鐮刀型紅血球疾病
维基百科，自由的百科全书
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| 鐮刀型紅血球細胞 | ||
| ICD-10 | D57. | |
| ICD-9 | 282.6 | |
| OMIM | 603903 | |
| DiseasesDB | 1206 | |
| MedlinePlus | 000527 | |
| eMedicine | emerg/26 | |
| MeSH | C15.378.071.141.150.150 | |
鐮刀型紅血球疾病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，紅血球皆因失常的鐘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，尤其是在非洲撒哈拉以南地區的人和其後裔們。但無論如此，鐮刀型紅血球疾病可能發生在任何膚色和任何人種身上。
目录 |
[编辑] 類型和術語
「鐮刀型細胞貧血症」是一種特定類型的鐮刀型紅血球疾病的名稱，其病因在於同型結合子而產生了Hgb S的突變。其他類型的包括：
- 鐮刀型血紅蛋白C疾病
- 鐮刀型β+地中海貧血
- 鐮刀型β0地中海貧血
- 血紅蛋白SS疾病
和鐮刀型細胞貧血症不同，其他類型的鐮刀型紅血球疾病的病因在於異型結合，使得一個複製成導致Hgb S的突變，一個複製成異常的血紅蛋白基因。必須要知道的是，「鐮刀型細胞貧血症」是「鐮刀型紅血球疾病」一特定類型的名稱，而「鐮刀型紅血球疾病」則不是。因為不同類型的鐮刀型紅血球疾病都極不一樣，所以必須在治療前，先分辦出疾病的確切類型。
[编辑] 徵兆及症狀
罹患了鐮刀型細胞貧血症的人會有激烈變化的貧血症，和一般血紅蛋白濃度為6-9 g/dl相比。網織紅血球的數量開始提升，反映了新的紅血球細胞在取代快速遭破壞的舊細胞，紅血球的生命週期被此一疾病明顯地縮短了。通常，白血球和血小板的數量也會提升，並可能因此導致血管阻塞。
[编辑] 血管阻塞危機
血管阻塞危機是由於鐮刀型紅血球細胞會阻塞毛細血管而限制流至器官的血量，因而導致局部缺血、疼痛和器官的傷害。
因為脾臟細小的血管和負有清除不良紅血球的功能，所以常常會被影響到，通常在患者兒童期未期前便會形成梗塞。這種自體脾臟移除(autosplenectomy)會增加被encapsulated organisms感染的風險，對於這類脾功能缺乏者，預防性的抗生素和接種都被建議要有的。肝衰竭也有可能漸漸地出現。
骨頭，尤其是支撐體重的骨頭，也常是血管阻塞傷害的主要目標之一。如此會導致缺血性壞死(尤其是在股骨部位)和骨頭退化。患者感覺到的疼痛也是源於骨頭梗塞。
A recognized type of sickle crisis is the acute chest crisis, a condition characterized by fever, chest pain, hard breathing, and pulmonary infiltrate on chest X-ray. Given that pneumonia and intra-pulmonary sickling can both produce these symptoms, the patient is treated for both conditions. Treatment consists of admission, oxygen, close monitoring, and intravenous antibiotics.
[编辑] 其他危機
- Aplastic crisis. An acute worsening 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). 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.
- Splenic sequestration crisis. An acute, painful enlargement of the spleen. The abdomen becomes bloated and very hard. Management is supportive, sometimes with blood transfusion.
[编辑] Complications
Sickle-cell anemia can lead to various complications, including:
- Overwhelming post-(auto)splenectomy infection - 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 hematologists continuing treatment indefinitely. Patients benefit today from routine vaccination for Haemophilus influenzae, Pneumococcus and Meningococcus.
- Stroke - progressive vascular narrowing (occlusion) can prevent oxygen from reaching the brain, leading to stroke; cerebral infarction occurs in children, and cerebral hemorrhage in adults.
- Cholelithiasis and cholecystitis (gallstones) - prolonged hemolysis may lead to excessive bilirubin production and precipitation, leading to gallstones
- Avascular necrosis (aseptic bone necrosis) of the hip
- Decreased immune reactions due to hyposplenism (malfunctioning of the spleen)
- Priapism and infarction of the penis (in men)
- Osteomyelitis (bacterial bone infection) - salmonella is noted much more commonly than in the general population, but staphylococcus is still the most common pathogen.
- Opioid addiction (see below)
[编辑] Diagnosis
Attacks are diagnosed clinically, i.e. there is no gold standard diagnostic test. Hemolysis (anemia and jaundice) is often present, although for painful crises the diagnosis depends essentially on how the patient describes the pain.
Abnormal hemoglobin forms are detected on hemoglobin electrophoresis, a form of gel electrophoresis on which the various types of hemoglobin move at varying speed. Sickle cell hemoglobin (HbSS) and Hemoglobin C with sickling (HbSC)—the two most common forms—can be identified from there. Genetic testing is rarely performed.
[编辑] Pathophysiology
Sickle-cell anemia is caused by a mutation in the β-globin chain of hemoglobin, replacing glutamic acid with less polar 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.
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 ischemia.
[编辑] Genetics
The allele responsible for sickle cell anemia is autosomal recessive. 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. 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.
The gene defect is a known mutation of a single nucleotide (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 GTG codon mutation. This is normally a benign mutation, causing no apparent effects on the secondary, tertiary, or 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 fibrous precipitates, as described below, to form. In people heterozygous for HbS (carriers of sickling hemoglobin), the polymerization problems are minor. In people homozygous for HbS, 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 capillaries. Carriers only have symptoms if they are deprived of oxygen (for example, while climbing a mountain) or while severely dehydrated. For those afflicted with the disease, however, vasocclusive events can be a painful part of life (normally they occur 0.8 times per year per patient). This occurs when HbS becomes deoxygenated it undergoes an abnormal change in shape and consistency which can lead to a change in the shape and plasticity in the cell wall of the RBC, an occurrence called sickling.
