英文連結：https://en.wikipedia.org/wiki/Sickle-cell_disease
中文網址 : https://zh.wikipedia.org/wiki/%E9%90%AE%E5%88%80%E5%9E%8B%E7%B4%85%E8%A1%80%E7%90%83%E7%96%BE%E7%97%85
鐮刀型紅血球疾病，或稱鐮刀型細胞貧血症，是指由鐮刀型血紅蛋白（Hgb S或Hb S）所導致的一類遺傳性疾病的總稱。在其聚多的類型裡，紅血球皆因失常的鐮刀型血紅蛋白的聚合而改變形狀，以致於失去了攜帶氧氣的能力。這個過程會傷害紅血球的細胞膜，並使其阻塞在血管內。如此使得其下流的組織無法得到氧氣，因而會導致局部缺血和梗塞。這是一種慢性疾病，患者一般都生活得很好，但不時會有週期性的疼痛。患者的平均壽命會因此被縮至四十歲。這種疾病在瘧疾曾經或還是很普遍的地區很普遍，特別常見於撒哈拉以南的非洲人口，加勒比、印度、中東和地中海周圍尤其是在希臘和義大利[1]。鐮刀型紅血球疾病可能發生在任何膚色和任何人種身上。
Sickle-cell disease (SCD) is a group of genetically passed down blood disorders.[1] The most common type is known as sickle-cell anaemia (SCA). It results in an abnormality in the oxygen-carrying protein haemoglobin found in red blood cells. This leads to a rigid, sickle-like shape under certain circumstances.[1] Problems in sickle cell disease typically begin around 5 to 6 months of age. A number of health problems may develop, such as attacks of pain ("sickle-cell crisis"), anemia, bacterial infections, and stroke.[2] Long term pain may develop as people get older. The average life expectancy in the developed world is 40 to 60 years.[1]
鐮刀型貧血發生在一個人遺傳了兩個異常的血紅蛋白基因，一個來自父母。存在幾種類型，這取決於每個血紅蛋白基因的{{Link-en|突變|mutation}}。突變可能由溫度改變、壓力、{{Link-en|脫水|dehydration}}與到高海拔地帶等狀況引發。具有單一異常的人通常不具有症狀和聽說有{{Link-en|鐮狀細胞特徵|sickle-cell trait}}。這樣的人被稱之為攜帶者。診斷是通過{{Link-en|血液測試|blood test}}和一些國家測試所有嬰兒出生的疾病。在懷孕期間診斷也是可能的。
Sickle-cell disease occurs when a person inherits two abnormal copies of the haemoglobin gene, one from each parent.[3] Several subtypes exist, depending on the exact mutation in each haemoglobin gene.[1] An attack can be set off by temperature changes, stress, dehydration, and high altitude.[2] A person with a single abnormal copy does not usually have symptoms and is said to have sickle-cell trait.[3] Such people are also referred to as carriers.[4] Diagnosis is by a blood test and some countries test all babies at birth for the disease.[5] Diagnosis is also possible during pregnancy.[5]
照顧患有鐮刀型貧血的人可能包括用{{Link-en|抗生素|Antibiotics}}與{{Link-en|接種疫苗|Vaccination}}預防感染、大量攝入流質／液體、補充{{Link-en|葉酸|Folic acid}}、使用{{Link-en|止痛藥|Analgesic}}。其他措施可能包括{{Link-en|輸血|Blood transfusion}}和{{Link-en|羥基脲|hydroxycarbamide}}藥物。少部分的人可以透過{{Link-en|骨髓細胞移植|Hematopoietic stem cell transplantation}}的方式治癒。
The care of people with sickle-cell disease may include infection prevention with vaccination and antibiotics, high fluid intake, folic acid supplementation, and pain medication.[4][6] Other measures may include blood transfusion, and the medication hydroxycarbamide (hydroxyurea).[6] A small proportion of people can be cured by a transplant of bone marrow cells.[1]
截至2013年，約有320萬人患有鐮刀型紅血球疾病，另有4300萬人患有鐮狀細胞性狀。約80％的鐮刀型紅血球疾病發生在{{Link-en|撒哈拉以南非洲地區|sub-Saharan Africa}}。它也經常發生在印度的部分地區，{{Link-en|阿拉伯半島|Arabian peninsula}}，以及{{Link-en|非洲血統的人|people of African origin}}生活在世界其他地區。2013年，造成176,000人死亡，高於1990年的113,000人死亡。美國醫師{{Link-en|詹姆斯·赫里克|James B. Herrick}}（James B. Herrick）在1910年的醫學文獻中首次描述了這種情況。1949年，遺傳傳播由E.A.Betet和J.V.Neel確定。1954年描述了鐮狀細胞性狀對{{Link-en|瘧疾|malaria}}的保護作用。大多數發作持續了五到七天。
As of 2013 about 3.2 million people have sickle-cell disease while an additional 43 million have sickle-cell trait.[7] About 80% of sickle-cell disease cases are believed to occur in sub-Saharan Africa.[8] It also occurs relatively frequently in parts of India, the Arabian peninsula, and among people of African origin living in other parts of the world.[9] In 2013, it resulted in 176,000 deaths, up from 113,000 deaths in 1990.[10] The condition was first described in the medical literature by the American physician James B. Herrick in 1910.[11][12] In 1949 the genetic transmission was determined by E. A. Beet and J. V. Neel. In 1954 the protective effect against malaria of sickle-cell trait was described.[12]
