Beruflich Dokumente
Kultur Dokumente
1
2 2 GENETICS
The vaso-occlusive crisis is caused by sickle-shaped red Aplastic crises are acute worsenings of the patient’s
blood cells that obstruct capillaries and restrict blood flow baseline anaemia, producing pale appearance, fast heart
to an organ resulting in ischaemia, pain, necrosis, and rate, and fatigue. This crisis is normally triggered by
often organ damage. The frequency, severity, and du- parvovirus B19, which directly affects production of red
ration of these crises vary considerably. Painful crises blood cells by invading the red cell precursors and mul-
are treated with hydration, analgesics, and blood transfu- tiplying in and destroying them.[14] Parvovirus infection
sion; pain management requires opioid administration at almost completely prevents red blood cell production for
regular intervals until the crisis has settled. For milder two to three days. In normal individuals, this is of lit-
crises, a subgroup of patients manage on NSAIDs (such tle consequence, but the shortened red cell life of SCD
as diclofenac or naproxen). For more severe crises, patients results in an abrupt, life-threatening situation.
most patients require inpatient management for intra- Reticulocyte counts drop dramatically during the disease
venous opioids; patient-controlled analgesia devices are (causing reticulocytopenia), and the rapid turnover of red
commonly used in this setting. Vaso-occlusive crisis cells leads to the drop in haemoglobin. This crisis takes
involving organs such as the penis[5] or lungs are con- 4 days to one week to disappear. Most patients can be
sidered an emergency and treated with red-blood cell managed supportively; some need blood transfusion.[15]
transfusions. Incentive spirometry, a technique to en-
courage deep breathing to minimise the development of
1.5 Haemolytic crisis
atelectasis, is recommended.[6]
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
1.2.1 Splenic sequestration crisis with coexistent G6PD deficiency.[16] Management is
supportive, sometimes with blood transfusions.[6]
Because of its narrow vessels and function in clearing de-
fective red blood cells, the spleen is frequently affected.[7]
1.6 Other
It is usually infarcted before the end of childhood in in-
dividuals suffering from sickle-cell anemia. This spleen
One of the earliest clinical manifestations is dactylitis,
damage increases the risk of infection from encapsulated
presenting as early as six months of age, and may occur in
organisms;[8][9] preventive antibiotics and vaccinations
children with sickle-cell trait.[17] The crisis can last up to a
are recommended for those lacking proper spleen func-
month.[18] Another recognised type of sickle crisis, acute
tion.
chest syndrome, is characterised by fever, chest pain, dif-
Splenic sequestration crises are acute, painful enlarge- ficulty breathing, and pulmonary infiltrate on a chest X-
ments of the spleen, caused by intrasplenic trapping of ray. Given that pneumonia and sickling in the lung can
red cells and resulting in a precipitous fall in hemoglobin both produce these symptoms, the patient is treated for
levels with the potential for hypovolemic shock. Seques- both conditions.[19] It can be triggered by painful crisis,
tration crises are considered an emergency. If not treated, respiratory infection, bone-marrow embolisation, or pos-
patients may die within 1–2 hours due to circulatory fail- sibly by atelectasis, opiate administration, or surgery.
ure. Management is supportive, sometimes with blood
transfusion. These crises are transient, they continue for
3–4 hours and may last for one day.[10] 2 Genetics
Normally, humans have haemoglobin A, which consists
of two alpha and two beta chains, haemoglobin A2,
1.3 Acute chest syndrome which consists of two alpha and two delta chains, and
haemoglobin F, consisting of two alpha and two gamma
Acute chest syndrome (ACS) is defined by at least two of chains in their bodies. Of these, haemoglobin F dom-
the following signs or symptoms: chest pain, fever, pul- inates until about 6 weeks of age then A dominates
monary infiltrate or focal abnormality, respiratory symp- throughout life.
toms, or hypoxemia.[11] It is the second-most common Sickle-cell conditions have an autosomal recessive pat-
complication and it accounts for about 25% of deaths in tern of inheritance from parents. The types of
patients with SCD, majority of cases present with vaso- haemoglobin a person makes in the red blood cells de-
occlusive crises then they develop ACS.[12][13] Neverthe- pend on what haemoglobin genes are inherited from her
less, about 80% of patients have vaso-occlusive crises or his parents. If one parent has sickle-cell anaemia and
during ACS. the other has sickle-cell trait, then the child has a 50%
3
4 Diagnosis
In HbSS, the complete blood count reveals haemoglobin
levels in the range of 6–8 g/dl with a high reticulocyte
Unaffected Unaffected "Carrier" Affected
1 in 4 chance 2 in 4 chance 1 in 4 chance count (as the bone marrow compensates for the destruc-
tion of sickled cells by producing more red blood cells).
