sickle cell disease

File:The diseases of infancy and childhood (1920) (14768428942).jpg in the hands of an infant]]

File:Sickle cells.jpg

File:1911 Sickle Cells.jpg

Signs of sickle cell disease usually begin in early childhood. The severity of symptoms can vary from person to person, as can the frequency of crisis events.{{cite web |title=Sickle cell disease: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/sickle-cell-disease/ |access-date=13 November 2024 |website=National Library of Medicine}}{{cite journal |vauthors=Rees DC, Williams TN, Gladwin MT |date=December 2010 |title=Sickle-cell disease |journal=Lancet |volume=376 |issue=9757 |pages=2018–2031 |doi=10.1016/s0140-6736(10)61029-x |pmid=21131035 |s2cid=29909566}} Sickle cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.{{cite journal | vauthors = Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J | title = Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members | journal = The Journal of the American Medical Association | volume = 312 | issue = 10 | pages = 1033–1048 | date = September 2014 | pmid = 25203083 | doi = 10.1001/jama.2014.10517 | s2cid = 37681044 }}

When SCD presents within the first year of life, the most common problem is an episode of pain and swelling in the child's hands and feet, known as dactylitis or "hand-foot syndrome." Pallor, jaundice, and fatigue can also be early signs due to anaemia resulting from sickle cell disease.{{Cite journal |last1=Gill |first1=FM |last2=Sleeper |first2=LA |last3=Weiner |first3=SJ |last4=Brown |first4=AK |last5=Bellevue |first5=R |last6=Grover |first6=R |last7=Pegelow |first7=CH |last8=Vichinsky |first8=E |date=1995-07-15 |title=Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease [see comments] |url=http://dx.doi.org/10.1182/blood.v86.2.776.bloodjournal862776 |journal=Blood |volume=86 |issue=2 |pages=776–783 |doi=10.1182/blood.v86.2.776.bloodjournal862776 |issn=0006-4971}}

In children older than 2 years, the most common initial presentation is a painful episode of a generalized or variable nature, while a slightly less common presentation involves acute chest pain. Dactylitis is rare or almost never occurs in children over the age of 2.

Also termed "sickle cell crisis" or "sickling crisis", the vaso-occlusive crisis (VOC) manifests principally as extreme pain, most often affecting the chest, back, legs and/or arms.{{Cite web |date=3 August 2023 |title=Sickle Cell Disease |url=https://my.clevelandclinic.org/health/diseases/12100-sickle-cell-disease |access-date=25 October 2024 |website=Cleveland Clinic}} The underlying cause is sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in ischaemia, pain, necrosis, and often organ damage. The frequency, severity, and duration of these crises vary considerably. Milder crises can be managed with nonsteroidal anti-inflammatory drugs. For more severe crises, patients may require inpatient management for intravenous opioids. Vaso-occlusive crisis involving organs such as the penis or lungs are considered an emergency and treated with red blood cell transfusions.{{cite journal |vauthors=Olujohungbe A, Burnett AL |date=March 2013 |title=How I manage priapism due to sickle cell disease |journal=British Journal of Haematology |volume=160 |issue=6 |pages=754–765 |doi=10.1111/bjh.12199 |pmid=23293942 |doi-access=free |title-link=doi}}

A VOC can be triggered by anything which causes blood vessels to constrict; this includes physical or mental stress, cold, and dehydration.{{Cite web |date=2017-10-23 |title=Sickle cell disease - Symptoms |url=https://www.nhs.uk/conditions/sickle-cell-disease/symptoms/ |access-date=2024-10-25 |website=nhs.uk |language=en}} "After HbS deoxygenates in the capillaries, it takes some time (seconds) for HbS polymerization and the subsequent flexible-to-rigid transformation. If the transit time of RBC through the microvasculature is longer than the polymerization time, sickled RBC will lodge in the microvasculature."{{Cite journal |last1=Shah |first1=Payal |last2=Khaleel |first2=Maha |last3=Thuptimdang |first3=Wanwara |last4=Sunwoo |first4=John |last5=Veluswamy |first5=Saranya |last6=Chalacheva |first6=Patjanaporn |last7=Kato |first7=Roberta M. |last8=Detterich |first8=Jon |last9=Wood |first9=John C. |last10=Zeltzer |first10=Lonnie |last11=Sposto |first11=Richard |last12=Khoo |first12=Michael C. K. |last13=Coates |first13=Thomas D. |date=2020-01-01 |title=Mental stress causes vasoconstriction in subjects with sickle cell disease and in normal controls |url=https://haematologica.org/article/view/9478 |journal=Haematologica |language=en |volume=105 |issue=1 |pages=83–90 |doi=10.3324/haematol.2018.211391 |issn=1592-8721 |pmc=6939522 |pmid=30975906}}

The spleen is especially prone to damage in SCD due to its role as a blood filter. A splenic sequestration crisis, also known as a spleen crisis, is a medical emergency that occurs when sickled red blood cells block the spleen's filter mechanism, causing the spleen to swell and fill with blood. The accumulation of red blood cells in the spleen results in a sudden drop in circulating hemoglobin and potentially life-threatening anemia. Symptoms include pain on the left side, swollen spleen (which can be detected by palpation), fatigue, dizziness, irritability, rapid heartbeat, or pale skin. It most commonly affects young children, the median age of first occurrence is 1.4 years. By the age of 5 years repeated instances of sequestration cause scarring and eventual atrophy of the spleen.{{Cite journal |last1=Brousse |first1=Valentine |last2=Buffet |first2=Pierre |last3=Rees |first3=David |date=2014-07-01 |title=The spleen and sickle cell disease: the sick(led) spleen |journal=British Journal of Haematology |language=en |volume=166 |issue=2 |pages=165–176 |doi=10.1111/bjh.12950 |issn=1365-2141 |pmid=24862308 |s2cid=40448991 |doi-access=free}}{{Cite web |title=Splenic Sequestration Crisis {{!}} Texas DSHS |url=https://www.dshs.texas.gov/newborn-screening-program/sickle-cell-disease/more-about-sickle-cell/splenic-sequestration-crisis |access-date=2024-10-28 |website=www.dshs.texas.gov}}{{Citation |last1=Kane |first1=Ian |title=Splenic Sequestration Crisis |date=5 June 2023 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK553164/ |access-date=2024-10-28 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=31985957 |last2=Kumar |first2=Abhishek |last3=Atalla |first3=Eleftheria |last4=Nagalli |first4=Shivaraj}}

Treatment is supportive, with blood transfusion if hemoglobin levels fall too low. Full or partial splenectomy may be necessary.{{Cite web |title=Blood Transfusions for Sickle Cell Disease {{!}} HealthLink BC |url=https://www.healthlinkbc.ca/health-topics/blood-transfusions-sickle-cell-disease |access-date=2024-05-08 |website=www.healthlinkbc.ca |language=en}} Long term consequences of a loss of spleen function are increased susceptibility to bacterial infections.

Acute chest syndrome is caused by a VOC which affects the lungs, possibly triggered by infection or by emboli which have circulated from other organs. Symptoms include wheezing, chest pain, fever, pulmonary infiltrate (visible on x-ray), and hypoxemia. After sickling crisis (see above) it is the second-most common cause of hospitalization and it accounts for about 25% of deaths in patients with SCD. Most cases present with vaso-occlusive crises, and then develop acute chest syndrome.{{cite journal | vauthors = Paul RN, Castro OL, Aggarwal A, Oneal PA | title = Acute chest syndrome: sickle cell disease | journal = European Journal of Haematology | volume = 87 | issue = 3 | pages = 191–207 | date = September 2011 | pmid = 21615795 | doi = 10.1111/j.1600-0609.2011.01647.x | s2cid = 40320701 }}{{Citation |last1=Friend |first1=Amanda |title=Acute Chest Syndrome |date=25 November 2023 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK441872/ |access-date=2024-10-27 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722902 |last2=Settelmeyer |first2=Teagan P. |last3=Girzadas |first3=Daniel}}

Aplastic crises are instances of an acute worsening of the patient's baseline anaemia, producing pale appearance, fast heart rate, and fatigue. This crisis is normally triggered by parvovirus B19, which directly affects production of red blood cells by invading the red cell precursors and multiplying in and destroying them.{{cite book | vauthors = Kumar V, Abbas AK, Fausto N, Aster J | date = 28 May 2009 | title = Robbins and Cotran Pathologic Basis of Disease | edition = Professional Edition: Expert Consult – Online (Robbins Pathology) | pages = Kindle Location 33329| publisher = Elsevier Health }} Parvovirus infection {{Cite web |date=2023-08-24 |title=Parvovirus B19 |url=https://www.cdc.gov/parvovirusb19/index.html |access-date=2024-05-08 |website=Centers for Disease Control and Prevention |language=en-us}} almost completely prevents red blood cell production for two to three days (red cell aplasia). In normal individuals, this is of little consequence, but the shortened red cell life of SCD patients results in an abrupt, life-threatening situation. Reticulocyte count drops dramatically during the disease (causing reticulocytopenia), red cell production lapses, and the rapid destruction of existing red cells leads to acute and severe anemia. This crisis takes four to seven days to resolve. Most patients can be managed supportively; some need a blood transfusion.{{cite journal | vauthors = Slavov SN, Kashima S, Pinto AC, Covas DT | title = Human parvovirus B19: general considerations and impact on patients with sickle-cell disease and thalassemia and on blood transfusions | journal = FEMS Immunology and Medical Microbiology | volume = 62 | issue = 3 | pages = 247–262 | date = August 2011 | pmid = 21585562 | doi = 10.1111/j.1574-695X.2011.00819.x | doi-access = free | title-link = doi }}

Sickle cell anaemia can lead to various complications including:

