Microcytic

Overview of Microcytic Anemias

• Definition: A type of anemia characterized by red blood cells (RBCs) that are smaller than normal
• Key Indicator: Mean Corpuscular Volume (MCV) is less than 80 femtoliters (fL)
• Underlying Cause: Typically results from impaired hemoglobin synthesis
• Common Causes (Think “TICS”):
  • Thalassemia
  • Iron Deficiency Anemia (IDA)
  • Anemia of Chronic Disease/Inflammation
  • Sideroblastic Anemia

General Laboratory Findings in Microcytic Anemias

• Complete Blood Count (CBC):
  • Hemoglobin (HGB): Decreased (anemia)
  • Hematocrit (HCT): Decreased
  • Mean Corpuscular Volume (MCV): Decreased (< 80 fL)
  • Mean Corpuscular Hemoglobin (MCH): Decreased (hypochromia)
  • Mean Corpuscular Hemoglobin Concentration (MCHC): Decreased (hypochromia)
  • Red Cell Distribution Width (RDW): Often increased, but may be normal in some cases (e.g., thalassemia trait)
• Peripheral Blood Smear:
  • Microcytes (small RBCs)
  • Hypochromia (pale RBCs)
  • Anisocytosis (variation in RBC size)
  • Poikilocytosis (variation in RBC shape) - varies depending on the specific cause

Iron Deficiency Anemia (IDA)

• Definition: Anemia caused by inadequate iron stores, leading to decreased hemoglobin production
• Etiology:
  • Inadequate iron intake (dietary deficiency)
  • Increased iron loss (bleeding)
  • Impaired iron absorption
  • Increased iron requirements (e.g., pregnancy)
• Pathophysiology:
  • Iron is essential for heme synthesis
  • Insufficient iron leads to decreased hemoglobin production, resulting in smaller and paler red blood cells
• Clinical Manifestations:
  • General anemia symptoms: Fatigue, weakness, pallor
  • Specific IDA symptoms:
    • Pica (unusual cravings for non-food substances)
    • Koilonychia (spoon-shaped nails)
    • Angular cheilitis (inflammation at the corners of the mouth)
    • Glossitis (inflammation of the tongue)
• Laboratory Findings:
  • CBC:
    • Microcytic, hypochromic anemia
    • Increased RDW
  • Peripheral Blood Smear:
    • Microcytes
    • Hypochromia
    • Pencil cells (elongated, thin RBCs)
    • Target cells (less common than in thalassemia)
  • Reticulocyte Count:
    • Low or normal (inappropriately low for the degree of anemia)
  • Iron Studies:
    • Serum Iron: Decreased
    • Total Iron-Binding Capacity (TIBC): Increased
    • Transferrin Saturation: Decreased
    • Ferritin: Decreased (most specific indicator of iron deficiency)
• Treatment:
  • Identify and treat the underlying cause of iron loss (e.g., bleeding)
  • Oral iron supplementation (ferrous sulfate, ferrous gluconate)
  • Parenteral iron (IV iron) for patients who cannot tolerate or absorb oral iron
  • Dietary advice to increase iron intake

Anemia of Chronic Disease (ACD)

• Definition: Anemia associated with chronic inflammatory, infectious, or malignant conditions
• Etiology:
  • Chronic inflammatory diseases: Rheumatoid arthritis, systemic lupus erythematosus (SLE)
  • Chronic infections: Tuberculosis (TB), HIV
  • Malignancies: Cancer, lymphoma
• Pathophysiology:
  • Inflammatory cytokines (e.g., IL-6) stimulate the production of hepcidin by the liver
  • Hepcidin inhibits iron release from macrophages and enterocytes by binding to ferroportin, leading to iron trapping
  • EPO production may be suppressed
• Clinical Manifestations:
  • Often masked by the symptoms of the underlying chronic disease
  • Mild to moderate anemia symptoms: Fatigue, weakness
• Laboratory Findings:
  • CBC:
    • Usually normocytic and normochromic, but can be microcytic in some cases
  • Peripheral Blood Smear:
    • Usually normocytic and normochromic, but may show microcytes and hypochromia in some cases
  • Reticulocyte Count:
    • Low or normal (inappropriately low for the degree of anemia)
  • Iron Studies:
    • Serum Iron: Decreased
    • Total Iron-Binding Capacity (TIBC): Normal or decreased
    • Transferrin Saturation: Normal or decreased
    • Ferritin: Normal or increased (key differentiating factor from IDA)
  • Markers of Inflammation:
    • Elevated ESR and CRP
• Treatment:
  • Treat the underlying chronic condition
  • Erythropoiesis-stimulating agents (ESAs) in selected patients (e.g., CKD)
  • Iron supplementation (IV iron) if iron deficiency is present or for patients on ESAs
  • Blood transfusions for severe anemia

