Anaemia macrocytic

WILLS L, CLUTTERBUCK P w and EVANS PDF (1937) A new factor in the production and cure of certain macrocytic anaemias , iancei, 1, 311-14. 

Used for malaria chemoprophylaxis and treatment the dihydrofolate reductase inhibitors do not cause pharmacological side-effects in the host. In the higher dose used for toxoplasmosis macrocytic anaemia and other adverse effects may occur. 

Prescribing perspective is vital so that, if there is any doubt as to whether the macrocytic anaemia is due to shortage of folate acid or vitamin B12, then 1000 mg of the latter must be given by intramuscular injection prior to starting the oral replacement. This will protect the patient from inadvertent precipitation of irreversible damage to the spinal cord known as subacute combined degeneration. 

Pathophysiologically, there is a macrocytic anaemia with megaloblastic haematopoiesis that occurs in the face of normal folate and vitamin B12 and is refractory to therapeutic trials of these two nutrients. Patients are characterized as having a preleukaemic syndrome, which is currently regarded by many as a neoplastic process arising in the haematopoietic stem cells that is analogous to early acute myeloblas-tic leukaemia. 

Studies on growth factors required by certain microorganisms, for example Streptococcus faecalis and Lactobacillus casei, and of their relevance in animal nutrition, led to the isolation and characterization of folic acid, pteroylglutamic acid (104), the structure of which was determined in 1946. It is an essential vitamin for man and together with vitamin B12 it is involved in the development of blood cells. Deficiency causes macrocytic anaemia. Many microorganisms do not use exogenous folic acid, but synthesize their own, and some... 

Macrocytic anaemia. An anaemia in which abnormally large red blood cells are present. Myasthenia gravis. A disease in which the nerves fail to stimulate skeletal muscle, characterized by profound muscular weakness. 

Hoffman V and Provan D (1997) ABC of clinical haematology Macrocytic anaemias. British Medical Journal 314 430. 

As per BNF Hydroxocobalamin injection. Dose by intramuscular injection, pernicious anaemia and other macrocytic anaemias without neurological involvement, initially 1 mg three times a week for two weeks then 1 mg every three months. Pernicious anaemia and other macrocytic anaemias with neurological involvement, initially 1 mg on alternate days until no further improvement, then 1 mg every two months. 

Macrocytic anaemia is defined as one in which the red blood cells are larger than normal. Megaloblastic anaemia is the most common cause of macrocytic anaemia, caused by a deficiency of either vitamin B12 or fohc acid (or both). Deficiency in folate and/or vitamin B12 may result from either inadequate intake or malabsorption. Pernicious anaemia is caused by a lack of intrinsic factor, which is required to absorb vitamin B12 from food (see below). 

Macrocytic anaemia can also be caused by removal of the functional portion of the stomach, such as during gastric bypass surgery, leading to reduced vitamin B12 and folate absorption. 

Macrocytic anaemia can be further divided into megaloblastic anaemia and non-megaloblastic macrocytic anaemia . Megaloblastic anaemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. Non-megaloblastic macrocytic anaemias have different aetiologies (i.e. an unimpaired DNA globin synthesis). 

Drugs. Antiepilepsy drugs, particularly phenytoin, primidone and phenobarbital, occasionally cause a macrocytic anaemia that responds to folic acid. This may be due to enzyme induction by the antiepileptics increasing the need for folic acid to perform hydroxylation reactions (see Epilepsy) but other factors such as reduced absorption may be involved. Administration of folic acid causes a recurrence of seizures in some patients. Some anti-malarials, e.g. pyrimethamine, may interfere with conversion of folates to the active tetrahydrofolic acid, causing macrocytic anaemia. Methotrexate, another folate antagonist, may cause a megaloblastic anaemia especially when used long-term for leukaemia, rheumatoid arthritis or psoriasis. 

Sesso RM, Junes Y, Melo AC. Myeloneuropathy following nitrous oxide anesthaesia in a patient with macrocytic anaemia. Neuroradiology 1999 41(8) 588-90. 

W3. Wills, L., Studies in pernicious anaemia of pregnancy tropical macrocytic anaemia as a deficiency disease with special reference to the vitamin B complex. Indian J. Med. Res. 21, 669-681 (1934). 

Recurrence or metastatic spread of the breast cancer would need to be excluded in this woman by imaging her liver and skeleton. Alkaline phosphatase isoenzyme studies should be performed. However, if the increase is due to an increased bone activity, this does not necessarily represent metastatic spread of the tumour. In view of the history and symptoms, osteomalacia due to malnutrition or malabsorption may be the reason. If the patient has malabsorption or malnutrition she may have a macrocytic anaemia due to folate or deficiency and may be deficient in other micronutrients such as zinc and other vitamins. Malabsorption is often difficult to detect clinically and she should undergo tests of malabsorption such as faecal fat measurement. 

