A 46 year-old male arrives in the emergency room, complaining of ‘bone pains’, severe weakness and fatigue, easy bruising in the skin, gingival bleeding, nose bleeds, shortness of breath and vision change. On review of systems, you notice continuous headaches and weight loss of over 20 pounds in two months. He was also treated for three episodes of ‘sinusitis’ in the last 2 months. On a physical examination, you notice a thin young man who appears pale, confused and distressed due to dyspnea. His gums are swollen. Other remarkable things are hepatomegaly, lymphadenopathy and tenderness over the sternum, right tibia and left femur. Suspecting a serious underlying disorder, you ordered some laboratory tests. Bone marrow film showed most cells with cytoplasmic reddish-purple granules with several long slender inclusions (as shown in the image), highlighted by peroxidase stain and some lymphocytes are compressed among the cells. This patient was diagnosed with acute promyelocytic leukemia and was initiated on all-trans-retinoic acid (ATRA). After 6 days, he developed fever, shortness of breath, and chest pain. His temperature is 102 °F (38.8°C), heart rate is 108 beats/min, blood pressure is 164/94 mm Hg, respirations are 32 breaths/min, and oxygen saturation is 86% on room air. On examination, the patient is pale and distressful. Lung sounds are abnormal with pleural rub sounds. He has edema in both feet. Chest X showed bilateral pulmonary infiltrates with pleural effusion. Echocardiogram is normal except for pericardial effusions. His laboratory results are given below: Leukocyte count (WBC) 110,000/ mm³ 4500-11,000/mm³ Platelet count 24,000 150,000 – 400,000/mm³ Reticulocyte count 0.5% – 1.5% D-Dimer 900 ng/mL ≤250 ng/mL Partial thromboplastin time (aPTT) (activated) 56 seconds 25-40 seconds Prothrombin time (PT) 18 seconds 11-15 seconds fibrinogen 140 mg/dl 200 – 400 mg/dl fibrin degradation products 22 mcg/ml <10 mcg/ml Erythrocyte count (RBC) 3.2 million/mm³ Male: 4.3 - 5.9 million/mm³ Female: 3.5 - 5.5 million/mm³ proBNP 76 pg/ml < 100 pg/ml Creatinine 0.9 mg/dL 0.6 - 1.2 mg/dL Urea nitrogen 12 mg/dL 7-18 mg/dL Which of the following is the best explanation for the worsening of his condition?
