Megaloblastic anemia 1407166 225343543 2008-07-13T05:07:36Z SmackBot 433328 Date the maintenance tags or general fixes {{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]]