Anemia is a medical disorder in which there aren’t enough healthy red blood cells to carry sufficient oxygen throughout the body. Although iron deficiency is the most common cause of anemia, there are a number of other forms of the condition. Some are inherited, while others are acquired, according to the Mayo Clinic. Think of anemia like a fever: it’s a symptom of some other, underlying problem. Sometimes that problem is relatively minor and easily corrected; sometimes it’s serious and incurable. The severity of anemia doesn’t necessarily match the severity of the condition causing it, so it’s important to get to the bottom of even mild anemia (via the Merck Manual).
Anemia is extremely common. According to the Cleveland Clinic, it affects more than 2 billion people globally — more than 30% of the world’s population. It’s the most common blood disorder in the United States, affecting 3 million Americans. Anyone can get anemia, but some groups are more at risk than others. When it comes to iron deficiency anemia, women, infants and young children, the elderly, and those on blood thinners are at increased risk.
Anemia can be deadly if it (and its underlying cause) aren’t addressed. According to the Centers for Disease Control and Prevention (CDC), anemia leads to approximately 710,000 emergency room visits each year and kills more than 5,000 Americans annually.
Why red blood cells and hemoglobin are so important
Anemia is characterized by a lack of healthy red blood cells so, to understand the condition, you need to know a little bit about these microscopic VIPs. Red blood cells, also known as erythrocytes, are the most plentiful type of cell in blood, making up 40% to 45% of its volume. They also give blood its red color. Each cell is shaped like a disc with a flattened indentation in the center of each side (think the shape of a donut but without a hole). Red blood cells can easily change their shape to travel through the tiniest blood vessels of the body. But, over time, all this shape-shifting and squeezing through capillaries damages the cells, and an erythrocyte only survives about 120 days. Red blood cells are made in the bone marrow, where they mature for seven days before moving into the bloodstream. The hormone erythropoietin, secreted by the kidneys, controls production of red blood cells (via the American Society of Hematology).
Red blood cells carry a protein called hemoglobin. As a 2006 paper published by Baylor University Medical Center’s journal Proceedings explained, hemoglobin picks up oxygen from the lungs and delivers it to every cell in the body as red blood cells travel through arteries. Then, as red blood cells travel through the veins, hemoglobin binds to carbon dioxide and helps bring this waste product to the lungs, where it’s exhaled.
Iron deficiency is the most common cause of anemia
Iron is an essential component of hemoglobin. Adults have three to four grams of iron in their bodies, and most of this is found in hemoglobin. A small amount is stored in the form of ferritin for emergency use (via the National Institutes of Health). If you don’t have enough circulating iron and have exhausted your ferritin stores, your body won’t have the raw materials it needs to make hemoglobin, leading to iron deficiency anemia.
Iron deficiency is extremely common. According to WebMD, 20% of non-pregnant women, 50% of pregnant women, and 3% of men in the United States don’t have enough iron in their bodies. (It’s important to note, however, that you can have mild iron deficiency and not yet be anemic.) The Mayo Clinic outlined four potential causes of iron deficiency. Some individuals, particularly vegetarians and vegans, may not get enough iron in their diet. Others may have difficulty absorbing iron because of gastrointestinal surgery or a condition such as celiac disease that has damaged the lining of the intestines. A temporary increase in iron needs, such as during pregnancy, can also lead to deficiency because supply can’t keep up with demand. Blood loss, such as from a heavy period, ulcer, or physical trauma, can also rapidly deplete iron stores.
Not getting enough of certain vitamins can also cause anemia
Iron isn’t the only micronutrient needed to make healthy red blood cells, and a deficiency of folate (vitamin B9), vitamin B12 (cobalamin), or vitamin C can lead to anemia. According to a 2004 paper published in the Annual Review of Nutrition, stem cells in bone marrow need folate and vitamin B12 to help them turn into mature red blood cells. When it comes to vitamin C, a 2014 paper published in Free Radical Biology and Medicine explained that, not only does this micronutrient help the body absorb dietary iron, it also helps make iron more bioavailable for processes like hemoglobin creation. So, without adequate vitamin C, iron deficiency anemia is very likely. Additionally, vitamin C deficiency can cause excessive bleeding, which can also contribute to anemia (via Healthline).
