Anemia

Anemia, also spelled anaemia and sometimes called erythrocytopenia,[a] is a

decrease in the total amount of red blood cells (RBCs) or hemoglobin in the
blood[3][4] or a lowered ability of the blood to carry oxygen.[5] When anemia comes
on slowly, the symptoms are often vague and may include feeling tired, weakness,
shortness of breath, and a poor ability to exercise.[1] When the anemia comes on
quickly, symptoms may include confusion, lightheadedness, loss of
consciousness, and increased thirst.[1] Anemia must be significant before a
person becomes noticeably pale.[1] Additional symptoms may occur depending on
the underlying cause.[1] For people who require surgery, pre-operative anemia can
increase the risk of requiring a blood transfusion following surgery.[6]
 Anemia

Other names Anaemia, erythrocytopenia

Blood smear from a person with iron-deficiency anemia. Note the red cells are small and
pale.

Pronunciation /əˈniːmiə/

Specialty Hematology

Symptoms Feeling tired, pale skin, weakness, shortness of

breath, feeling like passing out[1]

Causes Bleeding, decreased red blood cell production,

increased red blood cell breakdown[1]

Diagnostic method Blood hemoglobin measurement[1]

Frequency 2.36 billion / 33% (2015)[2]

Anemia can be caused by bleeding, decreased red blood cell production, and
increased red blood cell breakdown.[1] Causes of bleeding include trauma and
gastrointestinal bleeding.[1] Causes of decreased production include iron
deficiency, vitamin B12 deficiency, thalassemia and a number of neoplasms of the
bone marrow.[1] Causes of increased breakdown include genetic conditions such
as sickle cell anemia, infections such as malaria, and certain autoimmune
diseases.[1] Anemia can also be classified based on the size of the red blood cells
and amount of hemoglobin in each cell.[1] If the cells are small, it is called
microcytic anemia; if they are large, it is called macrocytic anemia; and if they are
normal sized, it is called normocytic anemia.[1] The diagnosis of anemia in men is
based on a hemoglobin of less than 130 to 140 g/L (13 to 14 g/dL); in women, it is
less than 120 to 130 g/L (12 to 13 g/dL).[1][7] Further testing is then required to
determine the cause.[1][8]

Certain groups of individuals, such as pregnant women, benefit from the use of
iron pills for prevention.[1][9] Dietary supplementation, without determining the
specific cause, is not recommended.[1] The use of blood transfusions is typically
based on a person's signs and symptoms.[1] In those without symptoms, they are
not recommended unless hemoglobin levels are less than 60 to 80 g/L (6 to
8 g/dL).[1][10] These recommendations may also apply to some people with acute
bleeding.[1] Erythropoiesis-stimulating agents are only recommended in those with
severe anemia.[10]

Anemia is the most common blood disorder, affecting about a third of the global
population.[1][2][11] Iron-deficiency anemia affects nearly 1 billion people.[12] In
2013, anemia due to iron deficiency resulted in about 183,000 deaths – down
from 213,000 deaths in 1990.[13] This condition is more common in women than
men,[12] during pregnancy, and in children and the elderly.[1] Anemia increases
costs of medical care and lowers a person's productivity through a decreased
ability to work.[7] The name is derived from Ancient Greek: ἀναιμία anaimia,
meaning "lack of blood", from ἀν- an-, "not" and αἷμα haima, "blood".[14]

Anemia is one of the six WHO global nutrition targets for 2025 and diet-related
global NCD targets for 2025 (https://www.who.int/nmh/ncd-tools/definition-targe
ts/en/) , endorsed by World Health Assembly in 2012 and 2013. Efforts to reach
global targets contribute to reaching Sustainable Development Goals (SDGs),[15]
with anemia as one of the targets in SDG 2.[16]

Signs and symptoms

Main symptoms that may appear in anemia[17]

The hand of a person with severe anemia (on the left, with ring) compared to one without (on the right)

