Causes and Risk Factors of Anemia

Anemia, which is diminished red blood cell (RBC) quantity, size, or function, has several causes, including low RBC production, defective RBCs, and destruction or loss of RBCs.

A wide variety of medical conditions can cause anemia, such as nutritional deficiencies, hereditary sickle cell disease, and infectious malaria. You may have a health condition that increases your risk of anemia, and lifestyle factors can contribute as well. Because there are so many causes of anemia, the extent and the effects of the condition could be more serious for your overall health if you have more than one risk factor at a time.

Common Causes 

You can develop chronic anemia due to any disease that affects your RBCs. Or you can suddenly experience acute anemia as a result of a serious health event, such as rapid bleeding or acute shock. 

The most common causes of chronic anemia are vitamin B12 deficiency and iron deficiency. Both of these conditions can be related to your diet, but medical illnesses and toxins can also cause these nutritional deficiencies even if you consume enough of these nutrients in your food or take supplements. 

RBC Lifespan

RBCs are produced in the bone marrow in response to erythropoietin (EPO), a hormone that is released by the kidneys. Your body also needs nutrients, including vitamins, proteins, and iron to produce healthy RBCs.

Your RBCs typically circulate in your heart and blood vessels for about three months before they are broken down. Some components of the RBCs are recycled in the spleen.

Altered RBC Production

You may develop anemia due to glitches in your body’s production of RBCs. Some conditions result in a low number of RBCs and some conditions cause the body to produce defective RBCs that do not function properly. 

Anemia resulting from problems with RBC production include: 

Vitamin B12 deficiency: This is a common vitamin deficiency that can result from a lack of vitamin B12 in the diet or from inflammation in the stomach. Vitamin B12 is needed for healthy RBC formation, and it is found in animal products as well as foods that are fortified with the nutrient. Sometimes, a vegetarian diet or a diet that is heavy on junk food can predispose to this vitamin deficiency.

Vitamin B12 deficiency causes macrocytic anemia (also sometimes described as megaloblastic anemia), a condition in which the body produces extra-large RBCs that do not function as they should. 

Folate deficiency: This vitamin, also known as vitamin B9, is present in vegetables and grains. It works with vitamin B12 in the production of healthy RBCs. A deficiency is usually caused by a nutritional deficit and results in macrocytic anemia.

Iron deficiency: Your RBCs contain hemoglobin, a protein that carries oxygen. Iron, a mineral, is a vital component of hemoglobin. Iron deficiency anemia can develop due to low iron intake or ongoing bleeding (such as from an ulcer or cancer.) Foods that contain iron include green leafy vegetables, meat, and seafood. Iron deficiency anemia, characterized by a low number of RBCs that tend to be smaller than usual, is often described as microcytic anemia.

Malabsorption: When your stomach and/or intestines cannot adequately absorb nutrients, you may lack some of the vitamins and proteins needed for the formation of healthy RBCs. Conditions such as inflammatory bowel disease (IBD) or diarrhea can lead to malabsorption. And often, after a gastric resection for treatment of bowel disease or for weight loss, decreased nutrient absorption can lead to anemia. 

Pernicious anemia: This rare type of anemia results from a lack of intrinsic factor, a protein that helps your body absorb vitamin B12. Pernicious anemia is believed to be an autoimmune condition in which the body’s immune system damages the cells that produce intrinsic factor. It leads to vitamin B12 deficiency, but vitamin B12 deficiency is not always associated with pernicious anemia. 

Aplastic anemia: When the bone marrow is underactive in its production of RBCs, this is described as aplastic anemia. You can have primary aplastic anemia without a known cause, or it can occur in association with health issues such as cancer, radiation, or medications that interfere with bone marrow hematopoiesis (formation of RBCs).

Cancer: Anemia can develop due to many different health effects of various types of cancer. For example, intestinal cancers may cause bleeding and/or impair nutrient absorption, bone marrow cancers interfere with RBC production, and cancer that involves the kidneys disrupts EPO production. Furthermore, chemotherapy and radiation commonly inhibit RBC synthesis. And if cancer metastasizes (spreads) from one region of the body to another, it can cause anemia due to its impact in the organ that it metastasizes to. 

Kidney failure: If the kidneys cannot function as they normally would, they may not produce enough EPO to stimulate the bone marrow. In this instance, RBC synthesis would be inadequate, leading to anemia with a low number of RBCs.

Liver failure: If you develop severe liver failure, you may have difficulty metabolizing protein that is needed for the production of healthy RBCs, which results in anemia.

Anemia of chronic disease: Often, people who are very ill have chronic anemia. Sometimes, the exact cause is not clear, but factors such as malnutrition, liver failure, and kidney disease could be contributing elements.

Alcoholism: Chronic, heavy alcohol use leads to anemia through a number of mechanisms, including liver failure, liver cancer, malnutrition, and stomach damage. 

Loss of RBCs

Even if your body produces normal healthy RBCs, you can develop anemia if you lose too many RBCs before your body can replace them. This can happen suddenly or it can be a slow chronic process. 

Gastrointestinal (GI) bleeding: You can experience bleeding from your stomach, small intestine, or colon due to an ulcer, a polyp, inflammation, or GI cancer. This can occur slowly, resulting in chronic anemia. Severe GI bleeding may occur suddenly, resulting in acute, life-threatening anemia. 

Heavy menstruation: Very heavy menstrual bleeding can cause significant blood loss. Some women experience mild anemia for several days per month on a recurrent basis due to menstrual bleeding.

Urinary tract bleeding: In some instances, small amounts of bleeding can occur in association with a chronic urinary tract infection or bladder cancer, typically leading to low-grade anemia.

Acute hemorrhage: Major traumatic injuries such as a gunshot wound or a puncture wound can result in rapid blood loss with potentially fatal anemia. 

