What is the relationship between Nephrotic syndrome and Deep Vein Thrombosis (DVT)?

From the Guidelines

Nephrotic syndrome significantly increases the risk of deep vein thrombosis (DVT) due to urinary loss of anticoagulant proteins and increased production of procoagulant factors, and patients with nephrotic syndrome should receive prophylactic anticoagulation when the risk of thromboembolism exceeds the estimated patient-specific risks of an anticoagulation-induced serious bleeding event. According to the most recent guideline evidence 1, venous thromboembolic disease is a common cause of morbidity in nephrotic syndrome, particularly in membranous nephropathy. The risk of thromboembolism is increased when serum albumin levels fall below 2.9 g/dL.

Prophylactic Anticoagulation

• Low molecular weight heparin (LMWH) such as enoxaparin or warfarin are the preferred agents for treatment or prevention in those felt to have thromboembolic risk greater than bleeding risk 1.
• Factor Xa inhibitors and direct thrombin inhibitors are not recommended due to significant albumin binding and lack of pharmacokinetic studies in nephrotic syndrome 1.
• Prophylactic full-dose anticoagulation should be considered if serum albumin is less than 20-25g/l and other risk factors are present, such as proteinuria greater than 10g/d or body mass index greater than 35 kg/m² 1.

Therapeutic Anticoagulation

• For established DVT in nephrotic patients, therapeutic anticoagulation with enoxaparin or warfarin is indicated for at least 6-12 months and/or for the duration of the nephrotic syndrome 1.
• Regular monitoring of renal function, albumin levels, and coagulation parameters is essential during treatment.
• Patients should also be advised about symptoms of DVT and pulmonary embolism requiring immediate medical attention.

Mechanical Prophylaxis

• Mechanical prophylaxis with compression stockings provides additional benefit alongside pharmacological treatment.
• The hypercoagulable state in nephrotic syndrome results from urinary loss of antithrombin III, proteins C and S, and increased production of fibrinogen and factors V and VIII.

From the Research

Relationship Between Nephrotic Syndrome and Deep Vein Thrombosis (DVT)

• Nephrotic syndrome (NS) is associated with an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) 2, 3, 4, 5, 6
• The risk of thromboembolic events in NS patients varies with the nature of the underlying disease, with membranous nephropathy being a high-risk condition 5
• Other factors that may contribute to the increased risk of thromboembolic events in NS patients include low serum albumin levels, previous thromboembolic episodes, and genetically determined predisposition to thrombosis 5

Anticoagulation Therapy in NS Patients

• Anticoagulants are widely used in the prevention of VTE in NS patients, with direct oral anticoagulants (DOACs) being a potential option 2, 3, 6
• Studies have shown that DOACs have comparable efficacy to warfarin in preventing VTE in NS patients, with a lower risk of non-major bleeding 2, 3
• The optimal duration of prophylactic anticoagulation in NS patients is unknown, but it is likely to extend to the duration of the nephrotic state per se 5

Diagnostic Challenges and Treatment Modalities

• NS can present with unprovoked VTE, making diagnosis and treatment challenging 4
• The selection of an anticoagulant and the timing of diagnostic renal biopsy with necessary therapeutic anticoagulation require careful consideration of patient-specific risks and benefits 4
• Emerging treatment modalities, including the use of DOACs, may offer improved outcomes for NS patients with VTE 6