Editing Hemolysis (section)

==Inside the body==

Hemolysis inside the body can be caused by a large number of medical conditions, including some parasites (''e.g.'', ''[[Plasmodium]]''), some autoimmune disorders (''e.g.'', autoimmune haemolytic anaemia, drug-induced [[hemolytic anemia]], [[atypical hemolytic uremic syndrome]] (aHUS)<ref>{{Cite web|title=Atypical hemolytic-uremic syndrome|url=https://ghr.nlm.nih.gov/condition/atypical-hemolytic-uremic-syndrome|access-date=2020-08-18|website=Genetics Home Reference|language=en}}</ref>),<ref name=":0">{{Cite journal|last=Barcellini|first=Wilma|date=2015|title=Immune Hemolysis: Diagnosis and Treatment Recommendations|journal=Seminars in Hematology|volume=52|issue=4|pages=304–312|doi=10.1053/j.seminhematol.2015.05.001|issn=1532-8686|pmid=26404442}}</ref> some genetic disorders (''e.g.'', [[Sickle-cell disease]] or [[G6PD deficiency]]), or blood with too low a solute concentration ([[Tonicity#Hypotonicity|hypotonic]] to cells).<ref name=":1">{{Cite journal|last1=Beris|first1=Photis|last2=Picard|first2=Véronique|date=2015|title=Non-immune Hemolysis: Diagnostic Considerations|journal=Seminars in Hematology|volume=52|issue=4|pages=287–303|doi=10.1053/j.seminhematol.2015.07.005|issn=1532-8686|pmid=26404441}}</ref>

Hemolysis can lead to [[hemoglobinemia]] due to [[hemoglobin]] released into the [[blood plasma]], which plays a significant role in the [[pathogenesis]] of [[sepsis]]<ref name="Effenberger-Neidnicht 2018 1569–1581">{{Cite journal|last1=Effenberger-Neidnicht|first1=Katharina|last2=Hartmann|first2=Matthias|date=2018|title=Mechanisms of Hemolysis During Sepsis|journal=Inflammation|volume=41|issue=5|pages=1569–1581|doi=10.1007/s10753-018-0810-y|issn=1573-2576|pmid=29956069|s2cid=49526899}}</ref> and can lead to increased risk of infection due to its inhibitory effects on the [[innate immune system]].<ref name="Effenberger-Neidnicht 2018 1569–1581"/>

===Parasitic hemolysis===
Because the feeding process of the ''[[Plasmodium]]'' parasites damages red blood cells, [[malaria]] is sometimes called "parasitic hemolysis" in medical literature.{{citation needed|date=July 2022}}

===HELLP, pre-eclampsia, or eclampsia===
:See [[HELLP syndrome]], [[Pre-eclampsia]], and [[Eclampsia]]

===Hemolytic disease of the newborn===
{{main|Hemolytic disease of the newborn}}
Hemolytic disease of the newborn is an autoimmune disease resulting from the mother's antibodies crossing the placenta to the fetus. This most often occurs when the mother has previously been exposed to blood antigens present on the fetus but foreign to her, through either a blood transfusion or a previous pregnancy.<ref>{{Cite journal|date=2019-02-02|title=Erythrocyte Alloimmunization and Pregnancy: Overview, Background, Pathophysiology|url=https://emedicine.medscape.com/article/273995-overview}}</ref>

===Hemolytic anemia===
{{main|Hemolytic anemia}}
Because ''in vivo'' hemolysis destroys red blood cells, in uncontrolled, chronic or severe cases it can lead to [[hemolytic anemia]].

=== <span id="HemolyticCrisis"></span> Hemolytic crisis===
A hemolytic crisis, or hyperhemolytic crisis, is characterized by an accelerated rate of red blood cell destruction leading to [[anemia]], [[jaundice]], and [[reticulocytosis]].<ref>{{Cite web |url=http://www.innvista.com/health/ailments/anemias/sickle.htm |title=Innvista |access-date=2010-07-04 |archive-url=https://web.archive.org/web/20100624103223/http://www.innvista.com/health/ailments/anemias/sickle.htm |archive-date=2010-06-24 |url-status=dead }}</ref> Hemolytic crises are a major concern with [[sickle-cell disease]] and [[G6PD deficiency]].

===Toxic agent ingestion or poisoning===
''[[Paxillus involutus]]'' ingestion can cause hemolysis.

