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| {{Sickle-cell disease}} | | {{Sickle-cell disease}} |
| {{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
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| '''For patient information click [[Sickle-cell disease (patient information)|here]]''' | | '''For patient information click [[Sickle-cell disease (patient information)|here]]''' |
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| ==Overview==
| | {{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}, {{AN}}, {{shyam}} |
| '''Sickle-cell disease''' is a group of [[genetic disorders]] caused by sickle [[hemoglobin|hemoglobin]] (Hgb S or Hb S). In many forms of the disease, the [[red blood cell]]s change shape upon deoxygenation because of [[polymerization]] of the abnormal sickle hemoglobin, the hemoglobin sticks to each other, causing the cell to get a rigid surface and sickle shape. This process damages the red blood cell [[cell membrane|membrane]], and can cause the cells to become stuck in blood vessels. This deprives the downstream tissues of [[oxygen]] and causes [[ischemia]] and [[infarction]], which may cause organ damage, such as [[stroke]]. The disease is chronic and lifelong. Individuals are most often well, but their lives are punctuated by periodic painful attacks. Life-expectancy is shortened, but contemporary survival data is lacking. Older studies indicated that sufferers could live to an average of 40 to 50 years, with the average age for males being 42 and the average age for females being 48. Sickle-cell disease occurs more commonly in people (or their descendants) from parts of the world such as sub-Saharan Africa, where [[malaria]] is or was common, but it also occurs in people of other ethnicities. As a result, those with sickle cell disease are resistant to malaria since the red blood cells are not conducive to the parasites. The mutated [[allele]] is [[recessive]], meaning it must be inherited from each parent for the individual to have the disease. | |
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| ==History==
| | {{SK}} Anemia-sickle cell; hemoglobin S disease; hemoglobin SS disease; Hb SS; sickle cell anemia; SCA; drepanocytosis |
| This collection of clinical findings was unknown until the explanation of the sickle cells in 1910 by the Chicago cardiologist and professor of medicine [[James Herrick|James B. Herrick]] (1861-1954) whose intern Ernest Edward Irons (1877-1959) found "peculiar elongated and sickle shaped" cells in the [[blood]] of Walter Clement Noel, a 20 year old first year dental student from Grenada after Noel was admitted to the [[Presbyterian Hospital]] in December 1904 suffering from [[anemia]]. Noel was readmitted several times over the next three years for "muscular rheumatism" and "bilious attacks" while an undergraduate. Noel completed his studies and returned to 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.<ref>{{cite journal|last=Savitt|first=TL|coauthors=Goldberg MF|year=1989|title=Herrick's 1910 case report of sickle cell anemia. The rest of the story|url=|journal=[[Journal of the American Medical Association|JAMA]]|issn=0098-7484|volume=261|issue=2|pages=266-271|pmid=2642320}}</ref>
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| The disease was named "sickle-cell anemia" by Vernon Mason in 1922. In retrospect some elements of the disease had been recognised earlier: a paper in the Southern Journal of Medical Pharmacology in 1846 described the absence of a spleen in the [[autopsy]] of a runaway slave. The African medical literature reported this condition in the 1870s where it was known locally as ''ogbanjes'' ('children who come and go') because of the very high infant mortality in this condition. And a history of the condition tracked reports back to 1670 in one Ghanaian family.<ref>Konotey-Ahulu FID. Effect of environment on sickle cell disease in West Africa: epidemiologic and clinical considerations. In: Sickle Cell Disease, Diagnosis, Management, Education and Research. Abramson H, Bertles JF, Wethers DL, eds. CV Mosby Co, St. Louis. 1973; 20; cited in {{cite journal|last=Desai|first=D. V.|coauthors=Hiren Dhanani|year=2004|title=Sickle Cell Disease: History And Origin|url=http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijhe/vol1n2/sickle.xml|journal=The Internet Journal of Hematology|issn=1540-2649|volume=1|issue=2|pages=|doi=}}</ref> Also, the practice of using tar soap to cover blemishes caused by sickle cell sores was prevalent in the African American community.