• Increased risk of severe bacterial infections is due to loss of functioning spleen tissue. These infections are typically caused by bacteria such as Streptococcus pneumoniae and Haemophilus influenzae. Daily penicillin prophylaxis is the most commonly used treatment during childhood, with some haematologists continuing treatment indefinitely. Patients benefit from routine vaccination for S. pneumoniae.{{cite journal | vauthors = Kavanagh PL, Sprinz PG, Vinci SR, Bauchner H, Wang CJ | title = Management of children with sickle cell disease: a comprehensive review of the literature | journal = Pediatrics | volume = 128 | issue = 6 | pages = e1552–e1574 | date = December 2011 | pmid = 22123880 | doi = 10.1542/peds.2010-3686 | url = http://pediatrics.aappublications.org/content/128/6/e1552.long | url-status = live | s2cid = 14524078 | archive-url = https://web.archive.org/web/20160304105424/http://pediatrics.aappublications.org/content/128/6/e1552.long | archive-date = 4 March 2016 }}
• Stroke can result from blockage of blood vessels in the brain, causing numbness, confusion, or weakness which may be long lasting. Silent stroke causes no immediate symptoms, but is associated with damage to the brain. Silent stroke is probably five times as common as symptomatic stroke. About 10–15% of children with SCD have strokes, with silent strokes predominating in the younger patients.{{Cite web |date=2024-05-22 |title=Complications of Sickle Cell Disease |url=https://www.cdc.gov/sickle-cell/complications/index.html |access-date=2024-10-29 |website=Centers for Disease Control and Prevention |language=en-us}}{{cite journal | vauthors = Adams RJ, Ohene-Frempong K, Wang W | title = Sickle cell and the brain | journal = Hematology. American Society of Hematology. Education Program | volume = 2001 | issue = 1 | pages = 31–46 | year = 2001 | pmid = 11722977 | doi = 10.1182/asheducation-2001.1.31 | doi-access = free | title-link = doi }}{{cite journal | vauthors = Adams RJ | title = Big strokes in small persons | journal = Archives of Neurology | volume = 64 | issue = 11 | pages = 1567–1574 | date = November 2007 | pmid = 17998439 | doi = 10.1001/archneur.64.11.1567 | doi-access = free | title-link = doi }}
• Cholelithiasis (gallstones) and cholecystitis may result from excessive bilirubin production and precipitation due to prolonged haemolysis.{{cite web |url= https://www.lecturio.com/concepts/cholelithiasis/| title= Cholelithiasis|website=The Lecturio Medical Concept Library |access-date= 25 August 2021}}
• Avascular necrosis (aseptic bone necrosis) of the hip and other major joints may occur as a result of ischaemia.{{cite journal |vauthors=Martí-Carvajal AJ, Solà I, Agreda-Pérez LH |date=December 2019 |title=Treatment for avascular necrosis of bone in people with sickle cell disease |journal=The Cochrane Database of Systematic Reviews |volume=2019 |issue=12 |pages=CD004344 |doi=10.1002/14651858.CD004344.pub7 |pmc=6894369 |pmid=31803937}}
• Priapism and infarction of the penis{{cite journal | vauthors = Chrouser KL, Ajiboye OB, Oyetunji TA, Chang DC | title = Priapism in the United States: the changing role of sickle cell disease | journal = American Journal of Surgery | volume = 201 | issue = 4 | pages = 468–474 | date = April 2011 | pmid = 21421100 | doi = 10.1016/j.amjsurg.2010.03.017 }}
• Osteomyelitis (bacterial bone infection) as a result of damage to the spleen, commonly caused by either Staphylococcus aureus or species of Salmonella.
• Chronic kidney failure due to sickle-cell nephropathy manifests itself with hypertension, protein loss in the urine, loss of red blood cells in urine and worsened anaemia. If it progresses to end-stage kidney failure, it carries a poor prognosis.{{cite journal |vauthors=Powars DR, Elliott-Mills DD, Chan L, Niland J, Hiti AL, Opas LM, Johnson C |date=October 1991 |title=Chronic renal failure in sickle cell disease: risk factors, clinical course, and mortality |journal=Annals of Internal Medicine |volume=115 |issue=8 |pages=614–620 |doi=10.7326/0003-4819-115-8-614 |pmid=1892333}}{{Cite journal |last1=Saborio |first1=Pablo |last2=Scheinman |first2=Jon I. |date=January 1999 |title=Sickle Cell Nephropathy |url=https://journals.lww.com/00001751-199901000-00025 |journal=Journal of the American Society of Nephrology |language=en |volume=10 |issue=1 |pages=187–192 |doi=10.1681/ASN.V101187 |pmid=9890326 |issn=1046-6673}}
• Leg ulcers are relatively common in SCD and can be disabling.{{Cite journal |last1=Minniti |first1=Caterina P. |last2=Eckman |first2=James |last3=Sebastiani |first3=Paola |last4=Steinberg |first4=Martin H. |last5=Ballas |first5=Samir K. |date=October 2010 |title=Leg ulcers in sickle cell disease |journal=American Journal of Hematology |language=en |volume=85 |issue=10 |pages=831–833 |doi=10.1002/ajh.21838 |issn=0361-8609 |pmc=2953786 |pmid=20872960}}
• In eyes, background retinopathy, proliferative retinopathy, vitreous haemorrhages, and retinal detachments can result in blindness.{{cite journal | vauthors = Elagouz M, Jyothi S, Gupta B, Sivaprasad S | title = Sickle cell disease and the eye: old and new concepts | journal = Survey of Ophthalmology | volume = 55 | issue = 4 | pages = 359–377 | date = July 2010 | pmid = 20452638 | doi = 10.1016/j.survophthal.2009.11.004 }} Regular annual eye checks are recommended.
• During pregnancy, intrauterine growth restriction, spontaneous abortion, and pre-eclampsia
• Chronic pain: Even in the absence of acute vaso-occlusive pain, many patients have unreported chronic pain.{{cite journal | vauthors = Smith WR, Penberthy LT, Bovbjerg VE, McClish DK, Roberts JD, Dahman B, Aisiku IP, Levenson JL, Roseff SD | title = Daily assessment of pain in adults with sickle cell disease | journal = Annals of Internal Medicine | volume = 148 | issue = 2 | pages = 94–101 | date = January 2008 | pmid = 18195334 | doi = 10.7326/0003-4819-148-2-200801150-00004 | s2cid = 34924760 | citeseerx = 10.1.1.690.5870 }}
• Pulmonary hypertension (increased pressure on the pulmonary artery) can lead to strain on the right ventricle and a risk of heart failure; typical symptoms are shortness of breath, decreased exercise tolerance, and episodes of syncope.{{cite journal | vauthors = Lai YC, Potoka KC, Champion HC, Mora AL, Gladwin MT | title = Pulmonary arterial hypertension: the clinical syndrome | journal = Circulation Research | volume = 115 | issue = 1 | pages = 115–130 | date = June 2014 | pmid = 24951762 | pmc = 4096686 | doi = 10.1161/CIRCRESAHA.115.301146 | doi-access = free | title-link = doi }} 21% of children and 30% of adults have evidence of pulmonary hypertension when tested; this is associated with reduced walking distance and increased mortality.{{cite journal | vauthors = Caughey MC, Poole C, Ataga KI, Hinderliter AL | title = Estimated pulmonary artery systolic pressure and sickle cell disease: a meta-analysis and systematic review | journal = British Journal of Haematology | volume = 170 | issue = 3 | pages = 416–424 | date = August 2015 | pmid = 25854714 | doi = 10.1111/bjh.13447 | s2cid = 23920740 | doi-access = free | title-link = doi }}
• Cardiomyopathy and left ventricular diastolic dysfunction caused by fibrosis or scarring of cardiac tissues.{{cite journal | vauthors = Niss O, Quinn CT, Lane A, Daily J, Khoury PR, Bakeer N, Kimball TR, Towbin JA, Malik P, Taylor MD | title = Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease | journal = JACC. Cardiovascular Imaging | volume = 9 | issue = 3 | pages = 243–252 | date = March 2016 | pmid = 26897687 | pmc = 4788530 | doi = 10.1016/j.jcmg.2015.05.013 }}{{cite journal | vauthors = Niss O, Fleck R, Makue F, Alsaied T, Desai P, Towbin JA, Malik P, Taylor MD, Quinn CT | title = Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia | journal = Blood | volume = 130 | issue = 2 | pages = 205–213 | date = July 2017 | pmid = 28507082 | pmc = 5510791 | doi = 10.1182/blood-2017-02-767624 }} This also contributes to pulmonary hypertension, decreased exercise capacity, and arrhythmias.{{cite journal | vauthors = Rai P, Niss O, Malik P | title = A reappraisal of the mechanisms underlying the cardiac complications of sickle cell anemia | journal = Pediatric Blood & Cancer | volume = 64 | issue = 11 | pages = e26607 | date = November 2017 | pmid = 28453224 | doi = 10.1002/pbc.26607 | s2cid = 24444332 }}

File:Autorecessive.svg pattern.]]

File:Sickle Cell Anemia.svg{{See also|Introduction to genetics}}

Hemoglobin is an oxygen-binding protein, found in erythrocytes, which transports oxygen from the lungs (or in the fetus, from the placenta) to the tissues. Each molecule of hemoglobin comprises 4 protein subunits, referred to as globins.{{Citation |last1=Farid |first1=Yostina |title=Biochemistry, Hemoglobin Synthesis |date=2019 |work=StatPearls |url=http://www.ncbi.nlm.nih.gov/books/NBK536912/ |access-date=2019-04-10 |publisher=StatPearls Publishing |pmid=30725597 |last2=Lecat |first2=Paul}} Normally, humans have:-

• hemoglobin F (Fetal hemoglobin, HbF), consisting of two alpha (α-globin) and two gamma (γ-globin) chains. This dominates during development of the fetus and until about 6 weeks of age. Afterwards, haemoglobin A dominates throughout life.{{cite journal |vauthors=Sankaran VG, Orkin SH |date=January 2013 |title=The switch from fetal to adult hemoglobin |journal=Cold Spring Harbor Perspectives in Medicine |volume=3 |issue=1 |pages=a011643 |doi=10.1101/cshperspect.a011643 |pmc=3530042 |pmid=23209159}}
• hemoglobin A, (Adult hemoglobin, HbA) which consists of two alpha and two beta (β-globin) chains. This is the most common human hemoglobin tetramer, accounting for over 97% of the total red blood cell hemoglobin in normal adults.{{Cite web |date=April 2002 |title=Hemoglobinopathies |url=https://sickle.bwh.harvard.edu/hemoglobinopathy.html |access-date=2024-11-07 |website=Brigham and Women's Hospital}}
• hemoglobin A2, (HbA2) is a second form of adult hemoglobin and is composed of two alpha and two delta (δ-globin) chains. This hemoglobin typically makes up 1-3% of hemoglobin in adults.

β-globin is encoded by the HBB gene on human chromosome 11; mutations in this gene produce variants of the protein which are implicated with abnormal hemoglobins. The mutation which causes sickle cell disease results in an abnormal hemoglobin known as hemoglobin S (HbS), which replaces HbA in adults. The human genome contains a pair of genes for β-globin; in people with sickle cell disease, both genes are affected and the erythropoietic cells in the bone marrow will only create HbS. In people with sickle cell trait, only one gene is abnormal; erythropoiesis generates a mixture of normal HbA and sickle HbS. The person has very few if any symptoms of sickle cell disease but carries the gene and can pass it on to their children.{{cite web |title=Inheritance of Sickle Cell Anaemia |url=https://www.sicklecellsociety.org/resource/inheritance-sickle-cell-anaemia/ |url-status=live |archive-url=https://web.archive.org/web/20240108070519/https://www.sicklecellsociety.org/resource/inheritance-sickle-cell-anaemia/ |archive-date=8 January 2024 |access-date=8 January 2024 |website=Sickle Cell Society}}

File:Autorecessive.svg inheritance means acquiring two changed genes from each parent. If both parents are carriers for the autosomal recessive gene, there is a 25% chance of their child having and expressing the disorder. Other children will be unaffected, but may be carriers.]]

Sickle cell disease has an autosomal recessive pattern of inheritance from parents.{{cite web |title=Sickle Cell Disease |url=https://rarediseases.org/rare-diseases/sickle-cell-disease/ |access-date=10 June 2019 |website=NORD (National Organization for Rare Disorders)}} Both copies of the affected gene must carry the same mutation (homozygous condition) for a person to be affected by an autosomal recessive disorder. An affected person usually has unaffected parents who each carry one mutated gene and one normal gene (heterozygous condition) and are referred to as genetic carriers; they may not have any symptoms.{{Cite web |title=Inheritance Patterns for Single Gene Disorders |url=https://learn.genetics.utah.edu/content/disorders/inheritance/ |url-status=live |archive-url=https://web.archive.org/web/20190701160447/https://learn.genetics.utah.edu/content/disorders/inheritance/ |archive-date=2019-07-01 |access-date=2019-07-01 |website=learn.genetics.utah.edu}} When both parents have the sickle cell trait, any given child has a 25% chance of sickle cell disease; a 25% chance of no sickle cell alleles, and a 50% chance of the heterozygous condition (see diagram).{{Cite web |date=2017-10-23 |title=Sickle cell disease - Causes |url=https://www.nhs.uk/conditions/sickle-cell-disease/causes/ |access-date=2024-11-07 |website=National Health Service |language=en}}

There are several different haplotypes of the sickle cell gene mutation, indicating that it probably arose spontaneously in different geographic areas. The variants are known as Cameroon, Senegal, Benin, Bantu, and Saudi-Asian.{{cite web |title=Sickle-Cell Anemia: Haplotype {{!}} Learn Science at Scitable |url=https://www.nature.com/scitable/topicpage/sickle-cell-anemia-a-look-at-global-8756219/ |access-date=12 October 2023 |website=www.nature.com}} These are clinically important because some are associated with higher HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have milder disease.{{cite journal |vauthors=Green NS, Fabry ME, Kaptue-Noche L, Nagel RL |date=October 1993 |title=Senegal haplotype is associated with higher HbF than Benin and Cameroon haplotypes in African children with sickle cell anemia |journal=American Journal of Hematology |volume=44 |issue=2 |pages=145–146 |doi=10.1002/ajh.2830440214 |pmid=7505527 |s2cid=27341091}}

File:Sickle_Cell_Anemia.svg

The gene defect is a single nucleotide mutation of the β-globin gene, which results in glutamate being substituted by valine at position 6 of the β-globin chain.{{Cite journal |last1=Inusa |first1=Baba P. D. |last2=Hsu |first2=Lewis L. |last3=Kohli |first3=Neeraj |last4=Patel |first4=Anissa |last5=Ominu-Evbota |first5=Kilali |last6=Anie |first6=Kofi A. |last7=Atoyebi |first7=Wale |date=June 2019 |title=Sickle Cell Disease—Genetics, Pathophysiology, Clinical Presentation and Treatment |journal=International Journal of Neonatal Screening |language=en |volume=5 |issue=2 |pages=20 |doi=10.3390/ijns5020020 |doi-access=free |issn=2409-515X |pmc=7510211 |pmid=33072979}} Hemoglobin S with this mutation is referred to as HbS, as opposed to the normal adult HbA. Under conditions of normal oxygen concentration this causes no apparent effects on the structure of haemoglobin or its ability to transport oxygen around the body. However, the deoxy form of HbS has an exposed hydrophobic patch which causes HbS molecules to join to form long inflexible chains. Under conditions of low oxygen concentration in the bloodstream, such as exercise, stress, altitude or dehydration, HbS polymerization forms fibrous precipitates within the red blood cell.{{cite journal |vauthors=Odièvre MH, Verger E, Silva-Pinto AC, Elion J |date=October 2011 |title=Pathophysiological insights in sickle cell disease |journal=The Indian Journal of Medical Research |volume=134 |issue=1 |pages=532–537 |doi=10.1007/bf00168807 |pmc=3237253 |pmid=22089617}} In people homozygous for the sickle cell mutation, the presence of long-chain polymers of HbS distort the shape of the red blood cell from a smooth, doughnut-like shape to the sickle shape, making it fragile and susceptible to blocking or breaking within capillaries.

