Aplastic

Both chloramphenicol and thiamphenicol cause reversible bone marrow suppression (9). The irreversible, often fatal, aplastic anemia, however, is only seen for chloramphenicol (9). This rare (1 in 10,000—45,000) chloramphenicol toxicity has been linked to the nitroaromatic function (1,9). Thiamphenicol, which is less toxic than chloramphenicol in regard to aplastic anemia, lacks potency as can be seen in Table 1, and thiamphenicol has never found much usage in the United States. An analogue of thiamphenicol having antimicrobial potencies equivalent to chloramphenicol was sought. Florfenicol (2) was selected for further development from a number of closely related stmctures. 

Aplastic anemia and leukemia are not the only health effects ascribed to benzene exposure. A number of recent studies have associated benzene exposure with chromosomal changes (aberrations) (118). Other studies have shown abnormalities in porphyrin metabolism and decrease in leucocyte alkaline phosphatase activity in apparendy healthy workers exposed to 10—20 ppm benzene (119,120). Increases in leukoagglutinins, as well as increases in blood fibrinolytic activity, have also been reported and are believed to be responsible for the persistent hemorrhages in chronic benzene poisoning (121,122). 

Treatment for chronic benzene poisoning is supportive and symptomatic, with chemotherapy and bone marrow transplants as therapeutic agents for leukemia and aplastic anemia (127). 

Toxic Effects on the Blood-Forming Tissues Reduced formation of erythrocytes and other elements of blood is an indication of damage to the bone marrow. Chemical compounds toxic to the bone marrow may cause pancytopenia, in which the levels of all elements of blood are reduced. Ionizing radiation, benzene, lindane, chlordane, arsenic, chloramphenicol, trinitrotoluene, gold salts, and phenylbutazone all induce pancytopenia. If the damage to the bone marrow is so severe that the production of blood elements is totally inhibited, the disease state is termed aplastic anemia. In the occupational environment, high concentrations of benzene can cause aplastic anemia. 

For example, exposure to the air toxin benzene catr increase the risk of getting myelogenous leukemia or aplastic anemia, while exposure to ground-level ozone can cause a 15 to 20 percent decrease in lung capacity in some healthy adults. 

Aplastic anemia—anemia due to deficient red blood cell production in the bone marrow... 

Hematologic—neutropenia, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, agranulocytosis, and aplastic anemia... 

Hydroxychloroquine administration may result in irritability, nervousness, anorexia, nausea, vomiting, and diarrhea This drug also may have adverse effects on the eye, including blurred vision, comeal edema, halos around lights, and retinal damage. Hematologic effects, such as aplastic anemia and leukopenia, may also be seen. 

Administration of trimethadione (Tridione) may result in hematologic changes, such as pancytopenia (decrease in all the cellular components of the blood), leukopenia, aplastic anemia, and thrombocytopenia Also reported are various types of skin rashes, diplopia (double vision), vomiting, changes in blood pressure, CNS depression, photosensitivity, and fatal nephrosis. Because these dm have been associated with serious adverse reactions and fetal malformations, they should be used only when other less toxic dm are not effective in controlling seizures. The oxazolidinediones may precipitate a tonic-clonic seizure... 

BENZODIAZEPINES Carbamazepine may cause aplastic anemia and agranulocytosis. During treatment blood studies are performed frequently If evidence of bone marrow depression is obtained (eg, the patient s platelet... 

The most serious adverse reaction associated with these drugs is agranulocytosis (decrease in the number of white blood cells [eg, neutrophils, basophils, and eosinophils]). Reactions observed with agranulocytosis include hay fever, sore throat, skin rash, fever, or headache Other major reactions include exfoliative dermatitis, granulocytopenia, aplastic anemia, hypoprothrombinemia, and hepatitis. Minor reactions, such as nausea, vomiting, and paresthesias, also may be seen. 

McKinney LL, Weakley FB, Eldridge AC, et al. 1957. S-(dichlorovinyl)-L-cysteine an agent causing fatal aplastic anemia in calves. J Am Chem Soc 79 3932-3933. 

Anorexia, aplastic anemia, headache, hepatotoxicity, weight loss... 

Low reticulocyte counts may indicate a diseased bone marrow (e.g., aplastic anemia, myelodysplasia, or leukemia), especially if the white blood cells and platelets are low. 

Skeletal bone marrow (aplastic crisis), long bones, hand and feet (dactylitis)... 

Treatment of SCD is aimed at the preventing and/or minimizing acute and chronic complications, including infection, acute chest syndrome, neurologic damage, and the various forms of sickle cell crises, including vaso-occlusive pain, splenic sequestration, and aplastic crisis. The acute and chronic complications are summarized in Tables 65-2,65-3, and 65-4. 

Most patients in aplastic crisis will recover spontaneously. Therefore, treatment is supportive. If anemia is severe or symptomatic, transfusion may be indicated. Infection with human parvovirus B19 is the most common cause of aplastic crisis. Isolate infected patients because parvovirus is highly contagious. Pregnant women should avoid contact with infected patients because midtrimester infection with parvovirus may cause hydrops fetalis and stillbirth.6,27... 

---