ANEMIA

Anemia (pronounced /əˈniːmiə/, also spelled anaemia or anæmia; from Ancient

Greek ἀναιμία anaimia, meaning "lack of blood") is a decrease in normal number
of red blood cells (RBCs) or less than the normal quantity of hemoglobin in the
blood.[1][2] However, it can include decreased oxygen-binding ability of each
hemoglobin molecule due to deformity or lack in numerical development as in
some other types of hemoglobin deficiency.

Since hemoglobin (found inside RBCs) 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: the "kinetic" approach which involves evaluating
production, destruction and loss[3], 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.

Signs and symptoms

Anemia goes undetected in many people, and symptoms can be minor or vague.
The signs and symptoms can be related to the anemia itself, or the underlying
cause.

Most commonly, people with anemia report non-specific symptoms of a feeling of

weakness, or fatigue, general malaise and sometimes poor concentration. They
may also report shortness of breath, dyspnea, on exertion. In very severe anemia,
the body may compensate for the lack of oxygen carrying capability of the blood
by increasing cardiac output. The patient may have symptoms related to this, such
as palpitations, angina (if preexisting heart disease is present), intermittent
claudication of the legs, and symptoms of heart failure.

On examination, the signs exhibited may include pallor (pale skin, mucosal linings
and nail beds) but this is not a reliable sign. There may be signs of specific causes
of anemia, e.g., koilonychia (in iron deficiency), jaundice (when anemia results
from abnormal break down of red blood cells — in hemolytic anemia), bone
deformities (found in thalassaemia major) or leg ulcers (seen in sickle cell disease).

In severe anemia, there may be signs of a hyperdynamic circulation: a fast heart

rate (tachycardia), flow murmurs, and cardiac enlargement. There may be signs of
heart failure.

Pica, the consumption of non-food based items 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.

Restless legs syndrome is more common in those with iron deficiency anemia.

Less common symptoms may include swelling of the legs or arms, chronic
heartburn, vague bruises, vomiting, increased sweating, and blood in stool.

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.

WHO's Hemoglobin thresholds used to define anemia[5] (1 g/dL =

0.6206 mmol/L)[citation needed]

Age or gender group Hb threshold (g/dl) Hb threshold (mmol/l)

Children (0.5–5.0 yrs) 11.0 6.8

Children (5–12 yrs) 11.5 7.1

Children (12–15 yrs) 12.0 7.4

Women, non-pregnant (>15yrs) 12.0 7.4

Women, pregnant 11.0 6.8

Men (>15yrs) 13.0 8.1

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.

Classification
Production vs. destruction or loss

The "kinetic" approach to anemia yields what many argue is the most clinically
relevant classification of anemia. This classification depends on evaluation of
several hematological parameters, particularly the blood reticulocyte (precursor of
mature RBCs) count. This then yields the classification of defects by decreased
RBC production versus increased RBC destruction and/or loss. Clinical signs of
loss or destruction include abnormal peripheral blood smear with signs of
hemolysis; elevated LDH suggesting cell destruction; or clinical signs of bleeding,
such as guiaic-positive stool, radiographic findings, or frank bleeding.
The following is a simplified schematic of this approach:

Anemia

Reticulocyte production
Reticulocyte
index shows appropriate
production index
response to anemia =
shows inadequate
ongoing hemolysis or
production response
blood loss without RBC
to anemia.
production problem.

No clinical Clinical findings and

findings Clinical findings normal MCV= acute
consistent with and abnormal MCV: hemolysis or loss
hemolysis or hemolysis or loss without adequate
blood loss: pure and chronic disorder time for bone marrow
disorder of of production*. production to
production. compensate**.

