View source for Anemia

{{short description|Reduced ability of blood to carry oxygen}}
{{Other uses}}
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{{Infobox medical condition
| name = Anemia
| synonyms = Anaemia, erythrocytopenia
| image = Iron deficiency anemia blood film.jpg
| caption = [[Blood smear]] showing [[iron-deficiency anemia]], with small, pale [[red blood cell]]s
| field = [[Hematology]]
| pronounce = {{IPAc-en|ə|ˈ|n|iː|m|i|ə}}
| symptoms = [[Fatigue|Feeling tired]], [[Pallor|pale skin]], weakness, [[shortness of breath]], feeling faint<ref name=EBM2013 >{{cite journal|vauthors = Janz TG, Johnson RL, Rubenstein SD|title = Anemia in the emergency department: evaluation and treatment | journal = Emergency Medicine Practice | volume = 15 | issue = 11 | pages = 1–15; quiz 15–16 | date = November 2013 | pmid = 24716235 |url= http://www.ebmedicine.net/topics.php?paction=showTopic&topic_id=385 }}</ref>
| complications = 
| onset = 
| duration = 
| causes = [[Blood loss]], decreased red blood cell production, increased red blood cell breakdown<ref name=EBM2013 />
| risks = 
| diagnosis = [[Hemoglobin#Diagnostic uses|Blood hemoglobin measurement]]<ref name=EBM2013 />
| differential = 
| prevention = 
| treatment = 
| medication = 
| prognosis = 
| frequency = 1.92 billion / 24% (2021)<ref name="GBD2021">{{cite journal | last1=Gardner | first1=William M | last2=Razo | first2=Christian | last3=McHugh | first3=Theresa A | last4=Hagins | first4=Hailey | last5=Vilchis-Tella | first5=Victor M | last6=Hennessy | first6=Conor | last7=Taylor | first7=Heather Jean | last8=Perumal | first8=Nandita | last9=Fuller | first9=Kia | last10=Cercy | first10=Kelly M | last11=Zoeckler | first11=Leo Zucker | last12=Chen | first12=Catherine S | last13=Lim | first13=Stephen S | last14=Aali | first14=Amirali | last15=Abate | first15=Kalkidan Hassen | last16=Abd-Elsalam | first16=Sherief | last17=Abdurehman | first17=Ame Mehadi | last18=Abebe | first18=Getachew | last19=Abidi | first19=Hassan | last20=Aboagye | first20=Richard Gyan | last21=Abolhassani | first21=Hassan | last22=Aboye | first22=Girma Beressa Aboye | last23=Abtew | first23=Yonas Derso | last24=Accrombessi | first24=Manfred Mario Kokou | last25=Adane | first25=Denberu Eshetie Adane | last26=Adane | first26=Tigist Demssew | last27=Addo | first27=Isaac Yeboah | last28=Adesina | first28=Miracle Ayomikun | last29=Adeyinka | first29=Daniel Adedayo | last30=Adnani | first30=Qorinah Estiningtyas Sakilah | title=Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990–2021: findings from the Global Burden of Disease Study 2021 | journal=The Lancet Haematology | volume=10 | issue=9 | year=2023 | issn=2352-3026 | doi=10.1016/s2352-3026(23)00160-6 | doi-access=free | pages=e713–e734 | pmid=37536353 |display-authors=1| hdl=2164/22615 | hdl-access=free }}</ref>
| deaths = 
}}

'''Anemia''' (also spelt '''anaemia''' in  [[British English]]) is a [[blood disorder]] in which the [[blood]] has a reduced ability to carry [[oxygen]]. This can be due to a lower than normal number of [[red blood cell]]s, a reduction in the amount of [[hemoglobin]] available for oxygen transport, or abnormalities in hemoglobin that impair its function.<ref name="EMed">{{cite web |title=Anemia: Practice Essentials, Pathophysiology, Etiology |url=https://emedicine.medscape.com/article/198475-overview |access-date=8 February 2022 |date=9 November 2021}}</ref><ref name="nhlbi">{{cite web |title=Anemia {{!}} NHLBI, NIH |url=https://www.nhlbi.nih.gov/health/anemia |website=www.nhlbi.nih.gov |access-date=8 February 2022}}</ref> The name is derived {{ety|grc|''ἀν''- (an-)|not||''αἷμα'' (haima)|blood}}.<ref>{{cite web|title=anaemia|url=http://dictionary.reference.com/browse/anaemia|website=Dictionary.com|access-date=7 July 2014|url-status = live|archive-url=https://web.archive.org/web/20140714223241/http://dictionary.reference.com/browse/anaemia|archive-date=14 July 2014}}</ref>

When anemia comes on slowly, the symptoms are often vague, such as [[Fatigue|tiredness]], [[weakness]], [[shortness of breath]], [[headache]]s, and a [[Exercise intolerance|reduced ability to exercise]].<ref name="EBM2013" /> When anemia is acute, symptoms may include [[confusion]], [[lightheadedness|feeling like one is going to pass out]], [[Syncope (medicine)|loss of consciousness]], and [[polydipsia|increased thirst]].<ref name="EBM2013" /> Anemia must be significant before a person becomes noticeably [[Pallor|pale]].<ref name="EBM2013" /> Additional symptoms may occur depending on the underlying cause.<ref name="EBM2013" /> Anemia can be temporary or long-term and can range from mild to severe.<ref>{{cite web |title=Anemia – Symptoms and causes |url=https://www.mayoclinic.org/diseases-conditions/anemia/symptoms-causes/syc-20351360 |access-date=2022-04-01 |website=Mayo Clinic |language=en}}</ref>

Anemia can be caused by [[blood loss]], decreased red blood cell production, and increased [[hemolysis|red blood cell breakdown]].<ref name=EBM2013 /> Causes of blood loss include [[Gastrointestinal bleeding|bleeding due to inflammation of the stomach or intestines]], bleeding from [[surgery]], serious [[injury]], or [[blood donation]].<ref name="EBM2013" /> Causes of decreased production include [[iron deficiency]], [[folate deficiency]], [[vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]], [[thalassemia]] and a number of [[neoplasms of the bone marrow|bone marrow tumors]].<ref name="EBM2013" /> Causes of increased breakdown include [[genetic disorder]]s such as [[sickle cell anemia]], infections such as [[malaria]], and certain [[autoimmune disease]]s like [[autoimmune hemolytic anemia]].<ref name="EBM2013" />

Anemia can also be classified based on the [[mean corpuscular volume|size of the red blood cells]] and [[mean corpuscular hemoglobin|amount of hemoglobin in each cell]].<ref name="EBM2013" /> If the cells are small, it is called [[microcytic anemia]]; if they are large, it is called [[macrocytic anemia]]; and if they are normal sized, it is called [[normocytic anemia]].<ref name="EBM2013" /> The diagnosis of anemia in men is based on a hemoglobin of less than 130 to 140&nbsp;g/L (13 to 14&nbsp;g/dL); in women, it is less than 120 to 130&nbsp;g/L (12 to 13&nbsp;g/dL).<ref name="EBM2013" /><ref name="Smith2010">{{cite journal | vauthors = Smith RE | title = The clinical and economic burden of anemia | journal = The American Journal of Managed Care | volume = 16 Suppl Issues | pages = S59–66 | date = March 2010 | pmid = 20297873 }}</ref> Further testing is then required to determine the cause.<ref name="EBM2013" /><ref name="Stat2019">{{cite book |last1=Rhodes |first1=Carl E. |last2=Denault |first2=Deanna |last3=Varacallo |first3=Matthew |title=StatPearls |date=2024 |publisher=StatPearls Publishing |url=https://www.ncbi.nlm.nih.gov/books/NBK538336/ |chapter=Physiology, Oxygen Transport |pmid=30855920 }}</ref>

