Aplastic anemia treatment

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

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... 

Rappaport JM, Nathan DG Acquired aplastic anemias Pathophysiology and treatment. Adv Intern Med 27 547-590, 1982... 

In human case reports, chlordane exposure has been linked to neuroblastoma, aplastic anemia, and acute leukemia, but only circumstantially. In a 1987 report, 25 new cases of blood dyscrasia, including leukemias, production defects, and thrombocytopenic purpura (generally after home termite treatment with chlordane/heptachlor), were reported. The authors noted the rarity of many of the conditions and, hence, the difficulty of finding statistically significant results. 

Hematopoietic stem cells are used to treat people whose own blood-forming cells fail because of a rare condition called aplastic anemia, or to help people who have been accidentally exposed to very high doses of irradiation. Hematopoietic stem cells are most often used as part of the treatment for certain forms of cancer. Sometimes cancer patients are given very high doses of irradiation and/or chemotherapy drugs that destroy the blood-forming stem cells in the bone marrow. Transplants with the patient s own blood stem cells that were removed before the treatment, or stem cells from a healthy donor, allow the patient to recover. The transplant process is very simple The cells in a salt solution are slowly injected into a vein just like a blood transfusion. If the blood stem cells come from a donor, then the donor and the patient must share certain inherited proteins to make sure that the donor s immune system cells will not attack the treated patient. 

Mostly chloramphenicol is well tolerated with only mild gastrointestinal disturbances. However this antibiotic inhibits mitochondrial protein synthesis in red blood cell precursors in the bone marrow and thus may cause dose-dependent anemia. This dose dependent reaction should not be confused with the idiosyncratic aplastic anemia which is dose-independent and usually fatal. The onset of this idiosyncrasy which has an incidence of about 1 20 000-1 50 000 may be during the treatment or weeks to months after therapy. 

Anti-lymphocyte globulin (ALG) has been prepared as an highly purified solution of y-globulins with antilymphocyte activity by immunizing horses with human lymphocytes. It activates complement-mediated destruction of lymphocytes and thus decreases cellular immunity with only a limited effect on humoral immunity. Anti-lymphocyte globulin suppresses delayed type hypersensitivity reactions. It is used for the prevention and treatment of rejection episodes of transplanted organs. It also has some indication for the management of idiopathic aplastic anemia. Adverse effects include pain at the site of injection, erythema, serum sickness and rarely anaphylactic shock and thrombocytopenia. 

Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006 108 2509-19. 

Felbamate (Felbatol) was introduced with the expectation that it would become a major drug in the treatment of epilepsy. Felbamate exhibited few manifestations of serious toxicity in early clinical trials. Soon after its introduction, however, it became apparent that its use was associated with a high incidence of aplastic anemia. Consequently, felbamate is indicated only for patients whose epilepsy is so severe that the risk of aplastic anemia is considered acceptable. 

Chloramphenicol also is widely used for the topical treatment of eye infections. It is a very effective agent because of its extremely broad spectrum of activity and its ability to penetrate ocular tissue. The availability of safer, less irritating instilled ophthalmic antibiotics and the increase in fatal aplastic anemia associated with the use of this dosage form suggest that this agent might best be withdrawn. 

Aplastic anemia occurs in only about 1 in 24,000 to 40,000 cases of treatment. It is not a dose-related response and can occur either while the patient is taking chloramphenicol for days to months after completion of therapy. The aplastic or hypoplastic response involves all cellular elements of the marrow and is usually fatal. The mechanism is not known, but it occurs most frequently with oral or ocular administration. 

Unlabeled Uses Treatment of alopecia areata, aplastic anemia, atopic dermatitis, Behpet s disease, biliary cirrhosis, prevention of corneal transplant rejection... 

Considerable concern exists regarding the occurrence of idiosyncratic blood dyscrasias with carbamazepine, including fatal cases of aplastic anemia and agranulocytosis. Most of these have been in elderly patients with trigeminal neuralgia, and most have occurred within the first 4 months of treatment. The mild and persistent leukopenia seen in some patients is not necessarily an indication to stop treatment but requires careful monitoring. The most common idiosyncratic reaction is an erythematous skin rash other responses such as hepatic dysfunction are unusual. 