In people heterozygous for HbS (carriers of sickle cell disease), the polymerisation problems are minor because the normal allele can produce half of the haemoglobin. Sickle cell carriers have symptoms only if they are deprived of oxygen (for example, at altitude) or while severely dehydrated.{{Cite web |date=2024-05-22 |title=Sickle Cell Disease (SCD): What Is Sickle Cell Trait? |url=https://www.cdc.gov/sickle-cell/sickle-cell-trait/index.html |access-date=2024-11-07 |website=Centers for Disease Control and Prevention |language=en-us}}

File:Sickle cell distribution.jpg

File:Malaria distribution.jpg (no longer endemic in Europe)]]

File:Paludisme - Frequence statistique.pngSCD is most prevalent in areas which have historically been associated with endemic malaria. The sickle cell trait provides a carrier with a survival advantage against malaria fatality over people with normal hemoglobin in regions where malaria is endemic.{{Cite web |last=Pitone |first=Melanie L. |date=July 2023 |title=What's the Connection Between Sickle Cell Trait and Malaria? (for Teens) |url=https://kidshealth.org/en/teens/sickle-cell-trait-malaria.html |access-date=2024-10-31 |website=kidshealth.org |language=english}}{{Cite web |last=Morales-Brown |first=Louise |date=2024-02-09 |title=What is the connection between sickle cell anemia and malaria? |url=https://www.medicalnewstoday.com/articles/sickle-cell-anemia-and-malaria |access-date=2024-10-31 |website=www.medicalnewstoday.com |language=en}}

Infection with the malaria parasite affects asymptomatic carriers of the abnormal hemoglobin gene differently from patients with full SCD. Carriers (heterozygous for the gene) who catch malaria are less likely to suffer from severe symptoms than people with normal hemogolobin. SCD patients (homozygous for the gene) are similarly less likely to become infected with malaria; however once infected they are more likely to develop severe and life-threatening anemia.{{Cite journal |last1=Uyoga |first1=Sophie |last2=Olupot-Olupot |first2=Peter |last3=Connon |first3=Roisin |last4=Kiguli |first4=Sarah |last5=Opoka |first5=Robert O |last6=Alaroker |first6=Florence |last7=Muhindo |first7=Rita |last8=Macharia |first8=Alexander W |last9=Dondorp |first9=Arjen M |last10=Gibb |first10=Diana M |last11=Walker |first11=A Sarah |last12=George |first12=Elizabeth C |last13=Maitland |first13=Kathryn |last14=Williams |first14=Thomas N |date=September 2022 |title=Sickle cell anaemia and severe Plasmodium falciparum malaria: a secondary analysis of the Transfusion and Treatment of African Children Trial (TRACT) |journal=The Lancet Child & Adolescent Health |volume=6 |issue=9 |pages=606–613 |doi=10.1016/s2352-4642(22)00153-5 |issn=2352-4642 |pmc=7613576 |pmid=35785794}}{{Cite journal |last=Luzzatto |first=Lucio |date=2012-10-03 |title=Sickle Cell Anaemia and Malaria |url=https://www.mjhid.org/index.php/mjhid/article/view/2012.065 |journal=Mediterranean Journal of Hematology and Infectious Diseases |language=en |volume=4 |issue=1 |pages=e2012065 |doi=10.4084/mjhid.2012.065 |issn=2035-3006 |pmc=3499995 |pmid=23170194}}

The impact of sickle cell anemia on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria. Although the shorter life expectancy for those with the homozygous condition would tend to disfavour the trait's survival, the trait is preserved in malaria-prone regions because of the benefits provided by the heterozygous form; an example of natural selection.{{Cite web |date=2016-09-23 |title=5.21: Natural Selection |url=https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/Introductory_Biology_(CK-12)/05:_Evolution/5.21:_Natural_Selection |access-date=2024-10-31 |website=Biology LibreTexts |language=en}}

Due to the adaptive advantage of the heterozygote, the disease is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India, and the Middle East.{{cite journal | vauthors = Kwiatkowski DP | title = How malaria has affected the human genome and what human genetics can teach us about malaria | journal = American Journal of Human Genetics | volume = 77 | issue = 2 | pages = 171–192 | date = August 2005 | pmid = 16001361 | pmc = 1224522 | doi = 10.1086/432519 }} Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases.{{cite journal | vauthors = Ponçon N, Toty C, L'Ambert G, Le Goff G, Brengues C, Schaffner F, Fontenille D | title = Biology and dynamics of potential malaria vectors in Southern France | journal = Malaria Journal | volume = 6 | issue = 1 | pages = 18 | date = February 2007 | pmid = 17313664 | pmc = 1808464 | doi = 10.1186/1475-2875-6-18 | doi-access = free | title-link = doi }}

The malaria parasite has a complex lifecycle and spends part of it in red blood cells. There are two mechanisms which protect sickle cell carriers from malaria. One is that the parasite is hindered from growing and reproducing in a carrier's red blood cells; another is that a carrier's red cells show signs of damage when infected, and are detected and destroyed as they pass through the spleen.{{Cite journal |last=Arif |first=S. H. |date=2008-03-19 |title=Sickle cell disease and malaria |journal=Indian Journal of Hematology & Blood Transfusion |language=en |volume=23 |issue=3–4 |pages=70–72 |doi=10.1007/s12288-008-0001-3 |pmc=3453113 |pmid=23100918}}{{Cite journal |last1=Cao |first1=Huan |last2=Antonopoulos |first2=Aristotelis |last3=Henderson |first3=Sadie |last4=Wassall |first4=Heather |last5=Brewin |first5=John |last6=Masson |first6=Alanna |last7=Shepherd |first7=Jenna |last8=Konieczny |first8=Gabriela |last9=Patel |first9=Bhinal |last10=Williams |first10=Maria-Louise |last11=Davie |first11=Adam |last12=Forrester |first12=Megan A. |last13=Hall |first13=Lindsay |last14=Minter |first14=Beverley |last15=Tampakis |first15=Dimitris |date=2021-03-19 |title=Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance |journal=Nature Communications |language=en |volume=12 |issue=1 |pages=1792 |doi=10.1038/s41467-021-21814-z |issn=2041-1723 |pmc=7979802 |pmid=33741926|bibcode=2021NatCo..12.1792C }}

File:Sicklecells.jpg showing a mixture of red blood cells, some with round normal morphology, some with mild sickling showing elongation and bending]]

Under conditions of low oxygen concentration, HBS polymerises to form long strands within the red blood cell (RBC). These strands distort the shape of the cell and after a few seconds cause it to adopt an abnormal, inflexible sickle-like shape. This process reverses when oxygen concentration is raised and the cells resume their normal biconcave disc shape. If sickling takes place in the venous system, after blood has passed through the capillaries, it has no effect on the organs and the RBCs can unsickle when they become oxygenated in the lungs. Repeated switching between sickle and normal shapes damages the membrane of the RBC so that it eventually becomes permanently sickled.{{Cite journal |last1=Padilla |first1=F. |last2=Bromberg |first2=P. A. |last3=Jensen |first3=W. N. |date=1973-05-01 |title=The Sickle-Unsickle Cycle: A Cause of Cell Fragmentation Leading to Permanently Deformed Cells |url=https://ashpublications.org/blood/article/41/5/653/40264/The-SickleUnsickle-Cycle-A-Cause-of-Cell |journal=Blood |language=en |volume=41 |issue=5 |pages=653–660 |doi=10.1182/blood.V41.5.653.653 |pmid=4694082 |issn=0006-4971}}{{Cite journal |last=Maakaron |first=Joseph E |date=2024-09-25 |title=Sickle Cell Disease (SCD): Overview |url=https://emedicine.medscape.com/article/205926-overview#showall |journal=Medscape}}{{cite web |title=How Does Sickle Cell Cause Disease? |url=http://sickle.bwh.harvard.edu/scd_background.html |url-status=live |archive-url=https://web.archive.org/web/20100923165921/http://sickle.bwh.harvard.edu/scd_background.html |archive-date=23 September 2010 |access-date=27 November 2010}}

Normal red blood cells are quite elastic and have a biconcave disc shape, which allows the cells to deform to pass through capillaries. In sickle cell disease, low oxygen tension promotes red blood cell sickling and repeated episodes of sickling damage the cell membrane and decrease the cell's elasticity. These cells fail to return to normal shape when normal oxygen tension is restored. As a consequence, these rigid blood cells are unable to deform as they pass through narrow capillaries, leading to vessel occlusion and ischaemia.

Cells which have become sickled are detected as they pass through the spleen and are destroyed. In young children with SCD, the accumulation of sickled cells in the spleen can result in splenic sequestration crisis. In this, the spleen becomes engorged with blood, depriving the general circulation of blood cells and leading to severe anemia. The spleen initially becomes noticeably swollen but the lack of a healthy blood flow through the organ culminates in scarring of the spleen tissues and eventually death of the organ, generally before the age of 5 years.

The actual anaemia of the illness is caused by haemolysis, the destruction of the red cells, because of their shape. Although the bone marrow attempts to compensate by creating new red cells, it does not match the rate of destruction. Healthy red blood cells typically function for 90–120 days, but sickled cells only last 10–20 days.{{Cite web |date=17 December 2021 |title=Facts About Blood and Blood Cells |url=https://www.mskcc.org/cancer-care/patient-education/facts-about-blood-and-blood-cells |access-date=2024-11-11 |website=Memorial Sloan Kettering Cancer Center |language=en}}

The rapid breakdown of RBC's in SCD results in the release of free heme into the bloodstream exceeding the capacity of the body's protective mechanisms. Although heme is an essential component of hemoglobin, it is also a potent oxidative molecule. Free heme is also an alarmin - a signal of tissue damage or infection, which triggers defensive responses in the body and increases the risk of inflammation and vaso-occlusive events.{{Cite journal |last1=Gbotosho |first1=Oluwabukola T. |last2=Kapetanaki |first2=Maria G. |last3=Kato |first3=Gregory J. |date=2021-01-27 |title=The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease |journal=Frontiers in Immunology |language=English |volume=11 |doi=10.3389/fimmu.2020.561917 |doi-access=free |issn=1664-3224 |pmc=7873693 |pmid=33584641}}{{Cite journal |last1=Sundd |first1=Prithu |last2=Gladwin |first2=Mark T. |last3=Novelli |first3=Enrico M. |date=2019-01-24 |title=Pathophysiology of Sickle Cell Disease |journal=Annual Review of Pathology: Mechanisms of Disease |language=en |volume=14 |issue=1 |pages=263–292 |doi=10.1146/annurev-pathmechdis-012418-012838 |issn=1553-4006 |pmc=7053558 |pmid=30332562}}

Checking for SCD begins during pregnancy, with a prenatal screening questionnaire which includes, among other things, a consideration of health issues in the child's parents and close relatives. During pregnancy, genetic testing can be done on either a blood sample from the fetus or a sample of amniotic fluid. During the first trimester of pregnancy, chorionic villus sampling (CVS) is also a technique used for SCD prenatal diagnosis.Colah, R. B., Gorakshakar, A. C., & Nadkarni, A. H. (2011). Invasive & non-invasive approaches for prenatal diagnosis of haemoglobinopathies: experiences from India. The Indian Journal of Medical Research, 134(4), 552–560. A routine heel prick test, in which a small sample of blood is collected a few days after birth, is used to check conclusively for SCD as well as other inherited conditions.{{Cite web |date=5 September 2024 |title=Newborn blood spot test |url=https://www.nhs.uk/conditions/baby/newborn-screening/blood-spot-test/ |access-date=2024-11-20 |website=National Health Service |language=en}}

File:Schematic of alkaline hemoglobin electrophoresis.png

Where SCD is suspected, a number of tests can be used. Often a simpler, cheaper test is applied first with a more complex test such as DNA analysis used to confirm a positive result.{{Cite journal |last1=Arishi |first1=Wjdan A. |last2=Alhadrami |first2=Hani A. |last3=Zourob |first3=Mohammed |date=2021-05-05 |title=Techniques for the Detection of Sickle Cell Disease: A Review |journal=Micromachines |language=en |volume=12 |issue=5 |pages=519 |doi=10.3390/mi12050519 |doi-access=free |pmc=8148117 |pmid=34063111}}

Two tests which are specific for SCD:

• A blood smear is a thin layer of blood smeared on a glass microscope slide and then stained in such a way as to allow the various blood cells to be examined microscopically. This technique can be used to visually detect sickled cells, however it does not detect sickle carriers.
• A solubility test relies on the fact that HbS is less soluble than normal hemoglobin (HbA); it is highly reliable but does not distinguish between full SCD and carrier status.{{Cite journal |last1=Mendez-Marti |first1=Sebastian R. |last2=Zik |first2=Chad |last3=Alan |first3=Sheinei |last4=Wang |first4=Hongkun |last5=Ershler |first5=William B. |date=June 2024 |title=Sickle Cell Screening in Adults: A Current Review of Point-of-Care Testing |url=https://thejh.org/index.php/JH/article/view/1272 |journal=Journal of Hematology |language=en |volume=13 |issue=3 |pages=53–60 |doi=10.14740/jh1272 |issn=1927-1212 |pmc=11236353 |pmid=38993742}}

Tests which can be used for SCD as well as for other hemoglobinopathies:

• Hemoglobin electrophoresis is a test that can detect different types of hemoglobin. Hemoglobin is extracted from the red cells, then introduced into a porous gel and subjected to an electrical field. This separates the normal and abnormal types of hemoglobin which can then be identified and quantified.{{Cite web |title=Hemoglobin Electrophoresis: MedlinePlus Medical Test |url=https://medlineplus.gov/lab-tests/hemoglobin-electrophoresis/ |access-date=2024-11-20 |website=medlineplus.gov |language=en}}
• Isoelectric focusing (IEF) is a technique that can be used to diagnose sickle cell disease and other hemoglobinopathies. The technique separates molecules based on their isoelectric point, or the pH at which they have no net electrical charge. IEF uses an electric charge to separate and identify different types of hemoglobin, which become focused into sharp stationary bands. The technique can distinguish many types of abnormal hemoglobin.{{Citation |last=Garfin |first=David E. |title=[35] Isoelectric focusing |date=1990 |journal=Methods in Enzymology |volume=182 |pages=459–477 |editor-last=Deutscher |editor-first=Murray P. |url=https://linkinghub.elsevier.com/retrieve/pii/0076687990820373 |access-date=2024-11-20 |series=Guide to Protein Purification |publisher=Academic Press |doi=10.1016/0076-6879(90)82037-3|pmid=2314254 |isbn=978-0-12-182083-1 }}
• High-performance liquid chromatography (HPLC) is reliable, fully automated, and able to distinguish most types of sickle cell disease including heterozygous, The method separates and quantifies hemoglobin fractions by measuring their rate of flow through a column of absorbent material.
• DNA analysis using polymerase chain reaction (PCR), to amplify small samples of DNA. Variants of PCR used to diagnose SCD include Amplification-refractory mutation system (ARMS) and Allele-Specific Recombinase Polymerase Amplification. These tests can identify subtypes of SCD as well as combination hemoglobinopathies.

