Megaloblastic anemia
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2008-07-13T05:07:36Z
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{{Infobox_Disease
| Name = Megaloblastic anemia
| Image = Hypersegmented neutrophil.png
| Caption = Peripheral blood blood smear showing hypersegmented neutrophils, characteristic of megaloblastic anemia.
| DiseasesDB = 29507
| ICD10 = {{ICD10|D|51|1|d|50}}, {{ICD10|D|52|0|d|50}}, {{ICD10|D|53|1|d|50}}
| ICD9 = {{ICD9|281}}
| ICDO =
| OMIM =
| MedlinePlus =
| eMedicineSubj = med
| eMedicineTopic = 1420
| eMedicine_mult = {{eMedicine2|ped|2575}}
| MeshID = D000749
}}
'''Megaloblastic anemia''' is an [[anemia]] (of [[macrocytic anaemia|macrocytic]] classification) which results from inhibition of DNA synthesis in red blood cell production. It is often due to deficiency of [[vitamin B12|vitamin B{{ssub|12}}]] and/or [[folic acid]]. It can be the result of a lack of [[intrinsic factor]] (which lack interferes with B{{ssub|12}} absorption), causing [[pernicious anemia]], or with other antimetabolites which poison DNA production, such as chemotherapeutic agents.
It is characterized by many large immature and dysfunctional red blood cells ([[megaloblasts]]) in the bone marrow,<ref name="titleMegaloblastic (Pernicious) Anemia - Lucile Packard Childrens Hospital">{{cite web |url=http://www.lpch.org/DiseaseHealthInfo/HealthLibrary/hematology/megalob.html |title=Megaloblastic (Pernicious) Anemia - Lucile Packard Children's Hospital |accessdate=2008-03-12 |format= |work=}}</ref> and also by [[hypersegmented neutrophil|hypersegmented]] or [[multisegmented neutrophil|multisegmented]] [[neutrophil]]s.
==Causes==
* Vitamin B12 Deficiency:
** Deficient intake
** Deficient intrinsic factor ([[pernicious anaemia]] or [[gastrectomy]])
** Biological competition for B12 by [[diverticulosis]], [[fistula]], intestinal [[anastomosis]], [[achlorhydria]] and infection by the marine parasite ''[[Diphyllobothrium latum]]''
** Selective B12 malabsorption (congenital and drug-induced)
** Chronic [[pancreatitis]]
** Ileal resection and bypass
* Folate Deficiency:
** Deficient intake.
** Increased needs: [[pregnancy]], [[infant]], rapid cellular proliferation, and [[cirrhosis]]
** Malabsorption (congenital and drug-induced)
** Intestinal and jujenal resection
* Combined Dieficiency (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]] antagonists ([[6-mercaptopurine]])
** [[Pyrimidine]] antagonists ([[cytosine arabinoside]])
* [[Erythroleukemia]]
==Hematological findings==
The [[blood film]] can point towards vitamin deficiency:
*Decreased [[red blood cell]] (RBC) count and [[hemoglobin]] levels {{Fact|date=July 2008}}
*Increased [[mean corpuscular volume]] (MCV, >95 fl) and [[mean corpuscular hemoglobin]] (MCH)
*The [[reticulocyte]] count is normal.
*The [[platelet]] count may be reduced. {{Fact|date=July 2008}}
*[[Neutrophil granulocyte]]s may show [[multisegmented neutrophil|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. {{Fact|compensatory mechanism|date=July 2008}}
*[[Anisocytosis]] (increased variation in RBC size) and [[poikilocytosis]] (abnormally shaped RBCs).
*[[Macrocyte]]s (larger than normal RBCs) are present.
*[[Ovalocyte]]s (oval-shaped RBCs) are present.
*[[Bone marrow]] (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic [[hyperplasia]].
*[[Howell-Jolly body|Howell-Jolly bodies]] (chromosomal remnant) also present.
<br />
Blood chemistries will also show:
*Increased homocysteine and methylmalonic acid in B{{ssub|12}} deficiency
*Increased homocysteine in folate defiency
Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty. <ref>Savage DG; Lindenbaum J; Stabler SP; Allen RH: Am J Med 1994 Mar;96(3):239-46. PMID 8154512</ref>
==Analysis==
The [[Schilling test]] was performed in the past to determine the nature of the vitamin B{{ssub|12}} deficiency, but due to the lack of available radioactive B{{ssub|12}}, it is now largely a historical artifact. Vitamin B{{ssub|12}} is a necessary prosthetic group to the enzyme [[methylmalonyl-coenzyme A mutase]]. B{{ssub|12}} deficiency leads 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. Since the level of methylmalonic acid is not elevated in folic acid deficiency, this test provides a one tool in differentiating the two. However, since the test for elevated methylmalonic acid is not specific enough, the gold standard for the diagnosis of B{{ssub|12}} deficiency is a low blood level of B{{ssub|12}}. Unlike the Shilling test, which often included B{{ssub|12}} with intrinsic factor, a low level of blood B{{ssub|12}} gives no indication as to the etiology of the low B{{ssub|12}}, which may result from a number of mechanisms.
==References==
{{reflist}}
{{Hematology}}
[[Category:Blood disorders]]
[[es:Anemia megaloblástica]]
[[gl:Anemia megaloblástica]]
[[it:Anemia megaloblastica]]
[[he:אנמיה מגלובלסטית]]
[[pl:Niedokrwistość megaloblastyczna]]
[[pt:Anemia megaloblástica]]
[[ru:Пернициозная анемия]]
[[simple:Megaloblastic anemia]]
[[sl:Megaloblastna anemija]]
[[sr:Мегалобластна анемија]]
[[tr:Megaloblastik anemi]]