Bone marrow failure, anemia

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

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. 

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... 

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

Oxymetholone is an anabolic steroid that suppresses gonadotropic functions of the pituitary and may exert a direct effect upon the testes. It enhances the production and urinary excretion of erythropoietin in patients with anemias caused by bone marrow failure and stimulates erythropoie-sis in anemias caused by deficient RBC production. Oxymetholone is indicated in the treatment of anemias caused by deficient RBC production. Acquired aplastic anemia, congenital aplastic anemia, myelofibrosis, and the hypoplastic anemias caused by administration of myelotoxic drugs often respond to the drug. 

Bone marrow depression, anemia, leukopenia, and basophilic stippling are associated with chronic arsenic exposure. Arsine (AsHj) poisoning can produce widespread hemolysis. Cirrhosis, ascites, and destruction of renal tissues have been reported. Arsine exposure may also cause renal failure (Forth et al. 1996). 

Perturbed JAK/STAT signaling is associated with development of lymphoid and myeloid leukemias, severe congenital neutropenia, a condition in which levels of circulating neutrophils are severely reduced, and Fanconi anemia, which is characterized by bone marrow failure and increased susceptibility to malignancy. 

The anabolio steroid oxymetholone is used primarily to stimulate produotion of erythropoietin in the treatment of anemias resulting from bone marrow failure. 

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

Agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia, and thrombocytopenia have been reported and may occur within the first 12 wk of therapy at recommended doses. Caution should be used in patients with preexisting marrow failure or cytopenia,... 

Clinical pharmacology Erythropoietin is instrumental in the production of red cells from the erythroid tissues in the bone marrow. The majority of this hormone is produced in the kidney in response to hypoxia, with an additional 10% to 15% of synthesis occurring in the hver. Erythropoietin functions as a growth factor, stimulating the mitotic activity of the erythroid progenitor cells and early precursor cells. Chronic renal failure patients often manifest the sequelae of renal dysfunction, including anemia. Anemia in cancer patients may be related to the disease itself or the effect of concomitantly administered chemotherapeutic agents. 

Epoetin alfa Agonist of erythropoietin receptors expressed by red cell progenitors Stimulates erythroid proliferation and differentiation, and induces the release of reticulocytes from the bone marrow Treatment of anemia, especially anemia associated with chronic renal failure, HIV infection, cancer, and prematurity prevention of the need for transfusion in patients undergoing certain types of elective surgery IV or SC administration 1-3 times per week Toxicity Hypertension, thrombotic complications, and, very rarely, pure red cell aplasia to reduce the risk of serious CV events, hemoglobin levels should be maintained < 12 g/dL... 

The first approval of a therapeutic use for recombinant EPO was in 1989 for the treatment of anemia related to chronic renal failure. The treatment with EPO stimulates production of erythrocytes and improves the patient s quality of life, as well as reducing or eliminating the need for blood transfusion. There are other non-renal applications, such as the minimization of blood transfusion after surgery, the prevention of anemia after bone marrow transplantation, and the treatment of anemia caused by the use of antiretroviral drugs, by chemotherapy, and by prematurity. 

Deficiency of either folic acid or vitamin B12 restdts in megaloblastic anemia -the release into circulation of immature erythrocytes because of failure of the normal process of maturation in the bone marrow (Wickramasinghe, 1995, 1999). There may also be low white cell and platelet counts, as well as increased numbers of hypersegmented neutrophils. Iron deficiency may mask the megaloblastic anemia. 

The continued absorption of iron causes its deposition in various tissues starting with liver and spleen and followed by myocardium. Deposition of iron in the myocardium usually results in death by intractable cardiac failure. Patients suffer from hypoparathyroidism and hypogonadism. Patients with the severe form of thalassemia are more susceptible to bacterial infection, possibly due to the increase in serum iron, which may favor bacterial growth. Iron overload is less common in the adult forms of Q -thalassemia. This is most likely the result of a fundamental difference between a and -thalassemia. As mentioned, the excess of Q -globin chains cannot form viable tetramers and causes red-cell destruction. The excess jS-chains present in a-thalassemia are able to form solnble homodimers and do not precipitate in the bone marrow. This is paralleled in the fetal state when excess y-chains form solnble homodimers. Hence, a-thalassemia is characterized by a severe degree of inefficient erythropoiesis and a milder degree of anemia. 

Interactions of transfusion with transplantation can occur (200). Blood transfusions, and especially donor-specific transfusions, given before kidney transplantation have beneficial effects on graft survival the mechanism for this is not known (201-203). By contrast, pre-transplant transfusions in bone marrow recipients with aplastic anemia cause major complications, and can be responsible for graft rejection and marrow transplantation failure (204). 

The etiology of anemia in CKD is multifactorial. A major cause, however, is the loss of peritubular fibroblasts within the renal cortex that synthesize EPO. EPO is the glycoprotein hormone responsible for stimulating erythroid progenitor ceils within the bone marrow to produce red blood cells. Failure of production leads to inappropriately low... 

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