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Introduction
1. Anatomy
2. Microbiology
3. Physiology
4. Pathology
4.1 General pathology
4.2 Central and peripheral nervous system
4.3 Cardiovascular system
4.4 Respiratory system
4.5 Hematology and oncology
4.5.1 Coagulation cascade
4.5.2 Blood cell lineages
4.5.3 Anemia fundamentals
4.5.4 Thalassemia
4.5.5 Sideroblastic anemia
4.5.6 Macrocytic anemias
4.5.7 Hemolytic anemias
4.5.8 Sickle cell disease (SCD)
4.5.9 Hereditary spherocytosis (HS)
4.5.10 Disorders of coagulation
4.5.11 Hypercoagulable disorders (Thrombophilias)
4.5.12 Platelet disorders
4.5.13 Leukemias
4.5.14 Lymphomas
4.5.15 Polycythemia vera
4.5.16 Miscellaneous disorders
4.5.17 Additional information
4.6 Gastrointestinal pathology
4.7 Renal, endocrine and reproductive system
4.8 Musculoskeletal system
5. Pharmacology
6. Immunology
7. Biochemistry
8. Cell and molecular biology
9. Biostatistics and epidemiology
10. Genetics
11. Behavioral science
Wrapping up
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4.5.3 Anemia fundamentals
Achievable USMLE/1
4. Pathology
4.5. Hematology and oncology

Anemia fundamentals

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Anemia is a condition in which hemoglobin concentration and/or the RBC count is low, leading to decreased oxygen-carrying capacity of the blood. The World Health Organization (WHO) defines anemia as hemoglobin:

  • < 13 g/dL in men
  • < 12 g/dL in nonpregnant women
  • < 11 g/dL in pregnant women and the elderly

Classification of anemia: According to MCV, anemia can be classified as below.

Classification of anemias
Classification of anemias
  1. Microcytic: MCV<80 fL Seen in Iron deficiency anemia, Thalassemia, Sideroblastic anemia, Anemia of chronic disease, Lead toxicity, Copper deficiency

  2. Macrocytic: MCV>100 fL Seen in Megaloblastic anemia (deficiency of Vit B12, folate; Pernicious anemia), Aplastic anemia, Myelodysplastic syndrome (MDS), Hypothyroidism, Liver dysfunction, Alcoholism, own Syndrome, Hb F, Drugs (methotrexate, phenytoin, mercaptopurine, Antiretroviral drugs), Fanconi anemia, Paroxysmal nocturnal hemoglobinuria (PNH)

  3. Normocytic: MCV between 80-100 fL Seen in Acute blood loss, AOCD, Renal failure, Early stages of iron deficiency anemia, Hypothyroidism, Inflammation, Aplastic anemia, Hemolytic anemias

    I) Microcytic Anemias

    Microcytic anemia is defined as:

    • MCV < 80 fL in adults, or
    • MCV < 70 fL in children up to 12 years of age

    The most common causes are iron deficiency anemia (IDA) and thalassemia. Microcytosis results from deficient synthesis of heme and/or globin.

    Iron deficiency anemia (IDA): IDA is most commonly caused by:

    • Nutritional iron deficiency (especially in children)
    • Increased menstrual blood loss (in women)
    • Occult or gross blood loss in adults (e.g., bleeding hemorrhoids, colon cancer, peptic ulcer)

    In IDA, iron stores (ferritin) become depleted first. This is followed by decreased hemoglobin and the development of hypochromic, microcytic anemia.

    Clinical features include fatigue, hair loss, dyspnea on exertion, pallor, and pica. Patients with underlying CHD may develop angina due to reduced oxygen delivery.

    On examination, you may see mucosal and scleral pallor, a smooth tongue, and koilonychia (spoon-shaped nails).

    Iron studies show low serum iron, low ferritin, decreased Hb concentration, increased TIBC, decreased percent saturation of transferrin with iron, and increased free erythrocyte porphyrin. RDW is increased.

    Peripheral smear shows hypochromic, microcytic RBCs, thrombocytosis, and anisocytosis, with a typically normal reticulocyte count and decreased RBC count. Bone marrow shows erythroid hyperplasia and increased RBC precursors. Serum transferrin receptor levels are elevated.

    Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. The syndrome is caused due to iron deficiency. It is typically seen in middle-aged females. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Glossitis, angular cheilitis and koilonychia are associated. It carries an increased risk of squamous cell carcinoma of the pharynx and the esophagus.

