Editing Anemia (section)

==Diagnosis==
[[File:Iron deficiency anemia.jpg|thumb|Peripheral blood smear microscopy of a patient with [[iron-deficiency anemia]]]]
[[File:Fe- deficient anemia.jpg|thumb|A Giemsa-stained blood film from a person with iron-deficiency anemia. This person also had hemoglobin Kenya.]]

===Definitions===
There are a number of definitions of anemia; [[review article|reviews]] provide comparison and contrast of them.<ref name="pmid_16189263">{{cite journal | vauthors = Beutler E, Waalen J | title = The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration? | journal = Blood | volume = 107 | issue = 5 | pages = 1747–1750 | date = March 2006 | pmid = 16189263 | pmc = 1895695 | doi = 10.1182/blood-2005-07-3046 }}</ref> A strict but broad definition is an absolute decrease in red blood cell mass,<ref>{{EMedicine|article|198475|Anemia}}</ref> however, a broader definition is a lowered ability of the blood to carry [[oxygen]].<ref name="Ber2007">{{cite book|last=Rodak|first=Bernadette F.|url=https://books.google.com/books?id=6sfacydDNsUC&pg=PA220|title=Hematology: Clinical Principles and Applications|date=2007|publisher=Saunders|isbn=978-1-4160-3006-5|edition=3rd|location=Philadelphia|page=220|archive-url=https://web.archive.org/web/20160425061405/https://books.google.com/books?id=6sfacydDNsUC&pg=PA220|archive-date=2016-04-25|url-status=live}}</ref> An [[operational definition]] is a decrease in whole-blood [[hemoglobin]] concentration of more than 2 [[standard deviation]]s below the [[mean]] of an age- and sex-matched [[Reference ranges for blood tests#Hematology|reference range]].<ref name="PDMS2">{{cite book | first1 = Albert J. | last1 = Pomeranz | first2 = Svapna | last2 = Sabnis | first3 = Sharon | last3 = Busey | first4 = Robert M. | last4 = Kliegman |year=2016 |title=Pediatric Decision-Making Strategies |edition=2nd |publisher=Elsevier |isbn=978-0-323-29854-4 }}</ref>

It is difficult to directly measure RBC mass,<ref>{{cite book|last1=Polin|first1=Richard A.|last2=Abman|first2=Steven H.|last3=Rowitch|first3=David|last4=Benitz|first4=William E. | title = Fetal and Neonatal Physiology|date=2016|publisher=Elsevier Health Sciences|isbn=978-0-323-35232-1 |page=1085|edition=5|url=https://books.google.com/books?id=JootDAAAQBAJ&pg=PA1085|url-status = live|archive-url=https://web.archive.org/web/20161031150823/https://books.google.com/books?id=JootDAAAQBAJ&pg=PA1085|archive-date=2016-10-31}}</ref> so the [[hematocrit]] (amount of RBCs) or the hemoglobin (Hb) in the [[blood]] are often used instead to indirectly estimate the value.<ref>{{cite book|last1=Uthman|first1=Ed |title=Understanding Anemia|date=2009|publisher=Univ. Press of Mississippi|isbn=978-1-60473-701-1|page=23|url=https://books.google.com/books?id=2yBl75DJ8_kC&pg=PA23 |url-status = live|archive-url=https://web.archive.org/web/20161031150408/https://books.google.com/books?id=2yBl75DJ8_kC&pg=PA23|archive-date=2016-10-31}}</ref> Hematocrit; however, is concentration dependent and is therefore not completely accurate. For example, during pregnancy a woman's RBC mass is normal but because of an increase in blood volume the hemoglobin and hematocrit are diluted and thus decreased. Another example would be bleeding where the RBC mass would decrease but the concentrations of hemoglobin and hematocrit initially remains normal until fluids shift from other areas of the body to the intravascular space.{{citation needed|date=November 2021}}

