A 32-year-old male is seen in the ER with a nondisplaced fracture of the ulna after a fall. Incidentally, the intern noticed that the patient is jaundiced and has a palpable spleen. He orders a CBC which shows a Hgb of 10.2 g/dL. The patient reveals that he has chronic anemia and intermittently has been prescribed iron. On further questioning, he says that he had a cholecystectomy at age 23 and that he has family members with similar symptoms. The intern reviews the peripheral smear and finds spherocytes. What would be the best way to confirm this man's diagnosis?
- splenectomy
- Hgb electrophoresis
- osmotic fragility
- G6PD level
- indirect Coombs test
Answer(s): C
Explanation:
Hereditary spherocytosis (HS) is a familial hemolytic disorder with clinical features, ranging from an asymptomatic condition to a fulminant hemolytic anemia. The morphologic hallmark of HS is the microspherocyte, which result from membrane protein defects leading to cytoskeleton instability. Spectrin deficiency leads to loss of erythrocyte surface area, which produces spherical RBCs. Spherocytic RBCs are culled from the circulation by the spleen leading to the development of splenomegaly. Spectrin deficiency and the degree of deficiency correlate with the extent of spherocytosis, the degree of abnormality on osmotic fragility test results, and the severity of hemolysis. Hemolysis primarily is confined to the spleen and, therefore, is extravascular.
Although four abnormalities in red cell membrane proteins have been identified, spectrin deficiency is the most common. Spectrin deficiency results from impaired synthesis, whereas in other instances, it is caused by quantitative or qualitative deficiencies of other proteins that integrate spectrin into the cell membrane. In the absence of these binding proteins, free spectrin is degraded, leading to spectrin deficiency. The major complications are aplastic or megaloblastic crisis, hemolytic crisis, cholecystitis and cholelithiasis, and severe neonatal hemolysis. The classic laboratory features of HS include minimal or no anemia, reticulocytosis, an increased mean corpuscular hemoglobin concentration (MCHC), spherocytes on the peripheral blood smear, hyperbilirubinemia, and abnormal results on the osmotic fragility test. The most sensitive test to help detect HS is the osmotic fragility test performed after incubating RBCs for 1824 hours under sterile conditions at 37°C. Osmoti c fragility measures RBC resistance to hemolysis when exposed to a series of increasingly dilute saline solutions. The sooner hemolysis occurs, the greater the osmotic fragility of the cells.