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Anemia
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WHAT
IS ANEMIA AND SOME OF ITS CAUSES?
General
Description of Anemia
Anemia is an
abnormal reduction in red blood cells. It is a great problem globally
and worse in developing countries, but by no means absent in industrialized
nations. Anemia can occur from a malfunction at any point in the
production, recycling, or regulating of red blood cells. [See Box
Blood.] Anemia is not a single disease but
a condition, like fever, with many possible causes and many forms.
Anemia most commonly occurs as a result of the following conditions:
- Low iron
levels (iron deficiency anemia).
- Inhibition
of erythropoietin production by the immune system (anemia of
chronic disease).
- Vitamin
deficiencies (megaloblastic anemia).
- Premature
destruction of red blood cells (hemolytic anemia).
- Replacement
of normal bone marrow cells by cancer cells (myelophthisic anemia).
- Injury
to bone marrow (aplastic anemia).
- An inborn
structural defect in red blood cells (eg, sickle-cell anemia).
- An inability
to manufacture hemoglobin.
- An inability
or make use of normal or even high levels of iron (sideroblastic
anemia).
- Thyroid
deficiency.
It is impossible
to discuss each type of anemia here, so this report focuses on three
of the most common types:
- Iron deficiency
anemia.
- Megaloblastic
anemia.
- Anemia
of chronic disease (ACD).
Some less common
causes and types of anemia are included in the table below.
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BLOOD
Blood Components
Blood
has two major components:
-
Plasma is a clear yellow liquid that contains proteins,
nutrients, hormones, electrolytes, and other substances.
It constitutes about 55% of blood.
-
White and red blood cells and platelets make up the
balance of blood. The white cells are the infection
fighters for the body, and platelets are necessary for
blood clotting. The important factors in anemia, however,
are red blood cells.
Red Blood Cells
Red blood
cells (RBCs), also known as erythrocytes, carry oxygen
throughout the body to nourish tissues and sustain life.
Red blood cells are the most abundant cells in our bodies;
men have about 5,200,000 and women about 4,700,000 per cubic
millimeter of blood. To understand red blood cells and their
role in anemia, it is useful to know certain facts about
them.
Hemoglobin
Each
red blood cell contains between 200 and 300 hemoglobin
molecules. Hemoglobin is a complex molecule and the most
important component of red blood cells. It is composed of
protein and an iron-containing molecule called heme,
which binds oxygen in exchange for carbon dioxide in the
lungs. The oxygenated red blood cells are then transported
to the body's tissues, where the hemoglobin releases the
oxygen in exchange for carbon dioxide and the cycle repeats.
The oxygen is used in the mitochondria, the power
source within all cells.
Structure and Shape
Red blood
cells are extremely small and look something like tiny,
flexible inner tubes. This unique shape offers many advantages:
-
It provides a large surface area to absorb oxygen and
carbon dioxide.
-
Its flexibility allows it to squeeze through capillaries,
the tiny blood vessels that join the arteries and veins.
Blood Cell Production (Erythropoiesis)
The actual
process of making red blood cells is called erythropoiesis.
(In Greek, erythro means "red" and poiesis
means "the making of things.") The process of manufacturing,
recycling, and regulating the number of red blood cells
is complex and involves many parts of the body:
-
The body carefully regulates its production of red blood
cells so that enough are manufactured to carry oxygen
but not so many that the blood becomes thick or sticky
( viscous).
-
Most of the work of erythropoiesis occurs in the bone
marrow. In children younger than five years old, the
marrow in all the bones of the body is enlisted
for producing red blood cells. As a person ages, red
blood cells are eventually produced only in the marrow
of the spine, ribs, and pelvis.
-
If the body requires an increase in oxygen (at high
altitudes, for instance), the kidney triggers the release
of the hormone erythropoietin (EPO), a hormone
that acts in the bone marrow to increase the production
of red blood cells.
-
The life span of a red blood cell is between 90 and
120 days. Old red blood cells are removed from the blood
by the liver and spleen.
-
There they are broken down and iron is returned to the
bone marrow to make new cells.
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Iron
Deficiency Anemia
Iron deficiency
anemia occurs when the body lacks iron to produce the hemoglobin
it needs to make red blood cells. It can be caused by a number of
conditions.
Iron-Poor Diets. Lack of iron in the diet is not a common
cause of iron deficiency anemia. In fact, most Americans may be
consuming too much iron in their diet. Most of the iron in red blood
cells is recycled and reused. In general, most people need just
1 mg and menstruating women need 2 mg of extra iron each day, which
a healthy diet easily provides. Iron-poor diets are only a cause
of anemia in people with existing risks for iron deficiency.
Peptic Ulcers and their Causes. The bacteria H. pylori
are known to be primary causes of peptic ulcers, which, in
turn, is an important cause of anemia in older people. Anemia in
such cases may be less likely to result from bleeding ulcers but
more to impaired iron or vitamin B12 absorption caused by the presence
of the bacteria. The bacteria, in fact, may also bind to iron and
reduce its availability in the intestine causing iron deficiency
anemia. [See also Causes of Megaloblastic Anemia, below.]
Medications (NSAIDs). Aspirin and drugs such as ibuprofen
and naproxen are called nonsteroidal anti-inflammatory drugs (NSAIDs).
About 70% of long-term users of these medications have some sign
of gastrointestinal bleeding, although it is rarely significant
enough to cause anemia.
Bleeding due to Other Medical Conditions. Iron deficiencies
most commonly occur from internal blood loss due to other conditions
that range in severity from hemorrhoids, heavy menstruation, or
benign colon polyps to colon cancer. Very heavy periods (menorrhagia)
are the most common causes of anemia in premenopausal women. Cancers
of the gastrointestinal tract account for 2% of cases of iron deficiency
(the rate is higher when menorrhagia is excluded).
Pica. Pica is the craving for non-food substances such as
ice, starch, or clay. It is a possible cause of iron deficiency,
particularly in those who eat clay or starch, which interferes with
iron absorption in the stomach. To complicate matters, pica (particularly
ice cravings) may also be a symptom, rather than a cause, of anemia.
[See also What Are the Symptoms of Anemia? below.]
Hookworm. Hookworm infects about one billion people worldwide.
It is a major cause of anemia in areas where it occurs.
Impaired Absorption of Iron. Certain intestinal diseases
(e.g. inflammatory bowel disease, celiac disease) or surgical procedures
that affect the gastrointestinal tract can impair the ability of
the intestine to absorb iron. (Such conditions also often impair
folic acid absorption as well.)
Genetic Causes. Some people are born with iron deficiency.
Certain of these cases may be due to a mutation of the Nramp2 gene,
which regulates a protein responsible for delivering iron to the
cells.
Anemia
of Chronic Disease (ACD)
Anemia of chronic
disease (ACD) is generally a condition that is triggered by a persistent
inflammatory process that is, in turn, a by-product of the disease-fighting
immune system.
The Inflammatory Process and ACD. The process leading to
anemia of chronic disease may occur in the following way:
- The immune
system activates white blood cells and releases various compounds
that cause inflammation. (These blood cells may be triggered
to fight the disease or they may even be part of the disease
process itself.)
- White
blood cells called macrophages release small put powerful
proteins known as cytokines, which are critical in the development
of ACD.
- Cytokines
are indispensable for healing. However, often in chronic and
inflammatory diseases cytokines are overproduced and cause serious
tissue injury and in some cases, even organ damage. Specific
cytokines implicated in anemia are interleukin 1 (IL-1), tumor
necrosis factor (TNF), and interferons.
- One theory
on cytokines and other immune factors and their role in anemia
suggests that they change the dynamics of iron circulation,
causing iron to be held back from release into the developing
red blood cells in the marrow. In this case, iron stores are
high, but the usable iron in circulation is low. In some ACDs
(such as chronic kidney failure), cytokines may blunt the effects
of erythropoietin (EPO), the hormone that produces red
blood cells.