The anemia is also classified by severity into mild (110 g/L to normal), moderate (80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adults.<ref name=WHODefSeverity>{{cite book |title=Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity |date=2011 |publisher=World Health Organization |hdl=10665/85839 |hdl-access=free |last1=Organization |first1=World Health }}</ref> Different values are used in pregnancy and children.<ref name=WHODefSeverity/>

===Testing===
Anemia is typically diagnosed on a [[complete blood count]]. Apart from reporting the number of [[red blood cell]]s and the hemoglobin level, the [[Automated analyser|automatic counters]] also measure the size of the red blood cells by [[flow cytometry]], which is an important tool in distinguishing between the causes of anemia. Examination of a stained [[blood smear]] using a [[microscope]] can also be helpful, and it is sometimes a necessity in regions of the world where automated analysis is less accessible.{{cn|date=February 2024}}
{| class="wikitable"
|+ WHO's Hemoglobin thresholds used to define anemia<ref>{{cite book |author=World Health Organization |title=Worldwide prevalence of anaemia 1993–2005 |year=2008 |isbn=978-92-4-159665-7 |url=http://whqlibdoc.who.int/publications/2008/9789241596657_eng.pdf |access-date=2009-03-25 |publisher=World Health Organization |location=Geneva| archive-url= https://web.archive.org/web/20090312111339/http://whqlibdoc.who.int/publications/2008/9789241596657_eng.pdf| archive-date= 12 March 2009 <!--DASHBot-->|url-status = live}}</ref>
(1&nbsp;g/dL&nbsp;=&nbsp;0.6206&nbsp;mmol/L)
|-
! Age or gender group
! Hb threshold (g/dL)
! Hb threshold (mmol/L)
|-
| Children (0.5–5.0 yrs)
| 11.0
| 6.8
|-
| Children (5–12 yrs)
| 11.5
| 7.1
|-
| Teens (12–15 yrs)
| 12.0
| 7.4
|-
| Women, non-pregnant (>15yrs)
| 12.0
| 7.4
|-
| Women, pregnant
| 11.0
| 6.8
|-
| Men (>15yrs)
| 13.0
| 8.1
|}
A blood test will provide counts of white blood cells, red blood cells and platelets. If anemia appears, further tests may determine what type it is, and whether it has a serious cause. although of that, it is possible to refer to the genetic history and physical diagnosis.<ref>{{cite web|title=Anemia|url=https://www.radiologyinfo.org/en/info/anemia|access-date=2021-10-11|website=Radiologyinfo.org|language=en}}</ref> These tests may also include [[Ferritin|serum ferritin]], [[Serum iron|iron studies]], [[Serum vitamin B12|vitamin B<sub>12</sub>]], genetic testing, and a [[Bone marrow examination|bone marrow sample]], if needed.<ref name=":2">{{cite web |title=How Anemia Is Diagnosed and Treated |url=https://www.webmd.com/a-to-z-guides/understanding-anemia-treatment |access-date=2021-10-11 |website=WebMD |language=en}}</ref><ref name=":3">{{cite web |title=Anemia Types, Treatment, Symptoms, Signs, Causes & Iron Deficiency |url=https://www.emedicinehealth.com/anemia/article_em.htm |access-date=2021-10-11 |website=eMedicineHealth |language=en}}</ref>

Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A [[reticulocyte]] count is a quantitative measure of the [[bone marrow]]'s production of new red blood cells. The [[reticulocyte production index]] is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.

If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of [[erythropoiesis]] can help assess whether the bone marrow will be able to compensate for the loss and at what rate.

When the cause is not obvious, clinicians use other tests, such as: [[erythrocyte sedimentation rate|ESR]], serum iron, [[transferrin]], [[folate|RBC folate level]], [[hemoglobin electrophoresis]], [[renal function]] tests (e.g. [[serum creatinine]]) although the tests will depend on the clinical hypothesis that is being investigated.

