Anemia is a type of condition that arises whenever the hemoglobin amount within an individual’s blood dips below normal. Often, a reduction in hemoglobin is associated with a reduction in the number of hematocrit and red blood cells (or RBCs). Hemoglobin is contained inside of red blood cells, and it is necessary for transporting and delivering oxygen from a person’s lungs to the other parts of their body. If the supply of oxygen is not enough, many organs and tissues in the body may be affected adversely. Individuals with anemia might lack energy and experience weakness and fatigue.
Anemia is a common condition. It affects both women and men of all ethnic groups, races, and ages. However, certain individuals have an increased risk of developing anemia. Those people include ones with diets lacking in vitamin and irons, chronic diseases like inflammatory bowel disease, cancer, diabetes, and kidney disease, a family history for inheriting anemia, those with significant blood loss due to surgery or an injury, and chronic infections like HIV or tuberculosis. Anemia may be severe, moderate, or mild, depending on how much hemoglobin or RBC count is reduced.
The primary causes of anemia include the following:
- Decreased or impaired production of red blood cells by bone marrow because of a nutritional deficiency (e.g., B vitamin deficiencies or an iron deficiency)
- A disease involving bone marrow (e.g., solid tumor, lymphoma, or an infection)
- Bone marrow failure (e.g., myelodysplastic syndrome, aplastic anemia)
- Loss of red blood cells from bleeding or increased RBC destruction, as in hemolytic anemia
Anemia can be chronic or acute. Chronic anemic might develop over a long period of time with long-term illnesses like cancer, chronic kidney disease, or diabetes. In those circumstances, the anemia-related symptoms might not be apparent due to the underlying disease masking it and/or anemia is adapted to by the body when it is developed over an extended period. When anemia is present in chronic conditions, it often goes undetected for a while. It might only be discovered after examinations or tests are conducted for other conditions.
Anemia might also arise in acute episodes like with significant loss of blood (invasive surgery or extensive injury) or with specific conditions where a high number of red blood cells are destroyed. Symptoms and signs can become apparent very fast, and the cause may be determined through a combination of testing, medical history, and physical examination.
Types of Anemia
Anemias may also be described based on the size of the red blood cells and the concentration of hemoglobin that is contained inside of them. If the size of the cells is a lot smaller than normal, this is referred to as microcytic anemia. It is called macrocytic anemia when it is much larger than normal. Also, if the hemoglobin concentration is a lot lower than normal, it is referred to as hypochromic anemia. The RBCs are referred to as hyperchromic if the concentration is a lot higher than normal.
Within the two major categories of general anemia causes, several kinds have different specific causes. The following are some of the most common types, with each section containing information on each of them.
Iron-deficiency anemia is a common form of anemia that has many different causes. The symptoms relate to the level of hemoglobin and the overall reduction in the number of RBCs. In mild to moderate iron-deficiency anemia, there might not be any symptoms or signs. Along with the most common symptoms and signs, iron deficiency anemia has some that unique to it. It might appear in the form of iron stores inside bodies that are chronically depleted.
They can include the following:
- A craving for eating unusual non-food substances like dirt or ice (also referred to as “pica”)
- Difficulty in swallowing
- Ulcers or cracks in the corners of the mouth
- Sore or swollen tongue
- Spoon-shaped or brittle nails
Iron is a critical trace element that is needed for producing healthy red blood cells. It is a heme component, part of the hemoglobin, which is a protein inside of red blood cells that bind with oxygen and makes it possible for oxygen to be transported by RBCS throughout the entire body. If there is not a enough iron taken compared to what is needed by the body, then the iron that is stored inside of the body starts being used up. As the stores of iron are depleted, fewer RBCs are made by the body with a reduced amount of hemoglobin contained in them, which results in anemia.
Some iron deficiency causes include the following:
- Chronic bleeding – When there is excessive bleeding over an extended time (chronic), then the iron stored in the body is depleted gradually, and this results in the body being unable to produce a enough red blood cells and hemoglobin. Iron deficiency in women might be due to bleeding fibroids or heavy menstrual periods. In older men and women, the bleeding is generally from intestinal diseases like cancer and ulcers.
- Dietary deficiency – An iron deficiency might be caused by a diet that lacks a enough iron. Certain beans, dark leafy greens, iron-fortified foods, fish, poultry, and meat are all excellent iron sources. Children and nursing or pregnant women especially need to have more iron because they have increased requirements. Lack of iron in pregnant women may lead to premature delivery and low birth weight infants. Women who plan to become pregnant or who are pregnant take iron supplements regularly to prevent those complications from occurring. Newborns who nurse from a mother who is iron deficient will tend also to develop iron deficiency anemia.