Diseases Associated
with ACD. The chronic diseases that are associated with this
process are the following:
- Certain
Cancers. Examples include lymphomas and Hodgkin's disease.
- Autoimmune
Diseases. Examples include rheumatoid arthritis, systemic lupus
erythematosus, inflammatory bowel disease, and polymyalgia rheumatica.
Diabetes type 1 deserves a separate note. Although it is an
autoimmune disease and increases the risk for anemia, its effects
leading to anemia in most cases are cell damage and deterioration
of the stomach lining, which produce iron deficiency.
- Long-Term
Infections. Examples include urinary tract infections and osteomyelitis.
Common childhood infections, such as ear infections and urinary
tract infections, may also cause anemia due to inflammation.
This anemia often resolves on its own but may be confused with
iron deficiency.
- Congestive
Heart Disease. This heart problem has recently been added to
the list of chronic diseases associated with inflammation and
anemia.
These three disease
groups account for about 75% of anemia associated with chronic disease,
but not all cases are easily identified. It also should be noted
that not all chronic diseases involve the inflammatory process and
anemia. For example, high blood pressure is a chronic disease but
it does not affect red blood cells.
Combination Anemias. In some cases, a combination of iron
deficiencies and inflammation in ACD may be responsible for anemia
in a single patient, complicating both diagnosis and treatment.
For example:
- Internal
bleeding is common in some chronic diseases, particularly with
those, such as rheumatoid arthritis, that are treated with NSAIDs,
pain relievers that cause gastrointestinal bleeding.
- Inflammatory
bowel disease is an ACD that is also associated with iron deficiencies
from both intestinal malabsorption and GI bleeding.
- Cancer
patients may have anemia caused both by internal bleeding and
the disease process itself.
- Chronic
renal failure is a special case in which anemia is associated
with both ACD and deficiencies in erythropoietin. Hemodialysis
is used to treat this condition and also contributes to anemia.
Megaloblastic
Anemia
Megaloblastic
anemia is the end product of deficiencies in the B vitamins folate,
vitamin B12 (also called cobalamin), or both. Such deficiencies
produce abnormally large red blood cells ( megaloblastic)
that have a shortened life span. Neurologic problems are also associated
with these deficiencies. There are a number of conditions that can
cause these deficiencies.
Causes of Vitamin B12 Deficiency. Conditions that cause
vitamin B12 deficiencies include the following:
- Pernicious
anemia. Pernicious anemia is an autoimmune disease in which
antibodies are tricked into attacking stomach cells. This results
in impaired production of intrinsic factor (IF), a compound
that is critical for absorption of vitamin B12. Pernicious anemia
is diagnosed in about 1% of people over 60, with women having
a higher risk than men.
- H.
pylori and atrophic gastritis. A 2000 study suggested that
the H. pylori bacterium is a player in many cases of
vitamin B12 deficiency. The bacteria are not only major culprits
in peptic ulcers, but also are strongly associated with atrophic
gastritis. This condition is a gradual loss of the stomach lining
and is a known cause of vitamin B12 deficiency. (Some researchers
theorize that H. pylori -induced injuries in the stomach
lining may actually be the first step in the destructive process
that leads to pernicious anemia.)
- Complications
of gastrointestinal surgery. Surgeries such as stomach bypass
or stapling, which remove part or all of the stomach, pose a
15% to 30% chance of causing vitamin B12 deficiencies.
- Overgrowth
of intestinal bacteria.
- Tropical
sprue (an acquired malabsorption disease occurring in tropical
climates).
- Overexposure
to nitrous oxide.
It should be
noted that Vitamin B12 deficiency from diet is very rare, since
the liver stores over a three-year supply. It usually does not occur
even in alcoholism, vegetarianism, or in malnourished people with
kidney failure or cancer. Since animal products are the chief source,
however, true vegan vegetarians may need a supplement, fortified
food, or appropriate food selection known to contain adequate amounts
of this vitamin.
Causes of Folate Deficiency. The body stores only about
100 times its daily requirements for folate and can exhaust this
supply within about three months if the diet is deficient in folate.
- Poor diet
coupled with alcoholism is the most common cause of folate deficiency.
Alcohol abuse not only contributes to malnutrition, but alcohol
causes chemical changes that can result in lower folate levels.
Any condition
that disturbs the small intestine and impairs its absorption ability
can cause a deficiency. Such disorders include the following:
- Inflammatory
bowel disease.
- Celiac
sprue (a sensitivity reaction to gluten).
- Parasitic
diseases such as giardiasis.
- Short
bowel syndrome.
- Deficiencies
can also be caused by high demand for folic acid caused by conditions
such as cancer, pregnancy, severe psoriasis, severe hyperthyroidism,
and hemolytic anemia.
- Some drugs,
including Dilantin, methotrexate, trimethoprim, and triamterene,
may also hinder folate absorption.
Miscellaneous
Causes of Anemia
Kidney failure
and dialysis treatments are highly associated with anemia. Other
disorders not related to inflammation or bleeding that cause anemia
include AIDS, hypothyroidism, and leukemia. Certain conditions,
including cirrhosis, congestive heart failure, and enlarged spleens,
cause a back up of fluid. This produces a higher volume of blood
plasma (the liquid part of blood) which can dilute red blood cells
and cause anemia. Many medications increase the risk for anemia.
Among them are certain antibiotics, some antiseizure medications
(eg, phenytoin), immunosuppressive drugs (eg, methotrexate, azathioprine),
antiarrhythmic agents (procainamide, quinidine), anticlotting drugs
(aspirin, warfarin, heparin), and cancer treatments, including drugs
and radiation.
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Less Common Anemias
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Form
of Anemia
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Description
and Diagnosis
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Causes
and Risk Factors
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Treatments
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Aplastic Anemia
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Fat cells replace bone marrow. Reduction in all types of
blood cells. Formerly fatal, but now treatable. Symptoms
in addition to standard anemia are bleeding in mucous membranes
and skin, gingivitis, and shortness of breath.
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Very rare (two to six cases per one million people). Usually
found in younger patients. Cause can be a virus, self-attack
of the immune system (autoimmune disease), or chemicals
such as benzene and pesticides.
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Transfusions, antibiotics, bone marrow transplantation,
immunosuppressant drugs. (It is nearly always fatal if treated
with transfusions and antibiotics alone.)
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Thalassemia
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Genetic blood disease caused by a defect in the rate of
production of hemoglobin. The two major forms are thalassemia
minor and thalassemia major (Cooley's anemia, beta thalassemia).
Thalassemia minor is the more common and milder form, in
which life span is normal. Thalassemia major can be serious
but it is fortunately very rare.
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Affects males and females equally. Most common in people
of Mediterranean descent, especially Italians and Greeks.
Both types of thalassemia are found in an area that extends
from northern Africa and southern Europe to Thailand, including
Iran, Iraq, Indonesia, and southern China. Thalassemia major
is more common in families who intermarry.
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No treatment necessary for thalassemia minor. Transfusions
with deferoxamine (iron chelation therapy) are standard
therapy. Bone marrow transplantation.
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Hemolytic Anemias: Acquired
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Anemia caused by hemolysis (premature destruction of red
blood cells). Diagnosis considered when there is marked
increase in RBC production by bone marrow.
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Autoimmune hemolytic anemia is the primary type, in which
antibodies produced by the immune system damage RBCs. Cause
unknown or associated with disorders such as systemic lupus
erythematosus or lymphoma. Other causes are toxic agents,
including lead, copper, and benzene, snake and insect bites,
malaria, transfusions, post-surgical complications, and
drugs such as methyldopa.
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Corticosteroids for autoimmune hemolytic anemia.
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Hemolytic Anemias: Inherited
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Hemolysis (premature destruction of RBCs) caused by sphere-shaped
RBCs, which have difficulties circulating through the spleen.
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Inherited defects include membrane defects, hemoglobin abnormalities,
and enzyme deficiencies. Fava beans may trigger symptoms.
More likely and more serious in males than females.