When the diagnosis remains difficult, a [[bone marrow examination]] allows direct examination of the precursors to red cells, although is rarely used as is painful, invasive and is hence reserved for cases where severe pathology needs to be determined or excluded.{{medical citation needed|date=January 2016}}

===Red blood cell size===
In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the [[mean corpuscular volume]] (MCV). If the cells are smaller than normal (under 80 [[femtolitre|fl]]), the anemia is said to be [[microcytic anemia|microcytic]]; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as [[macrocytic anemia|macrocytic]]. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of [[Iron deficiency (medicine)|iron deficiency]]. 

In clinical workup, the MCV will be one of the first pieces of information available, so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.
Limitations of MCV include cases where the underlying cause is due to a combination of factors – such as iron deficiency (a cause of microcytosis) and vitamin [[B12 deficiency]] (a cause of macrocytosis) where the net result can be normocytic cells.{{medical citation needed|date=January 2016}}

===Production vs. destruction or loss===
The "kinetic" approach to anemia yields arguably the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyte (precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction or loss. Clinical signs of loss or destruction include abnormal [[peripheral blood smear]] with signs of hemolysis; elevated [[Lactate dehydrogenase|LDH]] suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding.{{medical citation needed|date=January 2016}}
The following is a simplified schematic of this approach:{{medical citation needed|date=January 2016}}
{{chart/start}}
{{chart | | | | | | | | | A01 | | | | | | |A01=Anemia}}
{{chart | | | | | | |,|-|-|^|-|-|.| | | | }}
{{chart | | | | | | C01 | | | | C02 | | | |C01=[[Reticulocyte production index]] shows inadequate production response to anemia.|C02=[[Reticulocyte production index]] shows appropriate response to anemia = ongoing hemolysis or blood loss without RBC production problem.}}
{{chart | | |,|-|-|-|+|-|-|-|.| | | | | }}
{{chart | | E01 | | E02 | | E03 | |E01=No clinical findings consistent with hemolysis or blood loss: pure disorder of production.|E02=Clinical findings and abnormal MCV: hemolysis or loss and chronic disorder of production*.|E03=Clinical findings and normal MCV= acute hemolysis or loss without adequate time for [[bone marrow]] production to compensate**.}}
{{chart | |,|+|-|-|+|-|-|-|-|.| | | | | }}
{{chart | F01 | | F02 | | | F03 | | | | |F01=[[Macrocytic anemia]] (MCV>100)|F02=[[Normocytic anemia]] (80<MCV<100)|F03=[[Microcytic anemia]] (MCV<80)}}
{{chart/end}}
''*'' ''For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B<sub>12</sub> and folate deficiency; and other instances of anemia with more than one cause.''<br />
''**'' ''Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.''
Here is a schematic representation of how to consider anemia with MCV as the starting point:
{{chart/start}}
{{chart | | | | | | | | | | | | A01 | | | | | | | | | A01=Anemia}}
{{chart | | | | |,|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|.| }}
{{chart | | | | B01 | | | | | | B02 | | | | | | B03 | B01 = [[Macrocytic anemia]] (MCV>100) | B02 = [[Normocytic anemia]] (MCV 80–100) | B03 = [[Microcytic anemia]] (MCV<80)}}
{{chart | | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | }}
{{chart | | | | | | | | C01 | | | | | | C02 | | | | |C01=High [[reticulocyte]] count|C02=Low [[reticulocyte]] count}}
{{chart/end}}

Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal [[white blood cell]]s may point to a cause in the [[bone marrow]].