Genetic counselling is the process by which people with a hereditary disorder are advised of the probability of transmitting it and the ways in which this may be prevented or ameliorated.{{Citation |last=Petrou |first=Mary |title=GENETIC COUNSELLING |date=2013 |work=Prevention of Thalassaemias and Other Haemoglobin Disorders: Volume 1: Principles [Internet]. 2nd edition |url=https://www.ncbi.nlm.nih.gov/books/NBK190461/ |access-date=2024-11-22 |publisher=Thalassaemia International Federation |language=en}}

People who are known carriers of the disease or at risk of having a child with sickle cell anemia may undergo genetic counseling. Genetic counselors work with families to discuss the benefits, limitations, and logistics of genetic testing options as well as the potential impact of testing and test results on the individual.{{cite web|title=National Society of Genetic Counselors : About Genetic Counselors|url=https://www.nsgc.org/page/aboutgeneticcounselors|access-date=24 February 2021|website=www.nsgc.org}} Counselling is best given before a child is conceived, and a number of possible courses could be suggested. These include adoption, the use of eggs or sperm from a healthy donor, and in-vitro fertilisation (IVF) when combined with pre-implantation genetic diagnosis of the embryos.{{Cite web |date=2017-10-23 |title=Sickle cell disease - Carriers |url=https://www.nhs.uk/conditions/sickle-cell-disease/carriers/ |access-date=2024-11-22 |website=nhs.uk |language=en}}

{{Further|Pain management in children}}

There are a number of precautions which can help reduce the risk of developing a sickling crisis. Lifestyle behaviours include maintaining good hydration and avoiding physical stress or exhaustion. Since sickling can be triggered by low oxygen levels, people with SCD should avoid high altitudes such as high mountains or flying in unpressurised aircraft.{{Cite web |date=2024-10-03 |title=Prevention and Treatment of SCD Complications |url=https://www.cdc.gov/sickle-cell/about/prevention-and-treatment.html |access-date=2024-11-28 |website=Centers for Disease Control and Prevention |language=en-us}}{{Cite web |date=30 November 2022 |title=Living with Sickle cell disease |url=https://www.nhs.uk/conditions/sickle-cell-disease/living-with/ |access-date=2024-11-28 |website=National Health Service |language=en}} People with SCD should avoid alcohol and smoking, as alcohol can cause dehydration and smoking can trigger acute chest syndrome. Stress can also trigger a sickle cell crisis, so relaxation techniques like breathing exercises can help.

Pneumococcal infection is a leading cause of death among children with SCD; penicillin is recommended daily during the first 5 years of life in order to minimise the risk of infection.{{Cite web |date=July 2021 |title=Sickle cell disease: Scenario: Prevention of complications |url=https://cks.nice.org.uk/topics/sickle-cell-disease/management/prevention-of-complications/ |access-date=2024-11-28 |website=National Institute for Health and Care Excellence}}{{Cite web |title=Penicillin in Sickle Cell Disease: Quick Facts For Parents |url=https://msdh.ms.gov/page/41,363,101.html |access-date=2024-11-29 |website=Mississippi State Department of Health}}

Dietary supplementation of folic acid is sometimes recommended, on the basis that it facilitates the creation of new red blood cells and may reduce anemia. A Cochrane review of its use in 2016 found "the effect of supplementation on anaemia and any symptoms of anaemia remains unclear" due to a lack of medical evidence.{{cite journal |vauthors=Dixit R, Nettem S, Madan SS, Soe HH, Abas AB, Vance LD, Stover PJ |date=March 2018 |title=Folate supplementation in people with sickle cell disease |journal=The Cochrane Database of Systematic Reviews |volume=3 |issue=4 |pages=CD011130 |doi=10.1002/14651858.CD011130.pub3 |pmc=5440187 |pmid=29546732}}{{cite web |date=January 2011 |title=Sickle-cell disease and other haemoglobin disorders Fact sheet N°308 |url=https://www.who.int/mediacentre/factsheets/fs308/en/ |url-status=dead |archive-url=https://web.archive.org/web/20160309034307/http://www.who.int/mediacentre/factsheets/fs308/en/ |archive-date=9 March 2016 |access-date=8 March 2016}}

People with SCD are recommended to receive all vaccinations which are recommended by health authorities in order to avoid serious infection which might trigger a sickling crisis.{{Cite web |last=Department of Clinical Illustration, New Cross Hospital, Wolverhampton |date=8 July 2024 |title=Vaccination advice for people with Sickle Cell Disorders |url=https://www.rwt.nhs.uk/PIL/MI_192414_23.06.21_V_2_public.pdf |access-date=3 December 2024 |website=The Royal Wolverhampton NHS Trust}}{{Cite journal |last1=Obeagu |first1=Emmanuel Ifeanyi |last2=Obeagu |first2=Getrude Uzoma |date=2024-09-20 |title=Immunization strategies for individuals with sickle cell anemia: A narrative review |journal=Medicine |language=en-US |volume=103 |issue=38 |pages=e39756 |doi=10.1097/MD.0000000000039756 |pmc=11419550 |pmid=39312357}}

Hydroxyurea was the first approved drug for the treatment of SCD, which has been shown to decrease the number and severity of attacks and possibly increase survival time.{{cite journal |vauthors=Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M |date=April 2003 |title=Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment |journal=The Journal of the American Medical Association |volume=289 |issue=13 |pages=1645–1651 |doi=10.1001/jama.289.13.1645 |pmid=12672732 |doi-access=free |title-link=doi}}{{cite journal |author-link=Samuel Charache |vauthors=Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR |date=May 1995 |title=Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia |journal=The New England Journal of Medicine |volume=332 |issue=20 |pages=1317–1322 |doi=10.1056/NEJM199505183322001 |pmid=7715639 |doi-access=free |title-link=doi}} This is achieved, in part, by reactivating fetal haemoglobin production in place of the haemoglobin S that causes sickling. Hydroxyurea lowers the expression of adhesion molecules on endothelial and red blood cells, which lowers the chance of small vessel blockages. Additionally, it encourages the release of nitric oxide, which enhances blood flow and inhibits the formation of clots.{{Cite journal |last1=McGann |first1=Patrick |last2=Ware |first2=Russell |date=September 14, 2015 |title=Hydroxyurea therapy for sickle cell anemia |journal=Expert Opinion in Drug Safety |volume=14 |issue=11 |pages=1749–1758 |doi=10.1517/14740338.2015.1088827 |pmid=26366626 |pmc=5868345}} Hydroxyurea had previously been used as a chemotherapy agent, and some concern exists that long-term use may be harmful.{{cite journal |vauthors=Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J |date=September 2014 |title=Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members |journal=The Journal of the American Medical Association |volume=312 |issue=10 |pages=1033–1048 |doi=10.1001/jama.2014.10517 |pmid=25203083 |s2cid=37681044}}{{cite journal |vauthors=Platt OS |date=March 2008 |title=Hydroxyurea for the treatment of sickle cell anemia |journal=The New England Journal of Medicine |volume=358 |issue=13 |pages=1362–1369 |doi=10.1056/NEJMct0708272 |pmid=18367739 |s2cid=351061}} A Cochrane review in 2022 found a weak evidence base for its use in SCD.{{cite journal |vauthors=Rankine-Mullings AE, Nevitt SJ |date=September 2022 |title=Hydroxyurea (hydroxycarbamide) for sickle cell disease |journal=The Cochrane Database of Systematic Reviews |volume=2022 |issue=10 |pages=CD002202 |doi=10.1002/14651858.CD002202.pub3 |pmc=9435593 |pmid=36047926}}

Voxelotor was received accelerated approval as a treatment for SCD in the United States in 2019, and was approved by the European Medicines Agency (EMA) in 2021.{{cite press release |title=New treatment for sickle cell disease |date=17 December 2021 |url=https://www.ema.europa.eu/en/news/new-treatment-sickle-cell-disease |access-date=18 December 2021 |website=European Medicines Agency (RMA)}} In trials, it had been shown to have disease-modifying potential by increasing hemoglobin levels and decreasing hemolysis indicators{{cite journal |vauthors=Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J |date=August 2019 |title=A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease |journal=The New England Journal of Medicine |volume=381 |issue=6 |pages=509–519 |doi=10.1056/NEJMoa1903212 |pmid=31199090 |doi-access=free}}{{cite web |author=Center for Drug Evaluation and Research |date=25 November 2019 |title=FDA approves voxelotor for sickle cell disease |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-voxelotor-sickle-cell-disease |access-date=9 December 2019 |website=FDA}} However, following an increased risk of vaso-occlusive seizures and death observed in registries and clinical trials, the manufacturer, Pfizer, withdrew it from the market worldwide.{{Cite web |date=2024-09-26 |title=EMA recommends suspension of sickle cell disease medicine Oxbryta {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/news/ema-recommends-suspension-sickle-cell-disease-medicine-oxbryta |access-date=2024-10-11 |website=www.ema.europa.eu |language=en}}{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2024-09-26 |title=FDA is alerting patients and health care professionals about the voluntary withdrawal of Oxbryta from the market due to safety concerns |url=https://www.fda.gov/drugs/drug-safety-and-availability/fda-alerting-patients-and-health-care-professionals-about-voluntary-withdrawal-oxbryta-market-due |journal=FDA |language=en}}

{{Main|Transfusion therapy (Sickle-cell disease)}}

A simple blood transfusion can be used to treat SCD when hemoglobin levels drop too low, or to prepare for an operation or pregnancy. It can also be used to protect against long-term complications, or to reduce the risk of stroke. The simple, or top-up transfusion is a procedure in which healthy blood cells from a donor are infused into the patient's bloodstream. This benefits by alleviating anemia and increasing oxygen levels in the tissues, reducing the risk of sickling and relieving sickling symptoms. A simple transfusion can be used to treat SCD when hemoglobin levels drop too low, or to prepare for an operation or pregnancy. It can also be used to protect against long-term complications, or to reduce the risk of stroke.{{Cite web |title=Simple blood transfusion - Overview |url=https://www.guysandstthomas.nhs.uk/health-information/simple-blood-transfusion |access-date=2024-12-01 |website=Guy's and St Thomas' NHS Foundation Trust |language=en-GB}}{{Cite journal |last1=Han |first1=Hyojeong |last2=Hensch |first2=Lisa |last3=Tubman |first3=Venée N. |date=2021-12-10 |title=Indications for transfusion in the management of sickle cell disease |url=https://ashpublications.org/hematology/article/2021/1/696/482990/Indications-for-transfusion-in-the-management-of |journal=Hematology |volume=2021 |issue=1 |pages=696–703 |doi=10.1182/hematology.2021000307 |issn=1520-4391 |pmc=8791131 |pmid=34889416}}

An exchange transfusion is a procedure in which blood is removed from the body, then processed to extract sickled cells, which are replaced by healthy red blood cells from a donor. The treated blood, including white cells and plasma, is then returned to the patient. Exchange transfusions are likely to be needed in an emergency, in severe cases of SCD, or to support a mother during pregnancy.{{Cite web |title=Exchange blood transfusion - Overview |url=https://www.guysandstthomas.nhs.uk/health-information/exchange-blood-transfusion |access-date=2024-12-01 |website=Guy's and St Thomas' NHS Foundation Trust |language=en-GB}}

Transcranial Doppler ultrasound (TCD) can detect children with sickle cell that have a high risk for stroke. The ultrasound test detects blood vessels partially obstructed by sickle cells by measuring the rate of blood into the brain, as blood flow velocity is inversely related to arterial diameter, and consequently, high blood-flow velocity is correlated with narrowing of the arteries.{{cite journal |vauthors=Adams RJ, McKie VC, Hsu L, Files B, Vichinsky E, Pegelow C, Abboud M, Gallagher D, Kutlar A, Nichols FT, Bonds DR, Brambilla D |date=July 1998 |title=Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography |journal=The New England Journal of Medicine |volume=339 |issue=1 |pages=5–11 |doi=10.1056/NEJM199807023390102 |pmid=9647873 |doi-access=free |title-link=doi}}