Schistosomiasis: A parasitic infection that can be transmitted in tropical climates, this organism invades the bladder, causing anemia due to bleeding, which may be seen in the urine.

Destruction of RBCs

Conditions that cause RBCs to rupture are described as hemolytic anemia. These illnesses may occur suddenly, causing a rapid decrease in the number of healthy RBCs. 

Malaria: While uncommon in the U.S., malaria infection is among the most common causes of anemia worldwide. This infection is caused by a parasite that enters the body through a mosquito bite. The parasite causes anemia by invading RBCs and causing them to rupture.

Shock: Physiologic shock is a medical emergency that involves dangerous physical disturbances such as extreme blood pressure fluctuations, body temperature changes, and alterations in fluid and electrolytes. Hemolytic anemia can result from severe organ dysfunction associated with physiologic shock.

Sepsis and infections: A septic blood infection can lead to hemolytic anemia. Sometimes milder infections can cause hemolysis as well, but the anemia is not usually as severe as the hemolytic anemia that can occur with sepsis.

Transfusion reaction: In rare instances, a mismatched blood transfusion can occur due to a medical error. When this happens, the body’s immune system attacks the unmatched donor RBCs and destroys them. This potentially fatal reaction causes rapid anemia and results in severe damage throughout the body’s organs. 

Lead: Lead toxicity and lead poisoning are associated with many harmful health effects, including hemolysis (breakdown) of the RBCs. The presence of lead in the blood can also inhibit the formation of the RBCs, contributing to aplastic anemia. 

Toxin exposure: Sometimes toxins in the environment, such as pesticides or industrial chemicals, can cause anemia. Toxins are often associated with hemolytic anemia, but they can cause aplastic anemia as well.

Paroxysmal nocturnal hemoglobinuria (PNH): A rare disease that occurs during adulthood and causes hemolysis, PNH is associated with a genetic mutation (change), but it is not believed to be inherited. The condition is believed to occur when immune cells attack the body’s RBCs. Episodes of hemolysis may occur due to infections, illnesses, or without an obvious trigger.

Medication Induced

A number of medications can cause anemia as a side effect—and they don’t all trigger the same type of anemia. For example, Tegretol (carbamazepine) and non-steroidal anti-inflammatories (NSAIDs) can cause aplastic anemia, while cephalosporins and penicillins can induce hemolytic anemia.

Some medications, such as chemotherapeutic agents, can cause both types of anemia.

Genetics 

There are a number of hereditary causes of anemia, including sickle cell anemia and glucose 6-phosphate dehydrogenase (G6PD) deficiency. Sometimes, hereditary anemia is exacerbated by factors such as infections and stress, which may lead to sudden, dangerously low RBC levels. 

Genetic causes of anemia include: 

Sickle cell anemia: This is a genetic condition that results in the production of abnormal RBCs. The RBCs can change into a sickle shape that resembles a half-moon. RBC sickling can occur in response to physical stress, such as infections and fevers. Sometimes RBC sickling can occur even without an obvious trigger.

This condition is associated with persistent anemia that may cause diminished energy (due to a low number and diminished function of RBCs) and episodic sickle cell crises, which cause the build-up of sickled blood cells in small blood vessels throughout the body (which can cause pain or blood clots).

Thalassemia: This type of anemia includes a group of inherited blood disorders, each of which is characterized by defective formation of the hemoglobin molecule. Thalassemia results in a low number of RBCs that have an impaired oxygen-carrying ability. 

Hereditary spherocytosis: There are several variations of hereditary spherocytosis, all of which are characterized by abnormally shaped RBCs. The RBCs in hereditary spherocytosis are destroyed in the spleen, resulting in anemia. The age of onset and severity differ with the different variations of hereditary spherocytosis, and some people may experience life-threatening anemia, while others may have low energy due to the condition.

G6PD deficiency: A hereditary X-linked condition, G6PD varies in severity. People who have this condition may experience hemolysis due to exposure to certain medications or food.

Cardiovascular 

The heart pumps blood throughout the body. Heart disease can affect blood and oxygen delivery to the organs, which makes the effects of anemia worse than they would be otherwise. Conditions such as heart failure, cardiac arrhythmias, and myocardial infarction (heart attack) may exacerbate the effects of anemia.

Heart disease is also associated with several types of anemia.

Severe heart failure can lead to decreased blood flow to the kidneys—leading to kidney failure. Anemia can develop due to low EPO. Heart failure is also associated with iron deficiency, although the reason for this link is not clear.

Pregnancy is often associated with anemia due to cardiovascular changes. The weight gain and increased fluid that occurs during pregnancy lower the body’s concentration of RBCs, resulting in anemia. Pregnant women may need higher intake of folic acid, vitamin B12, and iron to prevent anemia.

Lifestyle Risk Factors 

Because malnutrition is a contributor to anemia, diet and alcohol play a role. If you have a low intake of foods that are rich in folic acid, vitamin B12, and/or iron, you could develop nutritional anemia, even if you don't have other risk factors.

Heavy alcohol intake can harm your liver, stomach, and kidneys, leading to anemia. Alcohol is also associated with anemia due to malnutrition, even when these organs are not affected.

Exposure to lead through contaminated water or paint can lead to anemia as well. If you live in a home with lead paint or if your water source contains lead residue, this will likely increase your risk of lead exposure. You may be able to have your water supply and your home tested for evidence of lead contamination. 

A Word From Verywell

Anemia has numerous causes. It is more of a sign of disease than a disease of its own. If you have anemia, your medical team will work to identify the underlying cause so that it can be effectively treated.

Keep in mind that you may have more than one medical reason for your anemia, and you could become anemic again at some point due to another cause. That means that you need to pay close attention to your nutrition and your overall health so you can prevent anemia.