Anemia
Encyclopedia
Anemia is a decrease in number of red blood cell
s (RBCs) or less than the normal quantity of hemoglobin
in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency.
Because hemoglobin (found inside RBCs) normally carries oxygen
from the lungs to the tissues
, anemia leads to hypoxia
(lack of oxygen) in organs. Because all human cells depend on oxygen
for survival, varying degrees of anemia can have a wide range of clinical consequences.
Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few. The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis
) or deficient red blood cell production (ineffective hematopoiesis).
There are two major approaches: the "kinetic" approach which involves evaluating production, destruction and loss, and the "morphologic" approach which groups anemia by red blood cell size. The morphologic approach uses a quickly available and low cost lab test as its starting point (the MCV
). On the other hand, focusing early on the question of production may allow the clinician to expose cases more rapidly where multiple causes of anemia coexist.
Most commonly, people with anemia report non-specific symptoms of a feeling of weakness, or fatigue, general malaise
and sometimes poor concentration. They may also report dyspnea
(shortness of breath) on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output
. The patient may have symptoms related to this, such as palpitation
s, angina (if preexisting heart disease is present), intermittent claudication
of the legs, and symptoms of heart failure.
On examination, the signs exhibited may include pallor
(pale skin, mucosal linings and nail beds) but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia
(in iron deficiency), jaundice
(when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in 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 based items such as dirt, paper, wax, grass, ice, and hair, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin
.
Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced scholastic performance in children of school age.
Restless legs syndrome
is more common in those with iron-deficiency anemia.
Less common symptoms may include swelling of the legs or arms, chronic heartburn, vague bruises, vomiting, increased sweating, and blood in stool.
. Apart from reporting the number of red blood cell
s and the hemoglobin
level, the automatic counters
also measure the size of the red blood cells by flow cytometry
, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope
can also be helpful, and is sometimes a necessity in regions of the world where automated analysis is less accessible.
In modern counters, four parameters (RBC count, hemoglobin concentration, MCV
and RDW
) are measured, allowing others (hematocrit
, MCH
and MCHC
) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.
Reticulocyte counts, and the "kinetic" approach to anemia, have become more common than in the past in the large medical centers of the United States and some other wealthy nations, in part because some automatic counters now have the capacity to include reticulocyte counts. A reticulocyte
count is a quantitative measure of the bone marrow
's production of new red blood cells. The reticulocyte production index is a calculation of the ratio between the level of anemia and the extent to which the reticulocyte count has risen in response. If the degree of anemia is significant, even a "normal" reticulocyte count actually may reflect an inadequate response.
If an automated count is not available, a reticulocyte count can be done manually following special staining of the blood film. In manual examination, activity of the bone marrow can also be gauged qualitatively by subtle changes in the numbers and the morphology of young RBCs by examination under a microscope. Newly formed RBCs are usually slightly larger than older RBCs and show polychromasia. Even where the source of blood loss is obvious, evaluation of erythropoiesis
can help assess whether the bone marrow will be able to compensate for the loss, and at what rate.
When the cause is not obvious, clinicians use other tests: ESR
, ferritin
, serum iron
, transferrin
, RBC folate level, serum vitamin B12
, hemoglobin electrophoresis
, renal function
tests (e.g. serum creatinine).
When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells.
(precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction and/or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH
suggesting cell destruction; or clinical signs of bleeding, such as guaiac-positive stool, radiographic findings, or frank bleeding.
The following is a simplified schematic of this approach:
* 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.
(MCV). If the cells are smaller than normal (under 80 fl
), the anemia is said to be microcytic; if they are normal size (80–100 fl), normocytic; and if they are larger than normal (over 100 fl), the anemia is classified as macrocytic. This scheme quickly exposes some of the most common causes of anemia; for instance, a microcytic anemia is often the result of iron deficiency
. In clinical workup, the MCV will be one of the first pieces of information available; so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.
Here is a schematic representation of how to consider anemia with MCV as the starting point:
Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cell
s may point to a cause in the bone marrow
.
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.
Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (6–10 lobes). The non-megaloblastic macrocytic anemias have different etiologies (i.e. there is unimpaired DNA globin synthesis,) which occur, for example in alcoholism.
In addition to the non-specific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy
and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology. 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
.
) remains normal. Causes include:
infestation leading to deficiency of both iron
and vitamin B12
or folic acid
or following a blood transfusion
more than one abnormality of red cell indices may be seen. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.
form in the cytoplasm of RBCs and appear like small dark dots under the microscope. There are many causes of Heinz body anemia, and some forms can be drug induced. It is triggered in cat
s by eating onion
s or acetaminophen (paracetamol). It can be triggered in dogs by ingesting onions or zinc
, and in horses by ingesting dry red maple leaves.
. It is often seen secondary to myelodysplastic syndrome
s.
Iron deficiency anemia
may also be refractory as a clinical manifestation of gastrointestinal problems which disrupt iron metabolism
.
s), blood loss and fluid overload (hypervolemia
). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually doesn't cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency. (See Iron deficiency anemia
)
s. These are generally featuring jaundice
and elevated LDH
levels.