In children, preventive RBC transfusion therapy has been shown to reduce the risk of first stroke or silent stroke when transcranial Doppler ultrasonography shows abnormal cerebral blood flow. In those who have sustained a prior stroke event, it also reduces the risk of recurrent stroke and additional silent strokes.{{cite journal |vauthors=Gyang E, Yeom K, Hoppe C, Partap S, Jeng M |date=January 2011 |title=Effect of chronic red cell transfusion therapy on vasculopathies and silent infarcts in patients with sickle cell disease |journal=American Journal of Hematology |volume=86 |issue=1 |pages=104–106 |doi=10.1002/ajh.21901 |pmid=21117059 |doi-access=free |title-link=doi}}{{cite journal |vauthors=Mirre E, Brousse V, Berteloot L, Lambot-Juhan K, Verlhac S, Boulat C, Dumont MD, Lenoir G, de Montalembert M |date=March 2010 |title=Feasibility and efficacy of chronic transfusion for stroke prevention in children with sickle cell disease |journal=European Journal of Haematology |volume=84 |issue=3 |pages=259–265 |doi=10.1111/j.1600-0609.2009.01379.x |pmid=19912310 |s2cid=24316310}}

Most people with sickle cell disease have intensely painful episodes called vaso-occlusive crises (VOC). However, the frequency, severity, and duration of these crises vary tremendously. In a VOC, the circulation of blood vessels is obstructed by sickled red blood cells, causing ischemic injuries to the tissues, inflammation and pain. Recurrent episodes may cause irreversible organ damage.{{Cite web |date=2024-05-22 |title=Complications of Sickle Cell Disease |url=https://www.cdc.gov/sickle-cell/complications/index.html |access-date=2024-12-05 |website=Centers for Disease Control and Prevention |language=en-us}}{{Cite web |title=Sickle Cell Disease (SCD) Clinical Presentation: History, Physical Examination |url=https://emedicine.medscape.com/article/205926-clinical |access-date=2024-12-05 |website=emedicine.medscape.com |language=en}}

The most common and obvious symptom of a VOC is pain, which may be felt anywhere in the body but most commonly in the limbs and back. The degree of pain varies from mild to severe. Home treatment options include bedrest and hydration, and pain control using over-the-counter medication such as paracetamol or ibuprofen.{{Cite web |date=2017-10-23 |title=Sickle cell disease - Treatment |url=https://www.nhs.uk/conditions/sickle-cell-disease/treatment/ |access-date=2024-12-05 |website=National Health Service |language=en}} More severe cases may require prescription opioids such as codeine or morphine for pain control.{{Cite web |date=July 2021 |title=Scenario: Management - sickle cell crisis |url=https://cks.nice.org.uk/topics/sickle-cell-disease/management/management-sickle-cell-crisis/ |access-date=5 December 2024 |website=National Institute for Health and Care Excellence}}

In 2019, crizanlizumab, a monoclonal antibody targeting P-selectin, was approved in the United States to reduce the frequency of vaso-occlusive crisis in those 16 years and older.{{cite web |date=15 November 2019 |title=FDA approves crizanlizumab-tmca for sickle cell disease |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-crizanlizumab-tmca-sickle-cell-disease |access-date=12 December 2023 |publisher=U.S. Food and Drug Administration}} It had also been approved in the UK and Europe, but in both cases authorisation was subsequently withdrawn because of poor evidence of its effectiveness.{{Cite web |date=2023-05-26 |title=Adakveo - referral {{!}} European Medicines Agency (EMA) |url=https://www.ema.europa.eu/en/medicines/human/referrals/adakveo |access-date=2024-12-05 |website=www.ema.europa.eu |language=en}}{{Cite web |date=2024-02-01 |title=Crizanlizumab - end of NHS supply » Sickle Cell Society |url=https://www.sicklecellsociety.org/crizanlizumab-end-of-nhs-supply/ |access-date=2024-12-05 |website=Sickle Cell Society |language=}}

Acute chest syndrome is caused by vaso-occlusion occurring in the lungs. As with a VOC, treatment includes pain control and hydration. Antibiotics are required because there is a severe risk of pulmonary infection, and oxygen supplementation for hypoxia. Blood transfusion may also be required, or exchange transfusion in severe cases.{{Citation |last1=Friend |first1=Amanda |title=Acute Chest Syndrome |date=2024 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK441872/ |access-date=2024-12-06 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28722902 |last2=Settelmeyer |first2=Teagan P. |last3=Girzadas |first3=Daniel}}

When treating avascular necrosis of the bone in people with sickle cell disease, the aim of treatment is to reduce or stop the pain and maintain joint mobility. Treatment options include resting the joint, physical therapy, pain-relief medicine, joint-replacement surgery, or bone grafting.

Psychological therapies such as patient education, cognitive therapy, behavioural therapy, and psychodynamic psychotherapy, that aim to complement current medical treatments, require further research to determine their effectiveness.{{cite journal |vauthors=Anie KA, Green J |date=May 2015 |title=Psychological therapies for sickle cell disease and pain |journal=The Cochrane Database of Systematic Reviews |volume=2015 |issue=5 |pages=CD001916 |doi=10.1002/14651858.CD001916.pub3 |pmc=7063720 |pmid=25966336}}

Hematopoietic stem cells (HSC) are cells in the bone marrow that can develop into all types of blood cells, including red blood cells, white blood cells, and platelets.{{Cite web |date=December 12, 2022 |title=Hematopoiesis |url=https://my.clevelandclinic.org/health/articles/24287-hematopoiesis |access-date=6 December 2024 |website=Cleveland Clinic}} There are two possible ways to treat SCD and some other hemoglobinopathies by targeting HSCs. Since 1991, a small number of patients have received bone marrow transplants from healthy matched donors, although this procedure has a high level of risk.{{cite journal |vauthors=Walters MC, Patience M, Leisenring W, Eckman JR, Scott JP, Mentzer WC, Davies SC, Ohene-Frempong K, Bernaudin F, Matthews DC, Storb R, Sullivan KM |date=August 1996 |title=Bone marrow transplantation for sickle cell disease |journal=The New England Journal of Medicine |volume=335 |issue=6 |pages=369–376 |doi=10.1056/NEJM199608083350601 |pmid=8663884 |s2cid=25256772 |doi-access=free |title-link=doi}} More recently, it has become possible to use CRISPR gene editing technology to modify the patient's own HSCs in a way that reduces or eliminates the production of sickle hemoglobin HbS and replaces it with a non-sickling form of hemoglobin.{{Cite journal |last1=Olson |first1=Timothy S. |last2=Walters |first2=Mark C. |date=2023-10-01 |title=Allogeneic haematopoietic stem-cell transplantation versus gene therapy for haemoglobinopathies |url=https://linkinghub.elsevier.com/retrieve/pii/S2352302623002466 |journal=The Lancet Haematology |language=English |volume=10 |issue=10 |pages=e798–e800 |doi=10.1016/S2352-3026(23)00246-6 |issn=2352-3026 |pmid=37793770}}

All stem cell treatments must involve myeloablation of the patients' bone marrow in order to remove HSCs containing the faulty gene. This requires high doses of chemotherapy agents with side effects such as sickness and tiredness. A long hospital stay is necessary after infusion of the replacement HSCs while the cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin.{{Cite web |date=2017-10-23 |title=Stem cell transplant - What happens |url=https://www.nhs.uk/conditions/stem-cell-transplant/what-happens/ |access-date=2024-12-07 |website=nhs.uk |language=en}}{{Cite web |title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia |url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |access-date=2024-12-07 |website=GOV.UK |language=en}}

Gene therapy was first trialled in 2014 on a single patient,{{Cite journal |last1=Ribeil |first1=Jean-Antoine |last2=Hacein-Bey-Abina |first2=Salima |last3=Payen |first3=Emmanuel |last4=Magnani |first4=Alessandra |last5=Semeraro |first5=Michaela |last6=Magrin |first6=Elisa |last7=Caccavelli |first7=Laure |last8=Neven |first8=Benedicte |last9=Bourget |first9=Philippe |last10=Nemer |first10=Wassim El |last11=Bartolucci |first11=Pablo |last12=Weber |first12=Leslie |last13=Puy |first13=Hervé |last14=Meritet |first14=Jean-François |last15=Grevent |first15=David |date=2017-03-02 |title=Gene Therapy in a Patient with Sickle Cell Disease |url=https://www.nejm.org/doi/10.1056/NEJMoa1609677 |journal=New England Journal of Medicine |volume=376 |issue=9 |pages=848–855 |doi=10.1056/NEJMoa1609677 |pmid=28249145 |issn=0028-4793}} and followed by clinical trials in which a number of patients were successfully treated.{{cite web |date=5 December 2020 |title=CRISPR and another genetic strategy fix cell defects in two common blood disorders |url=https://www.science.org/content/article/crispr-and-another-genetic-strategy-fix-cell-defects-two-common-blood-disorders |access-date=7 December 2020 |website=ScienceMag.org |publisher=Science |quote="... teams report that two strategies for directly fixing malfunctioning blood cells have dramatically improved the health of a handful of people with these genetic diseases." |vauthors=Kaiser J}} In 2023, both exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) were approved for the treatment of sickle cell disease.{{cite press release |title=MHRA authorises world-first gene therapy that aims to cure sickle-cell disease and transfusion-dependent β-thalassemia |date=16 November 2023 |url=https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |access-date=8 December 2023 |url-status=live |archive-url=https://web.archive.org/web/20231125015409/https://www.gov.uk/government/news/mhra-authorises-world-first-gene-therapy-that-aims-to-cure-sickle-cell-disease-and-transfusion-dependent-thalassemia |archive-date=25 November 2023 |website=Medicines and Healthcare products Regulatory Agency (MHRA)}} Kendric Cromer in October 2024 became the first commercial case in the USA to receive gene therapy and was discharged from Children's National Hospital.{{Cite news |title=Life Without Sickle Cell Beckons Boy Who Completed Gene Therapy |url=https://www.nytimes.com/2024/10/21/health/sickle-cell-disease-gene-therapy-patient.html |work=The New York Times|date=21 October 2024 | vauthors = Kolata G, Holston K }} The one-off gene-editing therapy, Casgevy, also known as Exa-cel, is to be offered to patients on the National Health Service (NHS) in England as from 2025.{{Cite web |date=2025-01-31 |title=NHS to offer 'groundbreaking' sickle cell gene therapy |url=https://www.bbc.co.uk/news/articles/cx2yg9yny0ko |access-date=2025-01-31 |website=BBC News |language=en-GB}}

Both Casgevy and Lyfgenia work by first harvesting the patient's HSCs, then using CRISPR gene editing to modify their DNA in the laboratory. In parallel with this, the person with sickle cell disease's bone marrow is put through a myeloablation procedure to destroy the remaining HSCs. The treated cells are then infused back into the patient where they colonise the bone marrow and eventually resume production of blood cells. Casgevy works by editing the BCL11A gene, which normally inhibits the production of hemoglobin F (fetal hemoglobin) in adults. The edit has the effect of increasing production of HbF, which is not prone to sickling.{{Cite web |date=7 December 2024 |title=How does Casgevy work? |url=https://www.casgevy.com/sickle-cell-disease/how-casgevy-works |access-date=7 December 2024 |website=Vertex Pharmaceuticals Incorporated}} Lyfgenia introduces a new gene for T87Q-globin which coexists with the sickling beta-globin but reduces the incidence of sickling.{{Cite web |last=Kanter |first=Julie |title=New Weapons Against A Deadly Disease: Cutting-Edge Gene Therapy Could Deliver Breakthrough For Sickle Cell Disease - Medicine Magazine |url=https://www.uab.edu/medicine/magazine/winter-2023/new-weapons-against-a-deadly-disease |access-date=2024-12-07 |website=The University of Alabama at Birmingham |language=en-US}}

Hematopoietic stem cell transplantation (HSCT) involves replacing the dysfunctional stem cells from a person with sickle cell disease with healthy cells from a well-matched donor.{{Cite journal |last1=Rotin |first1=Lianne E. |last2=Viswabandya |first2=Auro |last3=Kumar |first3=Rajat |last4=Patriquin |first4=Christopher J. |last5=Kuo |first5=Kevin H.M. |date=2023-12-31 |title=A systematic review comparing allogeneic hematopoietic stem cell transplant to gene therapy in sickle cell disease |journal=Hematology |language=en |volume=28 |issue=1 |doi=10.1080/16078454.2022.2163357 |pmid=36728286 |issn=1607-8454|doi-access=free }} Finding a well matched donor is essential to the process' success. Different types of donors may be suitable and include umbilical cord blood, human leukocyte antigen (HLA) matched relatives, or HLA matched donors that are not related to the person being treated. Risks associated with HSCT can include graft-versus host disease, failure of the graft, and other toxicity related to the transplant.

