Abnormalities of nucleoprotein synthesis block or slow
DNA replication in proliferating cells.
In the case of RBCs slowing of DNA synthesis means that
large numbers of nucleated erythrocytes remain in the
synthesis phase of the mitotic cycle for long periods of
Because RNA synthesis is independent of DNA, not
requiring the same nucleotide mix and enzymes, the
production of cytoplasmic proteins is not greatly impaired.
Abnormalities of DNA synthesis usually result from
acquired deficiencies of Vitamin B12 or folate.
Several drugs inhibit DNA synthesis (hydroxyurea;
cytosine arabinoside), especially inhibitors of purine
(azathiaprine; 6-mercaptopurine) or pyrimidine
Rarely, inherited conditions interfer with DNA synthesis.
In addition, abnormalities of DNA synthesis are seen in
myelodysplastic syndromes, erythroleukemia, and congenital
dyserythropoietic anemia. The nature of the defects is not
clear in these cases.
Each of the above DNA synthetic abnormalities result in
macrocytosis of erythrocytes.
Although, not all macrocytosis is caused by abnormalities
of DNA synthesis.
Macrocytosis or an MCV of >100 is a common finding,
most often associated with alcohol intake. The second most
common cause of macrocytosis is abnormal DNA synthesis due
to B12 or folate deficiency.
Hypothyroidism, liver disease, and blood loss or
hemolysis are also associated with macrocytosis.
Macrocytic anemia resulting from abnormal DNA synthesis
is referred to as megaloblastic anemia.
Compare the size of the erythrocytes to the
small lymphocyte (ª7m diameter). Normal
erythrocytes are ª 7-8m in diameter. The
erythrocytes above are larger than the small
lymphocyte, an indication of macrocytosis.
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