NYACP Board Review Question of the Week
Every other Tuesday, NYACP members are sent a Board Review Question from ACP's MKSAP 18 to test professional knowledge and help prepare for the exam. Participant totals and answer percentages are distributed on the first Thursday of the month in IM Connected, the Chapter's eNewsletter, and are also published on this page.
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July 15, 2025
MKSAP 18 Hematology & Oncology, Question 58
A 67-year-old woman is evaluated for slowly worsening fatigue and exertional dyspnea of several months' duration, with more recent yellowing of the skin. Medical history is notable for Hashimoto thyroiditis diagnosed 30 years ago. Her only medication is levothyroxine.
On physical examination, temperature is 36.7 °C (98.0 °F), blood pressure is 125/75 mm Hg, pulse rate is 100/min, and respiration rate is 18/min. Jaundice is noted. The remainder of the examination is noncontributory.
A peripheral blood smear shows macrocytic erythrocytes with rare nucleated erythrocytes and scattered, six-lobed neutrophils. A direct antiglobulin (Coombs) test is negative.
Which of the following should be obtained next?
A. Bone marrow biopsy
B. Cobalamin and folate levels
C. Flow cytometry
D. Glucose-6-phosphate dehydrogenase level
Responses Received from Members (Graph is uploaded on Thursday afternoon):
The Correct Answer is: B. Cobalamin and folate levels
Educational Objective:
Evaluate megaloblastic anemia.
Serum cobalamin and folate levels should be obtained next. The clinical features, pancytopenia with macrocytic erythrocytes and hypersegmented neutrophils, suggest megaloblastic anemia, and serum levels of cobalamin and folate should be assessed. The patient described also has an elevated indirect bilirubin level and an elevated lactate dehydrogenase (LDH) level, which indicate ineffective erythropoiesis and intramedullary hemolysis seen in megaloblastic anemia. This constellation of findings is consistent with cobalamin deficiency, which often occurs simultaneously with other autoimmune conditions, such as Hashimoto thyroiditis. Similar hematologic findings are seen in folate deficiency, which would be more likely in patients with poor nutrition or alcohol dependence. A reasonable first step in evaluating suspected vitamin B12 deficiency is serum cobalamin measurement, with levels greater than 300 pg/mL (221 pmol/L) making deficiency unlikely and levels less than 200 pg/mL (148 pmol/L) strongly suggesting deficiency. If diagnostic uncertainty exists, methylmalonic acid and homocysteine measurement may be helpful. Both are elevated in 98% of patients with cobalamin deficiency, even in patients who have neurologic symptoms without anemia.
Methylmalonic acid and total homocysteine levels are helpful in differentiating cobalamin deficiency (both levels are elevated) from folate deficiency (elevated homocysteine level but normal methylmalonic acid level).
Bone marrow biopsy is seldom indicated to diagnose megaloblastic anemia. Although a marrow sample may be useful to diagnose myelodysplasia, which can also present as a macrocytic anemia, a bone marrow biopsy would not be the appropriate next test for this patient without first excluding vitamin B12 and folate deficiency.
Flow cytometry would not be helpful in the absence of abnormal leukocytes or other findings that raise suspicion for myelodysplasia or leukemia (for example, immature cells, leukopenia, or leukocytosis).
Patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency do not have a macrocytic anemia or hypersegmented neutrophils. During episodes of hemolysis, peripheral blood smears show typical bite cells and Heinz bodies, which are not present in this patient's peripheral smear.
Additionally, G6PD deficiency is an X-linked condition uncommon in women. Furthermore, patients with suspected G6PD deficiency should not have G6PD levels measured during an acute hemolytic event because G6PD levels are relatively preserved in the nonhemolyzed cells remaining in circulation, so false-negative results are common.
Key Point
Patients with pancytopenia, macrocytic erythrocytes, hypersegmented neutrophils, and findings consistent with intramedullary hemolysis should have vitamin B12 and folate levels assessed to determine the cause of megaloblastic anemia.
Bibliography
Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368:149-60. PMID: 23301732 doi:10.1056/NEJMcp1113996
Copyright 2018, American College of Physicians.
July 1, 2025
MKSAP 19 General Internal Medicine 1, Question 68
A 74-year-old man undergoes follow-up evaluation 4 weeks after an urgent care visit for benign paroxysmal positional vertigo. He is concerned about an upcoming trip and the possibility of falling. He has had no recent falls but did have a near fall. Medical history is significant for atrial fibrillation. Current medications are metoprolol, apixaban, and meclizine.
On physical examination, blood pressure and pulse rate are normal and without orthostatic changes. Cardiac examination reveals an irregular rhythm. Screening neurologic examination is normal.
The Timed Up and Go Test result is prolonged (16 seconds).
The patient undergoes canalith repositioning with the Epley maneuver.
Which of the following is the most appropriate additional management to reduce this patient's risk for falls?
Responses Received from Members (657 Responses):
The Correct Answer is: A. Discontinue meclizine
Educational Objective:
Prevent falls in an elderly patient.
The most appropriate measure to reduce this patient's risk for falls is to discontinue meclizine (Option A). Meclizine is a centrally acting antihistamine associated with increased fall risk in elderly patients. Many health conditions, physical characteristics, and behaviors increase risk for falling, but the greatest increases are associated with cognitive impairment, psychoactive medications, gait/balance problems, and decreased lower extremity strength. The presence of multiple risk factors has an additive effect on fall risk. Even fear of falling in the absence of falls decreases self-rated health and hastens functional decline. The Timed Up and Go (TUG) test is used to help assess fall risk. This test involves asking the patient to rise from a chair with armrests, walk 10 feet, turn, return to the chair, and sit down. A TUG Test result of more than 12 seconds should prompt intervention to reduce fall risk.
Benign paroxysmal positional vertigo (BPPV) is the most common form of vertigo. Symptoms lead to increased risk for falls and a decline in functional status. First-line therapy for BPPV is canalith repositioning with the Epley maneuver, which is effective in up to 85% of patients. Medication is not useful in the treatment of BPPV except when the episodes are frequent and disabling. In that situation, the vestibular suppressant betahistine (not available in the United States) may be helpful along with the Epley maneuver. Meclizine probably contributed to this patient's near fall and fear of falling and is not especially helpful in controlling the symptoms of BPPV; it should be discontinued.
Discontinuing metoprolol (Option B) places the patient at increased risk for poor rate control of his atrial fibrillation and, in the absence of orthostatic hypotension, will not reduce his risk for falls.
Prescription of an assistive device, such as a cane (Option C), in the absence of a gait abnormality is not recommended.
Vitamin D supplementation (Option D) is not recommended for fall risk reduction. Meta-analysis of randomized controlled trials of community-dwelling elderly adults showed no reduction in fall or fracture risk in patients without osteoporosis or known vitamin D deficiency.
Key Point
Many health conditions, physical characteristics, and behaviors increase risk for falling, but the greatest increases are associated with cognitive impairment, psychoactive medications, gait/balance problems, and decreased lower extremity strength.
Bibliography
Grossman DC, Curry SJ, Owens DK, et al; US Preventive Services Task Force. Interventions to prevent falls in community-dwelling older adults: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:1696-704. PMID: 29710141 doi:10.1001/jama.2018.3097
Copyright 2019, American College of Physicians.