Editing Megaloblastic anemia (section)

==Diagnosis==
The gold standard for the diagnosis of Vitamin B{{ssub|12}} deficiency is a low blood level of Vitamin B{{ssub|12}}. A low level of blood Vitamin B{{ssub|12}} is a finding that normally can and should be treated by injections, supplementation, or dietary or lifestyle advice, but it is not a diagnosis.  Hypovitaminosis B{{ssub|12}} can result from a number of mechanisms, including those listed above. For determination of cause, further patient history, testing, and empirical therapy may be clinically indicated.

A measurement of [[methylmalonic acid]] (methylmalonate) can provide an indirect method for partially differentiating Vitamin B{{ssub|12}} and folate deficiencies. The level of methylmalonic acid is not elevated in folic acid deficiency. Direct measurement of blood [[cobalamin]] remains the gold standard because the test for elevated methylmalonic acid is not specific enough. Vitamin B{{ssub|12}} is one necessary prosthetic group to the enzyme [[methylmalonyl-coenzyme A mutase]]. Vitamin B{{ssub|12}} 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 Vitamin B{{ssub|12}}, the [[Schilling test]] is now largely a historical artifact.{{Citation needed|date=December 2009}}  The [[Schilling test]] was performed in the past to help determine the nature of the vitamin B{{ssub|12}} deficiency.  An advantage of the [[Schilling test]] was that it often included Vitamin B{{ssub|12}} with intrinsic factor.

===Blood findings===
The [[blood film]] can point towards vitamin deficiency:
* Decreased [[red blood cell]] (RBC) count and [[hemoglobin]] levels<ref>{{cite web |title=Megaloblastic Anemia |url=https://www.nlm.nih.gov/medlineplus/ency/article/000567.htm |date=2012 |archive-url=https://web.archive.org/web/20121130153546/https://www.nlm.nih.gov/medlineplus/ency/article/000567.htm |archive-date=30 November 2012  |website=MedlinePlus |access-date=21 June 2015  |quote=Megaloblastic anemia is a blood disorder in which there is anemia with larger-than-normal red blood cells. Anemia is a condition in which the body does not have enough healthy red blood cells. Red blood cells provide oxygen to body tissues.}}</ref>
* Increased [[mean corpuscular volume]] (MCV, >100 [[Femtolitre|fL]]) and [[mean corpuscular hemoglobin]] (MCH)
* Normal [[mean corpuscular hemoglobin concentration]] (MCHC, 32–36 g/dL)
* Decreased [[reticulocyte]] count due to destruction of fragile and abnormal megaloblastic erythroid precursor.
* The [[platelet]] count may be reduced.<ref>{{cite web |url= https://www.lecturio.com/concepts/megaloblastic-anemia/| title= Megaloblastic Anemia
|website=The Lecturio Medical Concept Library |access-date= 10 August 2021}}</ref>
* [[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. {{Citation needed|reason=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.
* [[Howell-Jolly body|Howell-Jolly bodies]] (chromosomal remnant) also present.

[[Blood chemistry|Blood chemistries]] will also show:
* An increased [[lactic acid dehydrogenase]] (LDH) level. The isozyme is LDH-2 which is typical of the serum and hematopoietic cells.
* Increased [[homocysteine]] and [[methylmalonic acid]] in Vitamin B{{ssub|12}} deficiency
* Increased homocysteine in folate deficiency
Normal levels of both methylmalonic acid and total homocysteine rule out clinically significant cobalamin deficiency with virtual certainty.<ref>{{cite journal |vauthors=Savage DG, Lindenbaum J, Stabler SP, Allen RH |title=Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies |journal=Am. J. Med. |volume=96 |issue=3 |pages=239–46 |year=1994 |pmid=8154512 |doi= 10.1016/0002-9343(94)90149-X|doi-access= }}</ref> Elevated homocysteine and normal methylmalonic acid indicate folate deficiency, while elevated homocysteine and elevated methylmalonic acid indicate vitamin B{{ssub|12}} deficiency.

[[Bone marrow]] (not normally checked in a patient suspected of megaloblastic anemia) shows megaloblastic [[hyperplasia]].<ref>{{cite book |last=Hoffbrand |first=A. Victor |editor1-last=Longo |editor1-first=D. L. |editor2-last=Fauci |editor2-first=A. S. |editor2-link=Anthony S. Fauci |editor3-last=Kasper |editor3-first=D. L. |editor4-last=Hauser SL |editor4-first=S. L. |display-editors=etal |chapter=Chapter 105. Megaloblastic Anemias |chapter-url=http://accessmedicine.mhmedical.com/content.aspx?bookid=331&Sectionid=40726843 |chapter-url-access=subscription |title=Harrison's Principles of Internal Medicine |edition=18th |date=2012 |location=New York |publisher=McGraw-Hill |access-date=October 23, 2015}}</ref>