Macrocytic
Normocytic anemia Microcytic anemia
anemia
(80<MCV<100) (MCV<80)
(MCV>100)

* For instance, sickle cell anemia with superimposed iron deficiency; chronic
gastric bleeding with B12 and folate deficiency; and other instances of anemia
with more than one cause.
** Confirm by repeating reticulocyte count: ongoing combination of low
reticulocyte production index, normal MCV and hemolysis or loss may be seen in
bone marrow failure or anemia of chronic disease, with superimposed or related
hemolysis or blood loss.
Red blood cell size
In the morphological approach, anemia is classified by the size of red blood cells;
this is either done automatically or on microscopic examination of a peripheral
blood smear. The size is reflected in the mean corpuscular volume (MCV). If the
cells are smaller than normal (under 80 fl), the anemia is said to be microcytic; if
they are normal size (80–100 fl), normocytic; and if they are larger than normal
(over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes
some of the most common causes of anemia; for instance, a microcytic anemia is
often the result of iron deficiency. In clinical workup, the MCV will be one of the
first pieces of information available; so even among clinicians who consider the
"kinetic" approach more useful philosophically, morphology will remain an
important element of classification and diagnosis.

Here is a schematic representation of how to consider anemia with MCV as the

starting point:

Anemia

Macrocytic Microcytic Normocytic

anemia anemia anemia
(MCV>100) (MCV<80) (80<MCV<100)

High Low
reticulocyte reticulocyte
count count

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.
Microcytic anemia
Microcytic anemia is primarily a result of hemoglobin synthesis
failure/insufficiency, which could be caused by several etiologies:

 Heme synthesis defect

o Iron deficiency anemia
o Anemia of chronic disease (more commonly presenting as normocytic
anemia)
 Globin synthesis defect
o alpha-, and beta-thalassemia
o HbE syndrome
o HbC syndrome
o and various other unstable hemoglobin diseases
 Sideroblastic defect
o Hereditary sideroblastic anemia
o Acquired sideroblastic anemia, including lead toxicity
o Reversible sideroblastic anemia

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.

 Iron deficiency anemia is caused by insufficient dietary intake or absorption

of iron to replace losses from menstruation or losses due to diseases. [6] Iron
is an essential part of hemoglobin, and low iron levels result in decreased
incorporation of hemoglobin into red blood cells. In the United States, 20%
of all women of childbearing age have iron deficiency anemia, compared
with only 2% of adult men. The principal cause of iron deficiency anemia in
premenopausal women is blood lost during menses. Studies[who?] have shown
that iron deficiency without anemia causes poor school performance and
lower IQ in teenage girls. Iron deficiency is the most prevalent deficiency
state on a worldwide basis. Iron deficiency is sometimes the cause of
abnormal fissuring of the angular (corner) sections of the lips (angular
stomatitis).
 Iron deficiency anemia can also be due to bleeding lesions of the
gastrointestinal tract. Faecal occult blood testing, upper endoscopy and
lower endoscopy should be performed to identify bleeding lesions. In men
 and post-menopausal women the chances are higher that bleeding from the
gastrointestinal tract could be due to colon polyp or colorectal cancer.
 Worldwide, the most common cause of iron deficiency anemia is parasitic
infestation (hookworm, amebiasis, schistosomiasis and whipworm).[7]

Macrocytic anemia
 Megaloblastic anemia, the most common cause of macrocytic anemia, is due
to a deficiency of either vitamin B12, folic acid (or both). Deficiency in
folate and/or vitamin B12 can be due either to inadequate intake or
insufficient absorption. Folate deficiency normally does not produce
neurological symptoms, while B12 deficiency does.
o Pernicious anemia is caused by a lack of intrinsic factor. Intrinsic
factor is required to absorb vitamin B12 from food. A lack of intrinsic
factor may arise from an autoimmune condition targeting the parietal
cells (atrophic gastritis) that produce intrinsic factor or against
intrinsic factor itself. These lead to poor absorption of vitamin B12.
o Macrocytic anemia can also be caused by removal of the functional
portion of the stomach, such as during gastric bypass surgery, leading
to reduced vit B12/folate absorption. Therefore one must always be
aware of anemia following this procedure.
 Hypothyroidism
 Alcoholism commonly causes a macrocytosis, although not specifically
anemia. Other types of Liver Disease can also cause macrocytosis.
 Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-

megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily
a failure of DNA synthesis with preserved RNA synthesis, which result in
restricted cell division of the progenitor cells. The megaloblastic anemias often
present with neutrophil hypersegmentation (6–10 lobes). The non-megaloblastic
macrocytic anemias have different etiologies (i.e. there is unimpaired DNA globin
synthesis,) which occur, for example in alcoholism.