Deficiency in folate, vitamin B12, and vitamin C can happen if you don’t get enough of these micronutrients in your diet. It can also occur if you have trouble absorbing these vitamins because of certain chronic GI conditions (such as celiac disease or Crohn’s disease), surgery to remove a large part of your intestines, or bacterial overgrowth in your small intestines. Heavy alcohol consumption and the use of certain medications can hinder absorption of folate, while smoking impairs your body’s ability to absorb vitamin C. Increased demand for folate during pregnancy and breastfeeding can also lead to deficiency. In the case of B12, a substance secreted by stomach cells, called intrinsic factor, is needed to absorb B12. In some autoimmune conditions, the immune system attacks these cells, making it impossible for dietary B12 to enter the bloodstream. This particular form of B12 deficiency anemia is called pernicious anemia (via the Mayo Clinic).
Thalassemia can cause mild to severe anemia
Thalassemia is an inherited genetic condition that affects hemoglobin creation. A hemoglobin molecule is made up of alpha and beta chains, and the genetic mutations that cause thalassemia reduce production of one type of chain. There are four genes that regulate development of the alpha hemoglobin chain, and you inherit two from each parent. If only one of the four genes carries the thalassemia mutation, you’ll have no symptoms but could still pass the mutated gene on to your children. Two mutated genes produce mild symptoms, while three cause moderate to severe symptoms. Stillbirth usually occurs if all four genes are affected. There are two genes (one from each parent) involved in making the beta hemoglobin chain. Inheriting one defective copy produces mild symptoms. Babies who inherit two defective genes are usually healthy at birth but develop moderate to severe symptoms by age two.
Thalassemia is an inherited condition and is most common among African Americans and those of Mediterranean and Southeast Asian ancestry. If individuals have no symptoms or only very mild symptoms, they may never be diagnosed and can unknowingly pass the mutated genes on to their children. People who know they have thalassemia may want to consult with a genetic counselor before trying to have children; there’s a form of assisted reproduction that can minimize the chance of passing on the mutated genes (via the Mayo Clinic).
Sickle-shaped red blood cells can lead to anemia
Sickle cell disease (SCD) is another inherited condition that can cause anemia. Individuals with SCD have two mutated copies of the HBB gene, which provides instructions for making one part of hemoglobin. These mutated genes cause hemoglobin to form incorrectly which, in turn, distorts the shape of the red blood cells carrying the hemoglobin. Instead of being flexible discs, the red blood cells of people with SCD have an inflexible crescent shape. This causes them to clump together and get stuck in small blood vessels. They also break down faster than normal red blood cells, according to MedlinePlus. If an individual only has one mutated copy of the gene, they’ll produce both normal and sickle-shaped red blood cells. They’re unlikely to have anemia or any other symptoms, but they could pass the gene on to their children (via the Mayo Clinic).
According to the Centers for Disease Control and Prevention (CDC), SCD is most common among people whose ancestors came from sub-Saharan Africa, South and Central America, the Caribbean, India, and the Mediterranean. Malaria is or was common in these regions, and scientists believe that individuals who carry the sickle cell gene are less likely to suffer severe forms of this potentially deadly infection. An estimated 100,000 Americans have SCD. Approximately one in every 365 Black or African American individuals have the condition, while one in 13 is a carrier.
A lack of stem cells causes anemia
Although bones seem hard and solid, most actually contain a soft, spongy substance at their centers called bone marrow. Bone marrow contains stem cells that differentiate and mature into all sorts of specialized cells. The bone marrow found in flat bones like the pelvis and sternum contains hematopoietic stem cells, which transform into red blood cells, white blood cells, and platelets, according to the Moffitt Cancer Center.
Aplastic anemia is a rare and serious condition in which bone marrow is either aplastic (contains no stem cells) or hypoplastic (contains few stem cells). Without enough stem cells to serve as raw materials, the body can’t produce adequate numbers of the three types of blood cells. Aplastic anemia can have many causes, including autoimmune disorders, radiation and chemotherapy treatments for cancer, and exposure to toxic substances. Aplastic anemia can also be a rare complication of using certain medications, viral infections, and even pregnancy (via the Mayo Clinic). Aplastic anemia can also be caused by inherited genetic mutations that affect stem cell production. Fanconi anemia is the most common form of inherited aplastic anemia and results in bone marrow failure because damaged DNA can’t be properly repaired (via the National Organization for Rare Disorders).
Anemia can also be caused by chronic inflammation
According to the National Institute of Diabetes and Digestive and Kidney Diseases, anemia of inflammation, also known as anemia of chronic disease (ACD), is the second most-common form of anemia, behind iron deficiency anemia. A number of conditions are associated with chronic inflammation. These include long-term infections such as HIV or tuberculosis, cancer, autoimmune conditions like lupus and rheumatoid arthritis, kidney disease, inflammatory bowel disease, type 2 diabetes, and heart disease.