Anemia goes undetected in many people and symptoms can be minor. The
symptoms can be related to an underlying cause or the anemia itself. Most
commonly, people with anemia report feelings of weakness or fatigue, and
sometimes poor concentration. They may also report shortness of breath on
exertion. If the anemia continues slowly (chronic), the body may adapt and
compensate for this change; in this case, no symptoms may appear until the
anemia becomes more severe.Typical symptoms of anemia may include:

feeling tiredness and weakness[17][18]

feeling like passing out (lightheadedness), or dizziness[17][18]

 headaches[17]

lack of physical exertion;[17] extreme tiredness on the slightest exertion

(accompanied by shortness of breath and rapid heartbeat)[18]

breathlessness (rapid)[17][19]

difficulty concentrating[18]

irregular heartbeat (fluttering, or rapid heartbeat)[17][18]

cold hands and feet[19]

chest pain[17]

constantly feeling cold

soreness of the tongue

pallor[17][18]

nausea and poor appetite[18]

easy bruising and bleeding

muscle weakness

In very severe anemia, the body may compensate for the lack of oxygen-carrying
capability of the blood by increasing cardiac output. The person may have
symptoms related to this, such as palpitations, angina (if pre-existing heart
disease is present), intermittent claudication of the legs, and symptoms of heart
failure. On examination, the signs exhibited may include pallor (pale skin, mucosa,
conjunctiva and nail beds), but this is not a reliable sign. A blue coloration of the
sclera may be noticed in some cases of iron-deficiency anemia.[20] 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), nerve cell damage (vitamin B12 deficiency), bone deformities (found in
thalassemia major) or leg ulcers (seen in sickle-cell disease). In severe anemia,
there may be signs of a hyperdynamic circulation: tachycardia (a fast heart rate),
bounding pulse, flow murmurs, and cardiac ventricular hypertrophy (enlargement).
There may be signs of heart failure. Pica, the consumption of non-food items such
as ice, but also paper, wax, or grass, and even hair or dirt, 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
academic performance in children of school age. Restless legs syndrome is more
common in people with iron-deficiency anemia than in the general population.[21]

Causes

Figure shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-
section of a normal red blood cell with normal hemoglobin.[22]

The causes of anemia may be classified as impaired red blood cell (RBC)
production, increased RBC destruction (hemolytic anemias), blood loss and fluid
overload (hypervolemia). Several of these may interplay to cause anemia. The
most common cause of anemia is blood loss, but this usually does not cause any
lasting symptoms unless a relatively impaired RBC production develops, in turn,
most commonly by iron deficiency.[3]

Impaired production
Disturbance of proliferation and differentiation of stem cells
Pure red cell aplasia[23]

Aplastic anemia[23] affects all kinds of blood cells. Fanconi anemia is a hereditary
disorder or defect featuring aplastic anemia and various other abnormalities.

Anemia of kidney failure[23] due to insufficient production of the hormone

erythropoietin
 Anemia of endocrine disease[24]

Disturbance of proliferation and maturation of erythroblasts

Pernicious anemia[23] is a form of megaloblastic anemia due to vitamin B12
deficiency dependent on impaired absorption of vitamin B12. Lack of dietary B12
causes non-pernicious megaloblastic anemia.

Anemia of folate deficiency,[23] as with vitamin B12, causes megaloblastic anemia

Anemia of prematurity, by diminished erythropoietin response to declining

hematocrit levels, combined with blood loss from laboratory testing, generally
occurs in premature infants at two to six weeks of age.

Iron deficiency anemia, resulting in deficient heme synthesis[23]

Thalassemias, causing deficient globin synthesis[23]

Congenital dyserythropoietic anemias, causing ineffective erythropoiesis

Anemia of kidney failure[23] (also causing stem cell dysfunction)

Other mechanisms of impaired RBC production

Myelophthisic anemia[23] or myelophthisis is a severe type of anemia resulting
from the replacement of bone marrow by other materials, such as malignant
tumors, fibrosis, or granulomas.

