A 78-year-old woman is evaluated for progressive fatigue and dyspnea with exertion over the past 6 months. She has otherwise felt well with no nausea, vomiting, or changes in stool. Medical history is significant for hypertension and an aortic valve replacement at age 67 years. Medications are metoprolol and warfarin.

On physical examination, the patient appears well. Temperature is 37.0 °C (98.6 °F), blood pressure is 135/55 mm Hg, pulse rate is 65/min, and respiration rate is 14/min. BMI is 28. She has mild scleral icterus. The lungs are clear to auscultation. Examination of the heart reveals a mechanical S2, a grade 3/6 systolic murmur at the right upper sternal border radiating to the carotid arteries, and a soft diastolic murmur heard at the left sternal border. The spleen is not palpable, and no pedal edema is present. Stool guaiac testing is negative.

Laboratory studies:

Haptoglobin

32 mg/dL (320 mg/L)

Hemoglobin

6.5 g/dL (65 g/L)

Leukocyte count

5500/µL (5.5 × 109/L)

Mean corpuscular volume

71 fL

Platelet count

290,000/µL (290 × 109/L)

Reticulocyte count

2.9% of erythrocytes

Bilirubin, total

2.7 mg/dL (46.2 µmol/L)

Bilirubin, direct

1.0 mg/dL (17.1 µmol/L)

Ferritin

3.6 ng/mL (3.6 µg/L)

Lactate dehydrogenase

1200 U/L

Peripheral blood smear shows 3+ schistocytes and microcytic, hypochromic cells.

Which of the following is the most appropriate diagnostic test to perform next?