RBC and WBC morphologies
RBC and WBC morphologies

Anaemia morphology slides I-L. SLIDE I (Magnification x 1000): 1=rouleaux formation. SLIDE J (Magnification x 1000): 2=Howell jolly inclusion bodies in the cytoplasm of red cells of a 36 year old haemoglobin SS disease patient. SLIDE K (Magnification x 1000): 6=lymphoid blast (moderate size blast with scanty cytoplasm, high nuclear-cytoplasmic ratio, single prominent nucleolus). SLIDE L (Magnification x 1000, Inset x 400): 4=small (mature looking) lymphocyte; 5=Smear cells; Inset: Sea of mature looking, monomorphic lymphoid cells and smear cells seen in chronic lymphocytic leukaemia.

RBC morphologies
RBC morphologies

Anaemia morphology slides A-D. SLIDE A (Magnification x 1000): 1=microcyte. SLIDE B (Magnification x 1000): 2=oval macrocyte (compared to the nucleus of a mature lymphocyte). SLIDE C (Magnification x 1000): 3=tear drop red cell; 5=stomatocyte. SLIDE D (Magnification x 1000): 4=target red cell, 5=stomatocyte, 6=neutrophil hypersegmentation, 7=platelet/ thrombocyte.

Burr cells
Burr cells

Definition and Diagnosis of Anemia

  • Low hemoglobin and/or RBC count → decreased oxygen-carrying capacity
  • WHO criteria:
    • Men: Hb < 13 g/dL
    • Nonpregnant women: Hb < 12 g/dL
    • Pregnant women/elderly: Hb < 11 g/dL

Classification of Anemia by MCV

  • Microcytic: MCV < 80 fL
    • Causes: Iron deficiency, Thalassemia, Sideroblastic anemia, AOCD, Lead toxicity, Copper deficiency
  • Macrocytic: MCV > 100 fL
    • Causes: B12/folate deficiency, Aplastic anemia, MDS, Hypothyroidism, Liver dysfunction, Alcoholism, Drugs, Fanconi anemia, PNH
  • Normocytic: MCV 80–100 fL
    • Causes: Acute blood loss, AOCD, Renal failure, Early iron deficiency, Hypothyroidism, Inflammation, Aplastic anemia, Hemolytic anemias

Microcytic Anemias

  • Defined as MCV < 80 fL (adults), < 70 fL (children)
  • Most common: Iron deficiency anemia (IDA), Thalassemia
  • Pathophysiology: Deficient heme/globin synthesis

Iron Deficiency Anemia (IDA)

  • Causes:
    • Children: Nutritional deficiency
    • Women: Menstrual blood loss
    • Adults: Occult/gross blood loss (GI, GU)
  • Iron studies:
    • Low serum iron, low ferritin, increased TIBC, low transferrin saturation, increased free erythrocyte porphyrin, increased RDW
  • Peripheral smear: Hypochromic, microcytic RBCs, anisocytosis, thrombocytosis, normal reticulocyte count, decreased RBC count
  • Bone marrow: Erythroid hyperplasia, increased RBC precursors, elevated serum transferrin receptor
  • Clinical features: Fatigue, pallor, pica, hair loss, dyspnea, koilonychia, smooth tongue, mucosal/scleral pallor
  • Plummer-Vinson syndrome: Triad of dysphagia, iron-deficiency anemia, esophageal webs; increased risk of pharyngeal/esophageal SCC

Key RBC Morphologies

  • Microcyte: Small RBC (microcytic anemia)
  • Oval macrocyte: Large, oval RBC (macrocytic anemia)
  • Tear drop cell: Myelofibrosis, marrow infiltration
  • Target cell: Thalassemia, liver disease
  • Stomatocyte: Hereditary stomatocytosis, liver disease
  • Rouleaux formation: Multiple myeloma, chronic inflammation
  • Howell-Jolly bodies: Asplenia, hemolytic anemia
  • Burr cells (echinocytes): Uremia, pyruvate kinase deficiency
  • Neutrophil hypersegmentation: Megaloblastic anemia
  • Smudge cells: Chronic lymphocytic leukemia (CLL)

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Anemia fundamentals

Anemia is a condition in which hemoglobin concentration and/or the RBC count is low, leading to decreased oxygen-carrying capacity of the blood. The World Health Organization (WHO) defines anemia as hemoglobin:

  • < 13 g/dL in men
  • < 12 g/dL in nonpregnant women
  • < 11 g/dL in pregnant women and the elderly

Classification of anemia: According to MCV, anemia can be classified as below.

  1. Microcytic: MCV<80 fL Seen in Iron deficiency anemia, Thalassemia, Sideroblastic anemia, Anemia of chronic disease, Lead toxicity, Copper deficiency

  2. Macrocytic: MCV>100 fL Seen in Megaloblastic anemia (deficiency of Vit B12, folate; Pernicious anemia), Aplastic anemia, Myelodysplastic syndrome (MDS), Hypothyroidism, Liver dysfunction, Alcoholism, own Syndrome, Hb F, Drugs (methotrexate, phenytoin, mercaptopurine, Antiretroviral drugs), Fanconi anemia, Paroxysmal nocturnal hemoglobinuria (PNH)

  3. Normocytic: MCV between 80-100 fL Seen in Acute blood loss, AOCD, Renal failure, Early stages of iron deficiency anemia, Hypothyroidism, Inflammation, Aplastic anemia, Hemolytic anemias

    I) Microcytic Anemias

    Microcytic anemia is defined as:

    • MCV < 80 fL in adults, or
    • MCV < 70 fL in children up to 12 years of age

    The most common causes are iron deficiency anemia (IDA) and thalassemia. Microcytosis results from deficient synthesis of heme and/or globin.