鐮刀型紅血球疾病可能會導致各種急性和慢性併發症，其中有幾個具有很高的死亡率。
Sickle-cell disease may lead to various acute and chronic complications, several of which have a high mortality rate.[13]
鐮刀型紅血球疾病（Sickle-cell crisis）
“鐮狀紅血球疾病”或“鐮刀紅血球疾病”這詞可用於描述SCD患者發生的幾種獨立的急性病症。SCD導致貧血和危機，可能有許多類型，包括{{Link-en|血管阻塞性危機|vaso-occlusive crisis}}，{{Link-en|再生障礙危機|aplastic crisis}}，{{Link-en|隔離危機|sequestration crisis}}，{{Link-en|溶血性危機|haemolytic crisis}}等。大多數鐮刀型紅血球疾病發作持續了五到七天。“雖然感染，脫水和{{Link-en|酸中毒|acidosis}}（所有這些都有利於鐮刀紅血球）可以作為觸發因素，但在大多數情況下，並不會發現任何誘因。
The terms "sickle-cell crisis" or "sickling crisis" may be used to describe several independent acute conditions occurring in patients with SCD. SCD results in anemia and crises that could be of many types including the vaso-occlusive crisis, aplastic crisis, sequestration crisis, haemolytic crisis, and others. Most episodes of sickle-cell crises last between five and seven days.[14] "Although infection, dehydration, and acidosis (all of which favor sickling) can act as triggers, in most instances, no predisposing cause is identified."[15]
血管阻塞危機（Vaso-occlusive crisis）
{{Link-en|血管阻塞危機|vaso-occlusive crisis}}是由鐮狀紅血球細胞引起的，這些細胞會阻塞微血管並限制血液流向器官，從而導致{{Link-en|局部缺血|ischaemia}}，{{Link-en|疼痛|pain}}，{{Link-en|壞死|necrosis}}，以及器官損害。這些危機的頻率，嚴重程度和持續時間差異很大。痛苦的危機是用水分補充，{{Link-en|止痛藥|analgesics}}和{{Link-en|輸血治療|blood transfusion}}；疼痛管理需要定期使用{{Link-en|阿片類藥物|opioid}}直到危機已經解決。對於較輕的危機，一組患者使用{{Link-en|NSAIDs|NSAIDs}}（如{{Link-en|雙氯芬酸|diclofenac}}或{{Link-en|萘普生|naproxen}}）。對於更嚴重的危機，大多數病人需要住院治療靜脈注射阿片類藥物；{{Link-en|病人自控鎮痛|patient-controlled analgesia}}設備也常應用在此。血管阻塞性危機涉及的器官如陰莖或肺部被認為是緊急情況並處理與紅血球輸血治療。{{Link-en|誘發性肺量計|Incentive spirometry}}，鼓勵深呼吸，儘量減少{{Link-en|肺不張|atelectasis}}。
The vaso-occlusive crisis is caused by 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. Painful crises are treated with hydration, analgesics, and blood transfusion; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (such as diclofenac or naproxen). For more severe crises, most patients require inpatient management for intravenous opioids; patient-controlled analgesia devices are commonly used in this setting. Vaso-occlusive crisis involving organs such as the penis[16] or lungs are considered an emergency and treated with red-blood cell transfusions. Incentive spirometry, a technique to encourage deep breathing to minimise the development of atelectasis, is recommended.[17]
脾隔離危機（Splenic sequestration crisis）
由於其狹窄的血管和清除缺陷的紅血球的功能，{{Link-en|脾臟|spleen}}經常受到影響。在患有鐮刀型貧血的個體中，通常在兒童期結束之前{{Link-en|梗塞|infarcted}}。這種{{Link-en|脾損傷|spleen damage}}增加了從{{Link-en|包膜生物體|encapsulated organisms}}感染的風險；建議對那些{{Link-en|沒有適當的脾臟功能|lacking proper spleen function}}的人使用預防性抗生素和接種疫苗。
Because of its narrow vessels and function in clearing defective red blood cells, the spleen is frequently affected.[18] It is usually infarcted before the end of childhood in individuals suffering from sickle-cell anemia. This spleen damage increases the risk of infection from encapsulated organisms;[19][20] preventive antibiotics and vaccinations are recommended for those lacking proper spleen function.