Sickle cell disease is most prevalent in sub-saharan Africa. In areas without healthcare infrastructure, it is estimated that between 50% and 90% of children born with the disease die before the age of 5 years.{{Cite journal |last1=Grosse |first1=Scott D. |last2=Odame |first2=Isaac |last3=Atrash |first3=Hani K. |last4=Amendah |first4=Djesika D. |last5=Piel |first5=Frédéric B. |last6=Williams |first6=Thomas N. |date=2011-12-01 |title=Sickle Cell Disease in Africa: A Neglected Cause of Early Childhood Mortality |journal=American Journal of Preventive Medicine |language=English |volume=41 |issue=6 |pages=S398–S405 |doi=10.1016/j.amepre.2011.09.013 |issn=0749-3797 |pmc=3708126 |pmid=22099364}}

In contrast, life expectancy in the United States in 2010-2020 was 43 years{{Cite journal |last1=Karkoska |first1=Kristine |last2=McGann |first2=Patrick T. |date=2023-11-02 |title=Changing Trends in Sickle Cell Disease-Related Mortality in the United States over Four Decades |url=https://ashpublications.org/blood/article/142/Supplement%201/925/502077/Changing-Trends-in-Sickle-Cell-Disease-Related |journal=Blood |volume=142 |issue=Supplement 1 |pages=925 |doi=10.1182/blood-2023-177988 |issn=0006-4971}} and in the UK 67 years.{{Cite web |date=July 2021 |title=Sickle cell disease: What is the prognosis? |url=https://cks.nice.org.uk/topics/sickle-cell-disease/background-information/prognosis/ |access-date=2024-10-25 |website=National Institute for Health and Care Excellence}}

The HbS gene can be found in every ethnic group.{{cite book |author=((National Academies of Sciences, Engineering, and Medicine, Health and Medicine Division, Board on Population Health and Public Health Practice, Committee on Addressing Sickle Cell Disease)) |title=Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action |date=2020 |publisher=National Academies Press |location=Washington |isbn=978-0-309-66960-3 |page=1 |url=https://books.google.com/books?id=JsEXEAAAQBAJ |language=en}} The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Saharan Africa, tribal regions of India, and the Middle East.{{cite journal | vauthors = Weatherall DJ, Clegg JB | title = Inherited haemoglobin disorders: an increasing global health problem | journal = Bulletin of the World Health Organization | volume = 79 | issue = 8 | pages = 704–712 | year = 2001 | pmid = 11545326 | pmc = 2566499 }} About 80% of sickle cell disease cases are believed to occur in Sub-Saharan Africa. Migration of substantial populations from these high-prevalence areas to low-prevalence countries in Europe has dramatically increased in recent decades and in some European countries, sickle cell disease has now overtaken more familiar genetic conditions such as haemophilia and cystic fibrosis.{{cite journal | vauthors = Roberts I, de Montalembert M | title = Sickle cell disease as a paradigm of immigration hematology: new challenges for hematologists in Europe | journal = Haematologica | volume = 92 | issue = 7 | pages = 865–871 | date = July 2007 | pmid = 17606434 | doi = 10.3324/haematol.11474 | doi-access = free | title-link = doi }} In 2015, it resulted in about 114,800 deaths.{{cite journal |vauthors=Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, etal |date=October 2016 |title=Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015 |journal=Lancet |volume=388 |issue=10053 |pages=1459–1544 |doi=10.1016/S0140-6736(16)31012-1 |pmc=5388903 |pmid=27733281 |collaboration=GBD 2015 Mortality and Causes of Death Collaborators}}

Sickle cell disease occurs more commonly among people whose ancestors lived in tropical and subtropical sub-Saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle cell allele (trait) confers a heterozygote advantage; humans with one of the two alleles of sickle cell disease show less severe symptoms when infected with malaria.{{cite journal | vauthors = Wellems TE, Hayton K, Fairhurst RM | title = The impact of malaria parasitism: from corpuscles to communities | journal = The Journal of Clinical Investigation | volume = 119 | issue = 9 | pages = 2496–2505 | date = September 2009 | pmid = 19729847 | pmc = 2735907 | doi = 10.1172/JCI38307 }}

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Three-quarters of sickle cell cases occur in Africa. A WHO report dated 2006 estimated that around 2% of newborns in Nigeria were affected by sickle cell anaemia, giving a total of 150,000 affected children born every year in Nigeria alone. The carrier frequency ranges between 10 and 40% across equatorial Africa, decreasing to 1–2% on the North African coast and <1% in South Africa.{{cite web|title=Sickle-cell anaemia – Report by the Secretariat|url=http://apps.who.int/gb/ebwha/pdf_files/WHA59/A59_9-en.pdf|author=WHO|url-status=dead|archive-url=https://web.archive.org/web/20110104014531if_/http://apps.who.int/gb/ebwha/pdf_files/WHA59/A59_9-en.pdf|archive-date=4 January 2011|access-date=27 November 2010}}

Uganda has the fifth-highest sickle cell disease burden in Africa. One study indicates that 20 000 babies per year are born with sickle cell disease with the sickle cell trait at 13.3% and with disease 0.7%.{{cite journal | vauthors = Ndeezi G, Kiyaga C, Hernandez AG, Munube D, Howard TA, Ssewanyana I, Nsungwa J, Kiguli S, Ndugwa CM, Ware RE, Aceng JR | title = Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study | journal = The Lancet. Global Health | volume = 4 | issue = 3 | pages = e195–e200 | date = March 2016 | pmid = 26833239 | doi = 10.1016/S2214-109X(15)00288-0 | doi-access = free | title-link = doi }}

The number of people with the disease in the United States is about 100,000 (one in 3,300), mostly affecting Americans of sub-Saharan African descent.{{cite web|author=National Heart, Lung and Blood Institute|url=http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_Summary.html|title=Sickle cell anemia, key points|access-date=27 November 2010|url-status=live|archive-url=https://web.archive.org/web/20101202224231/http://www.nhlbi.nih.gov/health/dci/Diseases/Sca/SCA_Summary.html|archive-date=2 December 2010}} In the United States, about one out of 365 African-American children and one in every 16,300 Hispanic-American children have sickle cell anaemia.{{cite web |date=31 August 2016 |title=Data & Statistics on Sickle Cell Disease |url=https://www.cdc.gov/NCBDDD/sicklecell/data.html |access-date=13 December 2019 |website=Centers for Disease Control and Prevention}} The life expectancy for men with SCD is approximately 42 years of age while women live approximately six years longer.{{cite web |title=September is Sickle Cell Awareness Month |url=https://www.cdc.gov/Features/SickleCellAwareness/ |url-status=live |archive-url=https://web.archive.org/web/20100927162235/http://www.cdc.gov/Features/SickleCellAwareness/ |archive-date=27 September 2010 |access-date=6 February 2011 |website=Centers for Disease Control and Prevention |publisher=}} An additional 2{{nbsp}}million are carriers of the sickle cell trait.{{cite web |title=Sickle Cell Trait |url=https://www.hematology.org/Patients/Anemia/Sickle-Cell-Trait.aspx |website=American Society of Hematology |access-date=13 December 2019 |date=8 September 2017}} Most infants with SCD born in the United States are identified by routine neonatal screening. As of 2016 all 50 states include screening for sickle cell disease as part of their newborn screen.{{cite web|title=Disorder Name: Sickle Cell Disease|url=http://www.newbornscreening.info/Parents/otherdisorders/SCD.html|publisher=New Born Screening|access-date=11 October 2016|url-status=live|archive-url=https://web.archive.org/web/20160928052252/http://www.newbornscreening.info/Parents/otherdisorders/SCD.html|archive-date=28 September 2016}} The newborn's blood is sampled through a heel-prick and is sent to a lab for testing. The baby must have been eating for a minimum of 24 hours before the heel-prick test can be done. Some states also require a second blood test to be done when the baby is two weeks old to ensure the results.{{cite web|url=https://www.stanfordchildrens.org/en/topic/default?id=newborn-screening-tests-90-P01967|title=default – Stanford Children's Health|website=www.stanfordchildrens.org|access-date=14 March 2020}}

Sickle cell anemia is the most common genetic disorder among African Americans. Approximately 8% are carriers and 1 in 375 are born with the disease.{{cite journal | vauthors = Edwards QT, Seibert D, Macri C, Covington C, Tilghman J | title = Assessing ethnicity in preconception counseling: genetics—what nurse practitioners need to know | journal = Journal of the American Academy of Nurse Practitioners | volume = 16 | issue = 11 | pages = 472–480 | date = November 2004 | pmid = 15617360 | doi = 10.1111/j.1745-7599.2004.tb00426.x | s2cid = 7644129 }} Patient advocates for sickle cell disease have complained that it gets less government and private research funding than similar rare diseases such as cystic fibrosis, with researcher Elliott Vichinsky saying this shows racial discrimination or the role of wealth in health care advocacy.{{cite news|title=Sickle Cell Patients Endure Discrimination, Poor Care And Shortened Lives|url=https://www.npr.org/sections/health-shots/2017/11/04/561654823/sickle-cell-patients-endure-discrimination-poor-care-and-shortened-lives|date=4 November 2017|website=NPR.org|access-date=12 November 2017}} Overall, without considering race, approximately 1.5% of infants born in the United States are carriers of at least one copy of the mutant (disease-causing) gene.{{Cite journal |last1=Vlachadis |first1=Nikolaos |last2=Vrachnis |first2=Nikolaos |date=2022-11-15 |title=A Review of Sickle Cell Disease |url=https://jamanetwork.com/journals/jama/fullarticle/2798413 |journal=JAMA |language=en |volume=328 |issue=19 |pages=1979 |doi=10.1001/jama.2022.16732 |pmid=36378213 |issn=0098-7484}}

File:Percentage of newborns screened for sickle cell disease within Metropolitan France from 2006 to 2018.svg

As a result of population growth in African-Caribbean regions of overseas France and immigration from North and sub-Saharan Africa to mainland France, sickle cell disease has become a major health problem in France.{{cite journal | vauthors = Bardakdjian J, Wajcman H | title = [Epidemiology of sickle cell anemia] | language = fr | journal = La Revue du Praticien | volume = 54 | issue = 14 | pages = 1531–1533 | date = September 2004 | pmid = 15558961 }} SCD has become the most common genetic disease in the country, with an overall birth prevalence of one in 2,415 in mainland France, ahead of phenylketonuria (one in 10,862), congenital hypothyroidism (one in 3,132), congenital adrenal hyperplasia (one in 19,008) and cystic fibrosis (one in 5,014) for the same reference period.{{Cite journal|title=Prevalence and cost of sickle cell disease in France: real-world analysis using data from the Echantillon Généraliste des Bénéficiaires|first1=Maud|last1=Beillat|first2=Isabelle|last2=Durand-Zaleski|first3=France|last3=Pirenne|first4=Stève|last4=Bénard|first5=Louis|last5=Chillotti|first6=Frédéric|last6=Galacteros|date=21 September 2023|journal=Frontiers in Public Health|volume=11|pages=1215605|doi=10.3389/fpubh.2023.1215605|doi-access=free |pmid=37808997|pmc=10552641 }}

File:Sickle Cell disease screening of newborns in Metropolitan France in 2018.png

Since 2000, neonatal screening of SCD has been performed at the national level for all newborns defined as being "at-risk" for SCD based on ethnic origin (defined as those born to parents originating from sub-Saharan Africa, North Africa, the Mediterranean area (South Italy, Greece, and Turkey), the Arabic peninsula, the French overseas islands, and the Indian subcontinent).{{cite journal | vauthors = Thuret I, Sarles J, Merono F, Suzineau E, Collomb J, Lena-Russo D, Levy N, Bardakdjian J, Badens C | title = Neonatal screening for sickle cell disease in France: evaluation of the selective process | journal = Journal of Clinical Pathology | volume = 63 | issue = 6 | pages = 548–551 | date = June 2010 | pmid = 20498028 | doi = 10.1136/jcp.2009.068874 | s2cid = 22391674 }}

In the United Kingdom, between 12,000 and 15,000 people are thought to have sickle cell disease {{cite web|url=http://www.nhs.uk/Livewell/Blackhealth/Pages/Sicklecellanaemia.aspx|title=Inheriting sickle cell anaemia – Live Well – NHS Choices|work=www.nhs.uk|url-status=live|archive-url=https://web.archive.org/web/20141202042027/http://www.nhs.uk/Livewell/Blackhealth/Pages/Sicklecellanaemia.aspx|archive-date=2 December 2014|date=23 October 2017}} with an estimated 250,000 carriers of the condition in England alone. As the number of carriers is only estimated, all newborn babies in the UK receive a routine blood test to screen for the condition.{{cite web|url=http://www.nhs.uk/conditions/sickle-cell-anaemia/Pages/Introduction.aspx|title=Sickle cell anaemia – NHS Choices|work=www.nhs.uk|url-status=live|archive-url=https://web.archive.org/web/20111213004103/http://www.nhs.uk/conditions/Sickle-cell-anaemia/Pages/Introduction.aspx|archive-date=13 December 2011|date=23 October 2017}} Due to many adults in high-risk groups not knowing if they are carriers, pregnant women and both partners in a couple are offered screening so they can get counselling if they have the sickle cell trait.{{cite web|url=http://www.sct.screening.nhs.uk/who|title=Who is offered screening and when?|work=screening.nhs.uk|url-status=live|archive-url=https://web.archive.org/web/20141231011755/http://www.sct.screening.nhs.uk/who|archive-date=31 December 2014}} In addition, blood donors from those in high-risk groups are also screened to confirm whether they are carriers and whether their blood filters properly.{{cite news|url=http://www.blood.co.uk/resources/leaflets/sickle-cell/|title=Give Blood – Resources – Sickle Cell and Blood Donation|work=Give Blood|url-status=live|archive-url=https://web.archive.org/web/20141231013358/http://www.blood.co.uk/resources/leaflets/sickle-cell/|archive-date=31 December 2014}} Donors who are found to be carriers are informed and their blood, while often used for those of the same ethnic group, is not used for those with sickle cell disease who require a blood transfusion.{{cite web|title=Why is Blood from Afro-Caribbean Donors Special?|url=http://sicklecellsociety.org/resources/why-is-blood-from-afro-caribbean-donors-special/|work=sicklecellsociety.org|url-status=dead|archive-url=https://web.archive.org/web/20141230223500/http://sicklecellsociety.org/resources/why-is-blood-from-afro-caribbean-donors-special/|archive-date=30 December 2014}}

