Abstract
Background
Venous thromboembolism (VTE) is a multifactorial disorder, accounting for high morbidity and mortality rates, due to a complex interplay of several variables classifiable as inherited (mutated Leiden V factor, prothrombin, protein C, protein S and antithrombin) and acquired (lupus anticoagulants, pregnancy, major surgery procedures, cancer and inflammatory diseases) risk factors.
The association of VTE with the nephrotic syndrome, particularly deep vein and renal vein thrombosis (DVT and RVT, respectively) is tightly established. This risk is particularly high in patients with idiopathic membranous nephropathy. In fact, thromboembolic events occur with a frequency between <10% and 45% in this disease. The reason(s) underlying the hypercoagulable status in nephrotic patients are not clearly understood. Multiple hemostatic abnormalities have been described, including decreased levels of antithrombin and plasminogen (due to urinary losses), increased platelet activation, reduced plasminogen activation, overproduction of fibrinogen and factors V and VIII as a compensatory response to hypoalbuminemia. The risk of thrombosis seems to be related to the severity and duration of the nephrotic status and seems to be particularly increased with serum albumin concentrations ≤2.0 g/dl (20 g/L).
Case report
We report the case of a 28 year-old male with nephrotic syndrome due to membranous nephropathy positive for serum anti-phospholipase-A2 receptor antibody. The patient was asymptomatic for VTE, but abdominal ultrasound showed endoluminal obstruction of both renal veins. Abdominal Computer Tomography confirmed the extensive bilateral renal vein thrombosis and also revealed an extension of the thrombosis to the inferior cava vein and the left common iliac vein. He was treated with low-molecular weight heparin for six months. According to our internal protocol, a complete Thrombophilia Molecular Study was performed and showed a normal Leiden V factor, but a rare homozygous mutation of the G20210A gene encoding for prothrombin. The prevalence of this is less than 5% in the general population, but is highly variable with ethnicity. The G20210A mutation confers a mildly increased thrombotic risk that is amplified by the presence of other risk factors, such as nephrotic syndrome.
Conclusions
In our case report, the association of a nephrotic syndrome secondary to a primitive membranous glomerulonephritis and the mutation in homozygous of the G20210A prothrombin, a rare mutation associated with a high thrombotic risk, led to a severe VTE in an still asymptomatic 28-year-old patient. Based on this experience, we would highlight the importance of the genetic screening for polymorphisms associated with inherited thrombophilia in nephrotic patients complicated with VTE.
Spectrum of thrombotic complications and their outcomes in Chinese children with primary nephrotic syndrome