Treatment depends on the specific cause. Certain groups of individuals, such as pregnant women, can benefit from the use of [[iron pill]]s for prevention.<ref name="EBM2013" /><ref>{{cite journal | vauthors = Bhutta ZA, Das JK, Rizvi A, Gaffey MF, Walker N, Horton S, Webb P, Lartey A, Black RE | s2cid = 11748341 | title = Evidence-based interventions for improvement of maternal and child nutrition: what can be done and at what cost? | journal = Lancet | volume = 382 | issue = 9890 | pages = 452–477 | date = August 2013 | pmid = 23746776 | doi = 10.1016/S0140-6736(13)60996-4 }}</ref> [[Dietary supplement]]ation, without determining the specific cause, is not recommended.<ref name="EBM2013" /> The use of [[blood transfusion]]s is typically based on a person's signs and symptoms.<ref name="EBM2013" /> In those without symptoms, they are not recommended unless hemoglobin levels are less than 60 to 80&nbsp;g/L (6 to 8&nbsp;g/dL).<ref name="EBM2013" /><ref name="Amir2013" /> These recommendations may also apply to some people with acute bleeding.<ref name="EBM2013" /> [[Erythropoiesis-stimulating agent]]s are only recommended in those with severe anemia.<ref name="Amir2013">{{cite journal | vauthors = Qaseem A, Humphrey LL, Fitterman N, Starkey M, Shekelle P | title = Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians | journal = Annals of Internal Medicine | volume = 159 | issue = 11 | pages = 770–779 | date = December 2013 | pmid = 24297193 | doi = 10.7326/0003-4819-159-11-201312030-00009 | s2cid = 4712203 | doi-access =  }}</ref>

Anemia is the most common blood disorder, affecting about a fifth to a third of the global population.<ref name="EBM2013" /><ref name="GBD2015">{{cite journal |title=Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015 |journal=Lancet |volume=388 |issue=10053 |pages=1545–1602 |date=October 2016 |pmid=27733282 |pmc=5055577 |doi=10.1016/S0140-6736(16)31678-6 |url=|last1=Vos |first1=Theo |last2=Allen |first2=Christine |last3=Arora |first3=Megha |last4=Barber |first4=Ryan M. |last5=Bhutta |first5=Zulfiqar A. |last6=Brown |first6=Alexandria |last7=Carter |first7=Austin |last8=Casey |first8=Daniel C. |last9=Charlson |first9=Fiona J. |last10=Chen |first10=Alan Z. |last11=Coggeshall |first11=Megan |last12=Cornaby |first12=Leslie |last13=Dandona |first13=Lalit |last14=Dicker |first14=Daniel J. |last15=Dilegge |first15=Tina |last16=Erskine |first16=Holly E. |last17=Ferrari |first17=Alize J. |last18=Fitzmaurice |first18=Christina |last19=Fleming |first19=Tom |last20=Forouzanfar |first20=Mohammad H. |last21=Fullman |first21=Nancy |last22=Gething |first22=Peter W. |last23=Goldberg |first23=Ellen M. |last24=Graetz |first24=Nicholas |last25=Haagsma |first25=Juanita A. |last26=Hay |first26=Simon I. |last27=Johnson |first27=Catherine O. |last28=Kassebaum |first28=Nicholas J. |last29=Kawashima |first29=Toana |last30=Kemmer |first30=Laura |display-authors=1 }}</ref><ref>{{cite journal |last1=Peyrin-Biroulet |first1=Laurent |last2=Williet |first2=Nicolas |last3=Cacoub |first3=Patrice |title=Guidelines on the diagnosis and treatment of iron deficiency across indications: a systematic review |journal=The American Journal of Clinical Nutrition |date=1 December 2015 |volume=102 |issue=6 |pages=1585–1594 |doi=10.3945/ajcn.114.103366 |pmid=26561626 |doi-access=free }}</ref><ref name="2019MarketStudy">{{cite press release |date=2019-04-26 |title=Anemia Treatment Drugs: 2019 Global Market Study; Analyzed by Type of Anemia, Type of Drug, and Geography |url=https://www.globenewswire.com/news-release/2019/04/26/1810348/0/en/Anemia-Treatment-Drugs-2019-Global-Market-Study-Analyzed-by-Type-of-Anemia-Type-of-Drug-and-Geography.html |access-date=2023-08-02 |website=GlobeNewswire}}</ref> [[Iron-deficiency anemia]] is the most common cause of anemia worldwide, and affects nearly one billion people.<ref name="LancetEpi2012">{{cite journal | vauthors = Vos T |display-authors=etal | title = Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010 | journal = Lancet | volume = 380 | issue = 9859 | pages = 2163–2196 | date = December 2012 | pmid = 23245607 |pmc=6350784 | doi = 10.1016/S0140-6736(12)61729-2 }}</ref> In 2013, anemia due to iron deficiency resulted in about 183,000 deaths – down from 213,000 deaths in 1990.<ref name="GBD2013">{{cite journal |title=Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 |journal=Lancet |volume=385 |issue=9963 |pages=117–71 |date=January 2015 |pmid=25530442 |pmc=4340604 |doi=10.1016/S0140-6736(14)61682-2 |url=|author1=((GBD 2013 Mortality Causes of Death Collaborators))}}</ref> This condition is most prevalent in children<ref>{{cite web|title=WHO Global Anaemia estimates, 2021 Edition |url=https://www.who.int/data/gho/data/themes/topics/anaemia_in_women_and_children|work=World Health Organization|access-date=27 February 2022}}</ref><ref>{{cite journal |last1=Islam |first1=Md Azmir Ibne |title=Modeling the impact of campaign program on the prevalence of anemia in children under five: Anemia model |journal=Journal of Mathematical Analysis and Modeling |date=6 December 2021 |volume=2 |issue=3 |pages=29–40 |doi=10.48185/jmam.v2i3.362 |url=https://www.sabapub.com/index.php/jmam/article/view/362 |language=en |issn=2709-5924|doi-access=free }}</ref> with also an above average prevalence in elderly<ref name="EBM2013" /> and women of reproductive age (especially during pregnancy).<ref name="LancetEpi2012" /> Anemia is one of the six [[WHO]] global nutrition targets for 2025 and for diet-related global targets endorsed by [[World Health Assembly]] in 2012 and 2013. Efforts to reach global targets contribute to reaching [[Sustainable Development Goals]] (SDGs),<ref>{{cite web|title=WHO {{!}} Interventions by global target|url=https://www.who.int/elena/global-targets/en/ |archive-url=https://web.archive.org/web/20160814083405/http://www.who.int/elena/global-targets/en/ |archive-date=August 14, 2016 |website=www.who.int |publisher=World Health Organization}}</ref> with anemia as one of the targets in [[SDG 2]] for achieving zero world hunger.<ref>{{cite web|date=14 June 2016|publisher=Devex|title=The case for action on anemia|url=https://www.devex.com/news/sponsored/the-case-for-action-on-anemia-leave-no-one-behind-88283}}</ref>{{TOC limit|3}}

==Signs and symptoms==
[[File:Symptoms of anemia.png|thumb|upright=1.2|Main symptoms that may appear in anemia<ref name=":4">[http://www.emedicinehealth.com/anemia/page3_em.htm eMedicineHealth > anemia article] {{webarchive|url=https://web.archive.org/web/20090417032231/http://www.emedicinehealth.com/anemia/page3_em.htm |date=2009-04-17 }} Author: Saimak T. Nabili, MD, MPH. Editor: Melissa Conrad Stöppler, MD. Last Editorial Review: 12/9/2008. Retrieved on 4 April 2009</ref>]] [[File:Anemia.JPG|thumb|upright=1.2|The hand of a person with severe anemia (on the left, with ring) compared to one without (on the right)]]
A person with anemia may not have any symptoms, depending on the underlying cause, and no symptoms may be noticed, as the anemia is initially mild, and then the symptoms become worse as the anemia worsens. A patient with anemia may report [[Fatigue|feeling tired]], weak, decreased ability to concentrate, and sometimes [[shortness of breath]] on [[exertion]].<ref>{{cite web|title=Exercising With Anemia: Prescription for Health|url=http://www.medscape.com/viewarticle/719391|access-date=2022-01-08|website=Medscape|language=en}}</ref> These symptoms are unspecific and none of the symptoms alone or in combination show a good predictive value for the presence of anemia in non-clinical patients.<ref>{{cite journal |last1=Weckmann |first1=Gesine |last2=Kiel |first2=Simone |last3=Chenot |first3=Jean-François |last4=Angelow |first4=Aniela |date=2023-01-24 |title=Association of Anemia with Clinical Symptoms Commonly Attributed to Anemia – Analysis of Two Population-Based Cohorts |journal=Journal of Clinical Medicine |language=English |volume=12 |issue=3 |page=921 |doi= 10.3390/jcm12030921 |pmid=36769569 |pmc=9918126 |doi-access=free }}</ref>