In other forms of sickle-cell disease, Hb levels tend to be
Sickle-cell disease is inherited in the autosomal recessive pattern. 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 in-
5.3 Vaso-occlusive crisis 5
duced by the addition of sodium metabisulfite. The pres- 5.3 Vaso-occlusive crisis
ence of sickle haemoglobin can also be demonstrated with
the “sickle solubility test”. A mixture of haemoglobin S Most people with sickle-cell disease have intensely
(Hb S) in a reducing solution (such as sodium dithion- painful episodes called vaso-occlusive crises. However,
ite) gives a turbid appearance, whereas normal Hb gives the frequency, severity, and duration of these crises vary
a clear solution. tremendously. Painful crises are treated symptomatically
with pain medications; pain management requires opioid
Abnormal haemoglobin forms can be detected on
administration at regular intervals until the crisis has set-
haemoglobin electrophoresis, a form of gel electrophore-
tled. For milder crises, a subgroup of patients man-
sis on which the various types of haemoglobin move
age on NSAIDs (such as diclofenac or naproxen). For
at varying speeds. Sickle-cell haemoglobin (HgbS) and
more severe crises, most patients require inpatient man-
haemoglobin C with sickling (HgbSC)—the two most
agement for intravenous opioids; patient-controlled anal-
common forms—can be identified from there. The di-
gesia (PCA) devices are commonly used in this setting.
agnosis can be confirmed with high-performance liquid
Diphenhydramine is also an effective agent that doctors
chromatography. Genetic testing is rarely performed,
frequently prescribe to help control itching associated
as other investigations are highly specific for HbS and
with the use of opioids.
HbC.[27]
An acute sickle-cell crisis is often precipitated by infec-
tion. Therefore, a urinalysis to detect an occult urinary 5.4 Acute chest crisis
tract infection, and chest X-ray to look for occult pneu-
monia, should be routinely performed.[28] Management is similar to vaso-occlusive crisis, with the
People who are known carriers of the disease often un- addition of antibiotics (usually a quinolone or macrolide,
dergo genetic counseling before they have a child. A test since cell wall-deficient ["atypical"] [31]
bacteria are thought
to see if an unborn child has the disease takes either a to contribute to the syndrome), oxygen supplementa-
blood sample from the fetus or a sample of amniotic fluid. tion for hypoxia, and close observation. Should the pul-
Since taking a blood sample from a fetus has greater risks, monary infiltrate worsen or the oxygen requirements in-
the latter test is usually used. Neonatal screening provides crease, simple blood transfusion or exchange transfusion
not only a method of early detection for individuals with is indicated. The latter involves the exchange of a sig-
sickle-cell disease, but also allows for identification of the nificant portion of the patients red cell mass for normal
groups of people that carry the sickle cell trait.[29] 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
[11]
5 Management
5.5 Hydroxyurea
5.1 Folic acid and penicillin
The first approved drug for the causative treatment of
Children born with sickle-cell disease undergo close ob- sickle-cell anaemia, hydroxyurea, was shown to decrease
servation by the pediatrician and require management by the number and severity of attacks in a study in 1995
a haematologist to assure they remain healthy. These pa- (Charache et al.)[32] and shown to possibly increase sur-
tients take a 1 mg dose of folic acid daily for life. From vival time in a study in 2003 (Steinberg et al.).[33] This is
birth to five years of age, they also have to take penicillin achieved, in part, by reactivating fetal haemoglobin pro-
daily due to the immature immune system that makes duction in place of the haemoglobin S that causes sickle-
them more prone to early childhood illnesses. 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 ben-
efits outweigh the risks.[2][34]
5.2 Malaria chemoprophylaxis
The protective effect of sickle-cell trait does not ap- 5.6 Transfusion therapy
ply to people with sickle cell disease; in fact, they are
more vulnerable to malaria, since the most common cause Blood transfusions are often used in the management of
of painful crises in malarial countries is infection with sickle-cell disease in acute cases and to prevent complica-
malaria. It has therefore been recommended that people tions by decreasing the number of red blood cells (RBC)
with sickle-cell disease living in malarial countries should that can sickle by adding normal red blood cells.[35]
receive anti-malarial chemoprophylaxis for life.[30] In children prophylactic chronic red blood cell (RBC)
6 6 PROGNOSIS
transfusion therapy has been shown to be efficacious to a • Cholelithiasis (gallstones) and cholecystitis may re-
certain extent in reducing the risk of first stroke or silent sult from excessive bilirubin production and precip-
stroke when transcranial Doppler (TCD) ultrasonography itation due to prolonged haemolysis.
shows abnormal increased cerebral blood flow velocities.