- Absorption problem – Certain conditions affect iron being absorbed from the food inside of the gastrointestinal (GI) tract. Malabsorption can result in anemia over time. Those conditions include Crohn disease, celiac disease, intestinal surgery like gastric bypass, and a reduction in stomach acid due to the use of prescription medicines.
Typically, initial blood tests will include conducting a complete blood count (CBC). Test results might show:
Hemoglobin (Hb) – levels might be normal during the early phases of the disease, but as anemia worsens, it will decrease.
Red blood cell indices – During the early stages, the red blood cells might be a normal color (normocytic, normochromic) and size. However, as the anemia continues to progress, the red blood cells become paler (hypochromic) and smaller (microcytic) than average.
The average size of red blood cells (MCV, mean corpuscular volume) – decreased
Average amounts of hemoglobin contained in red blood cells (MCH, mean corpuscular hemoglobin) – decreased
Hemoglobin concentration (MCHC, mean corpuscular hemoglobin concentration) – decreased
Increased variations in red blood cell size (RDW, red cell distribution width)
A blood smear might reveal red blood cells that are paler and smaller than normal and red blood cells that vary in shape (poikilocytosis) and size (anisocytosis).
If a healthcare professional suspects that an iron deficiency is causing a person’s anemia, then several follow-up tests might be conducted to confirm the suspected iron deficiency. They can include the following:
Serum iron – the iron level in a person’s blood, normally decreased ferritin – which is a protein used for storing iron. The small amount of ferritin released in the blood reflects the amount of iron that is stored in the body and is usually low with iron deficiency anemia. It is viewed as the most specific test to identify iron deficiency anemia unless there is inflammation or infection present.
Total iron-binding capacity (TIBC) and transferrin – transferrin is a type of protein that binds to iron and carries it throughout the blood; TIBC reflects the amount of transferrin that is available for binding to iron. With iron deficiency anemia, TIBC and the transferrin level are both high.
Reticulocyte count – the reticulocytes are immature, young red blood cells. There is a low number of reticulocytes contained in iron deficiency anemia since there is insufficient iron for producing new red blood cells.
Soluble transferrin receptor (sTfR) – the test is mainly ordered to help with distinguishing between anemia caused by a chronic illness or inflammation and anemia that is caused by an iron deficiency. It might be ordered instead of ferritin whenever an individual has inflammation suspected or present or has a chronic illness. In iron deficiency, it is high.
If iron deficiency is believed to be caused by chronic loss of blood, like with GI tract bleeding, other procedures and tests might be conducted. Lab tests that might have the ability to detect GI bleeding are fecal immunochemical test (FIT) or fecal occult blood test (FOBT).
Testing for Helicobacter pylori might detect a bacterium that might cause ulcers within the GI tract that could be due to chronic bleeding. If there are any positive test results, or if there is a strong suspicion that GI bleeding does exist, then procedures like colonoscopy or endoscopy might be performed in order to find where the bleeding is located so that it may be treated.
Typically, treating iron deficiency involves changes in diet and/or iron supplements. Vitamin C can also help with absorbing iron. However, if it is suspected that iron deficiency is the result of abnormal blood loss, additional testing may be necessary in order to determine what is causing the bleeding. Individuals who have severe iron deficiency might need iron therapy via injections or intravenous (IV) or a transfusion of blood cells. Once the underlying cause has been discovered and treated, the anemia usually resolves.
Pernicious anemia as well as Other Types of B Vitamin Deficiencies
Pernicious anemia is where not enough vitamin B12 is absorbed by the body to produce a enough RBCs. This occurs whenever the body does not produce enough of a substance referred to as “intrinsic factor,” which is a protein that the cells inside the stomach lining produce that binds with vitamin B12 so that it can be absorbed inside of the small intestine. When there is an insufficient amount of intrinsic factor, the body is unable to absorb vitamin B12 from the person’s diet, which reduces the body’s ability to produce a enough healthy red blood cells. This leads to anemia. Other causes of anemia and vitamin B12 deficiency include dietary deficiency as well as conditions affecting the absorption of vitamin B12 from the small intestines like infections, digestive disorders (Chrohn disease, celiac disease), certain drugs, and surgery. The most common of the causes of B12 deficiency is pernicious anemia.
