Bone marrow failure

Aplastic anaemia describes bone marrow failure, characterized by serious reduction in the number of stem cells present. 

AIDS is associated with aberrant lymphocyte production and it has been proposed that Li+ may have a potential role in reversing this. Additionally, 3 -azido-3"deoxythymidine (AZT, zidovudine), an effective inhibitor of viral reverse transcriptase that reduces mortality in AIDS patients, induces hematopoietic suppression in patients resulting in anemia, neutropenia, and overall bone-marrow failure [220]. In murine AIDS, the coadministration of Li+ effectively moderates this toxicity of AZT in vivo [221,222]. There are several case reports where Li+ has been administered to help reduce the hematopoietic suppression in HIV-infected patients taking AZT (for example, see ref. 223). To date, the use of Li+ has been limited to a few weeks of treatment, and varying degrees of success have been achieved nevertheless the outlook in this field is quite hopeful. 

Bone marrow failure Anemia of chronic disease Renal failure Endocrine disorders Myelodysplastic anemias... 

Normochromic and normocytic cells Bone marrow failure Chronic inflammation Antibody production... 

Bhatia M, Davenport V, Cairo MS. 2007. The role of interleukin-11 to prevent chemotherapy-induced cytopenia in patients with solid tumors, lymphomas, acute myeloid leukemia and bone marrow failure syndromes. Leuk Lymph. 48 9-15. 

In selected patients, erythropoietin may also be useful for the treatment of anemia due to primary bone marrow disorders and secondary anemias. This includes patients with aplastic anemia and other bone marrow failure states, myeloproliferative and myelodysplastic disorders, multiple myeloma and perhaps other chronic bone marrow malignancies, and the anemias associated with chronic inflammation, AIDS, and cancer. Patients with these disorders who have disproportionately low serum erythropoietin levels for their degree of anemia are most likely to respond to treatment with this growth factor. Patients with endogenous erythropoietin levels of less than 100 IU/L have the best chance of response, though patients with erythropoietin levels between 100 and 500 IU/L respond occasionally. These patients generally require higher erythropoietin doses (150-300 IU/kg three times a week) to achieve a response, and responses are often incomplete. 

Williams DA, Croop J, Kelly P. Gene therapy in the treatment of Fanconi anemia, a progressive bone marrow failure syndrome. Curr Opin Mol Therapeut 2005 5 461-6. 

Aphytic zone Parts of the lake floor where vegetation is not available Aplastic anemia Bone marrow failure with markedly decreased production of white blood cells, red blood cells, and platelets, leading to increased risk of infection and bleeding... 

If high plasma concentrations are maintained for more than 24-48 hours, irreversible bone marrow failure may occur. Toxicity from high blood concentrations can be prevented by administration of antidote (folinic acid) any time before 48 hours after injection. 

Hypertension, arrhythmias, muscle paralysis Renal and bone marrow failure, hepatotoxicity Heart failure, inhibition of spermatogenesis Respiratory arrest, topical irritation Hypothermia, anxiety, seizures, arrhythmias, respiratory arrest... 

Initially, most of the adverse effects seen with zidovudine use (in particular hematological effects) were attributed to interference with cellular DNA replication. However, DNA replication also occurs in mitochondria. Mitochondrial DNA encodes some of the enzymes used for oxidative phosphorylation. Only recently has it been hjrpothesized that inhibition of this pathway could lead to mitochondrial toxicity and be responsible for most of the toxicity seen with NRTIs, including polyneuropathy, myopathy, cardiomyopathy, steatosis, lactic acidosis, exocrine pancreas failure, bone marrow failure, and proximal tubular dysfunction (11). These adverse effects are also a compilation of the clinical features seen in several genetic mitochondrial cytopathies. 

Co-trimoxazole should not be given to patients with malnutrition, pregnancy, severe liver damage, megaloblastic anemia, agranulocytosis, or bone marrow failure (12,14,87). 

Very rare effects include bone-marrow suppression associated with platelet autoantibodies and coagulopathy, transient leukopenia, lethal bone-marrow failure due to self-poisoning, reversible intravascular hemolysis, and pure red cell aplasia (SED-12,134) (65-68). 

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... 

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