In those who have sustained a prior stroke event it also • Avascular necrosis (aseptic bone necrosis) of the
reduces the risk of recurrent stroke and additional silent hip and other major joints may occur as a result of
strokes.[36][37] ischaemia.[44]
Bone marrow transplants have proven effective in chil- • Priapism and infarction of the penis[46]
dren. Bone marrow transplants are the only known cure
for SCD.[38] However, bone marrow transplants are diffi- • Osteomyelitis (bacterial bone infection), the
cult to obtain because of the specific HLA typing neces- most common cause of osteomyelitis in SCD
sary. Ideally, a twin family member (syngeneic) or close is Salmonella (especially the atypical serotypes
relative (allogeneic) would donate the bone marrow nec- Salmonella typhimurium, Salmonella enteritidis,
essary for transplantation. Salmonella choleraesuis and Salmonella paraty-
phi B), followed by Staphylococcus aureus and
Gram-negative enteric bacilli perhaps because
intravascular sickling of the bowel leads to patchy
6 Prognosis ischaemic infarction.[47]
About 90% of patients survive to age 20, and close to 50% • Opioid tolerance can occur as a normal, physiologic
survive beyond the fifth decade.[39] In 2001, according response to the therapeutic use of opiates. Addic-
to one study performed in Jamaica, the estimated mean tion to opiates occurs no more commonly among in-
survival for sickle-cell patients was 53 years old for men dividuals with sickle-cell disease than among other
and 58 years old for women with homozygous SCD.[40] individuals treated with opiates for other reasons.
The highest frequency of sickle cell disease is found in As a result of population growth in African-Caribbean
tropical regions, particularly sub-Saharan Africa, tribal regions of overseas France and immigration from North
regions of India and the Middle-East.[53] Migration of and sub-Saharan Africa to mainland France, sickle-cell
substantial populations from these high prevalence areas disease has become a major health problem in France.[65]
to low prevalence countries in Europe has dramatically SCD has become the most common genetic disease in the
increased in recent decades and in some European coun- country, with an overall birth prevalence of 1/2,415 in
tries sickle-cell disease has now overtaken more familiar mainland France, ahead of phenylketonuria (1/10,862),
genetic conditions such as haemophilia and cystic fibro- congenital hypothyroidism (1/3,132), congenital adrenal
sis.[54] In 2013 it resulted in 176,000 deaths due to SCD hyperplasia (1/19,008) and cystic fibrosis (1/5,014) for
up from 113,000 deaths in 1990.[1] the same reference period. In 2010, 31.5% of all new-
borns in mainland France (253,466 out of 805,958) were
Sickle-cell disease occurs more commonly among peo- screened for SCD (this percentage was 19% in 2000).
ple whose ancestors lived in tropical and sub-tropical sub- 341 newborns with SCD and 8,744 heterozygous car-
Saharan regions where malaria is or was common. Where riers were found representing 1.1% of all newborns in
malaria is common, carrying a single sickle-cell allele mainland France. The Paris metropolitan district (Île-de-
(trait) confers a selective advantage—in other words, be- France) is the region that accounts for the largest num-
ing a heterozygote is advantageous. Specifically, humans ber of newborns screened for SCD (60% in 2010). The
with one of the two alleles of sickle-cell disease show less second largest number of at-risk is in Provence-Alpes-
severe symptoms when infected with malaria.[55] Côte d'Azur at nearly 43.2% and the lowest number is in
Brittany at 5.5%.[66][67]
7.1 Africa
7.6 India and Nepal were elucidated by James V. Neel and E.A. Beet.[82] 1949
was the year when Linus Pauling described the unusual
Sickle-cell disease is common in the tribal people of cen- chemical behaviour of haemoglobin S, and attributed this
tral India who share a genetic linkage with the African to an abnormality in the molecule itself.[82][86] The ac-
race, where the prevalence has ranged from 9.4 to 22.2% tual molecular change in HbS was described in the late
in endemic areas of Madhya Pradesh, Rajasthan and 1950s BY Vernon Ingram.[82] The late 1940s and early
Chhattisgarh.[75] It is also endemic among Tharu people 1950s saw further understanding in the link between
of Nepal and India, however, they have a sevenfold lower malaria and sickle cell disease. In 1954, the introduction
incidence of malaria despite living in a malaria infested of haemoglobin electrophoresis allowed the discovery of
zone.[76] particular subtypes, such as HbSC disease.[82]
Large scale natural history studies and further interven-
7.7 Caribbean Islands tion studies were introduced in the 1970s and 1980s, lead-
ing to the more widespread use of prophylaxis against
In Jamaica, 10% of the population carries the sickle-cell pneumococcal infections amongst other interventions. In
gene, making it the most prevalent genetic disorder in the 1972, Bill Cosby's Emmy-winning TV movie, To All My
country.[77] Friends on Shore, depicted the story of the parents of
a child suffering from sickle-cell disease.[87] The 1990s
saw the development of hydroxycarbamide, and reports
of cure through bone marrow transplantation appeared in
8 History 2007.[82]
production.[94] [9] Wong WY, Powars DR, Chan L, Hiti A, Johnson C, Over-
turf G (Mar 1992). “Polysaccharide encapsulated bac-
A 1 clinical trials of gene therapy for sickle cell disease in terial infection in sickle cell anaemia: a thirty year epi-
humans were started in 2014.[95][96] As of 2014 however demiologic experience”. Am J Hematol 39 (3): 176–82.
no randomized controlled trials have been reported.[97] doi:10.1002/ajh.2830390305. PMID 1546714.
[10] Khatib R, Rabah R, Sarnaik SA (January 2009). “The
spleen in the sickling disorders: an update”. Pediatric Ra-
10 See also diology 39 (1): 17–22. doi:10.1007/s00247-008-1049-9.
PMID 19002450.
