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Sickle-cell disease
From Wikipedia, the free encyclopedia

This article is about the disease itself.
For the genetic transmission of
sickle-cell disease and its carrier state,
see sickle cell trait.
Sickle-cell disease
Classification and external resources

Normal and sickle-shaped red blood cells
ICD-10 D57.
ICD-9 282.6
OMIM 603903
DiseasesDB 12069
MedlinePlus 000527
eMedicine med/2126 oph/490 ped/2096
emerg/26 emerg/406
MeSH C15.378.071.141.150.150

Sickle-cell disease or sickle-cell anaemia (or anemia) is a life-
long blood disorder 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, with studies
reporting an average life expectancy of 42
and 48 years for males and females, respectively.[1]

Sickle-cell disease, usually presenting in childhood, occurs
more commonly in people (or their descendants) from parts
of tropical and sub-tropical regions where malaria is or was
common. One-third of all aboriginal
inhabitants of Sub-Saharan Africa
carry the gene[2] because in areas
where malaria is common, there is
a survival value in carrying only
a single sickle-cell gene (sickle
cell trait).[3] Those with only one
of the two alleles of the sickle-cell
disease are more resistant to malaria,
since the infestation of the malaria plasmodium is halted by
the sickling of the cells which it infests.

The prevalence of the disease in the United States is
approximately 1 in 5,000, mostly affecting African Americans
according to National Institute of Health. But people of
other ethnic or racial heritage may also inherit the disease,
or be infected with the disease through other means.

Contents:
1 Classification
2 Signs and symptoms
2.1 Vaso-occlusive crisis
2.2 Other sickle-cell crises
2.3 Complications
2.4 Heterozygotes
3 Diagnosis
4 Pathophysiology
5 Genetics
5.1 Inheritance
6 Treatment
6.1 Cyanate
6.2 Painful (vaso-occlusive) crisis
6.3 Folic acid and penicillin
6.4 Acute chest crises
6.5 Hydroxyurea
6.6 Bone marrow transplants
6.7 Future treatments
7 Situation of carriers
8 History
9 References
10 External links

Classification:

Sickle-cell anaemia is the name of a specific form of sickle-
cell disease in which there is homozygosity for the mutation
that causes HbS. Sickle-cell anaemia is also referred to as
"HbSS," "SS disease," "haemoglobin
S," or permutations thereof. In heterozygous
people, only 1 sickle gene and one
normal adult hemoglobin gene, it is
referred to as "HbAS" or sickle cell
trait. Other, rarer forms of sickle-cell
disease include sickle-haemoglobin C
disease (HbSC), sickle
beta-plus-thalassaemia (HbS/β+) and
sickle beta-zero-thalassaemia (HbS/β0).
These other forms of sickle-cell disease
are compound heterozygous states in which the person has
only one copy of the mutation that causes HbS and one
copy of another abnormal haemoglobin allele.

The term "disease" is applied since the inherited abnormality
causes a pathological condition that can lead to death and
severe complications. Not all inherited variants of
haemoglobin are detrimental, a concept known as genetic
polymorphism.

Sickle cell anemia usually occurs in black children but
sometimes occurs in hispanic children. About one in five
hundred black children have it and about one in 36,000
hispanic children have sickle cell anemia.[4]

Signs and symptoms:

Sickle-cell disease may lead to various acute and chronic
complications, several of which are potentially lethal.

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 ischemia, pain, and often organ
damage. The frequency, severity, and duration of these
crises vary considerably. Painful crises are treated with
hydration and 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
sometimes effective for the itching associated with the
opioid use. Incentive spirometry, a technique to encourage
deep breathing to minimise the development of atelectasis,
is recommended.

Because of its narrow vessels and function in clearing
defective red blood cells, the spleen is frequently affected. It
is usually infarcted before the end of childhood in
individuals suffering from sickle-cell anaemia. This
autosplenectomy increases the risk of infection from
encapsulated organisms;[5][6] preventive antibiotics and
vaccinations are recommended for those with such asplenia.

