Anticoagulation in Cancer Associated Thrombosis

Cancer raises the risk of venous thromboembolism and recurrence, and also the risk of bleeding on anticoagulation. Treatment is chosen by cancer site, bleeding risk, platelet count, kidney function, drug interactions and patient preference, and continues while the cancer is active.

Aims. Prevent recurrence and extension, minimise bleeding, and fit around chemotherapy, procedures and thrombocytopenia.

• Apixaban 10 mg twice daily for 7 days, then 5 mg twice daily.
• Rivaroxaban 15 mg twice daily with food for 21 days, then 20 mg once daily with food.
• Edoxaban 60 mg once daily after at least 5 days of low molecular weight heparin (30 mg if weight is 60 kg or less or creatinine clearance is 15 to 50 mL/min).
• Dalteparin 200 units/kg once daily for the first month, then 150 units/kg once daily; or enoxaparin 1 mg/kg twice daily.
• Warfarin target INR 2.0 to 3.0 is a lower-preference option.

Caution with direct oral anticoagulants. Luminal gastrointestinal and genitourinary cancers carry a higher risk of bleeding with edoxaban and rivaroxaban, so apixaban or low molecular weight heparin is preferred. Avoid with strong inducers or inhibitors of CYP3A4 and P-glycoprotein (some chemotherapy, azole antifungals, enzyme-inducing antiepileptics).

Duration. At least 6 months, and continue while the cancer is active or under treatment. After 6 months, apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily may be used for extended treatment.

Thrombocytopenia. Platelets over 50 x 10^9/L: full dose. Platelets 25 to 50 x 10^9/L: half dose or prophylactic dose, and specialist advice. Under 25 x 10^9/L: stop and consider an inferior vena cava filter in acute clot.

Kidney impairment. Under 30 mL/min: unfractionated heparin or reduced low molecular weight heparin with anti-Xa monitoring.

Brain tumours. Anticoagulation is generally safe in primary and metastatic brain tumours without recent haemorrhage; monitor with imaging.

Prophylaxis in outpatients. For ambulatory patients on chemotherapy with high risk (Khorana score 2 or more), apixaban 2.5 mg twice daily or rivaroxaban 10 mg once daily may be given for up to 6 months.

Special groups. Pregnant patients with cancer need low molecular weight heparin. In East Africa, cancers presenting late, HIV-associated malignancy and infusion line catheter clots are frequent, and access to direct oral anticoagulants is limited by cost.

Monitoring. Full blood count before each chemotherapy cycle, creatinine, liver tests, and review of interactions. Review dose and bleeding at each visit.

Referral and escalation. Escalate recurrence on treatment (switch to low molecular weight heparin or increase the dose by 25%), bleeding, catheter-related clot and brain metastases.

Stopping. Do not stop at 6 months while cancer is active. Stop when cancer is in remission and the risk has fallen, as directed by the specialist.