• Haematopoietic ulcer [11] Glassberg, J (August 2011). “Evidence-based manage-
ment of sickle cell disease in the emergency department.”.
Emergency medicine practice 13 (8): 1–20; quiz 20. PMID
22164362.
11 References
[12] Mekontso Dessap A, Leon R, Habibi A, Nzouakou R,
Roudot-Thoraval F, Adnot S, Godeau B, Galacteros F,
[1] GBD 2013 Mortality and Causes of Death, Collabora- Brun-Buisson C, Brochard L, Maitre B (2008). “Pul-
tors (17 December 2014). “Global, regional, and national monary hypertension and cor pulmonale during severe
age-sex specific all-cause and cause-specific mortality for acute chest syndrome in sickle cell disease”. Am.
240 causes of death, 1990-2013: a systematic analysis for J. Respir. Crit. Care Med. 177 (6): 646–53.
the Global Burden of Disease Study 2013.”. Lancet 385: doi:10.1164/rccm.200710-1606OC. PMID 18174543.
117–171. doi:10.1016/S0140-6736(14)61682-2. PMC
4340604. PMID 25530442. [13] Paul RN, Castro OL, Aggarwal A, Oneal PA (2011).
“Acute chest syndrome: sickle cell disease”. Eur. J.
[2] Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Haematol. 87 (3): 191–207. doi:10.1111/j.1600-
Hassell KL, James AH, Jordan L, Lanzkron SM, Lotten- 0609.2011.01647.x. PMID 21615795.
berg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH,
[14] Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster,
Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-
Jon (2009-05-28). Robbins and Cotran Pathologic Basis
Sowah J (Sep 10, 2014). “Management of sickle cell
of Disease, Professional Edition: Expert Consult - Online
disease: summary of the 2014 evidence-based report by
(Robbins Pathology) (Kindle Location 33329). Elsevier
expert panel members.”. JAMA 312 (10): 1033–48.
Health. Kindle Edition.
doi:10.1001/jama.2014.10517. PMID 25203083.
[15] Slavov SN, Kashima S, Pinto AC, Covas DT (Au-
[3] “BestBets: How long should an average sickle cell crisis gust 2011). “Human parvovirus B19: general con-
last?". Retrieved 2010-11-27. siderations and impact on patients with sickle-cell dis-
ease and thalassemia and on blood transfusions”. FEMS
[4] Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster, Immunology and Medical Microbiology 62 (3): 247–
Jon (2009-05-28). Robbins and Cotran Pathologic Basis 62. doi:10.1111/j.1574-695X.2011.00819.x. PMID
of Disease, Professional Edition: Expert Consult - Online 21585562.
(Robbins Pathology) (Kindle Locations 33498-33499).
Elsevier Health. Kindle Edition. [16] Balgir RS (March 2012). “Community expansion and
gene geography of sickle cell trait and G6PD defi-
[5] Olujohungbe A, Burnett AL (2013). “How I manage ciency, and natural selection against malaria: experience
priapism due to sickle cell disease”. British Journal of from tribal land of India”. Cardiovascular & Hema-
Haematology 160 (6): 754–65. doi:10.1111/bjh.12199. tological Agents in Medicinal Chemistry 10 (1): 3–13.
PMID 23293942. doi:10.2174/187152512799201190. PMID 22264009.
[17] Jadavji T, Prober CG (April 1985). “Dactylitis in a child
[6] Glassberg J (August 2011). “Evidence-based manage- with sickle cell trait”. Can Med Assoc J 132 (7): 814–5.
ment of sickle cell disease in the emergency department”. ISSN 0008-4409. PMC 1345873. PMID 3978504.
Emergency Medicine Practice 13 (8): 1–20; quiz 20.
PMID 22164362. [18] Worrall VT, Butera V (1976). “Sickle-cell dactylitis”. J
Bone Joint Surg Am 58 (8): 1161–3. PMID 1002763.
[7] Anie KA, Green J (2012). Anie, Kofi A, ed. “Psy-
[19] Miller ST (May 2011). “How I treat acute chest syndrome
chological therapies for sickle cell disease and pain”.
in children with sickle cell disease”. Blood 117 (20):
Cochrane Database of Systematic Reviews (Online) 2:
5297–305. doi:10.1182/blood-2010-11-261834. PMID
CD001916. doi:10.1002/14651858.CD001916.pub2.
21406723.
PMID 22336781.