| | ==[[Sickle-cell disease overview|Overview]]== |
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| Proof that sickle-cell disease was associated with an alteration of hemoglobin was published in 1949 by [[Linus Pauling]] and coworkers. This was the first time a genetic disease was linked to a mutation of a specific protein, a milestone in the [[history of molecular biology]].
| | ==[[Sickle-cell disease historical perspective|Historical Perspective]]== |
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| The origin of the mutation that led to the sickle cell gene was initially thought to be in the Arabian peninsula, spreading to Asia and Africa. It is now known, from evaluation of chromosome structures, that there have been at least four independent mutational events, three in Africa and a fourth in either Saudi Arabia or central India.<ref>{{cite journal|last=Desai|first=D. V.|coauthors=Hiren Dhanani|year=2004|title=Sickle Cell Disease: History And Origin|url=http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ijhe/vol1n2/sickle.xml|journal=The Internet Journal of Hematology|issn=1540-2649|volume=1|issue=2|pages=|doi=}}</ref> These independent events occurred between 3,000 and 6,000 generations ago, approximately 70,000-150,000 years.
| | ==[[Sickle-cell disease classification|Classification]]== |
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| ==Types and terminology== | | ==[[Sickle-cell disease pathophysiology|Pathophysiology]]== |
| "Sickle-cell anemia" is the name of a specific form of sickle-cell disease in which there is [[homozygote|homozygosity]] for the [[genetic mutation|mutation]] that causes Hgb S. Sickle cell anemia is also referred to as "SS disease," "Hemoglobin S," or permutations thereof. Other forms of sickle-cell disease include:
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| * sickle-[[hemoglobin C]] disease
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| * sickle beta-plus-[[thalassaemia]]
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| * sickle beta-zero-thalassaemia
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| These other forms of sickle-cell disease are [[compound heterozygous]] states in which the person has only one copy of the mutation that causes Hgb S and one copy of another abnormal [[hemoglobin]] [[allele]]. "Sickle-cell anemia" is a synonym for "sickle-cell disease".
| | ==[[Sickle-cell disease causes|Causes]]== |
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| The term "disease" is applied here since the inherited abnormality causes a pathological condition that can lead to death and severe complications. Not all inherited variants of [[hemoglobin]] are detrimental, a concept known as [[genetic polymorphisms]]. [[Hemoglobin]] is one of the best-characterized proteins in terms of inherited variants; some variants manifest as severe [[thalassaemia]], such as beta-zero-[[thalassaemia]], and other variants manifest as a milder thalassaemia, such as beta-plus-[[thalassaemia]].
| | ==[[Sickle-cell disease differential diagnosis|Differentiating Sickle-Cell Disease from Other Diseases]]== |
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| ==Signs and symptoms== | | ==[[Sickle-cell disease epidemiology and demographics|Epidemiology and Demographics]]== |
| Patients with sickle-cell anemia can have symptoms that vary in severity.
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| ===Vaso-occlusive crises=== | | ==[[Sickle-cell disease risk factors|Risk Factors]]== |
| A vaso-occlusive crisis is caused by sickle-shaped red blood cells that obstruct capillaries and restrict blood flow to an organ, resulting in [[ischemia]], [[Pain and nociception|pain]], and organ damage.
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| Because of its narrow vessels and function in clearing defective red blood cells, the [[spleen]] is frequently affected. It is usually [[infarction|infarcted]] before the end of childhood in individuals suffering from sickle-cell anemia. This [[autosplenectomy]] increases the risk of infection from [[encapsulated organisms]];<ref>{{cite journal |author=Pearson H |title=Sickle cell anemia and severe infections due to encapsulated bacteria |journal=J Infect Dis |volume=136 Suppl |issue= |pages=S25-30 |year= |pmid=330779}}</ref><ref>{{cite journal |author=Wong W, Powars D, Chan L, Hiti A, Johnson C, Overturf G |title=Polysaccharide encapsulated bacterial infection in sickle cell anemia: a thirty year epidemiologic experience |journal=Am J Hematol |volume=39 |issue=3 |pages=176-82 |year=1992 |pmid=1546714}}</ref> preventive antibiotics and vaccinations are recommended for those with such [[asplenia]].
