What are the causes of microcytic anemia?

October 1, 2025 •

4 min read

According to the World Health Organization, iron deficiency anemia is the most common nutritional disorder globally, often presenting as a type of microcytic anemia. This condition, characterized by smaller-than-normal red blood cells, can arise from various causes beyond a simple lack of iron, including inherited disorders and chronic inflammation.

Quick Summary

Microcytic anemia, characterized by abnormally small red blood cells, results from defective hemoglobin synthesis or iron availability. Primary causes include iron deficiency, thalassemia, anemia of chronic disease, and sideroblastic anemia.

Key Points

Leading Cause: Iron Deficiency Anemia (IDA) is the most frequent cause of microcytic anemia, often resulting from chronic blood loss, poor diet, or malabsorption issues.
Genetic Factors: Thalassemias are inherited genetic disorders affecting hemoglobin production, leading to microcytic red blood cells. They range in severity depending on the specific gene mutation.
Inflammatory Conditions: Anemia of Chronic Disease (ACD) occurs when chronic inflammation from conditions like autoimmune disorders, cancer, or kidney disease impairs the body's ability to use iron effectively.
Dysfunctional Heme Synthesis: Sideroblastic anemia involves a failure to incorporate iron into hemoglobin, causing iron to build up in red blood cell precursors. It can be inherited or acquired.
Proper Diagnosis is Key: Microcytic anemia is a symptom, not a diagnosis. Differentiating between the causes requires specific laboratory tests, as treatment strategies vary significantly based on the underlying issue.
Environmental Exposure: Lead poisoning can cause microcytic anemia by interfering with the enzymes responsible for creating heme, a component of hemoglobin.

Understanding microcytic anemia

Microcytic anemia is not a single disease but a description of red blood cells that are smaller than normal. A routine blood test, called a complete blood count (CBC), measures the mean corpuscular volume (MCV), with a reading below 80 femtoliters (fL) indicating microcytosis in adults. The reduced size is typically due to insufficient hemoglobin production, which can be caused by defects in globin, heme synthesis, or iron availability. The most common causes can be remembered by the acronym T.A.I.S., which stands for Thalassemia, Anemia of chronic disease, Iron deficiency, and Sideroblastic anemia.

Iron deficiency anemia (IDA)

Iron deficiency is the leading cause of microcytic anemia worldwide and often presents as microcytic, hypochromic anemia, where red blood cells are both small and pale. Iron is crucial for producing hemoglobin, the protein in red blood cells that carries oxygen. When iron levels are low, hemoglobin production is hampered, leading to smaller, paler cells.

Chronic blood loss: This is a major cause in adults. In premenopausal women, heavy menstrual bleeding is a common culprit. In men and postmenopausal women, gastrointestinal (GI) bleeding from sources like ulcers, polyps, or cancer is a primary concern.
Decreased iron intake: A diet lacking iron-rich foods can lead to IDA. This is particularly relevant for infants, children, and those following vegetarian or vegan diets without proper supplementation.
Impaired absorption: Conditions affecting the small intestine, such as celiac disease or H. pylori infection, can interfere with iron absorption. Gastric bypass surgery can also limit absorption.
Increased demand: During pregnancy or rapid growth spurts in children, the body’s iron needs increase significantly.

Thalassemias

Thalassemias are a group of inherited blood disorders that disrupt the normal production of hemoglobin. Unlike iron deficiency, the problem here is not iron availability but a genetic defect in the globin protein chains that make up hemoglobin. The two main types are alpha-thalassemia and beta-thalassemia, named after the specific globin chain affected.

Alpha-thalassemia: Caused by defective or missing alpha globin genes, this form is common among people of African, Mediterranean, or Southeast Asian descent. The severity depends on how many of the four alpha genes are affected, ranging from a silent carrier state to the fatal hydrops fetalis.
Beta-thalassemia: This type involves mutations in the beta globin genes and is prevalent in people of Mediterranean, Middle Eastern, and Asian ancestry. It can manifest as the mild thalassemia trait (minor), the moderate intermedia, or the severe and transfusion-dependent thalassemia major (Cooley's anemia).

Anemia of chronic disease (ACD)

ACD, also known as anemia of inflammation, is the second most common type of anemia after IDA. It occurs in the context of chronic inflammatory conditions, which can lead to microcytic anemia over time, though it often begins as normocytic. The underlying inflammation causes the body to sequester iron, making it unavailable for red blood cell production.