[20] Green NS, Fabry ME, Kaptue-Noche L, Nagel RL (Oct
[8] Pearson HA (Aug 1977). “Sickle cell anemia and 1993). “Senegal haplotype is associated with higher HbF
severe infections due to encapsulated bacteria” (Free than Benin and Cameroon haplotypes in African children
full text). J Infect Dis. 136 Suppl: S25–30. with sickle cell anemia”. Am. J. Hematol. 44 (2): 145–6.
doi:10.1093/infdis/136.Supplement.S25. ISSN 0022- doi:10.1002/ajh.2830440214. ISSN 0361-8609. PMID
1899. PMID 330779. 7505527.
10 11 REFERENCES
[21] Allison AC (October 2009). “Genetic control of resis- Bridges K, Waclawiw M, Bonds D, Terrin M (April
tance to human malaria”. Current Opinion in Immunology 2003). “Effect of hydroxyurea on mortality and mor-
21 (5): 499–505. doi:10.1016/j.coi.2009.04.001. PMID bidity in adult sickle cell anemia: risks and benefits up
19442502. to 9 years of treatment”. JAMA 289 (13): 1645–51.
doi:10.1001/jama.289.13.1645. PMID 12672732.
[22] Kwiatkowski DP (Aug 2005). “How Malaria Has Af-
fected the Human Genome and What Human Genetics [34] Platt OS (Mar 2008). “Hydroxyurea for the treatment of
Can Teach Us about Malaria”. Am. J. Hum. Genet. sickle cell anemia”. N. Engl. J. Med. 358 (13): 1362–9.
77 (2): 171–92. doi:10.1086/432519. ISSN 0002-9297. doi:10.1056/NEJMct0708272. PMID 18367739.
PMC 1224522. PMID 16001361.
[35] Drasar E, Igbineweka N, Vasavda N, Free M, Awog-
[23] Ponçon N, Toty C, L'Ambert G, Le Goff G, Brengues
bade M, Allman M, Mijovic A, Thein SL (March 2011).
C, Schaffner F, Fontenille D (2007). “Biology and dy-
“Blood transfusion usage among adults with sickle cell
namics of potential malaria vectors in Southern France”.
disease - a single institution experience over ten years”.
Malar. J. 6 (1): 18. doi:10.1186/1475-2875-6-18. PMC
Br. J. Haematol. 152 (6): 766–70. doi:10.1111/j.1365-
1808464. PMID 17313664.
2141.2010.08451.x. PMID 21275951.
[24] Lesi FE, Bassey EE (July 1972). “Family study in sickle
cell disease in Nigeria”. J Biosoc Sci 4 (3): 307–13. [36] Gyang E, Yeom K, Hoppe C, Partap S, Jeng M (Jan-
doi:10.1017/S0021932000008622. PMID 5041262. uary 2011). “Effect of chronic red cell transfusion ther-
apy on vasculopathies and silent infarcts in patients with
[25] “How Does Sickle Cell Cause Disease?". Retrieved 2010- sickle cell disease”. Am. J. Hematol. 86 (1): 104–6.
11-27. doi:10.1002/ajh.21901. PMID 21117059.
[26] “Sickle Cell Anemia: eMedicine Emergency Medicine”. [37] Mirre E, Brousse V, Berteloot L, Lambot-Juhan K, Verl-
Retrieved 2010-11-27. hac S, Boulat C, Dumont MD, Lenoir G, de Mon-
talembert M (March 2010). “Feasibility and efficacy
[27] Clarke GM, Higgins TN (August 2000). “Laboratory in-
of chronic transfusion for stroke prevention in children
vestigation of hemoglobinopathies and thalassemias: re-
with sickle cell disease”. Eur. J. Haematol. 84 (3):
view and update”. Clin. Chem. 46 (8 Pt 2): 1284–90.
259–65. doi:10.1111/j.1600-0609.2009.01379.x. PMID
PMID 10926923.
19912310.
[28] “BestBets: Does routine urinalysis and chest radiography
detect occult bacterial infection in sickle cell patients pre- [38] Walters MC, Patience M, Leisenring W, Eckman JR,
senting to the accident and emergency department with Scott JP, Mentzer WC, Davies SC, Ohene-Frempong K,
painful crisis?". Retrieved 2010-11-27. Bernaudin F, Matthews DC, Storb R, Sullivan KM (Au-
gust 1996). “Bone marrow transplantation for sickle
[29] Lee, C., Davies, S.,& Dezatoux, C. (2000). Neonatal cell disease”. N. Engl. J. Med. 335 (6): 369–76.
Screening for sickle cell disease. The Cochrane Collab- doi:10.1056/NEJM199608083350601. PMID 8663884.
oration. John Wiley & Sons, Ltd.
[39] Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson; Aster,
[30] Oniyangi O, Omari AA (2006). Oniyangi, Oluseyi, Jon (2009-05-28). Robbins and Cotran Pathologic Basis
ed. “Malaria chemoprophylaxis in sickle cell dis- of Disease, Professional Edition: Expert Consult - Online
ease”. Cochrane Database of Systematic Reviews 13 (4): (Robbins Pathology) (Kindle Locations 33530-33531).
CD003489. doi:10.1002/14651858.CD003489.pub2. Elsevier Health. Kindle Edition.
PMID 17054173.
[40] Wierenga KJ, Hambleton IR, Lewis NA (2001). “Survival
[31] Aldrich TK, Nagel RL. (1998). “Pulmonary Complica-
estimates for patients with homozygous sickle-cell disease
tions of Sickle Cell Disease.”. In Reynolds HY, Bone RC,
in Jamaica: A clinic-based population study”. Lancet 357
Dantzker DR, George RB, Matthay RA. Pulmonary and
(9257): 680–683. doi:10.1016/s0140-6736(00)04132-5.
