Bone marrow anaemia

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

Treatment of anaemia associated with chronic disease Treatment of anaemia associated with cancer/chemotherapy Treatment of anaemia associated with prematurity To facilitate autologous blood donations before surgery To reduce transfusion requirements after surgery To prevent anaemia after bone marrow transplantation... 

Various malignancies can also induce an anaemic state. This is often associated with decreased serum EPO levels, although iron deficiency, blood loss or tumour infiltration of the bone marrow can be complicating factors. In addition, chemotherapeutic agents administered to this patient group often adversely affect stem cell populations, thus rendering the anaemia even more severe. 

There are many causes of the clinical condition referred to as anaemia. One particular type, whose cause can be traced to a genuine metabolic defect is megaloblastic anaemia and is due to a deficiency of the vitamins B12 (cobalamin) and/or folate. These vitamins are required for normal cell division in all tissues, but the rapid production of red cells makes them more susceptible to deficiency. In megaloblastic anaemia the blood haemoglobin concentration falls the synthesis of haem is not impaired. Examination of the blood reveals the appearance of larger then normal cells called macrocytes and megaloblasts are found in the bone marrow. 

Bone marrow transplantation, particularly allogenic transplantation, is often a treatment of choice for individuals suffering from acute or chronic leukaemia, aplastic anaemia or various stem cell-related genetic disorders (e.g. thalassaemias). 

Bone marrow depression includes aplastic anaemia, leukopenia, agranulocytosis, thrombocytopenia. 

Adverse effects include abdominal discomfort, vomiting, diarrhoea, intestinal obstruction, nausea, stomatitis, anorexia, bone marrow suppression (primarily neutropenia, anaemia and thrombocytopenia). 

Adverse effects include drowsiness, restlessness, anaemia, leucopenia, thrombocytopenia, bone marrow toxicity and disulfiram like reaction with alcohol. 

Nitromethane caused mild degeneration of the olfactory epithelium of exposed rats and mice and microcytic anaemia with minimal to mild hyperplasia of the bone marrow in rats. 

Toluene, also known as methylbenzene, is the simplest member of the series known as alkylbenzenes, where an alkyl group, e.g. CH3, is directly attached to the benzene ring. As the use of benzene as a nonpolar solvent has long been prohibited because of its adverse effect on the central nervous system (CNS) and on bone marrow, as well as its carcinogenic property, toluene has replaced benzene as a nonpolar solvent. Although it has a CNS depressant property like benzene, it does not cause leukaemia or aplastic anaemia. 

Anecdotal exposure to pentachlorophenol has been associated with aplastic anaemia and/or red-cell aplasia (Roberts, 1983). Thirteen cases of industrial, home and accidental pentachlorophenol exposure in 11 men and two women having aplastic anaemia, pure red cell aplasia and associated disorders were reported. Exposure levels were not known except for one patient, who had concentrations in the serum of 250 ng/mL and in bone marrow of 330 ng/mL (Roberts, 1990). 

Aplastic anaemia, manifesting itself by a fall of the number of red and white corpuscles, caused by the dysfunction of the bone marrow. Almost all of these cases end in death. 

Q10 Adult red blood cells are produced by the bone marrow at the ends of long bones and in the pelvis, skull, ribs and sternum. In response to severe anaemia the active bone marrow in the long bones becomes more extensive. Normally, the total number of circulating red blood cells is maintained constant. Production is stimulated by the glycoprotein erythropoietin (EP), which is mainly produced by the endothelial cells of the kidney. EP production is stimulated by hypoxia and a decrease in haemoglobin concentration. EP stimulates the stem cells in bone marrow to differentiate into mature erythrocytes. 

Normocytic, normochromic anaemia (normal size, normal haemoglobin content) can be caused by damage to the bone marrow or by blood loss. Macrocytic (or megaloblastic), normochromic anaemia (large cells, normal amount of haemoglobin) is due to deficiency of folic acid or B12, or both. Microcytic, hypochromic anaemia (small cells, small amount of haemoglobin) is the most common type and is due to iron deficiency. 

Classification according to cause includes, for example, aplastic anaemia, which is due to bone marrow damage haemorrhagic anaemia due to blood loss haemolytic anaemia due to damage to red cell membranes iron deficiency anaemia due to lack of iron pernicious anaemia due to deficiency in B12 and so on. 

