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Please note that there are separate articles entitled 'Anaemia in Childhood' and 'Anaemia
in Pregnancy' that cover iron deficiency anaemia in these patient groups.
Iron deficiency anaemia (IDA) occurs when the body is iron deficient to the extent that
red blood cell production is reduced.1,2 A state of non-anaemic iron deficiency usually
precedes actual anaemia. Iron deficiency is the most common cause of anaemia
worldwide.
Failure to investigate IDA properly by practitioners in primary care can cause significant
delay in final diagnosis with associated morbidity.3 This article is based on the Clinical
Knowledge Summary Guidance on iron deficiency anaemia.4
Epidemiology
• In the developed world, 2-5% of adult men and post-menopausal women have
iron deficiency anaemia.5
• In other countries, infestation of the gut may cause IDA, especially with
hookworm and schistosomiasis.
• Χολονιχ χαρχινοµα
• Γαστριχ χαρχινοµα
• Ανγιοδψσπλασια
• Heavy menstruation
• Ηαεµορρηοιδσ
• Ποστ−παρτυµ ηαεµορρηαγε
• Recurrent epistaxis
Dietary inadequacy
• Dietary iron deficiency is fairly uncommon.
• Meat tends to be more rich in iron than vegetables and so vegetarians are at
greater risk. However, green vegetables are a good source of iron and a proper
vegetarian diet should not lead to deficiency.
• Growing children and elderly people with iron-poor diets may become deficient.
• Iron can be absorbed in the ferrous state much more readily than in the ferric
state.
• Some drugs can bind to iron and prevent absorption. Tetracyclines and
quinolones chelate with iron so that neither the antibiotic nor the iron is
absorbed.
• If the diet is not adequate, an intake that would otherwise be sufficient becomes
inadequate. For example in:
Presentation
Iron deficiency anaemia is often an incidental finding rather than a presenting feature.
Chronic, slow blood loss can lead to compensation by the body and little in the way of
symptoms. If symptoms occur, they can include:
• Fatigue
• Shortness of breath on exertion
• Παλπιτατιονσ
• Πρυριτισ
• Ηεαδαχηε
• Τιννιτυσ
• Very rarely, there may be dysphagia due to an oesophageal web with chronic iron
deficiency. This is the Paterson-Brown-Kelly or Plummer-Vinson Syndrome and
there is an association with oesophageal carcinoma.
Symptoms of severe anaemia (usually not occurring until Hb is <7 g/dL) include:
shortness of breath at rest, angina and ankle swelling. These symptoms may occur at
higher Hb levels if there is co-existing cardiorespiratory disease).4
History
To look for potential causes, cover the following points:
• Any overt bleeding seen by patient - e.g. nosebleeds, rectal bleeding etc.
• History of recent illness - could suggest gastrointestinal bleeding, e.g. weight loss,
change in bowel habit, dyspepsia
• Travel history - e.g. hookworm infestation is possible if recent travel to the tropics
• Perform a rectal examination to look for signs of bleeding, malaena and masses.
Signs
• Pallor (best seen in the mucosa of tongue and mouth, especially in people with
dark skin)
• Ατροπηιχ γλοσσιτισ
• Pigmentation of the lips and oral mucosa may suggest Peutz-Jeghers syndrome
• Full blood count: shows a hypochromic microcytic anaemia (although there may
be a mixed picture with coexistent B12 or folate deficiency).
• Blood film: anisocytosis (variation in size between red blood cells) and
poikilocytosis (abnormally shaped red blood cells) can be seen.
Differential diagnosis
Other causes of microcytic anaemia including:
• Thalassaemia
• Sideroblastic anaemia
• Λεαδ ποισονινγ
Investigations
The following groups of people do not usually require investigation before treatment is started:4
• Otherwise healthy young people in whom the history clearly suggests a cause (e.g.
regular blood donors).
However, consider investigations if there is a poor response to treatment or the anaemia recurs
with no obvious cause.
If menorrhagia is thought to be the cause of iron deficiency anaemia, please refer to the separate
article on menorrhagia for details about appropriate investigations.
Who should be referred to secondary care?4
• If someone has profound anaemia and signs of acute heart failure, they should be
admitted urgently to hospital.
• People of any age with dyspepsia and iron deficiency anaemia should be referred
for endoscopy, or to a specialist in upper gastrointestinal cancer, within 2 weeks.
• Men of any age with unexplained iron deficiency anaemia and a haemoglobin of
11 g/dL or below, should be referred within 2 weeks to a gastroenterologist.
• Women who are not menstruating with unexplained iron deficiency anaemia and
a haemoglobin of 10 g/dL or below should be referred within 2 weeks to a
gastroenterologist.
Clinical judgement should be used in people with unexplained iron deficiency anaemia who do
not fall into the above categories. They will still need referral for further investigation but the
clinician will have to determine the urgency.
Sideroblastic Anaemia
Synonyms: Refractory anemia with ringed sideroblasts (RARS)
Sideroblastic anaemias are a heterogeneous group of refractory anaemias. They are
characterized by the presence of abnormal ringed sideroblasts in bone marrow aspirate.
The sideroblasts form due to reduced haemoglobin synthesis, resulting in the
accumulation of iron within red blood cell precursors. Cases can, rarely, be congenital but
are more usually acquired and sometimes represent a stage in the development of
myelodysplastic syndromes.
Epidemiology
This accounts for 5-15% of all myelodysplastic syndromes.1 70% of all patients are aged
>50years old.
Hereditary forms of sideroblastic anaemia are X-linked and more common in males.
Cases can be related to ataxia and the condition may not present until the fourth decade or
later if mild.2
Aetiology
In addition to the myelodysplastic syndromes, sideroblastic anaemia can also occur in
other bone marrow diseases including:
• Myeloma
• Μψελοσχλεροσισ
• Λευκαεµιασ
• Chronic infections
• Χηρονιχ αλχοηολισµ
• Ηαεµολψτιχ αναεµια
• Μαλαβσορπτιον syndromes
• Μψξοεδεµα
• Λεαδ ποισονινγ
• Πρεγνανχψ
Presentation
Clinical features are those related to anaemia in general. Symptoms reflect the
cytopenias, i.e. anaemia, infection, bruising and haemorrhage.
There are no specific signs or symptoms related to sideroblastic anaemia alone.
Investigations
• The blood film shows a dimorphic population of both normal and hypochromic
red blood cells.
Non-Drug
• Treatment is mainly supportive.
Iron chelation with desferrioxamine should be considered after 20-25 units of red
cells have been received.3
Anemia (AmE) or anæmia/anaemia (BrE), from the Greek (Ἀναιμία) (an-haîmia)
meaning "without blood," is defined as a qualitative or quantitative deficiency of
hemoglobin, a molecule found inside red blood cells (RBCs). Since hemoglobin normally
carries oxygen from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in
organs. Since all human cells depend on oxygen for survival, varying degrees of anemia
can have a wide range of clinical consequences.
The three main classes of anemia include excessive blood loss (acutely such as a
hemorrhage or chronically through low-volume loss), excessive blood cell destruction
(hemolysis) or deficient red blood cell production (ineffective hematopoiesis).
