<prompt> Answer this question truthfullyWhat are the two major causes of acute severe anemia in sickle cell disease, and what is the main differentiating feature between them?  <response>: <reason> The two major causes of acute severe anemia in sickle cell disease are aplastic crisis caused by Parvo B19 and splenic sequestration caused by vaso-occlusion. The main differentiating feature between them is the reticulocyte count, which is low in aplastic crisis and high in splenic sequestration. 