What anticoagulants should not be given to a patient with a recent pulmonary embolism and active malignancy who is about to start immunotherapy?

Anticoagulants to Avoid in Cancer Patients with Recent PE Starting Immunotherapy

Vitamin K antagonists (warfarin) should not be given to cancer patients with recent pulmonary embolism who are about to start immunotherapy, as they are inferior to both low-molecular-weight heparin (LMWH) and direct oral anticoagulants (DOACs) for cancer-associated thrombosis. 1, 2

Primary Contraindications

Warfarin/Vitamin K Antagonists

• Warfarin is explicitly not recommended as it demonstrates inferior efficacy compared to LMWH and DOACs in cancer-associated VTE 1, 2
• The CLOT trial demonstrated that LMWH reduced recurrent VTE by 52% compared to warfarin plus initial heparin (HR 0.48; 95% CI 0.30-0.77) in cancer patients 1
• Warfarin should not be used when superior alternatives (LMWH or DOACs) are available 2, 3

Unfractionated Heparin (Long-term)

• IV unfractionated heparin is acceptable only for initial use in hemodynamically unstable patients, but should not be continued long-term 1
• LMWH is preferred over unfractionated heparin due to lower bleeding risk and superior efficacy 1, 3

Conditional Contraindications Based on Cancer Type

DOACs in Gastrointestinal Malignancies

• Apixaban, rivaroxaban, and edoxaban should not be given to patients with gastrointestinal or gastroesophageal malignancies due to significantly higher bleeding risk 2, 4
• The Hokusai VTE-Cancer trial showed edoxaban had a 77% increased major bleeding risk compared to LMWH (HR 1.77; 95% CI 1.03-3.04), with GI cancers accounting for much of this excess 1
• For GI/gastroesophageal cancers, LMWH is mandatory as first-line therapy 2

High-Dose Infliximab

• Infliximab is contraindicated at high doses (>5 mg/kg) in patients with moderate-to-severe heart failure 1
• While infliximab is used to manage immune-related adverse events from checkpoint inhibitors, it should be avoided in patients with significant cardiac dysfunction 1

Specific Situations Requiring Alternative Approaches

Severe Renal Impairment

• All DOACs (apixaban, rivaroxaban, edoxaban, dabigatran) are contraindicated when creatinine clearance is <30 mL/min 2, 4
• LMWH should be used with caution and anti-Xa monitoring, or unfractionated heparin should be substituted 2

Active Bleeding or High Bleeding Risk

• Anticoagulation should be avoided entirely in the presence of intracranial bleeding, recent surgery, thrombocytopenia with platelet count <50,000/μL, or active coagulopathy 1
• Patients with bronchiectasis/pulmonary cavitation, active gastroduodenal ulcer, or bleeding in the previous 3 months had excess bleeding with rivaroxaban in the MAGELLAN trial 5

Triple-Positive Antiphospholipid Syndrome

• DOACs (including apixaban) are not recommended for patients with triple-positive antiphospholipid syndrome due to increased rates of recurrent thrombotic events compared to vitamin K antagonists 6

Recommended Anticoagulation Strategy

First-Line Options for Non-GI Cancers

• LMWH (enoxaparin, dalteparin, tinzaparin) remains the gold standard 1, 2
• Edoxaban, rivaroxaban, or apixaban are acceptable alternatives for at least 6 months, preferred over warfarin 1
• Dabigatran is listed as an option for initial treatment but is less commonly used 1

Duration Considerations

• Anticoagulation should continue while on immunotherapy and for an additional 6 months following completion of immunotherapy 1
• For active or metastatic cancer, indefinite anticoagulation is recommended 2, 4

Critical Pitfalls to Avoid

• Never use warfarin as first-line therapy when LMWH or appropriate DOACs are available 2, 3
• Do not prescribe DOACs to patients with GI malignancies without first considering LMWH 2, 4
• Avoid assuming all DOACs are equivalent—drug-drug interactions with immunotherapy agents must be verified before prescribing 1
• Do not continue unfractionated heparin long-term when transitioning to outpatient management 1