In addition to the non-specific symptoms of anemia, specific features of vitamin

B12 deficiency include peripheral neuropathy and subacute combined degeneration
of the cord with resulting balance difficulties from posterior column spinal cord
pathology.[8] Other features may include a smooth, red tongue and glossitis.
The treatment for vitamin B12-deficient anemia was first devised by William
Murphy who bled dogs to make them anemic and then fed them various substances
to see what (if anything) would make them healthy again. He discovered that
ingesting large amounts of liver seemed to cure the disease. George Minot and
George Whipple then set about to chemically isolate the curative substance and
ultimately were able to isolate the vitamin B12 from the liver. All three shared the
1934 Nobel Prize in Medicine.[9]

Normocytic anemia
Normocytic anemia occurs when the overall hemoglobin levels are always
decreased, but the red blood cell size (Mean corpuscular volume) remains normal.
Causes include:

 Acute blood loss

 Anemia of chronic disease
 Aplastic anemia (bone marrow failure)
 Hemolytic anemia

Dimorphic anemia
When two causes of anemia act simultaneously, e.g., macrocytic hypochromic, due
to hookworm infestation leading to deficiency of both iron and vitamin B12 or
folic acid [10] or following a blood transfusion more than one abnormality of red
cell indices may be seen. Evidence for multiple causes appears with an elevated
RBC distribution width (RDW), which suggests a wider-than-normal range of red
cell sizes.

Heinz body anemia

Heinz bodies form in the cytoplasm of RBCs and appear like small dark dots under
the microscope. There are many causes of Heinz body anemia, and some forms can
be drug induced. It is triggered in cats by eating onions[11] or acetaminophen
(Tylenol). It can be triggered in dogs by ingesting onions or zinc, and in horses by
ingesting dry red maple leaves.
Cause
 Anemia of prematurity occurs in premature infants at 2 to 6 weeks of age
and results from diminished erythropoietin response to declining hematocrit
levels.
 Aplastic anemia is a condition generally unresponsive to anti-anemia
therapies where bone marrow fails to produce enough red blood cells.
 Fanconi anemia is a hereditary disorder or defect featuring aplastic anemia
and various other abnormalities.
 Hemolytic anemia causes a separate constellation of symptoms (also
featuring jaundice and elevated LDH levels) with numerous potential causes.
It can be autoimmune, immune, hereditary or mechanical (e.g. heart
surgery). It can result (because of cell fragmentation) in a microcytic
anemia, a normochromic anemia, or (because of premature release of
immature red blood cells from the bone marrow), a macrocytic anemia.
 Hereditary spherocytosis is a hereditary defect that results in defects in the
RBC cell membrane, causing the erythrocytes to be sequestered and
destroyed by the spleen. This leads to a decrease in the number of circulating
RBCs and, hence, anemia.
 Sickle-cell anemia, a hereditary disorder, is due to homozygous hemoglobin
S genes.
 Warm autoimmune hemolytic anemia is an anemia caused by autoimmune
attack against red blood cells, primarily by IgG.
 Cold agglutinin hemolytic anemia is primarily mediated by IgM.
 Pernicious anemia is a form of megaloblastic anemia due to vitamin B12
deficiency dependent on impaired absorption of vitamin B12.
 Myelophthisic anemia or Myelophthisis is a severe type of anemia resulting
from the replacement of bone marrow by other materials, such as malignant
tumors or granulomas.
 Anemia of Pregnancy is anemia that is induced by blood volume expansion
experienced in pregnancy.
Possible complications
Anemia diminishes the capability of affected individuals to perform physical
activities, a result of one's muscles being forced to depend on anaerobic
metabolism. The lack of iron associated with anemia can cause many
complications, including hypoxemia, brittle or rigid fingernails, cold intolerance,
and possible behavioral disturbances in children. Hypoxemia resulting from
anemia can worsen the cardio-pulmonary status of patients with pre-existing
chronic pulmonary disease. Cold intolerance occurs in one in five patients with
iron deficiency anemia, and becomes visible through numbness and tingling. [citation
needed]

Anemia during pregnancy

Anemia affects 20 percent of all women of childbearing age in the United
States[citation needed]. Due to the subtlety of the symptoms, affected women are often
unaware that they have this disorder, as they attribute the symptoms to the stresses
of their daily lives. Possible problems for the fetus include increased risk of growth
retardation, prematurity, intrauterine death, rupture of the amnion and infection.

