Anticoagulation in Glomerulonephritis
Anticoagulation is not universally needed for all glomerulonephritis, but prophylactic anticoagulation should be employed in patients with nephrotic syndrome when serum albumin falls below 20-25 g/L (2.0-2.5 g/dl) and additional thrombotic risk factors are present, as the risk of life-threatening thromboembolism exceeds bleeding risk in this hypercoagulable state. 1, 2
Risk Stratification Algorithm
The decision to anticoagulate depends on albumin level and additional risk factors:
High-Risk Patients Requiring Prophylactic Anticoagulation
Initiate prophylaxis when serum albumin <20-25 g/L PLUS any of the following: 1, 2
- Proteinuria >10 g/day 1, 2
- Body mass index >35 kg/m² 1, 2
- Heart failure (NYHA class III or IV) 1, 2
- Recent orthopedic or abdominal surgery 1, 2
- Prolonged immobilization 1, 2
- Membranous nephropathy diagnosis (carries particularly high thrombotic risk) 1, 2
Moderate-Risk Patients
Consider aspirin 75 mg daily when serum albumin is 20-30 g/L (2.0-3.0 g/dl) without other high-risk features. 1, 3
Absolute Contraindications to Prophylaxis
- Active bleeding diathesis or hemorrhage risk 1
- Prior gastrointestinal bleeding 1
- CNS lesions prone to bleeding 1
- High fall risk/frailty 1
- Patient inability to adhere to monitoring 1
Recommended Anticoagulation Regimen
First-Line Agent: Warfarin
Warfarin remains the anticoagulant of choice for nephrotic syndrome due to extensive long-term experience and predictable pharmacokinetics despite hypoalbuminemia. 4, 2
- Start with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin as bridging therapy 1, 2
- Use higher than usual heparin dosing due to urinary loss of antithrombin III 1, 2
- Transition to warfarin with target INR 2-3 1, 2
- Monitor INR frequently (more often than standard practice) since warfarin-protein binding fluctuates with changing serum albumin levels 1, 2
Alternative for Transient High-Risk Events
Low-molecular-weight heparin at prophylactic doses can be used for short-term situations, though dose reduction is advised when creatinine clearance <30 ml/min. 1
Why NOT Direct Oral Anticoagulants (DOACs)
Factor Xa inhibitors (apixaban, rivaroxaban, edoxaban) are NOT recommended in nephrotic syndrome despite their use in renal impairment, because they are heavily albumin-bound (55-95%), which substantially affects their half-lives in hypoalbuminemic states. 1, 4 These agents require additional safety and efficacy studies before they can be recommended in nephrotic patients. 1
Similarly, direct thrombin inhibitors (dabigatran, argatroban) have not been systematically studied in nephrotic syndrome and their modest protein binding (35-54%) affects pharmacokinetics unpredictably. 1
Evidence Supporting Prophylaxis
A 2014 retrospective study of 143 nephrotic patients (40% with membranous nephropathy, median albumin 1.5 g/dl) using albumin-based prophylaxis showed zero VTE events in patients established on prophylaxis for >1 week, with only 0.69% experiencing major bleeding. 3 This represents the highest quality recent evidence demonstrating efficacy and safety.
A 1994 decision analysis model demonstrated that prophylactic anticoagulation in membranous nephropathy yielded a gain of 2.5 months of quality-adjusted life expectancy for a 50-year-old patient remaining nephrotic for 2 years, with fatal emboli prevented exceeding fatal bleeding events. 5
Duration of Therapy
Continue anticoagulation for 6-12 months and/or for the duration of nephrotic syndrome. 1 Discontinue when nephrotic syndrome remits (albumin normalizes and proteinuria resolves). 1, 5
Critical caveat: One case report documented recurrent renal vein thrombosis 6 months after discontinuing anticoagulation despite ongoing proteinuria >4 g/24hr, emphasizing that anticoagulation should continue as long as significant proteinuria persists. 6
Full-Dose Anticoagulation for Established Thrombosis
Full anticoagulation is mandatory for patients with documented thromboembolic events (venous thrombosis, pulmonary embolus, arterial thrombosis, renal vein thrombosis) occurring in the context of nephrotic syndrome. 1 This is non-negotiable regardless of bleeding risk assessment.
Special Populations
Pediatric Patients
Consider formal hematology consultation for evaluation of VTE and bleeding risk, as the Framingham Risk Score is not validated in children. 1
Crescentic/Rapidly Progressive GN
Historical data from 1977 suggested anticoagulation combined with immunosuppression improved outcomes in children with severe glomerulonephritis characterized by glomerular necrosis and crescents, though this was based on the hypothesis of intravascular coagulation rather than nephrotic syndrome. 7 This is not standard practice today and should not influence decisions about anticoagulation in typical nephrotic syndrome.