Anticoagulant Prescribing in Kidney Disease

Kidney disease raises both thrombotic and bleeding risk and changes the clearance of most anticoagulants. Dose by Cockcroft-Gault clearance, not indexed eGFR, and recalculate with each illness.

Clearance share. Renal elimination of the oral agents is about 80 percent for dabigatran, 50 percent for edoxaban, 35 percent for rivaroxaban and 27 percent for apixaban. Enoxaparin accumulates. Unfractionated heparin and warfarin do not depend on the kidney.

Warfarin. It needs no renal dose adjustment but lower doses and tighter control are usual in chronic kidney disease, with an INR target of 2 to 3.

Choice by clearance.

• Over 50 mL/min: any oral agent at the usual dose.

• 30 to 50: apixaban, rivaroxaban or edoxaban at the reduced doses given for each agent; dabigatran with caution.

• 15 to 29: apixaban, or edoxaban or rivaroxaban at reduced dose with caution; avoid dabigatran.

• Under 15 or dialysis: unfractionated heparin for acute use, warfarin or apixaban by specialist decision. Benefit of anticoagulation for atrial fibrillation on dialysis is uncertain.

Special groups.

• Pregnancy: use enoxaparin or unfractionated heparin, and avoid warfarin and oral anticoagulants.

• Children: specialist dosing.

• Older adults and low weight: lower doses apply under the labelled criteria.

• East Africa: warfarin is often the available option, so ensure access to INR testing before starting.

• Apixaban (atrial fibrillation): 5 mg twice daily. 2.5 mg twice daily with two of age 80 or over, weight 60 kg or under, creatinine 133 micromol/L or over, or clearance 15 to 29. Avoid under 15.

• Apixaban (venous thromboembolism treatment): 10 mg twice daily for 7 days, then 5 mg twice daily. Use caution under 30.

• Rivaroxaban: atrial fibrillation 20 mg once daily with food, 15 mg at 15 to 49. Treatment of thrombosis 15 mg twice daily for 21 days then 20 mg once daily (15 mg if clearance is 15 to 49). Avoid under 15.

• Edoxaban: 60 mg once daily, 30 mg at 15 to 50 or weight 60 kg or under. Avoid under 15.

• Dabigatran: 150 mg twice daily, 110 mg twice daily for age 80 or over or high bleeding risk. Avoid under 30.

• Enoxaparin: prophylaxis 40 mg once daily, or 20 mg if clearance is under 30. Treatment 1 mg/kg twice daily, or 1 mg/kg once daily if clearance is under 30.

• Unfractionated heparin: 80 units/kg intravenous bolus, then 18 units/kg/h, adjusted to the local anti-Xa or aPTT range.

Monitoring. Check full blood count, creatinine and liver function at baseline and at least every 6 months in chronic kidney disease. Review at intervals in months of about the clearance divided by 10. With treatment-dose enoxaparin and clearance under 30, measure anti-Xa 4 hours after the third dose, aiming for 0.5 to 1.0 IU/mL (twice daily) or 1.0 to 2.0 IU/mL (once daily).

Stop rules. Hold the anticoagulant for active bleeding, falling clearance under the labelled limit, and procedures (usually 24 to 48 hours before low-risk procedures, longer if clearance is under 50).

Referral and escalation. Major bleeding needs reversal: idarucizumab 5 g intravenously for dabigatran; andexanet alfa or prothrombin complex concentrate 25 to 50 units/kg for factor Xa inhibitors; and vitamin K 5 to 10 mg intravenously with prothrombin complex for warfarin. Seek specialist advice for dialysis patients.

Common errors. Using indexed eGFR, giving full-dose enoxaparin, continuing dabigatran after clearance falls, and not rechecking function during illness.