ANEMIA
Anemia : is usually defined as a decrease in amount of
(RBCs) or the amount
of hemoglobin in the blood .It can also be defined as a lowered ability of the blood to
carry oxygen.
Types of anemia :
The most common types of anaemia are:
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Iron deficiency anaemia.
Aplastic anaemia.
Haemolytic anaemia.
Sickle cell anaemia.
Pernicious anaemia.
Fanconi anaemia.
Symptoms and signs :Symptoms related to anemia can result from two factors:
decreased oxygen delivery to tissues, and, in patients with acute and marked bleeding, the
added insult of hypovolemia. There is some reduction in blood volume but not plasma volume
after acute severe hemolysis, due to the fall in RBC mass. In comparison, total blood volume
remains normal in anemia due to chronic, low-grade bleeding, since there is ample time for
equilibration with the extravascular space and renal retention of salt and water.
Symptoms of impaired oxygen delivery reflect the fall in hemoglobin concentration. The
extraction of oxygen by the tissues can increase from a baseline of 25 percent to a maximum
of about 60 percent in the presence of anemia or hypoperfusion. Thus, normal oxygen
delivery of 5 volumes percent can be maintained by enhanced extraction alone down to a
hemoglobin concentration of 8 to 9 g/dL.
When the added compensation of increases in stroke volume and heart rate (and therefore
cardiac output) are included, oxygen delivery can be maintained at rest at a hemoglobin
concentration as low as 5 g/dL (equivalent to a hematocrit of 15 percent), assuming that the
intravascular volume is maintained.
Symptoms will occur when the hemoglobin concentration falls below this level at rest, at
higher hemoglobin concentrations during exertion, or when cardiac compensation is impaired
because of underlying heart disease. The primary symptoms include exertional dyspnea,
dyspnea at rest, varying degrees of fatigue, and signs and symptoms of the hyperdynamic
state, such as bounding pulses, palpitations, and "roaring in the ears". More severe anemia
may lead to lethargy and confusion and potentially life-threatening complications such as
congestive failure, angina, arrhythmia, and/or myocardial infarction.
Anemia induced by acute bleeding is with the added complication of intracellular and
extracellular volume depletion. The earliest symptoms include easy fatigability, lassitude,
and . This can progress to postural dizziness, lethargy, syncope, and, in severe cases, to
persistent hypotension, shock, and death.
Causes of anemia: There are two general approaches one can use to help identify
the cause of anemia:
●A kinetic approach, addressing the mechanism(s) responsible for the fall in hemoglobin
concentration
●A morphologic approach categorizing anemias via alterations in RBC size (ie, mean
corpuscular volume) and the reticulocyte response .
Kinetic approach : Anemia can be caused by one or more of three independent
mechanisms: decreased RBC production, increased RBC destruction, and blood loss.
Decreased RBC production :Anemia will ultimately result if the rate of RBC production is
less than that of RBC destruction.
The more common causes for reduced (effective) RBC production include:
●Lack of nutrients, such as iron, B12, or folate. This can be due to dietary lack,
malabsorption (eg, pernicious anemia, sprue), or blood loss (iron deficiency).
●Bone marrow disorders (eg, aplastic anemia, pure RBC aplasia, myelodysplastic
syndromes, tumor infiltration)
●Bone marrow suppression (eg, drugs, chemotherapy, irradiation).
●Low levels of trophic hormones, which stimulate RBC production, such as EPO (eg,
chronic renal failure), thyroid hormone and androgens (eg, hypogonadism)
•A rare cause of anemia due to reduced EPO production has been described in
patients with autonomic dysfunction and orthostatic hypotension.
•Acquired inhibitors of EPO or the EPO receptor have also been described as
causes of anemia.
●The anemia of inflammation, associated with infectious, inflammatory, or malignant
disorders, is characterized by reduced availability of iron due to decreased absorption
from the gastrointestinal tract and decreased release from macrophages, a relative
reduction in erythropoietin levels, and a mild reduction in RBC lifespan.
Increased RBC destruction — A RBC life span below 100 days is the operational definition
of hemolysis.
