Pathology

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 time.

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 (5-fluorouracil) synthesis.

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

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.