[[File:Symptoms of anemia are written in Bengali, Hindi and English language on a board at AIIMS Kalyani - 1.jpg|thumb|left|Symptoms of anemia are written in [[Bengali language|Bengali]], Hindi and English language on a board at [[All India Institute of Medical Sciences, Kalyani|AIIMS Kalyani]], [[West Bengal]].]]
Symptoms of anemia can come on quickly or slowly.<ref name=":0">{{cite web |date=2022-03-24 |title=What Are Symptoms of Anemia? |url=https://www.nhlbi.nih.gov/health/anemia/symptoms |access-date=2022-06-26 |website=National Heart, Lung, and Blood Institute.}}</ref> Early on there may be few or no symptoms.<ref name=":0" /> If the anemia continues slowly (chronic), the body may adapt and compensate for this change. In this case, no symptoms may appear until the anemia becomes more severe.<ref name=":4" /><ref name=":7">{{cite web |title=Anemia |url=https://www.hematology.org:443/education/patients/anemia |access-date=2022-01-08 |website=www.hematology.org |language=en}}</ref> Symptoms can include feeling tired, weak, [[dizziness]], headaches, [[Exercise intolerance|intolerance to physical exertion]], shortness of breath, difficulty concentrating, [[Arrhythmia|irregular]] or [[Tachycardia|rapid]] heartbeat, cold hands and feet, [[Cold sensitivity|cold intolerance]], [[pallor|pale]] or [[Jaundice|yellow]] skin, [[poor appetite]], easy bruising and bleeding, and [[muscle weakness]].<ref name=":0" />

Anemia that develops quickly, often, has more severe symptoms, including, [[Lightheadedness|feeling faint]], [[Angina|chest pain]], sweating, increased thirst, and confusion.<ref name=":0" /><ref>{{cite journal |last1=Stevens |first1=Gretchen A |last2=Finucane |first2=Mariel M |last3=De-Regil |first3=Luz Maria |last4=Paciorek |first4=Christopher J |last5=Flaxman |first5=Seth R |last6=Branca |first6=Francesco |last7=Peña-Rosas |first7=Juan Pablo |last8=Bhutta |first8=Zulfiqar A |last9=Ezzati |first9=Majid |title=Global, regional, and national trends in haemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995–2011: a systematic analysis of population-representative data |journal=The Lancet Global Health |date=July 2013 |volume=1 |issue=1 |pages=e16–e25 |doi=10.1016/s2214-109x(13)70001-9 |pmc=4547326 |pmid=25103581}}</ref><ref>{{cite journal |last1=Balarajan |first1=Yarlini |last2=Ramakrishnan |first2=Usha |last3=Özaltin |first3=Emre |last4=Shankar |first4=Anuraj H |last5=Subramanian |first5=Sv |title=Anaemia in low-income and middle-income countries |journal=The Lancet |date=December 2011 |volume=378 |issue=9809 |pages=2123–2135 |doi=10.1016/s0140-6736(10)62304-5 |pmid=21813172 }}</ref><ref>{{Cite journal |last1=Haas |first1=Jere D. |last2=Brownlie |first2=Thomas |date=2001-02-01 |title=Iron Deficiency and Reduced Work Capacity: A Critical Review of the Research to Determine a Causal Relationship |journal=The Journal of Nutrition |volume=131 |issue=2 |pages=676S–690S |doi=10.1093/jn/131.2.676s |pmid=11160598 |doi-access=free }}</ref> There may be also additional symptoms depending on the underlying cause.<ref name="EBM2013" />

In more severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing [[cardiac output]]. The person may have symptoms related to this, such as [[palpitations]], [[angina]] (if pre-existing [[heart disease]] is present), intermittent [[claudication]] of the legs, and symptoms of [[heart failure]].<ref>{{cite journal |last1=De Franceschi |first1=Lucia |last2=Iolascon |first2=Achille |last3=Taher |first3=Ali |last4=Cappellini |first4=Maria Domenica |title=Clinical management of iron deficiency anemia in adults: Systemic review on advances in diagnosis and treatment |journal=European Journal of Internal Medicine |date=July 2017 |volume=42 |pages=16–23 |doi=10.1016/j.ejim.2017.04.018 |pmid=28528999 }}</ref>

On examination, the signs exhibited may include [[pallor]] (pale skin, [[mucosa]], [[conjunctiva]], and [[nail beds]]), but this is not a reliable sign.

Iron-deficiency anemia may give symptoms that can include [[Koilonychia|spoon-shaped]] nails, restless legs syndrome, and pica (the desire to eat things which are not food, such as ice, dirt, etc.).<ref name=":6" /> A blue coloration of the [[sclera]] may be noticed in some cases of iron-deficiency anemia.<ref>{{cite book |last1=Weksler |first1=Babette |url=https://books.google.com/books?id=FTwtDwAAQBAJ&pg=PT105 |title=Wintrobe's Atlas of Clinical Hematology |date=2017 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4511-5454-2 |page=PT105 |language=en}}</ref> Vitamin B<sub>12</sub> deficiency anemia may result in decreased ability to think, memory loss, confusion, personality or mood changes, depression, difficulty walking, blurred vision, and irreversible nerve damage.<ref>{{Cite journal |last1=Hector |first1=M. |last2=Burton |first2=J. R. |date=December 1988 |title=What are the psychiatric manifestations of vitamin B12 deficiency? |journal=Journal of the American Geriatrics Society |volume=36 |issue=12 |pages=1105–1112 |doi=10.1111/j.1532-5415.1988.tb04397.x |issn=0002-8614 |pmid=3057051}}</ref><ref name=":5" /> Other specific causes of anemia may have signs and/or complications such as, [[jaundice]] with the rapid break down of [[red blood cell]]s as with [[hemolytic anemia]], bone abnormalities with [[Beta thalassemia|thalassemia major]], or leg [[ulcer]]s as seen in [[sickle cell disease]].

In severe anemia, there may be signs of a [[hyperdynamic circulation]]: [[tachycardia]] (a fast heart rate), [[bounding pulse]], [[Functional murmur|flow murmurs]], and [[cardiac]] [[ventricular hypertrophy]] (enlargement). There may be signs of [[heart failure]].
[[Pica (disorder)|Pica]], the consumption of non-food items such as ice, paper, wax, grass, hair or dirt, may be a symptom of iron deficiency;<ref name=":6">{{cite web |title=Mental Health and Pica |url=https://www.webmd.com/mental-health/mental-health-pica |access-date=2022-04-26 |website=WebMD |language=en}}</ref> although it occurs often in those who have normal levels of [[hemoglobin]]. Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced academic performance in children of school age. [[Restless legs syndrome]] is more common in people with [[iron-deficiency anemia]] than in the general population.<ref>{{cite journal |last1=Allen |first1=Richard P. |last2=Auerbach |first2=Sarah |last3=Bahrain |first3=Huzefa |last4=Auerbach |first4=Michael |last5=Earley |first5=Christopher J. |title=The prevalence and impact of restless legs syndrome on patients with iron deficiency anemia |journal=American Journal of Hematology |date=April 2013 |volume=88 |issue=4 |pages=261–264 |doi=10.1002/ajh.23397 |pmid=23494945 |s2cid=35587006 |doi-access=free }}</ref>

==Causes==
[[File:Modified sickle cell 01.jpg|thumb|Figure shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin.<ref>{{cite web |title=Sickle Cell Disease |url=https://www.nhlbi.nih.gov/health/sickle-cell-disease |website=National Heart, Lung, and Blood Institute |date=22 July 2022 }}</ref>]]
The causes of anemia may be classified as impaired red [[Erythropoiesis|blood cell (RBC) production]], increased [[Hemolysis|RBC destruction]] (hemolytic anemia), blood loss, and fluid overload ([[hypervolemia]]). Several of these may interplay to cause anemia. The most common cause of anemia is blood loss, but this usually does not cause any lasting symptoms unless a relatively impaired RBC production develops, in turn, most commonly by [[iron deficiency]].<ref name=nhlbi/>