Anemia is the most common disorder of the blood. There are several kinds of anemia,
produced by a variety of underlying causes. Anemia can be classified in a variety of
ways, based on the morphology of RBCs, underlying etiologic mechanisms, and
discernible clinical spectra, to mention a few.
There are two major approaches of classifying anemias, the "kinetic" approach which
involves evaluating production, destruction and loss[1], and the "morphologic" approach
which groups anemia by red blood cell size. The morphologic approach uses a quickly
available and cheap lab test as its starting point (the MCV). On the other hand, focusing
early on the question of production may allow the clinician more rapidly to expose cases
where multiple causes of anemia coexist.
Contents
[hide]
• 2 ∆ιαγνοσισ
• 3 Χλασσιφιχατιον
• 4 Specific anemias
• 5 Ποσσιβλε χοµπλιχατιονσ
• 8 References
• 9 Βοοκσ
• 10 Σεε αλσο
• 11 Εξτερναλ λινκσ
[edit] Signs and symptoms
Anemia goes undetected in many people, and symptoms can be small and vague. Most
commonly, people with anemia report a feeling of weakness or fatigue in general or
during exercise, general malaise and sometimes poor concentration. People with more
severe anemia often report dyspnea (shortness of breath) on exertion. Very severe anemia
prompts the body to compensate by increasing cardiac output, leading to palpitations and
sweatiness, and to heart failure.
Pallor (pale skin, mucosal linings and nail beds) is often a useful diagnostic sign in
moderate or severe anemia, but it is not always apparent. Other useful signs are cheilosis
and koilonychia.
Pica, the consumption of non-food such as dirt, paper, wax, grass, ice and hair, may be a
symptom of iron deficiency, although it occurs often in those who have normal levels of
hemoglobin.
Chronic anemia may result in behavioral disturbances in children as a direct result of
impaired neurological development in infants, and reduced scholastic performance in
children of school age.
[edit] Diagnosis
Generally, clinicians request complete blood counts in the first batch of blood tests in the
diagnosis of an anemia. Apart from reporting the number of red blood cells and the
hemoglobin level, the automatic counters also measure the size of the red blood cells by
flow cytometry, which is an important tool in distinguishing between the causes of
anemia. Examination of a stained blood smear using a microscope can also be helpful,
and is sometimes a necessity in regions of the world where automated analysis is less
accessible.
In modern counters, four parameters (RBC count, hemoglobin concentration, MCV and
RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated,
and compared to values adjusted for age and sex. Some counters estimate hematocrit
from direct measurements. For adult men, a hemoglobin level less than 13.0 g/dl (grams
per deciliter) is diagnostic of anemia, and for adult women, the diagnostic threshold is
below 12.0 g/dl.
Reticulocyte counts, and the "kinetic" approach to anemia, have become more common
than in the past in the large medical centers of the United States and some other wealthy
nations, in part because some automatic counters now have the capacity to include
reticulocyte counts. A reticulocyte count is a quantitative measure of the bone marrow's
production of new red blood cells. The reticulocyte production index is a calculation of
the ratio between the level of anemia and the extent to which the reticulocyte count has
risen in response. If the degree of anemia is significant, even a "normal" reticulocyte
count actually may reflect an inadequate response.
If an automated count is not available, a reticulocyte count can be done manually
following special staining of the blood film. In manual examination, activity of the bone
marrow can also be gauged qualitatively by subtle changes in the numbers and the
morphology of young RBCs by examination under a microscope. Newly formed RBCs
are usually slightly larger than older RBCs and show polychromasia. Even where the
source of blood loss is obvious, evaluation of erythropoiesis can help assess whether the
bone marrow will be able to compensate for the loss, and at what rate.
When the cause is not obvious, clinicians use other tests: ESR, ferritin, serum iron,
transferrin, RBC folate level, serum vitamin B12, hemoglobin electrophoresis, renal
function tests (e.g. serum creatinine).
When the diagnosis remains difficult, a bone marrow examination allows direct
examination of the precursors to red cells.
[edit] Classification
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Other characteristics visible on the peripheral smear may provide valuable clues about a
more specific diagnosis; for example, abnormal white blood cells may point to a cause in
the bone marrow.
• HbE syndrome
• HbC syndrome
• Sideroblastic defect
Iron deficiency anemia is the most common type of anemia overall and it has many
causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than
usual) when viewed with a microscope.
• Ηεµολψτιχ ανεµια
• 1.3 Αλχοηολ
• 2 References
Megaloblastic Anaemia
In this group of anaemias the erythroblasts in the bone marrow show a delay of the
maturation of the nucleus relative to that of the cytoplasm. The delay in the maturation of
the nucleus is due to defective DNA synthesis. This may be caused by:
• Φολατε δεφιχιενχψ
Both vitamin B12 and folate are required for the synthesis of DNA. Folate is needed in its
tetrahydrofolate form (FH4) as a cofactor in DNA synthesis. Vitamin B12 is a cofactor
required for the conversion of homocysteine to methionine which enables cells to receive
FH4 for synthesis of methylene FH4, the coenzyme required for the conversion of
deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) in the
formation of DNA.
Vitamin B12 Deficiency
The natural source of B12 is from the diet. Vitamin B12 is synthesised only by bacteria
and is found in meat, fish, eggs, and milk, but not in plants, and it is not usually destroyed
by cooking. A normal diet contains a large excess of B12 compared with daily needs. B12
is combined with intrinsic factor (IF), a glycoprotein synthesised by gastric parietal cells.
The IF-B12 complex binds to a specific receptor protein for IF, cubulin, in the distal
ileum, where B12 is then absorbed.
In Western countries, B12 deficiency is usually caused by pernicious anaemia, an
autoimmune disorder. The majority of patients have IgG autoantibodies targeted against
gastric parietal cells and IF, leading to atrophy of the gastric mucosa with consequent
failure of IF production. Gastritis affecting the fundus is present with plasma cell and
lymphoid infiltration. The parietal and chief cells are replaced by mucin-secreting cells.
Achlorhydria (failure to produce hydrochloric acid) occurs and secretion of IF is absent
or almost absent.
Less commonly, it may also be caused by:
• gastrectomy
• ileal resection
• tropical sprue
• fish tapeworm
• congenital malabsorption
The deficiency takes at least 2 years to develop - i.e. the time needed for body stores to
deplete at a rate of 1-2µg each day when there is no new B12 entering the body from the
diet.
Folate Deficiency
Humans are unable to synthesise folate and so require preformed folate as a vitamin in
the diet. It is found in green vegetables such as spinach broccoli, and offal, such as liver
and kidney. Cooking causes loss of 60-90% of the folate.
The main cause of folate deficiency is poor dietary intake, which may occur alone or
with excessive utilisation or malabsorption (Table 1). It may also be caused by antifolate
drugs.
Poor Dietary Intake Malabsorption
• Anticonvulsants (phenytoin,
• Pregnancy and lactation primidone)
• Haemolytic anaemia • Sulphasalazine
• Myeloproliferative / • Methotrexate
malignant / inflammatory
disorders • Pyrimethamine
• Trimethoprim
On a deficient diet, folate deficiency develops over about 4 months, but deficiency may
develop more rapidly in patients who have both a poor intake and excess utilisation of
folate, as in ITU patients.