| | ==[[Sickle-cell disease screening|Screening]]== |
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| [[Bone]]s, especially weight-bearing bones, are also a common target of vaso-occlusive damage. This is due to bone ischemia.
| | ==[[Sickle-cell disease natural history|Natural History, Complications, and Prognosis]]== |
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| A recognised type of sickle crisis is the ''acute chest crisis'', a condition characterised by fever, chest pain, hard breathing, and pulmonary infiltrate on chest X-ray. Given that pneumonia and intrapulmonary sickling can both produce these symptoms, the patient is treated for both conditions.
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| ===Other sickle-cell crises===
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| *'''Aplastic crises''' are acute worsenings of the patient's baseline anemia producing pallor, tachycardia, and fatigue. This crisis is triggered by [[parvovirus B19]], which directly affects [[erythropoiesis]] (production of red blood cells). Parvovirus infection nearly completely prevents red blood cell production for 2-3 days. In normal individuals this is of little consequence but the shortened red cell life of sickle-cell patients results in an abrupt, life-threatening situation. [[Reticulocyte]] counts drop dramatically during the illness and the rapid turnover of red cells leads to the drop in hemoglobin. Most patients can be managed supportively; some need blood transfusion.
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| *'''Splenic sequestration crises''' are acute, painful enlargements of the spleen. The abdomen becomes bloated and very hard. Management is supportive, sometimes with blood transfusion.
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| ===Complications===
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| Sickle-cell anemia can lead to various complications, including: | |
| * Vaso-occlusive crisis (otherwise known as painful crisis): Most patients with sickle-cell disease have periodic intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises vary tremendously. Painful crises are treated with hydration and analgesics; pain management requires [[opiate|opioid]] administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manage on [[NSAID]]s (such as [[diclofenac]] or [[naproxen]]). For more severe crises most patients require inpatient management for intravenous opioids; patient-controlled analgesia (PCA) devices are commonly used in this setting. [[Diphenhydramine]] is effective for the itching associated with the opioid use. Incentive spirometry, a technique to encourage deep breathing to minimise the development of [[atelectasis]], is recommended.
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| * [[Acute chest syndrome]] is a life-threatening condition characterised by chest pain, shortness of breath, fever, hypoxaemia and pulmonary infiltrates on chest X-ray. It can be triggered by pain crisis, respiratory infection, bone-marrow embolization, or possibly by [[atelectasis]], such as can be caused by opiate administration, or surgery.
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| * [[Overwhelming post-splenectomy infection|Overwhelming post-(auto)splenectomy infection]] is due to functional asplenia, caused by encapsulated organisms 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 today from routine vaccination for ''H. influenzae'', ''S. pneumoniae'' and ''Neisseria meningitidis''.
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| * [[Cerebrovascular accident|Stroke]] can result from a progressive vascular narrowing of blood vessels, preventing oxygen from reaching the [[human brain|brain]]. Cerebral infarction occurs in children, and cerebral hemorrhage in adults.
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| * [[Cholelithiasis]] and [[cholecystitis]] ([[gallstone]]s) may result from excessive [[bilirubin]] production and precipitation due to prolonged [[haemolysis]].
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| * Avascular necrosis ([[aseptic bone necrosis]]) of the hip may occur as a result of ischemia.
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| * Decreased [[immune system|immune reactions]] due to [[hyposplenism]] (malfunctioning of the spleen)
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| * [[Priapism]] and [[infarction]] of the penis.
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| * [[Osteomyelitis]] (bacterial bone infection) - ''[[Salmonella]]'' is noted much more commonly than in the general population, although ''[[Staphylococcus]]'' is still the most common.