Critical Care Medicine (6th ed.). St. Louis: Mosby. pp.
PMID 11247552.
1–10. ISBN 0-8151-1371-4.
[32] Charache S, Terrin ML, Moore RD, Dover GJ, Bar- [41] Kavanagh PL, Sprinz PG, Vinci SR, Bauchner H, Wang
ton FB, Eckert SV, McMahon RP, Bonds DR (May CJ (2011). “Management of children with sickle cell dis-
1995). “Effect of hydroxyurea on the frequency of ease: a comprehensive review of the literature”. Pediatrics
painful crises in sickle cell anemia. Investigators of 128 (6): e1552–74. doi:10.1542/peds.2010-3686. PMID
the Multicenter Study of Hydroxyurea in Sickle Cell 22123880.
Anemia”. N. Engl. J. Med. 332 (20): 1317–
22. doi:10.1056/NEJM199505183322001. ISSN 0028- [42] Adams RJ, Ohene-Frempong K, Wang W (2001). “Sickle
4793. PMID 7715639. cell and the brain”. Hematology Am Soc Hematol Educ
Program 2001 (1): 31–46. doi:10.1182/asheducation-
[33] Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas 2001.1.31. PMID 11722977.
SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eck-
man J, Varma M, Ramirez G, Adler B, Smith W, Car- [43] Adams RJ (November 2007). “Big strokes in small
los T, Ataga K, DeCastro L, Bigelow C, Sauntharara- persons”. Arch. Neurol. 64 (11): 1567–74.
jah Y, Telfer M, Vichinsky E, Claster S, Shurin S, doi:10.1001/archneur.64.11.1567. PMID 17998439.
11
[44] Martí-Carvajal, A; Dunlop, R; Agreda-Perez, L (18 Oc- to communities”. J. Clin. Invest. 119 (9): 2496–
tober 2004). “Treatment for avascular necrosis of bone in 505. doi:10.1172/JCI38307. PMC 2735907. PMID
people with sickle cell disease.”. The Cochrane database 19729847.
of systematic reviews (4): CD004344. PMID 15495103.
[56] WHO. “Sickle-cell anaemia - Report by the Secretariat”
[45] Kenny MW, George AJ, Stuart J (July 1980). “Platelet (PDF). Retrieved 2010-11-27.
hyperactivity in sickle-cell disease: a consequence of hy-
posplenism”. Journal of Clinical Pathology 33 (7): 622– [57] Aidoo M, Terlouw DJ, Kolczak MS, McElroy PD, ter
5. doi:10.1136/jcp.33.7.622. PMC 1146172. PMID Kuile FO, Kariuki S, Nahlen BL, Lal AA, Udhayaku-
7430367. Retrieved 2011-03-23. mar V (2002). “Protective effects of the sickle cell gene
against malaria morbidity and mortality”. Lancet 359
[46] Chrouser KL, Ajiboye OB, Oyetunji TA, Chang (9314): 1311–2. doi:10.1016/S0140-6736(02)08273-9.
DC (April 2011). “Priapism in the United PMID 11965279.
States: the changing role of sickle cell disease”.
American Journal of Surgery 201 (4): 468–74. [58] National Heart, Lung and Blood Institute. “Sickle cell
doi:10.1016/j.amjsurg.2010.03.017. PMID 21421100. anemia, key points”. Retrieved 2010-11-27.
[53] Weatherall DJ, Clegg JB (2001). “Inherited haemoglobin [67] Le dépistage néonatal de la drépanocytose en France.
disorders: an increasing global health problem”. Bull. Numéro thématique. La drépanocytose en France : des
World Health Organ. 79 (8): 704–12. PMC 2566499. données épidémiologiques pour améliorer la prise en
PMID 11545326. charge, Bardakdjian-Michau J, INVS, July 2012
[55] Wellems TE, Hayton K, Fairhurst RM (September 2009). [71] “Give Blood - Resources - Sickle Cell and Blood Dona-
“The impact of malaria parasitism: from corpuscles tion”. Give Blood.
12 12 FURTHER READING
[72] “Why is Blood from Afro-Caribbean Donors Special?". [86] Pauling L, Itano HA (1949). “Sickle cell anemia, a
sicklecellsociety.org. molecular disease”. Science 110 (2865): 543–548.
doi:10.1126/science.110.2865.543. PMID 15395398.
[73] Jastaniah W (2011). “Epidemiology of sickle cell dis-
ease in Saudi Arabia”. Annals of Saudi Medicine 31 (3): [87] “Foster, Gloria”. Facts On File History Database. Re-
289–93. doi:10.4103/0256-4947.81540. PMC 3119971. trieved 2015-02-25.
PMID 21623060.