=== Space hemolysis ===
Spaceflight can cause hemolysis.<ref>{{Cite web |last=Guzman |first=Ana |date=2022-02-24 |title=Scientists Find Increased Red Blood Cell Destruction in Space |url=http://www.nasa.gov/mission_pages/station/research/news/find-increase-red-blood-cell-destruction |access-date=2022-06-09 |website=NASA}}</ref>

===Intrinsic causes===

Hemolysis may result from intrinsic defects in the red blood cell itself:<ref name="Jacobasch Rapoport 1996 pp. 143–70">{{cite journal | last1=Jacobasch | first1=G | last2=Rapoport | first2=SM | title=Hemolytic anemias due to erythrocyte enzyme deficiencies. | journal=Molecular Aspects of Medicine | volume=17 | issue=2 | year=1996 | issn=0098-2997 | pmid=8813716 | pages=143–70| doi=10.1016/0098-2997(96)88345-2 }}</ref><ref name="Bossi Russo 1996 pp. 171–88">{{cite journal | last1=Bossi | first1=D | last2=Russo | first2=M | title=Hemolytic anemias due to disorders of red cell membrane skeleton. | journal=Molecular Aspects of Medicine | volume=17 | issue=2 | year=1996 | issn=0098-2997 | pmid=8813717 | pages=171–88| doi=10.1016/0098-2997(96)88346-4 }}</ref>
* Defects of red blood cell membrane production (as in [[hereditary spherocytosis]] and [[hereditary elliptocytosis]])
* Defects in hemoglobin production (as in [[thalassemia]], [[sickle-cell disease]] and [[congenital dyserythropoietic anemia]])
* Defective red cell metabolism (as in [[glucose-6-phosphate dehydrogenase deficiency]] and [[pyruvate kinase deficiency]])
* [[Paroxysmal nocturnal hemoglobinuria]] (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia.

===Extrinsic causes===

Extrinsic hemolysis is caused by the red blood cell's environment:<ref name=":0" /><ref name=":1" />
* Immune-mediated causes could include transient factors as in ''[[Mycoplasma pneumoniae]]'' infection ([[cold agglutinin disease]]) or permanent factors as in [[autoimmune disease]]s like [[autoimmune hemolytic anemia]]<ref name=":0" /> (itself more common in diseases such as [[systemic lupus erythematosus]], [[rheumatoid arthritis]], [[Hodgkin's lymphoma]], and [[B-cell chronic lymphocytic leukemia|chronic lymphocytic leukemia]]).
* [[Spur cell hemolytic anemia]]
* Any of the causes of [[hypersplenism]] (increased activity of the spleen), such as [[portal hypertension]].
* Acquired hemolytic anemia is also encountered in [[burn]]s and as a result of certain infections (e.g. [[malaria]]).
* [[Lead poisoning]] or poisoning by [[arsine]] or [[stibine]] causes non-immune hemolytic anemia.<ref name=":1" />
* [[Running|Runners]] can develop hemolytic anemia due to "[[Mechanical hemolytic anemia|footstrike hemolysis]]", the destruction of red blood cells in feet at foot impact.<ref>{{cite journal |vauthors=Telford RD, Sly GJ, Hahn AG, Cunningham RB, Bryant C, Smith JA |title=Footstrike is the major cause of hemolysis during running |journal=J. Appl. Physiol. |volume=94 |issue=1 |pages=38–42 |date=January 2003 |pmid=12391035 |doi=10.1152/japplphysiol.00631.2001 |s2cid=5750453 }}</ref><ref>{{cite journal |vauthors=Lippi G, Schena F, Salvagno GL, Aloe R, Banfi G, Guidi GC |title=Foot-strike haemolysis after a 60-km ultramarathon |journal=Blood Transfus |pages=377–383 |date=July 2012 |pmc=3417738 |pmid=22682343 |doi=10.2450/2012.0167-11 |volume=10 |issue=3}}</ref>
* Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%.<ref>{{Cite book | url = https://books.google.com/books?id=bJF2zgOhJcoC&q=Biomaterials+Engineering+and+Devices-Human+applications+D.L.Wise&pg=PA203 | title = Biomaterials Engineering and Devices: Orthopedic, dental, and bone graft applications | isbn = 978-0-89603-859-2 | last1 = Wise | first1 = Donald Lee | year = 2000 | publisher = Humana Press }}{{Dead link|date=November 2023 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>

===Intravascular hemolysis===
{{main|Intravascular hemolysis}}

'''Intravascular hemolysis''' describes hemolysis that happens mainly inside the [[vasculature]].<ref name="Stanley 2018">{{cite web | title=Diagnosis of hemolytic anemia in the adult | website=UpToDate | url=https://www.uptodate.com/contents/diagnosis-of-hemolytic-anemia-in-the-adult | access-date=2019-05-04 | author=Stanley L Schrier | editor1=William C Mentzer | editor2=Jennifer S Tirnauer | archive-url=https://web.archive.org/web/20171226181455/http://www.uptodate.com/contents/diagnosis-of-hemolytic-anemia-in-the-adult | archive-date=2017-12-26 | url-status=dead }}</ref> As a result, the contents of the red blood cell are released into the general circulation, leading to [[hemoglobinemia]]<ref name="eClinpath Intravascular hemolysis">{{cite web|url=http://eclinpath.com/hematology/anemia/mechanisms-of-anemia/intravascular-hemolysis-new/|title=Intravascular hemolysis|website=eClinpath|access-date=2019-05-08}}</ref> and increasing the risk of ensuing [[hyperbilirubinemia]].<ref name="Muller Jacobsen Healy McMickan 2006 pp. 229–241">{{cite journal | last1=Muller | first1=Andre | last2=Jacobsen | first2=Helene | last3=Healy | first3=Edel | last4=McMickan | first4=Sinead | last5=Istace | first5=Fréderique | last6=Blaude | first6=Marie-Noëlle | last7=Howden | first7=Peter | last8=Fleig | first8=Helmut | last9=Schulte | first9=Agnes | title=Hazard classification of chemicals inducing haemolytic anaemia: An EU regulatory perspective | journal=Regulatory Toxicology and Pharmacology | publisher=Elsevier BV | volume=45 | issue=3 | year=2006 | issn=0273-2300 | doi=10.1016/j.yrtph.2006.04.004 | pmid=16793184 | pages=229–241 | url=https://rivm.openrepository.com/bitstream/handle/10029/5596/muller.pdf?sequence=1&isAllowed=y | archive-url=https://web.archive.org/web/20190503184457/https://rivm.openrepository.com/bitstream/handle/10029/5596/muller.pdf?sequence=1&isAllowed=y | url-status=dead | archive-date=2019-05-03 | access-date=2019-05-04| hdl=10029/5596 | hdl-access=free }}</ref>