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| * [[Opioid]] tolerance can occur as a normal, physiologic response to the therapeutic use of opiates. Addiction to opiates occurs no more commonly among individuals with sickle cell disease than among other individuals treated with opiates for other reasons.
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| * Acute papillary necrosis in the kidneys.
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| * Leg ulcers
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| * In eyes, background retinopathy, proliferative retinopathy, vitreous hemorrhages and retinal detachments can occur. Regular annual eye checks are required.
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| *During [[pregnancy]], [[intrauterine growth retardation]], spontaneous [[abortion]] and [[pre-eclampsia]] are the possibilities.
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| ==Diagnosis== | | ==Diagnosis== |
| Full blood count will reveal [[haemoglobin]] levels in the range of 6-8 g/dL with a high reticulocyte count.
| | [[Sickle-cell disease history and symptoms|History and Symptoms]] | [[Sickle-cell disease physical examination|Physical Examination]] | [[Sickle-cell disease laboratory tests|Laboratory Tests]] | [[Sickle-cell disease x ray|X Ray]] | [[Sickle-cell disease CT|CT]] | [[Sickle-cell disease MRI|MRI]] | [[Sickle-cell disease echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Sickle-cell disease other imaging findings|Other Imaging Findings]] | [[Sickle-cell disease other diagnostic studies|Other Diagnostic Studies]] |
| On a peripheral blood film, one can observe features of [[hyposplenism]] i.e., target cells and Howell-Jolie Bodies.
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| Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulphite.
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| Another test is Sickle Solubility test. A mixture of haemoglobin S (Hb S) in a reducing solution e.g., sodium dithionite gives a turbid appearance while normal Hb gives a clear solution.
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| Abnormal [[hemoglobin]] forms can be detected on [[hemoglobin electrophoresis]], a form of [[gel electrophoresis]] on which the various types of hemoglobin move at varying speed. Sickle-cell hemoglobin (HgbS) and [[hemoglobin C]] with sickling (HgbSC)—the two most common forms—can be identified from there. [[Genetic testing]] is rarely performed.
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| === Laboratory Findings ===
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| ====X-Ray====
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| (Images shown below are courtesy of RadsWiki)
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| '''Patient #1: SCD patient with H shaped vertebrae'''
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| <div align="left">
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| <gallery heights="125" widths="125">
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| Image:Sickle cell disease H shaped vertebral bodies 001.jpg|H shaped vertebral bodies
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| Image:Sickle cell disease H shaped vertebral bodies 002.jpg|H shaped vertebral bodies
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| Image:Sickle cell disease H shaped vertebral bodies 003.jpg|H shaped vertebral bodies
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| </gallery>
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| </div>
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| '''Patient #1: SCD patient with H shaped vertebrae'''
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| <gallery>
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| Image:
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| Sickle cell disease CXR PA.jpg
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| Image:
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| Sickle cell disease CXR lateral.jpg
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| </gallery>
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| ===Pathology===
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| [[Image:SCD.jpg|thumb|left|SCD<ref>http://picasaweb.google.com/mcmumbi/USMLEIIImages</ref>]] | |
| <br clear="left"/>
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| ==Pathophysiology==
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| Sickle-cell anemia is caused by a point [[mutation]] in the β-globin chain of [[hemoglobin]], replacing the amino acid [[glutamic acid]] with the less polar amino acid [[valine]] at the sixth position of the β chain. The association of two [[wild-type]] α-globin subunits with two mutant β-globin subunits forms hemoglobin S, which polymerises under low [[oxygen]] conditions causing distortion of red blood cells and a tendency for them to lose their elasticity. | |
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| New [[erythrocytes]] are quite elastic, which allows the cells to deform to pass through capillaries. Often a cycle occurs because as the cells sickle, they cause a region of low oxygen concentration which causes more red blood cells to sickle. Repeated episodes of sickling causes loss of this elasticity and the cells fail to return to normal shape when oxygen concentration increases. These rigid red blood cells are unable to flow through narrow capillaries, causing vessel occlusion and [[ischaemia]].