脾臟隔離危機是由於紅血球細胞的脾内引起的脾臟急性痛苦的增大，並導致血红蛋白水平的急遽下降，具有{{Link-en|血容量不足|hypovolemic}}的可能性。這被認為是緊急情況。如果不治療，患者可能在1-2小時內死於循環衰竭。給予支持性的管理，有時輸血。這些危機是短暫的，他們持續3-4個小時，可能持續一天。
Splenic sequestration crises are acute, painful enlargements of the spleen, caused by intrasplenic trapping of red cells and resulting in a precipitous fall in hemoglobin levels with the potential for hypovolemic shock. Sequestration crises are considered an emergency. If not treated, patients may die within 1–2 hours due to circulatory failure. Management is supportive, sometimes with blood transfusion. These crises are transient, they continue for 3–4 hours and may last for one day.[21]
急性胸部綜合症（Acute chest syndrome）
{{Link-en|急性胸部綜合症|Acute chest syndrome}} (ACS) 由以下症狀或症状中的至少兩種定義︰ 胸痛、 發熱、 肺浸潤或局部性異常、 呼吸道症狀或低氧血症。這是第二常見的併發症，占SCD患者死亡人數的25％，多數病例存在血管阻塞性危機，然后演變成ACS。然而，約80%的患者在ACS期間有血管阻塞性危機。
Acute chest syndrome (ACS) is defined by at least two of the following signs or symptoms: chest pain, fever, pulmonary infiltrate or focal abnormality, respiratory symptoms, or hypoxemia.[22] It is the second-most common complication and it accounts for about 25% of deaths in patients with SCD, majority of cases present with vaso-occlusive crises then they develop ACS.[23][24] Nevertheless, about 80% of patients have vaso-occlusive crises during ACS.
再生不良性危機（Aplastic crisis）
再生不良危機是患者基線貧血的嚴重惡化，產生{{Link-en|蒼白的外表|pale appearance}}，{{Link-en|心跳加快|fast heart rate}}，疲勞。這場危機通常是由{{Link-en|細小病毒B19|parvovirus B19}}引起的，细菌病毒B19透過入侵紅血球直接影響{{Link-en|紅血球的產生|production of red blood cells}}，並使其繁殖並摧毀它們。細小病毒感染幾乎完全阻止紅血球的產生兩到三天。在正常人中，並没有什么影響，但是在SCD患者的紅血球壽命縮短導致突然危及生命的情况。疾病期間{{Link-en|網狀紅血球|Reticulocyte}}數量顯著下降（引起{{Link-en|網狀紅血球過少|reticulocytopenia}}），紅血球快速轉換導致血红蛋白下降。這場危機需要4天到1週的時間才會消失。大多數患者可以支持性的管理；有些需要輸血。
Aplastic crises are acute worsenings 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.[25] Parvovirus infection almost completely prevents red blood cell production for two to three days. 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 counts drop dramatically during the disease (causing reticulocytopenia), and the rapid turnover of red cells leads to the drop in haemoglobin. This crisis takes 4 days to one week to disappear. Most patients can be managed supportively; some need blood transfusion.[26]
溶血性危機（Haemolytic crisis）
溶血性危機是血紅蛋白急劇加速下降。紅血球以很快的速度分解。特別常見於合併{{Link-en|G6PD缺乏症|G6PD deficiency}}的患者。支持性的管理，有時輸血。
Haemolytic crises are acute accelerated drops in haemoglobin level. The red blood cells break down at a faster rate. This is particularly common in patients with coexistent G6PD deficiency.[27] Management is supportive, sometimes with blood transfusions.[17]
其他（Other）
One of the earliest clinical manifestations is dactylitis, presenting as early as six months of age, and may occur in children with sickle-cell trait.[28] The crisis can last up to a month.[29] Another recognised type of sickle crisis, acute chest syndrome, is characterised by fever, chest pain, difficulty breathing, and pulmonary infiltrate on a chest X-ray. Given that pneumonia and sickling in the lung can both produce these symptoms, the patient is treated for both conditions.[30] It can be triggered by painful crisis, respiratory infection, bone-marrow embolisation, or possibly by atelectasis, opiate administration, or surgery.[citation needed] Hematopoietic ulcers may also occur.[31]
遺傳學（Genetics）
