Editing Iron overload (section)

==Treatment==

=== Phlebotomy ===

[[Phlebotomy]], [[bloodletting]] or [[venesection]] is the mainstay of treatment in iron overload, consisting of regularly scheduled blood draws to remove red blood cells (and iron) from the body.<ref name="NEJM Olynyk" /> Upon initial diagnosis of iron overload, the phlebotomies may be performed weekly or twice weekly, until iron levels are normalized. Once the serum ferritin and transferrin saturation are within the normal range, maintenance phlebotomies may be needed in some (depending upon the rate of reabsorption of iron), scheduled at varying frequencies to keep iron stores within normal range.<ref name="AASLD guidelines" /> A phlebotomy session typically draws between 450 and 500 mL of blood.<ref>{{cite journal|last1=Barton|first1=James C.|title=Management of Hemochromatosis|journal=Annals of Internal Medicine|date=1 December 1998|volume=129|issue=11_Part_2|pages=932–39|doi=10.7326/0003-4819-129-11_Part_2-199812011-00003|pmid=9867745|s2cid=53087679}}</ref> Routine phlebotomy may reverse liver fibrosis and alleviate some symptoms of hemochromatosis, but chronic arthritis is usually not responsive to treatment.<ref name="NEJM Olynyk" /> In those with hemochromatosis; the blood drawn during phlebotomy is safe to be [[blood donation|donated]].<ref>{{cite web|author=NIH blood bank|title=Hemochromatosis Donor Program|url=https://clinicalcenter.nih.gov/blooddonor/donationtypes/hemochromatosis.html}}</ref><ref name="AASLD guidelines" />

Phlebotomy is associated with improved survival if it is initiated before the onset of cirrhosis or diabetes.<ref name="AASLD guidelines" />

=== Diet ===

The human diet contains iron in two forms: [[heme]] iron and [[Non-heme iron protein|non-heme iron]]. Heme iron is usually found in red meat, whereas non-heme iron is found in plant based sources. Heme iron is the most easily absorbed form of iron. In those with hemochromatosis undergoing phlebotomy for treatment; restriction of dietary iron is not required.<ref name="AASLD guidelines">{{cite journal |last1=Bacon |first1=Bruce R. |last2=Adams |first2=Paul C. |last3=Kowdley |first3=Kris V. |last4=Powell |first4=Lawrie W. |last5=Tavill |first5=Anthony S. |title=Diagnosis and management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases |journal=Hepatology |date=July 2011 |volume=54 |issue=1 |pages=328–43 |doi=10.1002/hep.24330|pmid=21452290 |s2cid=9311604 |pmc=3149125 }}</ref><ref name="ACG guidelines">{{cite journal |last1=Kowdley |first1=Kris V. |last2=Brown |first2=Kyle E. |last3=Ahn |first3=Joseph |last4=Sundaram |first4=Vinay |title=ACG Clinical Guideline: Hereditary Hemochromatosis |journal=American Journal of Gastroenterology |date=August 2019 |volume=114 |issue=8 |pages=1202–18 |doi=10.14309/ajg.0000000000000315|pmid=31335359 |s2cid=198192589 |doi-access=free }}</ref><ref name="NEJM Olynyk" /> However, those who do restrict dietary iron usually require less phlebotomy (about 0.5–1.5 liters of blood less per year).<ref name="American Journal of Clinical Nutrition">{{cite journal |journal= The American Journal of Clinical Nutrition|doi=10.3945/ajcn.112.048264 |title=Relevance of dietary iron intake and bioavailability in the management of HFE hemochromatosis: A systematic review |year=2013 |last1=Moretti |first1=Diego |last2=Van Doorn |first2=Gerrigje M. |last3=Swinkels |first3=Dorine W. |last4=Melse-Boonstra |first4=Alida |volume=98 |issue=2 |pages=468–79 |pmid=23803887 |doi-access=free }}</ref> Vitamin C and iron supplementation should be avoided as vitamin C accelerates intestinal absorption of iron and mobilization of body iron stores.<ref name="AASLD guidelines" /><ref name="ACG guidelines" /> Raw seafood should be avoided because of increased risk of infections from iron-loving pathogens (called [[Siderophilic bacteria|siderophilic]]) such as ''[[Vibrio vulnificus]]''.<ref name="NEJM Olynyk" /><ref name="JAMA 1991">{{cite journal |last1=Bullen |first1=John J. |title=Hemochromatosis, Iron, and Septicemia Caused by Vibrio vulnificus |journal=Archives of Internal Medicine |date=1 August 1991 |volume=151 |issue=8 |pages=1606–09 |doi=10.1001/archinte.1991.00400080096018|pmid=1872665 }}</ref> Alcohol consumption should be avoided due to the risk of compounded liver damage with iron overload.<ref name="NEJM Olynyk" />