Abnormalities of Vitamin B12 or Folate Metabolism
These include:
Clinical Features
Onset: insidious
Glossitis
Angular stomatitis
Sterility
Investigations
Haematological findings:
Serum vitamin B12: (<160ng/l). Very low in pernicious anaemia. Can be assayed
using radioisotope dilution or immunological assays
Autoantibodies:
Vitamin B12 absorption tests: Schilling test - patient swallows B12 labelled with
radioactive cobalt and absorption is usually measured in directly by quantifying
urinary excretion. Normal subjects excrete >10% of the radioactive dose. The test
is then repeated with IF added.
If excretion is now normal (malabsorption is corrected) = pernicious anaemia or
gastrectomy
If excretion is still abnormal = terminal ileum lesion or bacterial overgrowth.
Duodenal biopsy
Treatment
Most cases only require administering the appropriate vitamin (Table 2). However, it
is important not to give folate in vitamin B12 deficiency since the neuropathy may be
aggravated. B12 deficiency must be excluded before commencing large doses of folic
acid. In the elderly, correct any heart failure with diuretics and oral potassium
supplements given for 10 days. Avoid blood transfusion as it may cause circulatory
overload.
Vitamin B12
Folate Deficiency
Deficiency
Compound Hydroxycobalamin Folic acid
Route IM, PO, SL PO
Prophylacti
c Total gastrectomy Pregnancy, severe haemolytic
Ileal resection anaemias, dialysis, prematurity
Liver disease
Myxoedema
Myelodysplastic syndromes
• Cytotoxic drugs
• Aplastic anaemia
• Pregnancy
• Smoking
• Reticulocytosis
• Myeloma
• Neonatal
It is important to exclude B12 or folate deficiency before these diagnoses are made.
White cell and platelet counts are normal unless the underlying marrow disease affects
these. The red cells are circular rather than oval, hypersemented neutrophils are absent
and the marrow is normoblastic.
Red Cell Production and Anaemia
Anaemia is defined as a reduction in haemoglobin concentration. This varies between
sexes but is usually defined as a haemoglobin less than 13.5g/dl in males and 11.5 g/dl in
females. The reduction in haemoglobin is generally accompanied by a fall in the red cell
count and the packed cell volume or 'haematocrit'. Alterations in plasma volume will alter
haemoglobin concentrations. A reduction in plasma volume, as in dehydration, will cause
an artificial elevation of the haemoglobin concentration and may mask anaemia. An
increase in plasma volume, as in pregnancy, may cause an apparent anaemia. Anaemia is
not immediately apparent in acute major blood loss when the total blood volume is
reduced. It generally takes over 24 hours before anaemia is evident.
Clinical features of anaemia
These are very variable and depend on the speed of onset of the anaemia and the co-
existence of other medical conditions. In general, a slowly progressive anaemia may be
relatively asymptomatic and the patient may be able to adapt. However, co-existent
cardiac or pulmonary disease may exacerbate the symptoms. The symptoms that are
defined include lethargy, shortness of breath, exacerbation of angina. The physical signs
on examination of the patient are generally unreliable but it is possible that pallor of the
mucous membranes or, very rarely, koilonychia (spooning of nails) may be observed.
Classification of anaemia
There are many different causes of anaemia and 2 major classification systems exist; in
practice a combination of the two are used.
A – a classification based on the cause of the anaemia:
(i) those patients who have reduced production of red cells
(ii) patients whose red cells function poorly
(iii) situations where there is increased loss or destruction of red cells.
B – Classification of anaemia based on the size of red cells - the mean cell volume
(MCV); the normal range for this parameter is 80-100fl.
(i) macrocytic (large red cells)
(ii) normocytic (normal sized red cells)
(iii) microcytic (small red cells).
The second classification is widely used. It is practical because the vast majority of
peripheral blood counts measured in the United Kingdom are analysed on modern
electronic cell counters. These counters identify a number of parameters related to red
cell size, red cell number and the concentration of haemoglobin in red cells.
The macrocytic anaemias
Causes of a macrocytic anaemia (raised MCV) are listed below:
B12 and folate deficiency
Vitamin B12 and folic acid are closely involved in the production of DNA. Deficiency of
either one of these vitamins causes a macrocytic anaemia. Vitamin B12 is absorbed from
the ileum as a complex with intrinsic factor produced in the gastric parietal cells; folate
on the other hand is absorbed in the duodenum and jejunum. Deficiencies of either can
result from diseases of the site of absorption. Folic acid is widely distributed in food-
stuffs but vitamin B12 is confined to meat products. Consequently, vitamin B12
deficiency can be seen in strict vegans. In non-vegans the main cause of vitamin B12
deficiency is pernicious anaemia, which is an auto-immune condition with antibodies
being produced against gastric parietal cells in 90% and intrinsic factor in 70% of
patients. Folic acid deficiency can often be related to a poor diet or to malabsorption
within the gut, eg coeliac disease.
Alcoholism and liver disease
Many forms of liver disease, including alcoholic cirrhosis and, indeed, alcoholism per se,
can lead to a macrocytic anaemia. There is often co-existent folate deficiency.
Impaired red cell production
Aplastic anaemia, where there is bone marrow failure or myelodysplasia, where there is
ineffective red cell production, can both cause a macrocytic anaemia. The causes of
aplastic anaemia are varied but can include certain viruses, eg hepatitis B, excessive
doses of cytotoxic drugs or radiation, or idiosyncratic reactions to drugs. The treatment of
aplastic anaemia is either bone marrow transplantation or immunotherapy.
Myelodysplasia is a heterogeneous group of conditions which may be pre-leukaemic.
There is no satisfactory treatment for these conditions other than blood product support,
eg red cell transfusion. In some patients, cytotoxic therapy or bone marrow
transplantation may be indicated.
Haemolytic anaemias
There are many causes of haemolytic anaemia. Destruction of red cells may take place
either within the circulation (intra-vascular haemolysis) or outside the circulation mainly
in the spleen (extra-vascular haemolysis). In these conditions the reticulocyte count is
usually raised. Reticulocytes are large red cells, and so their presence in increased
numbers can cause a raised MCV. It is possible to have a haemolytic anaemia with a
normal MCV; in these cases the degree of reticulocytosis is less. The aetiology of
haemolytic anaemia may be divided into stimuli outside the red cell membrane, problems
within the red cell membrane and defects within the red cell itself. An example of a
haemolytic anaemia where the stimulus lies outside the red cell membrane is auto-
immune haemolytic anaemia. In these cases the direct Coomb's test is positive; i.e. there
is an antibody active against red cells, which is present in the plasma. This causes
increased destruction of red cells in the spleen. Auto-immune anaemia can be idiopathic,
i.e. without an identified precipitating cause or secondary to a lymphoma, an auto-
immune disease, eg. rheumatoid arthritis or systemic lupus erythematosus, (but these
diseases can also suppress red cell production); certain drugs induce auto-immune
haemolytic anaemia; more rarely it may occur in association with an infection.
An example of a haemolytic anaemia secondary to an inherent problem within the red
cell membrane is hereditary spherocytosis. This is a congenital condition that has a
Mendelian pattern of inheritance characterised by a chronic haemolytic anaemia but with
a negative direct Coomb's test. It is best treated by splenectomy.
