Atezolizumab
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Deep vein thrombosis and nonbacterial thrombotic endocarditis secondary to hypercoagulability: case report A 66-year-old woman developed deep vein thrombosis and nonbacterial thrombotic endocarditis (NBTE) secondary to hypercoagulability during treatment with atezolizumab for lung adenocarcinoma. The woman was diagnosed with stage IIIB lung adenocarcinoma, cT2aN3 M0 in early February 2017. In April 2017, she started receiving chemotherapy with carboplatin and pemetrexed, followed by pemetrexed monotherapy. However, in July 2018, tests revealed disease progression; therefore, in September 2017, she started receiving second-line therapy with atezolizumab [route and dosage not stated]. However, towards the end of September 2017, on day 24 of atezolizumab therapy, she was found to exhibit femoral oedema. Venous ultrasound of her lower extremities revealed deep vein thrombosis. The woman was treated with edoxaban; however, on day 51 of atezolizumab therapy (mid-October 2017), she developed weakness of her right forearm, accompanied by melaena; hence, she was hospitalised. Examination following admission revealed the following: clear consciousness, body temperature 36.7°C, HR 123 beats/min, BP 119/63mm Hg, oxygen saturation 99% (on room air), palpebral conjunctiva anaemia-like symptoms, flat abdomen with no tenderness, cold left forearm, which became pale, weakness in the right forearm, clear respiratory and heart sounds; however, heart sounds were irregular in the left border of the third intercostal thoracic bone. No neurological findings were noted. Laboratory results revealed anaemia, elevated CRP, low platelet count, fibrinogen and fibrin-fibrinogen degradation product (FDP), elevated PIC and TAT, with activation of the coagulation/ fibrinolytic systems. Autoantibodies revealed positivity for anti-ssDNA antibodies and anti-dsDNA antibodies, while anticardiolipine antibodies, antiphospholipid antibodies and ANCA were found negative. Chest abdominal CT scan showed obstruction in the cubital region of her right brachial artery, infarction in her right kidney, and active bleeding from her ascending colon. Therefore, emergency lower gastrointestinal endoscopy was performed. Haemostasis was achieved with clipping. Edoxaban was discontinued. Transthoracic echography and transoesophageal echography revealed warts in the mitral valve. Subsequent head MRI revealed multiple cerebral infarctions. Blood smears and cultures were found negative. Of note, despite the increase in CRP, there was no increase in her WBC count or fever. No findings suspicious of infection were noted. The results of blood tests revealed hypercoagulability, thrombocytopenia and decreased fibrinogen. Multiple infarctions associated with NBTE were differentiated. Mitral valve replacement was performed on day 5 of her illness. Pathology results of the excised mitral valve showed no bacterial mass, hemosiderin deposition, bleeding or chronic inflammatory cell infiltration of lymphocytes. Based on her clinical course and pathology findings, a diagnosis of
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