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Indirect antiglobulin (Coombs) test
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Direct antiglobulin (Coombs) test
Serum homocysteine and methylmalonic acid levels
Red blood cell osmotic fragility testing
Hemoglobin electrophoresis
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This patient's laboratory values and peripheral blood smear are consistent with hereditary spherocytosis. This diagnosis can be confirmed with red blood cell osmotic fragility testing. Hereditary spherocytosis is an autosomal dominant, intrinsic hemolytic anemia often caused by a deficiency in spectrin, a red blood cell membrane protein. As a result, red blood cells are spherical instead of discoid in shape and have a reduced surface area to volume ratio. The osmotic fragility test relies on these cells' increased lysis in hypotonic solutions because of their altered membrane properties. Hereditary spherocytosis can also be diagnosed using acidified glycerol lysis and eosin-5-maleimide binding tests. Dhaliwal et al. describe the characteristics of various types of hemolytic anemia. Hereditary spherocytosis usually presents with mild compensated anemia with an elevated MCHC. Most patients have little to no symptoms and treatment is not warranted. However, complete or partial splenectomy may be indicated in severe cases where Hgb<11 as well as when jaundice is present. Kobayashi et al. review studies of adults with hereditary spherocytosis and concomitant parvovirus B19 infection. Aplastic crisis is a known complication associated with parvovirus B19 infection in individuals with hereditary spherocytosis. Other common symptoms of parvovirus B19 infection include fever, abdominal pain, and nausea/vomiting/diarrhea. Confirmation of parvovirus B19 infection can be made by assessing serum parvovirus B19 antibody or RNA levels. Figure A shows a peripheral blood smear with spherocytes. Illustration A shows how defects in red blood cell membrane proteins leads to the formation of spherocytes via loss of micro vesicles. Spherocytes are trapped and destroyed in the spleen. Incorrect Answers: Answer 1: The indirect antiglobulin (Coombs) test detects the presence of antibodies against red blood cells in a patient's serum. It is used for cross-matching for blood transfusions and in antenatal antibody screening. Answer 2: A positive direct antiglobulin (Coombs) test is seen with autoimmune hemolytic anemia, not hereditary spherocytosis. Answer 3: Serum homocysteine and methylmalonic acid levels can be used to distinguish between vitamin B12 and folate deficiency. Elevated homocysteine levels are seen with both vitamin B12 and folate deficiency, while methylmalonic acid levels are increased only in vitamin B12 deficiency. Answer 5: Hemoglobin electrophoresis is used to diagnose hemoglobinopathies including sickle cell disease and the thalassemias.
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