Microcytic Anemias

From WikiLectures

Microcytic anemia refers to a group of anemias in which red blood cells are smaller than normal, with a mean corpuscular volume (MCV) of less than 80 fL. The underlying problem in almost all cases is impaired hemoglobin synthesis. Because hemoglobin production is reduced, red blood cells undergo extra divisions during development, which results in smaller, microcytic cells.

Main Causes of Microcytic Anemia[edit | edit source]

1. Iron Deficiency Anemia

(O’Leary, Finn, et al., IDA smear, 2025)
(O’Leary, Finn, et al., IDA - spoon shaped nails, 2025)

Iron deficiency anemia is the most common cause of microcytic anemia worldwide. It develops when the body’s iron stores become insufficient to support normal hemoglobin synthesis. Usually results from chronic blood loss (such as gastrointestinal bleeding or menorrhagia, blood loss in excess of 10-20 mL of blood per day [> 5-10 mg of iron]), increased physiological demand (such as pregnancy or growth), or inadequate intake or absorption of iron (celiac disease or post-gastrectomy). Initially, iron is depleted from storage sites, causing ferritin levels to fall first. As the deficiency progresses, serum iron levels decrease, and the bone marrow receives less iron for erythropoiesis. As iron is essential for heme synthesis, reduced iron leads to decreased hemoglobin production and developing red blood cells compensate by undergoing extra cell divisions, resulting in smaller (microcytic) and paler (hypochromic) cells. At the same time, the liver increases production of transferrin to capture more iron, which explains the rise in TIBC.

Laboratory Findings

  • Decreased Hemoglobin and decreased MCV = anemia with small RBCs
  • Decreased Ferritin = reflects depleted iron stores (most specific finding)
  • Decreased Serum iron = less circulating iron available
  • Increased TIBC = increased transferrin production to bind more iron
  • Decreased Transferrin saturation = little iron bound to transferrin
  • Increased RDW = variation in RBC size due to mixed populations

Clinical Symptoms

  • General anemia symptoms such as fatigue, weakness, pallor, and shortness of breath on exertion
  • More specific findings include pica (especially craving ice), koilonychia (spoon-shaped nails), brittle hair, and sometimes glossitis and angular cheilitis.

2. Thalassemia

(Needs, Todd, et al., B-Thalassemia minor, 2023)

Thalassemia is a genetic disorder affecting globin chain production, either alpha or beta chains. In beta-thalassemia, there is reduced or absent production of beta chains, while in alpha-thalassemia, alpha chain production is impaired. This imbalance leads to excess unmatched globin chains, which precipitate inside red blood cell precursors. These precipitates damage the cells, causing ineffective erythropoiesis in the bone marrow and increased destruction of red blood cells (hemolysis). The bone marrow compensates by increasing red blood cell production, causing the red blood cell count to be often normal or elevated despite anemia.

Laboratory Findings

  • Decreased MCV (often very low) = severe microcytosis
  • Normal or increased serum iron and ferritin = iron metabolism is not impaired
  • Normal TIBC = no need to increase iron transport
  • Normal RDW = cells are uniformly small
  • Increased RBC count = compensatory marrow response

Clinical Symptoms

  • Mild forms (thalassemia trait) are often asymptomatic and discovered incidentally.
  • More severe forms present with anemia symptoms, along with splenomegaly due to increased red cell destruction.
  • Chronic marrow stimulation can lead to bone deformities, especially in the face and skull.
  • In severe cases, patients may also develop iron overload due to repeated transfusions.

3. Anemia of Chronic Disease

Anemia of chronic disease occurs in the setting of chronic inflammation, such as infections, autoimmune diseases, or malignancy. Inflammatory cytokines stimulate the liver to produce hepcidin (hormone for regulation of iron metabolism), which inhibits iron release from macrophages and decreases intestinal iron absorption. As a result, iron becomes trapped in storage sites, and less iron is available for red blood cell production. Additionally, inflammation suppresses erythropoietin production and reduces the responsiveness of bone marrow to erythropoietin, further decreasing red blood cell production.