) causes decreased hemoglobin concentration and apparent anemia:
Iron deficiency from nutritional causes is rare in men and post-menopausal women. The diagnosis of iron deficiency mandates a search for potential sources of loss such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate
, ferrous fumarate, or ferrous gluconate. When taking iron supplements, it is very common to experience stomach upset and/or darkening of the feces. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C
aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.
Vitamin supplements given orally (folic acid
) or intramuscularly (vitamin B-12
) will replace specific deficiencies.
In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with renal disease, some clinicians prescribe recombinant erythropoietin
, epoetin alfa
, to stimulate red-cell production.
In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be necessary.
in general, since multiple lines of evidence point to increased adverse patient clinical outcomes with more intensive transfusion strategies. The physiological principle that reduction of oxygen delivery associated with anemia leads to adverse clinical outcomes is balanced by the finding that transfusion does not necessarily mitigate these adverse clinical outcomes.
In severe, acute bleeding, transfusions of donated blood are often lifesaving. Improvements in battle
field casualty survival is attributable, at least in part, to the recent improvements in blood banking and transfusion techniques.
Transfusion of the stable but anemic hospitalized patient has been the subject of numerous clinical trials.
Four randomized controlled clinical trials have been conducted to evaluate aggressive versus conservative transfusion strategies in critically ill patients. All four of these studies failed to find a benefit with more aggressive transfusion strategies.
In addition, at least two retrospective studies have shown increases in adverse clinical outcomes in critically ill patients that underwent more aggressive transfusion strategies.
. The use of HBO is indicated when oxygen
delivery to tissue is not sufficient in patients who cannot be transfused
for medical or religious reasons. HBO may be used for medical reasons when threat of blood product
incompatibility or concern for transmissible disease
are factors. The beliefs of some religions (ex: Jehovah's Witnesses
) may require they use the HBO method.
In 2002, Van Meter reviewed the publications
surrounding the use of HBO in severe anemia and found that all publications report a positive result.
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s (RBCs) or less than the normal quantity of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin deficiency.
Because hemoglobin (found inside RBCs) normally carries oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
from the lungs to the tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, anemia leads to hypoxia
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
(lack of oxygen) in organs. Because all human cells depend on oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
for survival, varying degrees of anemia can have a wide range of clinical consequences.
Anemia is the most common disorder of the blood. There are several kinds of anemia, produced by a variety of underlying causes. Anemia can be classified in a variety of ways, based on the morphology of RBCs, underlying etiologic mechanisms, and discernible clinical spectra, to mention a few. The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
) or deficient red blood cell production (ineffective hematopoiesis).
There are two major approaches: the "kinetic" approach which involves evaluating production, destruction and loss, and the "morphologic" approach which groups anemia by red blood cell size. The morphologic approach uses a quickly available and low cost lab test as its starting point (the MCV
Mean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
). On the other hand, focusing early on the question of production may allow the clinician to expose cases more rapidly where multiple causes of anemia coexist.
Signs and symptoms
Anemia goes undetermined in many people, and symptoms can be minor or vague. The signs and symptoms can be related to the anemia itself, or the underlying cause.Most commonly, people with anemia report non-specific symptoms of a feeling of weakness, or fatigue, general malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
and sometimes poor concentration. They may also report dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
(shortness of breath) on exertion. In very severe anemia, the body may compensate for the lack of oxygen-carrying capability of the blood by increasing cardiac output
Cardiac output
Cardiac output is the volume of blood being pumped by the heart, in particular by a left or right ventricle in the time interval of one minute. CO may be measured in many ways, for example dm3/min...
. The patient may have symptoms related to this, such as palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
s, angina (if preexisting heart disease is present), intermittent claudication
Claudication
Claudication, literally 'limping' , is a medical term usually referring to impairment in walking, or pain, discomfort or tiredness in the legs that occurs during walking and is relieved by rest. The perceived level of pain from claudication can be mild to extremely severe. Claudication is most...
of the legs, and symptoms of heart failure.
On examination, the signs exhibited may include pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....
(pale skin, mucosal linings and nail beds) but this is not a reliable sign. There may be signs of specific causes of anemia, e.g., koilonychia
Koilonychia
Koilonychia is a nail disease that can be a sign of hypochromic anemia, especially iron-deficiency anemia. Koilonychia literally means "spoon nails." It refers to abnormally thin nails which have lost their convexity, becoming flat or even concave in shape...
(in iron deficiency), jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
(when anemia results from abnormal break down of red blood cells — in hemolytic anemia), bone deformities (found in thalassemia major) or leg ulcers (seen in sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
).
In severe anemia, there may be signs of a hyperdynamic circulation: tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
(a fast heart rate), bounding pulse
Bounding pulse
Bounding pulse is a medical sign characterized as a leaping and forceful pulse that quickly disappears. To feel a bounding pulse, the radial artery is lightly palpated at the distal palmar edge. It is best detected when the arm is held aloft....
, flow murmurs, and cardiac ventricular hypertrophy
Ventricular hypertrophy
Ventricular hypertrophy is the enlargement of ventricles in the heart. Although left ventricular hypertrophy is more common, enlargement can also occur in the right ventricle, or both ventricles.- Physiology :...