The inflammation seen with these diseases can affect the process of making healthy red blood cells in a number of ways. Most often, it interferes with the body’s ability to store and use iron normally. Inflammation can also cause your kidneys to produce less erythropoietin (the hormone that regulates production of red blood cells) or can make your bone marrow less responsive to this hormone. Inflammation can also shorten the lifespan of red blood cells. Anemia of inflammation usually develops slowly, since chronic diseases also develop slowly. Severe acute infections and trauma, however, can cause a sudden surge in inflammation and can rapidly bring on anemia.
Anemia can occur when red blood cells are destroyed faster than they can be created
Not all anemias happen on the production side of things. Even if red blood cells are being turned out at a normal rate, if they’re destroyed faster than they can be replaced, this can lead to a condition called hemolytic anemia. Red blood cells usually live for about 120 days, at which point they’re removed from the circulation by the spleen. But, in a process known as hemolysis, red blood cells rupture prematurely, releasing their hemoglobin into the bloodstream. If hemolysis happens too frequently or on too large a scale, it can cause anemia, according to MedicineNet.
Hemolysis can happen for a number of reasons. Some inherited conditions, such as sickle cell anemia, can cause structural defects in red blood cells that cause them to break down. Red blood cells can also suffer damage as they pass through mechanical heart valves. An overactive spleen, viral or bacterial infections, blood cancers, autoimmune conditions, and medications such as penicillin and anti-malaria drugs can sometimes trigger hemolysis. A severe reaction to a blood transfusion can also cause hemolytic anemia. Depending on the underlying cause of ramped-up red blood cell destruction, symptoms can range from mild to life-threatening, and the condition may be temporary or lifelong (via Johns Hopkins Medicine).
Anemia has a wide range of symptoms
There’s a range for both red blood cells and hemoglobin, so everyone’s "normal" is slightly different and people can begin experiencing symptoms at different laboratory levels. In addition, the severity of anemia symptoms doesn’t necessarily match the seriousness of the underlying cause (via the Merck Manual). Regardless of what’s driving anemia, having too few healthy red blood cells means your tissues and organs aren’t getting enough oxygen. This leads to a set of common symptoms that can include extreme fatigue, weakness, shortness of breath, dizziness, chest pain, irregular heartbeat, headaches, pale skin, and cold hands and feet, according to the Mayo Clinic.
Other symptoms are unique to the underlying cause of anemia. In iron deficiency anemia, for example, individuals may have a condition known as pica in which they eat ice or nonfood substances like dirt or chalk. While pica can have many causes, it’s often a sign your body is trying to get vital micronutrients that it’s missing, like iron (via Healthline). Those with sickle cell anemia may experience episodes of extreme pain when the crescent-shaped red blood cells get stuck in small blood vessels (via the Mayo Clinic). Because aplastic anemia also affects the production of white blood cells and platelets, individuals can experience additional symptoms, such as frequent infections because of a lack of white blood cells, excessive bleeding, and easy bruising because of a lack of platelets (via the Mayo Clinic).
Anemia can lead to serious complications
It’s probably no surprise that a condition that affects your body’s ability to circulate oxygen can have dire consequences if not treated. In particular, anemia can negatively affect the heart. As the Mayo Clinic explained, "When you’re anemic, your heart must pump more blood to make up for the lack of oxygen in the blood." Over time, untreated anemia can lead to an enlarged heart or heart failure. One 2006 paper published in the Texas Heart Institute Journal reported that between one-third and two-thirds of patients with severe anemia had an enlarged heart, and the left ventricle (the chamber of the heart that pumps oxygen-rich blood into the body) was the area most likely to be affected. Fortunately, the researchers also noted that heart size and function returned to normal within a few weeks of treating the anemia.
Other complications are specific to the underlying cause of anemia. Iron deficiency anemia has been linked to premature birth and low birthweight infants when it occurs during pregnancy, and growth problems when it occurs in young children. Severe thalassemia can cause bone deformities, slowed growth, an enlarged spleen, and buildup of iron in the body to toxic levels. Sickle-shaped red blood cells that get stuck in blood vessels can cause stroke, organ damage, and blindness (via the Mayo Clinic). According to the Centers for Disease Control and Prevention (CDC), 5,254 Americans died in 2019 due to anemia.
How anemia is diagnosed
According to the Merck Manual, most doctors don’t proactively screen for anemia; they usually wait until a patient has symptoms that sound like they could be anemia. In addition to conducting a physical exam and asking about health and family history, a doctor’s first step is to order a complete blood count (CBC). This collection of tests measures a number of things but, when it comes to anemia, doctors are looking at the total number of red blood cells, the hematocrit level (the percent volume of blood the red blood cells take up, which is based on both their number and size), and the hemoglobin level. If the CBC results indicate anemia, additional tests will need to be done to determine what’s causing it. These may include tests related to iron and vitamin levels, bone marrow biopsies, or genetic testing (via the Mayo Clinic).