====Microcytic====
{{main|Microcytic anemia}}
Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:
{{columns-list|
* [[Heme]] synthesis defect
** [[Iron-deficiency anemia]] (microcytosis is not always present)
** [[Anemia of chronic disease]] (more commonly presenting as normocytic anemia)
* [[Globin]] synthesis defect
** Alpha-, and beta-[[thalassemia]]
** HbE syndrome
** HbC syndrome
** Various other unstable hemoglobin diseases
* [[Sideroblastic]] defect
** Hereditary sideroblastic anemia
** Acquired sideroblastic anemia, including [[lead poisoning|lead toxicity]]<ref>{{cite book |doi=10.1515/9783110434330-016 |chapter=Toxicology of Lead and Its Damage to Mammalian Organs |title=Lead – Its Effects on Environment and Health |date=2017 |series=Metal Ions in Life Sciences |volume=17 |pages=501–534 |pmid=28731309 |isbn=978-3-11-043433-0 | vauthors = Caito S, Lopes AC, Paoliello MM, Aschner M }}</ref>
** Reversible sideroblastic anemia
}}
Iron-deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
* Iron-deficiency anemia is due to insufficient dietary intake or absorption of [[iron]] to meet the body's needs. Infants, toddlers, and pregnant women have higher than average needs. Increased iron intake is also needed to offset blood losses due to digestive tract issues, frequent blood donations, or [[Menorrhagia|heavy menstrual periods]].<ref name=irond>[https://www.cdc.gov/nccdphp/dnpa/nutrition/nutrition_for_everyone/iron_deficiency/index.htm Recommendations to Prevent and Control Iron Deficiency in the United States] {{webarchive|url=https://web.archive.org/web/20070420203221/http://www.cdc.gov/nccdphp/dnpa/nutrition/nutrition_for_everyone/iron_deficiency/index.htm |date=2007-04-20 }} MMWR 1998;47 (No. RR-3) p. 5</ref> Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 12% of all women of childbearing age have iron deficiency, compared with only 2% of adult men. The incidence is as high as 20% among African American and Mexican American women.<ref>{{cite journal|title=Iron Deficiency – United States, 1999–2000|journal=MMWR|date=October 11, 2002|volume=51|issue=40|pages=897–899|pmid=12418542|url=https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5140a1.htm|access-date=21 April 2012|url-status = live|archive-url=https://web.archive.org/web/20120505040540/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5140a1.htm|archive-date=5 May 2012|author1=Centers for Disease Control Prevention (CDC)}}</ref> In India it is even more than 50%.<ref>{{cite web |title=Global Iron-Deficiency Anemia Therapy Market – Industry Trends and Forecast to 2027 – |url=https://www.databridgemarketresearch.com/reports/global-iron-deficiency-anemia-therapy-market |access-date=2023-08-02 |website=Data Bridge Market Research}}</ref> Studies have linked iron deficiency without anemia to poor school performance and lower [[IQ]] in teenage girls, although this may be due to socioeconomic factors.<ref name=halterman1>{{cite journal | vauthors = Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG | s2cid = 33404386 | title = Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States | journal = Pediatrics | volume = 107 | issue = 6 | pages = 1381–1386 | date = June 2001 | pmid = 11389261 | doi = 10.1542/peds.107.6.1381 }}</ref><ref name=mcgregor1>{{cite journal | vauthors = Grantham-McGregor S, Ani C | title = A review of studies on the effect of iron deficiency on cognitive development in children | journal = The Journal of Nutrition | volume = 131 | issue = 2S–2 | pages = 649S–666S; discussion 666S–668S | date = February 2001 | pmid = 11160596 | doi = 10.1093/jn/131.2.649S | doi-access = free }}</ref> Iron deficiency is the most prevalent deficiency state on a worldwide basis. It is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips ([[angular stomatitis]]).
* In the United States, the most common cause of iron deficiency is bleeding or blood loss, usually from the [[gastrointestinal tract]]. [[Fecal occult blood|Fecal occult blood testing]], [[esophagogastroduodenoscopy|upper endoscopy]] and [[colonoscopy|lower endoscopy]] should be performed to identify bleeding lesions. In older men and women, the chances are higher that bleeding from the gastrointestinal tract could be due to [[Polyp (medicine)|colon polyp]]s or [[colorectal cancer]].
* Worldwide, the most common cause of iron-deficiency anemia is parasitic infestation ([[hookworm]]s, [[amebiasis]], [[schistosomiasis]] and [[Trichuris trichiura|whipworm]]s).<ref>{{cite web |url=https://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf |title=Iron Deficiency Anaemia: Assessment, Prevention, and Control: A guide for programme managers |access-date=2010-08-24 |url-status = dead|archive-url=https://web.archive.org/web/20110516122938/http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf |archive-date=2011-05-16  }}</ref>
The [[Mentzer index]] (mean cell volume divided by the RBC count) predicts whether microcytic anemia may be due to iron deficiency or thalassemia, although it requires confirmation.<ref>{{cite journal | vauthors = Mentzer WC | title = Differentiation of iron deficiency from thalassaemia trait | journal = Lancet | volume = 1 | issue = 7808 | pages = 882 | date = April 1973 | pmid = 4123424 | doi = 10.1016/s0140-6736(73)91446-3 }}</ref>{{citation needed|date=August 2013}}