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Blood transfusions may be necessary for some types of hemolytic
anemia. Experimental trials use immune globulin. Removal
of the spleen (splenectomy) may help some patients.
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Sideroblastic Anemias
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Group of anemias caused by impaired ability of bone marrow
to produce normal RBCs. Normal to high iron levels, but
iron cannot be used to make hemoglobin. In addition to the
standard symptoms of anemia are jaundice, enlarged liver
and spleen, fever, headache, loss of appetite, vomiting,
and leg sores. Symptoms can be mild. Usually appears in
childhood. Infections, trauma, and pregnancy may trigger
symptoms.
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Inherited or acquired after excessive alcohol use, certain
medications, including chloramphenicol, or other disorders,
including some cancers and rheumatoid arthritis. More common
in the elderly.
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Deferoxamine (Desferal) is used to remove iron. Effectiveness
is increased when ascorbate is added to the regimen. Folate
and pyridoxine are used, but their effectiveness is under
question.
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Sickle Cell Anemia
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Serious, life-threatening, inherited disease. The sickle-shaped,
inflexible RBC has impaired ability to squeeze through vessels.
Short life span of RBC (10-20 days) causes anemia. In addition
to anemia symptoms, joint and bone pain, infections, and
heart failure can occur.
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Disease occurs in 0.6% and the trait is found in the genetic
makeup of 9% of African Americans. Also occurs in people
from India and Spanish-speaking and Mediterranean regions.
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Measures to avoid cycling and control pain. Including hydration,
hydroxyurea, NSAIDs and Narcotic analgesics. Bone marrow
transplantation. [
58,
Sickle-Cell Disease. ]
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WHO
BECOMES ANEMIC?
General
Risk Factors for Iron Deficiency
Population
Groups. Although nutritional iron-deficiency anemia has declined
in industrialized nations, 500 to 600 million people (one-sixth
of the world's population) are still affected by it. Even in the
US, iron deficiency is the most prevalent nutritional deficiency
and is highly associated with poverty.
Age and Gender. Young children and premenopausal women are
at highest risk, with those in lower socioeconomic groups having
double the risk of those who are middle or upper class.
Adolescent and adult men and postmenopausal women have the lowest
risk. Men, in fact, are at risk for iron overload, probably because
of their higher meat intake.
Risk
Factors in Infants and Young Children
In general, full-term
infants who are breast fed by their mothers are born with sufficient
iron stores got about six months. After that, they must rely on
other sources for iron. An estimated 8% of children in the US have
anemia, but the percentage varies according to region. A New York
study, for example, found that 10% of children under three were
anemic, and a 1999 Alaskan study reported twice the prevalence in
Native American children as the national average. The risk is highest
in low-income homes. No child, however, is immune to iron deficiency.
Iron-deficiency anemia in infants and small children can be due
to one or more of the following factors:
- Prematurity.
- Too early
an introduction of cow's milk.
- The use
of formula that isn't iron-fortified.
- The toddler's
own preferences for iron-poor food.
- Low consumption
of foods that enhance iron absorption, such as citrus fruits.
(It should be noted, however, that iron deficiency anemia in
children has been associated with drinking too much fruit juice.)
- Strict
vegetarianism in small children.
- Experts
have now identified an anemia in children that is associated
with inflammation from infections such as ear infections, urinary
tract infections, or others.
- One study
suggested that high fat diets in children were associated with
lower iron stores.
Risk
Factors for Premenopausal Women
According to
one report, 10% of women in their reproductive years have iron deficiencies,
and between 2% and 5% have iron levels low enough to cause anemia.
The risk for anemia (usually mild) in women occurs with one or more
of the following conditions.
- Heavy
menstruation for longer than five days.
- Abnormal
uterine bleeding, such as from fibroids.
- Pregnancy.
About 20% of women in industrialized countries have iron deficiency
during pregnancy. Multiple pregnancies and births significantly
increase the risk. [ See Box Anemia
and the Pregnant Woman.]
Risk
Factors for Older Adults
Although a number
of studies have reported that anemia is common and even underdiagnosed
in older adults, middle- to upper-class older Americans are unlikely
to be iron deficient. Studies suggest in fact that only about 1%
of this group actually has iron deficiency anemia. (In fact, experts
are concerned that many older people may be consuming too much iron,
particularly from meat-rich diets. In one study, 12.9% of older
middle class people had elevated iron levels, nearly all from diet.)
If iron deficiency occurs in the elderly, it is most likely to be
due causes other than diet, particularly gastrointestinal bleeding
or from blood loss during surgery. Elderly people without teeth
whose diets depend on canned foods are vulnerable to anemia from
folic acid and other vitamin deficiencies.
People
with Alcoholism
People with alcoholism
are at risk for anemia both from internal bleeding and vitamin B
deficiencies.
People
with Iron-Poor Diets
Although indications
are that most Americans are consuming too much iron in their diets,
some people may be at risk for dietary iron deficiencies:
- People
whose diets are high in processed foods and lack any meat.
- Strict
vegetarians. Vegetarians who avoid all animal products may have
a slightly higher risk for deficiencies in iron and some B vitamins.
Although dried beans and green vegetables often contain iron,
it is less easily absorbed from plants than from meat. Fortunately,
most commercial cereals are fortified with vitamin B12 and folic
acid (the synthetic form of folate). Studies on the prevalence
of anemia in vegetarians are weak. A 2001 study of British resident
reported that anemia was more common in vegetarians than in
meat eaters. One 1999 study found no significant differences
in hemoglobin measurements between vegetarians and non-vegetarians,
but a large percentage of both groups (18% of vegetarians and
13% of non-vegetarians) had low iron stores.
Chronic
Illnesses
Anyone with a
chronic disease that causes inflammation or bleeding is at risk
for anemia.
Athletes
Working out regularly
may cause some iron loss, which is comparable to that from menstruation
and rarely worrisome. One 2000 study suggests that dietary choices
may account for most cases of sports anemia. Intense, sustained
exercise, such as that performed by marathon runners, may cause
a condition called sports anemia, which may be due to slight gastrointestinal
bleeding, damaged red blood cells, low iron intake, or poor intestinal
absorption of iron.
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ANEMIA AND THE PREGNANT WOMAN
The Effect of Pregnancy on Anemia
Iron
deficiency occurs in 20% of pregnant women in developed
countries. Even worse, 50% or more of women in nonindustrialized
nations become iron deficient and between 30% and 50% are
deficient in folic acid. Severe anemia is associated with
a higher mortality rate among pregnant women. Mild to moderate
anemia, however, does not pose any elevated risk.
Pregnancy increases the risk for anemia in different ways:
-
Pregnancy increases the body's demand for folic acid
and therefore poses a risk for deficiencies and an increased
risk for megaloblastic anemia. Low levels of folate
during pregnancy increase the risk of neural tube defects
in newborns.
-
Pregnancy also increases the demand for iron thus posing
a risk for iron deficiency anemia. Pregnant or nursing
women require 30 mg of iron per day. Maternal iron deficiency
anemia is associated with increased weight or size of
the placenta, a condition that may pose a risk for later
high blood pressure in the offspring. Pregnant women
with low hemoglobin levels (the iron-bearing component
in the blood) have an elevated risk for pre-term or
low birth weight infants. (It should be noted, however,
that iron supplements do not appear to have any effect
on these complications.)
-
Pregnancy is also associated with fluid retention, which
in turn may produce high volumes of plasma (the fluid
component of blood). This can dilute red blood cells,
which may lead to anemia.
-
After delivery, heavy bleeding, which occurs in 5% to
10% of women who have given birth, can cause symptoms
of anemia.
Diagnosing of Iron Deficiency during Pregnancy
A diagnosis
of iron deficiency is problematic in pregnant women. The
standard test is a measurement of ferritin levels, which
are low in most people with iron deficiency. Pregnant women,
however, may have high ferritin blood levels into their
third trimester but still be iron deficient. A newer test
that measures a factor called serum transferrin receptor
may prove to be a useful way of diagnosing iron deficiency
in women.