Intravascular hemolysis may occur when red blood cells are targeted by [[Autoantibody|autoantibodies]], leading to [[Complement system|complement]] fixation, or by damage by parasites such as ''[[Babesia]]''.<ref name="eClinpath Bilirubin and hemolytic anemia">{{cite web | title=Bilirubin and hemolytic anemia | website=eClinpath | url=http://eclinpath.com/chemistry/liver/cholestasis/bilirubin/bilirubin-and-hemolysis/ | access-date=2019-05-08}}</ref> Additionally, thrombotic microangiopathy (TMA) can result in hemolysis of red blood cells.<ref>{{Cite web|title=Thrombotic Microangiopathy (TMA)|url=https://unckidneycenter.org/kidneyhealthlibrary/glomerular-disease/thrombotic-microangiopathy-tma/|access-date=2020-08-19|website=UNC Kidney Center|language=en-US}}</ref> TMA is frequently observed in [[Atypical hemolytic uremic syndrome|aHUS]] patients where clots form in the small vessels of the kidney resulting in damaged red blood cells as they attempt to pass through the restricted vessels.<ref>{{Cite web|title=Atypical Hemolytic Uremic Syndrome|url=https://rarediseases.org/rare-diseases/atypical-hemolytic-uremic-syndrome/|access-date=2020-08-19|website=NORD (National Organization for Rare Disorders)|language=en-US}}</ref>

===Extravascular hemolysis===

'''Extravascular hemolysis''' refers to hemolysis taking place in the [[liver]], [[spleen]], [[bone marrow]], and [[lymph nodes]].<ref name="Stanley 2018" /> In this case little hemoglobin escapes into [[blood plasma]].<ref name="Muller Jacobsen Healy McMickan 2006 pp. 229–241" /> The [[macrophages]] of the [[reticuloendothelial system]] in these organs [[phagocytosis|engulf and destroy]] structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation.<ref name="Rhodes Varacallo 2019">{{cite journal | last1=Rhodes | first1=Carl E. | last2=Varacallo | first2=Matthew | title=Physiology, Oxygen Transport | website=NCBI Bookshelf | date=2019-03-04 | pmid=30855920 | url=https://www.ncbi.nlm.nih.gov/books/NBK538336/ | access-date=2019-05-04}}</ref><ref name=Sokol81>{{cite journal |vauthors=Sokol RJ, Hewitt S, Stamps BK |title=Autoimmune haemolysis: an 18-year study of 865 cases referred to a regional transfusion centre |journal=Br Med J (Clin Res Ed) |volume=282 |issue=6281 |pages=2023–7 |date=June 1981 |pmid=6788179 |pmc=1505955 |doi=10.1136/bmj.282.6281.2023 }}</ref> Typically, the spleen destroys mildly abnormal red blood cells or those coated with [[Immunoglobulin G|IgG-type antibodies]],<ref name="BRAUNSTEIN.EVAN 2019">{{cite web | author=Braunstein, Evan | title=Overview of Hemolytic Anemia – Hematology and Oncology | website=Merck Manuals Professional Edition | date=2019-05-03 | url=https://www.merckmanuals.com/professional/hematology-and-oncology/anemias-caused-by-hemolysis/overview-of-hemolytic-anemia?query=Autoimmune%20Hemolytic%20Anemia | language=la | access-date=2019-05-05}}</ref><ref name="Hypersplenism 2019">{{cite web | title=Hypersplenism: MedlinePlus Medical Encyclopedia | website=MedlinePlus | date=2019-04-30 | url=https://medlineplus.gov/ency/article/001314.htm | access-date=2019-05-08}}</ref> while severely abnormal red blood cells or those coated with [[Immunoglobulin M|IgM-type antibodies]] are destroyed in the circulation or in the liver.<ref name="BRAUNSTEIN.EVAN 2019" />

If extravascular hemolysis is extensive, [[hemosiderin]] can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in [[hemosiderosis]].<ref name="Muller Jacobsen Healy McMickan 2006 pp. 229–241"/>