Correspondence

Megaloblastosis

N Engl J Med 1996; 335:2000-2001December 26, 1996

Article

To the Editor:

The Image in Clinical Medicine of the peripheral-blood smear from a patient with vitamin B₁₂ deficiency (Aug. 1 issue)1 beautifully captures many of the features of megaloblastic anemia. The author mentions that the patient's mean corpuscular volume of 103 μm³ was “very low for pure vitamin B₁₂ deficiency of this severity and might have suggested an additional hematologic problem,” but no additional abnormality was found. In fact, many patients with severe megaloblastic anemia have mean corpuscular volumes that are very elevated at first but later decline to the levels seen in this patient, while the red-cell–distribution width increases. Inspection of the peripheral-blood smear in such patients reveals the presence of schistocytes. The small size of the schistocytes lowers the mean corpuscular volume and raises the red-cell–distribution width. Schistocytes may be due to a further decline in the effectiveness of erythropoiesis in the bone marrow. The field shown in the image does not reveal schistocytes; however, they may be present in other fields.

Justine Meehan Carr, M.D.
Beth Israel Hospital, Boston, MA 02215

1 References

1
Moll S. Vitamin B₁₂ deficiency. N Engl J Med 1996;335:323-323
Full Text | Web of Science | Medline

To the Editor:

Moll describes a 72-year-old man with vitamin B₁₂ deficiency and states that “a bone marrow biopsy showed marked megaloblastic changes consistent with the diagnosis of vitamin B₁₂ deficiency.” Your readers should not accept the idea that a bone marrow biopsy is the procedure of choice to confirm megaloblastosis. When Moll wrote that sentence, he was probably thinking of bone marrow aspiration. Evaluation of the cytoplasmic and nuclear morphology of hematopoietic precursors in aspirate smears allows precise assessment of megaloblastic changes. Bone marrow biopsy, which mainly provides histologic information, is not useful for this purpose.

José M. Raya, M.D.
Hospital Universitario de Canarias, 38320 La Laguna, Spain

To the Editor:

In the August 1 issue, which also included a review of the evaluation of dementia,1 Dr. Moll tantalized us in the legend to the Image in Clinical Medicine by not divulging whether the patient's neuropsychiatric response matched his excellent hematologic response to replacement therapy.

Mark N. Lowenthal, M.B.
Soroka Medical Center and Ben Gurion University of the Negev, Beer Sheva 84101, Israel

1 References

1
Geldmacher DS, Whitehouse PJ. Evaluation of dementia. N Engl J Med 1996;335:330-336
Full Text | Web of Science | Medline

Author/Editor Response

Dr. Moll replies:

To the Editor: I am thankful to Dr. Carr for her comment on the contribution of schistocytes to the relatively low mean corpuscular volumes in some patients with severe vitamin B₁₂ deficiency. In keeping with her observation, small, fragmented red cells were present on the blood film of our patient in areas not shown on the image. Her observation that the mean corpuscular volume in many patients is high early in the course of vitamin B₁₂ deficiency and lower later in the course is interesting. An elevated mean corpuscular volume can decrease with worsening vitamin B₁₂ deficiency if additional iron deficiency develops. If a patient with vitamin B₁₂ deficiency is treated with folic acid only, the hematologic values often improve (the hemoglobin level increases and the mean corpuscular volume decreases), in spite of worsening vitamin B₁₂ deficiency.1 Progression from a high to a low mean corpuscular volume is otherwise not documented in the literature. Although Prentice and Evans2 did note a steady increase in the mean corpuscular volume with worsening anemia, down to a red-cell count of 1.5 × 10¹² per liter, and below this value a fall in the mean corpuscular volume, this decline was not statistically significant. Stabler et al.,3 on the other hand, found a poor correlation between the degree of anemia and the mean corpuscular volume.

Raya correctly points out that bone marrow morphology is best evaluated by examination of bone marrow aspirates. To diagnose vitamin B₁₂ deficiency, a bone marrow biopsy is not necessary. In fact, even bone marrow aspiration is, in many cases, unnecessary. The clinical presentation of a patient and the physical and laboratory findings may, however, require bone marrow examination to rule out leukemia or a myeloinfiltrative process.

The patient's short-term memory returned to normal after vitamin B₁₂–replacement therapy. A sensory examination to follow up on the loss of vibration sense was not reported by the patient's primary physician.

Stephan Moll, M.D.
Durham, NC 27705

3 References

1
Hall BE, Watkins CH. Experience with pteroylglutamic (synthetic folic) acid in the treatment of pernicious anemia. J Clin Lab Med 1947;32:622-634
Medline

2
Prentice AG, Evans IL. Megaloblastic anaemia with normal mean cell volume. Lancet 1979;1:606-607
CrossRef | Web of Science | Medline

3
Stabler SP, Allen RH, Savage DG, Lindenbaum J. Clinical spectrum and diagnosis of cobalamin deficiency. Blood 1990;76:871-881
Web of Science | Medline

Citing Articles (1)