====Macrocytic====
{{main|Macrocytic anemia}}
* [[Megaloblastic anemia]], the most common cause of macrocytic anemia, is due to a deficiency of either [[vitamin B12|vitamin B<sub>12</sub>]], [[folic acid]], or both.<ref>{{cite journal |last1=Long |first1=Brit |last2=Koyfman |first2=Alex |title=Emergency Medicine Evaluation and Management of Anemia |journal=Emergency Medicine Clinics of North America |date=August 2018 |volume=36 |issue=3 |pages=609–630 |doi=10.1016/j.emc.2018.04.009 |pmid=30037447 }}</ref> Deficiency in folate or vitamin B<sub>12</sub> can be due either to inadequate intake or [[malabsorption|insufficient absorption]]. Folate deficiency normally does not produce neurological symptoms, while B<sub>12</sub> deficiency does.
** [[Pernicious anemia]] is caused by a lack of [[intrinsic factor]], which is required to absorb vitamin B<sub>12</sub> from food. A lack of intrinsic factor may arise from an [[autoimmune]] condition targeting the [[parietal cell]]s (atrophic gastritis) that produce intrinsic factor or against intrinsic factor itself. These lead to poor absorption of vitamin B<sub>12</sub>.
** Macrocytic anemia can also be caused by the removal of the functional portion of the stomach, such as during [[gastric bypass]] surgery, leading to reduced vitamin B<sub>12</sub>/folate absorption. Therefore, one must always be aware of anemia following this procedure.
* [[Hypothyroidism]]
* [[Alcoholism]] commonly causes a [[macrocytosis]], although not specifically anemia. Other types of [[liver disease]] can also cause macrocytosis.
* Drugs such as [[methotrexate]], [[zidovudine]], and other substances may inhibit [[DNA replication]] such as [[heavy metals]]
Macrocytic anemia can be further divided into "megaloblastic anemia" or "nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which results in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (six to 10 lobes). The nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired DNA globin synthesis,) which occur, for example, in alcoholism.
In addition to the nonspecific symptoms of anemia, specific features of vitamin B<sub>12</sub> deficiency include [[peripheral neuropathy]] and [[subacute combined degeneration of the cord]] with resulting balance difficulties from posterior column spinal cord pathology.<ref>[http://www.emedicine.com/NEURO/topic439.htm eMedicine – "Vitamin B-12 Associated Neurological Diseases": Article by Niranjan N Singh], July 18, 2006. {{webarchive|url=https://web.archive.org/web/20070315044706/http://www.emedicine.com/neuro/topic439.htm|date=2007-03-15}}.</ref> Other features may include a smooth, red tongue and [[glossitis]].
The treatment for vitamin B<sub>12</sub>-deficient anemia was first devised by [[William Murphy (scientist)|William Murphy]], who bled dogs to make them anemic, and then fed them various substances to see what (if anything) would make them healthy again. He discovered that ingesting large amounts of liver seemed to cure the disease. [[George Richards Minot|George Minot]] and [[George Whipple]] then set about to isolate the curative substance chemically and ultimately were able to isolate the [[vitamin B12|vitamin B<sub>12</sub>]] from the liver. All three shared the 1934 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Medicine]].<ref>{{cite web|url=http://nobelprize.org/nobel_prizes/medicine/laureates/1934/press.html |title=Physiology or Medicine 1934 – Presentation Speech |publisher=Nobelprize.org |date=1934-12-10 |access-date=2010-08-24| archive-url= https://web.archive.org/web/20100828134134/http://nobelprize.org/nobel_prizes/medicine/laureates/1934/press.html| archive-date= 28 August 2010 <!--DASHBot-->|url-status = live}}</ref>