Anaemias are classified according to the size and haemoglobin content of erythrocytes or to the cause of the condition. In the latter classification bone marrow damage causes aplastic anaemia haemorrhagic and haemolytic anaemia are due to blood loss or damaged red cell membranes respectively, iron deficiency and pernicious anaemia are due to deficiency of iron and vitamin B12 respectively. 

Q4 When the supply of iron is greatly diminished, haemoglobin synthesis is restricted. Erythropoiesis continues and is controlled by erythropoietin from the kidney. Release of this hormone is increased in anaemia, in response to a reduced concentration of circulating haemoglobin. The bone marrow will then be stimulated to produce more red cells, but of smaller size and with smaller haemoglobin content a blood film may show red cells of unequal sizes this is known as anisocytosis. 

Parietal cells also secrete intrinsic factor, which is necessary for the absorption of vitamin B12. Vitamin B12 is a cofactor of enzymes which synthesise tetrahydrofolic acid, which in turn is needed for the synthesis of DNA components. An impairment of DNA synthesis will affect rapidly dividing cell populations, among them the haematopoietic cells of the bone marrow, which may result in pernicious anaemia. This condition may result from a destruction of the gastric mucosa by, for example, autoimmune gastritis or the resection of large parts of the lower ileum, which is the main site of vitamin B12 absorption, or of the stomach. 

The number of leukocytes in the blood is often an indicator of disease. There are normally between 4 and 11 x 10 white blood cells per litre of blood, making up approximately 1% of blood in a healthy adult. In conditions such as leukaemia (cancer of the blood or bone marrow), the number of leukocytes may be much higher than normal, while in types of leukopaenia the number is much lower (associated for example with chemo/radiotherapy, aplastic anaemia, human immunodeficiency virus (HIV) and malaria). 

The main hazardous effects of benzene are to the blood system. Workers chronically exposed suffer from anaemia, due to damage to and sometimes complete destruction of the cells in the bone marrow, where the cells found in the blood are formed. Benzene exposure can lead to low levels of both red and white blood cells. A more serious effect is leukaemia, which is cancer of the blood system. Because of the hazards it poses, the use of benzene has been dramatically curtailed. 

Iron therapy is indicated only for the prevention or cure of iron deficiency. In general terms, making 25 mg of iron per day available to the bone marrow will allow an iron deficiency anaemia to respond with a rise of 1% of haemoglobin (0.15 g Hb/100 ml) per day a reticulocyte response occurs between 4 and 12 days. An increase in the haemoglobin of at least 2 g/dl after 3 weeks of therapy is a reasonable criterion of an adequate response. Oral preparations are the treatment of choice for almost all patients due to their effectiveness, safety and low cost. Parenteral preparations should be restricted to the few patients unable to absorb or tolerate oral preparations. Red cell transfusion is necessary only in patients with severe symptomatic rmaemia or where chronic blood loss exceeds the possible rate of oral or parenteral replacement. 

Contraindications. It is illogical to give iron in the anaemia of chronic infection where utilisation of iron stores is impaired but such patients may also have true iron deficiency. This may be difficult to diagnose without direct visualisation of stores in a bone marrow aspirate. Iron should not be given in haemolytic anaemias unless there is also haemo-globinuria, for the iron from the lysed cells remains in the body. Moreover the increased erythropoiesis associated with chronic haemolytic states stimulates increased iron absorption and adding to the iron load may cause haemosiderosis. 

Another major use of G-CSF is for patients with neutropenia as a result of cytotoxic chemotherapy, to shorten the duration of neutropenia and reduce morbidity due to infection. It is also used for the same purpose after autologous and allogeneic bone marrow transplantation, in aplastic anaemia, AIDS, and congenital, cyclical and idiopathic neutropenia. In combination with epoetin, G-CSF can be effective in the management of some patients with myelo-dysplastic syndromes. G-CSF not only improves the neutrophil count, but dramatically improves the proportion of patients with a raised haemoglobin in response to epoetin possibly by reduction of erythroid apoptosis (the cause of ineffective erythropoiesis). 

Carboplacin Nausea and vomicing Bone marrow depression peripheral neuropathy (uncommon) hearing loss transient cortical blindness haemolytic anaemia... 

Interferon alfia Fever chills myalgias facigue headache arthralgias hypotension Bone marrow depression anorexia neutropenia anaemia confusion depression renal toxicity hepatic toxicity, facial and peripheral oedema cardiac arrhythmias... 

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