Thalassemia

• Definition: A group of inherited blood disorders characterized by decreased or absent synthesis of one or more globin chains (alpha or beta) that make up hemoglobin
• Genetic Basis: Mutations in the alpha- or beta-globin genes
• Pathophysiology:
  • Reduced globin chain synthesis leads to:
    • Decreased hemoglobin production, resulting in microcytic, hypochromic anemia
    • Imbalance in globin chain ratios, leading to precipitation of excess globin chains within RBC precursors, causing cellular damage and premature destruction (ineffective erythropoiesis)
• Classification:
  • Alpha (α) Thalassemia: Decreased or absent synthesis of alpha-globin chains
  • Beta (β) Thalassemia: Decreased or absent synthesis of beta-globin chains
• Clinical Features: Varies widely depending on the specific genetic defect and the number of affected genes
• Laboratory Findings:
  • CBC:
    • Microcytic, hypochromic anemia
    • RBC count may be normal or elevated relative to the degree of anemia
  • Peripheral Blood Smear:
    • Microcytes
    • Hypochromia
    • Target cells
    • Basophilic stippling
    • Nucleated RBCs (in severe cases)
  • Reticulocyte Count:
    • Elevated
  • Iron Studies:
    • Normal or elevated (not iron deficient)
  • Hemoglobin Electrophoresis:
    • Abnormal hemoglobin patterns (e.g., elevated HbA2 in beta-thalassemia trait, presence of HbH in alpha-thalassemia)
• Diagnosis:
  • Based on clinical presentation, peripheral blood smear, hemoglobin electrophoresis, and genetic testing
• Treatment:
  • Varies depending on the severity of the disease:
    • Mild thalassemia: No treatment or folic acid supplementation
    • Moderate thalassemia: Occasional blood transfusions
    • Severe thalassemia (thalassemia major): Regular blood transfusions, iron chelation therapy, hematopoietic stem cell transplantation (HSCT)

Sideroblastic Anemia

• Definition: A group of disorders characterized by ineffective erythropoiesis and the presence of ringed sideroblasts in the bone marrow
• Pathophysiology:
  • Impaired ability of the bone marrow to incorporate iron into hemoglobin
  • Iron accumulates in the mitochondria of erythroblasts, forming ringed sideroblasts
• Classification:
  • Hereditary Sideroblastic Anemias
  • Acquired Sideroblastic Anemias
    • Reversible (e.g., alcohol-induced, drug-induced, copper deficiency)
    • Irreversible (e.g., myelodysplastic syndromes)
• Clinical Features:
  • Anemia symptoms: Fatigue, weakness, pallor
  • Iron overload: Can lead to liver damage, heart failure, and endocrine dysfunction
• Laboratory Findings:
  • CBC:
    • MCV may be low, normal, or high
    • Dimorphic red cell population (mixture of normal and abnormal RBCs)
  • Peripheral Blood Smear:
    • Microcytes
    • Hypochromia
    • Pappenheimer bodies (iron-containing inclusions in RBCs)
    • Basophilic stippling
  • Reticulocyte Count:
    • Low or normal
  • Iron Studies:
    • Serum Iron: Increased
    • Total Iron-Binding Capacity (TIBC): Decreased or normal
    • Transferrin Saturation: Increased
    • Ferritin: Increased
  • Bone Marrow Aspiration and Biopsy:
    • Hypercellular marrow with erythroid hyperplasia
    • Ringed sideroblasts (erythroblasts with iron-laden mitochondria encircling the nucleus)
• Diagnosis:
  • Based on CBC, peripheral blood smear, iron studies, and bone marrow examination
• Treatment:
  • Identify and treat the underlying cause
  • Pyridoxine (vitamin B6) supplementation (may be effective in some cases)
  • Blood transfusions for severe anemia
  • Iron chelation therapy to prevent iron overload

Differential Diagnosis of Microcytic Anemias

Feature	Iron Deficiency Anemia (IDA)	Anemia of Chronic Disease (ACD)	Thalassemia	Sideroblastic Anemia
MCV	Decreased	Decreased or Normal	Decreased	Decreased or Normal
MCH	Decreased	Decreased or Normal	Decreased	Decreased or Normal
RDW	Increased	Normal or Increased	Normal or Increased	Increased
Serum Iron	Decreased	Decreased	Normal or Increased	Increased
TIBC	Increased	Normal or Decreased	Normal	Decreased or Normal
Transferrin Saturation	Decreased	Normal or Decreased	Normal	Increased
Ferritin	Decreased	Normal or Increased	Normal	Increased
Peripheral Blood Smear	Pencil Cells	Mild abnormalities	Target Cells	Pappenheimer Bodies
Bone Marrow (if performed)	Decreased Iron Stores	Normal or Increased Iron Stores	Normal	Ringed Sideroblasts
Hemoglobin Electrophoresis	Normal	Normal	Abnormal	Normal

Key Terms

• Microcytic Anemia: Anemia characterized by small RBCs (MCV < 80 fL)
• Iron Deficiency Anemia (IDA): Anemia caused by inadequate iron stores
• Ferritin: The storage protein for iron
• Anemia of Chronic Disease (ACD): Anemia associated with chronic inflammation
• Hepcidin: Hormone that regulates iron homeostasis
• Thalassemia: Inherited blood disorder with decreased globin chain synthesis
• Sideroblastic Anemia: Anemia characterized by ringed sideroblasts in the bone marrow
• Ringed Sideroblasts: Erythroblasts with iron-laden mitochondria