====Normocytic====
{{main|Normocytic anemia}}
Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size ([[mean corpuscular volume]]) remains normal. Causes include:
{{columns-list|
* Acute [[hemorrhage|blood loss]]
* [[Anemia of chronic disease]]
* [[Aplastic anemia]] (bone marrow failure)
* [[Hemolytic anemia]]
}}

====Dimorphic====
A dimorphic appearance on a peripheral blood smear occurs when there are two simultaneous populations of red blood cells, typically of different size and hemoglobin content (this last feature affecting the color of the red blood cell on a stained peripheral blood smear). For example, a person recently transfused for iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and the donor RBCs of normal size and color. Similarly, a person transfused for severe folate or vitamin B12 deficiency would have two cell populations, but, in this case, the patient's RBCs would be larger and paler than the donor's RBCs. 

A person with sideroblastic anemia (a defect in heme synthesis, commonly caused by alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare congenital diseases) can have a dimorphic smear from the sideroblastic anemia alone. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in common nutritional anemia.{{citation needed|date=January 2016}}

====Heinz body anemia====
[[Heinz body|Heinz bodies]] form in the cytoplasm of RBCs and appear as small dark dots under the microscope. In animals, Heinz body anemia has many causes. It may be drug-induced, for example in cats and dogs by [[acetaminophen]] (paracetamol),<ref name="Harvey 2012"/> or may be caused by eating various plants or other substances:
* In [[cat]]s and dogs after eating either raw or cooked plants from the genus ''[[Allium]]'', for example, [[onion]]s or garlic.<ref>{{cite book|editor1-last=Hovda|editor1-first=L|editor2-last=Brutlag|editor2-first=A|editor3-last=Poppenga|editor3-first=RH|editor4-last=Peterson|editor4-first=K | title=Blackwell's Five-Minute Veterinary Consult Clinical Companion: Small Animal Toxicology|date=2016|publisher=John Wiley & Sons|isbn=978-1-119-03652-4|pages=515–520|edition=2nd|chapter=Chapter 69: Onions and garlic}}</ref>
* In dogs after ingestion of [[zinc]], for example, after eating [[Penny (United States coin)|U.S. pennies]] minted after 1982.<ref name="Harvey 2012">{{cite book|last1=Harvey|first1=John W. |title=Veterinary hematology: a diagnostic guide and color atlas|date=2012|publisher=Elsevier/Saunders|location=St. Louis, MO|isbn=978-1-4377-0173-9|page=104}}</ref>
* In horses which eat dry or wilted [[Acer rubrum|red maple]] leaves.<ref>{{cite book |doi=10.1016/B978-1-4557-4555-5.00117-5 |chapter=Hemolytic Disorders |title=Robinson's Current Therapy in Equine Medicine |date=2015 |pages=492–495 |isbn=978-1-4557-4555-5 | vauthors = Peek SF }}</ref>

===Hyperanemia===
Hyperanemia is a severe form of anemia, in which the [[hematocrit]] is below 10%.<ref>{{cite journal | vauthors = Wallerstein RO | title = Laboratory evaluation of anemia | journal = The Western Journal of Medicine | volume = 146 | issue = 4 | pages = 443–451 | date = April 1987 | pmid = 3577135 | pmc = 1307333 }}</ref>

