Hematological Toxicity of Chloramphanicol

Dr. Ahmad Najmi, Index Medical College, Indore
The most important adverse effect of chloramphenicol is on the bone marrow. Chloramphenicol affects the hematopoietic system in two ways: a dose-related toxicity that presents as anemia, leukopenia, or thrombocytopenia; and an idiosyncratic response manifested by aplastic anemia, leading in many cases to fatal pancytopenia.
Pancytopenia seems to occur more commonly in individuals who undergo prolonged therapy and especially in those who are exposed to the drug on more than one occasion.
A genetic predisposition is suggested by the occurrence of pancytopenia in identical twins. Although the incidence of the reaction is low¾1 in approximately 30,000 or more courses of therapy¾the fatality rate is high when bone-marrow aplasia is complete, and there is an increased incidence of acute leukemia in those who recover.
Aplastic anemia accounts for approximately 70% of cases of blood dyscrasias due to chloramphenicol, while hypoplastic anemia, agranulocytosis, and thrombocytopenia make up the remainder.
The exact biochemical mechanism has not yet been elucidated but is hypothesized to involve conversion of the nitro group to a toxic intermediate by intestinal bacteria.

The risk of aplastic anemia does not contraindicate the use of chloramphenicol in situations in which it may be life-saving. The drug should never be used, however, in undefined situations or in diseases readily, safely, and effectively treatable with other antimicrobial agents.

Dose-related, reversible erythroid suppression probably reflects an inhibitory action of chloramphenicol on mitochondrial protein synthesis in erythroid precursors, which in turn impairs iron incorporation into heme.
Leukopenia and thrombocytopenia also may occur. Bone marrow suppression occurs regularly when plasma concentrations are 25 mg/ml or higher and is observed with the use of large doses of chloramphenicol, prolonged treatment, or both. Dose-related suppression of the bone marrow may progress to fatal aplasia if treatment is continued, but most cases of bone marrow aplasia develop suddenly, without prior dose-related marrow suppression.
Some patients who developed chronic bone marrow hypoplasia after chloramphenicol treatment subsequently developed acute myeloblastic leukemia.

The administration of chloramphenicol in the presence of hepatic disease frequently depresses erythropoiesis. About one-third of patients with severe renal insufficiency exhibit the same reaction.
Reference: Goodman & Gillmans Pharmacological Basis of Therapeutics , 11th edition