Vitamin B12 deficiency may result in general anemia symptoms in addition to nerve problems. They might include the following:
- Unsteady walking
- Loss of balance
- Slow reflexes
- Muscle weaknesses
- Tingling and numbness that begins in the feet and hands (from nerve damage)
- In severe cases, dementia, depressions, memory loss, and/or confusion
Another B vitamin is folic acid, and deficiency in that vitamin might also result in anemia. Folic acid, which is also called folate, is contained in numerous foods, particularly in leafy, green vegetables. In the U.S., folic acid gets added to most grain products, so folic acid is seen only rarely in the U.S. these days. During pregnancy, folic acid is required for the regular development of the spinal cord and brain. It is essential for women who are considering pregnancy to ingest the right amounts of folate supplements before becoming pregnant and throughout their pregnancies, to ensure they do not become folate deficient.
Anemia that results from a folate or vitamin B12 deficiency is frequently called “megaloblastic anemia” since the red blood cells are bigger than normal. Lacking these vitamins does not allow red blood cells to develop in a normal way, which results in their larger size. That results in anemia and a reduced number of abnormally larger sized RBCs.
Additional tests are normally conducted to ensure the diagnosis. Some of those include the following:
- Vitamin B12 level – When vitamin B12 is deficient, blood levels might be low
- Folic acid level – the blood levels might be low if this B vitamin is deficient
- Homocysteine – might be high with either vitamin B or folate deficiency.
- MMA (Methylmalonic acid) – might be high when there is vitamin B12 deficiency
- Reticulocyte count -” a low number of reticulocytes, or young RBCs
- Antibodies against parietal cell or intrinsic factor – might be present with pernicious anemia
A biopsy or bone marrow aspiration might be performed sometimes to find out if the appearance of the marrow is consistent with megaloblastic anemia as well as to rule other types of bone marrow disorders out that might cause anemia as well with larger red blood cells.
Treatment for these conditions involves supplementation with whatever vitamin is deficient. If the deficiency is caused by the inability to absorb vitamin B12 out of the digestive tract, the vitamin might be given in the form of injections. Treating underlying causes like infection or digestive disorders might also help with resolving anemia.
Aplastic Anemia is a rare disease that is caused by a reduction in the number of all blood cell types that are produced by the bone marrow. The bone marrow normally produces a enough new platelets, white blood cells, and red blood cells for normal body functioning. Each kind of cell enters the blood circulates and finally dies within a certain amount of time. For example, red blood cells have a normal lifespan of around 120 days. If bone marrow is unable to produce a enough blood cells as replacements for the ones that die, then several symptoms might result, including those caused by anemia. This type of anemia may be severe, and in some cases, fatal.
Aplastic anemia symptoms might develop slowly or appear abruptly. Some of the common general symptoms to various kinds of anemia might appear first and due to the reduction in red blood cells.
Some additional symptoms and signs that might arise with aplastic anemia include ones that are due to a reduction in platelets include the following:
- Heavy menstrual bleeding
- Blood within the stool
- Pinpoint red spots on the skin
- Easy bruising
- Frequent bleeding gums and nose bleeds
- Prolonged bleeding
- There might also be symptoms and signs as a result of low white blood cell count:
- Increased severity and frequency of infections
- Usually, aplastic anemia causes are related to damage to stem cells within the bone marrow, which are responsible for producing blood cells. Some of the factors that might be involved with damage to bone marrow that might result in aplastic anemia include the following:
- Medicines like chloramphenicol (this is an antibiotic that is used rarely in the U.S.)
- Viral infections like CMV, EBV, HIV, or hepatitis
- Autoimmune disorders like rheumatoid arthritis or lupus
- Cancer therapy (chemotherapy or radiation)
- Exposure to certain toxic substances such as pesticides, benzene (contained in gasoline), or arsenic
- Aplastic anemia is rarely due to a genetic (inherited) disorder like Fanconi anemia. Consult the Fanconi Anemia Research website for more on the rare blood condition
- Other genetic disorders that lead to aplastic anemia include dyskeratosis congenita and Shwachman-Diamond syndrome
Complete blood count (CBC) is the initial anemia test, and it can reveal many different abnormal results, including the following:
Differential white blood counts are reduced in most kinds of cells other than lymphocytes
- Usually, red blood indices are normal
- Low platelet count
- White blood cell and red blood cell counts are low
- Hematocrit and/or hemoglobin levels might be low
- Some of the additional tests that might be conducted to help determine the cause and type of anemia include the following:
- ANA – for determining if autoimmune disease is the cause
- Vitamin B12 tests or iron tests might be performed for ruling out other causes
- Tests for the heavy metal arsenic and other toxins
- Tests for infections like CMV, EBV, HIV, and hepatitis can help with determining what the cause is
- Biopsy or bone marrow aspiration will show a reduction in the number of all kinds of cells
- Erythropoietin – normally is increased in aplastic anemia
- Reticulocyte count – the count is low
A complete medical history or physical examination might reveal potential aplastic anemia causes, like prior cancer treatment, certain drugs (such as chloramphenicol), or exposure to toxins. Some aplastic anemia cases are temporary, but others permanently damage the bone marrow. So, the treatment will depend on what the cause is. Eliminating or reducing exposure to certain drugs or toxins might help with resolving the condition. Medications might be given in order to stimulate the production of the bone marrow, for treating infections, and with autoimmune disorder cases to suppress the immune system. In severe cases, a bone marrow transplant and blood transfusions might be necessary.
