A 7-year-old boy is brought to the office due to "yellow eyes" over the past few months. His parents state that he has been tired, pale, and frequently uninterested in playing. The boy's father has had similar symptoms throughout his life. The patient takes no daily medications. Physical examination shows a tired-appearing boy with pale conjunctivae, scleral icterus, and generalized jaundice. The tip of the spleen is palpable. Laboratory results are as follows: Peripheral smear shows anisocytosis, spherocytes, and polychromatophilia. Direct and indirect antiglobulin (Coombs) tests are negative. Which of the following laboratory tests is the best next step in evaluation of this patient?

Question

A 7-year-old boy is brought to the office due to "yellow eyes" over the past few months.  His parents state that he has been tired, pale, and frequently uninterested in playing.  The boy's father has had similar symptoms throughout his life.  The patient takes no daily medications.  Physical examination shows a tired-appearing boy with pale conjunctivae, scleral icterus, and generalized jaundice.  The tip of the spleen is palpable.  Laboratory results are as follows:  Peripheral smear shows anisocytosis, spherocytes, and polychromatophilia.  Direct and indirect antiglobulin (Coombs) tests are negative.  Which of the following laboratory tests is the best next step in evaluation of this patient?

Quizplus · Accepted Answer

11ec25c8_d6a0_ec5a_bc81_3f0d1c7d82bd_MD0003_00 This patient's Coombs-negative hemolytic anemia (low hemoglobin, reticulocytosis, hyperbilirubinemia), family history of anemia, and spherocytes on peripheral smear are due to hereditary spherocytosis (HS). HS is the most common hemolytic anemia in the northern European population and is usually inherited in an autosomal dominant pattern. HS is due to a red blood cell (RBC) membrane defect that results in extravascular hemolysis as RBCs pass through the splenic circulation. spherocytes Disease severity varies but typically manifests as a triad of hemolytic anemia, jaundice, and splenomegaly, as seen in this patient. A key laboratory finding is elevated mean corpuscular hemoglobin concentration (>36% Hb/cell) due to cellular dehydration and membrane loss. In addition, spherocytes burst easily due to their decreased surface-area-to-volume ratio, and diagnosis can be confirmed by assessing RBC fragility with either the eosin-5-maleimide (EMA) binding test (flow cytometry) or acidified glycerol lysis test. (Choice A) Bone marrow evaluation is indicated when multiple cell lines are depressed. This patient's leukocytes and platelets are normal, and HS can be diagnosed by clinical presentation, hematologic parameters, and a noninvasive EMA binding test. (Choice C) Paroxysmal nocturnal hemoglobinuria (PNH) is diagnosed by erythrocyte CD55 and CD59 protein testing. Clinical manifestations of PNH include hemolytic anemia, cytopenias, and hypercoagulability. However, spherocytes are not seen in PNH. (Choice D) Glucose-6-phosphate dehydrogenase deficiency can present with hemolytic anemia and jaundice following oxidative stress. Mean corpuscular hemoglobin concentration would not be elevated as seen in this patient's laboratory evaluation. (Choice E) Hemoglobin electrophoresis is used to diagnose hemoglobinopathies such as sickle cell disease or thalassemia. Spherocytes are not seen in these conditions. (Choice F) Macrocytic anemia (mean corpuscular volume >100 µm³) can be caused by vitamin B₁₂ or folate deficiency. High RBC turnover from hemolysis can deplete folate, but B₁₂ levels should not be affected. (Choice G) Iron deficiency can cause a hypochromic, microcytic anemia. Mean corpuscular hemoglobin concentration and reticulocytes would be low, and spherocytes would not be present. Educational objective: Hereditary spherocytosis typically manifests as a triad of Coombs-negative hemolytic anemia, jaundice, and splenomegaly. It should be suspected in patients with reticulocytosis, hyperbilirubinemia, spherocytosis, and family history of anemia. Eosin-5-maleimide binding and acidified glycerol lysis tests are diagnostic. References: Hereditary spherocytosis, elliptocytosis, and other red cell membrane disorders. (http://www.ncbi.nlm.nih.gov/pubmed/23664421) Diagnostic power of laboratory tests for hereditary spherocytosis: a comparison study in 150 patients grouped according to molecular and clinical characteristics. (http://www.ncbi.nlm.nih.gov/pubmed/22058213) Guidelines for the diagnosis and management of hereditary spherocytosis-2011 update. (http://www.ncbi.nlm.nih.gov/pubmed/22055020)

A 7-Year-Old Boy Is Brought to the Office Due to "Yellow