Preventing Anemia in Pregnant Women
Iron
Supplements. For the past 40 years, iron supplements
have been recommended for all pregnant women. This practice
has been challenged recently, however. There is no clear-cut
evidence that the mild iron deficiency in most pregnant
women experience is harmful. In addition, iron supplement
may not be completely harmless.
Some experts suggest iron supplements for the following
women:
-
All pregnant women whose hemoglobin levels are less
than 11 g/dl, and
-
For those whose serum ferritin levels are low in their
20th to 24th weeks of pregnancy.
On the
other hand, one 1999 study conducted in Singapore suggested
that women who did not take iron supplements faced an 11-fold
higher risk for anemia compared to those who took supplements,
but it is unknown if this risk would apply to women in other
populations. More research is needed.
Folic Acid Supplements. Women who are trying to conceive,
who are pregnant, and who are breast-feeding should take
400 mcg of folic acid a day. (They should be sure this is
folic acid and not folate, which is the natural form but
supplements at the same dose are half as potent.)
Treating Anemia during Pregnancy
Pregnant
women who become anemic and require treatment may be given
oral iron supplements or transfusions in severe cases. Alternatives
under investigation are intravenous iron sucrose (a newer
and safer form of IV iron) and erythropoietin (a hormone
that stimulates red blood cell production.)
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HOW
SERIOUS IS ANEMIA?
Effect
on Exercise Capacity
Most cases of
anemia are mild, including those that occur as a result of chronic
disease. Nevertheless, even mild anemia can reduce oxygen transport
in the blood, causing fatigue and a diminished physical capacity.
Moderate to severe iron-deficiency anemia is known to reduce endurance.
(Some studies indicate that even iron deficiency without
anemia can produce a subtle but still lower capacity for exercise.)
Complications
of Severe or Prolonged Anemia
Because a reduction
in red blood cells decreases the ability to absorb oxygen from the
lungs, overtime serious problems can occur in prolonged and severe
anemia that is not treated. Anemia can lead to secondary organ dysfunction
or damage, including heart arrhythmia and congestive heart failure.
Certain inherited forms of anemia, including thalassemia major,
pernicious anemia, and sickle-cell anemia can be life threatening.
Thalassemia major and sickle-cell anemia affect children and are
particularly devastating.
Effects
of Anemia in Pregnant Women
Pregnant women
who are anemic have an increased risk for poor pregnancy outcomes,
particularly if they are anemic in the first trimester. [ See
Box Anemia and the Pregnant Woman.]
Complications
from Anemia in Children and Adolescents
In children,
severe anemia can impair growth and motor and mental development.
Proof is lacking, but one small well-conducted trial suggested that
iron therapy in anemic children under two may help reverse some
of these problems. (Iron deficiency in vegetarian children without
anemia may cause mental impairment, but it appears to be temporary.)
A long-term 2000 study reported that 11- to 15-year old children
who had been severely iron-deficient during their infant years scored
lower than normal children in all subjects, but particularly in
written expression. They also tended to have more behavioral, general
health, and emotional problems. Another study reported that teenage
girls with iron deficiency, even without anemia, may have temporary
memory and concentration loss.
Effects
of Anemia in the Elderly
Anemia is common
in older people and can have significantly more severe complications
than anemia in younger adults. The following are examples of its
effects from different studies:
- A 1999
study reported higher mortality rates in anemic individuals
85 and older compared to their nonanemic peers. (The rates were
higher in anemic men than in women.)
- One study
found that anemia was a strong predictor of future serious problems
that were not present at the time anemia was first detected.
For example, 13% of elderly people with anemia developed cancer
over a ten-year period compared to 5% of nonanemic individuals.
Rates of infection and peptic ulcer rates were also higher in
anemic patients.
- Elderly
patients who are anemic for more than two days before heart
surgery have a greater risk for complications and death.
- According
to a 2001 study, elderly patients who have hematocrit levels
below 30% have lower survival rates after a heart attacks than
those without anemia. (It should be noted that in the same study,
half of the subjects were anemic when they had a heart attack.)
- A strong
association was noted between an increased incidence of falls
and the presence of anemia.
- One 1999
study also found an association between anemia and vascular
dementia. (This form of dementia is caused by lack of oxygen
to the brain. It is not related to Alzheimer's disease.)
- Effects
of Vitamin B12 Deficiencies and Pernicious Anemia.
In addition to
anemia, vitamin B12 deficiency can cause neurologic damage, which
can be irreversible if it continues for long periods without treatment.
People with pernicious anemia, which results in an inability to
absorb the vitamin, are not only at risk for neurologic damage,
but also have a higher risk for stomach cancer and possibly cancer
of the throat and mouth.
Anemia
in Cancer Patients
Anemia is particularly
serious in cancer patients. In people with many common cancers,
the presence of anemia is associated with a shorter survival times.
Anemia may exacerbate the toxicity of chemotherapy in elderly cancer
patients.
|
EFFECTS OF EXCESS IRON
High
iron stores can be dangerous and may be overlooked as a
problem, particularly in industrialized nations. High amounts
of iron have been associated with an increased risk for
cirrhosis, cardiomyopathy (a disease of the heart muscles),
diabetes, and certain cancers. Although a 2000 study found
no higher risk for heart disease in Caucasian males with
high iron stores, more research is needed to see if these
results can be confirmed, especially in women and other
population groups.
Excess Dietary Iron
High-meat
intake in Western countries has been associated with excess
iron stores. In fact, one study found that 91% of the older
American population had an iron intake that was higher than
recommended.
Hemochromatosis
An inherited
disease called hemochromatosis is a condition in which the
intestinal tract absorbs too much iron from food, which,
over time can damage organs and joints. About 10% of Caucasians
carry the gene. Progression is very slow, however, and the
disease is treatable if diagnosed before it has caused internal
injury.
|
WHAT
ARE THE SYMPTOMS OF ANEMIA?
Common
Symptoms
Symptoms of anemia
vary depending on the severity of the condition. Anemia may occur
without symptoms and be detected only during a medical examination
that includes a blood test. When they occur, symptoms may include
the following:
- Weakness
and fatigue are the most common symptoms of even mild anemia.
(Even iron deficiency without anemia can reduce working capacity
in some people.)
- Shortness
of breath on exertion.
- Rapid
heartbeat.
- Lightheadedness
or dizziness.
- Headache.
- Ringing
in the ears (tinnitus).
- Irritability
and other mood disturbances.
- Pale skin
(it should be noted, however, that healthy-looking skin color
does not rule out anemia if a patient has risk factors and other
symptoms of anemia) .
- Restless
leg syndrome and other sleep disturbances.
- Mental
confusion.
- Loss of
sexual drive.
Unusual
Symptoms
Pica.
One odd symptom, and in some cases a cause of iron deficiency is
pica. This is the habit of eating unusual substances, such
as ice (called pagophagia), clay, cardboard, foods that crunch,
or raw starch. For example, in one study, half of people whose pica
took the form of pagophagia (eating at least one tray of ice every
day for two months) or eating foods that crunch (such as raw potatoes,
carrots, or celery) were iron deficient. The pica often stops, particularly
in children, when iron supplements are given. Pica is difficult
to detect because patients are often ashamed to admit to such cravings.
Frequent Breath Holding. Studies have also indicated that
children who hold their breath frequently, even to the point of
fainting, when angry or upset may be iron-deficient. In one study,
taking iron supplements reduced this phenomenon in 88% of treated
children.
Symptoms
of Megaloblastic Anemia and its Causes
Symptoms of
Megaloblastic Anemia. The symptoms of megaloblastic anemia
from vitamin B12 or folic acid deficiencies not only include standard
anemic symptoms and also the following:
- Inflammation
of the mouth ( stomatitis).
- Inflammation
of the tongue ( glossitis), which involves shrinkage
at the surface and edges of the tongue.