An expectant woman should be especially aware of the symptoms of anemia, as an

adult female loses an average of two milligrams[citation needed] of iron daily.
Therefore, she must intake a similar quantity of iron in order to compensate for this
loss. Additionally, a woman loses approximately 500 milligrams[citation needed] of iron
with each pregnancy, compared with a loss of 4–100 milligrams[citation needed] of iron
with each period. Possible consequences include cardiovascular symptoms,
reduced physical and mental performance, reduced immune function, fatigue,
reduced peripartal blood reserves and increased need for blood transfusion in the
postpartum period. This may severely affect the health of the child.

Treatments
There are many different treatments for anemia and the treatment depends on
severity and the cause.

Iron deficiency from nutritional causes is rare in non-menstruating adults (men and
post-menopausal women). The diagnosis of iron deficiency mandates a search for
potential sources of loss such as gastrointestinal bleeding from ulcers or colon
cancer. Mild to moderate iron deficiency anemia is treated by oral iron
supplementation with ferrous sulfate, ferrous fumarate, or ferrous gluconate. When
taking iron supplements, it is very common to experience stomach upset and/or
darkening of the feces. The stomach upset can be alleviated by taking the iron with
food, however this decreases the amount of iron absorbed. Vitamin C aids in the
body's ability to absorb iron, so taking oral iron supplements with orange juice is of
benefit.

Vitamin supplements given orally (folic acid) or subcutaneously (vitamin B-12)

will replace specific deficiencies.

In anemia of chronic disease, anemia associated with chemotherapy, or anemia

associated with renal disease, some clinicians prescribe recombinant
erythropoietin, epoetin alfa, to stimulate red cell production.

In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be
necessary.

Blood transfusions
Doctors attempt to avoid blood transfusion in general, since multiple lines of
evidence point to increased adverse patient clinical outcomes with more intensive
transfusion strategies. The physiological principle that reduction of oxygen
delivery associated with anemia leads to adverse clinical outcomes is balanced by
the finding that transfusion does not necessarily mitigate these adverse clinical
outcomes.

In severe, acute bleeding, transfusions of donated blood are often lifesaving.

Improvements in battlefield casualty survival is attributable, at least in part, to the
recent improvements in blood banking and transfusion techniques.[citation needed]

Transfusion of the stable but anemic hospitalized patient has been the subject of
numerous clinical trials, and transfusion is emerging as a deleterious intervention.

Four randomized controlled clinical trials have been conducted to evaluate

aggressive versus conservative transfusion strategies in critically ill patients. All
four of these studies failed to find a benefit with more aggressive transfusion
strategies.[12][13][14][15]

In addition, at least two retrospective studies have shown increases in adverse

clinical outcomes with more aggressive transfusion strategies. [16][17]
Hyperbaric oxygen
Treatment of exceptional blood loss (anemia) is recognized as an indication for
hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society.[18][19]
The use of HBO is indicated when oxygen delivery to tissue is not sufficient in
patients who cannot be transfused for medical or religious reasons. HBO may be
used for medical reasons when threat of blood product incompatibility or concern
for transmissible disease are factors.[18] The beliefs of some religions (ex: Jehovah's
Witnesses) may prohibit the receipt of transfused blood products. [18]

In 2002, Van Meter reviewed the publications surrounding the use of HBO in
severe anemia and found that all publications report a positive result. [20]
 CONTENTS
 1 Signs and symptoms

 2 Diagnosis

 3 Classification

o 3.1 Production vs. destruction or loss

o 3.2 Red blood cell size

 3.2.1 Microcytic anemia

 3.2.2 Macrocytic anemia

 3.2.3 Normocytic anemia

 3.2.4 Dimorphic anemia

 3.2.5 Heinz body anemia

 4 Cause

 5 Possible complications

 6 Anemia during pregnancy

 7 Treatments

o 7.1 Blood transfusions

o 7.2 Hyperbaric oxygen