Myelodysplastic syndrome[23]

anemia of chronic inflammation[23]

Leukoerythroblastic anemia is caused by space-occupying lesions in the bone

marrow that prevent normal production of blood cells.[25]

Increased destruction

Anemias of increased red blood cell destruction are generally classified as

hemolytic anemias. These are generally featuring jaundice and elevated lactate
dehydrogenase levels.[26][27]

Intrinsic (intracorpuscular) abnormalities[23] cause premature destruction. All of

these, except paroxysmal nocturnal hemoglobinuria, are hereditary genetic
disorders.[28]
Hereditary spherocytosis[23] is a hereditary defect that results in defects in the
RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by
the spleen.
 Hereditary elliptocytosis[23] is another defect in membrane skeleton proteins.

Abetalipoproteinemia,[23] causing defects in membrane lipids

Enzyme deficiencies
Pyruvate kinase and hexokinase deficiencies,[23] causing defect glycolysis

Glucose-6-phosphate dehydrogenase deficiency and glutathione synthetase

deficiency,[23] causing increased oxidative stress

Hemoglobinopathies
Sickle cell anemia[23]

Hemoglobinopathies causing unstable hemoglobins[23]

Paroxysmal nocturnal hemoglobinuria[23]

Extrinsic (extracorpuscular) abnormalities

Antibody-mediated
Warm autoimmune hemolytic anemia is caused by autoimmune attack against
red blood cells, primarily by IgG. It is the most common of the autoimmune
hemolytic diseases.[29] It can be idiopathic, that is, without any known cause, drug-
associated or secondary to another disease such as systemic lupus
erythematosus, or a malignancy, such as chronic lymphocytic leukemia.[30]

Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be

idiopathic[31] or result from an underlying condition.

Rh disease,[23] one of the causes of hemolytic disease of the newborn

Transfusion reaction to blood transfusions[23]

Mechanical trauma to red blood cells

Microangiopathic hemolytic anemias, including thrombotic thrombocytopenic
purpura and disseminated intravascular coagulation[23]

Infections, including malaria[23]

Heart surgery

Haemodialysis

Blood loss
Anemia of prematurity, from frequent blood sampling for laboratory testing,
combined with insufficient RBC production
 Trauma[23] or surgery, causing acute blood loss

Gastrointestinal tract lesions,[23] causing either acute bleeds (e.g. variceal lesions,
peptic ulcers) or chronic blood loss (e.g. angiodysplasia)

Gynecologic disturbances,[23] also generally causing chronic blood loss

From menstruation, mostly among young women or older women who have
fibroids

Many type of cancers, including colorectal cancer and cancer of the urinary
bladder, may cause acute or chronic blood loss, especially at advanced stages

Infection by intestinal nematodes feeding on blood, such as hookworms[32] and

the whipworm Trichuris trichiura [33]

Iatrogenic anemia, blood loss from repeated blood draws and medical
procedures.[34][35]

The roots of the words anemia and ischemia both refer to the basic idea of "lack
of blood", but anemia and ischemia are not the same thing in modern medical
terminology. The word anemia used alone implies widespread effects from blood
that either is too scarce (e.g., blood loss) or is dysfunctional in its oxygen-
supplying ability (due to whatever type of hemoglobin or erythrocyte problem). In
contrast, the word ischemia refers solely to the lack of blood (poor perfusion).
Thus ischemia in a body part can cause localized anemic effects within those
tissues.