(enlargement). There may be signs of heart failure.
Pica
Pica (disorder)
Pica is characterized by an appetite for substances largely non-nutritive . For these actions to be considered pica, they must persist for more than one month at an age where eating such objects is considered developmentally inappropriate...
, the consumption of non-food based items such as dirt, paper, wax, grass, ice, and hair, may be a symptom of iron deficiency, although it occurs often in those who have normal levels of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
.
Chronic anemia may result in behavioral disturbances in children as a direct result of impaired neurological development in infants, and reduced scholastic performance in children of school age.
Restless legs syndrome
Restless legs syndrome
Restless legs syndrome or Willis-Ekbom disease is a neurological disorder characterized by an irresistible urge to move one's body to stop uncomfortable or odd sensations. It most commonly affects the legs, but can affect the arms, torso, and even phantom limbs...
is more common in those with iron-deficiency anemia.
Less common symptoms may include swelling of the legs or arms, chronic heartburn, vague bruises, vomiting, increased sweating, and blood in stool.
Diagnosis
Anemia is typically diagnosed on a complete blood countComplete blood count
A complete blood count , also known as full blood count or full blood exam or blood panel, is a test panel requested by a doctor or other medical professional that gives information about the cells in a patient's blood...
. Apart from reporting the number of red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s and the hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
level, the automatic counters
Automated analyser
An automated analyser is a medical laboratory instrument designed to measure different chemicals and other characteristics in a number of biological samples quickly, with minimal human assistance....
also measure the size of the red blood cells by flow cytometry
Flow cytometry
Flow cytometry is a technique for counting and examining microscopic particles, such as cells and chromosomes, by suspending them in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and/or chemical...
, which is an important tool in distinguishing between the causes of anemia. Examination of a stained blood smear using a microscope
Microscope
A microscope is an instrument used to see objects that are too small for the naked eye. The science of investigating small objects using such an instrument is called microscopy...
can also be helpful, and is sometimes a necessity in regions of the world where automated analysis is less accessible.
In modern counters, four parameters (RBC count, hemoglobin concentration, MCV
Mean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
and RDW
Red blood cell distribution width
The red blood cell distribution width is a measure of the variation of red blood cell width that is reported as part of a standard complete blood count. Usually red blood cells are a standard size of about 6–8 μm. Certain disorders, however, cause a significant variation in cell size. Higher...
) are measured, allowing others (hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
, MCH
Mean corpuscular hemoglobin
The mean corpuscular hemoglobin, or "mean cell hemoglobin" , is the average mass of hemoglobin per red blood cell in a sample of blood. It is reported as part of a standard complete blood count...
and MCHC
Mean corpuscular hemoglobin concentration
The mean corpuscular hemoglobin concentration, or MCHC, is a measure of the concentration of hemoglobin in a given volume of packed red blood cells. It is reported as part of a standard complete blood count....
) to be calculated, and compared to values adjusted for age and sex. Some counters estimate hematocrit from direct measurements.
| 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 |
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
Reticulocyte
Reticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
count is a quantitative measure of the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
'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
Erythropoiesis
Erythropoiesis is the process by which red blood cells are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin...
can help assess whether the bone marrow will be able to compensate for the loss, and at what rate.
When the cause is not obvious, clinicians use other tests: ESR
Erythrocyte sedimentation rate
The erythrocyte sedimentation rate , also called a sedimentation rate or Biernacki Reaction, is the rate at which red blood cells sediment in a period of 1 hour...
, ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
, serum iron
Serum iron
Serum iron is a medical laboratory test that measures the amount of circulating iron that is bound to transferrin. Clinicians order this laboratory test when they are concerned about iron deficiency, which can cause anemia and other problems....
, transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...
, RBC folate level, serum vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
, hemoglobin electrophoresis
Hemoglobin electrophoresis
Hemoglobin electrophoresis is a blood test that can detect different types of hemoglobin. It uses the principles of gel electrophoresis to separate out the various types of hemoglobin and is a type of native gel electrophoresis...
, renal function
Renal function
Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate describes the flow rate of filtered fluid through the kidney...
tests (e.g. serum creatinine).
When the diagnosis remains difficult, a bone marrow examination allows direct examination of the precursors to red cells.
Production vs. destruction or loss
The "kinetic" approach to anemia yields what many argue is the most clinically relevant classification of anemia. This classification depends on evaluation of several hematological parameters, particularly the blood reticulocyteReticulocyte
Reticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
(precursor of mature RBCs) count. This then yields the classification of defects by decreased RBC production versus increased RBC destruction and/or loss. Clinical signs of loss or destruction include abnormal peripheral blood smear with signs of hemolysis; elevated LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
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:
* For instance, sickle cell anemia with superimposed iron deficiency; chronic gastric bleeding with B12 and folate deficiency; and other instances of anemia with more than one cause.
** Confirm by repeating reticulocyte count: ongoing combination of low reticulocyte production index, normal MCV and hemolysis or loss may be seen in bone marrow failure or anemia of chronic disease, with superimposed or related hemolysis or blood loss.
