A 19-year-old man presents to the clinic because he has been feeling extremely tired and has noticed several small, red spots on his arms and legs over the past three weeks. He also reports a recent sore throat and fever that have not resolved. He has no significant past medical history and takes no medications. Vital signs are within normal limits. On physical examination, he appears pale, and there are scattered petechiae and ecchymoses on his trunk and extremities. There is no lymphadenopathy, and the spleen is not palpable.
Laboratory evaluation reveals the following:
Hemoglobin: 7.0 g/dL
Platelet count: 18,000/μL
White blood cell count: 1,500/μL (with 400 neutrophils/μL)
Mean corpuscular volume (MCV): 98 fL
Which of the following is the most appropriate next step to confirm the diagnosis?
The correct answer is:
A) Bone marrow aspiration and biopsy
This patient presents with pancytopenia which is anemia, thrombocytopenia, and leukopenia/neutropenia. The clinical picture of severe pancytopenia in the absence of splenomegaly or lymphadenopathy is highly suggestive of aplastic anemia from bone marrow failure. In aplastic anemia, the hematopoietic stem cells are damaged, leading to the replacement of normal marrow elements with fat. The gold standard for diagnosis is a bone marrow biopsy, which typically shows a hypocellular marrow (often <25% cellularity) with increased fat spaces.
Answer choice B: Computed tomography of the chest, abdomen, and pelvis, is incorrect. While imaging can help rule out malignancy such as lymphoma or leukemia causing marrow infiltration, it is not the primary diagnostic test. Aplastic anemia is a diagnosis of exclusion that is confirmed by the marrow findings. Splenomegaly is notably absent in classic aplastic anemia, which helps distinguish it from infiltrative processes or hypersplenism.
Answer choice C: Hemoglobin electrophoresis, is incorrect. Hemoglobin electrophoresis is used to diagnose hemoglobinopathies like sickle cell disease or thalassemia. While thalassemia can cause microcytic anemia, it does not explain the profound pancytopenia or the specific presentation of petechiae and recent infections seen in this patient.
Answer choice D: Peripheral blood smear with manual differential, is incorrect. A peripheral smear is useful to look for abnormal cells such as blasts or schistocytes, and it may show a lack of precursor cells in aplastic anemia. However, it cannot definitively diagnose the condition or provide the degree of cellularity assessment required for confirmation. It is an adjunct, not the definitive diagnostic step.
Answer choice E: Vitamin B12 and folate levels, is incorrect. Deficiencies in these vitamins can cause megaloblastic anemia, which presents with pancytopenia and an elevated MCV, as seen in this patient. However, aplastic anemia is the leading diagnosis when the clinical presentation includes severe, symptomatic bleeding (petechiae) and neutropenic infections without other systemic signs. While ordering these vitamin levels is often part of the initial workup, the bone marrow biopsy is the confirmatory diagnostic test.
Key Learning Point
Aplastic anemia is characterized by hematopoietic failure resulting in pancytopenia. The classic triad of symptoms includes fatigue from anemia, bleeding from thrombocytopenia, and recurrent infections from neutropenia. A key clinical clue is the absence of splenomegaly. Its presence should prompt a search for alternative diagnoses like leukemia or lymphoma. The definitive diagnosis requires a bone marrow biopsy showing a hypocellular, fatty marrow.