So, what constitutes abnormal values on a CBC? For red blood cells, the normal range is 4.5 million to 5.9 million cells/microliter of blood for men and 4.1 million to 5.1 million for women. The acceptable range for hemoglobin is 14 to 17.5 grams per deciliter of blood for men and 12.3 to 15.3 for women. Hematocrit should fall between 41.5% and 50.4% for men and 35.9% to 44.6% for women. Mean corpuscular volume (MCV), which is a measure of the size of your blood cells, can also be an important clue to diagnosing anemia, since both high and low values correspond to different forms of anemia. Normal values range from 80 to 96 (via WebMD).
Getting more of the micronutrients you need can correct some forms of anemia
Treatment for anemia is based on the underlying cause. For those whose condition is the result of not enough iron, folate, vitamin B12, or vitamin C, the good news is that getting more of the missing micronutrients is usually all that’s required. The richest sources of iron include red meat and poultry, dark-green leafy vegetables, and fortified bread. For folate, fortified grains and cereals, legumes, and certain vegetables are your best options. Vitamin B12 is plentiful in all types of meat, milk and cheese, and fortified products. A wide variety of fruits and vegetables contain significant amounts of vitamin C, notes Harvard Medical School. These micronutrients can also be taken as dietary supplements, either alone or as part of a multivitamin.
For those who have trouble absorbing micronutrients through their digestive system, there are alternatives for getting the vitamins and minerals they need. Iron can be given intravenously as an infusion, which is also effective if iron levels need to be raised quickly (via Healthline). For individuals with vitamin B12-deficiency anemia caused by malabsorption or lack of intrinsic factor (pernicious anemia), vitamin B12 shots are the standard treatment. Initially these shots may be given every other day but, eventually, may only be needed once a month to maintain healthy B12 levels (via the Mayo Clinic).
Blood transfusions may be necessary
For severe cases of anemia, especially those caused by genetic mutations that affect how the body produces red blood cells, blood transfusions may be necessary. During this procedure, which is usually performed at a hospital or outpatient clinic, individuals receive blood through an IV. Depending on the cause of anemia, individuals may receive either whole blood or just red blood cells. (For example, those with aplastic anemia are most likely to receive whole blood, since they have difficulty making all three blood cell types.) The procedure usually takes one to four hours, depending on which components of blood are being given and how much is needed, according to the Mayo Clinic.
While blood transfusions are generally considered very safe, there are potential risks, particularly with repeated transfusions. Fever is one relatively common side effect of transfusions. Although donated blood is screened before it’s transfused, there’s still a chance it may carry a bloodborne infection, such as hepatitis B or C. Even when you’re given the correct blood type, it’s possible to have an allergic reaction to the transfused blood. In severe cases, individuals can even go into life-threatening anaphylaxis. Your body can also mount an immune response after a transfusion, causing either immediate or delayed breakdown of red blood cells, both of which are medical emergencies. Frequent transfusions can also lead to hemochromatosis, in which iron builds up to dangerous levels in body tissues, particularly damaging the heart and liver (via WebMD).
Other treatments for anemia
In addition to blood transfusions, those with aplastic anemia — especially young individuals — may be treated with a bone marrow transplant to replace damaged stem cells. Chemotherapy or radiation treatments are used to destroy the aplastic bone marrow, and then stem cells from a matched donor are injected into the bloodstream and migrate to the bone marrow. If a transplant isn’t an option, individuals may receive medications to help stimulate the bone marrow to grow more blood cells, or immunosuppressants if their aplastic anemia is the result of an autoimmune condition. Stem cell transplants can also be used to treat thalassemia, according to the Mayo Clinic.
For those with sickle cell anemia, treatment usually focuses on trying to prevent blood cells from clumping in blood vessels, which is both painful and potentially life-threatening. Medications such as hydroxyurea, crizanlizumab, and voxelotor can be useful. Stem cell transplants are also sometimes considered (via the Mayo Clinic). Depending on the cause, treatments for hemolytic anemia may include stem cell transplants, drugs to suppress the immune system, removal of the spleen, and plasmapheresis — a process in which antibodies that would normally attack red blood cells are mechanically filtered out of the blood (via the Hematology-Oncology Associates of CNY). In the case of anemia of chronic disease, treatment largely focusses on managing the underlying condition (via the National Institute of Diabetes and Digestive and Kidney Diseases).