Red blood cell size
In the morphological approach, anemia is classified by the size of red blood cells; this is either done automatically or on microscopic examination of a peripheral blood smear. The size is reflected in the mean corpuscular volumeMean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
(MCV). If the cells are smaller than normal (under 80 fl
Femtolitre
The femto litre is the metric unit of volume equal to 10−15 litre, or one quinine cillionth or one quadrillionth litre. It is abbreviated FL or fl. One femto litre is the same as 1 μm3.1....
), 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
Iron deficiency (medicine)
Iron deficiency is one of the most common of the nutritional deficiencies. Iron is present in all cells in the human body, and has several vital functions...
. In clinical workup, the MCV will be one of the first pieces of information available; so even among clinicians who consider the "kinetic" approach more useful philosophically, morphology will remain an important element of classification and diagnosis.
Here is a schematic representation of how to consider anemia with MCV as the starting point:
Other characteristics visible on the peripheral smear may provide valuable clues about a more specific diagnosis; for example, abnormal white blood cell
White blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s may point to a cause in the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
.
Microcytic
Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies:- HemeHemeA heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
synthesis defect- Iron deficiency anemiaIron deficiency anemiaIron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
- Anemia of chronic diseaseAnemia of chronic diseaseAnemia of chronic disease, also referred to as anemia of inflammatory response is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy...
(more commonly presenting as normocytic anemia)
- Iron deficiency anemia
- GlobinGlobinGlobins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
synthesis defect- alpha-, and beta-thalassemiaThalassemiaThalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
- HbE syndrome
- HbC syndrome
- and various other unstable hemoglobin diseases
- alpha-, and beta-thalassemia
- Sideroblastic defect
- Hereditary sideroblastic anemia
- Acquired sideroblastic anemia, including lead toxicityLead poisoningLead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
- Reversible sideroblastic anemia
Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope.
- Iron deficiency anemia is caused by insufficient dietary intake or absorption of ironIronIron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
to replace losses from menstruation or losses due to diseases. Iron is an essential part of hemoglobin, and low iron levels result in decreased incorporation of hemoglobin into red blood cells. In the United States, 20% of all women of childbearing age have iron deficiency anemia, compared with only 2% of adult men. The principal cause of iron deficiency anemia in premenopausal women is blood lost during mensesMenstruationMenstruation is the shedding of the uterine lining . It occurs on a regular basis in sexually reproductive-age females of certain mammal species. This article focuses on human menstruation.-Overview:...
. Studies have shown that iron deficiency without anemia causes poor school performance and lower IQ in teenage girls, although this may be due to socioeconomic factors. Iron deficiency is the most prevalent deficiency state on a worldwide basis. Iron deficiency is sometimes the cause of abnormal fissuring of the angular (corner) sections of the lips (angular stomatitis). - Iron deficiency anemia can also be due to bleeding lesions of the gastrointestinal tractGastrointestinal tractThe human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
. Fecal occult blood testingFecal occult bloodFecal occult blood refers to blood in the feces that is not visibly apparent. A fecal occult blood test checks for hidden blood in the stool...
, upper endoscopyEsophagogastroduodenoscopyFor other expansions of the initialism "OGD", see the disambiguation page.In medicine , esophagogastroduodenoscopy is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract up to the duodenum...
and lower endoscopyColonoscopyColonoscopy is the endoscopic examination of the large bowel and the distal part of the small bowel with a CCD camera or a fiber optic camera on a flexible tube passed through the anus. It may provide a visual diagnosis and grants the opportunity for biopsy or removal of suspected...
should be performed to identify bleeding lesions. In men and post-menopausal women the chances are higher that bleeding from the gastrointestinal tract could be due to colon polypPolyp (medicine)A polyp is an abnormal growth of tissue projecting from a mucous membrane. If it is attached to the surface by a narrow elongated stalk, it is said to be pedunculated. If no stalk is present, it is said to be sessile. Polyps are commonly found in the colon, stomach, nose, sinus, urinary bladder...
or colorectal cancerColorectal cancerColorectal cancer, commonly known as bowel cancer, is a cancer caused by uncontrolled cell growth , in the colon, rectum, or vermiform appendix. Colorectal cancer is clinically distinct from anal cancer, which affects the anus....
. - Worldwide, the most common cause of iron deficiency anemia is parasitic infestation (hookwormHookwormThe hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...
, amebiasis, schistosomiasisSchistosomiasisSchistosomiasis is a parasitic disease caused by several species of trematodes , a parasitic worm of the genus Schistosoma. Snails often act as an intermediary agent for the infectious diseases until a new human host is found...
and whipworm).
Macrocytic
- Megaloblastic anemiaMegaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12Vitamin B12Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
, folic acidFolic acidFolic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
(or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does.- Pernicious anemiaPernicious anemiaPernicious anemia is one of many types of the larger family of megaloblastic anemias...
is caused by a lack of intrinsic factor. Intrinsic factor is required to absorb vitamin B12 from food. A lack of intrinsic factor may arise from an autoimmune condition targeting the parietal cellParietal cellParietal cells, or oxyntic cells, are the stomach epithelium cells that secrete gastric acid and intrinsic factor.Acetylcholine and gastrin . The histamine receptors act by increasing intracellular cAMP, whereas the muscarinic and gastrin receptors increase intracellular Ca2+ levels...
s (atrophic gastritis) that produce intrinsic factorIntrinsic factorIntrinsic factor also known as gastric intrinsic factor is a glycoprotein produced by the parietal cells of the stomach. It is necessary for the absorption of vitamin B12 later on in the small intestine...
or against intrinsic factor itself. These lead to poor absorption of vitamin B12. - Macrocytic anemia can also be caused by 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.
