Sickle cell disease (NORD)

 A 3-year-old boy is brought to the clinic by his mother for a check-up. Recent laboratory data has demonstrated a persistent normocytic anemia, with the most recent hematocrit is 32.1%.  A peripheral blood smear is suggestive of a hemolytic anemia. His mother reports occasional difficulty with breathing, intermittent chest pain, and occasional pain in his fingers. The patient’s mother is concerned about these intermittent episodes and asks about the possibility of an underlying disease. Evaluation of the patient’s peripheral blood under high-powered microscopy is demonstrated distortions of the red blood cell architecture. Which of the following pathophysiologic mechanisms best describes the underlying disease?