An example of a chronic haemolytic anaemia due to an inherent problem within the red
cell is glucose 6 phosphate dehydrogenase deficiency. This is an x-linked condition and
therefore affects only males. It leads to a chronic haemolytic state which is exacerbated
by certain drugs, infection and the ingestion of favar beans. Treatment is avoidance of
precipitating agents.
Normochromic anaemia
Anaemia of chronic disease
Most chronic coexistent medical conditions can cause such an anaemia. The mechanism
is thought to be due to failure to use iron efficiently. Examples of chronic conditions
include chronic inflammatory diseases such as rheumatoid arthritis, chronic infections
including tuberculosis or malignancy. Some cases of anaemia of chronic disease are
hypochromic, microcytic, ie, low MCH, low MCV but with a normal ferritin.
Acute blood loss
As mentioned previously, acute major blood loss will cause a normochromic, normocytic
anaemia which becomes apparent after about 24 hours.
Mixed deficiency anaemia
There are rare cases of a mixed deficiency anaemia, eg. combined iron deficiency with
B12 or folate deficiency. The result is an anaemia which is normocytic.
Bone marrow failure
This may occur in individuals whose marrow is infiltrated by malignancy, are post-
chemotherapy or have chronic renal disease.
Microcytic anaemias
Causes of microcytic anaemia include:
Iron deficiency anaemia
This is the most common cause of anaemia in the UK. The most likely cause of iron
deficiency anaemia is chronic blood loss. In women this may be due to excessive periods
(menorrhagia) but overall it is usually due to chronic blood loss from the gastro-intestinal
tract. This may be due to any bleeding pathology in the gut. Blood loss of 4ml per day
will, in time, render an individual iron-deficient. The diagnosis of an iron deficiency
anaemia is confirmed by a reduced serum ferritin. Once it has been ascertained that the
patient has an iron deficient anaemia, then investigation to find the source of blood loss is
required. This usually involves investigation of the G1 tract with barium studies or
endoscopy. Treatment of the iron ferrous sulphate tablets, but it is important to remember
that the cause of the anaemia must be found.
Haemoglobinopathies, e.g., thalassaemia
The thalassaemias are a complicated group of conditions which are inherited. They are
prevalent in certain parts of the world including the Mediterranean basin, parts of Africa,
the Middle East, Indian sub-continent and South-East Asia. In the severe forms of the
disease the patient is chronically anaemic with a hypochromic, microcytic picture but a
raised red cell count. Treatment is by repeated transfusion which can cause iron overload.
Attention then needs to be given to the treatment of the iron overload, generally using
Desferrioxamine. In some patients bone marrow transplantation can be curative.
Other rare causes of a microcytic anaemia include lead poisoning and some types of
sideroblastic anaemia Sideroblastic anaemia is a rare condition which may be either
congenital when it usually occurs in males, or is secondary to certain drugs, particularly
those used to treat tuberculosis.
Anemia, like a fever, is a symptom of disease that requires investigation to determine the
underlying etiology. Often, practicing physicians overlook mild anemia. This is similar to
failing to seek the etiology of a fever. The purpose of this article is to provide a method
of determining the etiology of an anemia.
Anemia is strictly defined as a decrease in red blood cell (RBC) mass. Methods for
measuring RBC mass are time consuming, are expensive, and usually require transfusion
of radiolabeled erythrocytes. Thus, in practice, anemia is usually discovered and
quantified by measurement of the RBC count, hemoglobin (Hb) concentration, and
hematocrit (Hct). These values should be interpreted cautiously because they are
concentrations affected by changes in plasma volume. For example, dehydration elevates
these values, and increased plasma volume in pregnancy can diminish them without
affecting the RBC mass.
Pathophysiology
Erythroid precursors develop in bone marrow at rates usually determined by the
requirement for sufficient circulating Hb to oxygenate tissues adequately. Erythroid
precursors differentiate sequentially from stem cells to progenitor cells to erythroblasts to
normoblasts in a process requiring growth factors and cytokines. This process of
differentiation requires several days. Normally, erythroid precursors are released into
circulation as reticulocytes.
Reticulocytes remain in the circulation for approximately 1 day before reticulin is excised
by reticuloendothelial cells with the delivery of the mature erythrocyte into circulation.
The mature erythrocyte remains in circulation for about 120 days before being engulfed
and destroyed by phagocytic cells of the reticuloendothelial system.
Erythrocytes are highly deformable and increase their diameter from 7 µm to 13 µm
when they traverse capillaries with a 3-µm diameter. They possess a negative charge on
their surface, which may serve to discourage phagocytosis. Because erythrocytes have no
nucleus, they lack a Krebs cycle and rely on glycolysis via the Embden-Meyerhof and
pentose pathways for energy. Many enzymes required by the aerobic and anaerobic
glycolytic pathways decrease within the cell as it ages. In addition, the aging cell has a
decrease in potassium concentration and an increase in sodium concentration. These
factors contribute to the demise of the erythrocyte at the end of its 120-day lifespan.
RBCs contain fluid Hb encased in a lipid membrane supported by a cytoskeleton.
Abnormalities of the membrane, the chemical composition of the Hb, or certain
glycolytic enzymes can reduce the lifespan of RBCs to cause anemia. Basically, only 3
causes of anemia exist: blood loss, increased RBC destruction (hemolysis), and decreased
production of RBCs. Each of these 3 causes includes a number of etiologies that require
specific and appropriate therapy. Often, the etiology can be determined if the RBCs are
altered in either size or shape or if they contain certain inclusion bodies. For example,
Plasmodium falciparum malaria is suggested by the presence of more than one ring form
in an RBC and produces pan-hemolysis of RBCs of all ages.
Frequency
United States
The prevalence of anemia in population studies of healthy nonpregnant people depends
on the Hb concentration chosen for the lower limit of normal values. The World Health
Organization chose 12.5 g/dL for both adult males and females. In the United States,
limits of 13.5 g/dL for men and 12.5 g/dL for women are probably more realistic. Using
these values, approximately 4% of men and 8% of women have values lower than those
cited. A significantly greater prevalence is observed in patient populations. Less
information is available regarding studies using RBC or Hct.
International
The prevalence of anemia in Canada and northern Europe is believed to be similar to that
in the United States. In underprivileged countries, limited studies of purportedly healthy
subjects show the prevalence of anemia to be 2-5 times greater than that in the United
States. Although geographic diseases, such as sickle cell anemia, thalassemia, malaria,
hookworm, and chronic infections, are responsible for a portion of the increase,
nutritional factors with iron deficiency and, to a lesser extent, folic acid deficiency play
major roles in the increased prevalence of anemia. Populations with little meat in the diet
have a high incidence of iron deficiency anemia because heme iron is better absorbed
from food than inorganic iron.
Mortality/Morbidity
• The morbidity and mortality of anemias vary greatly depending on the etiology.
• Sickle cell disease may be associated with frequent painful crises and a
shortened lifespan, or patients with sickle cell disease may remain
relatively asymptomatic with a nearly normal lifespan.
• Most patients with beta-0 homozygous thalassemia die during the second
or third decade of life unless they undergo bone marrow transplantation.