In Saudi Arabia, about 4.2% of the population carry the sickle cell trait and 0.26% have sickle cell disease. The highest prevalence is in the Eastern province, where approximately 17% of the population carry the gene and 1.2% have sickle cell disease.{{cite journal | vauthors = Jastaniah W | title = Epidemiology of sickle cell disease in Saudi Arabia | journal = Annals of Saudi Medicine | volume = 31 | issue = 3 | pages = 289–293 | year = 2011 | pmid = 21623060 | pmc = 3119971 | doi = 10.4103/0256-4947.81540 | doi-access = free | title-link = doi }}

In 2005, Saudi Arabia introduced a mandatory premarital test including HB electrophoresis, which aimed to decrease the incidence of SCD and thalassemia.{{cite journal | vauthors = Memish ZA, Saeedi MY | title = Six-year outcome of the national premarital screening and genetic counseling program for sickle cell disease and β-thalassemia in Saudi Arabia | journal = Annals of Saudi Medicine | volume = 31 | issue = 3 | pages = 229–235 | year = 2011 | pmid = 21623050 | pmc = 3119961 | doi = 10.4103/0256-4947.81527 | doi-access = free | title-link = doi }}

In Bahrain, a study published in 1998 that covered about 56,000 people in hospitals in Bahrain found that 2% of newborns have sickle cell disease, 18% of the surveyed people have the sickle cell trait, and 24% were carriers of the gene mutation causing the disease.{{cite journal| vauthors = Al Arrayed S |date=1995|title=Features of sickle-cell disease in Bahrain|url=http://www.emro.who.int/emhj-volume-1-1995/volume-1-issue-1/article13.html|url-status=live|journal=Eastern Mediterranean Health Journal|volume=1|issue=1|archive-url=https://web.archive.org/web/20161008110750/http://www.emro.who.int/emhj-volume-1-1995/volume-1-issue-1/article13.html|archive-date=8 October 2016}} The country began screening of all pregnant women in 1992, and newborns started being tested if the mother was a carrier. In 2004, a law was passed requiring couples planning to marry to undergo free premarital counseling. These programs were accompanied by public education campaigns.{{cite journal | vauthors = Al Arrayed S, Al Hajeri A | title = Public awareness of sickle cell disease in Bahrain | journal = Annals of Saudi Medicine | volume = 30 | issue = 4 | pages = 284–288 | date = 2010 | pmid = 20622345 | pmc = 2931779 | doi = 10.4103/0256-4947.65256 | doi-access = free | title-link = doi }}

Sickle cell disease is common in some ethnic groups of central India,{{cite web|url=http://www.hematology.org/Patients/Anemia/Sickle-Cell.aspx|title=Sickle Cell Anemia|date=16 December 2014|website=American Society of Hematology|access-date=1 May 2017|url-status=live|archive-url=https://web.archive.org/web/20170625204302/http://www.hematology.org/Patients/Anemia/Sickle-Cell.aspx|archive-date=25 June 2017}} where the prevalence has ranged from 9.4 to 22.2% in endemic areas of Madhya Pradesh, Rajasthan, and Chhattisgarh.{{cite journal|vauthors=Awasthy N, Aggarwal KC, Goyal PC, Prasad MS, Saluja S, Sharma M|year=2008|title=Sickle cell disease: Experience of a tertiary care center in a nonendemic area|journal=Annals of Tropical Medicine and Public Health|volume=1|issue=1|pages=1–4|doi=10.4103/1755-6783.43069 |doi-access = free | title-link = doi |doi-broken-date=1 November 2024 }} It is also endemic among Tharu people of Nepal and India; however, they have a sevenfold lower rate of malaria despite living in a malaria infested zone.{{cite web|url=http://nepalitimes.com/article/nation/Life-%20with-sickle-cell,1460|title=Life with sickle cell – Nation – Nepali Times |url-status=live|archive-url=https://web.archive.org/web/20150624141919/http://nepalitimes.com/article/nation/Life-%20with-sickle-cell%2C1460|archive-date=24 June 2015}}

In Jamaica, 10% of the population carry the sickle cell gene, making it the most prevalent genetic disorder in the country.{{cite journal | vauthors = Asnani MR, McCaw-Binns AM, Reid ME | title = Excess risk of maternal death from sickle cell disease in Jamaica: 1998–2007 | journal = PLOS ONE | volume = 6 | issue = 10 | pages = e26281 | year = 2011 | pmid = 22039456 | pmc = 3200316 | doi = 10.1371/journal.pone.0026281 | doi-access = free | title-link = doi | bibcode = 2011PLoSO...626281A }}

The first modern report of sickle cell disease may have been in 1846, where the autopsy of an executed runaway slave was discussed; the key finding was the absence of the spleen.{{cite journal| vauthors = Lebby R | year=1846 | title=Case of absence of the spleen | journal=Southern J of Med Pharmacol | volume=1 | pages=481–3}}{{cite journal | vauthors = Ballas SK, Gupta K, Adams-Graves P | title = Sickle cell pain: a critical reappraisal | journal = Blood | volume = 120 | issue = 18 | pages = 3647–3656 | date = November 2012 | pmid = 22923496 | doi = 10.1182/blood-2012-04-383430 | doi-access = free | title-link = doi | url = https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1101&context=medfp }} Reportedly, African slaves in the United States exhibited resistance to malaria, but were prone to leg ulcers. The abnormal characteristics of the red blood cells, which later lent their name to the condition, was first described by Ernest E. Irons (1877–1959), intern to Chicago cardiologist and professor of medicine James B. Herrick (1861–1954), in 1910. Irons saw "peculiar elongated and sickle-shaped" cells in the blood of a man named Walter Clement Noel, a 20-year-old first-year dental student from Grenada. Noel had been admitted to the Chicago Presbyterian Hospital in December 1904 with anaemia.{{cite journal |vauthors=Herrick JB |title=Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia |journal=Archives of Internal Medicine |date=1 November 1910 |volume=6 |issue=5 |pages=179–184 |doi=10.1001/archinte.1910.00050330050003|pmid= |pmc= }}; reprinted as {{cite journal | vauthors = Herrick JB | title = Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. 1910 | journal = The Yale Journal of Biology and Medicine | volume = 74 | issue = 3 | pages = 179–184 | year = 2001 | pmid = 11501714 | pmc = 2588723 }} Noel was readmitted several times over the next three years for "muscular rheumatism" and "bilious attacks" but completed his studies and returned to the capital of Grenada (St. George's) to practice dentistry. He died of pneumonia in 1916 and is buried in the Catholic cemetery at Sauteurs in the north of Grenada. Shortly after the report by Herrick, another case appeared in the Virginia Medical Semi-Monthly with the same title, "Peculiar Elongated and Sickle-Shaped Red Blood Corpuscles in a Case of Severe Anemia."{{cite journal | vauthors = Washburn RE | title = Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia | journal = The Virginia Medical Semi-Monthly | volume = 15 | issue = 21 | pages = 490–493 | year = 1911}} This article is based on a patient admitted to the University of Virginia Hospital on 15 November 1910.{{cite web |url=http://exhibits.hsl.virginia.edu/centennial/beginnings/ |title=UVa Hospital Celebrating 100 Years |publisher=University of Virginia |access-date=28 January 2015 |url-status=live |archive-url=https://web.archive.org/web/20150131172259/http://exhibits.hsl.virginia.edu/centennial/beginnings/ |archive-date=31 January 2015 }} In the later description by Verne Mason in 1922, the name "sickle cell anemia" is first used.{{cite journal | vauthors = Mason VR | title = Sickle cell anemia | journal = The Journal of the American Medical Association | volume = 79 | issue = 16 | pages = 1318–1320 | year = 1922 | doi = 10.1001/jama.1922.02640160038012 | url = https://zenodo.org/record/1423425 }} Reprinted in {{cite journal | vauthors = Mason VR | title = Landmark article Oct. 14, 1922: Sickle cell anemia. By V.R. Mason | journal = The Journal of the American Medical Association | volume = 254 | issue = 14 | pages = 1955–1957 | date = October 1985 | pmid = 3900438 | doi = 10.1001/jama.254.14.1955 }} Childhood problems related to sickle cells disease were not reported until the 1930s, despite the fact that this cannot have been uncommon in African-American populations.

Memphis physician Lemuel Diggs, a prolific researcher into sickle cell disease, first introduced the distinction between sickle cell disease and trait in 1933, although until 1949, the genetic characteristics had not been elucidated by James V. Neel and E.A. Beet. 1949 was the year when Linus Pauling described the unusual chemical behaviour of haemoglobin S, and attributed this to an abnormality in the molecule itself.{{cite journal | vauthors = Pauling L, Itano HA | title = Sickle cell anemia a molecular disease | journal = Science | volume = 110 | issue = 2865 | pages = 543–548 | date = November 1949 | pmid = 15395398 | doi = 10.1126/science.110.2865.543 | bibcode = 1949Sci...110..543P | s2cid = 31674765 }} The molecular change in HbS was described in 1956 by Vernon Ingram.{{cite journal | vauthors = Ingram VM | title = A specific chemical difference between the globins of normal human and sickle-cell anaemia haemoglobin | journal = Nature | volume = 178 | issue = 4537 | pages = 792–794 | date = October 1956 | pmid = 13369537 | doi = 10.1038/178792a0 | s2cid = 4167855 | bibcode = 1956Natur.178..792I }} The late 1940s and early 1950s saw further understanding in the link between malaria and sickle cell disease. In 1954, the introduction of haemoglobin electrophoresis allowed the discovery of particular subtypes, such as HbSC disease.

Large-scale natural history studies and further intervention studies were introduced in the 1970s and 1980s, leading to widespread use of prophylaxis against pneumococcal infections amongst other interventions. Bill Cosby's Emmy-winning 1972 TV movie, To All My Friends on Shore, depicted the story of the parents of a child with sickle cell disease.{{cite web| title = Foster, Gloria| work = Facts On File History Database| access-date = 25 February 2015| url = http://www.fofweb.com/History/HistRefMain.asp?iPin=AFEBW0772&SID=2&DatabaseName=African%2DAmerican+History+Online&InputText=%22sickle+cell+anemia%22&SearchStyle=&dTitle=Foster%2C+Gloria&TabRecordType=Biography&BioCountPass=11&SubCountPass=3&DocCountPass=0&ImgCountPass=1&MapCountPass=0&FedCountPass=&MedCountPass=1&NewsCountPass=0&RecPosition=10&AmericanData=&WomenData=&AFHCData=Set&IndianData=&WorldData=&AncientData=&GovernmentData=| url-status = dead| archive-url = https://web.archive.org/web/20160305194344/http://www.fofweb.com/History/HistRefMain.asp?iPin=AFEBW0772&SID=2&DatabaseName=African-American+History+Online&InputText=%22sickle+cell+anemia%22&SearchStyle=&dTitle=Foster%2C+Gloria&TabRecordType=Biography&BioCountPass=11&SubCountPass=3&DocCountPass=0&ImgCountPass=1&MapCountPass=0&FedCountPass=&MedCountPass=1&NewsCountPass=0&RecPosition=10&AmericanData=&WomenData=&AFHCData=Set&IndianData=&WorldData=&AncientData=&GovernmentData=| archive-date = 5 March 2016}} The 1990s had the development of hydroxycarbamide, and reports of cure through bone marrow transplantation appeared in 2007.

Some old texts refer to it as drepanocytosis.{{cite journal | vauthors = Richard-Lenoble D, Toublanc JE, Zinsou RD, Kombila M, Carme B | title = [Results of a systematic study of drepanocytosis in 1,500 Gabonese using hemoglobin electrophoresis] | language = fr | journal = Bulletin de la Société de Pathologie Exotique et de ses Filiales | volume = 73 | issue = 2 | pages = 200–206 | date = 1980 | pmid = 7460122 | trans-title = Results of a systematic study of drepanocytosis in 1,500 Gabonese using hemoglobin electrophoresis }}

Sickle cell disease is frequently contested as a disability.{{cite journal | url=https://academic.oup.com/hsw/advance-article/doi/10.1093/hsw/hlad014/7197405?guestAccessKey=2a0168b7-dc7e-47b2-a53a-91fed46c479f&login=false | doi=10.1093/hsw/hlad014 | title=Contested Disability: Sickle Cell Disease | date=2023 | last1=Srikanthan | first1=Sinthu | journal=Health & Social Work | volume=48 | issue=3 | pages=209–216 | pmid=37315205 }} Effective 15 September 2017, the U.S. Social Security Administration issued a Policy Interpretation Ruling providing background information on sickle cell disease and a description of how Social Security evaluates the disease during its adjudication process for disability claims.{{cite web |url= https://www.ssa.gov/OP_Home/rulings/di/01/SSR2017-03-di-01.html |title=Social Security Ruling: SSR 2017-3p | publisher = U.S. Social Security Administration |access-date=15 January 2018 }}{{cite web|url=https://www.gpo.gov/fdsys/pkg/FR-2017-09-15/html/2017-19551.htm|title=Federal Register, Volume 82 Issue 178 (Friday, September 15, 2017)|website=U.S. Government Publishing Office (GPO)|access-date=15 January 2018}}

