What anticoagulant (Anti-Coagulant) therapy is recommended for patients with nephrotic syndrome (NS) at high risk of thrombosis (Blood Clots)?

Anticoagulation in Nephrotic Syndrome at High Risk of Thrombosis

Warfarin is the recommended anticoagulant of choice for patients with nephrotic syndrome at high risk of thrombosis, with a target INR of 2-3, due to extensive clinical experience and established monitoring protocols. 1, 2

Risk Assessment for Prophylactic Anticoagulation

Prophylactic anticoagulation should be initiated when:

• Serum albumin <20-25 g/L AND at least one of the following:
  • Proteinuria >10 g/day
  • BMI >35 kg/m²
  • Heart failure (NYHA class III or IV)
  • Recent orthopedic or abdominal surgery
  • Prolonged immobilization 1, 2

Note: Membranous nephropathy carries a particularly high risk of thromboembolic events

Contraindications to Prophylactic Anticoagulation

• Bleeding diathesis
• Central nervous system lesions affecting warfarin metabolism/efficacy
• Frailty with high fall risk
• Prior gastrointestinal bleeding
• Poor medication adherence 1

Anticoagulation Regimens

For Therapeutic Anticoagulation (Established Thrombosis)

• Full-dose anticoagulation for 6-12 months and/or for the duration of nephrotic syndrome
• Intravenous heparin followed by bridging to warfarin is preferred
• Target INR 2-3 1, 2

For Prophylactic Anticoagulation (High-Risk Patients)

• Low-molecular-weight heparin (LMWH):
  • Dose reduction advised with CrCl <30 ml/min
  • Enoxaparin 40 mg daily has been used successfully 3
• Unfractionated heparin: 5000 U subcutaneous twice daily
• Transition to warfarin with target INR 2-3 1

Special Considerations for Warfarin in Nephrotic Syndrome

• Higher than usual heparin dosing may be required due to antithrombin III urinary loss
• Monitor INR frequently as warfarin-protein binding fluctuates with changing serum albumin
• Be vigilant for drug interactions with warfarin 1, 2

Novel Oral Anticoagulants (NOACs)

Despite some favorable case reports 4, 5, NOACs are not currently recommended as first-line therapy due to:

1. Limited systematic studies in nephrotic syndrome
2. Variable protein binding affecting drug half-lives:
   • Apixaban (92-94% protein bound)
   • Rivaroxaban (92-95% protein bound)
   • Edoxaban (55% protein bound)
3. Varying degrees of renal clearance:
   • Apixaban (27% renal clearance)
   • Edoxaban (50% renal clearance)
   • Rivaroxaban (66% renal clearance) 1

Duration of Anticoagulation

• For therapeutic anticoagulation: 6-12 months and/or for the duration of nephrotic syndrome
• For prophylactic anticoagulation: Until serum albumin rises above 30 g/L 2, 6

Monitoring Recommendations

• Regular INR monitoring (more frequent initially and with changes in albumin)
• Monitor serum albumin levels
• Assess for bleeding complications
• Evaluate for resolution of nephrotic syndrome 1, 2

Common Pitfalls to Avoid

1. Failing to recognize high-risk patients who would benefit from prophylactic anticoagulation
2. Inadequate heparin dosing (higher doses often needed due to antithrombin III loss)
3. Infrequent INR monitoring despite fluctuating albumin levels
4. Using NOACs without considering their high protein binding and variable pharmacokinetics in nephrotic syndrome
5. Not reassessing the need for continued anticoagulation as nephrotic syndrome improves 1, 2, 6