===Impaired production===
* Disturbance of proliferation and differentiation of stem cells
** [[Pure red cell aplasia]]<ref name=Robbins12-1>Table 12-1 in: {{cite book | last1 = Mitchell | first1 = Richard Sheppard | last2 = Kumar | first2 = Vinay | last3 = Abbas | first3 =  Abul K. | last4 = Fausto | first4 = Nelson | title = Robbins Basic Pathology | publisher = Saunders | location=Philadelphia |year= 2007|isbn=978-1-4160-2973-1 | edition = 8th}}</ref>
** [[Aplastic anemia]]<ref name=Robbins12-1/> affects all kinds of [[blood cell]]s. [[Fanconi anemia]] is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities.
** Anemia of [[kidney failure]]<ref name=Robbins12-1/> due to insufficient production of the [[hormone]] [[erythropoietin]]
** Anemia of [[endocrine disease]]<ref>{{cite book|last1=Gregg|first1=XT|last2=Prchal|first2=JT|title=Williams Hermatology|date=2007|publisher=McGraw-Hill|chapter=Anemia of Endocrine Disorders}}</ref>
* Disturbance of proliferation and maturation of [[erythroblast]]s
** [[Pernicious anemia]]<ref name=Robbins12-1/> is a form of [[megaloblastic anemia]] due to [[vitamin B12 deficiency|vitamin B<sub>12</sub> deficiency]] dependent on impaired absorption of [[Vitamin B12|vitamin B<sub>12</sub>]]. Lack of dietary B<sub>12</sub> causes non-pernicious megaloblastic anemia.
** Anemia of [[folic acid deficiency|folate deficiency]],<ref name=Robbins12-1/> as with vitamin B<sub>12</sub>, causes [[megaloblastic anemia]]
** [[Anemia of prematurity]], by diminished erythropoietin response to declining [[hematocrit]] levels, combined with blood loss from laboratory testing, generally occurs in premature infants at two to six weeks of age.
** Iron-deficiency anemia, resulting in deficient heme synthesis<ref name=Robbins12-1/>
** [[Thalassemia]]s, causing deficient globin synthesis<ref name=Robbins12-1/>
** [[Congenital dyserythropoietic anemia]]s, causing ineffective erythropoiesis
** Anemia of kidney failure<ref name=Robbins12-1/> (also causing stem cell dysfunction)
* Other mechanisms of impaired RBC production
** [[Myelophthisic anemia]]<ref name=Robbins12-1/> or [[myelophthisis]] is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors, fibrosis, or granulomas.
** [[Myelodysplastic syndrome]]<ref name=Robbins12-1/>
** anemia of [[chronic inflammation]]<ref name=Robbins12-1/>
** Leukoerythroblastic anemia is caused by space-occupying lesions in the [[bone marrow]] that prevent normal production of blood cells.<ref>{{cite web|url=https://www.dictionary.com/browse/leukoerythroblastosis|title=the definition of leukoerythroblastosis|website=www.dictionary.com|language=en|access-date=2018-12-02|archive-date=2 December 2018|archive-url=https://web.archive.org/web/20181202070610/https://www.dictionary.com/browse/leukoerythroblastosis}}</ref>

===Increased destruction===
{{Further|Hemolytic anemia}}
Anemias of increased [[hemolysis|red blood cell destruction]] are generally classified as [[hemolytic anemia]]s. These types generally feature [[jaundice]], and elevated levels of [[lactate dehydrogenase]].<ref>{{cite web |url= https://www.lecturio.com/concepts/anemia-overview/ | title= Overview of hemolytic anemias in children | last1= Despotovic | first1= J | last2= Mahoney | first2= D | last3= Armsby | first3= C | publisher= UpToDate
|date= 2021 |website= The Lecturio Medical Concept Library |access-date= 28 June 2021}}</ref><ref>{{cite book|last=Capriotti, Theresa|title=Pathophysiology: introductory concepts and clinical perspectives|others=Frizzell, Joan Parker|year=2016|isbn=978-0-8036-1571-7|location=Philadelphia|oclc=900626405}}</ref>
* Intrinsic (intracorpuscular) abnormalities<ref name=Robbins12-1/> cause premature destruction. All of these, except [[paroxysmal nocturnal hemoglobinuria]], are hereditary [[genetic disorder]]s.<ref name=Robbins432>{{cite book | last1 = Mitchell | first1 = Richard Sheppard | last2 = Kumar | first2 = Vinay | last3 = Abbas | first3 =  Abul K. | last4 = Fausto | first4 = Nelson | title = Robbins Basic Pathology | publisher = Saunders | location=Philadelphia |page= 432 |isbn=978-1-4160-2973-1 | edition = 8th | year = 2007 }}</ref>
** [[Hereditary spherocytosis]]<ref name=Robbins12-1/> is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the [[spleen]].
** [[Hereditary elliptocytosis]]<ref name=Robbins12-1/> is another defect in membrane skeleton proteins.
** [[Abetalipoproteinemia]],<ref name=Robbins12-1/> causing defects in membrane lipids
** Enzyme deficiencies
*** [[Pyruvate kinase]] and [[hexokinase]] deficiencies,<ref name=Robbins12-1/> causing defect [[glycolysis]]
*** [[Glucose-6-phosphate dehydrogenase deficiency]] and [[glutathione synthetase]] deficiency,<ref name=Robbins12-1/> causing increased [[oxidative stress]]
** [[Hemoglobinopathies]]
*** [[Sickle cell anemia]]<ref name=Robbins12-1/>
*** Hemoglobinopathies causing unstable hemoglobins<ref name=Robbins12-1/>
** [[Paroxysmal nocturnal hemoglobinuria]]<ref name=Robbins12-1/>
* Extrinsic (extracorpuscular) abnormalities
** [[Antibody]]-mediated
*** [[Warm autoimmune hemolytic anemia]] is caused by an autoimmune attack against red blood cells, primarily by IgG. It is the most common of the [[Autoimmune diseases|autoimmune]] [[Hemolysis|hemolytic]] diseases.<ref name="isbn0-7216-0187-1">{{cite book | last1 = Cotran | first1 = Ramzi S. | last2 = Kumar | first2 = Vinay | last3 = Fausto | first3 = Nelson | last4 = Robbins | first4 = Stanley L. | last5 = Abbas | first5 = Abul K. | title=Robbins and Cotran pathologic basis of disease |publisher=Elsevier Saunders |location=St. Louis, Mo |year=2005 |page=637 |isbn=978-0-7216-0187-8 }}</ref> It can be [[idiopathic]], that is, without any known cause, drug-associated or secondary to another disease such as [[systemic lupus erythematosus]], or a malignancy, such as [[chronic lymphocytic leukemia]].<ref name=Jenkins>[http://www.trcc.org/blood/10b_autoimmune.pdf "Autoimmune Hemolytic Anemia (AIHA)"] By J.L. Jenkins. The Regional Cancer Center. 2001 {{webarchive |url=https://web.archive.org/web/20091007084816/http://www.trcc.org/blood/10b_autoimmune.pdf |date=October 7, 2009 }}</ref>
*** [[Cold agglutinin hemolytic anemia]] is primarily mediated by IgM. It can be idiopathic<ref name="pmid17891600">{{cite journal | vauthors = Berentsen S, Beiske K, Tjønnfjord GE | title = Primary chronic cold agglutinin disease: an update on pathogenesis, clinical features and therapy | journal = Hematology | volume = 12 | issue = 5 | pages = 361–370 | date = October 2007 | pmid = 17891600 | pmc = 2409172 | doi = 10.1080/10245330701445392 }}</ref> or result from an underlying condition.
*** [[Rh disease]],<ref name=Robbins12-1/> one of the causes of [[hemolytic disease of the newborn]]
*** [[Transfusion reaction]] to [[blood transfusion]]s<ref name=Robbins12-1/>
** Mechanical trauma to red blood cells
*** [[Microangiopathic hemolytic anemia]]s, including [[thrombotic thrombocytopenic purpura]] and [[disseminated intravascular coagulation]]<ref name=Robbins12-1/>
*** Infections, including [[malaria]]<ref name=Robbins12-1/>
*** [[Heart surgery]]{{medical citation needed|date=January 2016}}
*** [[Haemodialysis]]{{medical citation needed|date=January 2016}}
** Parasitic
*** ''[[Trypanosoma congolense]]'' alters the surfaces of RBCs of its host and this may explain ''T. c.'' induced anemia<ref name="Stijlemans-et-al-2007">{{cite journal |last1=Stijlemans |first1=Benoît |last2=Guilliams |first2=Martin |last3=Raes |first3=Geert |last4=Beschin |first4=Alain |last5=Magez |first5=Stefan |last6=De Baetselier |first6=Patrick |title=African trypanosomosis: From immune escape and immunopathology to immune intervention |journal=Veterinary Parasitology |date=August 2007 |volume=148 |issue=1 |pages=3–13 |doi=10.1016/j.vetpar.2007.05.005 |pmid=17560035 }}</ref>