- Pernicious anemia
- HypothyroidismHypothyroidismHypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
- AlcoholismAlcoholismAlcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
commonly causes a macrocytosisMacrocytosisMacrocytosis is the enlargement of red blood cells with near-constant hemoglobin concentration, and is defined by a mean corpuscular volume of greater than 100 femtolitres .- Causes :...
, although not specifically anemia. Other types of liver diseaseLiver diseaseLiver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...
can also cause macrocytosis. - MethotrexateMethotrexateMethotrexate , abbreviated MTX and formerly known as amethopterin, is an antimetabolite and antifolate drug. It is used in treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. It acts by inhibiting the metabolism of folic acid. Methotrexate...
, zidovudineZidovudineZidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
, and other drugs that inhibit DNA replicationDNA replicationDNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
.
Macrocytic anemia can be further divided into "megaloblastic anemia" or "non-megaloblastic macrocytic anemia". The cause of megaloblastic anemia is primarily a failure of DNA synthesis with preserved RNA synthesis, which result in restricted cell division of the progenitor cells. The megaloblastic anemias often present with neutrophil hypersegmentation (6–10 lobes). The non-megaloblastic macrocytic anemias have different etiologies (i.e. there is unimpaired DNA globin synthesis,) which occur, for example in alcoholism.
In addition to the non-specific symptoms of anemia, specific features of vitamin B12 deficiency include peripheral neuropathy
Peripheral neuropathy
Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of or trauma to the nerve or the side-effects of systemic illness....
and subacute combined degeneration of the cord with resulting balance difficulties from posterior column spinal cord pathology. Other features may include a smooth, red tongue and glossitis
Glossitis
Glossitis is inflammation of the tongue. It causes the tongue to swell and change color. Finger-like projections on the surface of the tongue may be lost, causing the tongue to appear smooth....
.
The treatment for vitamin B12-deficient anemia was first devised by William Murphy
William Murphy (scientist)
William Parry Murphy was an American physician who shared the Nobel Prize in Physiology or Medicine in 1934 with George Richards Minot and George Hoyt Whipple for their combined work in devising and treating macrocytic anemia .Murphy was born on February 6, 1892, at Stoughton, Wisconsin...
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
George Whipple
George Hoyt Whipple was an American physician, pathologist, biomedical researcher, and medical school educator and administrator...
then set about to isolate the curative substance chemically and ultimately were able to isolate the vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
from the liver. All three shared the 1934 Nobel Prize in Medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...
.
Normocytic
Normocytic anemia occurs when the overall hemoglobin levels are decreased, but the red blood cell size (mean corpuscular volumeMean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
) remains normal. Causes include:
- Acute blood loss
- Anemia of chronic diseaseAnemia of chronic diseaseAnemia of chronic disease, also referred to as anemia of inflammatory response is a form of anemia seen in chronic illness, e.g. from chronic infection, chronic immune activation, or malignancy...
- Aplastic anemiaAplastic anemiaAplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...
(bone marrow failure) - Hemolytic anemiaHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
Dimorphic
When two or more causes of anemia act simultaneously, e.g., macrocytic hypochromic, due to hookwormHookworm
The hookworm is a parasitic nematode that lives in the small intestine of its host, which may be a mammal such as a dog, cat, or human. Two species of hookworms commonly infect humans, Ancylostoma duodenale and Necator americanus. A. duodenale predominates in the Middle East, North Africa, India...
infestation leading to deficiency of both iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
and vitamin B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
or folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
or following a blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
more than one abnormality of red cell indices may be seen. Evidence for multiple causes appears with an elevated RBC distribution width (RDW), which suggests a wider-than-normal range of red cell sizes.
Heinz body anemia
Heinz bodiesHeinz body
Heinz bodies are inclusions within red blood cells composed of denatured hemoglobin.-History:They are named after Robert Heinz , a German physician who in 1890 described these inclusions in connection with cases of hemolytic anemia.-Form and appearance:Heinz bodies appear as small round inclusions...
form in the cytoplasm of RBCs and appear like small dark dots under the microscope. There are many causes of Heinz body anemia, and some forms can be drug induced. It is triggered in cat
Cat
The cat , also known as the domestic cat or housecat to distinguish it from other felids and felines, is a small, usually furry, domesticated, carnivorous mammal that is valued by humans for its companionship and for its ability to hunt vermin and household pests...
s by eating onion
Onion
The onion , also known as the bulb onion, common onion and garden onion, is the most widely cultivated species of the genus Allium. The genus Allium also contains a number of other species variously referred to as onions and cultivated for food, such as the Japanese bunching onion The onion...
s or acetaminophen (paracetamol). It can be triggered in dogs by ingesting onions or zinc
Zinc
Zinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
, and in horses by ingesting dry red maple leaves.
