Anemia folate deficiency

Sulfonamides have adverse effects on all bone marrow-derived cell lines. The resulting disturbances include hemolytic anemia, folate deficiency anemia, neutropenia, thrombocytopenia, and pancytopenia. While adverse effects on erythrocytes are rare, the rates of leukopenia, neutropenia, and thrombocytopenia are highly variable. In a hospital drug monitoring program, leukopenia or neutropenia occurred in 0.4% of 1809 patients treated with co-trimox-azole (54), and thrombocytopenia of mild-to-moderate degree in 0.1% (54,55), similar to figures recorded in other studies (56,57). Pancytopenia is an extremely rare form of adverse reaction to sulfonamides (58). 

Importance of thiamine An important water-soluble vitamin used as a cofactor in enzymatic reactions involving the transfer of an aldehyde group. Without thiamine, individuals can develop dementia, macrocytic anemia (folate deficiency), gastritis, peptic ulcer disease, liver disease, depression, nutritional deficiencies, cardiomyopathy, and pancreatitis. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Pernicious anemia arises when vitamin B,2 deficiency blocks the metabohsm of folic acid, leading to functional folate deficiency. This impairs erythropoiesis, causing immature precursors of erythrocytes to be released into the circulation (megaloblastic anemia). The commonest cause of pernicious anemia is failure of the absorption of vitamin B,2 rather than dietary deficiency. This can be due to failure of intrinsic factor secretion caused by autoimmune disease of parietal cells or to generation of anti-intrinsic factor antibodies. 

Current NKF guidelines define anemia as a hemoglobin (Hgb) level less than 11 g/dL (6.8 mmol/L).31 A number of factors can contribute to the development of anemia, including deficiencies in vitamin B12 or folate, hemolysis, bleeding, or bone marrow suppression. Many of these can be detected by alterations in RBC indices, which should be included in the evaluation for anemia. A complete blood cell count is also helpful in evaluating anemia to determine overall bone marrow function. 

Vitamin B12- and folate-deficiency anemias are characterized by pallor, icterus, and gastric mucosal atrophy. Vitamin B12 anemia is distinguished by neuropsychiatric abnormalities (e.g., numbness, paresthesias, irritability), which are absent in patients with folate-deficiency anemia. 

Macrocytic anemias are characterized by increased mean corpuscular volume (110 to 140 fL). One of the earliest and most specific indications of macrocytic anemia is hypersegmented polymorphonuclear leukocytes on the peripheral blood smear. Vitamin B12 and folate concentrations can be measured to differentiate between the two deficiency anemias. A vitamin B12 value of less than 150 pg/mL, together with appropriate peripheral smear and clinical symptoms, is diagnostic of vitamin B12-deficiency anemia. A decreased RBC folate concentration (less than 150 ng/mL) appears to be a better indicator of folate-deficiency anemia than a decreased serum folate concentration (less than 3 ng/mL). 

Diagnosis of anemia of chronic disease is usually one of exclusion, with consideration of coexisting iron and folate deficiencies. Serum iron is usually decreased but, unlike iron-deficiency anemia, serum ferritin is normal or increased and TIBC is decreased. The bone marrow reveals an abundance of iron the peripheral smear reveals normocytic anemia. 

Oral folate 1 mg daily for 4 months is usually sufficient for treatment of folate-deficiency anemia, unless the etiology cannot be corrected. If malabsorption is present, the daily dose should be increased to 5 mg. 

Vitamin deficiency can cause a megaloblastic anemia of the same type seen in folate deficiency (discussed in Chapter 17). In a patient with megaloblastic anemia, it is important to determine the underlying cause because Bjj defidency, if not corrected, produces a peripheral neuropathy owing to aberrant fatty acid incorporation into the myelin sheets associated with inadequate methylmalonyl CoA mutase activity. Excretion of methylmalonic acid indicates a vitamin Bjj deficiency rather than folate. 

Megaloblastic anemia results from insufficient active THF to support cell division in the bone marrow. Methotrexate inhibits DHF reductase, making it a useful antineoplastic drug. Folate deficiencies may be seen during pregnancy and in alcoholism. 

Answer A. Pregnant woman with megaloblastic anemia and elevated serum homocysteine strongly suggests folate deficiency. Iron deficiency presents as microcytic, hypochromic anemia and would not elevate homocysteine. deficiency is not most likely in this presentation. 

Answen B. Methyhnalonyl CoA mutase requires Bj but not folate for activity. Macrocytic anemia, elevated homocysteine, and macrocytic anemia can be caused by either B,2 or folate deficiency. 