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| ==Genetics==
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| [[Image:Sickle_cell_hemoglobin.png|right|thumb|120px|A single amino acid change causes hemoglobin proteins to form fibers.]]
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| In people [[heterozygous]] for HgbS (carriers of sickling hemoglobin), the polymerisation problems are minor. In people [[homozygous]] for HgbS, the presence of long chain polymers of HbS distort the shape of the red blood cell, from a smooth donut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within [[capillary|capillaries]]. Carriers only have symptoms if they are deprived of oxygen (for example, while climbing a mountain) or while severely [[dehydration|dehydrated]]. Normally these painful crises occur 0.8 times per year per patient. The sickle cell disease occurs when the sixth amino acid, glutamic acid is replaced by valine to change is structure and function.
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| [[Image:Sickle cell distribution.jpg|thumb|right|150px| distribution of the sickle cell trait]] | |
| [[Image:Malaria distribution.jpg|thumb|right|150px|distribution of [[Malaria]] ]]
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| The gene defect is a known [[mutation]] of a single [[nucleotide]] (see [[single nucleotide polymorphism]] - SNP) (A to T) of the β-globin gene, which results in [[glutamic acid]] to be substituted by [[valine]] at position 6. hemoglobin S with this mutation are referred to as HbS, as opposed to the normal adult HbA. The genetic disorder is due to the [[mutation]] of a single nucleotide, from a GAG to GUG [[codon]] [[mutation]]. This is normally a benign mutation, causing ''no'' apparent effects on the [[secondary structure|secondary]], [[tertiary structure|tertiary]], or [[quaternary structure|quaternary]] structure of hemoglobin. What it does allow for, under conditions of low [[oxygen]] concentration, is the [[polymerization]] of the HbS itself. The deoxy form of hemoglobin exposes a hydrophobic patch on the protein between the E and F helices. The hydrophobic residues of the valine at position 6 of the beta chain in hemoglobin are able to bind to the hydrophobic patch, causing hemoglobin S molecules to aggregate and form fibrous precipitates.
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| The [[allele]] responsible for sickle-cell anemia is [[autosomal recessive]] and can be found on the 11th chromosome. A person who receives the defective gene from both father and mother develops the disease; a person who receives one defective and one healthy allele remains healthy, but can pass on the disease and is known as a ''[[Asymptomatic carrier|carrier]]''. If two parents who are carriers have a child, there is a 1-in-4 chance of their child developing the illness and a 1-in-2 chance of their child just being a carrier. Since the [[sickle cell trait|gene]] is incompletely recessive, carriers have a few sickle red blood cells at all times, not enough to cause symptoms, but enough to give resistance to malaria. Because of this, heterozygotes have a higher [[fitness (biology)|fitness]] than either of the homozygotes. This is known as [[heterozygote advantage]].
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| Due to the evolutionary advantage of the heterozygote, the illness is still prevalent, especially among people with recent ancestry in malaria-stricken areas, such as Africa, the Mediterranean, India and the Middle East<ref>{{cite journal | author=Kwiatkowski, DP | title=[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16001361 How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria]| journal=Am J Hum Genet | year=2005 | volume=77 | pages=171-92 |id=PMID 16001361}}</ref>.
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| The [[Price equation]] is a simplified mathematical model of the genetic evolution of sickle cell anemia.
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| The malaria parasite has a complex life cycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cell to rupture, making the [[plasmodium]] unable to reproduce. Further, the polymerization of Hb affects the ability of the parasite to digest Hb in the first place. Therefore, in areas where malaria is a problem, people's chances of survival actually increase if they carry sickle cell trait (selection for the heterozygote).
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| In the USA, where there is no endemic malaria, the incidence of sickle cell anemia amongst African Americans is lower (about 8%) than in West Africa and is falling. Without endemic malaria from Africa, the condition is purely disadvantageous, and will tend to be breed out of the affected population.