Fluid overload

Fluid overload (hypervolemia) causes decreased hemoglobin concentration and

apparent anemia:

General causes of hypervolemia include excessive sodium or fluid intake, sodium

or water retention and fluid shift into the intravascular space.[36]

From the 6th week of pregnancy, hormonal changes cause an increase in the
mother's blood volume due to an increase in plasma.[37]

Intestinal inflammation

Certain gastrointestinal disorders can cause anemia. The mechanisms involved

are multifactorial and not limited to malabsorption but mainly related to chronic
intestinal inflammation, which causes dysregulation of hepcidin that leads to
decreased access of iron to the circulation.[38][39][40]

Helicobacter pylori infection.[41]

Gluten-related disorders: untreated celiac disease[40][41] and non-celiac gluten

sensitivity.[42] Anemia can be the only manifestation of celiac disease, in absence
of gastrointestinal or any other symptoms.[43]

Inflammatory bowel disease.[44][45]

Diagnosis

Peripheral blood smear microscopy of a patient with iron-deficiency anemia

A Giemsa-stained blood film from a person with iron-deficiency anemia. This person also had
hemoglobin Kenya.
Definitions

There are a number of definitions of anemia; reviews provide comparison and

contrast of them.[46] A strict but broad definition is an absolute decrease in red
blood cell mass,[47] however, a broader definition is a lowered ability of the blood
to carry oxygen.[5] An operational definition is a decrease in whole-blood
hemoglobin concentration of more than 2 standard deviations below the mean of
an age- and sex-matched reference range.[48]

It is difficult to directly measure RBC mass,[49] so the hematocrit (amount of

RBCs) or the hemoglobin (Hb) in the blood are often used instead to indirectly
estimate the value.[50] Hematocrit; however, is concentration dependent and is
therefore not completely accurate. For example, during pregnancy a woman's RBC
mass is normal but because of an increase in blood volume the hemoglobin and
hematocrit are diluted and thus decreased. Another example would be bleeding
where the RBC mass would decrease but the concentrations of hemoglobin and
hematocrit initially remains normal until fluids shift from other areas of the body
to the intravascular space.

The anemia is also classified by severity into mild (110 g/L to normal), moderate
(80 g/L to 110 g/L), and severe anemia (less than 80 g/L) in adult males and adult
non pregnant females.[51] Different values are used in pregnancy and children.[51]

Testing

Anemia is typically diagnosed on a complete blood count. 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 it is sometimes
a necessity in regions of the world where automated analysis is less accessible.
WHO's Hemoglobin thresholds used to define anemia[52]
(1 g/dL = 0.6206 mmol/L)
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

Teens (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

A blood test will provide counts of white blood cells, red blood cells and platelets.
If anemia appears, further tests may determine what type it is, and whether it has
a serious cause. although of that, it is possible to refer to the genetic history and
physical diagnosis.[53] These tests may include:

complete blood count (CBC); a CBC is used to count the number of blood cells in
a sample of the blood. For anemia, it will likely to be interested in the levels of the
red blood cells contained in blood (hematocrit), hemoglobin, mean corpuscular
volume.[54]

determine the size and shape of red blood cells; some of red blood cells might
also be examined for unusual size, shape and color.[55]

serum ferritin; This protein helps store iron in the body, a low levels of ferritin
usually indicates a low levels of stored iron.[55]

serum vitamin B12; low levels usually develop an anemia, vitamin B12 is needed to
make red blood cells, which carry oxygen to all parts of human body.[55]

blood tests to detect rare causes; such as an immune attack on red blood cells,
red blood cell fragility, and defects of enzymes, hemoglobin, and clotting.[54]

a bone marrow sample; when the cause is unclear, a bone marrow test is
performed, most often, when some blood cell defect is suspected.[54]

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, such as: ESR, serum iron, transferrin, RBC
folate level, hemoglobin electrophoresis, renal function tests (e.g. serum
creatinine) although the tests will depend on the clinical hypothesis that is being
investigated. When the diagnosis remains difficult, a bone marrow examination
allows direct examination of the precursors to red cells, although is rarely used as
is painful, invasive and is hence reserved for cases where severe pathology needs
to be determined or excluded.