Normally, humans have haemoglobin A, which consists of two alpha and two beta chains, haemoglobin A2, which consists of two alpha and two delta chains, and haemoglobin F, consisting of two alpha and two gamma chains in their bodies. Of these, haemoglobin F dominates until about 6 weeks of age. Afterwards, haemoglobin A dominates throughout life.[citation needed]
Sickle-cell conditions have an autosomal recessive pattern of inheritance from parents. The types of haemoglobin a person makes in the red blood cells depend on what haemoglobin genes are inherited from her or his parents. If one parent has sickle-cell anaemia and the other has sickle-cell trait, then the child has a 50% chance of having sickle-cell disease and a 50% chance of having sickle-cell trait. When both parents have sickle-cell trait, a child has a 25% chance of sickle-cell disease, 25% do not carry any sickle-cell alleles, and 50% have the heterozygous condition.[32]
Sickle-cell gene mutation probably arose spontaneously in different geographic areas, as suggested by restriction endonuclease analysis. These variants are known as Cameroon, Senegal, Benin, Bantu, and Saudi-Asian. Their clinical importance is because some are associated with higher HbF levels, e.g., Senegal and Saudi-Asian variants, and tend to have milder disease.[33]
In people heterozygous for HgbS (carriers of sickling haemoglobin), the polymerisation problems are minor, because the normal allele is able to produce over 50% of the haemoglobin. In people homozygous for HgbS, the presence of long-chain polymers of HbS distort the shape of the red blood cell from a smooth doughnut-like shape to ragged and full of spikes, making it fragile and susceptible to breaking within capillaries. Carriers have symptoms only if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated. The sickle-cell disease occurs when the sixth amino acid, glutamic acid, is replaced by valine to change its structure and function; as such, sickle-cell anemia is also known as E6V. Valine is hydrophobic, causing the haemoglobin to collapse on itself occasionally. The structure is not changed otherwise. When enough haemoglobin collapses on itself the red blood cells become sickle-shaped.[citation needed]
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 (E/Glu) being substituted by valine (V/Val) at position 6. Note, historic numbering put this glutamic acid residue at position 6 due to skipping the methionine (M/Met) start codon in protein amino acid position numbering. Current nomenclature calls for counting the methionine as the first amino acid, resulting in the glutamic acid residue falling at position 7. Many references still refer to position 6 and both should likely be referenced for clarity. Haemoglobin S with this mutation is 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 GTG codon on the coding strand, which is transcribed from the template strand into a GUG codon. Based on genetic code, GAG codon translates to glutamic acid (E/Glu) while GUG codon translates to valine (V/Val) amino acid at position 6. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or quaternary structures of haemoglobin in conditions of normal oxygen concentration. What it does allow for, under conditions of low oxygen concentration, is the polymerization of the HbS itself. The deoxy form of haemoglobin exposes a hydrophobic patch on the protein between the E and F helices. The hydrophobic side chain of the valine residue at position 6 of the beta chain in haemoglobin is able to associate with the hydrophobic patch, causing haemoglobin S molecules to aggregate and form fibrous precipitates.