Symptoms of
Pernicious Anemia. Early neurologic symptoms of pernicious anemia
are due to B12 deficiency. They include numbness and tingling, depression,
memory loss, and irritability. Advanced nerve damage can cause loss
of balance and staggering, confusion, dementia, spasticity, loss
of bladder control, and erectile dysfunction. Folic acid deficiency
does not cause neurologic damage, although people with this deficiency
can be irritable, forgetful, and experience personality changes.
Of concern for patients with pernicious anemia and B12 deficiency
anemia is that folic acid supplements can mask the presence of this
disease in its early stages but not cure it. (Only vitamin B12 is
a cure.)
HOW
IS ANEMIA DIAGNOSED?
Medical
History and Physical Examination
The first step
in any diagnosis is a physical examination to determine if the patient
has symptoms of anemia and any complications. [ See What
are the Symptoms of Anemia?] Because anemia may be the first symptom
of a serious illness, determining its cause is very important. This
may be difficult, particularly in the elderly, malnourished, or
people with chronic diseases, whose anemia may be caused by one
or more of a number of factors. A detailed medical, personal, and
dietary history should report the following:
- Any family
or personal history of anemia.
- A history
of gallbladder disease, jaundice, or enlarged spleen.
- Heavy
menstrual bleeding in women.
- Any occurrence
of blood in the stool or other signs of internal bleeding. (Even
if the patient has not observed any bleeding, nonvisible blood
may present so a rectal exam and stool test are essential.)
- Any dietary
history, particularly in people who are elderly, poor, or both.
The physician
should examine the patient carefully, especially checking for swollen
lymph nodes, an enlarged spleen, and pale skin and nail color.
Blood
Tests to Determine the Presence of any Anemia
For anemia from
any cause, specific blood tests are given to determine anemia from
any cause.
Blood and Hemoglobin Counts. A complete blood count (CBC)
test is always performed to determine the presence of anemia. The
red blood cells, or erythrocytes, and their iron-bearing
component, hemoglobin, are measured.
For example, severe anemia in adults is defined by the World Health
Organization as follows:
- Hemoglobin
concentrations below 7.5 mmol/L (120 g/L) in women.
- Below
8.1 mmol/L (130 g/L) in men.
A low red blood
cell (RBC) count could indicate a number of problems including bleeding
or a failure by bone marrow to manufacture red blood cells.
Hematocrit. Calculating the percentage of red blood cells
in blood plasma (a measurement called the hematocrit)
is also important. Plasma is the liquid portion of blood. People
with a high volume of plasma may be anemic even if their blood count
is normal because the blood cells have become diluted.
Normal percentages are highest in the very youngest individuals
and decline as people age. They also vary by gender. The following
are some examples of normal range:
- Newborns:
42% to 60%
- Children:
35% to 45%
- Adult
males: 41% to 53%
- Adult
women: 36% to 46%
Smokers, people
at high altitudes, and those who are dehydrated tend to have higher
than normal hematocrit levels. Those at greater risk for low hematocrit
levels include pregnant women and patients with cirrhosis, congestive
heart failure, and in patients with splenomegaly.
Reticulocyte Count. Reticulocytes are immature red blood
cells, and their count reflects the rate of red blood cell production.
The upper normal limit is about 100.000/mL. A low count, when bleeding
isn't the cause, suggests problems in production in the bone marrow.
An abnormally high count indicates that the red blood cells are
being destroyed in high numbers and indicates hemolytic anemia.
Blood Morphology. A blood smear viewed under a microscope
allows an expert to classify the blood by its color, size, and shape
(its morphology). Generally red blood cells are categorized
in the following ways:
- Pale-colored
( hypochromic) and abnormally small ( microcytic).
- Normal
colored and normal sized ( normochromic, normocytic).
- Abnormally
large ( macrocytic).
The shape of
the red blood cells, which can be distorted in many blood disorders,
is also important in determining a diagnosis.
Diagnosing
Iron Deficiency Anemia and its Causes
There are two
steps in making diagnosis in patients with symptoms of iron deficiency
anemia:
- The first
step is to determine if a person is actually deficient in iron.
- If iron
stores are low, then the second step is to diagnose the cause
of the iron deficiencies, which will help determine treatment.
Determining
if Iron Stores are Low: The following findings are important
in determining that a person is iron deficient:
- Blood
cells viewed under the microscope are pale-colored and abnormally
small ( microcytic). They are also mostly uneven in shape.
(These findings suggest iron deficiency but can also appear
in anemia of chronic disease and thalassemia, however.)
- Hemoglobin
and iron levels are low. (These findings further suggest iron
deficiency but can also occur in anemia of chronic disease.)
- Ferritin
levels are low. Ferritin is a protein that binds to iron
and low levels always mean reduced iron stores. High levels
in the blood, however, do not always mean that iron stores are
sufficient. For example, pregnant women may have high ferritin
blood levels into their third trimester but still be iron deficient.
(Ferritin levels may also be normal in patients with inflammation
from ACD, even if they also have low iron stores. [ See below.
])
- In children,
reticulocyte hemoglobin levels are low. (Reticulocytes
are immature red blood cells and this test may be the most effective
approach for diagnosing iron deficiency in children.)
Determining
Causes of Iron Deficiency. When iron deficiency anemia is diagnosed,
the next step is to determine what causes the iron deficiency itself.
- Dietary
iron deficiency is most common in children and infants. It rarely
is an issue in adult anemia.
- Heavy
menstrual or abnormal uterine bleeding is usually the cause
of iron deficiencies in young women. Increased need for iron
stores during pregnancy is also a common cause in this population.
- If internal
bleeding is suspected as the cause, the gastrointestinal tract
is usually the first choice as the source. A diagnosis in such
cases can be often be made if the patient has noticed blood
in the stools, which can be black and tarry as well as red-streaked.
Often, however, bleeding may be present but not visible. In
such cases, stool tests for this hidden ( occult) blood
are required. Additional tests may then be needed to diagnose
the precipitating condition. Endoscopy, a fiber optic tube used
to view into the gastrointestinal tract, may be used in some
patients, particularly the elderly when the source of bleeding
is unclear. Although endoscopy is not always performed in iron
deficient patients if there are no signs of GI bleeding, one
study suggested that this procedure could reveal other causes,
including some cancers, in many patients.
If the patient's
diet suggests low iron intake and other causes cannot be established
using inexpensive or noninvasive techniques, then the patient may
simply be given a monthly trial of iron supplements. If the patient
fails to respond, further evaluation is needed.
Diagnosing
Anemia of Chronic Disease (ACD)
Usually anemia
of chronic disease is recognized during the management of the primary
disease and, if the anemia is mild, additional diagnostic tests
are rarely needed. The following are typical findings in ACD:
- The blood
cells are normal looking.
- Blood
tests may typically show low levels of iron in the blood, but
ferritin levels are normal or even high. (Low levels of ferritin,
a protein that binds to iron, indicate iron deficiency.)
Differentiating
between ACD and Iron Deficiency. If a patient has symptoms and
test results suggestive of both anemia of chronic disease and iron
deficiency anemia, bone marrow examination may be performed, although
it is expensive and can be painful.
Simpler tests are being investigated as alternatives for differentiating
iron deficiency form ACD. A very promising test measures a factor
called serum transferrin receptor (TfR). Levels of TfR
are high in iron deficiency anemia, even in patients with ACD, but
they are normal or only slightly raised in ACD alone. Another test
measures levels of unsaturated iron-binding capacity (UIBC)
.
Diagnosing
Vitamin B-Related Anemias
Physicians need
a multi-step diagnostic procedure for determining vitamin B deficiencies
and the anemias that cause or are caused by them. Physicians may
arrive at a diagnosis of vitamin B12 or folic acid deficiencies
from different routes:
- They may
diagnose deficiencies after detecting megaloblastic anemia from
abnormal blood tests.
- They may
suspect vitamin deficiencies first from symptoms and history
and then look for anemia.