In the US, there are stigmas surrounding SCD that discourage people with SCD from receiving necessary care. These stigmas mainly affect people of African American and Latin American ancestries, according to the National Heart, Lung, and Blood Institute. People with SCD experience the impact of stigmas of the disease on multiple aspects of life including social and psychological well-being. Studies have shown that those with SCD frequently feel as though they must keep their diagnosis a secret to avoid discrimination in the workplace and also among peers in relationships.{{cite journal | vauthors = Bulgin D, Tanabe P, Jenerette C | title = Stigma of Sickle Cell Disease: A Systematic Review | journal = Issues in Mental Health Nursing | volume = 39 | issue = 8 | pages = 675–686 | date = August 2018 | pmid = 29652215 | pmc = 6186193 | doi = 10.1080/01612840.2018.1443530 }} In the 1960s, the US government supported initiatives for workplace screening for genetic diseases in an attempt to be protective towards people with SCD. By having this screening, it was intended that employees would not be placed in environments that could potentially be harmful and trigger SCD.{{cite book| vauthors = Washington HA |title=Medical apartheid : the dark history of medical experimentation on Black Americans from colonial times to the present|date=2006|publisher=Harlem Moon|isbn=978-0-7679-1547-2|edition=1st paperback |location=New York|oclc=192050177}}

Uganda has the 5th highest sickle cell disease (SCD) burden in the world.{{cite journal | vauthors = Tusuubira SK, Naggawa T, Nakamoga V | title = To Join Or Not To Join? A Case Of Sickle Cell Clubs, Stigma And Discrimination In Secondary Schools In Butambala District, Uganda | journal = Adolescent Health, Medicine and Therapeutics | volume = 10 | pages = 145–152 | date = October 2019 | pmid = 31632168 | pmc = 6778728 | doi = 10.2147/AHMT.S223956 | doi-access = free | title-link = doi }} In Uganda, social stigma exists for those with sickle cell disease because of the lack of general knowledge of the disease. The general gap in knowledge surrounding sickle cell disease is noted among adolescents and young adults due to the culturally sanctioned secrecy about the disease. While most people have heard generally about the disease, a large portion of the population is relatively misinformed about how SCD is diagnosed or inherited. Those who are informed about the disease learned about it from family or friends and not from health professionals. Failure to provide the public with information about sickle cell disease results in a population with a poor understanding of the causes of the disease, symptoms, and prevention techniques.{{cite journal | vauthors = Tusuubira SK, Nakayinga R, Mwambi B, Odda J, Kiconco S, Komuhangi A | title = Knowledge, perception and practices towards sickle cell disease: a community survey among adults in Lubaga division, Kampala Uganda | journal = BMC Public Health | volume = 18 | issue = 1 | pages = 561 | date = April 2018 | pmid = 29703184 | pmc = 5924488 | doi = 10.1186/s12889-018-5496-4 | doi-access = free | title-link = doi }} The differences, physically and socially, that arise in those with sickle cell disease, such as jaundice, stunted physical growth, and delayed sexual maturity, can also lead them to become targets of bullying, rejection, and stigma.

The data compiled on sickle cell disease in Uganda has not been updated since the early 1970s. The deficiency of data is due to a lack of government research funds, even though Ugandans die daily from SCD.{{cite web|title=Sickle Cell Association of Uganda|url=http://www.sicklecelluganda.org/|access-date=7 April 2021|website=Sickle Cell Association of Uganda}} Data shows that the trait frequency of sickle cell disease is 20% of the population in Uganda. It is also estimated that about 25,000 Ugandans are born each year with SCD and 80% of those people do not live past five years old. SCD also contributes 25% to the child mortality rate in Uganda. The Bamba people of Uganda, located in the southwest of the country, carry 45% of the gene which is the highest trait frequency recorded in the world. The Sickle Cell Clinic in Mulago is only one sickle cell disease clinic in the country and on average sees 200 patients a day.

The stigma around the disease is particularly bad in regions of the country that are not as affected. For example, Eastern Ugandans tend to be more knowledgeable of the disease than Western Ugandans, who are more likely to believe that sickle cell disease resulted as a punishment from God or witchcraft.{{cite journal | vauthors = Okwi AL, Byarugaba W, Ndugwa CM, Parkes A, Ocaido M, Tumwine JK | title = Knowledge gaps, attitude and beliefs of the communities about sickle cell disease in Eastern and Western Uganda | journal = East African Medical Journal | volume = 86 | issue = 9 | pages = 442–449 | date = September 2009 | pmid = 21644415 | doi = 10.4314/eamj.v86i9.54167 | doi-access = free | title-link = doi }} Other misconceptions about SCD include the belief that it is caused by environmental factors but, in reality, SCD is a genetic disease.{{cite journal | vauthors = Marsh VM, Kamuya DM, Molyneux SS | title = 'All her children are born that way': gendered experiences of stigma in families affected by sickle cell disorder in rural Kenya | journal = Ethnicity & Health | volume = 16 | issue = 4–5 | pages = 343–359 | date = August 2011 | pmid = 21797722 | pmc = 3534410 | doi = 10.1080/13557858.2010.541903 }} There have been efforts throughout Uganda to address the social misconceptions about the disease. In 2013, the Uganda Sickle Cell Rescue Foundation was established to spread awareness of sickle cell disease and combat the social stigma attached to the disease.{{cite web|title=Our Vision and Mission – Uganda Sickle Cell Rescue Foundation|date=13 May 2017 |url=https://www.uscrfuganda.org/our-vision-and-mission/|access-date=6 April 2021}} In addition to this organization's efforts, there is a need for the inclusion of sickle cell disease education in preexisting community health education programs in order to reduce the stigmatization of sickle cell disease in Uganda.

The deeply rooted stigma of SCD from society causes families to often hide their family members' sick status for fear of being labeled, cursed, or left out of social events.{{cite web|title=Background – Uganda Sickle Cell Rescue Foundation|date=13 May 2017 |url=https://www.uscrfuganda.org/background/|access-date=6 April 2021}} Sometimes in Uganda, when it is confirmed that a family member has sickle cell disease, intimate relationships with all members of the family are avoided. The stigmatization and social isolation people with sickle cell disease tend to experience is often the consequence of popular misconceptions that people with SCD should not socialize with those free from the disease. This mentality robs people with SCD of the right to freely participate in community activities like everyone else SCD-related stigma and social isolation in schools, especially, can make a life for young people living with sickle cell disease extremely difficult. For school-aged children living with SCD, the stigma they face can lead to peer rejection. Peer rejection involves the exclusion from social groups or gatherings. It often leads the excluded individual to experience emotional distress and may result in their academic underperformance, avoidance of school, and occupational failure later in life. This social isolation is also likely to negatively impact people with SCD's self-esteem and overall quality of life.

Mothers of children with sickle cell disease tend to receive disproportionate amounts of stigma from their peers and family members. These women will often be blamed for their child's diagnosis of SCD, especially if SCD is not present in earlier generations, due to the suspicion that the child's poor health may have been caused by the mother's failure to implement preventative health measures or promote a healthy environment for her child to thrive. The reliance on theories related to environmental factors to place blame on the mother reflects many Ugandans’ poor knowledge of how the disease is acquired as it is determined by genetics, not environment. Mothers of children with sickle cell disease are also often left with very limited resources to safeguard their futures against the stigma of having SCD. This lack of access to resources results from their subordinating roles within familial structures as well as the class disparities that hinder many mothers' ability to satisfy additional childcare costs and responsibilities.

Women living with SCD who become pregnant often face extreme discrimination and discouragement in Uganda. These women are frequently branded by their peers as irresponsible for having a baby while living with sickle cell disease or even engaging in sex while living with SCD.[https://www.sciencedirect.com/science/article/pii/S2214109X15002880 Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study] The criticism and judgement these women receive, not only from healthcare professionals but also from their families, often leaves them feeling alone, depressed, anxious, ashamed, and with very little social support.[https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(15)00288-0/fulltext Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study - The Lancet Global Health] Most pregnant women with SCD also go on to be single mothers as it is common for them to be left by their male partners who claim they were unaware of their partner's SCD status.[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402737/ Unprepared and Misinformed Parents of Children with Sickle Cell Disease: Time to Rethink Awareness Campaigns] Not only does the abandonment experienced by these women cause emotional distress for them, but this low level of parental support can be linked to depressive symptoms and overall lower quality of life for the child once they are born.{{cite journal | vauthors = Sehlo MG, Kamfar HZ | title = Depression and quality of life in children with sickle cell disease: the effect of social support | journal = BMC Psychiatry | volume = 15 | issue = 1 | pages = 78 | date = April 2015 | pmid = 25880537 | pmc = 4394397 | doi = 10.1186/s12888-015-0461-6 | doi-access = free | title-link = doi }}

In 2021 many patients were found to be afraid to visit hospitals, so purchased pain relief to treat themselves outside the NHS. They were often waiting a long time for pain relief, and sometimes suspected of "drugs-seeking" behaviour. Delays to treatment, failure to inform the hospital haematology team and poor pain management had caused deaths. Specialist haematology staff preferred to work in bigger, teaching hospitals, leading to shortages of expertise elsewhere.{{cite news |title=London Eye: Shouldn't need an improvement programme |url=https://www.hsj.co.uk/london-eye-shouldnt-need-an-improvement-programme/7032893.article |url-access=subscription |access-date=28 September 2022 |work=Health Service Journal |date=27 July 2022}}{{quotation needed|date=February 2025}} In 2021, the NHS initiated its first new treatment in 20 years for Sickle Cell. This involved the use of Crizanlizumab, a drug given via transfusion drips, which reduces the number of visits to A&E by sufferers. The treatment can be accessed, via consultants, at any of ten new hubs set up around the country.{{cite news |date=October 2022 |title=Better protection and support for people with sickle cell disease |pages=16–17 |work=The Voice |url=https://www.voice-online.co.uk/entertainment/sponsored/2022/10/06/better-protection-and-support-for-people-with-sickle-cell-disease/ |access-date=7 October 2022}} In the same year, however, an All-Party Parliamentary Group produced a report on Sickle Cell and Thalassaemia entitled 'No-one is listening'.{{cite web |last=Rylatt |first=Aidan |date=7 October 2022 |title=No-one is Listening |url=https://www.sicklecellsociety.org/wp-content/uploads/2021/11/No-Ones-Listening-Final.pdf}} Partly in response to this, on 19 June 2022, World Sickle Cell Day, the NHS launched a campaign called "Can you tell it's sickle cell?". The campaign had twin aims. One was to increase awareness of the key signs and symptoms of the blood disorder so that people would be as alert to signs of a sickle cell crisis as they are to an imminent heart attack or stroke. The second aim was to set up a new training programme to help paramedics, Accident and Emergency staff, carers and the general public to care effectively for sufferers in crisis.{{cite web |date=7 October 2022 |title=NHS launches lifesaving sickle cell campaign |url=https://www.england.nhs.uk/2022/06/nhs-launches-lifesaving-sickle-cell-campaign/#:~:text=The%20campaign%2C%20dubbed%20'Can%20you,carers%20and%20the%20wider%20public.}}

{{Reflist}}

{{Library resources box |lcheading=Sickle cell anemia }}

{{refbegin}}

• {{cite book| veditors = Brown RT |title=Comprehensive handbook of childhood cancer and sickle cell disease: a biopsychosocial approach |publisher=Oxford University Press |year=2006 |isbn=978-0-19-516985-0 |url=https://books.google.com/books?id=O2sq8EeKTdwC|ref=none}}
• {{cite book| vauthors = Hill SA |title=Managing Sickle Cell Disease in Low-Income Families |publisher=Temple University Press |year=2003 |isbn=978-1-59213-195-2 |url=https://books.google.com/books?id=YG0Oi9mAaoQC |ref=none}}
• {{cite book| vauthors = Serjeant GR, Serjeant BE |title=Sickle Cell Disease|publisher=Oxford University Press|year=2001|isbn=978-0-19-263036-0|url=https://books.google.com/books?id=SetrAAAAMAAJ|ref=none}}
• {{cite book | vauthors = Tapper M |title=In the blood: sickle cell anemia and the politics of race |publisher=University of Pennsylvania Press |year=1999 |isbn=978-0-8122-3471-8 |url=https://archive.org/details/inbloodsicklecel00tapp|url-access=registration |ref=none}}

{{refend}}

{{Commons category|Sickle-cell disease}}

{{Medical condition classification and resources

|DiseasesDB = 12069

|ICD11 = {{ICD11|3A51.0}}, {{ICD11|3A51.1}}, {{ICD11|3A51.2}}, {{ICD11|3A51.3}}, {{ICD11|3A51.4}}

|ICD10 = {{ICD10|D|57||d|55}}

|ICD9 = {{ICD9|282.6}}

|OMIM = 603903

|MedlinePlus = 000527

|eMedicineSubj = med

|eMedicineTopic = 2126

|eMedicine_mult = {{eMedicine2|oph|490}} {{eMedicine2|ped|2096}} {{eMedicine2|emerg|26}} {{eMedicine2|emerg|406}}

|MeshName = Sickle+Cell+anemia

|MeshNumber = C15.378.071.141.150.150

|GeneReviewsNBK = NBK1377

|GeneReviewsName = Sickle Cell Disease

|Orphanet = 232

}}

{{Diseases of RBCs}}

{{Medicine}}

{{Portal bar | Medicine}}

{{Authority control}}

{{DEFAULTSORT:Sickle Cell Disease}}

Category:Autosomal recessive disorders

Category:Chronic pain syndromes

Category:Disorders of globin and globulin proteins

Category:Health in Africa

Category:Hereditary hemolytic anemias

Category:Wikipedia medicine articles ready to translate

Category:Wikipedia infectious disease articles ready to translate