{{Link-en|HBB|HBB}}基因（負責鐮狀細胞性貧血）位於第15染色體11號短（p）臂上
HBB gene (responsible for sickle-cell anaemia) is located on the short (p) arm of chromosome 11 at position 15.5
The allele responsible for sickle-cell anaemia can be found on the short arm of chromosome 11, more specifically 11p15.5. 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 carrier or heterozygote. Heterozygotes are still able to contract malaria, but their symptoms are generally less severe.[34]
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.[35] Malaria was historically endemic to southern Europe, but it was declared eradicated in the mid-20th century, with the exception of rare sporadic cases.[36]
The malaria parasite has a complex lifecycle and spends part of it in red blood cells. In a carrier, the presence of the malaria parasite causes the red blood cells with defective haemoglobin to rupture prematurely, making the Plasmodium parasite 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).
In the USA, with no endemic malaria, the prevalence of sickle-cell anaemia among African Americans is lower (about 0.25%) than in West Africa (about 4.0%) and is falling. Without endemic malaria, the sickle-cell mutation is purely disadvantageous, and tends to decline in the affected population by natural selection, and now artificially through prenatal genetic screening. However, the African American community descends from a significant admixture of several African and non-African ethnic groups, and also represents the descendants of survivors of slavery and the slave trade. Thus, a lower degree of endogamy and, particularly, abnormally high health-selective pressure through slavery may be the most plausible explanations for the lower prevalence of sickle-cell anaemia (and, possibly, other genetic diseases) among African Americans compared to West Africans. Another factor that limits the spread of sickle-cell genes in North America is the absence of cultural proclivities to polygamy, which allows affected males to continue to seek unaffected children with multiple partners.[37]
病理生理學（Pathophysiology）
The loss of red blood cell elasticity is central to the pathophysiology of sickle-cell disease. Normal red blood cells are quite elastic, 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.
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.[38] Healthy red blood cells typically function for 90–120 days, but sickled cells only last 10–20 days.[39]
診斷（Diagnosis）
In HbSS, the complete blood count reveals haemoglobin levels in the range of 6–8 g/dl with a high reticulocyte count (as the bone marrow compensates for the destruction of sickled cells by producing more red blood cells). In other forms of sickle-cell disease, Hb levels tend to be higher. A blood film may show features of hyposplenism (target cells and Howell-Jolly bodies).
Sickling of the red blood cells, on a blood film, can be induced by the addition of sodium metabisulfite. The presence of sickle haemoglobin can also be demonstrated with the "sickle solubility test". A mixture of haemoglobin S (Hb S) in a reducing solution (such as sodium dithionite) gives a turbid appearance, whereas normal Hb gives a clear solution.
Abnormal haemoglobin forms can be detected on haemoglobin electrophoresis, a form of gel electrophoresis on which the various types of haemoglobin move at varying speeds. Sickle-cell haemoglobin (HgbS) and haemoglobin C with sickling (HgbSC)—the two most common forms—can be identified from there. The diagnosis can be confirmed with high-performance liquid chromatography. Genetic testing is rarely performed, as other investigations are highly specific for HbS and HbC.[40]
An acute sickle-cell crisis is often precipitated by infection. Therefore, a urinalysis to detect an occult urinary tract infection, and chest X-ray to look for occult pneumonia, should be routinely performed.[41]
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 fetus or a sample of amniotic fluid. Since taking a blood sample from a fetus has greater risks, the latter test is usually used. Neonatal screening provides not only a method of early detection for individuals with sickle-cell disease, but also allows for identification of the groups of people that carry the sickle cell trait.[42]
葉酸和青黴素（Folic acid and penicillin）
建議每天使用{{Link-en|葉酸|Folic acid}}。 從出生到五歲，青黴素每天建議由於未成熟的免疫系統，使他們更容易發生早期兒童疾病。
Folic acid daily for life is recommended. From birth to five years of age, penicillin daily due to the immature immune system that makes them more prone to early childhood illnesses is also recommended.