===Blood loss===
* [[Anemia of prematurity]], from frequent blood sampling for laboratory testing, combined with insufficient RBC production
* [[Physical trauma|Trauma]]<ref name=Robbins12-1/> or [[surgery]], causing acute blood loss
* Gastrointestinal tract lesions,<ref name=Robbins12-1/> causing either acute bleeds (e.g. variceal lesions, [[peptic ulcers]], [[hemorrhoid]]s<ref>{{cite web | url=https://lacolon.com/article/hemorrhoids-iron-deficiency-can-hemorrhoids-cause-iron-deficiency-anemia | title=Do Hemorrhoids Cause Iron Deficiency Anemia? | date=26 June 2018 }}</ref>) or chronic blood loss (e.g. [[angiodysplasia]])
* Gynecologic disturbances,<ref name=Robbins12-1/> also generally causing chronic blood loss
* From [[menstruation]], mostly among young women or older women who have [[fibroma|fibroids]]
* Many types of cancers, including colorectal [[cancer]] and cancer of the [[urinary bladder]], may cause acute or chronic blood loss, especially at advanced stages
* Infection by intestinal [[nematodes]] feeding on blood, such as [[hookworm]]s<ref>{{cite journal | vauthors = Brooker S, Hotez PJ, Bundy DA | title = Hookworm-related anaemia among pregnant women: a systematic review | journal = PLOS Neglected Tropical Diseases | volume = 2 | issue = 9 | article-number = e291 | date = September 2008 | pmid = 18820740 | pmc = 2553481 | doi = 10.1371/journal.pntd.0000291 | doi-access = free }}</ref> and the whipworm ''[[Trichuris trichiura]]'' <ref>{{cite journal | vauthors = Gyorkos TW, Gilbert NL, Larocque R, Casapía M | title = Trichuris and hookworm infections associated with anaemia during pregnancy | journal = Tropical Medicine & International Health | volume = 16 | issue = 4 | pages = 531–537 | date = April 2011 | pmid = 21281406 | doi = 10.1111/j.1365-3156.2011.02727.x | s2cid = 205391965 | doi-access =  }}</ref>
* [[Iatrogenic anemia]], blood loss from repeated blood draws and medical procedures.<ref name="Whitehead2019">{{cite journal |last1=Whitehead |first1=Nedra S. |last2=Williams |first2=Laurina O. |last3=Meleth |first3=Sreelatha |last4=Kennedy |first4=Sara M. |last5=Ubaka-Blackmoore |first5=Nneka |last6=Geaghan |first6=Sharon M. |last7=Nichols |first7=James H. |last8=Carroll |first8=Patrick |last9=McEvoy |first9=Michael T. |last10=Gayken |first10=Julie |last11=Ernst |first11=Dennis J. |last12=Litwin |first12=Christine |last13=Epner |first13=Paul |last14=Taylor |first14=Jennifer |last15=Graber |first15=Mark L. |title=Interventions to prevent iatrogenic anemia: a Laboratory Medicine Best Practices systematic review |journal=Critical Care |date=December 2019 |volume=23 |issue=1 |page=278 |doi=10.1186/s13054-019-2511-9 |pmid=31399052 |pmc=6688222 |doi-access=free }}</ref><ref name="MartinScantling2015">{{cite journal |last1=Martin |first1=Niels D. |last2=Scantling |first2=Dane |title=Hospital-Acquired Anemia: A Contemporary Review of Etiologies and Prevention Strategies |journal=Journal of Infusion Nursing |date=September 2015 |volume=38 |issue=5 |pages=330–338 |doi=10.1097/NAN.0000000000000121 |pmid=26339939 |s2cid=30859103 }}</ref>

The roots of the words ''anemia'' and ''ischemia'' both refer to the basic idea of "lack of blood", but anemia and [[ischemia]] are not the same thing in modern medical terminology. The word ''anemia'' used alone implies [[Systemic effect|widespread]] ''effects'' from blood that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In contrast, the word ''ischemia'' refers solely to the lack of blood (poor [[perfusion]]). Thus, ischemia in a body part can cause localized anemic effects within those tissues.<ref>{{cite journal |last1=Bellotto |first1=Fabio |last2=Cati |first2=Arianna |title=Anemia ed ischemia miocardica: relazioni ed interferenze |trans-title=Anemia and myocardial ischemia: relationships and interferences |language=it |journal=Recenti Progressi in Medicina |date=March 2006 |volume=97 |issue=3 |pages=153–164 |doi=10.1701/121.1312 |pmid=16700423 }}</ref>

===Fluid overload===
Fluid overload (hypervolemia) causes decreased hemoglobin concentration and apparent anemia:<ref>{{cite journal |last1=Hung |first1=Szu-Chun |last2=Kuo |first2=Ko-Lin |last3=Peng |first3=Ching-Hsiu |last4=Wu |first4=Che-Hsiung |last5=Wang |first5=Yi-Chun |last6=Tarng |first6=Der-Cherng |title=Association of Fluid Retention With Anemia and Clinical Outcomes Among Patients With Chronic Kidney Disease |journal=Journal of the American Heart Association |year=2015 |volume=4 |issue=1 |article-number=e001480 |doi=10.1161/JAHA.114.001480 |pmc=4330071 |pmid=25559015}}</ref>
* General causes of hypervolemia include excessive sodium or fluid intake, sodium or water retention, and fluid shifts into the intravascular space.<ref name=Hagerstwon>{{cite book | chapter = Fluid imbalances|title=Portable Fluids and Electrolytes (Portable Series) |publisher=Lippincott Williams & Wilkins|location=Hagerstwon, MD |year=2007 |page= 62 |isbn=978-1-58255-678-9 }}</ref>
* From the sixth week of pregnancy, hormonal changes cause an increase in the mother's blood volume due to an increase in plasma.<ref>{{cite web|url=http://www.isbtweb.org/working-parties/clinical-transfusion/8-obstetric-anaemia/|title=ISBT: 8. Obstetric anaemia|website=www.isbtweb.org|language=en|access-date=2018-05-22}}</ref>

