What is the best course of action for a patient with a history of antiphospholipid syndrome, deep vein thrombosis (DVT), hypertension, depression, and noncompliance with Eliquis (apixaban) and Plavix (clopidogrel), presenting with acute non-occlusive DVT, sepsis of unknown origin, lymphadenopathy, shortness of breath, and hypoxemia?

Management of Acute DVT with Sepsis in Antiphospholipid Syndrome Patient with Anticoagulation Failure

This patient requires immediate transition to therapeutic unfractionated heparin (UFH) or low molecular weight heparin (LMWH) given the acute DVT with documented noncompliance to Eliquis in the setting of antiphospholipid syndrome, while simultaneously addressing the sepsis and investigating the cause of hypoxemia. 1

Immediate Anticoagulation Management

Switch from Eliquis to heparin-based anticoagulation immediately given the history of antiphospholipid syndrome and documented medication noncompliance. 1

• Antiphospholipid syndrome is an absolute contraindication to NOACs like apixaban (Eliquis) - these patients require either warfarin or heparin-based therapy. 2, 1
• Most patients with antiphospholipid thrombosis syndrome fail warfarin therapy and require LMWH or unfractionated heparin for effective secondary prevention. 3, 4
• Initiate therapeutic UFH or LMWH immediately for the acute non-occlusive DVT. 2
• UFH is preferred over LMWH in this septic patient given concerns about subcutaneous absorption in the setting of sepsis and potential hemodynamic instability. 2

Address the Hypoxemia Despite Negative PE Workup

The hypoxemia (PO2 72 mmHg) with hypocapnia (PCO2 33.1 mmHg) suggests an A-a gradient abnormality that requires explanation beyond PE. 2

• Consider subsegmental PE not detected on CT, septic pulmonary emboli from the infected groin lymph nodes, or ARDS from sepsis. 2
• The enlarged lymph nodes in the right groin on the same side as the DVT raise concern for septic thrombophlebitis or infected thrombus.
• Obtain bilateral lower extremity venous duplex ultrasound to fully characterize the DVT extent and exclude proximal propagation. 2
• Blood cultures and imaging of the groin lymph nodes (ultrasound or CT) are essential to identify the septic source. 2

Sepsis Management Considerations

The sepsis must be aggressively treated while maintaining anticoagulation, as infection can worsen the hypercoagulable state in antiphospholipid syndrome. 5

• Broad-spectrum antibiotics should be initiated immediately after obtaining blood cultures.
• The groin lymphadenopathy may represent septic thrombophlebitis, which would require prolonged anticoagulation and antibiotics.
• Monitor for signs of hemodynamic instability (systolic BP <90 mmHg) that would change management. 2

Long-Term Anticoagulation Strategy

This patient will require indefinite anticoagulation given antiphospholipid syndrome with recurrent thrombosis (history of DVT plus current acute DVT). 2, 6

• Transition to warfarin (target INR 2.0-3.0) after acute phase stabilization is the recommended long-term therapy for antiphospholipid syndrome. 2, 6, 5
• Indefinite treatment with warfarin is specifically recommended for patients with antiphospholipid antibody syndrome. 2
• Continue heparin bridging for minimum 5 days and until INR ≥2.0 for at least 24 hours before discontinuing heparin. 2
• Alternative: Extended LMWH monotherapy may be considered if warfarin monitoring is problematic or if the patient continues to have thrombotic events on warfarin. 1, 3, 4

Testing for Antiphospholipid Antibodies

Confirm antiphospholipid syndrome diagnosis with comprehensive testing if not previously documented:

• Lupus anticoagulant, anticardiolipin antibodies (IgG, IgA, IgM), and beta-2-glycoprotein I antibodies (IgG, IgA, IgM). 3, 4, 5
• Testing should be repeated at 12 weeks to confirm persistent positivity. 7
• Note that lupus anticoagulant only prolongs aPTT in 40-50% of cases, so negative aPTT does not exclude the diagnosis. 3, 4

Critical Pitfalls to Avoid

• Never restart Eliquis or any other NOAC in confirmed antiphospholipid syndrome - this is an absolute contraindication. 2, 1
• Do not assume PE is excluded based solely on negative CT chest - subsegmental PE or other causes of hypoxemia must be considered. 2
• The combination of DVT, sepsis, and groin lymphadenopathy suggests possible septic thrombophlebitis requiring both anticoagulation and prolonged antibiotics.
• Noncompliance history suggests need for directly observed therapy or simplified regimen during hospitalization.
• Plavix (clopidogrel) has no role in VTE treatment and should be discontinued unless there is a separate indication (e.g., coronary stents). 2

Monitoring During Hospitalization

• Daily assessment of bleeding risk, hemodynamic status, and response to antibiotics.
• Serial arterial blood gases to monitor oxygenation response.
• Renal function monitoring as sepsis may worsen renal function affecting anticoagulant dosing. 1
• Consider echocardiography if hemodynamic deterioration occurs to assess for right ventricular strain. 2