Cerebral embolism during edoxaban administration for venous
In March 2017, a 63-year-old woman with no smoking or major medical history was incidentally observed to have a tumor in the left upper lobe on a computed tomography (CT) scan. As a result of a detailed examination, she was diagnosed as stage IVa (cT2aN3M1b) lung adenocarcinoma without active mutation, and the PD-L1 tumor proportion score was 90%. Brain metastasis and cerebral infarction were not observed at this time. Thereafter, chemotherapy with carboplatin and pemetrexed was initiated. Simultaneously, the patient had high D-dimer levels and was diagnosed with asymptomatic VTE such as deep vein thrombosis and pulmonary thromboembolism. Therefore, anticoagulation therapy with 60 mg/day edoxaban was initiated. The patient showed a partial response to chemotherapy, and D-dimer level decreased to reach the normal range. However, the lung cancer subsequently progressed.

As a secondary treatment, pembrolizumab administration was initiated. At this point, plasma D-dimer levels increased to 2.3 μg/mL. On day 11 of pembrolizumab administration, she suddenly developed motility aphasia, and other neurologic examinations were repetitive defect as a higher brain dysfunction, right facial paralysis, right hypoglossal nerve paralysis. Blood test showed a further increase in plasma D-dimer levels (25.5 μg/mL) and a sustained increase in carcinoembryonic antigen. Thrombotic predisposition, such as protein C/S deficiency or antiphospholipid antibody syndrome, was not detected.

Diffusion-weighted magnetic resonance imaging revealed acute ischemic lesions in the left temporal lobe. Additionally, several small ischemic lesions occurred in the left occipital lobe and right parietal lobe. However, vascular stenosis was not observed on a magnetic resonance angiogram. Findings from carotid ultrasonography and 24-hour electrocardiographic monitoring were normal. Transesophageal echocardiography showed no non-bacterial thrombotic endocarditis findings and patent foramen ovale. From these observations, the cerebral infarction was diagnosed as Trousseau syndrome. Contrast-enhanced CT showed a large tumor, measuring 48 × 20 mm in size, in the left upper lobe and an enlarged mediastinal lymph node. VTE that existed during the initial diagnosis was not observed on the CT scan.

For treating ATE lesions, edoxaban administration was switched to intravenous heparin administration at a dosage of 15,000 units/day. On day 11 of admission, the mode of administration was changed to a subcutaneous one. Consequently, plasma D-dimer levels rapidly began to decrease (being 1.1 μg/mL on day 17 after heparin administration). Aphasia and cranial nerve symptoms also improved completely. Additionally, pembrolizumab administration achieved a partial response. On September 2018, lung cancer progression and Trousseau syndrome recurrence were not observed.

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