===Intestinal inflammation===
Certain gastrointestinal disorders can cause anemia. The mechanisms involved are multifactorial and not limited to malabsorption but mainly related to chronic intestinal inflammation, which causes dysregulation of [[hepcidin]] that leads to decreased access of iron to the circulation.<ref name=VermaCherayil2017>{{cite journal | vauthors = Verma S, Cherayil BJ | title = Iron and inflammation – the gut reaction | journal = Metallomics | volume = 9 | issue = 2 | pages = 101–111 | date = February 2017 | pmid = 28067386 | pmc = 5321802 | doi = 10.1039/c6mt00282j | type = Review }}</ref><ref name="GuagnozziLucendo2014">{{cite journal | vauthors = Guagnozzi D, Lucendo AJ | title = Anemia in inflammatory bowel disease: a neglected issue with relevant effects | journal = World Journal of Gastroenterology | volume = 20 | issue = 13 | pages = 3542–3551 | date = April 2014 | pmid = 24707137 | pmc = 3974521 | doi = 10.3748/wjg.v20.i13.3542 | type = Review | doi-access = free }}</ref><ref name=LefflerGreen2015 />
* ''[[Helicobacter pylori]]'' infection.<ref name="SteinConnor2016">{{cite journal | vauthors = Stein J, Connor S, Virgin G, Ong DE, Pereyra L | title = Anemia and iron deficiency in gastrointestinal and liver conditions | journal = World Journal of Gastroenterology | volume = 22 | issue = 35 | pages = 7908–7925 | date = September 2016 | pmid = 27672287 | pmc = 5028806 | doi = 10.3748/wjg.v22.i35.7908 | type = Review | doi-access = free }}</ref>
* Gluten-related disorders: untreated [[celiac disease]]<ref name=LefflerGreen2015>{{cite journal |last1=Leffler |first1=Daniel A. |last2=Green |first2=Peter H. R. |last3=Fasano |first3=Alessio |title=Extraintestinal manifestations of coeliac disease |journal=Nature Reviews Gastroenterology & Hepatology |date=October 2015 |volume=12 |issue=10 |pages=561–571 |doi=10.1038/nrgastro.2015.131 |pmid=26260366 |s2cid=15561525 }}</ref><ref name=SteinConnor2016 /> and [[non-celiac gluten sensitivity]].<ref name="CatassiBai2013">{{cite journal | vauthors = Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A, Castillejo G, Ciacci C, Cristofori F, Dolinsek J, Francavilla R, Elli L, Green P, Holtmeier W, Koehler P, Koletzko S, Meinhold C, Sanders D, Schumann M, Schuppan D, Ullrich R, Vécsei A, Volta U, Zevallos V, Sapone A, Fasano A | title = Non-Celiac Gluten sensitivity: the new frontier of gluten related disorders | journal = Nutrients | volume = 5 | issue = 10 | pages = 3839–3853 | date = September 2013 | pmid = 24077239 | pmc = 3820047 | doi = 10.3390/nu5103839 | type = Review | doi-access = free }}</ref> Anemia can be the only manifestation of celiac disease, in absence of gastrointestinal or any other symptoms.<ref name=NIHConsensus2004>{{cite journal |last1=James |first1=Stephen P. |title=National Institutes of Health Consensus Development Conference statement on Celiac Disease, June 28–30, 2004 |journal=Gastroenterology |date=April 2005 |volume=128 |issue=4 |pages=S1–S9 |doi=10.1053/j.gastro.2005.02.007 |pmid=15825115 }}</ref>
* [[Inflammatory bowel disease]].<ref name="Lomer2011">{{cite journal | vauthors = Lomer MC | title = Dietary and nutritional considerations for inflammatory bowel disease | journal = The Proceedings of the Nutrition Society | volume = 70 | issue = 3 | pages = 329–335 | date = August 2011 | pmid = 21450124 | doi = 10.1017/S0029665111000097 | type = Review | doi-access = free }}</ref><ref name="Gerasimidis2011">{{cite journal | vauthors = Gerasimidis K, McGrogan P, Edwards CA | title = The aetiology and impact of malnutrition in paediatric inflammatory bowel disease | journal = Journal of Human Nutrition and Dietetics | volume = 24 | issue = 4 | pages = 313–326 | date = August 2011 | pmid = 21564345 | doi = 10.1111/j.1365-277X.2011.01171.x | type = Review | doi-access = free }}</ref>

==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 several definitions of anemia; [[review article|reviews]] provide a 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 remain 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.{{citation needed|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 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 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 it is rarely used as it 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 the 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}}
{{tree chart/start}}
{{tree chart| | | | | | | | | A01 | | | | | | |A01=Anemia}}
{{tree chart| | | | | | |,|-|-|^|-|-|.| | | | }}
{{tree 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.}}
{{tree chart| | |,|-|-|-|+|-|-|-|.| | | | | }}
{{tree 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**.}}
{{tree chart| | |!|,|-|-|+|-|-|-|.}}
{{tree chart| | F01 | | F02 | | F03 |F01=[[Macrocytic anemia]] (MCV>100)|F02=[[Normocytic anemia]] (80<MCV<100)|F03=[[Microcytic anemia]] (MCV<80)}}
{{tree 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:
{{tree chart/start}}
{{tree chart| | | | | | | | | | | | A01 | | | | | | | | | A01=Anemia}}
{{tree chart| | | | |,|-|-|-|-|-|-|-|+|-|-|-|-|-|-|-|.| }}
{{tree chart| | | | B01 | | | | | | B02 | | | | | | B03 | B01 = [[Macrocytic anemia]] (MCV>100) | B02 = [[Normocytic anemia]] (MCV 80–100) | B03 = [[Microcytic anemia]] (MCV<80)}}
{{tree chart| | | | | | | | |,|-|-|-|^|-|-|-|.| | | | | }}
{{tree chart| | | | | | | | C01 | | | | | | C02 | | | | |C01=High [[reticulocyte]] count|C02=Low [[reticulocyte]] count}}
{{tree 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 |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 | page = 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, with excessive alcohol use.
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 transfusions 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=978-0-7020-3625-5 |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=978-1-4160-2246-6 |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=978-0-323-37822-2 |page=1131.e2 |url=https://books.google.com/books?id=bbLSCQAAQBAJ&pg=PA1131-IA2 |language=en}}</ref>

==Treatment==
The global market for anemia treatments is estimated at more than USD 23 billion per year and is growing rapidly because of the rising prevalence and awareness of anemia. The types of anemia treated with drugs are iron-deficiency anemia, [[thalassemia]], aplastic anemia, [[hemolytic anemia]], [[sickle cell disease|sickle cell anemia]], and pernicious anemia, the most important of them being deficiency and sickle cell anemia with together 60% of market share because of highest prevalence as well as higher treatment costs compared with other types.<ref name=2019MarketStudy/> Treatment for anemia depends on cause and severity. Vitamin supplements given orally ([[folic acid]] or vitamin B<sub>12</sub>) or intramuscularly ([[Cyanocobalamin|vitamin B<sub>12</sub>]]) will replace specific deficiencies.<ref name=EBM2013 />

Apart from that, iron supplements, antibiotics, immunosuppressants, bone marrow stimulants, corticosteroids, gene therapy, and iron chelating agents are forms of anemia treatment drugs, with immunosuppressants and corticosteroids accounting for 58% of the market share. A paradigm shift towards gene therapy and monoclonal antibody therapies is observed.<ref name=2019MarketStudy/>

===Oral iron===

Nutritional iron deficiency is common in developing nations. An estimated two-thirds of children and women of childbearing age in most developing nations are estimated to have iron deficiency without anemia, with one-third of them having an iron deficiency with anemia.<ref name="pmid8901803">{{cite journal | vauthors = West CE | title = Strategies to control nutritional anemia | journal = The American Journal of Clinical Nutrition | volume = 64 | issue = 5 | pages = 789–790 | date = November 1996 | pmid = 8901803 | doi =  10.1093/ajcn/64.5.789| doi-access = free }}</ref> Iron deficiency due to inadequate dietary iron intake is rare in men and postmenopausal women. The diagnosis of iron deficiency mandates a search for potential sources of blood loss, such as gastrointestinal bleeding from ulcers or colon cancer.{{citation needed|date=November 2021}}

Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with [[Iron(II) sulfate|ferrous sulfate]], [[ferrous fumarate]], or [[ferrous gluconate]]. Daily iron supplements are effective in reducing anemia in women of childbearing age.<ref>{{cite journal |last1=Low |first1=MS |last2=Speedy |first2=J |last3=Styles |first3=CE |last4=De-Regil |first4=LM |last5=Pasricha |first5=SR |title=Daily iron supplementation for improving anaemia, iron status and health in menstruating women. |journal=The Cochrane Database of Systematic Reviews |date=18 April 2016 |volume=2016 |issue=4 |article-number=CD009747 |doi=10.1002/14651858.CD009747.pub2 |pmid=27087396|pmc=10182438 }}</ref> When taking iron supplements, stomach upset or darkening of the feces are commonly experienced. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. [[Vitamin C]] aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.<ref>{{cite journal | vauthors = Sezer S, Ozdemir FN, Yakupoglu U, Arat Z, Turan M, Haberal M | title = Intravenous ascorbic acid administration for erythropoietin-hyporesponsive anemia in iron loaded hemodialysis patients | journal = Artificial Organs | volume = 26 | issue = 4 | pages = 366–370 | date = April 2002 | pmid = 11952508 | doi = 10.1046/j.1525-1594.2002.06888.x }}</ref>

In the anemia of chronic kidney disease, [[recombinant protein|recombinant]] [[erythropoietin]] or [[epoetin alfa]] is recommended to stimulate RBC production, and if iron deficiency and inflammation are also present, concurrent [[parenteral iron]] is also recommended.<ref>{{cite web |url=http://guidance.nice.org.uk/CG114/Guidance/pdf/English |title=Anaemia management in people with chronic kidney disease &#124; Guidance and guidelines &#124; NICE |date=9 February 2011 |access-date=2013-08-09 |url-status = live|archive-url=https://web.archive.org/web/20130624124919/http://guidance.nice.org.uk/CG114/Guidance/pdf/English |archive-date=2013-06-24  }}</ref>