Hyperanemia
Hyperanemia is a severe form of anemia, in which the hematocrit is below 10%.Refractory anemia
Refractory anemia is an anemia which does not respond to treatmentTherapy
This is a list of types of therapy .* Adventure therapy* Animal-assisted therapy* Aquatic therapy* Aromatherapy* Art and dementia* Art therapy* Authentic Movement* Behavioral therapy* Bibliotherapy* Buteyko Method* Chemotherapy...
. It is often seen secondary to myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
s.
Iron deficiency anemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
may also be refractory as a clinical manifestation of gastrointestinal problems which disrupt iron metabolism
Human iron metabolism
Human iron metabolism is the set of chemical reactions maintaining human homeostasis of iron. Iron is an essential element for most life on Earth, including human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health and disease...
.
Causes
Broadly, causes of anemia may be classified as impaired red blood cell (RBC) production, increased RBC destruction (hemolytic anemiaHemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
s), blood loss and fluid overload (hypervolemia
Hypervolemia
Hypervolemia, or fluid overload, is the medical condition where there is too much fluid in the blood.The opposite condition is hypovolemia, which is too little fluid volume in the blood.-Causes:Excessive sodium or fluid intake:* IV therapy...
). Several of these may interplay to cause anemia eventually. Indeed, the most common cause of anemia is blood loss, but this usually doesn't cause any lasting symptoms unless a relatively impaired RBC production develops, in turn most commonly by iron deficiency. (See Iron deficiency anemia
Iron deficiency anemia
Iron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
)
Impaired production
- Disturbance of proliferation and differentiation of stem cells.
- Pure red cell aplasia
- Aplastic anemiaAplastic anemiaAplastic anemia is a condition where bone marrow does not produce sufficient new cells to replenish blood cells. The condition, per its name, involves both aplasia and anemia...
, affecting all kinds of blood cellBlood cellA blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...
s. Fanconi anemiaFanconi anemiaFanconi anemia is a genetic disease with an incidence of 1 per 350,000 births, with a higher frequency in Ashkenazi Jews and Afrikaners in South Africa.FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair...
is a hereditary disorder or defect featuring aplastic anemia and various other abnormalities. - Anemia of renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
, by insufficient erythropoietinErythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
production - Anemia of endocrine disorders
- Disturbance of proliferation and maturation of erythroblasts
- Pernicious anemiaPernicious anemiaPernicious anemia is one of many types of the larger family of megaloblastic anemias...
is a form of megaloblastic anemiaMegaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
due to vitamin B12Vitamin B12Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
deficiency dependent on impaired absorption of vitamin B12. - Anemia of folic acid deficiency. As with vitamin B12, it causes megaloblastic anemiaMegaloblastic anemiaMegaloblastic anemia is an anemia that results from inhibition of DNA synthesis in red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis stage...
- Anemia of prematurityAnemia of prematurityAnemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.-Pathophysiology:Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life...
, by diminished erythropoietin response to declining hematocrit levels, combined with blood loss from laboratory testing. It generally occurs in premature infants at 2 to 6 weeks of age. - Iron deficiency anemiaIron deficiency anemiaIron-deficiency anemia is a common anemia that occurs when iron loss occurs, and/or the dietary intake or absorption of iron is insufficient...
, resulting in deficient heme synthesis - thalassemiaThalassemiaThalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
s, causing deficient globin synthesis - Congenital dyserythropoietic anemiaCongenital dyserythropoietic anemiaCongenital dyserythropoietic anemia is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells in the body and a less than normal quantity of hemoglobin in...
s, causing ineffective erythropoiesis - Anemia of renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
(also causing stem cell dysfunction)
- Pernicious anemia
- Other mechanisms of impaired RBC production
- Myelophthisic anemia or myelophthisisMyelophthisisMyelophthisic anemia is a severe kind of anemia found in some people with diseases that affect the bone marrow. Myelophythisis refers to the displacement of hemopoietic bone-marrow tissue into the peripheral blood, either by fibrosis, tumors or granulomas.-Causes:Myelophythisis can occur in the...
is a severe type of anemia resulting from the replacement of bone marrow by other materials, such as malignant tumors or granulomas. - Myelodysplastic syndromeMyelodysplastic syndromeThe myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
- anemia of chronic inflammation
- Myelophthisic anemia or myelophthisis
Increased destruction
Anemias of increased red blood cell destruction are generally classified as hemolytic anemiaHemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
s. These are generally featuring jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
and elevated LDH
Lactate dehydrogenase
Lactate dehydrogenase is an enzyme present in a wide variety of organisms, including plants and animals.Lactate dehydrogenases exist in four distinct enzyme classes. Two of them are cytochrome c-dependent enzymes, each acting on either D-lactate or L-lactate...
levels.
- Intrinsic (intracorpuscular) abnormalities, where there the red blood cells have defects that cause premature destruction. All of these, except paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...