• The 2-year fatality rate for severe aplastic anemia is 70% without bone
marrow transplantation or a response to immunosuppressive therapy.
• Many symptoms associated with anemia are not caused by diminished RBC mass.
Patients with pernicious anemia are often asymptomatic when they are detected
incidentally with an Hb of 6 g/dL. In contrast, ice chewing, calf cramps, and
diminished capability to perform muscular work occur in iron-deficiency anemia
with an Hb of 10-11 g/dL because of depletion of iron-containing proteins other
than Hb.
• Race
• Certain races and ethnic groups have an increased prevalence of genetic factors
associated with certain anemias. Examples are hemoglobinopathies, thalassemia,
and G-6-PD deficiency. Each of these disorders has different morbidity and
mortality in different populations due to differences in the genetic abnormality
producing the disorder. For example, G-6-PD deficiency and thalassemia have
less morbidity in African Americans than in Sicilians because of differences in the
genetic fault. Conversely, sickle cell anemia has a greater morbidity and mortality
in African Americans than among Saudi Arabians.
Sex
• Overall, anemia is twice as prevalent in females as in males. This difference is
significantly greater during the childbearing years due to pregnancies and menses.
• Approximately 65% of body iron is incorporated into circulating Hb. Each gram
of Hb contains 3.46 mg of iron (1 mL of blood with Hb of 15 g/dL = 0.5 mg of
iron). Each healthy pregnancy depletes the mother of approximately 500 mg of
iron. While a man must absorb about 1 mg of iron to maintain equilibrium, a
premenopausal woman must absorb an average of 2 mg daily. Further, because
women eat less food than men, they must be more than twice as efficient as men
in the absorption of sufficient iron to avoid iron deficiency.
• Women have a markedly lower incidence of anemia from X-linked anemias, such
as G-6-PD deficiency and sex-linked sideroblastic anemias.
Age
• Severe genetically acquired anemias (eg, sickle cell disease, thalassemia, Fanconi
syndrome) are more commonly found in children because they do not survive to
adulthood.
• During the childbearing years, women are more likely to become iron deficient.
• Neoplasia increases in prevalence with each decade of life and can produce
anemia from bleeding, from the replacement of bone marrow with tumor, or from
the development of anemia associated with chronic disorders. Use of aspirin,
nonsteroidal anti-inflammatory drugs (NSAIDs), and Coumadin increases with
age and can produce gastrointestinal bleeding.
CLINICAL
Section 3 of 11
• Ιντροδυχτιον
• Χλινιχαλ
• ∆ιφφερεντιαλσ
• Ωορκυπ
• Τρεατµεντ
• Μεδιχατιον
• Φολλοω−υπ
• Μισχελλανεουσ
• Μυλτιµεδια
• Ρεφερενχεσ
History
Carefully obtain a history and perform a physical examination in every patient with
anemia because the findings usually provide important clues to the etiology of the
underlying disorder. From the standpoint of the investigation of the anemia, asking
questions in addition to those conventionally explored during a routine examination is
important. Areas of inquiry found valuable are briefly described below.
• Obtain a careful family history not only for anemia but also for jaundice,
cholelithiasis, splenectomy, bleeding disorders, and abnormal Hbs. Carefully
document the patient's occupation, hobbies, prior medical treatment, drugs
(including over-the-counter medications and vitamins), and household exposures
to potentially noxious agents. Patients are unlikely to volunteer exposures to
tranquilizers, insecticides, paints, solvents, and hair dyes unless specifically
queried.
• Abnormal urine color can occur in renal and hepatic disease and in hemolytic
anemia.
• Changes in body weight are important with regard to dietary intake and
can suggest the presence of malabsorption or an underlying wasting
disease of infectious, metabolic, or neoplastic origin.
• Patients with folate deficiencies may have a sore tongue, cheilosis, and
symptoms associated with steatorrhea.
• Color, bulk, frequency, and odor of stools and whether the feces float or
sink can be helpful in detecting malabsorption. More sensitive questions to
detect steatorrhea include whether the toilet needs to be flushed more than
once to rid it of stool and whether an oily substance is floating on the
water surface after the first flush.
• The relation of dark urine to either physical activity or time of day can be
important in march hemoglobinuria and paroxysmal nocturnal hemoglobinuria.
• Physical
• Too often, the physician rushes into the physical examination without looking at the
patient for an unusual habitus or appearance of underdevelopment, malnutrition, or
chronic illness. These findings can be important clues to the underlying etiology of
disease and provide information related to the duration of illness. The skin and
mucous membranes are often bypassed so that pallor, abnormal pigmentation, icterus,
spider nevi, petechiae, purpura, angiomas, ulcerations, palmar erythema, coarseness
of hair, puffiness of the face, thinning of the lateral aspects of the eyebrows, nail
defects, and a usually prominent venous pattern on the abdominal wall are missed in
the rush to examine the heart and the lungs.
• Examine optic fundi carefully but not at the expense of the conjunctivae and the
sclerae, which can show pallor, icterus, splinter hemorrhages, petechiae, comma
signs in the conjunctival vessels, or telangiectasia that can be helpful in planning
additional studies.
• The neurologic examination should include tests of position sense and vibratory
sense, examination of the cranial nerves, and testing for tendon reflexes. The heart
should not be ignored because enlargement may provide evidence of the duration
and the severity of the anemia, and murmurs may be the first evidence of a
bacterial endocarditis that could explain the etiology of the anemia.
Causes
Causes of anemia are numerous and multifaceted. A family history may be useful in
detecting hereditary etiology. Diet and exposure to drugs and chemicals can be useful. A
geographic history and a thorough knowledge of the patient's health can be important in
establishing an etiology.
• Genetic
• Hemoglobinopathies
• Thalassemias
• Rh null disease
• Hereditary xerocytosis
• Abetalipoproteinemia
• Fanconi anemia
• Nutritional
• Iron deficiency
• Folate deficiency
• Hemorrhage
• Physical effects
• Trauma
• Burns
• Frostbite
• Aplastic anemia
• Megaloblastic anemia
• Renal disease
• Hepatic disease
• Chronic infections
• Neoplasia
• Infections
• DIFFERENTIALS
• Section 4 of 11
• Ιντροδυχτιον
• Χλινιχαλ
• ∆ιφφερεντιαλσ
• Ωορκυπ
• Τρεατµεντ
• Μεδιχατιον
• Φολλοω−υπ
• Μισχελλανεουσ
• Μυλτιµεδια
• Ρεφερενχεσ
•
Aplastic Anemia
Cooley Anemia
Hemolytic Anemia
Iron Deficiency Anemia
Low LDL Cholesterol (Hypobetalipoproteinemia)
Megaloblastic Anemia
Myelophthisic Anemia
Pernicious Anemia
Sickle Cell Anemia
Spur Cell Anemia
Thalassemia, Alpha
Thalassemia, Beta
• WORKUP
• Section 5 of 11
• Ιντροδυχτιον
• Χλινιχαλ
• ∆ιφφερεντιαλσ
• Ωορκυπ
• Τρεατµεντ
• Μεδιχατιον
• Φολλοω−υπ
• Μισχελλανεουσ
• Μυλτιµεδια
• Ρεφερενχεσ
Lab Studies
• The first step in the diagnosis of anemia is detection with reliable accurate tests so
that important clues to underlying disease are not overlooked and patients are not
subjected to unnecessary tests for and treatment of nonexistent anemia. Detection
of anemia involves the adoption of arbitrary criteria.