Diagnosing
Megaloblastic Anemia. Very large oval red blood cells indicate
megaloblastic anemia. Abnormally shaped neutrophils (certain white
blood cells) may also be present. Bone marrow aspiration may need
to be performed if the disease is strongly suspected but the diagnosis
is not clear.
Determining Vitamin Deficiency. Once megaloblastic anemia
has been diagnosed, the physician will need to determine which vitamin
deficiency is causing it. This is extremely important because if
a vitamin B12-deficient patient receives folate replacement only,
then irreversible nerve injuries may develop. (Even if blood tests
for megaloblastic anemia are normal, patients with neurologic and
psychiatric abnormalities that have no detectable cause should still
be tested for vitamin B12 deficiency.)
Deficiencies may be suggested by the presence of other disorders:
- Malnutrition,
alcohol abuse, pregnancy, a history of sprue, severe psoriasis,
or the use of antiseizure drugs may indicate a folic acid deficiency.
- A history
of stomach surgery, eating raw fish (which raises the possibility
of tapeworm), inflammatory bowel disease, or hypothyroidism
suggests vitamin B12 deficiency.
Often, vitamin
B deficiencies cannot be determined by a history or symptoms alone.
Blood tests are the primary indicators of both vitamin B12 and folic
acid deficiencies, but even blood tests for these vitamins are not
always straightforward:
- Folic
acid and vitamin B12 levels must always be measured at the same
time because each vitamin may affect the other.
- Folate
levels may be temporarily low in some people who are not truly
deficient.
- Folate
levels may temporarily rise in deficient people if they have
just eaten foods containing the vitamin.
- Antibiotics
can interfere with B12 levels.
Measuring methylmalonic
acid and homocysteine, substances in the blood that increase when
levels of one or both vitamins are low, improves accuracy.
Tests for Pernicious Anemia. Once a vitamin B12 deficiency
has been established and the physician has not found any intestinal
abnormalities or other factors to account for the deficiency, the
doctor presumes a diagnosis of pernicious anemia.
Until recently, the only methods for diagnosing pernicious anemia
were either a trial of vitamin B12 injections or a urine test known
as the Schilling test, which is not completely reliable. Some clinicians
no longer use it because of improvement in blood tests. Other tests
are used to detect antibodies to intrinsic factor and stomach cells
damaged by pernicious anemia.
Pernicious anemia is simple to treat (with vitamin replacement)
but it is easily missed, particularly in patients whose diets are
rich in folic acid. Folic acid can mask the early symptoms of pernicious
anemia but not cure it. Consequently the disease may persist until
serious neurologic symptoms occur. With folic acid now a required
additive in many commercial foods, some experts are concerned about
an increased incidence in pernicious anemia.
HOW
IS ANEMIA PREVENTED?
Dietary
Recommendations for Preventing Anemia
Foods for
Maintaining Healthy Iron Stores. The following are some suggestions
for increasing iron levels in the diet:
- The best
foods for increasing or maintaining healthy iron levels contain
absorbable iron, called heme iron . Such foods include
(in order of iron-richness) clams, oysters, organ meats, beef,
pork, poultry, and fish.
- About
60% of iron in meat is poorly absorbed; this is a form called
non-heme iron . Eggs, dairy products, and vegetables
that contain iron only have the non-heme form. Such plants
include dried beans and peas, iron-fortified cereals, bread,
and pasta products, dark green leafy vegetables (chard, spinach,
mustard greens, kale), dried fruits, nuts, and seeds. (One study
reported that even though non-heme iron is normally less easily
absorbed, people who were iron deficient absorbed 10 times the
amount of non-heme iron as people with normal iron levels.)
- Increasing
intake of vitamin-C rich foods can enhance absorption of non-heme
iron during a single meal, although regular intake of vitamin
C does not appear to have any significant effect on iron stores.
In any case, vitamin-C rich foods are healthful and include
broccoli, cabbage, citrus fruits, melon, tomatoes, and strawberries.
One orange or six ounces of orange juice can double the amount
of iron your body absorbs from plant foods.
- Foods
containing riboflavin (vitamin B2) may help enhance the response
of hemoglobin to iron. Sources include liver, dried fortified
cereals, and yogurt.
- Cooking
in cast iron pans and skillets is well known to increase iron
content of food. According to one study, however, boiling, steaming,
or stir-frying many vegetables in utensils composed of any
material significantly increases the release of iron stored
in plants so it is available to the body.
- Certain
nutrients, such as tannin (found in tea) or phytic acid (found
in foods such as seeds and bran) impedes the body's absorption
of dietary iron. (It is commonly believed that fiber impedes
iron absorption, but researchers report that it most likely
has no effect.)
Sources of
Vitamins B12 and Folate. Vitamins B12 and folate are important
for prevention of megaloblastic anemia and good health in general.
- The only
natural dietary sources of B12 are animal products, such as
meats, dairy products, eggs, and fish (clams and oily fish are
very high in B12); like other B vitamins, however, B12 is added
to commercial dried cereals. The RDA is 2.4 mcg a day. Deficiencies
are rare in young people, although the elderly may have trouble
absorbing natural vitamin B12 and require synthetic forms from
supplements and fortified foods.
- Folate
is best found in avocado, bananas, orange juice, cold cereal,
asparagus, fruits, green, leafy vegetables, dried beans and
peas, and yeast. The synthetic form, folic acid, is now added
to commercial grain products. Vitamins are usually made from
folic acid, which is about twice as potent as folate. Many experts
now recommend that adults have 400 mcg of folic acid daily,
which is considerably higher than standard recommendations of
400 mcg of folate, which does not take into consideration
the possible benefits of folate on the heart. Women who are
trying to conceive, who are pregnant, and who are breast feeding
should take 400 mcg of folic acid. [ See Box Anemia
and the Pregnant Woman.]
|
Recommended Daily Allowance for Iron
The Recommended
Daily Allowance of iron for people who are not iron deficient
varies by age group and other risk factors. (Iron supplements
are rarely recommended in people without evidence of iron
deficiency or anemia.)
Children between the ages of one and three: 10 mg per day
Teenage boys: 12 mg
Premenopausal girls and women: 15 mg per day
Pregnant or nursing women: 30 mg per day
Adult men (up to age 50): 10 mg per day
Older men and women (over age 50): 10 mg
|
Preventing
Anemia in Infants and Small Children
The main source
of iron for an infant from birth to one year of age is in milk,
either from breast milk, iron-fortified infant formula, or cereal.
The best methods for preventing iron deficiency during infancy are
the following:
- Prolonged
breast feeding. Breast fed babies have enough iron to last
four to six months assuming that the mother had adequate iron
stores during pregnancy. Some infants who are only breast fed
for the first year do not become iron-deficient although it
is not determined what factors in the mother, child, or both
are responsible for this protection. Breast milk itself is low
in iron, but if the mother's diet is healthy, vitamin C and
lactose in the breast milk may enhance iron absorption.
- Avoiding
cow's milk and unfortified formulas. If infants are given
formula, the American Academy of Pediatrics strongly discourages
the use of low-iron formulas (less than 4.0 mg/L). A 2000 study
found no adverse effects in even older infants and toddlers
who had been given a high-iron containing formula.
- Introducing
iron-fortified foods or supplements. Foods supplemented
with iron and vitamin C are usually introduced at around six
months of age in full-term infants. Premature infants should
receive iron supplements no later than two months after birth.
Supplements should continue for the first year of life in these
children. Some experts even recommend that all children
between ages one and two be given daily iron drops or iron-fortified
vitamins or drinks, although this is controversial.
WHAT
ARE THE TREATMENTS FOR ANEMIA?