Anemia is rarely due to problems causing red blood cells to be destroyed or die prematurely. Red blood cells normally live within the blood for around four months. The time is shortened with hemolytic anemia, to just a few days in some cases. The bone marrow is unable to produce new red blood cells fast enough to replace the ones that have been destroyed. The lack of red blood cells leads to a reduced capacity for supplying oxygen to the body’s tissues. That results in typical anemia symptoms.
Depending on what the cause is, hemolytic anemia might be acute, developing, and last for a long time, or chronic. The various types may have a wide range of symptoms and signs. For more information on this, see the discussions on the various kinds below.
The various hemolytic anemia causes fall into two major categories:
- Acquired forms where some factor results in red blood cells being destroyed early.
- Inherited forms where genes or a gene is passed from generation to generation that may result in abnormal hemoglobin or red blood cells.
Inherited Hemolytic Anemia
Thalassemia and sickle cell anemia are two of the more common inherited hemolytic anemia causes:
Sickle cell anemia is a type of disorder where the body produces abnormal hemoglobin. Sickle cell anemia causes the RBCs to become crescent-shaped, and under certain conditions, sickle cells. This “trait” (where one mutated gene is carried from one parent) may cause some minor difficulties. This “disease” (where two mutated genes are carried, one from each parent) can cause severe clinical issues. Misshapen blood cells are very unstable and lead to hemolysis. These misshaped blood cells may block blood vessels, which causes anemia and pain. Usually, newborns are screened for sickle cell anemia, especially those of African descent, since it is more likely that they will have this inherited trait. Screening is sometimes done prenatally on an amniotic fluid sample. Hemoglobin variant follow-up tests might be conducted in order to confirm a diagnosis. Usually, treatment is based on the severity, frequency, and type of symptoms.
Thalassemia is a type of inherited blood disorder that has an imbalance in the production of hemoglobin globin chains that result in smaller red blood cells and anemia. The red blood cells only break apart (hemolysis) in rare cases and have reduced lifespans. The “beta major” form (which is also referred to as Cooley’s anemia) might result in severe anemia, jaundice, and growth problems. There is not any significant hemolysis in milder forms. The “beta minor” minor form (which is sometimes referred to as beta thal trait) has no obvious symptoms and might cause mild anemia.
Some of the other less common kinds of inherited hemolytic anemia forms include the following:
- Hereditary spherocytosis – This results in abnormally shaped red blood cells (spherocytes) that might be observed on a blood smear. The cells are quite rigid and unable to pass through the spleen the way that normal red blood cells can and, therefore, are prematurely destroyed.
- Hereditary elliptocytosis – this is another cause of red blood cells that are abnormally oval-shaped that may be observed on blood smears.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency – This is an enzyme that is required for red blood cell survival. If deficient, red blood cells will encounter specific substances within the blood, and the cells will rupture and be destroyed. The substances may include fava beans, antimalarial medications, or naphthalene. G6PD deficiency can be diagnosed by testing for activity.
- Pyruvate kinase deficiency – this is another enzyme that is essential for red blood cell survival. Its deficiency causes significant anemia. This disease is rare and can be diagnosed with an enzyme activity test.
Given that some of the inherited forms might have mild symptoms, they might be initially detected on a routine blood smear and complete blood count (CBC), which may reveal different abnormal results that provide clues as to what the cause might be. Then usually, follow-up tests are conducted to make the diagnosis. Some of those tests include the following:
- Osmotic fragility test – red blood cells are detected that are more fragile than normal, that is sometimes found with hereditary spherocytosis
- G6PD test – for detecting a deficiency of this enzyme
- DNA analysis – is not performed routinely but may be used to help with diagnosing thalassemia, hemoglobin variants, and for determining carrier status
- Hemoglobinopathy evaluation
- There are no cures for these genetic disorders. However, frequently the symptoms that result from anemia can be alleviated with treatment.
