Chapter 100. Megaloblastic Anemias (Part 6)

Psychiatric disturbance is common in both folate and cobalamin deficiencies. This, like the neuropathy, has been attributed to a failure of the synthesis of SAM, which is needed in methylation of biogenic amines (e.g., dopamine) as well as of proteins, phospholipids, and neurotransmitters in the brain (Fig. 100-1). Associations between lower serum folate or cobalamin levels and higher homocysteine levels and the development of Alzheimers disease have been reported. A 2-year double-blind placebo-controlled randomized clinical trial involving healthy subjects 65 years old given folate, cobalamin, and vitamin B 6 supplements showed no benefit on cognitive performance, whereas a 3-year...
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Chapter 100. Megaloblastic Anemias (Part 6) Chapter 100. Megaloblastic Anemias (Part 6) Psychiatric disturbance is common in both folate and cobalamindeficiencies. This, like the neuropathy, has been attributed to a failure of thesynthesis of SAM, which is needed in methylation of biogenic amines (e.g.,dopamine) as well as of proteins, phospholipids, and neurotransmitters in the brain(Fig. 100-1). Associations between lower serum folate or cobalamin levels andhigher homocysteine levels and the development of Alzheimers disease have beenreported. A 2-year double-blind placebo-controlled randomized clinical trialinvolving healthy subjects >65 years old given folate, cobalamin, and vitamin B 6supplements showed no benefit on cognitive performance, whereas a 3-year(FACIT) study did show benefit. Hematologic Findings Peripheral Blood Oval macrocytes, usually with considerable anisocytosis and poikilocytosis,are the main feature (Fig. 100-2A ). The MCV is usually >100 fL unless a cause ofmicrocytosis (e.g., iron deficiency or thalassemia trait) is present. Some of theneutrophils are hypersegmented (more than five nuclear lobes). There may beleukopenia due to a reduction in granulocytes and lymphocytes, but this is usually>1.5 x 109/L; the platelet count may be moderately reduced, rarely to A. The peripheral blood in severe megaloblastic anemia. B. The bonemarrow in severe megaloblastic anemia. [Reprinted from Hoffbrand AV et al (eds)Postgraduate Haematology, 5th ed, Blackwell Publishing, Oxford, UK 2005; withpermission.] Bone Marrow In the severely anemic patient, the marrow is hypercellular with anaccumulation of primitive cells due to selective death by apoptosis of more matureforms. The erythroblast nucleus maintains a primitive appearance despitematuration and hemoglobinization of the cytoplasm. The cells are larger thannormoblasts, and an increased number of cells with eccentric lobulated nuclei ornuclear fragments may be present (Fig. 100-2B). Giant and abnormally shapedmetamyelocytes and enlarged hyperpolyploid megakaryocytes are characteristic.In less anemic patients, the changes in the marrow may be difficult to recognize.The terms intermediate, mild, and early have been used. The term megaloblastoiddoes not mean mildly megaloblastic. It is used to describe cells with bothimmature appearing nuclei and defective hemoglobinization and is usually seen inmyelodysplasia. Chromosomes Bone marrow cells, transformed lymphocytes, and other proliferating cellsin the body show a variety of changes including random breaks, reducedcontraction, spreading of the centromere, and exaggeration of secondarychromosomal constrictions and overprominent satellites. Similar abnormalitiesmay be produced by antimetabolite drugs (e.g., cytosine arabinoside, hydroxyurea,and methotrexate) that either interfere with DNA replication or folate metabolismand that also cause megaloblastic appearances.