Laboratory Findings

  • Decreased Serum iron = iron is not available in circulation
  • Decreased TIBC = liver decreases transferrin production
  • Increased or normal ferritin = iron stores are adequate or increased
  • MCV normal or mildly decreased = may become microcytic later

Clinical Symptoms

  • Usually mild and often overshadowed by the underlying chronic disease (usually clinical features of the underlying condition is more prominent).
  • Patients may experience fatigue and weakness, but the anemia is typically less severe.

4. Sideroblastic Anemia

Sideroblastic anemia occurs when the bone marrow is able to absorb iron normally but cannot properly incorporate it into heme inside developing red blood cells. The defect lies in the enzymes responsible for heme synthesis, which function within the mitochondria. As heme cannot be formed, iron that enters the developing erythrocytes is not used. Instead, iron accumulates inside the mitochondria surrounding the nucleus of erythroblasts, creating a characteristic ring-like pattern called ring sideroblasts, which can be seen on bone marrow examination. As a result, the body produces red blood cells that are abnormal and inefficient, leading to anemia despite the presence of adequate or even increased iron stores. Common acquired causes include chronic alcohol use, vitamin B6 deficiency, certain medications (such as isoniazid), and toxins like lead.

Laboratory Findings

  • Increased Serum iron = iron accumulates in the blood
  • Increased Ferritin = increased iron storage
  • Normal or decreased TIBC = no need to increase iron transport
  • Peripheral smear = dimorphic RBC population

Clinical Symptoms

  • Symptoms are similar to other anemias, including fatigue and weakness.
  • In acquired forms, symptoms related to the underlying cause are important, such as alcohol use or drug exposure.
  • In chronic cases, iron overload may develop, potentially affecting organs like the liver and heart.

5. Lead Poisoning

Lead poisoning causes microcytic anemia by inhibiting key enzymes involved in heme synthesis, particularly ALA dehydratase and ferrochelatase. This inhibition prevents the proper formation of heme, leading to decreased hemoglobin synthesis and accumulation of precursor substances, resulting red blood cells to become microcytic and dysfunctional.

Laboratory Findings

  • Increased free erythrocyte protoporphyrin = due to blocked heme synthesis
  • Peripheral smear = basophilic stippling (aggregated ribosomal RNA)
  • May also show mild microcytic anemia

Clinical Symptoms

  • May develop abdominal pain (lead colic), constipation, and neurological symptoms (such as irritability or cognitive impairment)
  • In children may cause developmental delay
  • Chronic exposure may also lead to anemia and fatigue

Comparison of Microcytic Anemias[edit | edit source]

Feature Iron Deficiency Anemia (IDA) Thalassemia Anemia of Chronic Disease Sideroblastic Anemia
Iron ↓ ↑ / normal ↓ ↑
Ferritin ↓ ↑ ↑ ↑
TIBC ↑ normal ↓ ↓ / normal
RDW ↑ normal normal ↑
RBC count ↓ normal / ↑ ↓ ↓

Treatment[edit | edit source]

1. Iron Deficiency Anemia (IDA)

  • First- line = Oral iron supplementation (e.g., ferrous sulfate)
  • IV iron if = poor oral tolerance, malabsorption, and severe deficiency
  • Treat underlying cause = GI bleeding (ulcer, malignancy), menorrhagia, or dietary deficiency

2. Thalassemia

  • Mild = no treatment required
  • Moderate–severe =
    • Regular blood transfusions
    • Folic acid supplementation
    • Iron chelation therapy (to prevent overload)
  • Other option = Bone marrow or stem cell transplant

3. Anemia of Chronic Disease

  • Treat underlying disease (most important) = infection, autoimmune disease, or malignancy
  • If symptomatic = erythropoietin (EPO) therapy in selected cases

4. Sideroblastic Anemia

  • Remove cause = stop alcohol, stop offending drugs (e.g., isoniazid), and remove toxins
  • Vitamin B6 (pyridoxine) supplementation
  • Avoid iron supplementation (iron already high)
  • Blood transfusions if severe anemia
  • Iron chelation if iron overload develops

5. Lead Poisoning

  • Remove source of lead exposure
  • Chelation therapy = EDTA or Dimercaprol (in severe cases)
  • Supportive treatment

References[edit | edit source]

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