Acquired Hemolytic Anemia
Some factors or conditions involved with acquired hemolytic anemia forms include the following:
- Autoimmune disorders – conditions where antibodies are produced by the body that act against their very own blood cells. There is not a good understanding of why this might happen. However, it accounts for around half of all hemolytic anemia cases. Certain diseases like hepatitis, HIV, and lupus can increase the risk that a person has for it.
- Transfusion reaction from an incompatible blood donor. It occurs only rarely. However, it may have serious complications when it does.
- Infections, like infectious mononucleosis (mono) and malaria
- Incompatibility of the mother-baby blood group – can result in the newborn developing hemolytic disease.
- Medications – there are certain medications like penicillin that may trigger the body to start producing antibodies that are directed against the red blood cells or cause the RBCs to be destroyed.
- Physical destruction of the red blood cells by, for instance, a cardiac bypass machine utilized during open-heart surgery or an artificial heart valve
- Paroxysmal Nocturnal Hemoglobinuria (PNH) – this is a rare condition where different kinds of blood cells, which include platelets, white blood cells, and red blood cells are abnormal due to lacking certain surface proteins. Since the red blood cells are defective, they are destroyed by the body earlier than what their normal lifespan would be. The disease happens due to a mutation or change in the gene PIGA within the stem cells that produce blood. Although this is a genetic disorder, it is not passed down from generation to generation (it is not an inherited condition). People who are affected frequently pass dark urine because of the hemoglobin that is released by the destroyed red blood cells. It is most noticeable in the morning since that is when urine is in its most concentrated form.
Quite often, hemolytic anemias are initially identified by symptoms and signs, by medical history, and during physical examination. For example, medical history may reveal cardiac surgery, penicillin treatment, or a recent transfusion. A blood smear and/or CBC might show different abnormal results. Depending on what the findings are, additional follow-up tests might be conducted. Some of them might include the following:
- Flow cytometry when PNH is suspected
- Reticulocyte count – which tends to be high
- Haptoglobin – normally is low
- Direct antiglobulin test (DAT) – in cases of autoimmune hemolytic anemia, mother-baby blood type incompatibility, or transfusion reaction
- Autoantibody tests for autoimmune disorders that are suspected
- Hemolytic anemia treatments are just as varied as their causes are. However, they have the same goal: treating the anemia’s underlying cause to stop or reduce the destruction of red blood cells and increase hemoglobin level and/or RBC count in order to alleviate symptoms. That might involve the following:
- Drugs used for suppressing the production of the autoantibodies that destroy red blood cells
- Blood transfusions for increasing the number of healthy red blood cells
- Bone marrow transplant – for increasing the production of normal red blood cells
- Avoiding triggers that may cause anemia, like the cold in some autoimmune hemolytic anemia forms, or for those who have G6PD deficiency, certain medicines, naphthalene, or fava beans.
- Anemia That is Caused by Certain Chronic Diseases
Some long-term or chronic illnesses can cause anemia. Anemia that is caused by chronic disease often goes undetected until a complete blood count (CBC) or other routine test shows abnormal results. That can result in several follow-up tests being utilized to determine what the underlying cause is. There are numerous chronic diseases and conditions that may cause anemia, including the following:
Kidney disease – the bone marrow produces red blood cells in response to the erythropoietin hormone, which is primarily made by the kidneys. Anemia can be caused by chronic kidney disease from too little of this hormone being produced. Erythropoietin injections can be used to treat the anemia.
Anemia from chronic disease – when chronic diseases are stimulating the inflammatory response of the body, the bone marrow’s ability to respond to erythropoietin is reduced. This mainly due to iron regulation being impaired in the body. Rheumatoid arthritis, for example, (which is a serious joint disease and autoimmune disease that is caused when the body attacks its own joints) may cause anemia via this mechanism. Other diseases that might produce anemia this way include such chronic infections as tuberculosis or HIV.
Several tests may be utilized to follow up on the abnormal results derived from initial tests like a blood smear and CBC for determining the chronic anemia’s underlying cause. Some of the tests might include the following:
- Comprehensive metabolic panel (CMP) – this is used for detecting chronic disorders
- Reticulocyte count – typically is low
- Tests for anemia caused by chronic disease might include the following:
- Soluble transferrin receptor (sTfR) – typically is low or normal
- Transferrin and Iron (TIBC) – both are typically low
- Tests for infections like TB and HIV
- Erythropoietin – typically it is mildly increased
- Tests for inflammation like CRP
Usually, treating anemia caused by chronic conditions involves resolving and/or determine the underlying disease. In the short term, blood transfusions might be used for treating the condition.