, are hereditary genetic disorderGenetic disorderA genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
s.- Hereditary spherocytosisHereditary spherocytosisHereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped , and therefore more prone to hemolysis.-Symptoms:As in non-hereditary spherocytosis,...
is a hereditary defect that results in defects in the RBC cell membrane, causing the erythrocytes to be sequestered and destroyed by the spleenSpleenThe spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
. - Hereditary elliptocytosisHereditary elliptocytosisHereditary elliptocytosis, also known as ovalocytosis, is an inherited blood disorder in which an abnormally large number of the sufferer's erythrocytes are elliptical rather than the typical biconcave disc shape. It is one of many red-cell membrane defects. In its severe forms, this disorder...
, another defect in membrane skeleton proteins - AbetalipoproteinemiaAbetalipoproteinemiaAbetalipoproteinemia, or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a deficiency of apolipoprotein B-48 and B-100, which are used in the synthesis and exportation of...
, causing defects in membrane lipids - Enzyme deficiencies
- Pyruvate kinasePyruvate kinasePyruvate kinase is an enzyme involved in glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate to ADP, yielding one molecule of pyruvate and one molecule of ATP.-Reaction:The reaction with pyruvate kinase:...
and hexokinaseHexokinaseA hexokinase is an enzyme that phosphorylates a six-carbon sugar, a hexose, to a hexose phosphate. In most tissues and organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate the most important product....
deficiencies, causing defect glycolysisGlycolysisGlycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+... - Glucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
and glutathione synthetaseGlutathione synthetaseGlutathione synthetase is the second enzyme in the glutathione biosynthesis pathway. It catalyses the condensation of gamma-glutamylcysteine and glycine, to form glutathione.In eukaryotes, this is a homodimeric enzyme...
deficiency, causing increased oxidative stressOxidative stressOxidative stress represents an imbalance between the production and manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage...
- Pyruvate kinase
- Hemoglobinopathies
- Sickle cell anemia
- Hemoglobinopathies causing unstable hemoglobins
- Paroxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuriaParoxysmal nocturnal hemoglobinuria , sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterised by complement-induced intravascular hemolytic anemia , red urine and thrombosis...
- Hereditary spherocytosis
- Extrinsic (extracorpuscular) abnormalities
- AntibodyAntibodyAn antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
-mediated- Warm autoimmune hemolytic anemiaWarm autoimmune hemolytic anemiaWarm Antibody Autoimmune Hemolytic Anemia is the most common of the autoimmune hemolytic diseases. About half of the cases are idiopathic, with the other half attributable to a predisposing condition or medications being taken.-Pathophysiology:...
is an anemia caused by autoimmune attack against red blood cells, primarily by IgG. It is the most common of the autoimmune hemolyticHemolysisHemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
diseases. It can be idiopathicIdiopathicIdiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
, that is, without any known cause, drug-associated or secondary to another disease such as systemic lupus erythematosusSystemic lupus erythematosusSystemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...
, or a malignancy, such as chronic lymphocytic leukemiaChronic lymphocytic leukemiaB-cell chronic lymphocytic leukemia , also known as chronic lymphoid leukemia , is the most common type of leukemia. Leukemias are cancers of the white blood cells . CLL affects B cell lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes, and normally fight infection by...
(CLL) - Cold agglutinin hemolytic anemia is primarily mediated by IgM. It can be idiopathic or result from an underlying condition.
- Rh diseaseRh diseaseRh disease is one of the causes of hemolytic disease of the newborn...
, one of the causes of hemolytic disease of the newbornHemolytic disease of the newbornHemolytic disease of the newborn, also known as hemolytic disease of the fetus and newborn, HDN, HDFN, or erythroblastosis fetalis, is an alloimmune condition that develops in a fetus, when the IgG molecules produced by the mother pass through the placenta... - Transfusion reaction to blood transfusionBlood transfusionBlood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s
- Warm autoimmune hemolytic anemia
- Mechanical trauma to red cells
- Microangiopathic hemolytic anemiaMicroangiopathic hemolytic anemiaIn medicine microangiopathic hemolytic anemia is a microangiopathic subgroup of hemolytic anemia caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.-Presentation:It is referred as Runner's anemia...
s, including thrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpuraThrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
and disseminated intravascular coagulationDisseminated intravascular coagulationDisseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood... - Infections, including malariaMalariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
- heart surgery
- Microangiopathic hemolytic anemia
- Antibody
Blood loss
- Anemia of prematurityAnemia of prematurityAnemia of prematurity refers to a form of anemia affecting preterm infants with decreased hematocrit.-Pathophysiology:Preterm infants are often anemic and typically experience heavy blood losses from frequent laboratory testing in the first few weeks of life...
from frequent blood sampling for laboratory testing, combined with insufficient RBC production. - TraumaPhysical traumaTrauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death...
or surgerySurgerySurgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
, causing acute blood loss - Gastrointestinal tract lesions, causing a rather chronic blood loss
- Gynecologic disturbances, also generally causing chronic blood loss
Fluid overload
Fluid overload (hypervolemiaHypervolemia
Hypervolemia, or fluid overload, is the medical condition where there is too much fluid in the blood.The opposite condition is hypovolemia, which is too little fluid volume in the blood.-Causes:Excessive sodium or fluid intake:* IV therapy...
