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Sickel Cell Desorder
Sickel Cell Desorder
603903
OMIM
DiseasesDB 12069
MedlinePlus 000527
med/2126 oph/490
ped/2096 emerg/26
eMedicine
emerg/406
C15.378.071.141.150.150
MeSH
GeneReviews Sickle-cell disease
Sickle-cell disease (SCD), or sickle-cell anemia (or anemia,
SCA) or drepanocytosis, is an autosomal recessive genetic
blood disorder with overdominance, characterized by red blood
cells that assume an abnormal, rigid, sickle shape. Sickling
decreases the cells' flexibility and results in a risk of various
complications. The sickling occurs because of a mutation in the
hemoglobin gene. Life expectancy is shortened. In 1994, in the
US, the average life expectancy of persons with this condition
was estimated to be 42 years in males and 48 years in females,[1]
but today, thanks to better management of the disease, patients
can live into their 50s or beyond.[2] In the UK, the current life
expectancy is estimated to be 5360 years of age.[3]
Sickle-cell disease occurs more commonly in people (or their
descendants) from parts of tropical and sub-tropical regions
where malaria is or was common. In areas where malaria is
common, there is a fitness benefit in carrying only a single
sickle-cell gene (sickle cell trait). Those with only one of the
two alleles of the sickle-cell disease, while not totally resistant,
are more tolerant to the infection and thus show less severe
symptoms when infected.[4]
2 Pathophysiology
3 Genetics
o 3.1 Inheritance
4 Diagnosis
5 Management
o 5.1 Folic acid and penicillin
o 5.2 Malaria chemoprophylaxis
o 5.3 Vaso-occlusive crisis
o 5.4 Acute chest crisis
o 5.5 Hydroxyurea
o 5.6 Transfusion therapy
o 5.7 Bone marrow transplants
6 Epidemiology
o 6.1 Africa
o 6.2 United States
o 6.3 France
o 6.4 United Kingdom
o 6.5 Middle East
o 6.6 India
7 History
8 See also
9 References
10 Further reading
11 External links
Sickle cells in human blood: both normal red blood cells and
sickle-shaped cells are present
Sickle-cell disease may lead to various acute and chronic
complications, several of which have a high mortality rate.[5]
[edit] Sickle cell crisis
The term "sickle cell crisis" is used to describe several
independent acute conditions occurring in patients with sickle
cell disease. Sickle cell disease results in anemia and crisis 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.[6]
[edit] Vaso-occlusive crisis
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
transient, they continue for 34 hours and may last for one
day.[11]
[edit] Aplastic crisis
Aplastic crises are acute worsenings of the patient's baseline
anaemia, producing pallor, tachycardia, and fatigue. This crisis
is triggered by parvovirus B19, which directly affects
erythropoiesis (production of red blood cells) by invading the
red cell precursors and multiplying in them and destroying them.
Parvovirus infection nearly 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 sickle-cell
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.[12]
[edit] Haemolytic crisis
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 co-existent G6PD
deficiency.[13] Management is supportive, sometimes with blood
transfusions.[7]
[edit] Other
One of the earliest clinical manifestations is dactylitis,
presenting as early as six months of age, and may occur in
children with sickle trait.[14] The crisis can last up to a month.[15]
[edit] Heterozygotes
The heterozygous form (sickle cell trait) is almost always
asymptomatic, and the only usual significant manifestation is the
renal concentrating defect presenting with isosthenuria.
[edit] Pathophysiology
blood cells typically live 90120 days, but sickle cells only
survive 1020 days.[30]
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 A makes up around 96-97% of the normal
haemoglobin in humans.
[edit] Genetics
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 springs from the fact that some of them are
associated with higher HbF levels, e.g., Senegal and SaudiAsian variants, and tend to have milder disease.[31]
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. Under normal circumstances, these painful
crises occur about 0.8 times per year per patient.[citation needed] The
sickle-cell disease occurs when the seventh amino acid (if the