瘧疾防治（Malaria prevention）
The protective effect of sickle-cell trait does not apply to people with sickle cell disease; in fact, they are more vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It has therefore been recommended that people with sickle-cell disease living in malarial countries should receive anti-malarial chemoprophylaxis for life.[43]
血管阻塞性危機（Vaso-occlusive crisis）
Most people with sickle-cell disease have intensely painful episodes called vaso-occlusive crises. However, the frequency, severity, and duration of these crises vary tremendously. Painful crises are treated symptomatically with pain medications; pain management requires opioid administration at regular intervals until the crisis has settled. For milder crises, a subgroup of patients manage on NSAIDs (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 also an effective agent that doctors frequently prescribe to help control itching associated with the use of opioids.[citation needed]
急性胸部危機（Acute chest crisis）
Management is similar to vaso-occlusive crisis, with the addition of antibiotics (usually a quinolone or macrolide, since cell wall-deficient ["atypical"] bacteria are thought to contribute to the syndrome),[44] oxygen supplementation for 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 of haemoglobin S in the patient’s blood. The patient with suspected acute chest syndrome should be admitted to the hospital with worsening A-a gradient an indication for ICU admission.[22]
羥基脲（Hydroxyurea）
The first approved drug for the causative treatment of sickle-cell anaemia, hydroxyurea, was shown to decrease the number and severity of attacks in a study in 1995 (Charache et al.)[45] and shown to possibly increase survival time in a study in 2003 (Steinberg et al.).[46] This is achieved, in part, by reactivating fetal haemoglobin production in place of the haemoglobin S that causes sickle-cell anaemia. Hydroxyurea had previously been used as a chemotherapy agent, and there is some concern that long-term use may be harmful, but this risk has been shown to be either absent or very small and it is likely that the benefits outweigh the risks.[13][47]
輸血（Blood transfusion）
Blood transfusions are often used in the management of sickle-cell disease in acute cases and to prevent complications by decreasing the number of red blood cells (RBC) that can sickle by adding normal red blood cells.[48] In children preventative red blood cell (RBC) transfusion therapy has been shown to reduce the risk of first stroke or silent stroke when transcranial Doppler (TCD) ultrasonography shows abnormal cerebral blood flow.[6] In those who have sustained a prior stroke event it also reduces the risk of recurrent stroke and additional silent strokes.[49][50]
骨髓移植（Bone marrow transplant）
Bone marrow transplants have proven effective in children. Bone marrow transplants are the only known cure for SCD.[51] However, bone marrow transplants are difficult to obtain because of the specific HLA typing necessary. Ideally, a close relative (allogeneic) would donate the bone marrow necessary for transplantation.
About 90% of people survive to age 20, and close to 50% survive beyond the fifth decade.[52] In 2001, according to one study performed in Jamaica, the estimated mean survival for people with sickle-cell was 53 years old for men and 58 years old for women with homozygous SCD.[53] The specific life expectancy in much of the developing world is unknown.[54]
併發症（Complications）
Sickle-cell anaemia can lead to various complications, including:
The highest frequency of sickle cell disease is found in tropical regions, particularly sub-Saharan Africa, tribal regions of India and the Middle-East.[67] 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.[68] In 2013 it resulted in 176,000 deaths due to SCD up from 113,000 deaths in 1990.[10]
Sickle-cell disease occurs more commonly among people whose ancestors lived in tropical and sub-tropical sub-Saharan regions where malaria is or was common. Where malaria is common, carrying a single sickle-cell allele (trait) confers a selective advantage—in other words, being a heterozygote is advantageous. Specifically, humans with one of the two alleles of sickle-cell disease show less severe symptoms when infected with malaria.[69]
非洲（Africa）
Three quarters of sickle-cell cases occur in Africa. A recent WHO report 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.[70] There have been studies in Africa that show a significant decrease in infant mortality rate, ages 2–16 months, because of the sickle-cell trait. This happened in predominant areas of malarial cases.[71]
United States
The number of people with the disease in the United States is approximately 1 in 5,000, mostly affecting Americans of Sub-Saharan African descent, according to the National Institutes of Health.[72] In the United States, about one out of 500 African-American children and one in every 36,000 Hispanic-American children have sickle-cell anaemia.[73] It is estimated that sickle-cell disease affects 90,000 Americans.[74] Most infants with SCD born in the United States are now identified by routine neonatal screening. Forty-four states along with the District of Columbia, Puerto Rico and the Virgin Islands currently provide universal neonatal screening for SCD.[75][76] Sickle cell trait occurs among about 1:13 African-Americans and 1:100 Hispanic-Americans.[77] It is estimated that 2.5 million Americans are heterozygous carriers for the sickle-cell trait.[78]
法國（France）
