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| Megaloblastic anemia Classification and external resources |
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| Peripheral blood blood smear showing hypersegmented neutrophils, characteristic of megaloblastic anemia. | |
| ICD-10 | D51.1, D52.0, D53.1 |
| ICD-9 | 281 |
| DiseasesDB | 29507 |
| eMedicine | med/1420 ped/2575 |
| MeSH | D000749 |
Megaloblastic anemia is an anemia (of macrocytic classification) which results from inhibition of DNA synthesis in red blood cell production. This is often due to deficiency of vitamin B12 and/or folic acid. Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites which poison DNA production, such as some chemotherapeutic agents.
It is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow,[1] and also by hypersegmented or multisegmented neutrophils.
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Causes
- Vitamin B12 Deficiency:
- achlorhydria-induced malabsorption
- Deficient intake
- Deficient intrinsic factor (pernicious anaemia or gastrectomy)
- Biological competition for B12 by diverticulosis, fistula, intestinal anastomosis, and infection by the marine parasite Diphyllobothrium latum
- Selective B12 malabsorption (congenital and drug-induced)
- Chronic pancreatitis
- Ileal resection and bypass
- Folate Deficiency:
- alcoholism
- Deficient intake.
- Increased needs: pregnancy, infant, rapid cellular proliferation, and cirrhosis
- Malabsorption (congenital and drug-induced)
- Intestinal and jujenal resection
- Combined Deficiency (Tropical Sprue): Vitamin B12 & Folate.
- Inherited DNA Synthesis Disorders: Deficient thiamine and factors (e.g. enzymes) responsible for folate metabolism.
- Toxins and Drugs:
- Folic acid antagonists (methotrexate)
- Purine synthesis antagonists (6-mercaptopurine)
- Pyrimidine antagonists (cytosine arabinoside)
Hematological findings
The blood film can point towards vitamin deficiency:
- Decreased red blood cell (RBC) count and hemoglobin levelscitation needed
- Increased mean corpuscular volume (MCV, >95 fl) and mean corpuscular hemoglobin (MCH)
- The reticulocyte count is normal.
- The platelet count may be reduced.citation needed
- Neutrophil granulocytes may show multisegmented nuclei ("senile neutrophil"). This is thought to be due to decreased production and a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.citation needed
- Anisocytosis (increased variation in RBC size) and poikilocytosis (abnormally shaped RBCs).
- Macrocytes (larger than normal RBCs) are present.
- Ovalocytes (oval-shaped RBCs) are present.
- Howell-Jolly bodies (chromosomal remnant) also present.
Blood chemistries will also show:
- Increased homocysteine and methylmalonic acid in B12 deficiency
- Increased homocysteine in folate defiency
Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty. [2]
Bone marrow (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic hyperplasia.
Analysis
The gold standard for the diagnosis of B12 deficiency is a low blood level of B12. A low level of blood B12 is a symptom which normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis. Hypovitaminosis B12 can result from a number of mechanisms, including those listed above. For determination of etiology, further patient history, testing, and empirical therapy may be clinically indicated.
A measurement of methylmalonic acid can provide an indirect method for partially differentiating B12 and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. But direct measurement of blood cobalamin remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B12 is one necessary prosthetic group to the enzyme methylmalonyl-coenzyme A mutase. B12 deficiency is but one among the conditions that can lead to dysfunction of this enzyme and a buildup of its substrate, methylmalonic acid, the elevated level of which can be detected in the urine and blood.
Due to the lack of available radioactive B12, the Shilling test is now largely a historical artifact. The Schilling test was performed in the past to help determine the nature of the vitamin B12 deficiency. An advantage of the Shilling test was that it often included B12 with intrinsic factor.
References
- ^ "Megaloblastic (Pernicious) Anemia - Lucile Packard Children's Hospital". Retrieved on 2008-03-12.
- ^ Savage DG, Lindenbaum J, Stabler SP, Allen RH (1994). "Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies". Am. J. Med. 96 (3): 239–46. PMID 8154512.
Wikipedia content modification information:
- This page was last modified on 4 October 2008, at 18:55.
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