Anemia will ensue when the bone marrow is unable to keep up with the need to replace more
than about 5 percent of the RBC mass per day, corresponding to a RBC survival of about 20
days.
Examples include:
●Inherited hemolytic anemias (eg, hereditary spherocytosis, sickle cell disease,
thalassemia major)
●Acquired hemolytic anemias (eg, Coombs'-positive autoimmune hemolytic anemia,
thrombotic thrombocytopenic purpura, malaria, paroxysmal nocturnal hemoglobinuria)
Blood loss — Iron deficiency in the United States and Western Europe is almost always due
to blood loss, which may be obvious, occult, or underappreciated, as follows:
●Obvious bleeding (eg, trauma, melena, hematemesis, severe menometrorrhagia)
●Occult bleeding (eg, slowly bleeding ulcer or carcinoma).
●Induced bleeding (eg, repeated diagnostic testing , hemodialysis losses, excessive
blood .
●Underappreciated menstrual blood loss.
There are a number of situations in which blood loss can occur and not be easily recognized.
These include:
●Factitious bleeding, secondary to surreptitious blood drawing by the patient.
●Bleeding during or after surgical procedures may be extremely difficult to quantitate,
and is often underestimated.
●Bleeding into the upper thigh and/or retroperitoneal space can often be significant, but
may not be clinically obvious. Such patients may, however, have associated symptoms
of abdominal pain or mass, groin or hip pain, leg paresis, or hypotension . This
complication may be more common in patients taking anticoagulants, even when results
of coagulation tests are within the therapeutic range. CT imaging of the abdomen and
thigh is often helpful if this is suspected.
In addition to the loss of RBCs from the body, which the bone marrow must replace, loss of
the iron contained in these cells will ultimately lead to iron deficiency, once tissue stores of
iron have been depleted. This usually occurs in males and females after losses of ≥1200 mL
and ≥600 mL, respectively. However, since approximately 25 percent of menstruant females
have absent iron stores, any amount of bleeding will result in anemia in this subpopulation.
So causes of anemia in general:
Basically, only three causes of anemia exist: blood loss, increased RBC destruction
(hemolysis), and decreased production of RBCs. Each of these causes includes a number of
etiologies that require specific and appropriate therapy.
Genetic etiologies include the following:
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Hemoglobinopathies
Thalassemias
Enzyme abnormalities of the glycolytic pathways
Defects of the RBC cytoskeleton
Congenital dyserythropoietic anemia
Rh null disease
Hereditary xerocytosis
Abetalipoproteinemia
Fanconi anemia
Nutritional etiologies include the following:
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Iron deficiency
Vitamin B-12 deficiency
Folate deficiency
Starvation and generalized malnutrition
Physical etiologies include the following:
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Trauma
Burns
Frostbite
Prosthetic valves and surfaces
Chronic disease and malignant etiologies include the following:
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Renal disease
Hepatic disease
Chronic infections
Neoplasia
Collagen vascular diseases
Infectious etiologies include the following:
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Viral - Hepatitis, infectious mononucleosis, cytomegalovirus
Bacterial - Clostridia, gram-negative sepsis
Protozoal - Malaria, leishmaniasis, toxoplasmosis.
Laboratory findings:
Initial testing of the anemic patient should include a complete blood count (CBC) and white
blood cell (WBC) count. A WBC differential, platelet count, and reticulocyte count are not part
of the routine CBC in some medical centers; these may have to be or dered separately. Thus,
to avoid confusion, the clinician should specifically request a CBC with platelets, WBC
differential, and reticulocytes.
The normal CBC :
Laboratory test.
Normal value .
RBC(million/mm3)
Hb(g/dL)
Hct(%)
MCV(Fl)
MCH(pg/cell)
MCHC(g/dl)
)%(Red cell distribution
Reticuocyte count(%)
Fe
Vitsmin B12
Folate (folic acid)
RBC Folate
Transferrin
TIBC
Transferrin saturation
(Fe/TIBC%)
Adult male:5.4+-0.7 adult female:4.8+- 6
Adult male:16+-2
adult female: 14+-2
Adult male:47+-5
adult female: 42+-2
80-100
26-34
31-37
11-16
0.5-1.5
Adult male:50-160 adult female:40-150
>200
7-25
140-960
170-370
250-400
20-50
Ferritin
Erythropoietin
Adult male:15-200 adult female:12-150
4-26
Treatment of anemia :
Treatment for anemia depends on the type, cause, and severity of the condition.