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. Limitations of MCV include
cases where the underlying cause is due to a combination of factors – such as
iron deficiency (a cause of microcytosis) and vitamin B12 deficiency (a cause of
macrocytosis) where the net result can be normocytic cells.
Production vs. destruction or loss

The "kinetic" approach to anemia yields arguably 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 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
guaiac-positive stool, radiographic findings, or frank bleeding. The following is a
simplified schematic of this approach:
 Anemia

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

Clinical
No clinical findings and
findings abnormal Clinical findings and normal
consistent with MCV: MCV= acute hemolysis or loss
hemolysis or hemolysis or without adequate time for bone
blood loss: loss and marrow production to
pure disorder chronic compensate**.
of production. disorder of
production*.

Macrocytic Normocytic
anemia anemia Microcytic anemia (MCV<80)
(MCV>100) (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. Here is a schematic representation of how to consider anemia with
MCV as the starting point:
 Anemia

Macrocytic Normocytic Microcytic

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

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

Microcytic anemia is primarily a result of hemoglobin synthesis

failure/insufficiency, which could be caused by several etiologies:

Heme synthesis defect

Iron deficiency anemia (microcytosis is not always present)

Anemia of chronic disease (more commonly presenting as normocytic anemia)

Globin synthesis defect

Alpha-, and beta-thalassemia

HbE syndrome

HbC syndrome

Various other unstable hemoglobin diseases

Sideroblastic defect
Hereditary sideroblastic anemia

Acquired sideroblastic anemia, including lead toxicity[56]

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 due to insufficient dietary intake or absorption of iron to

meet the body's needs. Infants, toddlers, and pregnant women have higher than
average needs. Increased iron intake is also needed to offset blood losses due to
digestive tract issues, frequent blood donations, or heavy menstrual periods.[57]
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, 12% of all
women of childbearing age have iron deficiency, compared with only 2% of adult
men. The incidence is as high as 20% among African American and Mexican
American women.[58] Studies have shown iron deficiency without anemia causes
poor school performance and lower IQ in teenage girls, although this may be due
to socioeconomic factors.[59][60] Iron deficiency is the most prevalent deficiency
state on a worldwide basis. It is sometimes the cause of abnormal fissuring of the
angular (corner) sections of the lips (angular stomatitis).

In the United States, the most common cause of iron deficiency is bleeding or
blood loss, usually from the gastrointestinal tract. Fecal occult blood testing,
upper endoscopy and lower endoscopy should be performed to identify bleeding
lesions. In older men and women, the chances are higher that bleeding from the
gastrointestinal tract could be due to colon polyps or colorectal cancer.

Worldwide, the most common cause of iron deficiency anemia is parasitic

infestation (hookworms, amebiasis, schistosomiasis and whipworms).[61]

The Mentzer index (mean cell volume divided by the RBC count) predicts whether
microcytic anemia may be due to iron deficiency or thalassemia, although it
requires confirmation.[62]

Macrocytic
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 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.
Pernicious anemia is caused by a lack of intrinsic factor, which 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.

Macrocytic anemia can also be caused by the removal of the functional portion of
the stomach, such as during gastric bypass surgery, leading to reduced vitamin
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.

Drugs such as methotrexate, zidovudine, and other substances may inhibit DNA
replication such as heavy metals

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

"nonmegaloblastic macrocytic anemia". The cause of megaloblastic anemia is
primarily a failure of DNA synthesis with preserved RNA synthesis, which results
in restricted cell division of the progenitor cells. The megaloblastic anemias often
present with neutrophil hypersegmentation (six to 10 lobes). The
nonmegaloblastic macrocytic anemias have different etiologies (i.e. unimpaired
DNA globin synthesis,) which occur, for example, in alcoholism. In addition to the
nonspecific 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.[63]
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 isolate the curative substance chemically and ultimately were
able to isolate the vitamin B12 from the liver. All three shared the 1934 Nobel Prize
in Medicine.[64]

Normocytic

Normocytic anemia occurs when the overall hemoglobin levels are 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