General
Guidelines
Treatment
of Iron Deficiency. Iron supplements are the most effective
agents for restoring iron levels in anyone who is deficient, but
they should be used only when dietary measures have failed. It should
be noted that they will not correct anemias that are not due to
iron deficiency. One study reported that physicians prescribed iron
pills for 64% of patients with anemia without performing tests to
confirm whether iron deficiency was actually the cause. The study
suggested that iron replacement was appropriate in less than half
of these patients. Iron replacement therapy can cause gastrointestinal
problems, sometimes severe ones. Excess iron may also contribute
to heart disease, diabetes, and certain cancers. No one should take
iron supplements if they have a healthy diet and no indications
of iron deficiency anemia.
Treatment of Anemia of Chronic Disease. In general, the best
treatment for anemia of chronic diseases is treating the disease
itself. In some cases, iron deficiency accompanies the condition
and requires iron replacement. Erythropoietin, most often administered
with intravenous iron, is being investigated with success in some
patients.
Treatment of Megaloblastic Anemia. The standard treatments
for megaloblastic anemia are vitamin B12 injections and folic acid
replacement.
Iron
Supplements
Supplement
Forms. To replace iron, the preferred forms of iron tablets
are ferrous salts, usually ferrous sulfate (Feosol, Fer-In-Sol,
Mol-Iron). Other forms include ferrous fumarate (Femiron, FerroSequels,
Feostat, Fumerin, Hemocyte, Ircon), ferrous gluconate (Fergon, Ferralet,
Simron), polysaccharide-iron complex (Niferex, Nu-Iron), and carbonyl
iron (Elemental Iron, Feosol Caplet, Ferra-Cap). Specific brands
and forms may have certain advantages. The following are some examples:
- Prolonged-release
ferrous sulfate (Slow Fe) may enhance iron absorption with fewer
side effects than standard ferrous sulfate pills.
- FerroSequels
contains a stool softener, which helps prevent constipation.
- Polysaccharide-iron
complex has fewer side effects and equal absorption rates compared
to ferrous salts. It is very expensive, however.
- Carbonyl
iron is composed of very fine tiny uniform spheres of iron powder
and may prove to be less toxic than ferrous iron.
- Coated
or combination pills do not appear to offer any additional advantages
and may hinder absorption of the iron.
- Regimen.
The general guidelines for iron replacement are as follows:
- For adults,
physicians usually advise one ferrous sulfate tablet (300 mg)
three times a day.
- Iron replacement
doses for children with deficiencies are significantly lower.
In general. They are given as drops or syrup administered three
times a day. A single-dose daily regimen is showing promise.
IMPORTANT: As few as three adult iron tablets can poison
children, even fatally. This includes any form of iron pill.
No one, even
adults, should take a double dose of iron if one is missed.
Other tips for taking iron are as follows:
- For best
absorption, iron should be taken between meals. (Iron may cause
stomach and intestinal disturbances, however, and some experts
believe that low doses of ferrous sulfate can be taken with
food and absorbed without side effects.)
- One should
always drink a full eight ounces of fluid with an iron pill.
- Tablets
should be kept in a cool place. (Bathroom medicine cabinets
may be too warm and humid, which may cause the pills to disintegrate.)
- One study
suggested that iron supplements impeded the absorption of non-heme
iron (found in legumes and other vegetables) but not heme iron
(contained in meat).
Full recovery
takes six to eight weeks. (Recovery will take longer in people with
internal bleeding that is not under control.) Iron replacement therapy
must continue for about six months, even if anemia has been reversed.
Treatment must be continued indefinitely for people with chronic
bleeding; in such cases, iron levels should be closely monitored.
Side Effects. Common side effects of iron supplements include
the following:
- Constipation
and diarrhea are very common. They are rarely severe, although
iron tablets can aggravate existing gastrointestinal problems
such as ulcers and ulcerative colitis.
- Nausea
and vomiting may occur with high doses, but can be controlled
by taking smaller amounts. Switching to ferrous gluconate may
help some people with severe gastrointestinal problems.
- Black
stools are normal when taking iron tablets. In fact, if they
do not turn black, the tablets may not be working effectively.
This tends to be a more common problem with coated or long-acting
iron tablets.
- If the
stools are tarry looking as well as black, if they have red
streaks, or if cramps, sharp pains, or soreness in the stomach
occur, gastrointestinal bleeding may be causing the iron deficiency
and the patient should call the physician promptly.
- Acute
iron poisoning is rare in adults but can be fatal in children
who take adult-strength tablets.
Interactions
with Other Drugs. Certain medications, including antacids,
can reduce iron absorption. Iron tablets may also reduce the effectiveness
of other drugs, including the antibiotics tetracycline, penicillamine,
and ciprofloxacin and the anti-Parkinson's Disease drugs methyldopa,
levodopa, and carbidopa. At least two hours should elapse between
doses of these drugs and iron supplements.
Supplementary Agents. The following agents may improve iron
absorption:
- Adding
either ascorbic acid (vitamin C) or succinic acid to ferrous
sulfate therapy will improve absorption of iron stores. Ascorbic
acid added to iron therapy, however, may exacerbate some of
the side effects. Succinic acid added to ferrous sulfate does
not appear to increase side effects.
- Some studies
have found that the addition of zinc to iron supplements increases
hemoglobin levels more than iron alone. (Some evidence for this
suggests that zinc affects a hormone called insulin-like growth
factor-I (IGF-I), which plays a role in the regulation of red
blood cell production.)
- A study
of young Asian women found that the addition of vitamin A to
iron and folate supplements increased the absorption of iron
and folate. It should be noted that vitamin A is toxic in high
levels and can be particularly dangerous during pregnancy. No
one should take vitamin A supplements without guidance from
a physician.
Intravenous
or Injected Iron
In some cases
iron is administered through muscular injections or intravenously.
Intravenous iron has the advantage of causing less gastrointestinal
discomfort and inconvenience. It may be in the form of iron dextran
(Dexferrum, InFed), sodium ferric gluconate complex in sucrose (Ferrlecit),
or iron sucrose (Venofer). Many experts expect that Ferrlecit or
Venofer will prove to be more effective and safer than iron dextran.
Candidates. The injected or intravenous forms should be limited
to the following patients with iron deficiency:
- People
with iron deficiency anemia in whom oral therapy has clearly
failed.
- Patients
with bleeding disorders in which blood loss continues to exceed
the rate at which oral iron is absorbed.
- In emergencies
when people need red blood cells but transfusion is not appropriate
or available.
- In people
with serious gastrointestinal disorders that are severely aggravated
by oral therapy.
- People
undergoing hemodialysis who receive supplemental erythropoietin
therapy. Sodium ferric gluconate complex in sucrose (Ferrlecit)
or iron sucrose (Venofer) is specifically approved as first-line
therapy for these patients.
Certain patients,
even if they meet these qualifications, may not be appropriate candidates
or should be monitored closely for complications. They include:
- Patients
with any underlying autoimmune disease.
- Malnourished
patients who also have an underlying infection.
- Patients
who are at risk for iron overload.
Side Effects.
Some side effects differ depending on how the iron is administered
and include the following:
- Muscular
injections include pain at the site.
- Intravenous
administration can cause pain in the vein, flushing, and metallic
taste, which are all brief.
For both methods
side effects and serious complications can include the following:
- Blood
clots.
- Fever.
- Joint
aches.
- Headache.
- Rashes.
- Iron toxicity.
Symptoms include nausea, dizziness, a sudden drop in blood pressure.
Sodium ferric gluconate in sucrose (Ferrlecit) or iron sucrose
(Venofer) may pose a lower risk for toxicity than iron dextran.
- Allergic
reactions. Allergic reactions that occur with intravenous iron
can be very serious and, in rare cases, even fatal. Iron dextran
appears to pose a much higher risk than sodium ferric gluconate
complex in sucrose or iron sucrose, although allergic reactions
can also occur with the latter forms.
Oral and injected
iron should never be given at the same time. Intravenous
iron therapy may be appropriate for some pregnant women who meet
these requirements, depending on the pregnancy term and other factors.
