From the Guidelines
Patients with nephrotic syndrome should receive anticoagulation therapy if they have additional risk factors for thrombosis or if their serum albumin is below 2.0-2.5 g/dL, as indicated by the KDIGO 2021 clinical practice guideline for the management of glomerular diseases 1. The preferred anticoagulant is warfarin with a target INR of 2.0-3.0, typically preceded by a 5-7 day course of heparin or low molecular weight heparin (LMWH) like enoxaparin 1 mg/kg twice daily, as suggested by the guideline 1. Some key points to consider when deciding on anticoagulation therapy in patients with nephrotic syndrome include:
- The risk of thromboembolic events is high in patients with nephrotic syndrome, particularly those with membranous nephropathy, severe hypoalbuminemia, and during the first 6 months of disease 1
- Prophylactic anticoagulation should be employed in patients with nephrotic syndrome when the risk of thromboembolism exceeds the estimated patient-specific risks of an anticoagulation-induced serious bleeding event 1
- The effects of hypoalbuminemia on drug dosing have not been studied for direct oral anticoagulants (DOACs) and direct thrombin inhibitors (DTI), and these drugs are heavily albumin-bound, which is likely to substantially affect their half-lives 1
- Direct oral anticoagulants (DOACs) are generally not recommended as first-line therapy due to limited data in nephrotic syndrome and potential altered pharmacokinetics with protein binding 1 Some important considerations for anticoagulant dosing in patients with nephrotic syndrome include:
- Low-dose anticoagulation (e.g., molecular-weight heparin: dose reduction may be advised with creatinine clearance < 30 ml/min; unfractionated heparin 5000 U subcutaneous twice per day) for prophylactic anticoagulation during transient high-risk events 1
- Full warfarin anticoagulation for thromboembolic events, with intravenous heparin followed by bridging to warfarin as the preferred approach 1
- Higher than usual heparin dosing may be required in nephrotic syndrome due to antithrombin III urinary loss 1
- International normalized ratio should be monitored frequently, as warfarin-protein binding may fluctuate with changing serum albumin 1
From the Research
Relationship Between Nephrotic Syndrome and Anticoagulation Therapy
The relationship between nephrotic syndrome and anticoagulation therapy is complex, with various studies investigating the effectiveness and safety of different anticoagulants in preventing thromboembolic events (TE) in patients with nephrotic syndrome.
- Nephrotic syndrome is associated with an increased risk of TE, and anticoagulation therapy is often recommended to prevent these events 2, 3, 4, 5, 6.
- Direct oral anticoagulants (DOACs) have been shown to be effective and safe in patients with nephrotic syndrome, with a low risk of bleeding complications 2, 3, 6.
- A study comparing DOACs to warfarin found that DOACs had comparable efficacy and a lower incidence of non-major bleeding 6.
- Another study found that enoxaparin, a low-molecular-weight heparin, was effective in preventing TE in patients with severe nephrotic syndrome, but the dose needed to be adjusted to achieve target anti-factor Xa activity 4.
- A retrospective analysis of a novel regimen for preventing VTE in patients with nephrotic syndrome found that low-dose prophylactic anticoagulation was effective in preventing VTE, with relatively few hemorrhagic complications 5.
Types of Anticoagulants Used
Different types of anticoagulants have been used in patients with nephrotic syndrome, including:
- Direct oral anticoagulants (DOACs) such as apixaban and rivaroxaban 2, 3, 6
- Low-molecular-weight heparin such as enoxaparin 4
- Warfarin 3, 5, 6
- Aspirin 5
Safety and Efficacy of Anticoagulants
The safety and efficacy of anticoagulants in patients with nephrotic syndrome have been evaluated in several studies.
- A study found that DOACs were safe and effective in patients with nephrotic syndrome, with a low risk of bleeding complications 2.
- Another study found that enoxaparin was effective in preventing TE in patients with severe nephrotic syndrome, but the dose needed to be adjusted to achieve target anti-factor Xa activity 4.
- A retrospective analysis found that low-dose prophylactic anticoagulation was effective in preventing VTE, with relatively few hemorrhagic complications 5.
- A study comparing DOACs to warfarin found that DOACs had comparable efficacy and a lower incidence of non-major bleeding 6.