[88] http://www.nejm.org/doi/full/10.1056/
[74] Memish ZA, Saeedi MY (2011). “Six-year outcome of NEJM199608083350601#t=article
the national premarital screening and genetic counsel-
ing program for sickle cell disease and β-thalassemia in [89] http://www.ajc.com/news/news/local-obituaries/
Saudi Arabia”. Annals of Saudi Medicine 31 (3): 229–35. keone-penn-27-medical-trailblazer-wanted-to-be-a-c/
doi:10.4103/0256-4947.81527. PMC 3119961. PMID nYXxF/
21623050.
[90] “About SB 148”. Savingthecure.org. Retrieved 11 June
[75] Awasthy N, Aggarwal KC, Goyal PC, Prasad MS, Saluja 2015.
S, Sharma M (2008). “Sickle cell disease: Experience
of a tertiary care center in a nonendemic area”. An- [91] http://www.journalnow.com/archives/
nals of Tropical Medicine and Public Health 1 (1): 1–4. breakthrough-baltimore-woman-becomes-one-of-the-first-adults-to/
doi:10.4103/1755-6783.43069. article_ba1d879b-4727-5cc1-a156-1a52403b4100.html
[76] http://nepalitimes.com/article/nation/Life-% [92] Pawliuk R, Westerman KA, Fabry ME, Payen E, Tighe R,
20with-sickle-cell,1460 Bouhassira EE, Acharya SA, Ellis J, London IM, Eaves
CJ, Humphries RK, Beuzard Y, Nagel RL, Leboulch P
[77] Asnani MR, McCaw-Binns AM, Reid ME (2011). (2001). “Correction of Sickle Cell Disease in Trans-
“Excess Risk of Maternal Death from Sickle Cell Dis- genic Mouse Models by Gene Therapy”. Science 294
ease in Jamaica: 1998–2007”. PLoS ONE 6 (10): (5550): 2368–71. doi:10.1126/science.1065806. PMID
e26281. doi:10.1371/journal.pone.0026281. PMC 11743206.
3200316. PMID 22039456.
[93] Wilson, Jennifer Fisher (18 March 2002). “Murine Gene
[78] Lebby R (1846). “Case of absence of the spleen”. South- Therapy Corrects Symptoms of Sickle Cell Disease”. The
ern J of Med Pharmacol 1: 481–3. Scientist – Magazine of the Life Sciences. Retrieved 17 De-
cember 2014.
[79] Ballas SK, Gupta K, Adams-Graves P (Nov 1, 2012).
“Sickle cell pain: a critical reappraisal.”. Blood 120 (18): [94] St. Jude Children’s Research Hospital (4 December
3647–56. doi:10.1182/blood-2012-04-383430. PMID 2008). “Gene Therapy Corrects Sickle Cell Disease In
22923496. Laboratory Study”. ScienceDaily. Retrieved 17 Decem-
ber 2014.
[80] Herrick JB (1910). “Peculiar elongated and sickle-
shaped red blood corpuscles in a case of severe ane- [95] (15 December 2014) Stem Cell Gene Therapy for
mia”. Arch. Intern. Med. 6 (5): 517–521. Sickle Cell Disease, ClinicalTrials.gov Identifier:
doi:10.1001/archinte.1910.00050330050003.; reprinted NCT02247843 ClinicalTrials.gov, U.S. National
as Herrick JB (2001). “Peculiar elongated and sickle- Institutes of Health, Retrieved 17 December 2014
shaped red blood corpuscles in a case of severe anemia.
1910”. The Yale journal of biology and medicine 74 (3): [96] (15 December 2014) Collection and Storage of Umbili-
179–84. PMC 2588723. PMID 11501714. cal Cord Stem Cells for Treatment of Sickle Cell Disease;
ClinicalTrials.gov Identifier: NCT00012545 ClinicalTri-
[81] Savitt TL, Goldberg MF (Jan 1989). “Herrick’s 1910 case als.gov, U.S. National Institutes of Health, Retrieved 17
report of sickle cell anemia. The rest of the story”. JAMA December 2014
261 (2): 266–71. doi:10.1001/jama.261.2.266. PMID
2642320. [97] Olowoyeye, A; Okwundu, CI (10 October 2014). “Gene
therapy for sickle cell disease.”. The Cochrane database
[82] Serjeant GR (Dec 2010). “One hundred years of sickle of systematic reviews 10: CD007652. PMID 25300171.
cell disease.”. British journal of haematology 151 (5):
425–9. doi:10.1111/j.1365-2141.2010.08419.x. PMID
20955412.
12 Further reading
[83] Washburn, R.E. (1911). “Peculiar elongated and sickle-
shaped red blood corpuscles in a case of severe anemia”. • Brown, Robert T., ed. (2006). Comprehensive
The Virginia Medical Semi-Monthly 15 (21): 490–493. handbook of childhood cancer and sickle cell dis-
[84] “UVa Hospital Celebrating 100 Years”. University of Vir- ease: a biopsychosocial approach. Oxford Univer-
ginia. Retrieved 28 January 2015. sity Press. ISBN 978-0-19-516985-0.