Folate, the anion of folic acid, is made up of three different components—a pteridine derivative, 4-aminobenzoate, and one or more glutamate residues. After reduction to tetrahydrofolate (THF), folate serves as a coenzyme in the Q metabolism (see p. 418). Folate deficiency is relatively common, and leads to disturbances in nucleotide biosynthesis and thus cell proliferation. As the precursors for blood cells divide particularly rapidly, disturbances of the blood picture can occur, with increased amounts of abnormal precursors for megalocytes megaloblastic anemia). Later, general damage ensues as phospholipid... 

Folic acid appears in the plasma approximately 15 to 30 minutes after an oral dose peak levels are generally reached within 1 hour. After IV administration, the drug is rapidly cleared from the plasma. Folic acid is metabolized in the liver. Normal serum levels of total folate have been reported to be 5 to 15 ng/mL normal CSF levels are approximately 16 to 21 ng/mL. In general, folate serum levels less than 5 ng/mL indicate folate deficiency, and levels less than 2 ng/mL usually result in megaloblastic anemia. A majority of the metabolic products appeared in the urine after 6 hours excretion was generally complete within 24 hours. 

Albumin (human) Epoetin alfa contains albumin, a derivative of human blood. Based on effective donor screening and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. No cases of transmission of viral diseases or Creutzfeldt-Jakob disease have ever been identified for albumin. Anemia Not intended for CRF patients who require correction of severe anemia epoetin alfa may obviate the need for maintenance transfusions but is not a substitute for emergency transfusion. Not indicated for treatment of anemia in HIV-infected patients or cancer patients due to other factors such as iron or folate deficiencies, hemolysis, or Gl bleeding, which should be managed appropriately. Hypertension Up to 80% of patients with CRF have a history of hypertension. Do not treat patients with uncontrolled hypertension monitor blood pressure adequately before initiation of therapy. Hypertensive encephalopathy and seizures have occurred in patients with CRF treated with epoetin. 

Flypersensitivity to TMP or SMZ megaloblastic anemia caused by folate deficiency ... 

Folic acid is used for the treatment of folate deficiency. Oral folic acid is usually the therapy of choice. For megaloblastic anemia doses of 5 mg daily for 4 months should be effective. Folinic acid is available in a parenteral formulation which may be indicated when oral therapy is not feasible and for rescue treatments following certain anti-cancer regimens. 

Contraindications Hypersensitivity to trimethoprim or any sulfonamides, megaloblastic anemia due to folate deficiency. 

Folic acid antagonist overdose PO 2-15 mg/day for 3 days or 5 mg every 3 days. Megaloblastic anemia secondary to folate deficiency IM 1 mg/day Colon cancer IV 200 mg/m followed by 370 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals or 20 mg/m followed by 425 mg/m fluorouracil daily for 5 days. Repeat course at 4-wk intervals for 2 courses then 4-5 wk intervals. 

Folate deficiency is associated with the increased risk of neural tube defects (spina bifida, anencephaly), cardiovascular diseases, megaloblastic anemia, and some cancers (Bailey et al., 2003 Finglas et al., 2006 Scott et al, 1999). Unfortunately, folate intake is suboptimal in most of the world s populations, even in developed countries (Scott et al., 2000). Therefore there is an urgent need to increase folate content and bioavailability in staple foods. Because of its large consumption worldwide, potato is an appealing target for enrichment. 

Reduced forms of folic acid are required for essential biochemical reactions that provide precursors for the synthesis of amino acids, purines, and DNA. Folate deficiency is not uncommon, even though the deficiency is easily corrected by administration of folic acid. The consequences of folate deficiency go beyond the problem of anemia because folate deficiency is implicated as a cause of congenital malformations in newborns and may play a role in vascular disease (see Folic Acid Supplementation A Public Health Dilemma). 

Folate deficiency results in a megaloblastic anemia that is microscopically indistinguishable from the anemia caused by vitamin B12 deficiency (see above). However, folate deficiency does not cause the characteristic neurologic syndrome seen in vitamin B12 deficiency. In patients with megaloblastic anemia, folate status is assessed with assays for serum... 

Folic acid deficiency can be caused by drugs. Methotrexate and, to a lesser extent, trimethoprim and pyrimethamine, inhibit dihydrofolate reductase and may result in a deficiency of folate cofactors and ultimately in megaloblastic anemia. Long-term therapy with phenytoin can also cause folate deficiency, but only rarely causes megaloblastic anemia. 

Contraindications Hypersensitivity to TMP or SMX Megaloblastic anemia due to folate deficiency Pregnancy at term and nursing Infants <2 months of age ... 

Anyone taking diuretics for longer than six months may experience a folate, or folic acid, deficiency. Folic acid plays a part in the health and reproduction of virtually every cell in the body. It is responsible for protein metabolism, the prevention of neural tube defects in pregnancy, blood cell production, and the synthesis of neurotransmitters. Individuals with folate deficiencies may suffer from anemia, depression and other mood disorders, and may give birth to babies with neural tube defects. Supplementation with folic acid may be useful in reversing these effects. 

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