S
Total Iron- Bone
Conditi eru
Binding Marr
on m Comment
Capacity ow
Iro
(TIBC) Iron
n
Iron
deficien ⇓ ⇑ 0 Responsive to iron therapy
cy
Chronic
inflamm ⇓ ⇓ ++ Unresponsive to iron therapy
ation
Thalass
Reticulocytosis and indirect
emia ⇑ N ++++
bilirubinemia
major
Thalass Elevation of A of fetal
emia N N ++ hemoglobin, target cells, and
minor poikilocytosis
Lead
poisonin N N ++ Basophilic stippling of RBCs
g
Siderobl
⇑ N ++++ Ring sideroblasts in marrow
astic
Hemogl
N N ++ Hemoglobin electrophoresis
obin
• Blood loss
• Every patient with iron deficiency anemia should have a stool examination
for occult blood. A positive result necessitates a careful search of the
gastrointestinal tract to identify the site of bleeding. Unfortunately, a
negative result does not exclude gastrointestinal blood loss because
bleeding can be intermittent and require several examinations for
detection. Also, less than 20-30 mL of blood in the stool per day may go
undetected due to the insensitivity of the test. The 2 methods used to
detect small daily losses of blood from the gut are as follows: (1) placing
the patient on a meat-free diet for several days and using more sensitive
methods, such as a benzidine test, and (2) labeling the patient's RBCs with
chromium 51 and collecting stool specimens for the detection of the
radioisotope.
• Other laboratory tests are available to detect hemolysis, but they are either
more expensive or less reliable.
Hereditary Acquired
Hereditary
spherocytos
is
Hereditary
elliptocytos
is
Hemoglobi
nopathies
Thalassemi
Intraco as Vitamin B-12 and folic acid deficiency
rpuscu Congenital Paroxysmal nocturnal
lar dyserythrop Hemoglobinuria
defect oietic Severe iron deficiency
anemias
Hereditary
RBC
enzymatic
deficiencies
Rarer
hereditary
abnormaliti
es
Extrac Physical agents: Burns, cold exposure
orpusc Traumatic: Prosthetic heart valves, march
ular hemoglobinemia, DIC, graft rejection
defect Chemicals: Drugs and venoms
Infectious agents: Malaria, toxoplasmosis,
mononucleosis, hepatitis, primary atypical
pneumonia, clostridial infections, bartonellosis,
leishmaniasis
Hepatic and renal disease
Collagen vascular disease
Malignancies: Particularly hematologic neoplasia
Transfusion of incompatible blood
Hemolytic disease of the newborn
Cold hemagglutinin
disease
Autoimmune hemolytic anemia Thrombotic
thrombocytopenic purpura (TTP) and hemolytic
uremic syndrome (HUS)
• Anemia solely due to hemolysis does not occur until RBCs are being
destroyed at 6-8 times the normal rate, reducing the mean RBC lifespan to
less than 20 days because of the bone marrow's capacity to undergo 6-fold
hypertrophy and hyperplasia. Thus, if the clinician relies on the presence
of anemia to detect hemolytic states, the clinician misses most of them
and, perhaps, an important clue to an underlying disorder. On the contrary,
if reticulocytosis and indirect bilirubinemia are used to detect hemolytic
states, they are usually found when the mean lifespan is less than 40-50
days. More sophisticated methods, such as measurements of RBC lifespan,
are required to detect less severe shortening of erythrocyte lifespan (50-
100 d) and are only occasionally needed in clinical practice.
• Whenever possible, a cause for the aplastic anemia should be uncovered because
cessation of exposure may lead to recovery. Identification of the offending agent
is likewise important in determining the prognosis.
• Chances of survival are poorer for patients with idiosyncratic aplasia caused by
chloramphenicol and viral hepatitis and better when paroxysmal nocturnal
hemoglobinuria or anti-insecticides are the probable etiology. The prognosis for
idiopathic aplasia lies between these 2 extremes, with an untreated mortality rate
of approximately 60-70% within 2 years after diagnosis.
• Certain patients with marrow hyperplasia may have refractory anemia for years,
but some of the group eventually develop acute myelogenous leukemia.
• Infiltration of the bone marrow with fibrous tissue, neoplastic cells, or other cells
that replace normal hematopoietic tissue can diminish the production of RBCs,
granulocytes, and platelets. The diagnosis of myelofibrosis or neoplastic
involvement of bone marrow is often suggested by evidence of myeloid
metaplasia in the peripheral smear (ie, erythroid and granulocyte precursors).
Replacement of bone marrow with nonhemopoietic cells leads to activation of
fetal sites of blood production in organs, such as the liver and the spleen, with
release of abnormally shaped erythrocytes and normoblasts, immature
granulocytes and normoblasts, immature granulocytes, and large platelets into the
peripheral blood. Myeloid metaplasia does not occur in aplastic disease. Thus, its
presence in a patient who is anemic suggests bone marrow infiltration, even
before the biopsy specimen is obtained.
• Imaging Studies
• Imaging studies are useful in the workup for anemia when a neoplastic etiology is
suggested. They permit discovery of the neoplasm or centrally located adenopathy.
Occasionally, they are useful in detecting or confirming the existence of
splenomegaly.
• Procedures
• Investigate gastrointestinal bleeding by endoscopy and radiographic studies to
identify the bleeding site. However, even these methods may leave a source of
gastrointestinal bleeding undetected because these procedures do not detect the
bleeding site or the lesion if small. Examples of these causes include coagulation
abnormalities induced by aspirin or platelet dysfunction, hookworm infestation,
hemangiomas of the small bowel, lymphosarcoma and other tumors, adenomas of
the gallbladder, and self-administration of anticoagulants.
• Bone marrow aspirates and biopsy findings are particularly useful in establishing
the etiology of anemia in patients with decreased production of RBCs. They help
differentiate aplasia; megaloblastic hyperplasia; and infiltration of marrow with
neoplasia, myelodysplasia, and myelofibrosis. In addition, they lead to a definitive
histologic diagnosis of leukemias, lymphomas, myelomas, and metastatic
carcinomas. These procedures are less useful in detecting hemolytic anemia
(except to detect lymphoma or leukemia), and they are less useful in diagnosing
congenital dyserythropoietic anemia, in which they reveal the multinuclearity of
erythroid precursors. Iron stains of the bone marrow aspirate can be used to
document the existence of iron deficiency anemia or the sideroblastic anemias.
Bone Marrow
• Decreased serum ferritin - this is the earliest indicator of iron depletion, usually
corresponding to marrow iron stores. This might be normal in the presence of
accompanying chronic disease, liver disease, or malignant neoplasm.11
• Increased iron binding capacity - this occurs only after storage iron is completely
depleted. The iron binding capacity is a measure of serum transferrin.