===Injectable iron===
In cases where oral iron has either proven ineffective, would be too slow (for example, pre-operatively), or where absorption is impeded (for example, in cases of inflammation), [[parenteral iron]] preparations can be used. Parenteral iron can improve iron stores rapidly and is also effective for treating people with postpartum haemorrhage, inflammatory bowel disease, and chronic heart failure.<ref name="Ng Keeler Mishra et al 2019">{{cite journal |last1=Ng |first1=Oliver |last2=Keeler |first2=Barrie D |last3=Mishra |first3=Amitabh |last4=Simpson |first4=J A |last5=Neal |first5=Keith |last6=Al-Hassi |first6=Hafid Omar |last7=Brookes |first7=Matthew J |last8=Acheson |first8=Austin G |date=7 December 2019 |title=Iron therapy for preoperative anaemia |journal=Cochrane Database of Systematic Reviews |volume=2019 |issue=12 |article-number=CD011588 |doi=10.1002/14651858.CD011588.pub3 |pmc=6899074 |pmid=31811820}}</ref> The body can absorb up to 6&nbsp;mg iron daily from the gastrointestinal tract. In many cases, the patient has a deficit of over 1,000&nbsp;mg of iron, which would require several months to replace. This can be given concurrently with [[erythropoietin]] to ensure sufficient iron for increased rates of [[erythropoiesis]].<ref>{{cite journal | vauthors = Auerbach M, Ballard H | title = Clinical use of intravenous iron: administration, efficacy, and safety | journal = Hematology. American Society of Hematology. Education Program | volume = 2010 | pages = 338–347 | date = 2010 | pmid = 21239816 | doi = 10.1182/asheducation-2010.1.338 | doi-access = free }}</ref>

===Blood transfusions===
Blood transfusions in those without symptoms is not recommended until the hemoglobin is below 60 to 80&nbsp;g/L (6 to 8&nbsp;g/dL).<ref name=EBM2013/> In those with [[coronary artery disease]] who are not actively bleeding transfusions are only recommended when the hemoglobin is below 70 to 80g/L (7 to 8 g/dL).<ref name=Amir2013/> Transfusing earlier does not improve survival.<ref name=Kan2013>{{cite journal | vauthors = Kansagara D, Dyer E, Englander H, Fu R, Freeman M, Kagen D | title = Treatment of anemia in patients with heart disease: a systematic review | journal = Annals of Internal Medicine | volume = 159 | issue = 11 | pages = 746–757 | date = December 2013 | pmid = 24297191 | doi = 10.7326/0003-4819-159-11-201312030-00007 | doi-access =  | s2cid = 27062899 }}</ref> Transfusions otherwise should only be undertaken in cases of cardiovascular instability.<ref>{{cite journal | vauthors = Goddard AF, James MW, McIntyre AS, Scott BB | title = Guidelines for the management of iron deficiency anaemia | journal = Gut | volume = 60 | issue = 10 | pages = 1309–1316 | date = October 2011 | pmid = 21561874 | doi = 10.1136/gut.2010.228874 | others = British Society of Gastroenterology | doi-access = free }}</ref>

A 2012 review concluded that when considering blood transfusions for anaemia in people with advanced cancer who have fatigue and breathlessness (not related to cancer treatment or haemorrhage), consideration should be given to whether there are alternative strategies that can be tried before a blood transfusion.<ref>{{cite journal |last1=Preston |first1=Nancy J |last2=Hurlow |first2=Adam |last3=Brine |first3=Jennifer |last4=Bennett |first4=Michael I |title=Blood transfusions for anaemia in patients with advanced cancer |journal=Cochrane Database of Systematic Reviews |date=15 February 2012 |volume=2012 |issue=2 |article-number=CD009007 |doi=10.1002/14651858.CD009007.pub2 |pmid=22336857 |pmc=7388847 }}</ref>

=== Vitamin B<sub>12</sub> intramuscular injections ===
In many cases, vitamin B<sub>12</sub> is used by [[intramuscular injection]] in severe cases or cases of malabsorption of dietary-B<sub>12</sub>. Pernicious anemia caused by loss of intrinsic factor cannot be prevented.<ref>{{cite web |title=Pernicious anemia: MedlinePlus Medical Encyclopedia |url=https://medlineplus.gov/ency/article/000569.htm |access-date=2022-08-04 |website=medlineplus.gov |language=en}}</ref> If there are other, reversible causes of low vitamin B<sub>12</sub> levels, the cause must be treated.<ref>{{cite book |last=Hankey |first=Graeme J. |title=Clinical neurology |date=2008 |publisher=Manson |others=Joanna M. Wardlaw |isbn=978-1-84076-518-2 |location=London |oclc=503441695}}</ref>

Vitamin B<sub>12</sub> deficiency anemia is usually easily treated by providing the necessary level of vitamin B<sub>12</sub> supplementation.<ref name=":1">{{cite journal |last1=Langan |first1=Robert C. |last2=Goodbred |first2=Andrew J. |date=2017-09-15 |title=Vitamin B12 Deficiency: Recognition and Management |url=https://www.aafp.org/pubs/afp/issues/2017/0915/p384.html |journal=American Family Physician |language=en-US |volume=96 |issue=6 |pages=384–389|pmid=28925645 }}</ref> The injections are quick-acting, and symptoms usually go away within one to two weeks.<ref name=":1" /> As the condition improves, doses are reduced to weeks and then can be given monthly. Intramuscular therapy leads to more rapid improvement and should be considered in patients with severe deficiency or severe [[Neurological disorder|neurologic]] symptoms.<ref name=":1" /> Treatment should begin rapidly for severe neurological symptoms, as some changes can become permanent.<ref name=":5">{{cite web |date=2017-09-14 |title=Pernicious Anemia Clinical Presentation: History, Physical Examination |url=http://emedicine.medscape.com/article/204930-clinical#b3 |access-date=2022-08-04 |website= |archive-url=https://web.archive.org/web/20170914062810/http://emedicine.medscape.com/article/204930-clinical#b3 |archive-date=14 September 2017 }}</ref> In some individuals lifelong treatment may be needed.<ref name=":5" />

===Erythropoiesis-stimulating agents===
The objective for the administration of an [[erythropoiesis-stimulating agent]] (ESA) is to maintain hemoglobin at the lowest level that both minimizes transfusions and meets the person's needs.<ref name="2007anemiaESA">{{cite journal | vauthors = Aapro MS, Link H | title = September 2007 update on EORTC guidelines and anemia management with erythropoiesis-stimulating agents | journal = The Oncologist | volume = 13 Suppl 3 | issue = Supplement 3 | pages = 33–36 | year = 2008 | pmid = 18458123 | doi = 10.1634/theoncologist.13-S3-33 }}</ref> They should not be used for mild or moderate anemia.<ref name=Kan2013/> They are not recommended in people with [[chronic kidney disease]] unless hemoglobin levels are less than 10 g/dL or they have symptoms of anemia. Their use should be along with parenteral iron.<ref name="2007anemiaESA"/><ref name="ASNfive">{{Citation |author1 = American Society of Nephrology |author1-link = American Society of Nephrology |title = Five Things Physicians and Patients Should Question |publisher = [[American Society of Nephrology]] |work = Choosing Wisely: an initiative of the [[ABIM Foundation]] |url = http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Neph.pdf |access-date = August 17, 2012 |url-status = live|archive-url = https://web.archive.org/web/20120416220524/http://choosingwisely.org/wp-content/uploads/2012/04/5things_12_factsheet_Amer_Soc_Neph.pdf |archive-date = April 16, 2012 }}</ref> The 2020 Cochrane Anaesthesia Review Group review of erythropoietin (EPO) plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery <ref>{{cite journal | vauthors = Kaufner L, Heymann C | title = Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery | journal = Cochrane Database of Systematic Reviews | year = 2020 | volume = 2020 | issue = 8 | article-number = CD012451 | doi = 10.1002/14651858.CD012451.pub2 | pmid = 32790892 | pmc = 8095002 }}</ref> demonstrated that patients were much less likely to require red cell transfusion, and in those transfused, the volumes were unchanged (mean difference -0.09, 95% CI -0.23 to 0.05). Pre-operative hemoglobin concentration was increased in those receiving 'high dose' EPO, but not 'low dose'.{{citation needed|date=November 2021}}