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| [[Image:Autorecessive.svg|right|thumb|200px|Sickle-cell disease is inherited in the autosomal recessive pattern.]]
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| ===Inheritance===
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| *Sickle-cell conditions are inherited from parents in much the same way as blood type, hair color and texture, eye color and other physical traits.
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| *The types of hemoglobin a person makes in the red blood cells depend upon what hemoglobin genes the person inherits from his or her parents.
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| ====Examples====
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| # If one parent has sickle-cell anemia ("rr" in the diagram above) and the other is Normal (RR), all of their children will have sickle cell trait (Rr).
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| # If one parent has sickle-cell anemia (rr) and the other has Sickle Cell Trait (Rr), there is a 50% chance (or 1 out of 2) of a child having sickle cell disease (rr) and a 50% chance of a child having sickle cell trait (Rr).
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| # When both parents have Sickle Cell Trait (Rr), they have a 25% chance (1 of 4) of a child having sickle cell disease (rr), as shown in the diagram above.
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| # Sickle-cell anemia is caused by a recessive allele. Two carrier parents have a one in four chance of having a child with the disease. The child will be homozygous recessive.
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| ==Treatment== | | ==Treatment== |
| | [[Sickle-cell disease medical therapy|Medical Therapy]] | [[Sickle-cell disease surgery|Surgery]] | [[Sickle-cell disease primary prevention|Primary Prevention]] | [[Sickle-cell disease secondary prevention|Secondary Prevention]] | [[Sickle-cell disease future or investigational therapies|Future or Investigational Therapies]] |
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| ===Febrile illness=== | | ==Case Studies== |
| Children with fever are screened for [[bacteremia]] i.e. [[complete blood count]], [[reticulocyte]] count and [[blood culture]] taken. Younger children (varies from center to center) are admitted for intravenous antibiotics while older children with reassuring white cell counts are managed at home with oral antibiotics. Children with previous bacteremic episodes should be admitted.
| | [[Sickle-cell disease case study one|Case #1]] |
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| ===Zn administration===
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| Zinc is given as it stablises cell membrane.
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| ===Painful (vaso-occlusive) crises===
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| Most people with sickle cell disease have intensely painful episodes called ''vaso-occlusive crises''. The frequency, severity, and duration of these crises, however, vary tremendously. Painful crises are treated symptomatically with [[analgesic]]s; pain management requires [[opioid]] administration at regular intervals until the crisis has settled. For milder crises a subgroup of patients manage on [[NSAID]]s (such as [[diclofenac]] or [[naproxen]]). For more severe crises most patients require inpatient management for intravenous opioids; [[patient-controlled analgesia]] (PCA) devices are commonly used in this setting. [[Diphenhydramine]] is effective for the itching associated with the opioid use.
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| ===Acute chest crises===
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| Management is similar to vaso-occlusive crises with the addition of antibiotics (usually a quinolone or macrolide, since wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome),<ref>{{cite book | title=Pulmonary and Critical Care Medicine | editor=Bone RC et al., editors | author=Aldrich TK, Nagel RL. | chapter=Pulmonary Complications of Sickle Cell Disease. | edition=6th edition | date=1998 | pages=pp.1-10 | publisher=Mosby | location=St. Louis}}</ref> oxygen supplementation for [[Hypoxia (medical)|hypoxia]], and close observation. Should the pulmonary infiltrate worsen or the oxygen requirements increase, simple [[blood transfusion]] or [[exchange transfusion]] is indicated. The latter involves the exchange of a significant portion of the patients red cell mass for normal red cells, which decreases the percent hemoglobin S in the patient's blood.