Treatments may include dietary changes or supplements, medicines, procedures, or
surgery to treat blood loss.
Goals of Treatment:
-The goal of treatment is to increase the amount of oxygen that your blood can carry. This
is done by raising the red blood cell count and/or hemoglobin level. (Hemoglobin is the
iron-rich protein in red blood cells that carries oxygen to the body.)
-Another goal is to treat the underlying cause of the anemia.
Dietary Changes and Supplements:
Low levels of vitamins or iron in the body can cause some types of anemia. These low
levels might be the result of a poor diet or certain diseases or conditions.
Iron:
Your body needs iron to make hemoglobin. Your body can more easily absorb iron from
meats than from vegetables or other foods.
Vitamin B12:
Low levels of vitamin B12 can lead to pernicious anemia. This type of anemia often is
treated with vitamin B12 supplements.
Good food sources of vitamin B12 include:
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Breakfast cereals with added vitamin B12
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Meats such as beef, liver, poultry, and fish
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Eggs and dairy products (such as milk, yogurt, and cheese)
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Foods fortified with vitamin B12, such as soy-based beverages and vegetarian
burgers.
Folic Acid: Folic acid (folate) is a form of vitamin B that's found in foods. Your body
needs folic acid to make and maintain new cells. Folic acid also is very important for
pregnant women. It helps them avoid anemia and promotes healthy growth of the fetus.
Vitamin C: Vitamin C helps the body absorb iron. Good sources of vitamin C are
vegetables and fruits, especially citrus fruits. Citrus fruits include oranges, grapefruits,
tangerines, and similar fruits. Fresh and frozen fruits, vegetables, and juices usually have
more vitamin C than canned ones.
Erythropoietin : A man-made version of erythropoietin to stimulate your body to make
more red blood cells. Its usually used to treat anemia caused by chemotherapy and
anemia of chronic diseases(END STAGE RENAL FALIURE).
Treatment of anemia must be individualized and according to the
causative agent.
1-Iron deficiency anemia :
It is a common anemia (low red blood cell or hemoglobin levels) caused by insufficient
dietary intake and absorption of iron, and/or iron loss from bleeding which can originate
from a range of sources such as the intestinal, uterine or urinary tract.
Treatment :
Oral iron therapy : Because oral iron is inexpensive and effective when taken as prescribed,
it is considered front line therapy.
There are numerous conditions, however, for which oral iron is either poorly tolerated
or ineffective:
Gastrointestinal side effects are extremely common and may result in poor adherence to
therapy.
•Various malabsorptive states (eg, celiac disease, Whipple's disease, bacterial overgrowth
syndromes) may be associated with an inability to absorb iron optimally.
•Treatment with oral iron may take as long as six to eight weeks in order to fully ameliorate
the anemia, and as long as six months in order to replete iron stores.
•In patients with inflammatory bowel disease, the use of oral iron has been associated with
worsening of the underlying disease, and may be poorly tolerated and ineffective
•In conditions such as heavy uterine bleeding, hereditary hemorrhagic telangiectasia, , or
other causes of heavy blood loss, absorption of oral iron, even in maximal doses, may be
unable to keep up with blood loss.