One of the earliest clinical manifestations is dactylitis,
presenting as early as 6 months of age, and may occur in
children with sickle trait.[7] The crisis can last up to a month.
[8] Another recognised type of sickle crisis is the acute
chest syndrome, a condition 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.[citation needed] It can be triggered by
painful crisis, respiratory infection, bone-marrow
embolisation, or possibly by atelectasis, opiate
administration, or surgery.

Most episodes of sickle cell crises last between 5 and 7 days.
[9]

Other sickle-cell crises:

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).
Parvovirus infection nearly completely prevents red blood
cell production for 2-3 days. In normal individuals, this is of
little consequence, but the shortened red cell life of sickle-
cell patients results in an abrupt, life-threatening situation.
Reticulocyte counts drop dramatically during the disease
and the rapid turnover of red cells leads to the drop in
haemoglobin. Most patients can be managed supportively;
some need blood transfusion.

Splenic sequestration crises are acute, painful enlargements
of the spleen. The abdomen becomes bloated and very hard.
Management is supportive, sometimes with blood
transfusion.

Hemolytic crises are acute accelerated drop in hemoglobin
level. The red blood cells break down at a faster rate. This is
particularly common in patients with co-existent G6PD
deficiency. Management is supportive, sometimes with blood
transfusions.

Complications:

Sickle-cell anaemia can lead to various complications,
including:

Overwhelming post-(auto)splenectomy infection (OPSI),
which is due to functional asplenia, caused by encapsulated
organisms such as Streptococcus pneumoniae and
Haemophilus influenzae. Daily penicillin prophylaxis is the
most commonly-used treatment during childhood, with some
haematologists continuing treatment indefinitely. Patients
benefit today from routine vaccination for H. influenzae, S.
pneumoniae, and Neisseria meningitidis.

Stroke, which can result from a progressive vascular
narrowing of blood vessels, preventing oxygen from
reaching the brain. Cerebral infarction occurs in children,
and cerebral hemorrhage in adults.

Cholelithiasis (gallstones) and cholecystitis, which may
result from excessive bilirubin production and precipitation
due to prolonged haemolysis.

Avascular necrosis (aseptic bone necrosis) of the hip and
other major joints, which may occur as a result of ischemia.
Decreased immune reactions due to hyposplenism
(malfunctioning of the spleen).

Priapism and infarction of the penis.

Osteomyelitis (bacterial bone infection), which is most
frequently caused by Salmonella in individuals with sickle-
cell disease, whereas Staphylococcus is the most common
causative organism in the general population.

Opioid tolerance, which can occur as a normal, physiologic
response to the therapeutic use of opiates. Addiction to
opiates occurs no more commonly among individuals with
sickle-cell disease than among other individuals treated with
opiates for other reasons.

Acute papillary necrosis in the kidneys.

Leg ulcers.

In eyes, background retinopathy, proliferative retinopathy,
vitreous haemorrhages and retinal detachments, resulting in
blindness. Regular annual eye checks are recommended.
During pregnancy, intrauterine growth retardation,
spontaneous abortion, and pre-eclampsia.

Chronic pain: Even in the absence of acute vaso-occlusive
pain, many patients have chronic pain that is not reported
[10]

Pulmonary hypertension (increased pressure on the
pulmonary artery), leading to strain on the right ventricle
and a risk of heart failure; typical symptoms are shortness
of breath, decreased exercise tolerance and episodes of
syncope[11]

Chronic renal failure - this develops in 4.2% and manifests
itself with hypertension (high blood pressure), proteinuria
(protein loss in the urine) and worsened anaemia. If it
progresses to end-stage renal failure, it carries a poor
prognosis.[12]

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.