• Decreased serum iron and transferrin saturation (<16% early, <10% late)
Bone Marrow
• Gluten enteropathy
• Lymphoma
• Amyloidosis
• Scleroderma
• Whipple's disease
• Decreased sideroblasts
ANAEMIA OF HYPOMETABOLISM
top
LABORATORY FINDINGS
HEREDITARY SPHEROCYTOSIS
top
LABORATORY FINDINGS
Peripheral Blood
• Normoblastic hyperplasia
GLUCOSE-6-PHOSPHATE
DEHYDROGENASE DEFICIENCY
top
LABORATORY FINDINGS
Diagnostic Laboatory Tests
No Haematologic Findings in the Absence of haemolysis
Haematologic Findings in the Prescence of Haemolysis
Phase 1
Phase 2
Phase 3
•
Πψρυϖατε κινασε δεφιχιενχψ αν αυτοσοµαλ
ρεχεσσιϖε δισορδερ χαυσινγ πολψχηροµασια,
ανισοχψτοσισ, ποικιλοχψτοσισ ωιτη βυρρ χελλσ ανδ
αχαντηοχψτεσ, ανδ ΝΡΒΧσ.
Ρεδυχεδ ΑΤΠ φορµατιον χαυσεσ ΡΒΧ µεµβρανε
ριγιδιτψ, ρεσυλτινγ ιν ηεµολψσισ. Σψµπτοµσ αρε
υσυαλλψ µιλδ ασ ινχρεασεδ 2,3−∆ΠΓ χαυσεσ α ριγητ
σηιφτ οφ τηε 02−δισσοχιατιον χυρϖε.
Περσονσ ηοµοζψγοτε φορ ΠΚ δεφιχιενχψ σηοω σεϖερε
ανεµια ανδ αρε υσυαλλψ δισχοϖερεδ ιν χηιλδηοοδ.
Σπλενοµεγαλψ, χηολελιτηιασισ ανδ ϕαυνδιχε αρε
φρεθυεντ.ΠΡΙςΑΤΕ
∀ΤΨΠΕ=ΠΙΧΤ;ΑΛΤ=∀0100090000034χ00000003001χ000
00000000400000003010600050000000χ025α1δδφ1707000
000φχ020000000000000000040000002δ01000008000000φ
α0200000000000000000000040000002δ0101001χ000000φ
β020χ00090000000000900100000000000202024δ53205361
6ε73205365726966000α0027008α0100000000φφφφφφφφ78
δ31300040000002δ010200030000000000
ΤΗΕ ΤΗΑΛΑΣΣΕΜΙΑΣ
ΗΨΠΕΡΛΙΝΚ ∴λ
∀τοπ∀0100090000034χ00000003001χ00000000000400000
003010600050000000χ029502110207000000φχ0200000000
00000000040000002δ01000008000000φα020000000000000
0000000040000002δ0101001χ000000φβ020χ000900000000
00900100000000000202024δ532053616ε732053657269660
00α0027008α0100000000φφφφφφφφ78δ31300040000002δ0
10200030000000000ΗΨΠΕΡΛΙΝΚ ∴λ
∀τοπ∀ΗΨΠΕΡΛΙΝΚ ∴λ ∀τοπ∀τοπ
∆εφινιτιον
Ηερεδιταρψ δισορδερσ χηαραχτεριζεδ βψ δεφεχτιϖε
προδυχτιον οφ ηεµογλοβιν, ωηιχη λεαδσ το ανεµια.
ΛΑΒΟΡΑΤΟΡΨ ΦΙΝ∆ΙΝΓΣ
Βετα−τηαλασσεµια Μινορ
Περιπηεραλ Βλοοδ
• Ταργετ χελλσ, πολψχηροµατοπηιλια, βασοπηιλιχ
στιππλινγ, οχχασιοναλ νυχλεατεδ ΡΒΧ, ανισοχψτοσισ,
ποικιλοχψτοσισ
• Σλιγητ ηψποχηροµιχ (ΜΧΗ 20 πγ−22πγ), µιχροχψτιχ
(ΜΧς 50 υµ3 − 70 υµ3) αναεµια (ηαεµογλοβιν 9 γ/δλ −
11 γ/δλ), ωιτη νορµαλ το ινχρεασεδ ΡΒΧ (>5.7
µιλλιον/υλ)
• Ινχρεασεδ ρετιχυλοχψτεσ (2% − 10%)
Βονε Μαρροω
• Σλιγητ νορµοβλαστιχ ηψπερπλασια; αβυνδαντ ιρον
δεποσιτσ
Οτηερ Λαβορατορψ Φινδινγσ
• Ελεχτροπηορεσισ σηοωσ ινχρεασεδ ΗβΑ2 (3.5% −
8%); ινχρεασεδ ΗβΦ (1% − 5%) ιν 50% οφ πατιεντσ;
ινχρεασεδ ΗβΑ2 ισ διαγνοστιχ
• ∆εχρεασεδ οσµοτιχ φραγιλιτψ; τηισ ηασ βεεν υσεδ ασ
α ραπιδ σχρεενινγ τεστ
• Νορµαλ το ινχρεασεδ σερυµ ιρον; νορµαλ σερυµ
φερριτιν
Image 1b
Βετα−τηαλασσεµια Μαϕορ
Περιπηεραλ Βλοοδ
• Μαρκεδ ανισοχψτοσισ, ποικιλοχψτοσισ, ταργετ
χελλσ (10% − 35%), σπηεροχψτεσ, φραγµεντεδ ΡΒΧ;
οχχασιοναλ νυχλεατεδ ΡΒΧ, βασοπηιλιχ στιππλινγ,
σιδεροχψτεσ; ινχλυσιον βοδιεσ ρεπρεσεντινγ
αγγρεγατεδ αλπηα χηαινσ
• Μαρκεδ ηψποχηροµιχ, µιχροχψτιχ αναεµια (Ηβ 2.5
γ/δλ − 6.5 γ/δλ)
• Ινχρεασεδ ρετιχυλοχψτεσ (4% − 10%) − τηισ ινχρεασε
ισ λοωερ τηαν τηατ ωηιχη νορµαλλψ οχχυρσ ωιτη
σεϖερε αναεµια ανδ ινδιχατεσ ιναδεθυατε µαρροω
ρεσπονσε
• Ινχρεασεδ ωηιτε βλοοδ χελλ (ΩΒΧ) χουντ (10,000/υλ −
25,000/υλ) ωιτη οχχασιοναλ ιµµατυρε γρανυλοχψτεσ
• Οχχασιοναλ τηροµβοχψτοπενια − ρεφλεχτσ εφφεχτ οφ
σεχονδαρψ ηψπερσπλενισµ
Βονε Μαρροω
• Μαρκεδ νορµοβλαστιχ ηψπερπλασια ωιτη ποορ
ηαεµογλοβινισατιον; βασοπηιλιχ στιππλινγ; αβυνδαντ
ιρον δεποσιτσ; ΡΒΧ χψτοπλασµιχ ινχλυσιονσ, ωηιχη
αρε φρεε αλπηα χηαινσ; χλινιχαλ σεϖεριτψ
χορρελατεσ ωιτη αµουντ οφ αλπηα−χηαιν
πρεχιπιτατιον
Οτηερ Λαβορατορψ Φινδινγσ
• Ελεχτροπηορεσισ σηοωσ ΗβΦ 10% − 100% δεχρεασεδ
ορ αβσεντ ΗβΑ; ΗβΑ2 1% − 8%
• ∆εχρεασεδ οσµοτιχ φραγιλιτψ
• Φινδινγσ οφ ηαεµολψσισ − ινχρεασεδ υνχονϕυγατεδ
βιλιρυβιν, ινχρεασεδ Λ∆Η, δεχρεασεδ ηαπτογλοβιν
• Ινχρεασεδ σερυµ ιρον ανδ τρανσφερριν σατυρατιον
• ∆εχρεασεδ σερυµ φολατε − ρεφλεχτσ ινχρεασεδ
µαρροω υτιλισατιον οφ φολατε
ΗΨΠΕΡΛΙΝΚ
∀ηττπ://ωωω.βλοοδλινε.νετ/στοριεσ/στορψΡεαδερ∃2344
∀Τηαλασσεµια Ιµαγε Σεριεσ(Λινκ το Ιµαγε
σουρχε)ΒΛΟΟ∆ΛΙΝΕ
Haemoglobin H (Link to image source)The blood film
shows hypchromia, microcytosis, and target
cells. HbH disease is due to deletion of three out
of four alpha globin genes, resulting in an
anaemia which varies from mild to severe.