•Dialysis patients, especially those being treated with erythropoiesis-stimulating agents
(ESAs), are unable to fully utilize iron administered orally
•Non-dialysis chronic patients have a number of reasons for their inability to absorb oral iron
(eg, impaired iron transport, concomitant use of calcium-containing salts, H2 blockers,
phosphate binders, generalized malabsorption
•Oral iron, unlike the intravenous preparations, does not synergize well with ESAs (eg,
erythropoietin, darbepoetin) in anemic cancer patients both on and off chemotherapy
•Inflammation-mediated induction of hepcidin, which regulates iron homeostasis, may result in
suboptimal gastrointestinal absorption of orally administered iron in iron deficient subjects
.Non-response to oral iron therapy does not rule out iron deficiency in such subjects, since
two-thirds of the non-responders to oral iron in one study responded to treatment with
intravenous iron
•Over a quarter of the world's population remains anemic; about half of this burden is due to
iron deficiency anemia (IDA). Strategies to control IDA include daily and intermittent iron
supplementation, home fortification with micronutrient powders, fortification of staple foods
and condiments, and activities to improve food security and dietary diversity .The safety of
routine iron supplementation in settings where infectious diseases such as malaria are
endemic remains uncertain.
Parenteral iron :Clinicians' historical reluctance to use parenteral iron preparations more
widely can be traced, at least in part, to severe side effects (eg, anaphylaxis, shock, death)
associated with earlier parenteral iron preparations, such as high molecular weight iron
dextran. However there are numerous settings in which the use of intravenous iron
preparations may be preferable. As examples:
•With the advent of parenteral iron formulations with improved toxicity profiles, the early
switch to intravenous iron should be considered in those intolerant to the use of oral iron
preparations.
•It has been estimated that the maximum amount of elemental iron that can be absorbed with
an oral iron preparation is 25 mg/day ,whereas, depending upon the preparation used, up to
1000 mg of elemental iron can be administered following a single infusion of intravenous iron.
•Intravenous iron is effective for those unresponsive to or intolerant of oral iron. Published
evidence supports the consideration of intravenous iron as an early for those with
inflammatory bowel disease (IBD) . As a result, intravenous iron is considered frontline
therapy in Europe for iron deficiency anemia associated with IBD with or without oral iron
intolerance or ineffectiveness .For patients with chemotherapy induced anemia, NCCN
Guidelines state that intravenous iron is the preferred route when iron supplementation is
indicated, and K/DOQI guidelines indicate its use for iron replacement in dialysis patients.
•Intravenous iron is required when the amount of iron lost through daily blood loss exceeds
the capacity of the gastrointestinal tract to absorb oral iron preparations.
•For those who have undergone and/or subtotal gastric resection, the limited ability of the
remaining stomach to provide acid to protect ferric iron from being converted to an insoluble
form, and for facilitating intestinal absorption of ferric as well as ferrous iron, makes
intravenous iron an especially good choice. Some patients, especially those having
undergone minimally invasive procedures, such as gastric banding, may tolerate oral iron.
This is less likely in Roux-en-Y or biliopancreatic diversion procedures. However, it is
important to remember that all patients have a host of other nutritional perturbations postoperatively, and intravenous iron may simplify care.
Blood transfusion:Blood transfusion should be reserved for the patient who is
hemodynamically unstable because of active bleeding and/or shows evidence for end-organ
ischemia.
Choice of preparation :The most appropriate oral iron therapy is use of a tablet containing
ferrous salts, such as:
●Ferrous fumarate : 106 mg elemental iron/tablet
●Ferrous sulfate :65 mg elemental iron/tablet
●Ferrous gluconate : 28 to 36 mg iron/tablet
The recommended oral daily dose for the treatment of iron deficiency in adults is in the range
of 150 to 200 mg/day of elemental iron. As an example, a single 325 mgferrous sulfate tablet
taken orally three times daily between meals provides an oral dose of 195 mg of elemental
iron per day. There is no evidence that one of the above iron preparations is more effective
than another for this purpose.
A large number of other oral iron preparations are available. They are generally more
expensive than those described above and some may be poorly absorbed
(eg, enteric coated, sustained release preparations).
Dosing in older adults : Appropriate dosing of iron for older adults with iron deficiency
anemia is unclear. In a randomized study in 90 iron deficient hospitalized patients >80 years
of age, daily doses of 15, 50, or 150 mg of elemental iron for two months were equally
effective in raising hemoglobin and ferritin concentrations, while adverse side effects were
significantly more common at the higher iron doses .