Diagnosis:

In HbSS, the full 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 sickle 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
speed. 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 (HPLC). Genetic
testing is rarely performed, as other investigations are
highly specific for HbS and HbC.[13]

An acute sickle cell crisis is often precipitated by infection.
Therefore a urinalysis to detect an occult UTI and CXR to
look for occult pneumonia should be routinely performed.[14]

Pathophysiology:

Sickle-cell anaemia is caused by a point mutation in the β-
globin chain of haemoglobin, causing the amino acid
glutamic acid to be replaced with the hydrophobic amino
acid valine at the sixth position. The β-globin gene is found
on the short arm of chromosome 11. The association of two
wild-type α-globin subunits with two mutant β-globin
subunits forms haemoglobin S (HbS). Under low-oxygen
conditions, the absence of a polar amino acid at position six
of the β-globin chain promotes the non-covalent
polymerisation (aggregation) of haemoglobin, which distorts
red blood cells into a sickle shape and decreases their
elasticity.

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 anemia of the illness is caused by hemolysis, the
destruction of the red cells inside the spleen, because of
their misshape. Although the bone marrow attempts to
compensate by creating new red cells, it does not match the
rate of destruction.[15] Healthy red blood cells typically live
90-120 days, but sickle cells only survive 10-20 days.[16]

Genetics:

A single amino acid change causes haemoglobin proteins to
form fibers.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 Saudi-Asian variants, and tend to have milder
disease.[17]

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 donut-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 0.8 times per year per patient.
[citation needed] The sickle-cell disease occurs when the
seventh amino acid (if we count the initial methionine),
glutamic acid, is replaced by valine to change its structure
and function.

Distribution of the sickle-cell trait shown in pink and purple
Historical distribution of malaria (no longer endemic in
Europe).

Modern distribution of malariaThe 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 glutamate to be substituted by valine at position 6.
Haemoglobin 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 haemoglobin. 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 residues of
the valine at position 6 of the beta chain in haemoglobin are
able to associate with the hydrophobic patch, causing
haemoglobin S molecules to aggregate and form fibrous
precipitates.

The allele responsible for sickle-cell anaemia is autosomal
recessive and can be found on the short arm of
chromosome 11. A person that receives the defective gene
from both father and mother develops the disease; a person
that 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's developing the disease and a
1-in-2 chance of their child's being just a carrier. Since the
gene is incompletely recessive, carriers can produce a few
sickled red blood cells, 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.

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.[18] Malaria was
historically endemic to southern Europe, but it was declared
eradicated in the mid 20th century with the exception of rare
sporadic cases.[19][20]

The Price equation is a simplified mathematical model of the
genetic evolution of sickle-cell anaemia.

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 cells with defective
haemoglobin to rupture prematurely, making the
plasmodium unable to reproduce. Further, the
polymerization of Hb affects the ability of the parasite to
digest Hb in the first place. Therefore, in areas where
malaria is a problem, people's chances of survival actually
increase if they carry sickle-cell trait (selection for the
heterozygote).

In the USA, where there is no endemic malaria, the
prevalence of sickle-cell anaemia among blacks is lower
(about 0.25%) than in West Africa (about 4.0%), and is
falling. Without endemic malaria from Africa, the condition is
purely disadvantageous, and will tend to be bred out of the
affected population. Another factor limiting the spread of
sickle-cell genes in North America is the absence of cultural
proclivities to polygamy. [21]

Sickle-cell disease is inherited in the autosomal recessive
pattern.

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 haemoglobin a person makes in the red blood
cells depend upon what haemoglobin genes are inherited
from his parents.

If one parent has sickle-cell anaemia (SS) and the other has
sickle-cell trait (AS), there is a 50% chance (or 1 out of 2) of
a child's having sickle-cell disease (SS) and a 50% chance of
a child's having sickle-cell trait (AS).

When both parents have sickle-cell trait (AS), they have a
25% chance (1 of 4) of a child's having sickle-cell disease
(SS).

Sickle-cell anemia appears to be caused by a recessive
allele. Two carrier parents have a one in four chance of
having a child with the disease. The child will be
homozygous-recessive.

It has been argued[22] that the allele, although appearing
outwardly recessive, is in fact co-dominant, due to the
resistance to a malaria that is obtained by those of the AS
genotype. Since a separate phenotype from that of Normal
(AA) has therefore been expressed, it is impossible to argue
that the S allele is homozygous-recessive.

