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Question 3#

A 35-year-old woman presents with several days of increasing fatigue and shortness of breath on exertion. She was recently diagnosed with Mycoplasma pneumoniae. Physical examination reveals BP 113/67, HR 114 beats/minute, and respiratory rate 20 breaths/minute. She appears icteric and in mild respiratory distress. Her hemoglobin is 9.0 g/dL and MCV is 110.

Which of the following is the best next diagnostic test? 

a. Serum protein electrophoresis
b. Flow cytometry
c. Peripheral blood smear
d. Glucose-6-PD level
e. Bone marrow biopsy

Correct Answer is C


Macrocytic anemia and indirect hyperbilirubinemia suggest hemolysis, which in this patient is likely due to immune-mediated IgM antibodies which may follow Mycoplasma infections. These antibodies are also called cold-reacting antibodies as they react at temperatures less than 37°C (98°F). Examination of the peripheral blood smear is the first step in evaluation of hemolytic anemia. The young red cells (which would show up as reticulocytes when properly stained) are much larger than mature RBCs, accounting for the macrocytosis (the MCV can be as high as 140 with vigorous reticulocytosis). The presence of microspherocytes suggests immune-mediated hemolysis, while the presence of fragmented RBCs or schistocytes suggest a mechanical cause of hemolysis, as seen in the microangiopathic hemolytic anemias. Serum protein electrophoresis is useful to diagnose multiple myeloma, which is rarely associated with hemolysis, but this would not be the best initial test; the anemia in multiple myeloma is normocytic. Flow cytometry can detect surface proteins like CD55, CD59 on granulocytes, and red blood cells in paroxysmal nocturnal hemoglobinuria (a rare cause of hemolysis), but again is not the best first test. Glucose-6-PD levels might be useful once hemolytic anemia is established by a peripheral smear and negative Coombs test. Bone marrow biopsy would show erythroid hyperplasia, but is usually not required to diagnose hemolytic anemia.