Bone marrow aplasia

Beagle dog inhalation "CeCl, AMAD t.5-2,4 ion a, 1.6-2.1 13-16 mos 70 life span (in progress) death, bone marrow aplasia and pancytopenia, radiation pneumonitis, pulmonary fibrosis, hepatic necrosis 11/48 Yes pulmonary adenoma, bronchtogenic adenocarcinoma 3/48 Yes he man- Yes giocarcinoma osteosarcoma, 6/48 leukemia 3/34 (primary) Benjamin et al. (1972b 1976c) Merickel et al. (1978)... 

Blood dyscrasias An irreversible type of marrow depression leading to aplastic anemia with a high rate of mortality is characterized by appearance of bone marrow aplasia or hypoplasia weeks or months after therapy. Peripherally, pancytopenia is most often observed, but only 1 or 2 of the 3 major cell types may be depressed. 

The effectiveness of chemotherapy is enhanced by adequate immune function however, some antibiotics suppress immune function. For example, tetracychnes can decrease leukocyte chemotaxis and complement activation. Rifampin decreases the number of T lymphocytes and depresses cutaneous hypersensitivity. Antibiotics such as the sulfonamides may induce granulocytopenia or bone marrow aplasia. These effects are not well understood but may be due to enteric bacterial metabohc byproducts of these antibiotics. 

Contraindications Bone marrow aplasia, historyofgold-induced pathologies (including blood dyscrasias, exfoliative dermatitis, necrotizing enterocolitis, and pulmonary fibrosis), severe blood dyscrasias... 

In chronic benzene intoxication, mild poisoning produces headache, dizziness, nausea, stomach pain, anorexia, and hypothermia. In severe cases, pale skin, weakness, blurred vision, and dyspnea occur on exertion. Hemorrhagic tendencies include petechia, easy bruising, and bleeding gums. Bone marrow depression produces a decrease in circulating peripheral erythrocytes and leucocytes (101). Fatalities from chronic exposure show at autopsy severe bone marrow aplasia, and necrosis or fatty degeneration of the heart, fiver, and adrenals (125). 

The most dangerous adverse reaction of sulfonylureas is agranulocytosis. Aplastic anemia (79), red cell aplasia (80), pure white cell aplasia (81), bone marrow aplasia, and hemolytic anemia have been described during treatment with chlorpropamide (82), glibenclamide (83), or tolbutamide (84). 

The most serious problem associated with chloramphenicol is the potential for bone marrow aplasia, which can lead to aplastic anemia and possibly death.16,83 Chloramphenicol is also associated with other blood dyscrasias such as agranulocytosis and thrombocytopenia. Because of these risks, chloram-... 

Mustard gas is also a radiomimetic (Sidell eta/., 1997). It destroys precursor cells in the bone marrow leading to leukopenia, thrombocytopenia, pancytopenia, and anemia (Borak and Sidell, 1992 Dacre and Goldman, 1996). Infection can be seen secondary to bone marrow damage (Sidell et al, 1997). Bone marrow aplasia and death can be seen in severe cases. 

In isolated cases, Stevens-Johnson syndrome together with cholestasis and bone marrow aplasia have been associated with either amoxicUhn alone (41) or with co-amoxiclav (42). 

Yamamoto K, Nagata K, Hamaguchi H. [Complete remission of essential thrombocythemia after recovery from severe bone marrow aplasia induced by busulfan treatment.] Gan To Kagaku Ryoho 1997 24(3) 365-9. 

The first death resulting from bone marrow aplasia induced by chloramphenicol eye-drops was described in 1955 (17). Chloramphenicol causes two types of bone marrow damage (18). 

A rare, late type of bone marrow aplasia, a hypersusceptibihty reaction, which is generally irreversible, and has a high mortality rate (aplastic anemia) (19-21). 

Although there is no evidence that these abnormalities progress to frank bone marrow aplasia, continuation of chloramphenicol after the appearance of early toxicity is thought to be hazardous. Pre-existing liver damage (for example due to infectious hepatitis or alcoholism) and impaired kidney function can lead to reduced elimination of chloramphenicol and its metabolites, thereby aggravating marrow toxicity. As a rule, this is not the irreversible type. 

Although bone marrow aplasia has not been related with certainty to either the daily or the total dose of chloramphenicol or to the sex or age of the patients, it has occurred almost exclusively in individuals who were taking prolonged therapy, particularly if they were exposed to the drug on more than one occasion (24). The condition is rare, occurring about once in every 18 000-50 000 subjects in various countries. These variations may in part depend on ethnic factors (25,26). For example, there have been very few cases reported in blacks (27). Bone marrow aplasia due to chloramphenicol has usually resulted in aplastic anemia with pancytopenia other forms, such as red cell hypoplasia, selective leukopenia, or thrombocytopenia, are less common. 

When bone marrow aplasia was complete, the fatality rate approached 100%. As a rule, it has been found that the longer the interval between the last dose of chloramphenicol and the appearance of the first sign of a blood dyscrasia, the more severe the resulting aplasia. Nearly all patients in whom the interval was longer than 2 months died as a result of this comphcation. However, fatal aplastic anemia can also occur shortly after normal doses of chloramphenicol (28). 

The pathogenesis of bone marrow aplasia after chloramphenicol is still uncertain. Compared with normal cells, bone marrow aspirates from patients with bone marrow aplasia are relatively resistant to the toxic effects of chloramphenicol in vitro. This has been... 