Treatment:

Cyanate:

Dietary cyanate, from foods containing cyanide derivatives,
has been used as a treatment for sickle cell anemia.[23] In
the laboratory, cyanate and thiocyanate irreversibly inhibit
sickling of red blood cells drawn from sickle cell anemia
patients.[24] However the cyanate would have to be
administered to the patient for a life time as each new red
blood cell created must be prevented from sickling at the
time of creation. Cyanate also would be expelled via the urea
of a patient every cycle of treatment.

Painful (vaso-occlusive) crisis:

Most people with sickle-cell disease have intensely painful
episodes called vaso-occlusive crises. The frequency,
severity, and duration of these crises, however, vary
tremendously. Painful crises are treated symptomatically
with 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 also an
effective agent that is frequently prescribed by doctors in
order to help control any itching associated with the use of
opioids.

Folic acid and penicillin:

Children born with sickle-cell disease will undergo close
observation by the pediatrician and will require management
by a hematologist to assure they remain healthy. These
patients will take a 1-mg dose of folic acid daily for life. From
the age of birth to 5 years of age, they will also have to take
penicillin daily, due to the immature immune system that
makes them more prone to early childhood illnesses.

Acute chest crises:

Management is similar to vaso-occlusive crises with the
addition of antibiotics (usually a quinolone or macrolide,
since wall-deficient ["atypical"] bacteria are thought to
contribute to the syndrome),[25] 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 haemoglobin S in the patient's
blood.

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)[26] and shown to possibly increase survival time in a
study in 2003 (Steinberg et al).[27] 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.[28]

Bone marrow transplants:

Bone marrow transplants have proven to be effective in
children.[29]

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 hemoglobin switching are
being investigated, including the use of phytochemicals
such as nicosan. Gene therapy is under investigation.

Another treatment being investigated is Senicapoc.

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 fetus or a sample of amniotic fluid. Since taking a
blood sample from a fetus has greater risks, the latter test is
usually used.

After the mutation responsible for this disease was
discovered in 1979, the U.S. Air Force required Black
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.[30]

History:

This collection of clinical findings was unknown until the
explanation of the sickle cells in 1904 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
Chicago Presbyterian Hospital in December 1904 suffering
from anaemia. Noel was readmitted several times over the
next three years for "muscular rheumatism" and "bilious
attacks." Noel 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.[31]

The disease was named "sickle-cell anaemia" by Vernon
Mason in 1922. However, 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 1870s, where
it was known locally as ogbanjes ("children who come and
go") because of the very high infant mortality rate caused by
this condition. A history of the condition tracked reports
back to 1670 in one Ghanaian family.[32] Also, the practice
of using tar soap to cover blemishes caused by sickle-cell
sores was prevalent in the Black community.[citation needed]

Linus Pauling and colleagues were the first, in 1949, to
demonstrate that sickle-cell disease occurs as a result of an
abnormality in the haemoglobin molecule. This was the first
time a genetic disease was linked to a mutation of a specific
protein, a milestone in the history of molecular biology, and
it was published in their paper "Sickle Cell Anemia, a
Molecular Disease".

The origin of the mutation that led to the sickle-cell gene
was initially thought to be in the Arabian peninsula,
spreading to Asia and Africa. It is now known, from
evaluation of chromosome structures, that there have been
at least four independent mutational events, three in Africa
and a fourth in either Saudi Arabia or central India. These
independent events occurred between 3,000 and 6,000
generations ago, approximately 70-150,000 years.[33]