Autoimmune diseases: Conditions like rheumatoid arthritis and lupus can cause chronic inflammation.
Chronic infections: Long-term infections, such as HIV/AIDS or tuberculosis, can trigger ACD.
Cancer: Various types of cancer can cause inflammation and lead to anemia.
Kidney disease: Chronic kidney disease is a common cause of ACD.

Sideroblastic anemia

This is a rare group of disorders that affect the body's ability to incorporate iron into hemoglobin, causing iron to accumulate in the mitochondria of developing red blood cells. These iron-laden cells are known as ring sideroblasts and are pathognomonic upon bone marrow examination. Sideroblastic anemia can be inherited or acquired.

Congenital (Inherited): This is caused by gene mutations, most commonly X-linked, that disrupt the heme synthesis pathway. This form is typically microcytic and hypochromic.
Acquired (Not Inherited): This can result from exposure to toxins or as part of a myelodysplastic syndrome (MDS). Common triggers include excessive alcohol use, certain medications (like isoniazid), lead poisoning, and copper deficiency.

Other causes of microcytic anemia

Lead poisoning: Lead exposure can inhibit enzymes necessary for heme synthesis, leading to microcytic anemia and causing iron to accumulate in the red blood cell precursors. Basophilic stippling on a blood smear is a characteristic finding. Lead poisoning often coexists with iron deficiency.
Copper deficiency and zinc toxicity: Copper is necessary for iron metabolism. A lack of copper or excessive zinc (which competes with copper absorption) can interfere with the body's ability to use iron, causing anemia.

How to differentiate between types of microcytic anemia

Several key laboratory markers can help distinguish the cause of microcytic anemia. The following table provides a comparison of typical lab results for the major types.


Lab Test	Iron Deficiency Anemia	Thalassemia	Anemia of Chronic Disease	Sideroblastic Anemia
Serum Iron	Decreased	Normal or increased	Decreased	Normal or increased
Serum Ferritin	Decreased	Normal or increased	Normal or increased	Normal or increased
Total Iron-Binding Capacity (TIBC)	Increased	Normal	Decreased	Normal or decreased
Transferrin Saturation	Decreased	Normal or increased	Decreased or normal	Increased
Red Blood Cell Distribution Width (RDW)	Increased	Normal or mildly increased	Normal or mildly increased	Increased (often)

Conclusion

Microcytic anemia is a significant medical finding that requires a thorough evaluation to uncover its specific cause. While iron deficiency is the most common reason, a range of other conditions, from genetic disorders like thalassemia to inflammatory states and rare metabolic issues, can also be responsible. A correct diagnosis is crucial, as the treatment for each underlying cause varies greatly—from simple iron supplementation to more complex management strategies for genetic or chronic conditions. For a definitive diagnosis, a healthcare provider relies on a combination of blood tests, a detailed medical history, and sometimes further specialized testing, emphasizing why self-diagnosis is ill-advised. For further reading and patient information, the National Heart, Lung, and Blood Institute (NHLBI) provides comprehensive resources.

Frequently Asked Questions

The most common cause of microcytic anemia is iron deficiency anemia (IDA). It typically results from a diet lacking iron, impaired iron absorption, or chronic blood loss, such as from heavy menstrual periods or gastrointestinal bleeding.

Besides iron deficiency, other main causes include thalassemia (an inherited blood disorder), anemia of chronic disease (due to long-term inflammation), and sideroblastic anemia (a rare disorder of heme synthesis).

Diagnosis begins with a routine blood test called a complete blood count (CBC) to measure the size of red blood cells (MCV). If microcytosis is found, further tests like iron studies (ferritin, serum iron, TIBC) and sometimes hemoglobin electrophoresis or genetic testing are used to pinpoint the cause.

Yes, a diet lacking in iron is a direct cause of iron deficiency anemia, the most common type of microcytic anemia. A lack of other nutrients like copper can also play a role, though this is less common.

The severity depends on the underlying cause. Mild cases, such as in thalassemia trait or mild iron deficiency, may be harmless. However, untreated iron deficiency or severe forms like thalassemia major can lead to serious complications, including heart problems and developmental delays in children.

You should see a doctor if you experience persistent fatigue, weakness, pale skin, shortness of breath, dizziness, or a rapid heartbeat. These are common symptoms associated with anemia that warrant evaluation.

Prevention depends on the cause. Iron deficiency can often be prevented by eating a diet rich in iron and vitamin C. Genetic causes like thalassemia cannot be prevented, but understanding your risk is important for appropriate monitoring and management.