SICKLE-CELL DISEASE
top
Sickle cell disease is an inherited blood
disorder in which there is a substitutive defect in
the formation of hemoglobin in the red blood
cells, producing a distinctive disease process.
This disease was first scientifically recorded in
1910 by Dr. James Herrick. While examining the
blood of a young West Indian student, he
observed that many of the red blood cells were
elongated with a curved shape instead of the
normal round configuration. It was after similar
repeated observations by other investigators
that the descriptive term "sickle cell anemia"
was used to describe this disease.
ΠΡΙςΑΤΕ
∀ΤΨΠΕ=ΠΙΧΤ;ΑΛΤ=∀0100090000034χ00000003001χ000
00000000400000003010600050000000χ0254104117070000
00φχ020000000000000000040000002δ01000008000000φα0
200000000000000000000040000002δ0101001χ000000φβ02
0χ00090000000000900100000000000202024δ532053616ε7
3205365726966000α0027008α0100000000φφφφφφφφ78δ31
300040000002δ010200030000000000
Ωελχοµε το τηε ΗΨΠΕΡΛΙΝΚ
∀ηττπ://ωωω.δεπτ.µεδ.υµν.εδυ/µεδιχινε/Χλινιχαλ_σερϖι
χεσ/Σιχκλε_Χελλ_∆ισεασε_Προγραµ/βοδψ_σιχκλε_χελ
λ_δισεασε_προγραµ.ητµλ∀Σιχκλε Χελλ ∆ισεασε
Προγραµ οφ τηε Υνιϖερσιτψ οφ Μιννεσοτα Ηεαλτη
Σψστεµ (ΥΜΗΣ).
ΛΑΒΟΡΑΤΟΡΨ ΦΙΝ∆ΙΝΓΣ
Σιχκλε Χελλ Τραιτ (ΗβΑΣ ∆ισεασε)
• Νορµαλ περιπηεραλ σµεαρ ανδ βονε µαρροω
• Νο αναεµια
• Ποσιτιϖε σιχκλε χελλ τεστ − ωηεν µορε τηαν
25% ΗβΣ ισ πρεσεντ, σιχκλινγ οφ ΡΒΧ µαψ βε
δεµονστρατεδ ιν α βλοοδ συσπενσιον βψ δεοξψγενατιον
οφ τηε βλοοδ
• Ποσιτιϖε σολυβιλιτψ τεστ φορ ΗβΣ − σιχκλε
τεστ Ηβ ισ ινσολυβλε ιν α πηοσπηατε βυφφερ σολυτιον
• Ηβ ελεχτροπηορεσισ − ΗβΑ 70% − 80%; ΗβΣ 30%
− 40%; ΗβΦ <2%. Πρεπονδερανχε οφ ΗβΑ οϖερ ΗβΣ ισ
α πρερεθυισιτε φορ τηισ διαγνοσισ. (Τηε ρεϖερσε
οχχυρσ ιν σιχκλε χελλ βετα−τηαλασσεµια)
• Λοω φιξεδ υρινε σπεχιφιχ γραϖιτψ ανδ
ηαεµατυρια οχχυρ ασ α ρεσυλτ οφ ρεναλ µεδυλλαρψ
µιχροινφαρχτσ.
Σιχκλε Χελλ Αναεµια (ΗβΣΣ ∆ισεασε)
Περιπηεραλ Βλοοδ
• Σιχκλε χελλσ, οϖαλοχψτεσ, µαρκεδ
ποικιλοχψτοσισ, ανισοχψτοσισ, νυχλεατεδ ΡΒΧ,
Ηοωελλ−ϑολλψ βοδιεσ, ταργετ χελλσ, σπηεροχψτεσ,
πολψχηροµατοπηιλια, στιππλεδ ΡΒΧ, σιδεροχψτεσ.
Τηεσε αβνορµαλ χελλσ αππεαρ ιν τηε χιρχυλατιον
βεχαυσε τηε ινφαρχτεδ σπλεεν ισ νο λονγερ αβλε το
ρεµοϖε τηεµ φροµ τηε χιρχυλατιον.
• Νορµοχψτιχ, νορµοχηροµιχ αναεµια (Ηβ 5 γ/δλ −
11 γ/δλ)
• Ινχρεασεδ ρετιχυλοχψτεσ (5% − 30%) −
δεχρεασεδ δυρινγ απλαστιχ χρισισ
• Ινχρεασεδ ΩΒΧ ωιτη λεφτ σηιφτ (10,000/υλ −
30,000/υλ) − δοεσ νοτ νεχεσσαριλψ σιγνιφψ αν
ινφεχτιον
• Ινχρεασεδ πλατελετσ (300,000/υλ − 500,000/υλ−
µαψ φαλλ δυρινγ αν ινφαρχτιϖε χρισισ
Βονε Μαρροω
• Ηψπερπλασια οφ αλλ ελεµεντσ βυτ εσπεχιαλλψ
οφ ΡΒΧ πρεχυρσορσ
• Ινχρεασεδ ιρον δεποσιτσ
Οτηερ Λαβορατορψ Φινδινγσ
• Ποσιτιϖε σιχκλε χελλ τεστ − ΡΒΧ τρανσφορµ το
σιχκλεδ φορµ ιν αν οξψγεν−ποορ ενϖιρονµεντ
• Ποσιτιϖε σολυβιλιτψ τεστ φορ ΗβΣ − σιχκλε
χελλ Ηβ ισ ινσολυβλε ιν α πηοσπηατε βυφφερ σολυτιον
ΗΑΕΜΟΓΛΟΒΙΝ Χ ∆ΙΣΕΑΣΕ
Haemoglobin C disease (link to image source)
Glutamine in the 6th position of the beta globin chain is replaced by lysine. In the
homozygous state (HbC disease), mild anaemia and splenomegaly is present. The
condition is found in Africa and the Middle East.
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LABORATORY FINDINGS
HbAC Trait
Bone Marrow
• Normoblastic hyperplasia