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.[79] SCD has become the most common genetic disease in the country, with an overall birth prevalence of 1/2,415 in mainland France, ahead of phenylketonuria (1/10,862), congenital hypothyroidism (1/3,132), congenital adrenal hyperplasia (1/19,008) and cystic fibrosis (1/5,014) for the same reference period. In 2010, 31.5% of all newborns in mainland France (253,466 out of 805,958) were screened for SCD (this percentage was 19% in 2000). 341 newborns with SCD and 8,744 heterozygous carriers were found representing 1.1% of all newborns in mainland France. The Paris metropolitan district (Île-de-France) is the region that accounts for the largest number of newborns screened for SCD (60% in 2010). The second largest number of at-risk is in Provence-Alpes-Côte d’Azur at nearly 43.2% and the lowest number is in Brittany at 5.5%.[80][81]
英國（United Kingdom）
In the United Kingdom (UK) it is thought that between 12,000 and 15,000 people have sickle cell disease [82] with an estimate of 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.[83] 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.[84] 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.[85] Donors who are found to be carriers are then 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.[86]
Middle East
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.[87] In 2005 in Saudi Arabia a mandatory pre-marital test including HB electrophoresis was launched and aimed to decrease the incidence of SCD and thalassemia.[88]
印度和尼泊爾（India and Nepal）
Sickle-cell disease is common in ethnic groups of central India who share a genetic linkage with African communities,[citation needed] where the prevalence has ranged from 9.4 to 22.2% in endemic areas of Madhya Pradesh, Rajasthan and Chhattisgarh.[89] It is also endemic among Tharu people of Nepal and India; however, they have a sevenfold lower incidence of malaria despite living in a malaria infested zone.[90]
加勒比群島（Caribbean Islands）
在{{Link-en|牙買加|Jamaica}}，10％的人口攜帶鐮狀細胞基因，使之成為最常見的遺傳性疾病的國家。
In Jamaica, 10% of the population carries the sickle-cell gene, making it the most prevalent genetic disorder in the country.[91]
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 findings was the absence of the spleen.[92][93] There were also reports amongst African slaves in the United States exhibiting resistance to malaria but being prone to leg ulcers.[93]
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 the 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 suffering from anaemia.[11][94] 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.[11][12] 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."[95] This article is based on a patient admitted to the University of Virginia Hospital on November 15, 1910.[96] In the later description by Verne Mason in 1922, the name "sickle cell anemia" is first used.[12][97]
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.[93]
The Memphis physician Lemuel Diggs, a prolific researcher into sickle cell disease, first introduced the distinction between sickle cell disease and trait in 1933, although it took until 1949 until the genetic characteristics were elucidated by James V. Neel and E.A. Beet.[12] 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.[12][98] The actual molecular change in HbS was described in the late 1950s BY Vernon Ingram.[12] 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.[12]
Large scale natural history studies and further intervention studies were introduced in the 1970s and 1980s, leading to the more 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 suffering from sickle-cell disease.[99] The 1990s saw the development of hydroxycarbamide, and reports of cure through bone marrow transplantation appeared in 2007.[12]
Some old texts refer to it as drepanocytosis.[citation needed]
請參見：List of sickle-cell disease researchers
See also: List of sickle-cell disease researchers
臍帶血移植（Umbilical cord blood transplant）
In December 1998, researchers from Emory University conducted an experimental bone marrow transplant procedure on a group of 22 children under 16 years old.[100] One of those patients, 12-year-old Keone Penn, was apparently the first person to be cured of sickle-cell disease through this method.[101] The stem cells were sourced from a donor unrelated to Penn. A 2007 Georgia Senate bill proposing the collection and donation of stem cell material, the "Saving the Cure Act", was nicknamed "Keone’s Law" in his honor.[102]
By mid-2007 a similar set of clinical trials in Baltimore had also cured several adults.[103]
基因治療（Gene therapy）
In 2001 it was reported that sickle-cell disease had been successfully treated in mice using gene therapy.[104][105] The researchers used a viral vector to make the mice—which have essentially the same defect that causes human sickle cell disease—express production of fetal hemoglobin (HbF), which an individual normally ceases to produce shortly after birth. In humans, using hydroxyurea to stimulate production of HbF has been known to temporarily alleviate sickle cell disease symptoms. The researchers demonstrated that this gene therapy method is a more permanent way to increase therapeutic HbF production.[106]
Phase 1 clinical trials of gene therapy for sickle cell disease in humans were started in 2014. The clinical trials will assess the safety and initial evidence for efficacy of an autologous transplant of lentiviral vector modified bone marrow for adults with severe sickle cell disease.[107][108] As of 2014, however, no randomized controlled trials have been reported.[109]
參考（References）