A dimorphic appearance on a peripheral blood smear occurs when there are two
simultaneous populations of red blood cells, typically of different size and
hemoglobin content (this last feature affecting the color of the red blood cell on a
stained peripheral blood smear). For example, a person recently transfused for
iron deficiency would have small, pale, iron deficient red blood cells (RBCs) and
the donor RBCs of normal size and color. Similarly, a person transfused for severe
folate or vitamin B12 deficiency would have two cell populations, but, in this case,
the patient's RBCs would be larger and paler than the donor's RBCs. A person with
sideroblastic anemia (a defect in heme synthesis, commonly caused by
alcoholism, but also drugs/toxins, nutritional deficiencies, a few acquired and rare
congenital diseases) can have a dimorphic smear from the sideroblastic anemia
alone. Evidence for multiple causes appears with an elevated RBC distribution
width (RDW), indicating a wider-than-normal range of red cell sizes, also seen in
common nutritional anemia.

Heinz body anemia

Heinz bodies form in the cytoplasm of RBCs and appear as small dark dots under
the microscope. In animals, Heinz body anemia has many causes. It may be drug-
induced, for example in cats and dogs by acetaminophen (paracetamol),[65] or
may be caused by eating various plants or other substances:

In cats and dogs after eating either raw or cooked plants from the genus Allium,
for example, onions or garlic.[66]

In dogs after ingestion of zinc, for example, after eating U.S. pennies minted after
1982.[65]

In horses which eat dry or wilted red maple leaves.[67]

Hyperanemia
Hyperanemia is a severe form of anemia, in which the hematocrit is below 10%.[68]

Refractory anemia

Refractory anemia, an anemia which does not respond to treatment,[69] is often

seen secondary to myelodysplastic syndromes.[70] Iron deficiency anemia may
also be refractory as a manifestation of gastrointestinal problems which disrupt
iron absorption or cause occult bleeding. [71]

Transfusion dependent

Transfusion dependent anemia is a form of anemia where ongoing blood

transfusion are required.[72] Most people with myelodysplastic syndrome develop
this state at some point in time.[73] Beta thalassemia may also result in
transfusion dependence.[74][75] Concerns from repeated blood transfusions
include iron overload.[73] This iron overload may require chelation therapy.[76]

Treatment

Treatment for anemia depends on cause and severity. Vitamin supplements given
orally (folic acid or vitamin B12) or intramuscularly (vitamin B12) will replace
specific deficiencies.[1]

Oral iron

Nutritional iron deficiency is common in developing nations. An estimated two-

thirds of children and of women of childbearing age in most developing nations
are estimated to have iron deficiency without anemia; one-third of them have iron
deficiency with anemia.[77] Iron deficiency due to inadequate dietary iron intake is
rare in men and postmenopausal women. The diagnosis of iron deficiency
mandates a search for potential sources of blood 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. Daily iron
supplements have been shown to be effective in reducing anemia in women of
childbearing age.[78] When taking iron supplements, stomach upset or darkening
of the feces are commonly experienced. 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.[79]

In the anemia of chronic kidney disease, recombinant erythropoietin or epoetin

alfa is recommended to stimulate RBC production, and if iron deficiency and
inflammation are also present, concurrent parenteral iron is also
recommended.[80]

Injectable iron

In cases where oral iron has either proven ineffective, would be too slow (for
example, pre-operatively), or where absorption is impeded (for example in cases
of inflammation), parenteral iron preparations can be used. Parenteral iron can
improve iron stores rapidly and is also effective for treating people with
postpartum haemorrhage, inflammatory bowel disease, and chronic heart
failure.[6] The body can absorb up to 6 mg iron daily from the gastrointestinal
tract. In many cases, the patient has a deficit of over 1,000 mg of iron which
would require several months to replace. This can be given concurrently with
erythropoietin to ensure sufficient iron for increased rates of erythropoiesis.[81]