===Hyperbaric oxygen===
Treatment of exceptional blood loss (anemia) is recognized as an indication for [[hyperbaric oxygen]] (HBO) by the [[Undersea and Hyperbaric Medical Society]].<ref name=uhms>{{cite web|url=http://www.uhms.org/ResourceLibrary/Indications/ExceptionalBloodLossAnemia/tabid/277/Default.aspx |title=Exceptional Blood Loss&nbsp;– Anemia |vauthors=((Undersea and Hyperbaric Medical Society)) |access-date=2008-05-19 |archive-url=https://web.archive.org/web/20080705205816/http://www.uhms.org/ResourceLibrary/Indications/ExceptionalBloodLossAnemia/tabid/277/Default.aspx |archive-date=July 5, 2008 }}</ref><ref>{{cite journal |vauthors=Hart GB, Lennon PA, Strauss MB |title=Hyperbaric oxygen in exceptional acute blood-loss anemia |journal=J. Hyperbaric Med |volume=2 |issue=4 |pages=205–210 |year=1987 |url=http://archive.rubicon-foundation.org/4352 |access-date=2008-05-19 |url-status=usurped |archive-url=https://web.archive.org/web/20090116015734/http://archive.rubicon-foundation.org/4352 |archive-date=2009-01-16 }}</ref> The use of HBO is indicated when [[oxygen]] delivery to tissue is not sufficient in patients who cannot be given [[blood transfusion]]s for [[medical]] or [[religious]] reasons. HBO may be used for medical reasons when the threat of [[blood product]] incompatibility or concern for [[Transmission (medicine)|transmissible disease]] are factors.<ref name=uhms/> The beliefs of some religions (ex: [[Jehovah's Witnesses and blood transfusions|Jehovah's Witnesses]]) may require they use the HBO method.<ref name=uhms/> A 2005 review of the use of HBO in severe anemia found that all publications reported positive results.<ref>{{cite journal | vauthors = Van Meter KW | title = A systematic review of the application of hyperbaric oxygen in the treatment of severe anemia: an evidence-based approach | journal = Undersea & Hyperbaric Medicine | volume = 32 | issue = 1 | pages = 61–83 | year = 2005 | pmid = 15796315 | url = http://archive.rubicon-foundation.org/4038 | archive-url = https://web.archive.org/web/20090116014923/http://archive.rubicon-foundation.org/4038 |url-status = usurped| archive-date = 2009-01-16 }}</ref>

=== Preoperative anemia ===
An estimated 30% of adults who require non-cardiac surgery have anemia.<ref name="Kaufner von Heymann Henkelmann et al 2020">{{cite journal |last1=Kaufner |first1=Lutz |last2=von Heymann |first2=Christian |last3=Henkelmann |first3=Anne |last4=Pace |first4=Nathan L |last5=Weibel |first5=Stephanie |last6=Kranke |first6=Peter |last7=Meerpohl |first7=Joerg J |last8=Gill |first8=Ravi |title=Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery |journal=Cochrane Database of Systematic Reviews |date=13 August 2020 |volume=2020 |issue=8 |article-number=CD012451 |doi=10.1002/14651858.CD012451.pub2 |pmid=32790892 |pmc=8095002 }}</ref> To determine an appropriate preoperative treatment, it is suggested that the cause of anemia be first determined.<ref>{{cite journal |last1=Kotzé |first1=Alwyn |last2=Harris |first2=Andrea |last3=Baker |first3=Charles |last4=Iqbal |first4=Tariq |last5=Lavies |first5=Nick |last6=Richards |first6=Toby |last7=Ryan |first7=Kate |last8=Taylor |first8=Craig |last9=Thomas |first9=Dafydd |title=British Committee for Standards in Haematology Guidelines on the Identification and Management of Pre-Operative Anaemia |journal=British Journal of Haematology |date=November 2015 |volume=171 |issue=3 |pages=322–331 |doi=10.1111/bjh.13623 |pmid=26343392 |s2cid=37709527 |doi-access=free }}</ref> There is moderate level medical evidence that supports a combination of iron supplementation and erythropoietin treatment to help reduce the requirement for red blood cell transfusions after surgery in those who have preoperative anemia.<ref name="Kaufner von Heymann Henkelmann et al 2020"/>

==Epidemiology==
Anemia affects 27% of the world's population, with iron-deficiency anemia accounting for more than 60% of it.<ref name="Science Direct">{{cite journal |title=The Global Burden of Anemia |year=2016 |volume=30 |issue=2 |pages=247–308 |doi=10.1016/j.hoc.2015.11.002 |pmid=27040955 |last1=Kassebaum |first1=Nicholas J. |author2=((GBD 2013 Anemia Collaborators ))|journal=Hematology/Oncology Clinics of North America |doi-access=free }}</ref> A moderate degree of iron-deficiency anemia affected approximately 610&nbsp;million people worldwide or 8.8% of the population.<ref name=LancetEpi2012/> It is somewhat more common in females (9.9%) than males (7.8%).<ref name=LancetEpi2012/> Mild iron-deficiency anemia affects another 375&nbsp;million.<ref name=LancetEpi2012/> Severe anaemia is prevalent globally, and especially in sub-Saharan Africa<ref>{{cite journal |last1=van Hensbroek |first1=MB |last2=Jonker |first2=F |last3=Bates |first3=I |title=Severe acquired anaemia in Africa: new concepts. |journal=British Journal of Haematology |date=September 2011 |volume=154 |issue=6 |pages=690–5 |doi=10.1111/j.1365-2141.2011.08761.x |pmid=21707575|s2cid=205268648 }}</ref> where it is associated with infections including malaria and invasive bacterial infections.<ref>{{cite journal |last1=Abuga |first1=KM |last2=Muriuki |first2=JM |last3=Williams |first3=TN |last4=Atkinson |first4=SH |title=How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children |journal=International Journal of Molecular Sciences |date=22 September 2020 |volume=21 |issue=18 |page=6976 |doi=10.3390/ijms21186976 |pmid=32972031|pmc=7555399 |doi-access=free }}</ref> Globally, the prevalence of anaemia in women aged 15 to 49 years increased from 28.5% in 2012 to 29.9% in 2019 and is projected to reach 32.3% by 2030, missing the [[Sustainable Development Goals|Sustainable Development Goal]] target of a 50 percent reduction by 2030.<ref name=":32">{{Cite book |last1=FAO |url=https://openknowledge.fao.org/handle/20.500.14283/cd1254en |title=The State of Food Security and Nutrition in the World 2024 |last2=IFAD |last3=UNICEF |last4=WFP |last5=WHO |date=2024 |publisher=FAO; IFAD; UNICEF; WFP; WHO |isbn=978-92-5-138882-2 |language=English |doi=10.4060/cd1254en}}</ref>

==History==
{{expand section|date=August 2020}}
Signs of severe anemia in human bones from 4000 years ago have been uncovered in Thailand.<ref>{{cite journal | vauthors = Tayles N | title = Anemia, genetic diseases, and malaria in prehistoric mainland Southeast Asia | journal = American Journal of Physical Anthropology | volume = 101 | issue = 1 | pages = 11–27 | date = September 1996 | pmid = 8876811 | doi = 10.1002/(SICI)1096-8644(199609)101:1<11::AID-AJPA2>3.0.CO;2-G }}</ref>

== Sources ==
{{Free-content attribution
| title = The State of Food Security and Nutrition in the World 2024
| author = FAO, IFAD, UNICEF, WFP and WHO
| publisher = FAO
| documentURL = https://openknowledge.fao.org/handle/20.500.14283/cd1254en
| license = CC BY 4.0
}}

== References ==
{{Reflist}}

== External links ==
{{Wiktionary}}

* [https://www.who.int/news-room/fact-sheets/detail/anaemia WHO fact sheet on anaemia]
* [https://medlineplus.gov/anemia.html Anemia, U.S. National Library of Medicine]

{{Medical condition classification and resources
| DiseasesDB     = 663
 | ICD10          = {{ICD10|D|50||d|50}}-{{ICD10|D|64||d|60}}
 | ICD9           = {{ICD9|280}}-{{ICD9|285}}
 | MedlinePlus    = 000560
 | eMedicineSubj  = med
 | eMedicineTopic = 132
 | eMedicine_mult = {{eMedicine2|emerg|808}} {{eMedicine2|emerg|734}}
 | MeshID         = D000740
}}

{{Diseases of RBCs}}
{{Medicine}}
{{Authority control}}

[[Category:Anemias]]
[[Category:Hematopathology]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia emergency medicine articles ready to translate]]
[[Category:Transfusion medicine]]