Dr. Liping JING & Dr. Wenrui YANG: Anemia and Microcytic Anemia - What You Need to Know
Summary: Dr. Liping JING and Dr. Wenrui YANG from the Anemia Diagnosis & Treatment Center at Beijing GoBroad Boren Hospital explain the common types of microcytic anemia, how they are differentiated, and how treatment approaches vary. The article reviews the three main causes and typical symptoms of iron-deficiency anemia, explains why ferritin is an important clue when distinguishing anemia of chronic disease from iron deficiency, and introduces the diagnosis and day-to-day management of hereditary spherocytosis and thalassemia. The goal is to help children with hematologic or oncologic conditions and their families better understand and manage anemia.
To help children with hematologic or oncologic conditions and their families better understand the common causes of microcytic anemia, how it is recognized, how it may relate to an underlying disease, and what monitoring and home-care measures may be appropriate, we invited Dr. Liping JING and Dr. Wenrui YANG from the Anemia Diagnosis & Treatment Center at Beijing GoBroad Boren Hospital to answer some common questions.
1. What Is Anemia? What Is Microcytic Anemia?
Anemia is more than simply "looking pale." Medically, anemia means that the red blood cell count, hemoglobin level, or hematocrit is below the normal range for a person's age, sex, and altitude.
So what does "microcytic anemia" mean? When you look at a complete blood count (CBC), in addition to hemoglobin and platelets, two red blood cell indices are especially useful:
1. MCV (mean corpuscular volume): This reflects the average size of red blood cells. In adults, the usual reference range is about 80-100 fL; an MCV below 80 fL is generally considered microcytic. In children, the cutoff varies with age and can be lower; around 70 fL may fall into the microcytic range in younger children.
2. MCHC (mean corpuscular hemoglobin concentration): This reflects the concentration of hemoglobin inside red blood cells.
When red blood cells are both smaller than usual and contain less hemoglobin, the pattern is called microcytic hypochromic anemia.
2. What Are the Common Types of Microcytic Anemia?
Common causes include:
◆ Iron-deficiency anemia - the most common type
◆ Anemia of chronic disease, also called anemia of inflammation
◆ Thalassemia and hereditary spherocytosis
◆ Rare forms such as sideroblastic anemia
◆ Anemia caused by lead poisoning
3. Iron-Deficiency Anemia
Put simply, iron-deficiency anemia occurs when the body does not have enough iron. Iron is a key building block for hemoglobin, the protein in red blood cells that carries oxygen. When iron is lacking, the body produces fewer red blood cells, and those cells tend to be smaller, paler, and less effective at carrying oxygen.
Why does iron deficiency happen? There are three main reasons:
1. Excessive blood loss - the most common cause
Examples include heavy menstrual bleeding in women of reproductive age, gastrointestinal bleeding such as from peptic ulcers or hemorrhoids, and acute blood loss after trauma or surgery.
2. Low iron intake or poor absorption
Examples include a long-term diet with insufficient iron-rich foods, or impaired absorption after major gastric or duodenal surgery.
3. Increased iron requirements
Iron requirements increase during pregnancy and breastfeeding, and in growing children as blood volume expands and the body develops.
What Symptoms Can Iron-Deficiency Anemia Cause?
◆ General symptoms: weakness, easy fatigue, dizziness, ringing in the ears, palpitations, and shortness of breath with activity.
◆ Physical changes: pale or sallow skin, reduced complexion, thin nails, and pale inner eyelids.
◆ In children: difficulty concentrating and reduced memory or attention.
◆ Other characteristic symptoms: pica (craving non-food substances such as soil or plaster), spoon-shaped nails (koilonychia), restless legs syndrome, cracks or inflammation at the corners of the mouth, and difficulty swallowing.
4. Anemia of Chronic Disease (Anemia of Inflammation)
Anemia of chronic disease, also known as anemia of inflammation, is caused by an underlying condition. Chronic infection, inflammatory disease, cancer, and rheumatologic or autoimmune disorders can all contribute.
What is happening in the body?
The mechanism is different from true iron deficiency. In iron-deficiency anemia, the body genuinely does not have enough iron. In anemia of chronic disease, iron may be present in adequate or even increased amounts, but inflammation causes much of it to be sequestered and less available to the bone marrow for red blood cell production. This is sometimes described as impaired iron utilization.
Inflammation can also suppress erythropoietin (EPO) production and shorten red blood cell survival. The result may also present with a microcytic, hypochromic pattern.
How Can Anemia of Chronic Disease Be Distinguished from Iron-Deficiency Anemia?
Ferritin is an important clue:
◆ Iron-deficiency anemia: ferritin is typically low.
◆ Anemia of chronic disease: ferritin is often normal or elevated.
This distinction matters because the treatment approaches are different. Ferritin should still be interpreted together with the overall clinical picture and other iron studies.
How Is Anemia of Chronic Disease Treated?
◆ Treat the underlying disease - this is the cornerstone of management.
◆ In selected patients, treatment may include erythropoiesis-stimulating therapy such as EPO or roxadustat.
◆ Iron supplementation is generally considered when true iron deficiency is also present.
5. Hereditary Spherocytosis
Hereditary spherocytosis is a genetic red blood cell disorder. The name is long, but the key idea is simple: the red blood cells become spherical rather than having their usual biconcave-disc shape.