Blood transfusions

Blood transfusions in those without symptoms is not recommended until the

hemoglobin is below 60 to 80 g/L (6 to 8 g/dL).[1] In those with coronary artery
disease who are not actively bleeding transfusions are only recommended when
the hemoglobin is below 70 to 80g/L (7 to 8 g/dL).[10] Transfusing earlier does not
improve survival.[82] Transfusions otherwise should only be undertaken in cases
of cardiovascular instability.[83]

A 2012 review concluded that when considering blood transfusions for anaemia
in people with advanced cancer who have fatigue and breathlessness (not related
to cancer treatment or haemorrhage), consideration should be given to whether
there are alternative strategies can be tried before a blood transfusion.[84]
Erythropoiesis-stimulating agents

The objective for the administration of an erythropoiesis-stimulating agent (ESA)

is to maintain hemoglobin at the lowest level that both minimizes transfusions
and meets the individual person's needs.[85] They should not be used for mild or
moderate anemia.[82] They are not recommended in people with chronic kidney
disease unless hemoglobin levels are less than 10 g/dL or they have symptoms of
anemia. Their use should be along with parenteral iron.[85][86] The 2020 Cochrane
Anaesthesia Review Group review of Erythropoietin plus iron versus control
treatment including placebo or iron for preoperative anaemic adults undergoing
non‐cardiac surgery [87] demonstrated that patients were much less likely to
require red cell transfusion and in those transfused, the volumes were unchanged
(mean difference -0.09, 95% CI -0.23 to 0.05). Pre-op Hb concentration was
increased in those receiving 'high dose' EPO, but not 'low dose'.

Hyperbaric oxygen

Treatment of exceptional blood loss (anemia) is recognized as an indication for

hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical Society.[88][89]
The use of HBO is indicated when oxygen delivery to tissue is not sufficient in
patients who cannot be given blood transfusions 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.[88] The beliefs of
some religions (ex: Jehovah's Witnesses) may require they use the HBO
method.[88] A 2005 review of the use of HBO in severe anemia found all
publications reported positive results.[90]

Pre-operative anemia

An estimated 30% of adults who require non-cardiac surgery have anemia.[91] In

order to determine an appropriate pre-operative treatment, it is suggested that the
cause of anemia be first determined.[92] There is moderate level medical evidence
that supports a combination of iron supplementation and erythropoietin treatment
to help reduce the requirement for red blood cell transfusions after surgery in
those who have pre-operative anemia.[91]
 Epidemiology

A moderate degree of iron-deficiency anemia affected approximately 610 million

people worldwide or 8.8% of the population.[12] It is slightly more common in
females (9.9%) than males (7.8%).[12] Mild iron deficiency anemia affects another
375 million.[12] Severe anaemia is prevalent globally, and especially in sub-Saharan
Africa[93] where it is associated with infections including malaria and invasive
bacterial infections.[94]

History

Signs of severe anemia in human bones from 4000 years ago have been
uncovered in Thailand.[95]

Notes

a. Erythrocyte, referring to red blood cells, and penia, meaning a lack of.

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 External links

Look up anemia in Wiktionary, the free dictionary.

"Anemia" (https://medlineplus.gov/anemia.html) . MedlinePlus. U.S. National

Library of Medicine.

"The case for action on Anemia- leave no one behind" (https://www.devex.com/ne

ws/sponsored/the-case-for-action-on-anemia-leave-no-one-behind-88283) .
devex.com.

"Interventions by global target" (https://www.who.int/elena/global-targets/en/) .

WHO.int.

Classification D
ICD-10: D50 (https://icd.who.int/browse10/201
9/en#/D50) -D64 •

ICD-9-CM: 280 (http://www.icd9data.com/getIC

D9Code.ashx?icd9=280) -285 •

MeSH: D000740 • DiseasesDB: 663

External resources MedlinePlus: 000560 •

eMedicine: med/132 (https://emedicine.medsca

pe.com/med/132-overview) emerg/808 (htt
p://www.emedicine.com/emerg/topic808.htm
#) emerg/734

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