural anticoagulation interruption—the existing filter should already be removed by this point 1, 2

Alternative consideration:

• Hysterectomy may ultimately be safer than UAE in this high-risk patient, as it definitively removes both the bleeding source and a potential mechanical cause of venous compression 6
• If hysterectomy is planned, continue LMWH peri-operatively with appropriate dosing adjustments (hold morning dose on day of surgery, resume 12–24 hours post-operatively) 3

Monitoring and Follow-Up

Laboratory surveillance on LMWH:

• Baseline CBC with platelets, renal function (creatinine clearance), and hepatic function prior to LMWH initiation 3
• Monitor hemoglobin/hematocrit every 2–3 days for the first 2 weeks, then every 2 weeks or as clinically indicated 3
• Platelet count monitoring to exclude heparin-induced thrombocytopenia (HIT)—check at baseline, day 3–5, and day 10–14 1
• Anti-Xa levels are NOT routinely needed but may guide dose escalation if recurrence occurs on standard LMWH dosing 1

Iron supplementation:

• Initiate oral iron supplementation (ferrous sulfate 325 mg daily to three times daily) given ongoing menorrhagia and anticoagulation 3
• Consider intravenous iron if oral supplementation is insufficient or poorly tolerated

Long-Term Anticoagulation Duration

Indefinite anticoagulation is strongly recommended:

• Recurrent VTE despite therapeutic anticoagulation is an indication for lifelong anticoagulation regardless of whether a "provoked" factor (estrogen, compression) is identified 1
• The combination of recurrent thrombosis, possible anatomic compression, and fibroid-related mass effect creates a persistently high-risk scenario 4
• Reassess anticoagulation duration only if: (1) definitive anatomic correction is achieved (venous stenting or hysterectomy), AND (2) thrombophilia workup is entirely negative, AND (3) patient remains event-free for ≥12 months 1

Quality of life consideration:

• LMWH injections may be burdensome long-term—warfarin transition can be considered after 3–6 months of stable LMWH therapy if patient preference strongly favors oral therapy, but LMWH remains superior for cancer-associated or high-risk VTE 1