Transfusions
If anemia is
severe, transfusions may be needed. They can be essential for anemic
patients who are hospitalized in the intensive care unit for their
illness, particularly if they have cardiovascular disease. In fact,
in a 2001 study, blood transfusions for heart attack patients with
hematocrit levels below 30% were associated with higher short-term
survival rates. It should be noted that if a heart attack patient's
hematocrit level is above 33%, a transfusion is likely to have a
negative effect and should not be performed.
Recombinant
Human Erythropoietin and Intravenous Iron
Erythropoietin,
the hormone that acts in the bone marrow to increase the production
of red blood cells, has been genetically engineered as recombinant
human erythropoietin, also called epoetin, EPO, or rHuEPO (Epogen).
AraNESP is a newer version. Experts have hoped that epoetin may
be helpful in certain patients with severe anemia of chronic diseases
and for patients with iron deficiencies due to dialysis.
Levels of erythropoietin are reduced in ACD. Epoetin dramatically
increases erythropoietin but also increases the requirements for
iron. In ACD patients intravenous iron must be used as well for
it to be effective. The older dextran-based IV iron is associated
with some very serious side effects. The newer forms using sodium
ferric gluconate complex in sucrose (Ferrlecit) or iron sucrose
(Venofer) may be safer and allow a wider use of epoetin in ACD.
The most effective dose of IV with the greatest safety margin is
not wholly known yet. [ See Intravenous or Injected Iron
under How Is Iron Deficiency Anemia Treated?]
At this point studies suggest the following use for epoetin.
- To date,
evidence on its benefits for ACD patients is strongest with
its use in those who have kidney failure. In such cases, it
reduces the risk of death from heart disease and improves quality
of life in patients on dialysis.
- Epoetin
is also beneficial for anemia associated with severe congestive
heart failure, which is now being recognized as one of the ACDs.
It is proving to improve both cardiovascular function and overall
health in patients with anemia and heart failure. In one study
it was particularly beneficial when administered with intravenous
iron.
- Although
epoetin alone is not useful for ACDs, such as rheumatoid arthritis
or inflammatory bowel disease, studies are suggesting that it
may be effective when used with the newer forms of intravenous
iron, sodium ferric gluconate complex in sucrose (Ferrlecit)
or iron sucrose (Venofer).
Epoetin in combination
with iron tablets, for example, may prove to help some patients,
including children, with inflammatory bowel disease who have not
responded to iron and vitamin therapy alone. Some experts are also
concerned that some patients may develop antibodies that react against
epoetin.
Epoetin is proving to be useful for other anemias not caused by
chronic diseases. [ See Box Other Uses of Recombinant Human
Erythropoietin in Anemia.]
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Other Uses of Recombinant Human Erythropoietin in Anemia
In addition
to some cases of ACD, recombinant human erythropoietin (Epogen)
is being used and investigated in the following conditions:
-
Epoetin is effective for treating cancer patients with
anemia on chemotherapy.
-
Epoetin is being used to treat anemia in premature babies,
but more studies are needed to determine its effectiveness
over time.
-
It may improve survival and enhance the quality of life
in HIV patients with anemia.
-
One European center reported that intravenous iron plus
epoetin benefited severely anemic pregnant women who
failed to respond to iron alone and who refused blood
transfusions.
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Antibiotics
for H. Pylori
H. pylori
, the bacteria that cause peptic ulcers, is associated with
anemias from vitamin B12 deficiency and iron deficiency. In one
2000 study, eradication of H. pylori with antibiotics corrected
both anemia and vitamin B12 deficiency in 40% of patients who had
both conditions. Studies are also showing that the eradication of
H. pylori i nfection with antibiotics can reverse anemia
in patients with iron deficiency anemia and lead to long-lasting
recovery.
Vitamin
Replacement for Megaloblastic Anemia
Vitamin B12
Therapy. Injections of vitamin B12 (usually formulations called
cyanocobalamin or hydroxocobalamin), oral folic acid therapy, or
both, rapidly reverse the production of abnormally large red blood
cells. (Treatments still may not reverse neurologic symptoms if
they are extensive or have continued for too long.)
A typical regimen for vitamin B12 replacement is as follows:
- If diagnostic
tests indicate pernicious anemia and neurologic symptoms are
present vitamin B12 therapy should begin immediately. (Usually
vitamin therapy is not an emergency, however.)
- Cyanocobalamin
or hydroxocobalamin injections are given every day for up to
two weeks. Only small doses are needed.
- This is
followed by injections twice a week for another month. (Hemoglobin
levels rise in the first week of therapy and reach normal in
eight weeks.)
- After
that, injections are usually given monthly.
- During
recovery, there is a risk of potassium deficiency as the new
red cells take up the existing supply, so potassium supplements
may be needed.
Other forms of
Vitamin B12 are also available and can be used to treat B12 deficiency.
Vitamin B12 by nasal spray offers the same advantage of avoiding
the need for absorbing the vitamin in the GI tract without the inconvenience
of the injections. Some experts feel that even oral B12 in high
doses (2,000 mcg/day) can maintain B12 levels once the deficiency
is treated.
The injections are safe and have no adverse side effects, but they
may mask an underlying medical or psychological condition.
It should be noted that some physicians give vitamin B12 injections
for fatigue and other vague symptoms of general mild discomfort.
In one study, 10% of patients in a rural clinic were given regular
B12 shots, with 6% of patients having no medical need for them.
Folic Acid Treatment. Folate deficiency is easily remedied
in four to five weeks with daily oral doses of one to two milligrams
of folic acid. Many doctors give vitamin B12 along with folic acid
unless B12 deficiency is definitely ruled out.
WHERE
ELSE CAN HELP FOR ANEMIA BE FOUND?
NIH/National
Heart, Lung and Blood Institute (NHLBI) Information Center
To contact a trained information specialist at the NHLBI Information
Center, Email (NHLBIinfo@rover.nhlbi.nih.gov)
Please include a valid E-mail address as well as a current postal
address, since many resources are available only as printed publications.
or on the Internet (https://www.nhlbi.nih.gov/index.htm)
Iron Disorders Institute Inc., P.O. Box 2031, Greenville, South
Carolina 29602 Call toll-free (888-565-4766) Leave your name and
how they may best reach you.
Or call (864-292-1175) or on the Internet (https://www.irondisorders.org/)
The American Academy of Pediatrics, PO Box 927, Elk Grove Village,
IL 60009-0927 or on the Internet (https://www.pediatrics.org)
National Organization for Rare Disorders (NORD), P.O. Box 8923,
New Fairfield, CT 06812-1783 Call (203-746-6518) or (800-999-6673)
or for the hearing impaired (203-746-6927) or on the Internet (https://www.rarediseases.org/)
American Autoimmune Related Diseases Association, Inc., 22100 Gratiot
Ave., Detroit, MI 48021 Call (800-776-3900) or on the Internet (https://www.aarda.org/)
Genetic Alliance, Inc., 4301 Connecticut Avenue, NW, Suite 404,
Washington DC, 20008-2304 Call (800-336-GENE) or (202-966-5557)
or on the Internet (https://www.geneticalliance.org/)
The Cooley's Anemia Foundation, Inc., 129-09 26th Avenue #203, Flushing,
NY 11354 Call (800-522-7222) or (718-321-2873) or on the Internet
(https://www.thalassemia.org)
Aplastic Anemia & MDS International Foundation of America AAFA,
Inc., P.O. Box 613, Annapolis, MD 21404-0613 Call (800-747-2820)
or (410) 867-0242 or on the Internet (https://www.aamds.org/)
On the Internet:
Please note: These sites are not reviewed by our physician editorial
board but our writers have found them to be helpful.
This site appears to have thoughtful dietary advice (https://www.dietitian.com/iron.html)
Australian Iron Status Advisory Panel (https://www.ironpanel.org.au/)
Iron Disorders Institute (https://www.irondisorders.org/)
ConsumerLab.com (https://www.ConsumerLab.com/)
This excellent site rates supplements and alternative products according
to quality and effectiveness. Their assessments now include iron
supplements. The site requires a paid subscription for full access,
but it is very useful.
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