The sufferers of the illness have a reduced life span. It is believed that carriers (sickle cell trait) are relatively resistant to malaria. Since the 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 than either of the homozygotes. This is known as heterozygote advantage.
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 anemia.
Due to the above phenomenon, 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. In fact, sickle-cell anemia is the most common genetic disorder among African Americans; about 1 in every 12 is a carrier.
The evolution of sickle-cell anaemia is probably an example of Baldwinian evolution, whereby humans modify their environment and thus change the selective pressures. As humans in tropical areas in Africa and elsewhere developed agriculture and animal husbandry, they expanded the niche for Anopheles mosquitoes that could transmit the malaria parasite.
In the USA, where there is no endemic malaria, the incidence of sickle cell anaemia amongst African Americans is much lower than in West Africa and falling. Without endemic malaria from Africa, the condition is purely disadvantageous, and will tend to be bred out of the affected population. See the Price equation article for a simplified mathematical model of the genetic evolution of sickle cell anemia.
[编辑] Inheritance
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. 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. Like most genes, hemoglobin genes are inherited in two sets…one from each parent.
Examples: If one parent has Sickle Cell Anemia and the other is Normal, all of the children will have sickle cell trait.
If one parent has Sickle Cell Anemia and the other has Sickle Cell Trait, there is a 50% chance (or 1 out of 2) of having a baby with either sickle cell disease or sickle cell trait with each pregnancy.
When both parents have Sickle Cell Trait, they have a 25% chance (1 of 4) of having a baby with sickle cell disease with each pregnancy.
[编辑] Treatment
[编辑] Febrile illness
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.
[编辑] Painful (vaso-occlusive) crises
Most patients with sickle cell disease have intensely painful episodes called vaso-occlusive crises. The frequency, severity, and duration of these crises vary tremendously, however. Painful crises are treated symptomatically with analgesics; 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 effective for the itching associated with the opioid use.
[编辑] Acute chest crises
Management is similar to vaso-occlusive crises with the addition of antibiotics (usually a third generation cephalosporin), 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 hemoglobin S in the patient's blood.
[编辑] Hydroxyurea
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) and shown to increase survival time in a study in 2003. This is achieved by reactivating fetal hemoglobin production in place of the hemoglobin 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 it is likely that the benefits outweigh the risks.
[编辑] Future treatments
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.
Gene therapy is under investigation.
[编辑] Situation of carriers
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.
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.
[编辑] History
The cause of this collection of clinical findings was unknown until the description of the sickle cells in 1910 by the Chicago cardiologist and professor of medicine 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 [1].
The disease is very occasionally called "Herrick's syndrome" for this reason.
The disease was named "sickle cell anemia" by Vernon Mason in 1922. In retrospect some elements of the disease had been recognized 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 1870's 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 Ghanian family [2]. Also, the practice of using tar soap to cover blemishes caused by sickle cell sores was prevalent in the African American community.
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 evaluaton 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 [3]. These independent events occurred between 3000 and 6000 generations ago, approximately 70000-150000 years.
[编辑] Notes
- ↑ Savitt TL, Goldberg MF. Herrick's 1910 case report of sickle cell anemia. The rest of the story. JAMA. 1989;261:266-271. PMID 2642320
- ↑ 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 D. V. Desai, Hiren Dhanani: Sickle Cell Disease: History And Origin. The Internet Journal of Hematology. 2004. Volume 1 Number 2
- ↑ D. V. Desai, Hiren Dhanani: Sickle Cell Disease: History And Origin. The Internet Journal of Hematology. 2004. Volume 1 Number 2
[编辑] 另見
- Thalassemia
- Dominance relationships
- Genetic counseling
- Sickle cell trait
- Exchange transfusion
[编辑] 參考
- 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. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 1995;332:1317-22. PMID 12672732.
- 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.
[编辑] 外部連結
- [1]-Teens Health
- Sickle Cell (Sickle Cell Information Center)
- Sickle cell anemia research - Recent primary literature on sickle cell anemia
- SCA clinical trials (ClinicalTrials.gov)
- Sickle Cell Anemia (University of Maryland Medical Center)
- Sickle Cell links (NCBI)
| 醫療科學 - 醫學 - 血液學 - 編輯 |
|---|
| 骨髓惡性腫瘤 和 白血球 |
| 淋巴系統: 淋巴型白血病 (急性, 慢性) | 淋巴瘤 (何杰金氏病, 非何杰金氏淋巴瘤) | 淋巴增殖性病變 | 骨髓癌 (多發性骨髓癌, 質漿細胞瘤) |
| 骨髓: 骨髓性白血病 (急性, 慢性) | 骨髓增殖性疾病 (原發性血小板增多症, 紅血球增多症) | 骨髓成形不良症候群 | 骨髓纖維化 | 嗜中性白血球過低症 |
| 紅血球 |
| 貧血 | 血色病 | 鐮刀型紅血球疾病 | 地中海貧血 | 溶血反應 | 再生不良性貧血 | 蠶豆症 | 遺傳性球形紅細胞增多症 | 遺傳性橢圓形紅血球增多症 | 其他血紅蛋白病 |
| 凝血因子和血小板 |
| 血栓形成 | 深靜脈血栓形成 | 肺栓塞 | 血友病 | 自發性血小板缺乏紫斑症 | 血栓性血小板缺乏紫斑症 | 彌散性血管內凝血 |