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^ Walters MC, Patience M, Leisenring W, et al (August 1996).
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Engl. J. Med. 335 (6): 369–76. PMID 8663884. http://content.
nejm.org/cgi/pmidlookup?
view=short&pmid=8663884&promo=ONFLNS19.
^ Anonymous (4 January 1981). "Air force academy sued
over sickle cell policy". New York Times. http://query.
nytimes.com/gst/fullpage.html?
sec=health&res=9807EFD7163BF937A35752C0A967948260.
Retrieved on 21 December 2008.
^ Savitt TL, Goldberg MF (1989). "Herrick's 1910 case report
of sickle cell anemia. The rest of the story". JAMA 261 (2):
266–71. doi:10.1001/jama.261.2.266. 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 Desai, D. V.; Hiren Dhanani (2004). "Sickle Cell
Disease: History And Origin". The Internet Journal of
Haematology 1 (2). ISSN 1540-2649. http://www.ispub.
com/ostia/index.php?xmlFilePath=journals/ijhe/vol1n2/sickle.
xml.
^ Desai, D. V.; Hiren Dhanani (2004). "Sickle Cell Disease:
History And Origin". The Internet Journal of Haematology 1
(2). ISSN 1540-2649. http://www.ispub.com/ostia/index.php?
xmlFilePath=journals/ijhe/vol1n2/sickle.xml.

External links:

Sickle cell at the Open Directory Project
Sickle cell (kids) at the Open Directory Project
Sickle Cell Disease Association of America
[hide]v • d • ePathology: hematology · myeloid hematologic
disease (primarily D50-D77 · 280-289)

RBCs ↑ Polycythemia · Macrocytosis

↓ Anemia Nutritional Micro-: Iron deficiency anemia
(Plummer-Vinson syndrome)
Macro-: Megaloblastic anemia (Pernicious anemia)

Hemolytic
(mostly Normo-;
thal.=Micro-) Hereditary enzymopathy: G6PD · glycolysis
(PK, TI, HK)
hemoglobinopathy: Thalassemia (alpha, beta, delta) · Sickle-
cell disease/trait · HPFH

membrane: Hereditary spherocytosis (Minkowski-Chauffard
syndrome) · Hereditary elliptocytosis (Ovalocytosis) ·
Hereditary stomatocytosis

Acquired Autoimmune (WAHA, CAD, PCH)

membrane (PNH)

MAHA · TM (HUS)

Drug-induced autoimmune hemolytic anemia · Drug-induced
nonautoimmune hemolytic anemia

Aplastic
(mostly Normo-) Hereditary: Fanconi anemia · Diamond-
Blackfan anemia
Acquired: PRCA · Sideroblastic anemia · Myelophthisic

Blood tests MCV (Normocytic, Microcytic, Macrocytic) ·
MCHC (Normochromic, Hypochromic)

Other Methemoglobinemia · Sulfhemoglobinemia ·
Reticulocytopenia

Coagulation/
coagulopathy/
bleeding diathesis ↑ Thrombocytosis Essential
thrombocytosis

Hypercoagulability primary: Antithrombin III deficiency ·
Protein C deficiency/Activated protein C resistance/Protein S
deficiency/Factor V Leiden · Hyperprothrombinemia
acquired: DIC (Congenital afibrinogenemia, Purpura
fulminans) · autoimmune (Antiphospholipid)

↓ Thrombocytopenia/purpura Nonthrombocytopenic
purpura: Henoch-Schönlein
Thrombocytopenic purpura: ITP (Evans syndrome) · TM
(TTP)

Heparin-induced thrombocytopenia

Platelet function adhesion (Bernard-Soulier syndrome) ·
aggregation (Glanzmann's thrombasthenia) · platelet storage
pool deficiency (Hermansky-Pudlak syndrome, Gray platelet
syndrome)

Clotting factor Hemophilia (A/VIII, B/IX, C/XI) • Von Willebrand
disease • Hypoprothrombinemia/II · XIII

Monocytes/
macrophages ↑ Histiocytosis · Chronic granulomatous
disease
-cytosis: Monocytosis

↓ -penia: Monocytopenia

Granulocytes ↑ -cytosis: granulocytosis (Neutrophilia,
Eosinophilia, Basophilia, Bandemia)

↓ -penia: Granulocytopenia/agranulocytosis
(Neutropenia/Kostmann syndrome · Eosinopenia ·
Basopenia)

see also myeloid malignancy and immune disorders

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