Genetic changes affect proteins in the red blood cell membrane skeleton. As a result, the cells become rounder, less flexible, and more fragile. They have difficulty passing through the spleen and are more likely to be trapped and destroyed.
Hereditary spherocytosis can be inherited in different ways:
◆ About 75% of cases follow a dominant inheritance pattern, meaning one parent may also be affected, sometimes so mildly that the condition has never been recognized.
◆ The remaining cases may involve recessive inheritance or a new spontaneous genetic change.
What Symptoms Can Hereditary Spherocytosis Cause?
Severity varies widely. Some people have such mild disease that it is never diagnosed, while others develop significant anemia from childhood. Common features include:
◆ Anemia and jaundice due to increased bilirubin.
◆ An enlarged spleen, which is common in affected patients.
◆ Gallstones caused by excess bilirubin released during red blood cell breakdown.
How Is Hereditary Spherocytosis Diagnosed?
◆ CBC findings may include a low MCV and MCH with a normal or elevated MCHC, producing a relatively hyperchromic pattern.
◆ A peripheral blood smear may show spherocytes, sometimes accounting for more than 15% of red blood cells.
◆ Further testing may include an eosin-5-maleimide (EMA) binding test by flow cytometry or genetic testing.
How Is Hereditary Spherocytosis Treated?
Splenectomy can reduce red blood cell destruction and is an effective treatment for selected patients, but not everyone needs surgery. Splenectomy is generally avoided in young children, especially those under 6 years of age, because the spleen plays an important role in immune defense and removing it too early can increase the risk of serious infection. Mild cases may only require observation. Infection prevention is also important because infections can trigger hemolytic or aplastic crises.
6. Thalassemia
1. Why Is It Called Thalassemia?
The name comes from the fact that the condition was first recognized around the Mediterranean. The genetic variants that cause thalassemia became more common in regions where malaria was historically widespread because carrying certain thalassemia traits could provide some protection against severe malaria. Today, however, those same variants can cause clinically significant anemia in affected individuals.
2. Where Is Thalassemia More Common in China?
Thalassemia is most common south of the Yangtze River, particularly in Guangdong, Guangxi, and Hainan, and is also seen frequently in Yunnan, Guizhou, Sichuan, and Jiangxi. According to the figures cited in the source article, alpha-thalassemia carrier rates exceed 40% in Hainan and approach 25% in Guangxi. With population movement, sporadic cases are now also seen in northern China.
3. What Causes Thalassemia?
Normal adult hemoglobin is made from two alpha-globin chains and two beta-globin chains. In thalassemia, genetic changes reduce or prevent production of either the alpha or beta chains. The resulting imbalance produces abnormal hemoglobin and unstable red blood cells that are more easily destroyed, leading to hemolytic anemia.
4. What Is Alpha-Thalassemia?
Alpha-thalassemia is most often caused by gene deletions. Each person normally has four alpha-globin genes - two inherited from each parent. The clinical picture depends largely on how many genes are affected:
◆ Silent carrier: Three genes function normally and one is affected. There is usually little or no anemia, and the CBC may be close to normal, so the condition can easily be missed.
◆ Alpha-thalassemia trait: Two genes function normally and two are affected. There may be no anemia or only mild anemia, usually with a microcytic, hypochromic pattern.
◆ Hemoglobin H (HbH) disease: Only one alpha-globin gene functions normally and three are affected. Babies may appear well at birth, but anemia and splenomegaly can develop after infancy.
◆ Hb Bart's hydrops fetalis: All four alpha-globin genes are absent or nonfunctional. This is the most severe form and can lead to fetal death or death soon after birth.
Important: Silent-carrier and mild thalassemia can easily be mistaken for iron-deficiency anemia. If iron supplementation does not improve the blood counts as expected, further evaluation may be needed.
5. What Is Beta-Thalassemia?
Beta-thalassemia is often classified by clinical severity:
◆ Mild / carrier form (heterozygous): Symptoms are usually mild, and many people are unaware they have it. Mild jaundice or enlargement of the liver and spleen may occur.
◆ Intermediate form: Severity falls between mild and severe disease, and anemia may worsen with age.
◆ Severe form: Significant anemia usually develops in the first 1-2 years of life, can affect growth and bone development, and often requires long-term transfusion support.
How Is Thalassemia Treated?
◆ Mild disease / silent carrier state: Treatment is usually not required. General health and infection prevention remain important because illness or other physiologic stress can worsen hemolysis in some patients.
◆ For patients who require regular transfusions: transfusion programs may aim to maintain hemoglobin above about 90 g/L to support normal growth and reduce skeletal complications in children. Long-term transfusion can cause iron overload, so iron chelation therapy may also be needed, using agents such as deferiprone, deferoxamine, or deferasirox.
◆ Luspatercept: This medicine promotes late-stage red blood cell maturation and can reduce transfusion burden in some patients. The source article notes an approximately 33% reduction in transfusion burden and states that the drug has been included in China's medical insurance coverage.
◆ Hematopoietic stem cell transplantation: This can be a potentially curative option for patients with severe beta-thalassemia. The source article reports transplant success rates above 90% in appropriate patients.
◆ Splenectomy: This may be considered in selected patients with massive splenomegaly, hypersplenism, or very high transfusion requirements, but it does not cure thalassemia.
◆ Gene therapy: Clinical studies are ongoing, and some patients have achieved transfusion independence. However, access remains limited and treatment costs are high.