Monitoring the activity of direct oral anticoagulants in a patient with severe nephrotic syndrome and pulmonary embolism. Lessons for the clinical nephrologist

A 74-year-old woman without any particular medical history except active smoking was referred to our hospital as she complained of oedema. Initial workup revealed nephrotic syndrome (protein-to-creatinine ratio 4.9 g/g, serum albumin 14 g/L), and an alteration in estimated Glomerular Filtration Rate (eGFR = 57 ml/min/1.73 m2). Testing for autoantibodies, including Anti-PLA2-R and anti-THSD7A was negative and kidney biopsy revealed stage 2 membranous nephropathy with polytypic IgG deposits (predominant IgG1 and IgG2) associated with mild acute tubulopathy. Immunohistochemical staining did not reveal positivity for anti-PLA2-R. Additional exams did not provide clear evidence for malignancies or any other associated disease, except the fixation of a small pulmonary nodule on positron emission tomography (PET) scan. A multidisciplinary expert meeting initially did not consider this image as significantly pathological. No further exploration was therefore performed, especially since the location of the nodule made the biopsy risky. Several weeks later, she was admitted to our hospital for dyspnea without signs of pulmonary infection. Computed tomography pulmonary angiography highlighted a bilateral pulmonary embolism. Anticoagulation was started with low-molecular-weight heparin (Enoxaparin 100 UI/kg twice a day), converted five days later to a Direct Oral Anticoagulant (DOAC), Rivaroxaban (15 mg twice a day). Due to severe hypoalbuminemia, we began monitoring DOAC by anti-Xa Rivaroxaban-specific activity dosage at trough and peak levels. As illustrated in Fig. 1, dosages were within the therapeutic range despite severe hypoalbuminemia (9 g/L) [1]. No bleeding event was observed during follow-up. A further computed tomography pulmonary angiography performed 4 days after initiation of Rivaroxaban showed complete resolution of the thrombosis. Due to the onset of vertigo (a known Rivaroxaban side effect), DOAC treatment was discontinued 8 days after its initiation and heparin therapy was resumed. However, as no improvement was observed, further neurological tests finally led to the diagnosis of paraneoplastic limbic encephalitis with anti-Hu antibodies. Bulbar syndrome then worsened, resulting in impaired alertness and coma. Methylprednisolone boluses did not improve her condition, and she died.