This has lent support to the hypothesis that abnormal metabolism may contribute to the susceptibility to bone marrow aplasia. The production of reduced derivatives by intestinal microbes may contribute to toxicity, but oral administration of chloramphenicol is not essential for the development of aplastic anemia... 

Brodsky E, Biger Y, Zeidan Z, Schneider M. Topical application of chloramphenicol eye ointment followed by fatal bone marrow aplasia. Isr J Med Sci 1989 25(1) 54. 

Bone marrow depression is common after colchicine overdose and intoxication and less common in therapeutic doses. Fatal cases of agranulocytosis are more often associated with bone marrow aplasia (SEDA-4, 70) (5). Bone marrow depression usually occurs between the third and sixth days of acute intoxication. Cytoplasmic inclusions in neutrophils and megaloblastic anemia have been described. Administration of therapeutic doses intravenously and orally to two patients with reduced renal function caused profound prolonged neutropenia complicated by septicemia, which ended in death (SEDA-13, 84). 

Sofroniadou K, Drossou M, Foundoulaki L, Konstantopoulos K, Kyriakoy D, Zervas J. Acute bone marrow aplasia associated with intravenous administration of deferoxamine (desferrioxamine). Drug Saf 1990 5(2) 152-4. 

Aplastic anemia occurred in one patient who had recovered 7 years earlier from bone-marrow aplasia ascribed to carbamazepine (SEDA-20, 63). Severe pure red cell aplasia in a patient with heterozygous beta-thalassemia reversed rapidly after lamotrigine withdrawal however,... 

Agranulocytosis (probably due to toxicity rather than hypersusceptibility) can be caused by sulindac (13), as can bone marrow aplasia (14) and severe thrombocytopenia (15,16), which may be the consequence of autoimmune platelet destruction in the presence of sulindac or its metabolite (SEDA-7, 109). Immune-mediated hemolytic anemia with a positive direct antiglobulin test has been reported (SEDA-18,103). 

Most reviewers have been impressed by the fact that the reported cases of peripheral cytopenia were never accompanied by bone marrow aplasia (8). There have been some doubtful case reports of marrow aplasia, in which factors such as advanced age (predisposing to antibiotic accumulation), neoplasia, concurrent treatment (myelotoxic drugs, anticoagulants), and major surgical interventions have to be mentioned. Even if these cases are to be ascribed to thiamphenicol, they fall within the normal spontaneous incidence of aplastic anemia (9-12). 

De Renzo A, Formisano S, Rotoh B. Bone marrow aplasia and thiamphenicol. Haematologica 1981 66(1) 98-104. 

Martinez-Dalmau A, Fernandez MN, BarboUa L. Haematological toxicity of thiamphenicol analysis of a case with total irreversible bone marrow aplasia and general review of the problem. [Hematologic toxicity of thiamphenicol. Analysis of a case of irreversible total medullary aplasia and general review of the problem.] Sangre (Bare) 1972 17(l) 59-66. 

Elias M, Reichman N, Flatau E. Bone marrow aplasia associated with ticlopidine therapy. Am J Hematol 1993 44(4) 289-90. 

Taillan B, Nectoux F, Vinti H, Fuzibet JG, Verdier JM, Dujardin P, Chichmanian RM, Vitetta A. Aplasie medullaire au cours d une polyarthrite rhumatoide traitee par tiopronine. [Bone marrow aplasia in rheumatoid polyarthritis treated with tiopronin.] Rev Rhum Mai Osteoartic 1990 57(5) 443. ... 

Toxic effects of sulfur mustard and ethyleneimine on animals were described in the 19th century. The powerful vesicant action of sulfur mustard led to its u.se in World War I. and medical examination of the victims revealed that tissues were damaged at sites distant from the area of contact." Such systemic elTects included leukopenia, bone marrow aplasia, lymphoid tissue suppression, and ulceration of the gastrointestinal tract. Sulfur mustard was shown to be active against animal tumors, but it was too nonspecific for clinical use. A variety of nitrogen mustards were synthesized between the two world wars. Some of these compounds (e.g.. 

The major toxicological manifestation of chronic benzene exposure in humans is bone marrow depression. Clinical manifestations include anemia, leuco-penia, and thrombocytopenia. In severe cases, bone marrow aplasia develops. Later stages of toxicity are manifested by pancytopenia and aplastic anemia. Death may result from aplastic anemia or from leukemia. The US Environmental Protection Agency (EPA) and International Agency for Research on Cancer classify benzene as a known human carcinogen. 

Busulfan is a potent cytotoxic drug. Early in development of the compound, in vivo experiments indicated that busulfan caused severe depression in the bone marrow. The most prevalent acute toxic effects associated with busulfan in animals are severe pancytopenia from bone marrow failure. Associated in vivo experiments show bone marrow aplasia, stromal cell damage, immunosuppression (impaired T-lymph-ocyte function), and pronounced adverse effects on reproductive glands, germ cells, and fertility in animals (lowest effective dose tested was 2 mg kg... 

MacVittie TJ, Farese A, Herodin F et al. (1996). Combination therapy for radiation-induced bone marrow aplasia in nonhuman primates using synthetic SC-55494 and recombinant human granulocyte-colony stimulating factor. Blood, 97, 4129 1135. 

Radioactive Strontium. In Chinese hamsters and mice, a single intraperitoneal injection of 32-5,000 Ci 90Sr/kg resulted in deaths from bone marrow aplasia at the highest doses, increased deaths from osteosarcoma at moderately high doses, and from lymphoreticular tumors at lower doses (Brooks et al. 1974 Nilsson et al. 1980a Reif and Triest 1982). 

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