[85] Mason VR (1922). “Sickle cell anemia”. JAMA 79 (14): • Hill, Shirley A. (2003). Managing Sickle Cell Dis-
1318–1320. doi:10.1001/jama.254.14.1955. PMID ease in Low-Income Families. Temple University
3900438. Press. ISBN 978-1-59213-195-2.
13
13 External links
• Sickle cell at DMOZ
• Sickle Cell Anaemia OER Project
14 14 TEXT AND IMAGE SOURCES, CONTRIBUTORS, AND LICENSES
Lizaweb, VictorianMutant, Forever Dusk, ResidentAnthropologist, YuriSuassuna, ClueBot NG, Jack Greenmaven, Shopiapiapia, Gilde-
rien, Satellizer, A520, Hunt'in brooks, KlingonDoctor, Kingmash, Pengortm, PwNeR3222, Braincricket, Mesoderm, O.Koslowski, Widr,
Danim, Mackattack1991, Mattemerson, Pratikmasti, Helpful Pixie Bot, Pamela jarmon, Fail32, Joe2003k, Kishor kumar bhumi, BZTMPS,
Lowercase sigmabot, BG19bot, Bmusician, Roberticus, Cocokur, Iselilja, Lowercase Sigma, MusikAnimal, Dan653, Mark Arsten, Jjco-
bos, MrBill3, Benjaminreid1, HolyBaloney, Backdbones, Jpt1908, Insidiae, Glacialfox, Omgitsrhys, Klilidiplomus, Achowat, BattyBot,
Jimw338, Jrodriguez2315, YFdyh-bot, Ulupoi, Roastfalcon3, 4neesan, TylerDurden8823, 09hailj, JYBot, Dexbot, Sicklecellanaemia, We-
bclient101, Bubbarachael, Mogism, Lugia2453, Frosty, Uwais98, Sbalfour, Vanamonde93, Fuqmuffins, Ahlalala 666, Tentinator, Ox-
alus, ElHef, DavidLeighEllis, Jsp4a, CensoredScribe, Babitaarora, Adedot, Garrettu12, Ginsuloft, CoolGuy202Cool, Atticus29, Pgcud-
ahy, AddWittyNameHere, SJ Defender, Anrnusna, Drsoumyadeepb, AMON2000, Magoo005, Nicktownsend12, Monkbot, ShawntheGod,
ADEL67, Vipster, EGARCIA123, NicolasCruz, Fniroanusi, Bluewhale22, BethNaught, SILVER KNIGHT CYRIL, Francesca McKenna,
Swagmaster420666, Amandal7815, Jan airon securata, Aaryaspatil786, DrKIyer, Haynes.239, Wulf.174, AlicjaMarie, Hukevin, PNMSC,
Tud50316, BU Rob13, Anish kingkhan, Stuartsugden and Anonymous: 1653
14.2 Images
• File:1911_Sickle_Cells.jpg Source: https://upload.wikimedia.org/wikipedia/commons/4/4b/1911_Sickle_Cells.jpg License: CC BY 3.0
Contributors: Anatomy & Physiology, Connexions Web site. http://cnx.org/content/col11496/1.6/, Jun 19, 2013. Original artist: OpenStax
College
• File:Autorecessive.svg Source: https://upload.wikimedia.org/wikipedia/commons/3/3e/Autorecessive.svg License: CC-BY-SA-3.0 Con-
tributors: Own work in Inkscape Original artist: en:User:Cburnett
• File:Commons-logo.svg Source: https://upload.wikimedia.org/wikipedia/en/4/4a/Commons-logo.svg License: ? Contributors: ? Original
artist: ?
• File:Malaria_distribution.jpg Source: https://upload.wikimedia.org/wikipedia/commons/6/65/Malaria_distribution.jpg License: CC-
BY-SA-3.0 Contributors: Transferred from en.wikipedia to Commons. Original artist: Muntuwandi at English Wikipedia
• File:Paludisme_-_Frequence_statistique.png Source: https://upload.wikimedia.org/wikipedia/commons/0/08/Paludisme_-_
Frequence_statistique.png License: CC-BY-SA-3.0 Contributors: CHU de Rouen - Frequence du paludisme Original artist: Percherie
• File:Sickle_cell_distribution.jpg Source: https://upload.wikimedia.org/wikipedia/commons/2/24/Sickle_cell_distribution.jpg License:
CC-BY-SA-3.0 Contributors: Transferred from en.wikipedia to Commons. Original artist: Muntuwandi at English Wikipedia
• File:Sickle_cells.jpg Source: https://upload.wikimedia.org/wikipedia/commons/a/a1/Sickle_cells.jpg License: CC BY-SA 3.0 Contribu-
tors: Own work Original artist: Dr Graham Beards
• File:Sicklecells.jpg Source: https://upload.wikimedia.org/wikipedia/commons/9/92/Sicklecells.jpg License: Public domain Contributors:
(US government agency) site at http://www.cc.nih.gov/ccc/ccnews/nov99/ . The photo is attributed to Drs. Noguchi, Rodgers, and
Schechter of NIDDK. Original artist: NIDDK