Review Question - QID 107020

This patient's clinical symptoms are consistent with hemolysis due to splenic sequestration, which causes extravascular hemolysis.

In extravascular hemolysis, spleen and liver macrophages either ingest small portions of the RBC membrane creating spherocytes or phagocytize the entire cell. Later in the course of the disease, patients with sickle cell disease typically undergo splenic autoinfarction, whereby the spleen cannot sequester or hemolyze RBCs. Serum haptoglobin levels decrease when hemolysis occurs intravascularly; in this patient with normal haptoglobin levels, this fact points away from intravascular hemolysis and suggests that the hemolysis is extravascular.

Wethers discusses acute splenic sequestration crisis. She notes that patients typically present before age 3 with a rapidly enlarging spleen. Lab findings include an increased reticulocyte count and decreased hematocrit, and severe cases can result in cardiovascular collapse. Of note, although heterozygous patients are less likely to present with sequestration crisis, those who do present may be of any age.

Urcar reviews hemolytic anemias. The majority of hemolytic disorders result in extravascular hemolysis. The causes of extravascular hemolysis can be broken down into several main categories: infections, drugs, or immunologic processes; red cell membrane defects, (e.g. hereditary spherocytosis); erythrocyte metabolic defects (e.g. pyruvate kinase deficiency or G6PD); and hemoglobin structural defects (e.g. sickle cell anemia or hemoglobin C).

Illustration A shows spherocytes, which are typically found in cases of extravascular hemolysis. Illustration B shows a CT with splenic sequestration, which is demonstrated by hypoabsorbence in the splenic periphery and hyperabsorbence in the splenic medulla. Illustration C highlights some of the differences between intravascular and extravascular hemolysis.

Incorrect Answers:
Answer 1: Splenic sequestration results in increased red blood cell production.
Answer 3: Intravascular hemolysis is seen with splenic dysfunction which can be seen in sickle cell patients after sufficient splenic autoinfarctions later in life. Haptoglobin levels would also be decreased.
Answer 4,5: Complement-mediated hemolysis and hemolytic uremic syndrome can cause hemolysis but would be a less likely explanation in a patient with sickle cell disease.