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| ===Hydroxyurea===
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| The first approved drug for the causative treatment of sickle cell anemia, [[hydroxyurea]], was shown to decrease the number and severity of attacks in a study in 1995 (Charache ''et al'')
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| <ref>{{cite journal |last=Charache |first= Samuel |authorlink= |coauthors=Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR |year=1995 |month=May |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=[[NEJM]] |volume=332 |issue=20 |pages=1317–1322 |id=PMID 7715639 |url=http://content.nejm.org/cgi/content/abstract/332/20/1317 |accessdate=2007-04-15}}</ref>
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| and shown to possibly increase survival time in a study in 2003 (Steinberg ''et al'')
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| <ref>{{cite journal |last=Steinberg |first=Martin H |authorlink= |coauthors= 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 |title=Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment |year=2003 |month=April |journal=[[Journal of the American Medical Association|JAMA]] |volume=289 |issue=13 |pages=1645–1651 |id=PMID 12672732 |url=http://jama.ama-assn.org/cgi/content/abstract/289/13/1645 |accessdate=2007-04-15}}</ref>.
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| This is achieved, in part, by reactivating [[fetal hemoglobin]] production in place of the hemoglobin S that causes sickle cell anemia. Hydroxyurea's clinical benefits can actually precede the induction of [[fetal hemoglobin]], however. Hydroxyurea had previously been used as a [[chemotherapy]] agent, and there is some concern that long-term use may be harmful, but it is likely that the benefits outweigh the risks.
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| ===Future treatments===
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| Various approaches are being sought for preventing sickling episodes as well as for the complications of sickle-cell disease. Other ways to modify Hb switching are being investigated, including the use of [[phytochemicals]] such as [[Nicosan]].
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| [[Gene therapy]] is under investigation.
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| ==Situation of carriers==
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| People who are known carriers of the disease often undergo [[genetic counseling]] before they have a child. A test to see if an unborn child has the disease takes either a [[blood]] sample from the unborn or a sample of [[amniotic fluid]]. Since taking a blood sample from a fetus has risks, the latter test is usually used.
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| After the mutation responsible for this disease was discovered in 1979, the U.S. Air Force required African American applicants to test for the mutation. It dismissed 143 applicants because they were carriers, even though none of them had the condition. It eventually withdrew the requirement, but only after a trainee filed a lawsuit.
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| ==References ==
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| {{Reflist|2}}
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| ==Additional Readings==
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| *Chestnut, D. (1994). Perceptions of ethnic and cultural factors in the delivery of services in the treatment of sickle cell disease. Journal of Health and Social Policy, 5(3/4), 236.
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| ==External Links==
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| * [http://clinicaltrials.gov/ct/gui/action/FindCondition?ui=D000755&recruiting=true SCA clinical trials] (ClinicalTrials.gov)
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| * [http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi?term=sickle+cell Sickle Cell links] (NCBI)
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| {{Hematology}} | | {{Hematology}} |
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| [[ar:فقر الدم المنجلي]]
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| [[de:Sichelzellenanämie]]
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| [[es:Anemia falciforme]]
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| [[eo:Serpoĉela anemio]]
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| [[fa:کمخونی داسیشکل]]
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| [[fr:Drépanocytose]]
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| [[ko:낫적혈구병]]
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| [[it:Anemia drepanocitica]]
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| [[he:אנמיה חרמשית]]
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| [[nl:Sikkelcelanemie]]
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| [[ja:鎌状赤血球症]]
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| [[pt:Anemia falciforme]]
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| [[ru:Серповидно-клеточная анемия]]
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| [[sl:Srpastocelična anemija]]
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| [[sr:Српаста анемија]]
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| [[fi:Sirppisoluanemia]]
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| [[sv:Sicklecellanemi]]
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| [[zh:鐮刀型紅血球疾病]]
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| [[pl:Anemia sierpowata]]
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| [[Category:Disease]] | | [[Category:Disease]] |
| [[Category:Hematology]] | | [[Category:Hematology]] |
| [[Category:Genetic disorders]] | | [[Category:FinalQCRequired]] |
| [[Category:Pain]]
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| [[Category:Chronic pain syndromes]]
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| [[Category:Mature chapter]]
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