Editing Anemia (section)

==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-topics/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 blood cell (RBC) production, increased 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|url-status=dead}}</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 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|hemorrhoids]]<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 type 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 | pages = 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 |pages=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 |pages=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 shift 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>