Under What Circumstances Does Nephrotic Syndrome Require Anticoagulation Therapy?

Nephrotic syndrome refers to the presence of massive proteinuria (urinary protein > 3.5 g/d) and hypoalbuminemia (serum albumin < 3 g/dl). Through this definition, we can know that nephrotic syndrome is not a definite diagnosis, but a state or stage that many kidney diseases may appear. Nephrotic syndrome is a dynamic process, and in this dynamic process, venous thrombosis requires particular attention, in which the risk of deep vein thrombosis (DVT) and renal vein thrombosis (RVT) is increased.

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Epidemiology shows that the incidence of arterial and venous thrombosis in patients with nephrotic syndrome is much higher than that in the general population. A retrospective study of 298 mostly adult subjects with nephrotic syndrome with an average follow-up of 10 years found that the risk of thrombosis was highest in the initial 6 months after diagnosis of nephrotic syndrome. The annual incidence of venous and arterial thrombosis was 9.9% and 5.5%, respectively.

Risk factors for thrombosis

Regarding the risk factors for thrombosis, two points should be paid special attention to:

1. Patients with membranous nephropathy appear to be at the highest risk of thrombosis by renal histopathological diagnosis;

2. The severity of hypoalbuminemia is also associated with thrombosis. The lower the blood albumin concentration, the higher the risk of thrombosis.

Pathogenesis

The exact cause of the hypercoagulable state in patients with nephrotic syndrome cannot be determined, but various hemostatic abnormalities have been found to be associated with it, such as: loss of natural anticoagulant proteins (antithrombin III, plasmin Symptoms include decreased levels of plasminogen and protein C and protein S); increased platelet activation; hyperfibrinogenemia; inhibition of plasminogen activation; and the presence of high molecular weight fibrinogen degradation fragments in the circulation.

When starting anticoagulation therapy, there are 3 points to pay attention to!

1. Do all patients with nephrotic syndrome need to start prophylactic anticoagulation?

The answer is obviously no, there are few things that are absolutely clinically beneficial, and bleeding risk must be considered when deciding whether to use prophylactic anticoagulation in all patients with nephrotic syndrome who have no contraindications to anticoagulation.

The main contraindications to anticoagulation that need to be considered clinically are:

Significant active bleeding

severe bleeding constitution

severe thrombocytopenia

major trauma

Invasive surgery or obstetric delivery (recent, urgent, or planned)

previous intracranial hemorrhage

intracranial or spinal tumor

Axonal anesthesia

severe, uncontrolled high blood pressure

There are also many predictive models for assessing bleeding risks, such as the Anticoagulation and Risk Factors for Atrial Fibrillation (TRIA) Risk Score or the HAS-BLED Bleeding Risk Score, but they are less commonly used in clinical practice. In general, prophylactic anticoagulation should be avoided in patients at higher risk of bleeding.

2. Which situations tend to initiate anticoagulation more aggressively?

As mentioned earlier, patients with membranous nephropathy, and those with very low serum albumin levels, are generally at higher risk for thrombosis. Starting prophylactic anticoagulation may be beneficial in two groups of patients:

1. Patients with membranous nephropathy with very low serum albumin level and low to moderate risk of severe bleeding;

2. Patients with nephrotic syndrome complicated by pregnancy (regardless of the cause).

3. Under what circumstances should anticoagulation therapy be considered for nephrotic syndrome?

1. Patients with membranous nephropathy

Such patients need to be determined by assessing bleeding risk and serum albumin concentration, which are generally recommended as follows:

Anticoagulation-related bleeding risk is high, or serum albumin level ≥ 3.0 g/dl, prophylactic anticoagulation is not given. Anticoagulation-related bleeding risk is low, serum albumin level is <3.0 g/dl, and prophylactic anticoagulation with low molecular weight heparin or warfarin is used.

Anticoagulation-related bleeding risk is moderate, serum albumin levels are <2.0 g/dl, and prophylactic anticoagulation with low-molecular-weight heparin or warfarin is used. If the bleeding risk associated with anticoagulation is moderate and the serum albumin level is 2.0-2.9 g/dl, prophylactic anticoagulation should be determined on an individual basis after weighing the pros and cons.

For such patients, some physicians prescribe aspirin for prophylactic antiplatelet therapy, some physicians prescribe low molecular weight heparin or warfarin when the patient's serum albumin level is 2.0-2.5g/dl, and when the patient's serum albumin level is When it is 2.6-2.9g/dl, prophylactic anticoagulation is not given.

2. Patients with nephrotic syndrome caused by other diseases

For patients with nephrotic syndrome due to nonpregnant, nonmembranous nephropathy (eg, minimal change nephropathy or focal segmental glomerulosclerosis), the following recommendations are based on available observational data:

Prophylactic anticoagulation was not administered if the patient had a high risk of bleeding associated with anticoagulation, or if the serum albumin level was ≥ 3.0 g/dl.

Low-molecular-weight heparin or warfarin is administered if the patient has a low or moderate risk of anticoagulation-related bleeding and a serum albumin level <2.0 g/dl.

In patients with a low or moderate risk of anticoagulation-related bleeding and a serum albumin level of 2.0-2.9 g/dl, prophylactic anticoagulation should be determined on an individual basis.

3. Patients with nephrotic syndrome combined with pregnancy

There is no research on the benefits and harms of prophylactic anticoagulation in patients with nephrotic syndrome in pregnancy. The following recommendations are mainly based on clinical experience:

Do not administer prophylactic anticoagulation if the patient has a high risk of bleeding associated with anticoagulation, or if the serum albumin level is ≥ 3.0 g/dl.

Administer low molecular weight heparin if the patient has an intermediate risk of anticoagulation-related bleeding and a serum albumin level <2.5 g/dl, regardless of the etiology of the nephrotic syndrome.

If the patient has membranous nephropathy, the risk of anticoagulation-related bleeding is low, and the serum albumin level is <3.0 g/dl, administer low molecular weight heparin.

Prophylactic anticoagulation with low molecular weight heparin or unfractionated heparin can be used during pregnancy, but warfarin should be avoided because it crosses the placenta and adversely affects the fetus, but it can be used in postpartum and lactating women.

The dosing regimen for anticoagulant therapy

When prophylactic anticoagulation is used in patients with nephrotic syndrome, the initial dosing regimen of low molecular weight heparin and warfarin is the same as that used to treat venous thromboembolism in the general population. Intermittent monitoring of anticoagulant factor Xa activity is recommended when using low molecular weight heparin, especially for long-term use. In particular, low molecular weight heparin should be used with caution in patients with significantly reduced and/or unstable renal function. When using warfarin anticoagulation, the dose should be adjusted to achieve a target international normalized ratio (INR) of 1.5-2.5.

The optimal duration of prophylactic anticoagulation in patients with nephrotic syndrome is unknown. Received low molecular weight heparin (enoxaparin, 20 mg once a day, subcutaneous injection) for 3 months, if nephrotic syndrome persists, then switch to warfarin, and continue anticoagulation therapy until the patient's nephrotic syndrome symptom remission or serum albumin level > 3.0g/dl.

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