Folic acid is an indispensable pro-vitamin for Man and other mammals, and lack of it quickly causes macrocytic anaemia and gastrointestinal disorders. Hence it was with some trepidation that chemists began to make metabolite antagonists based on the pteridine nucleus. Nevertheless, they were successful and many very valuable drugs have been obtained in this way. 

Methods to assess activity of vitamin B12. These include macrocytic anaemia improvements, homocysteine (Hey) reduction and methyl malonic acid (MMA) reduction. 

Macrocytic anaemia improvements. Vitamin B12 deficiency can cause macrocytic anaemia (large red blood cells). However, folate deficiency can do the same. If an individual with macrocytic anaemia is known to have adequate folate status and is fed food that is thought to have vitamin B12, and their anaemia improves, it is fairly safe to say that the food has some vitamin B12 activity for red blood cells. Unfortunately, it is not known for sure whether vitamin B12 that is active for blood cells is always active for nerve cells. 

Cobalamin (vitamin B12) a water-soluble B vitamin, normally involved in the human body metabolism, affecting DNA synthesis and regulation, fatty acid synthesis and energy production. Supplied by animal food, its defieiency leads to macrocytic anaemia, decreased bone marrow cell production, neurological problems, as well as metabolic issues (methylmalonyl-CoA acidosis, hyperhomocysteinemia). 

Low levels of serum folate are often associated with low levels of erythrocyte folate (intracellular). The mean corpuscular volume (MCV) of erythrocytes may increase slightly with low folate levels, though overt macrocytic anaemia occurs infrequently. Carbamazepine (CBZ) therapy may cause leukopenia and neutropenia. In a randomized trial in patients on CBZ, subjects on folic acid had higher leucocyte counts and less neutropenia compared with subjects without vitamin supplements. Other studies found no connection between folate and AED-induced haematological abnormalities. 

B vitamins also play important roles in haematopoiesis (Fishman et al. 2000). For example, folate deficiency by impairing DNA synthesis leads to ineffective erythropoiesis, and as a result a macrocytic anaemia develops. Deficiency of vitamin B12, by impairing functions of folic acid, leads to ineffective ery-thropoeisis and in turn to macrocytic anaemia. Vitamin Bg is also required in synthesis of haem, a component of haemoglobin and perhaps for mobilization of iron from stores. Vitamin B2 is known to mobilize stored iron from the liver and its deficiency is associated with anaemia. 

Macrocytic anaemia A type of anaemia in which the average size of red blood cell is larger than normal. 

Holtmann, M.H., Galle, P.R., Stremmel, W. et al. (1998) 3-Methylglutaconic aciduria associated with hepatospelomegaly, macrocytic anaemia, fever episodes, recurrent infections, cervical lymphadenopathy and progressive decrease of physical performance. I. Inher. Metab. Dis., 21, 683-685. 

Folic acid deficiency, when it occurs, results more commonly from a failure of utilization than from an inadequate dietary intake. It is manifested by macrocytic anaemia and leucopenia. As the name suggests, green leaves are good sources so is yeast. 

Folacin deficiency may lead to glossitis, diarrhoea, depression and confusion. Deficiency anaemia may develop especially in pregnancy and in elderly people. Symptoms of deficiency are similar to symptoms of cobalamine deficiency (known as macrocytic anaemia). Megaloblastic anaemia, the most common cause of macrocytic anaemia, is due to a deficiency of either cobalamine or folic acid (or both). Deficiency in the early stages of pregnancy can lead to developmental defects of the foetus (spinal cord defects and incomplete development of the brain). Women who are at increased risk will need increased daily intake of folic acid. 

A macrocytic anaemia which results from failure to absorb vitamin B12. In true pernicious anaemia it is due to failure of the... 

Haematologic A case of macrocytic anaemia in a 29-year-old male ocurring 2 months after the initiation of amisulpride is reported [89 ]. 

The case is described of a 57-year-old woman who, having taken a hypnotic mixture of chlorpromazine 500 mg, promethazine 30 mg, and amylobarbitone sodium 100 mg for 10 years, developed an autoimmune haemolytic anaemia. The blood and the bone marrow showed the changes of a macrocytic anaemia and a strongly positive Coombs test. There was urobilinogen in the urine. Liver function tests and serum protein were normal. When chlorpromazine was withdrawn her blood gradually returned to normal without other treatment, and over the course of 4—5 weeks all other parameters were similarly normalized (36 =). 

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