Diffuse Alveolar Hemorrhage as a Fatal Adverse Effect of Bevacizumab: An Autopsy Case

Abstract

A 71-year-old female with Stage IIIB primary adenocarcinoma was administered a three-drug combination therapy consisting of docetaxel, cisplatin and bevacizumab as a first-line treatment based on the Phase II clinical trial. On the 32nd day after the fourth course of chemotherapy, the patient developed bloody sputum. She was found dead at home on the 34th day. Autopsy revealed a diffuse alveolar hemorrhage without diffuse alveolar damage. Endothelial cells of the small arteries and capillaries were swollen and desquamated, indicating that alveolar capillaries were injured. The similar pathological changes in blood vessels were also observed in the kidney and the digestive tract. Because diffuse alveolar hemorrhage caused by cisplatin and docetaxel has never been reported apart from interstitial pneumonitis, bevacizumab is the most suspicious drug for diffuse alveolar hemorrhage in our case. Chest physicians and oncologists should be aware that although it is very rare, diffuse alveolar hemorrhage can develop during any course of chemotherapy with bevacizumab.