In which types of cancer is anticoagulation with Direct Oral Anticoagulants (DOACs) not recommended?

Direct Oral Anticoagulants (DOACs) Are Not Recommended in Specific Cancer Types

DOACs are not recommended in patients with gastrointestinal and genitourinary malignancies, especially those with intact intraluminal tumors, due to significantly increased bleeding risk. 1

Cancer Types Where DOACs Should Be Avoided

Gastrointestinal Cancers

• DOACs are associated with significantly higher bleeding rates in patients with gastrointestinal (GI) malignancies compared to low-molecular-weight heparins (LMWH) 1
• Subgroup analyses from the Hokusai VTE-Cancer trial showed that patients with GI cancer had a 13.2% bleeding rate with edoxaban versus 2.4% with dalteparin (p=0.0224) 1
• In the Select-D trial, patients with esophageal or gastroesophageal cancer experienced more bleeding with rivaroxaban versus dalteparin (36% versus 11%) 1
• Bleeding risk is particularly high in patients with:
  • Unoperated GI malignancies 1
  • Residual GI tumors 1
  • Active mucosal tumors in the GI tract 1

Genitourinary Cancers

• Patients with genitourinary (GU) malignancies also show increased bleeding risk with DOACs 1
• The trend toward higher rates of major bleeding with DOACs is largely due to increases in GI and urogenital bleeds 1
• Patients with unoperated or residual genitourinary malignancies should avoid DOACs 1
• Active mucosal tumors in the GU tract that absorb or renally clear the drug increase bleeding risk 1

Central Nervous System Malignancies

• DOACs should be avoided in patients with:
  • Intracranial or CNS bleeding within past 4 weeks 1
  • Treated brain metastases 1
  • Other CNS malignancies 1
  • Patients who have undergone cyberknife treatment 1
  • Intracranial or spinal lesions at high risk for bleeding 1

Hematological Malignancies

• Hematological malignancies increase the risk of bleeding with anticoagulation 1
• Patients with persistent thrombocytopenia (<50,000/mL) should avoid DOACs 1
• Severe thrombocytopenia (<20,000/mL) is an absolute contraindication to DOACs 1

Additional Contraindications for DOACs in Cancer Patients

Absolute Contraindications

• Active major bleeding in critical sites (intracranial, pericardial, retroperitoneal, intraocular, intra-articular, intraspinal) 1
• Severe, uncontrolled malignant hypertension 1
• Severe coagulopathy (e.g., liver failure) 1
• Concurrent use of potent P-glycoprotein or CYP3A4 inhibitors or inducers 1
• Severe renal dysfunction (creatinine clearance <15 mL/min) 1

Relative Contraindications

• Hemorrhagic malignant and non-malignant lesions 1
• Recent high-risk surgery or bleeding event 1
• Obesity (BMI >40 kg/m² or weight >120 kg) 1
• Serious nausea or vomiting that may preclude adequate oral DOAC intake 1
• Non-healed surgical site in the perioperative period 1

Alternative Anticoagulation Options

• Low-molecular-weight heparins (LMWH) are preferred for cancer patients with high bleeding risk 1
• LMWH represents a short-term anticoagulation option in patients not suitable for DOACs 1
• Vitamin K antagonists (VKAs) are indicated in patients with moderate-severe mitral stenosis or mechanical prosthetic valves 1
• Antiplatelet therapy is not recommended for stroke or systemic thromboembolism prevention in cancer patients with atrial fibrillation 1

Clinical Decision-Making Algorithm

1. Assess cancer type and location:

   • If GI or GU cancer with intact tumors → Avoid DOACs 1
   • If CNS malignancy or recent CNS bleeding → Avoid DOACs 1
   • If hematological malignancy with thrombocytopenia → Avoid DOACs 1

2. Evaluate bleeding risk factors:

   • Check platelet count (<50,000/mL is a relative contraindication) 1
   • Assess renal function (CrCl <15 mL/min is a contraindication) 1
   • Review potential drug interactions 1

3. Consider alternative anticoagulation:

   • For high bleeding risk: Use LMWH 1
   • For valvular AF: Use VKAs 1

4. Monitor closely:

   • Patients with cancer receiving anticoagulation require regular assessment of bleeding risk 1
   • Reassess anticoagulation strategy if cancer status changes 1

Remember that DOACs have shown increased risk of major and clinically relevant non-major bleeding compared to LMWH in cancer patients, particularly those with GI and GU malignancies 1, 2. The decision to use anticoagulation should always weigh the thrombotic risk against the bleeding risk in these vulnerable populations 1.