In our practice we treat iron deficiency in older adults by using 10 mL of iron sulfate elixir once
daily (elemental iron content 88 mg) mixed in one-fifth of a glass of orange juice and taken 30
minutes before . The dose of elixir can be reduced to 5 mL if the 10 mL dose causes irritation.
Similarly, a 50 or 100 mg tablet of ascorbic acid can be substituted for the orange juice.
2-Megloblastic anemia:
Its due to deficiencies in vitamin B12 or folate or the intrinsic factor or any drug
interfere with DNA synthesis .if the anemia is due to absence of intrinsic factor so is
called ( pernicious anemia).
Treatment :
With vitamin B12 and folic acid.
Vitamin B12:
Vitamin B12 deficiency:
Intranasal (Nascobal): 500 mcg in one nostril once weekly
Oral: 1000-2000 mcg daily for 1-2 weeks; maintenance: 1000 mcg daily .
IM, deep SubQ: May use initial treatment similar to that for pernicious anemia
depending on severity of deficiency: 100 mcg daily for 6-7 days; if improvement,
administer same dose on alternate days for 7 doses, then every 3-4 days for 2-3 weeks;
once hematologic values have returned to normal, maintenance dosage: 100 mcg
monthly.
Pernicious anemia: IM, deep SubQ (administer concomitantly with folic acid if needed, 1 mg
daily for 1 month): 100 mcg daily for 6-7 days; if improvement, administer same dose on
alternate days for 7 doses, then every 3-4 days for 2-3 weeks; once hematologic values
have returned to normal, maintenance dosage: 100 mcg monthly.
Folic acid:
Anemia: Oral, IM, IV, SubQ: 0.4 mg/day
Pregnant and lactating women: 0.8 mg/day
3-Aplastic anemia:
It is a disease in which the bone marrow, and the blood stem cells that reside there,
are damaged This causes a deficiency of all three blood cell types (pancytopenia): red
blood cells (anemia), white blood cells (leukopenia),
andplatelets (thrombocytopenia). Aplastic refers to inability of the stem cells to
generate the mature blood cells.
It is most prevalent in people in their teens and twenties, but is also common among the elderly. It
can be caused by exposure to chemicals, drugs, radiation, infection, immune disease, and heredity;
in about half the cases, the cause is unknown.
The definitive diagnosis is by bone marrow biopsy; normal bone marrow has 30-70% blood stem
cells, but in aplastic anemia, these cells are mostly gone and replaced by fat.
First line treatment for aplastic anemia consists of immunosuppressive drugs, typically either antilymphocyte globulin or anti-thymocyte globulin, combined
with corticosteroids and cyclosporine. Hematopoietic stem cell transplantation is also used,
especially for patients under 30 years of age with a related, matched marrow donor.
Treatment:
Severe or very severe aplastic anemia is a hematologic emergency, and care should be
instituted promptly. Clinicians must stress the need for patient compliance with therapy. The
specific medications administered depend on the choice of therapy and whether it is
supportive care only, immunosuppressive therapy, or hematopoietic cell transplantation.
Pharmacotherapy:
The following medications are used in patients with aplastic anemia:
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Immunosuppressive agents (eg, cyclosporine, methylprednisolone, equine antithymocyte
globulin, rabbit antithymocyte globulin, cyclophosphamide, alemtuzumab)
Hematopoietic growth factors (eg, eltrombopag, sargramostim, filgrastim)
Antimetabolite (purine) antineoplastic agents (eg, fludarabine)
Chelating agents (eg, deferoxamine, deferasirox)
Nonpharmacotherapy:
Nonpharmacologic management of aplastic anemia includes the following:
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Supportive care
Blood transfusions with blood products that have undergone leukocyte reduction and
irradiation.
Hematopoietic cell transplantation.
4-Hemolytic anemia( like thalasemia):
Hemolysis is the premature destruction of erythrocytes. A hemolytic anemia will develop if
bone marrow activity cannot compensate for the erythrocyte loss. The severity of the anemia
depends on whether the onset of hemolysis is gradual or abrupt and on the extent of
erythrocyte destruction. Mild hemolysis can be asymptomatic while the anemia in severe
hemolysis can be life threatening and cause angina and cardiopulmonary decompensation.
