Internal Medicine

0521779407-07 CUNY1086/Karliner 0 521 77940 7 June 4, 2007 21:10

Folic Acid/Cobalamin (Vitamin B12) Deficiency 577

Pregnancy, lactation, prematurity/infancy; increased hemato-

poietic turnover, malignancy, psoriasis

Tropical/nontropical sprue, regional enteritis

Drugs: antifolates, alcohol, sulfasalazine, triamterene, pyrime-

thamine, trimethoprim-sulfamethoxazole, carbamazepine,

diphenylhydantoin, barbiturates

tests

Macrocytosis and the evaluation of macrocytic anemia

Anemia is macrocytic if MCV >100 fl. If MCV <110 fl and corrected

reticulocyte is >2%, rule out response to acute blood loss or hemoly-

sis (immune hemolytic anemia, infectious or mechanical causes, glu-

cose 6-phosphate dehydrogenase deficiency, or paroxysmal nocturnal

hemoglobinuria).

If corrected reticulocyte count is normal or <0.5%, then differentiate

between macroovalocytes (central pallor occupies less than one third

of cell) and thin macrocytes (central pallor occupies more than one

third of cell).

Thin macrocytes (MCV 100–110 fl) are found in the post-splenectomy

state, liver disease with or without alcoholism, aplastic/hypoplastic

anemia, myelodysplastic (esp. 5q-) syndrome, myelopthisic anemia,

hypothyroidism, smoking, chronic lung disease, severe hyperglycemia,

and leukocytosis).

Macroovalocytes with MCV >110 fl and low reticulocyte counts

(0.5%) are usually induced by an intrinsic interference with DNA

synthesis leading to megaloblastic anemia (e.g., deficiency of cobal-

amin or folate, or by antineoplastic and immunosuppressive agents

[antimetabolites, alkylating agents, topoisomerase inhibitors], and

anti-retroviral therapy).

■Morphologic manifestations of megaloblastosis from cobalamin

and folate deficiency are similar: Peripheral smear=Increased

MCV with macroovalocytes, hypersegmented PMNs, thrombocy-

topenia (mild). Bone marrow aspirate=classic megaloblastosis

(trilineal hyperplasia, orthochromatic megaloblasts, giant meta-

myelocytes, hypersegmented PMNs, megakaryocytic pseudohyper-

diploidy)

■Other supporting tests: reticulocytopenia, hyperbilirubinemia,

decreased haptoglobin, increased LDH

■Masked megaloblastosis when inadequate hemoglobinization (iron

deficiency/defects in globin synthesis), but hypersegmented PMNs

present