) causes decreased hemoglobin concentration and apparent anemia:
- General causes of hypervolemiaHypervolemiaHypervolemia, or fluid overload, is the medical condition where there is too much fluid in the blood.The opposite condition is hypovolemia, which is too little fluid volume in the blood.-Causes:Excessive sodium or fluid intake:* IV therapy...
include excessive sodium or fluid intake, sodium or water retention and fluid shift into the intravascular space. - Anemia of pregnancy is anemia that is induced by blood volume expansion experienced in pregnancyPregnancyPregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
.
Treatments
Treatments for anemia depend on severity and cause.Iron deficiency from nutritional causes is rare in men and post-menopausal women. The diagnosis of iron deficiency mandates a search for potential sources of loss such as gastrointestinal bleeding from ulcers or colon cancer. Mild to moderate iron-deficiency anemia is treated by oral iron supplementation with ferrous sulfate
Iron(II) sulfate
Iron sulfate or ferrous sulfate is the chemical compound with the formula FeSO4. Known since ancient times as copperas and as green vitriol, the blue-green heptahydrate is the most common form of this material...
, ferrous fumarate, or ferrous gluconate. When taking iron supplements, it is very common to experience stomach upset and/or darkening of the feces. The stomach upset can be alleviated by taking the iron with food; however, this decreases the amount of iron absorbed. Vitamin C
Vitamin C
Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
aids in the body's ability to absorb iron, so taking oral iron supplements with orange juice is of benefit.
Vitamin supplements given orally (folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
) or intramuscularly (vitamin B-12
Cyanocobalamin
Cyanocobalamin is an especially common vitamer of the vitamin B12 family. It is the most famous vitamer of the family, because it is, in chemical terms, the most air-stable...
) will replace specific deficiencies.
In anemia of chronic disease, anemia associated with chemotherapy, or anemia associated with renal disease, some clinicians prescribe recombinant erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
, epoetin alfa
Epoetin alfa
Epoetin alfa is human erythropoietin produced in cell culture using recombinant DNA technology. It stimulates erythropoiesis and is used to treat anemia, commonly associated with chronic renal failure and cancer chemotherapy. Epoetin is marketed under the trade names Procrit and Epogen. Its...
, to stimulate red-cell production.
In severe cases of anemia, or with ongoing blood loss, a blood transfusion may be necessary.
Blood transfusions
Doctors attempt to avoid blood transfusionBlood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
in general, since multiple lines of evidence point to increased adverse patient clinical outcomes with more intensive transfusion strategies. The physiological principle that reduction of oxygen delivery associated with anemia leads to adverse clinical outcomes is balanced by the finding that transfusion does not necessarily mitigate these adverse clinical outcomes.
In severe, acute bleeding, transfusions of donated blood are often lifesaving. Improvements in battle
Battle
Generally, a battle is a conceptual component in the hierarchy of combat in warfare between two or more armed forces, or combatants. In a battle, each combatant will seek to defeat the others, with defeat determined by the conditions of a military campaign...
field casualty survival is attributable, at least in part, to the recent improvements in blood banking and transfusion techniques.
Transfusion of the stable but anemic hospitalized patient has been the subject of numerous clinical trials.
Four randomized controlled clinical trials have been conducted to evaluate aggressive versus conservative transfusion strategies in critically ill patients. All four of these studies failed to find a benefit with more aggressive transfusion strategies.
In addition, at least two retrospective studies have shown increases in adverse clinical outcomes in critically ill patients that underwent more aggressive transfusion strategies.
Hyperbaric oxygen
Treatment of exceptional blood loss (anemia) is recognized as an indication for hyperbaric oxygen (HBO) by the Undersea and Hyperbaric Medical SocietyUndersea and Hyperbaric Medical Society
The Undersea and Hyperbaric Medical Society is the primary source of information for diving and hyperbaric medicine physiology worldwide.-History:The Undersea Medical Society grew from the close associations of a small group of scientists...
. The use of HBO is indicated when oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
delivery to tissue is not sufficient in patients who cannot be transfused
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
for medical or religious reasons. HBO may be used for medical reasons when threat of blood product
Blood product
A blood product is any component of the blood which is collected from a donor for use in a blood transfusion. Whole blood is uncommonly used in transfusion medicine at present; most blood products consist of specific processed components such as red blood cells, blood plasma, or platelets.-Relation...
incompatibility or concern for transmissible disease
Transmission (medicine)
In medicine and biology, transmission is the passing of a communicable disease from an infected host individual or group to a conspecific individual or group, regardless of whether the other individual was previously infected...
are factors. The beliefs of some religions (ex: Jehovah's Witnesses
Jehovah's Witnesses and blood transfusions
Jehovah's Witnesses believe that the Bible prohibits ingesting blood and that Christians should therefore not accept blood transfusions or donate or store their own blood for transfusion...
) may require they use the HBO method.
In 2002, Van Meter reviewed the publications
Medical journal
A public health journal is a scientific journal devoted to the field of public health, including epidemiology, biostatistics, and health care . Public health journals, like most scientific journals, are peer-reviewed...
surrounding the use of HBO in severe anemia and found that all publications report a positive result.