Treatment :
There are numerous types of hemolytic anemia, and treatment may differ depending on the
type of hemolysis. Only the general care of hemolytic anemias and the management of the
most commonly encountered hemolytic anemias are discussed. The diagnosis and treatment
of cold agglutinin hemolytic anemia has been reviewed.
Folic acid, corticosteroids, and IVIG:
-Prophylactic folic acid is indicated because active hemolysis can consume folate and cause
megaloblastosis.
-Corticosteroids are indicated in autoimmune hemolytic anemia.
-Intravenous immunoglobulin G (IVIG) has been used for patients with AIHA, but only a few
patients have responded to this treatment, and the responses have been transient.
One should avoid transfusions unless absolutely necessary. However, transfusions may be
essential for patients with angina or a severely compromised cardiopulmonary status. It is
best to administer packed red blood cells slowly to avoid cardiac stress.
In autoimmune hemolytic anemia (AIHA), typing and cross-matching may be difficult. One
should use the least incompatible blood if transfusions are indicated. The risk of destruction of
transfused blood is high, but the degree of the hemolysis depends on the rate of infusion.
Therefore, one should slowly transfuse half units of packed red blood cells to prevent rapid
destruction of transfused blood.
Iron overload due to multiple transfusions for chronic anemia (eg, thalassemia or sickle cell
disorder) can be treated with chelation therapy. A systematic review that compared the oral
iron chelator deferasirox with the oral chelator deferiprone and the traditional parenteral agent
deferoxamine found little clinical difference between the 3 chelation agents in terms of
removing iron from the blood and liver.
5-Anemia of chronic disease(renal disease and IBD):
Its is a form of anemia seen in chronic infection, chronic immune activation, and
malignancy. These conditions all produce massive elevation of Interleukin-6, which
stimulates hepcidin production and release from the liver, which in turn reduces the iron
carrier protein ferroportin so that access of iron to the circulation is reduced. Other
mechanisms may also play a role, such as reduced erythropoiesis.
Anemia usually is grouped into three etiologic categories: decreased RBC production,
increased RBC destruction, and blood loss. Anemia of chronic illness and anemia of
chronic (CKD) both fall under the category of decreased RBC production. When the
classification of anemia is based on the morphology of the RBCs, both anemia of chronic
illness and chronic kidney disease usually fall under the classification of normochromic,
normocytic anemia.
Treatment:
In general, patients with anemia of chronic illness or chronic kidney disease can be treated on
an outpatient basis. Confounding factors that need to be addressed in both diseases include
concomitant blood loss, iron deficiency, or deficiencies of vitamin B12 and/or folic acid.
The preferred initial form of therapy for anemia of chronic illness is treatment of the underlying
disease. Use of erythropoiesis-stimulating agents (ESAs) and blood transfusion are reserved
for severe and symptomatic cases. Administration of ESAs is usually best done under the
auspices of a hematologist or nephrologist, who may be more adept regarding the latest
guidelines on the uses of such agents, as well as for insurance policy coverages.
6-Fanconi anemia:
FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair.
As a result, the majority of FA patients develop cancer, most often acute myelogenous
leukemia, and 90% develop bone marrow failure (the inability to produce blood cells)
by age 40.
Treatment :
The first line of therapy is androgens and hematopoietic growth factors
. Treatment is recommended for significant cytopenias, such as hemoglobin less than 8 g/dL,
platelets fewer than 30,000/µL, or neutrophils fewer than 500/µL. Patients should be referred
to centers with experience in the care of patients with Fanconi anemia as new information is
likely to change the treatment approach.
7-Sickle cell anemia:
It is a hereditary blood disorder, characterized by an abnormality in the oxygencarrying haemoglobin molecule in red blood cells that leads to a propensity for the cells
to assume an abnormal, rigid, sickle-like shape under certain circumstances. Sickle-cell
disease is associated with a number of acute and chronic health problems, such as
severe infections and attacks of severe pain.
Treatment of the whole disease with different agents .