Question

Difficulty: EasyHematology and Oncology

A 6565-year-old man comes to the clinic reporting progressive fatigue, weakness, and a "pins and needles" sensation in his feet for the past 44 months. His past medical history is significant for type 22 diabetes mellitus, for which he has been taking metformin for 1010 years. Vital signs are within normal limits. Physical examination reveals pale conjunctivae and decreased vibratory sensation in the bilateral toes and ankles.

Laboratory studies show:
TestResultReference Range
Hemoglobin10.210.2 g/dL13.5−17.513.5-17.5 g/dL
Mean corpuscular volume112112 fL80−10080-100 fL
Leukocyte count5,5005,500/mm³4,500−11,0004,500-11,000/mm³
Platelet count180,000180,000/mm³150,000−400,000150,000-400,000/mm³

Which of the following is the most appropriate next step in the evaluation of this patient's anemia?

  1. Measurement of serum vitamin B12 and folate levelsAnswer
  2. B
    Measurement of serum iron, total iron-binding capacity, and ferritin levels
  3. C
    Hemoglobin electrophoresis
  4. D
    Upper gastrointestinal endoscopy
  5. E
    Bone marrow aspiration and biopsy

Answer

Measurement of serum vitamin B12 and folate levels
The correct answer is measurement of serum vitamin B12 and folate levels. This patient presents with a classic picture of macrocytic anemia (MCV > 100100 fL) accompanied by peripheral neuropathy (diminished vibratory sensation). Long-term use of metformin is a well-established risk factor for vitamin B12 deficiency due to interference with calcium-dependent absorption of the B12-intrinsic factor complex in the terminal ileum. The next best step in the workup of macrocytic anemia is to check serum B12 and folate levels to distinguish between the two most common megaloblastic causes.

Step-by-Step Solution

1
Analyze the patient's laboratory findings.
The patient has anemia (hemoglobin 10.210.2 g/dL) with an elevated MCV (112112 fL), indicating a macrocytic anemia.
Identifying the morphological classification of anemia (microcytic, normocytic, macrocytic) directs the diagnostic algorithm.
2
Correlate the laboratory findings with the clinical presentation.
The patient presents with progressive fatigue and peripheral neuropathy (decreased vibratory sensation). He also has a history of long-term metformin use.
Macrocytic anemia combined with neurologic deficits strongly suggests vitamin B12 deficiency. Metformin is known to interfere with vitamin B12 absorption in the terminal ileum.
3
Determine the most appropriate next diagnostic step based on the suspected etiology.
The initial step in confirming suspected megaloblastic macrocytic anemia is measuring serum vitamin B12 and folate levels.
Definitive diagnosis requires biochemical confirmation before initiating therapy or pursuing more invasive investigations.

Key Concept

Evaluation of macrocytic anemia requires initial measurement of serum vitamin B12 and folate levels, particularly in patients with neurologic symptoms or risk factors such as chronic metformin use.
Estimated Time:1m 0s
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