5. Megaloblastic Anemia
Megaloblastic anemias are characterized by the presence of a hypercellular bone marrow with large, abnormal hematopoetic progenitor cells (megaloblasts). Leukopenia and thrombocytopenia also occur. Megaloblastic anemias can be congenital or acquired and most commonly are related to vitamin B12 (cobalamin) and folic acid deficiencies. While they are usually a result of malnutrition or defective absorption, they can also be drug-induced.
Drugs that act by interfering with DNA synthesis, such as antimetabolites and alkylating agents, some antinucleosides used against HIV and other viruses [14], can all induce megaloblastic anemia. Trimethoprim (in high, extended doses) and pyrimethamine, which bind with greater affinity to bacterial than human dihydrofolate reductase, have been associated with megaloblastic anemia, primarily among patients already at risk for folic acid deficiency. Antibiotics such as sulfasalazine and anticonvulsants such as phenytoin have been linked to folate-related changes which induce megaloblastic anemia, perhaps related to interference with absorption.
Decreased cobalamin levels have been reported with term use of histamine 2-receptor antagonists and proton pump inhibitors (e.g., omeprazole) [15, 16]. While protein bound B12 absorption may be impaired by these agents, clinically significant B12 deficiency seems rare despite widespread use.