G-CSF and GM-CSF have also proved to be effective in treating the neutropenia associated with congenital neutropenia, cyclic neutropenia, myelodysplasia, and aplastic anemia. Many patients with these disorders respond with a prompt and sometimes dramatic increase in neutrophil count. In some cases, this results in a decrease in the frequency of infections. Because neither G-CSF nor GM-CSF stimulates the formation of erythrocytes and platelets, they are sometimes combined with other growth factors for treatment of pancytopenia. 

In the past, large doses of androgens were employed in the treatment of refractory anemias such as aplastic anemia, Fanconi s anemia, sickle cell anemia, myelofibrosis, and hemolytic anemias. Recombinant erythropoietin has largely replaced androgens for this purpose. 

Warnings Deaths due to following severe reactions have occurred after treatment with SMX Stevens-Johnson syndrome Toxic epidermal necrolysis Fulminant hepatic necrosis Agranulocytosis Aplastic anemia Other blood dyscrasias Hypersensitivity of the respiratory tract Should not be used for the treatment of streptococcal pharyngitis o c D [Pg.43]

Androgens also have been used in the management and treatment of agnogenic myeloid metaplasia, aplastic anemia, breast cancer, hereditary angiodema, osteoporosis, paroxysmal nocturnal hemoglobinuria, and sideroblastic anemia. 

Chloramphenicol (CAP), florfenicol (FLO), and thiamphenicol (TAP) are broad-spectrum antibiotics suitable for the treatment of a variety of infectious organisms (5). Chloramphenicol, which could produce aplastic anemia in a small percentage of humans, is not approved for use in food-producing animals in the United States (129). Florfenicol is allowed for the treatment of bovine respiratory diseases in the United States. The FDA has set a level of 10 /Ug/L in milk (130). The maximum residue level of CAP is set by the EU at 10 yug/kg (15). In Table 6, the different HPLC methods can be found. 

Toyama M, Watanabe S, Kobayashi T, Iida K, Koseki S, Yamaguchi I, Sugishita Y. Two cases of acute myocardial infarction associated with aplastic anemia during treatment with anabohc steroids. Jpn Heart J 1994 35(3) 369-73. 

Jhung JW, Edelstein LM, Church A. Multiple halo nevi developing after oxymetholone treatment of aplastic anemia . Cutis 1973 12 56. 

Aplastic anemia developed in a 58-year-old woman taking thiamazole for the third time she responded well to drug withdrawal and treatment with human granulocyte colony stimulating factor (42). 

Mezquita P, Luna V, Munoz-Torres M, Torres-Vela E, Lopcz-Rodnguez F, Callejas JL, Escobar-Jimenez F. Methimazole-induced aplastic anemia in third exposure successful treatment with recombinant human granulocyte colony-stimulating factor. Thyroid I998 8(9) 791 t. 

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). 

Colchicine produces a temporary leukopenia that is soon replaced by a leukocytosis, sometimes because of a striking increase in the number of basophilic granulocytes. The site of action is apparently directly on the bone marrow. Myopathy and neuropathy also have been noted with colchicine treatment, especially in patients with decreased renal function. Long-term administration of colchicine entails some risk of agranulocytosis, aplastic anemia, myopathy, and alopecia azoospermia has also been described. 

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. 

The concomitant administration of ibuprofen antagonizes the irreversible platelet inhibition induced by aspirin. Thus, treatment with ibuprofen in patients with increased cardiovascular risk may limit the cardioprotective effects of aspirin. Rare hematologic effects include agranulocytosis and aplastic anemia. Effects on the kidney (as with all NSAIDs) include acute renal failure, interstitial nephritis, and nephrotic syndrome, but these occur very rarely. Finally, hepatitis has been reported. 

Phenylbutazone, a pyrazolone derivative, rapidly gained favor after its introduction in 1949 for the treatment of rheumatic syndromes, but its toxicities—particularly the hematologic effects (including aplastic anemia)—have resulted in its withdrawal from the North American and most European markets. It is rarely used today. 

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