===Refractory anemia===
Refractory anemia, an anemia which does not respond to treatment,<ref>{{cite web |url=http://www.medterms.com/script/main/art.asp?articlekey=5275 |title=MedTerms Definition: Refractory Anemia |publisher=Medterms.com |date=2011-04-27 |access-date=2011-10-31 |url-status = live|archive-url=https://web.archive.org/web/20111208232310/http://www.medterms.com/script/main/art.asp?articlekey=5275 |archive-date=2011-12-08  }}</ref> is often seen secondary to myelodysplastic syndromes.<ref>{{cite web |url=http://atlasgeneticsoncology.org/Anomalies/RAID1104.html |title=Good Source for later |publisher=Atlasgeneticsoncology.org |access-date=2011-10-31 |url-status = live|archive-url=https://web.archive.org/web/20111103180817/http://atlasgeneticsoncology.org/Anomalies/RAID1104.html |archive-date=2011-11-03  }}</ref> Iron-deficiency anemia may also be refractory as a manifestation of gastrointestinal problems which disrupt [[Human iron metabolism|iron absorption]] or cause [[occult bleeding]].
<ref name="pmid12571473">{{cite journal | vauthors = Mody RJ, Brown PI, Wechsler DS | s2cid = 38832868 | title = Refractory iron deficiency anemia as the primary clinical manifestation of celiac disease | journal = Journal of Pediatric Hematology/Oncology | volume = 25 | issue = 2 | pages = 169–172 | date = February 2003 | pmid = 12571473 | doi = 10.1097/00043426-200302000-00018 }}</ref>

===Transfusion dependent===
Transfusion dependent anemia is a form of anemia where ongoing blood transfusion are required.<ref>{{cite journal | vauthors = Gale RP, Barosi G, Barbui T, Cervantes F, Dohner K, Dupriez B, Gupta V, Harrison C, Hoffman R, Kiladjian JJ, Mesa R, Mc Mullin MF, Passamonti F, Ribrag V, Roboz G, Saglio G, Vannucchi A, Verstovsek S | display-authors = 6 | title = What are RBC-transfusion-dependence and -independence? | journal = Leukemia Research | volume = 35 | issue = 1 | pages = 8–11 | date = January 2011 | pmid = 20692036 | doi = 10.1016/j.leukres.2010.07.015 | pmc = 8215731 }}</ref> Most people with myelodysplastic syndrome develop this state at some point in time.<ref name=Mel2007/> [[Beta thalassemia]] may also result in transfusion dependence.<ref>{{cite book |last1=Hillyer |first1=Christopher D. |last2=Silberstein |first2=Leslie E. |last3=Ness |first3=Paul M. |last4=Anderson |first4=Kenneth C. |last5=Roback |first5=John D. |title=Blood Banking and Transfusion Medicine: Basic Principles and Practice |date=2006 |publisher=Elsevier Health Sciences |isbn=9780702036255 |page=534 |url=https://books.google.com/books?id=8iEPDQAAQBAJ&pg=PT556 }}</ref><ref>{{cite book |last1=Mandel |first1=Jess |last2=Taichman |first2=Darren |title=Pulmonary Vascular Disease |date=2006 |publisher=Elsevier Health Sciences |isbn=978-1416022466 |page=170 |url=https://books.google.com/books?id=v-pr4P34QjIC&pg=PA170 |language=en}}</ref> Concerns from repeated blood transfusions include [[iron overload]].<ref name=Mel2007>{{cite journal | vauthors = Melchert M, List AF | title = Management of RBC-transfusion dependence | journal = Hematology. American Society of Hematology. Education Program | volume = 2007 | pages = 398–404 | date = 2007 | pmid = 18024657 | doi = 10.1182/asheducation-2007.1.398 | doi-access = free }}</ref> This iron overload may require [[chelation therapy]].<ref>{{cite book |last1=Ferri |first1=Fred F. |title=BOPOD – Ferri's Clinical Advisor 2016 |date=2015 |publisher=Elsevier Health Sciences |isbn=978-0323378222 |page=1131.e2 |url=https://books.google.com/books?id=bbLSCQAAQBAJ&pg=PA1131-IA2 |language=en}}</ref>