Pernicious Anemia: Presentations Mimicking Acute Leukemia

Cristi Aitelli, BS; Lori Wasson, DO; Ray Page, DO, PHD


South Med J. 2004;97(3) 

In This Article


Vitamin B12 is a necessary cofactor required for DNA synthesis. A deficiency will result in defective nuclear maturation because of inadequate DNA but not RNA or protein, thus giving the characteristic appearance of asynchronism between the cytoplasmic maturation and nuclear maturation. The ineffective hematopoiesis results in megaloblastoid changes of the erythroid precursors in the bone marrow. Many of these developing red blood cells are destroyed in the bone marrow before they are released into the circulation. This results in the increased indirect bilirubin and LDH. Vitamin B12 deficiency can produce a variety of other effects on the body as well, such as in the alimentary tract and central nervous system. The fact that these symptoms may range from minimal to profound can sometimes make this simple and reversible diagnosis not quite so obvious. Because vitamin B12 is stored in the liver for several years, it may take 3 to 6 years to deplete. Therefore, the anemia may be severe when discovered, although there is a concurrent lack of symptoms. Pernicious anemia, the most common cause of vitamin B12 deficiency, is predominately a disease of the elderly, with the average patient presenting near 60 years of age. Coexisting morbidity can further cloud the diagnosis. In the case of the alcoholic patient we presented, the macrocytosis, increased LDH, and urobilinogen could be because of the alcohol or the vitamin B12 deficiency. This fact, in conjunction with the unusually marked blastic changes and atypical morphology of the bone marrow, made the preliminary diagnosis of acute leukemia a viable option. The conflict arises from the fact that these patients are at risk of erroneously receiving potentially fatal induction chemotherapy for acute leukemia, when all they require is a vitamin B12 injection. Dokal et al[1] previously acknowledged this possibility as well.

There have been several cases reported of concurrent pernicious anemia and myelodysplastic syndrome or acute myelogenous leukemia. Drabick et al[2] reported a case in which vitamin B12 replacement therapy resulted in the resolution of neurologic findings and macrocytosis; however, the anemia and monocytosis persisted. Cytogenetics continued to reveal a clonality and the MDS eventually converted to AML. They also pointed out that reversible cytogenetic abnormalities have been observed with megaloblastic anemia, even including karyotypes typically associated with MDS or AML. Vogelsang et al[3] reported another case in which 57-year-old women developed acute leukemia with coexisting pernicious anemia. There was a decline in circulating blasts after vitamin B12 replacement; however, the blast cells persisted in the bone marrow.

Ahman el al[4] went a step further with this issue, suggesting that excessive replacement of vitamin B12 may in some cases even accelerate underlying hematologic malignancies. This is based on the observation that patients with vitamin B12 deficiencies have an increased incidence of hematologic malignancies. They demonstrated in vitro that adding vitamin B12 could stimulate blast colony formation.


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