=== Medication ===

Medications are used for those unable to tolerate routine blood draws, there are [[chelating]] agents available for use.<ref>{{Cite journal| doi = 10.1021/cr00097a011| volume = 89| issue = 7| pages = 1563–79| last = Miller| first = Marvin J.| title = Syntheses and therapeutic potential of hydroxamic acid based siderophores and analogs| journal = Chemical Reviews| date = 1989-11-01}}</ref> The drug [[deferoxamine]] binds with iron in the bloodstream and enhances its elimination in urine and faeces. Typical treatment for chronic iron overload requires subcutaneous injection over a period of 8–12 hours daily.{{citation needed|date=May 2015}} Two newer [[Chelation therapy|iron-chelating drugs]] that are licensed for use in patients receiving regular blood transfusions to treat [[thalassaemia]] (and, thus, who develop iron overload as a result) are [[deferasirox]] and [[deferiprone]].<ref>{{cite journal|vauthors=Choudhry VP, Naithani R |title=Current status of iron overload and chelation with deferasirox |journal=Indian J Pediatr |volume=74 |issue=8 |pages=759–64 |year=2007 |pmid=17785900 |doi=10.1007/s12098-007-0134-7|s2cid=19930076 }}</ref><ref>{{cite journal|last1=Hoffbrand|first1=A. V.|title=Role of deferiprone in chelation therapy for transfusional iron overload|journal=Blood|date=20 March 2003|volume=102|issue=1|pages=17–24|doi=10.1182/blood-2002-06-1867|pmid=12637334|doi-access=free}}</ref>

===Chelating polymers===

A minimally invasive approach to [[hereditary haemochromatosis|hereditary hemochromatosis]] treatment is the [[maintenance therapy]] with [[Ion-exchange resin|polymeric chelators]].<ref name="Polomoscanik2005">{{cite journal|last1=Polomoscanik|first1=Steven C.|last2=Cannon|first2=C. Pat|last3=Neenan|first3=Thomas X.|last4=Holmes-Farley|first4=S. Randall|last5=Mandeville|first5=W. Harry|last6=Dhal|first6=Pradeep K.|title=Hydroxamic Acid-Containing Hydrogels for Nonabsorbed Iron Chelation Therapy: Synthesis, Characterization, and Biological Evaluation|journal=Biomacromolecules|volume=6|issue=6|year=2005|pages=2946–53|issn=1525-7797|doi=10.1021/bm050036p|pmid=16283713}}</ref><ref name="QianSullivan2017">{{cite journal|last1=Qian|first1=Jian|last2=Sullivan|first2=Bradley P.|last3=Peterson|first3=Samuel J.|last4=Berkland|first4=Cory|title=Nonabsorbable Iron Binding Polymers Prevent Dietary Iron Absorption for the Treatment of Iron Overload|journal=ACS Macro Letters|volume=6|issue=4|year=2017|pages=350–53|issn=2161-1653|doi=10.1021/acsmacrolett.6b00945|pmid=35610854 }}</ref><ref name="Groborz2020">{{cite journal|last1=Groborz|first1=Ondřej|last2=Poláková|first2=Lenka|last3=Kolouchová|first3=Kristýna|last4=Švec|first4=Pavel|last5=Loukotová|first5=Lenka|last6=Miriyala|first6=Vijay Madhav|last7=Francová|first7=Pavla|last8=Kučka|first8=Jan|last9=Krijt|first9=Jan|last10=Páral|first10=Petr|last11=Báječný|first11=Martin|last12=Heizer|first12=Tomáš|last13=Pohl|first13=Radek|last14=Dunlop|first14=David|last15=Czernek|first15=Jiří|last16=Šefc|first16=Luděk|last17=Beneš|first17=Jiří|last18=Štěpánek|first18=Petr|last19=Hobza|first19=Pavel|last20=Hrubý|first20=Martin|title=Chelating Polymers for Hereditary Hemochromatosis Treatment|journal=Macromolecular Bioscience|year=2020|volume=20|issue=12|pages=2000254|issn=1616-5187|doi=10.1002/mabi.202000254|pmid=32954629|s2cid=221827050}}</ref> These polymers or particles have a negligible or null systemic [[bioavailability|biological availability]] and they are designed to form stable complexes with Fe<sup>2+</sup> and Fe<sup>3+</sup> in the [[gastrointestinal tract|GIT]] and thus limiting their uptake and long-term accumulation. Although this method has only a limited efficacy, unlike [[chelation therapy|small-molecular chelators]], the approach has virtually no side effects in sub-chronic studies.<ref name="Groborz2020" /> Interestingly, the simultaneous chelation of Fe<sup>2+</sup> and Fe<sup>3+</sup> increases the treatment efficacy.<ref name="Groborz2020" />