Editing Hemolysis (section)

==Complications==
{{see also|Hemolytic anemia#Signs and symptoms}}

Pulmonary hypertension has been gaining recognition as a complication of chronic hereditary and acquired hemolysis.<ref name="Machado Gladwin 2010 pp. 30S–38S II">{{cite journal | last1=Machado | first1=Roberto F. | last2=Gladwin | first2=Mark T. | title=Pulmonary Hypertension in Hemolytic Disorders | journal=Chest | publisher=Elsevier BV | volume=137 | issue=6 | year=2010 | issn=0012-3692 | pmid=20522578 | pmc=2882115 | doi=10.1378/chest.09-3057 | pages=30S–38S}}</ref><ref name="Rother Bell Hillmen Gladwin p=1653">{{cite journal | last1=Rother | first1=Russell P. | last2=Bell | first2=Leonard | last3=Hillmen | first3=Peter | last4=Gladwin | first4=Mark T. | title=The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin | journal=JAMA | publisher=American Medical Association (AMA) | volume=293 | issue=13 | pages=1653–62 | date=2005-04-06 | issn=0098-7484 | pmid=15811985 | doi=10.1001/jama.293.13.1653 | doi-access=free }}</ref><ref name="Reiter Wang Tanus-Santos Hogg 2002 pp. 1383–1389 III">{{cite journal | last1=Reiter | first1=Christopher D. | last2=Wang | first2=Xunde | last3=Tanus-Santos | first3=Jose E. | last4=Hogg | first4=Neil | last5=Cannon | first5=Richard O. | last6=Schechter | first6=Alan N. | last7=Gladwin | first7=Mark T. | title=Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell disease | journal=Nature Medicine | publisher=Springer Nature | volume=8 | issue=12 | date=2002-11-11 | issn=1078-8956 | pmid=12426562 | doi= 10.1038/nm1202-799| pages=1383–1389| s2cid=19878520 }}</ref> Free hemoglobin released during hemolysis inactivates the [[vasodilator]] nitric oxide (NO).<ref name="Machado Gladwin 2010 pp. 30S–38S II"/> Hemolysis also releases [[arginase]] that depletes [[L-arginine]], the substrate needed for NO synthesis.<ref name="Machado Gladwin 2010 pp. 30S–38S II"/><ref name="Reiter Wang Tanus-Santos Hogg 2002 pp. 1383–1389 III"/> This reduces NO-dependent vasodilation<ref name="Machado Gladwin 2010 pp. 30S–38S II"/> and induces [[platelet]] activation, [[thrombin]] generation, [[procoagulant]] factors and [[tissue factor]] activation,<ref name="Machado Gladwin 2010 pp. 30S–38S II"/> contributing to the formation of [[thrombosis]].<ref name="Machado Gladwin 2010 pp. 30S–38S II"/> This can lead to [[esophageal spasm]] and [[dysphagia]], [[abdominal pain]], [[erectile dysfunction]], [[systemic hypertension]], [[hypoperfusion|decreased organ perfusion]], promotion of [[inflammation]] and [[coagulation]], and [[thrombosis]].<ref name="Rother Bell Hillmen Gladwin 2005 pp. 1653–1662 II">{{cite journal|last1=Rother|first1=Russell P.|last2=Bell|first2=Leonard|last3=Hillmen|first3=Peter|last4=Gladwin|first4=Mark T.|date=2005-04-06|title=The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin|journal=JAMA|volume=293|issue=13|pages=1653–1662|doi=10.1001/jama.293.13.1653|pmid=15811985|issn=0098-7484|quote=The systemic removal of nitric oxide has been shown to contribute to clinical morbidities, including severe esophageal spasm and dysphagia, abdominal pain, erectile dysfunction, and thrombosis.16,17,23-26 In addition, systemic release of hemoglobin is associated with pulmonary and systemic hypertension,17,20,53-55 decreased organ perfusion, and increased mortality.53-58 Plasma hemoglobin and its breakdown product heme can also directly activate endothelial cells and further promote inflammation and coagulation.27|doi-access=free}}</ref>

Chronic hemolysis may also lead to [[endothelial dysfunction]], heightened [[endothelin]]-1-mediated responses and [[vasculopathy]].<ref name="Machado Gladwin 2010 pp. 30S–38S II"/><ref name="Schaer Buehler Alayash Belcher pp. 1276–1284 II">{{cite journal | last1=Schaer | first1=D. J. | last2=Buehler | first2=P. W. | last3=Alayash | first3=A. I. | last4=Belcher | first4=J. D. | last5=Vercellotti | first5=G. M. | title=Hemolysis and free hemoglobin revisited: exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins | journal=Blood | publisher=American Society of Hematology | volume=121 | issue=8 | date=2012-12-20 | issn=0006-4971 | pmid=23264591 | pmc=3578950 | doi=10.1182/blood-2012-11-451229 | pages=1276–1284}}</ref>  The release of [[heme]] leads to the production of [[bilirubin]] and depletion of plasma proteins, such as [[albumin]], [[haptoglobin]], and [[hemopexin]], which may lead to [[jaundice]].<ref name="Smith McCulloh p.">{{cite journal|last1=Smith|first1=Ann|last2=McCulloh|first2=Russell J.|date=2015-06-30|title=Hemopexin and haptoglobin: allies against heme toxicity from hemoglobin not contenders|journal=Frontiers in Physiology|publisher=Frontiers Media SA|volume=6|pages=187|doi=10.3389/fphys.2015.00187|issn=1664-042X|pmc=4485156|pmid=26175690|doi-access=free }}</ref><ref name="Schaer Vinchi Ingoglia Tolosano p.">{{cite journal|last1=Schaer|first1=Dominik J.|last2=Vinchi|first2=Francesca|last3=Ingoglia|first3=Giada|last4=Tolosano|first4=Emanuela|last5=Buehler|first5=Paul W.|date=2014-10-28|title=Haptoglobin, hemopexin, and related defense pathways—basic science, clinical perspectives, and drug development|journal=Frontiers in Physiology|publisher=Frontiers Media SA|volume=5|pages=415|doi=10.3389/fphys.2014.00415|issn=1664-042X|pmc=4211382|pmid=25389409|doi-access=free }} [[File:CC-BY icon.svg|50px]] Material was copied from this source, which is available under a Creative Commons License.</ref> It may also lead to increased levels of the heme breakdown product [[stercobilin]] in the stool.<ref name="BRAUNSTEIN.EVAN 2019" />

[[Splenectomy]] of those with hemolytic disorders appears to increase risk of developing [[pulmonary thrombosis]].<ref name="Machado Gladwin 2010 pp. 30S–38S II"/>

Complications may also arise from the increased workload for the kidney as it secretes [[erythropoietin]] to stimulate the [[bone marrow]] to produce more [[reticulocyte]]s (red blood cell precursors) to compensate for the loss of red blood cells due to hemolysis.<ref name="BRAUNSTEIN.EVAN 2019"/>