    Iron deficiency anemia (IDA): IDA is most commonly caused by:

    • Nutritional iron deficiency (especially in children)
    • Increased menstrual blood loss (in women)
    • Occult or gross blood loss in adults (e.g., bleeding hemorrhoids, colon cancer, peptic ulcer)

    In IDA, iron stores (ferritin) become depleted first. This is followed by decreased hemoglobin and the development of hypochromic, microcytic anemia.

    Clinical features include fatigue, hair loss, dyspnea on exertion, pallor, and pica. Patients with underlying CHD may develop angina due to reduced oxygen delivery.

    On examination, you may see mucosal and scleral pallor, a smooth tongue, and koilonychia (spoon-shaped nails).

    Iron studies show low serum iron, low ferritin, decreased Hb concentration, increased TIBC, decreased percent saturation of transferrin with iron, and increased free erythrocyte porphyrin. RDW is increased.

    Peripheral smear shows hypochromic, microcytic RBCs, thrombocytosis, and anisocytosis, with a typically normal reticulocyte count and decreased RBC count. Bone marrow shows erythroid hyperplasia and increased RBC precursors. Serum transferrin receptor levels are elevated.

    Plummer-Vinson or Paterson-Kelly syndrome presents as a classical triad of dysphagia, iron-deficiency anemia and esophageal webs. The syndrome is caused due to iron deficiency. It is typically seen in middle-aged females. The dysphagia is usually painless and intermittent or progressive over years, limited to solids and sometimes associated with weight loss. Glossitis, angular cheilitis and koilonychia are associated. It carries an increased risk of squamous cell carcinoma of the pharynx and the esophagus.

Anaemia morphology slides I-L. SLIDE I (Magnification x 1000): 1=rouleaux formation. SLIDE J (Magnification x 1000): 2=Howell jolly inclusion bodies in the cytoplasm of red cells of a 36 year old haemoglobin SS disease patient. SLIDE K (Magnification x 1000): 6=lymphoid blast (moderate size blast with scanty cytoplasm, high nuclear-cytoplasmic ratio, single prominent nucleolus). SLIDE L (Magnification x 1000, Inset x 400): 4=small (mature looking) lymphocyte; 5=Smear cells; Inset: Sea of mature looking, monomorphic lymphoid cells and smear cells seen in chronic lymphocytic leukaemia.

Anaemia morphology slides A-D. SLIDE A (Magnification x 1000): 1=microcyte. SLIDE B (Magnification x 1000): 2=oval macrocyte (compared to the nucleus of a mature lymphocyte). SLIDE C (Magnification x 1000): 3=tear drop red cell; 5=stomatocyte. SLIDE D (Magnification x 1000): 4=target red cell, 5=stomatocyte, 6=neutrophil hypersegmentation, 7=platelet/ thrombocyte.

Key points

Definition and Diagnosis of Anemia

  • Low hemoglobin and/or RBC count → decreased oxygen-carrying capacity
  • WHO criteria:
    • Men: Hb < 13 g/dL
    • Nonpregnant women: Hb < 12 g/dL
    • Pregnant women/elderly: Hb < 11 g/dL

Classification of Anemia by MCV

  • Microcytic: MCV < 80 fL
    • Causes: Iron deficiency, Thalassemia, Sideroblastic anemia, AOCD, Lead toxicity, Copper deficiency
  • Macrocytic: MCV > 100 fL
    • Causes: B12/folate deficiency, Aplastic anemia, MDS, Hypothyroidism, Liver dysfunction, Alcoholism, Drugs, Fanconi anemia, PNH
  • Normocytic: MCV 80–100 fL
    • Causes: Acute blood loss, AOCD, Renal failure, Early iron deficiency, Hypothyroidism, Inflammation, Aplastic anemia, Hemolytic anemias

Microcytic Anemias

  • Defined as MCV < 80 fL (adults), < 70 fL (children)
  • Most common: Iron deficiency anemia (IDA), Thalassemia
  • Pathophysiology: Deficient heme/globin synthesis

Iron Deficiency Anemia (IDA)

  • Causes:
    • Children: Nutritional deficiency
    • Women: Menstrual blood loss
    • Adults: Occult/gross blood loss (GI, GU)
  • Iron studies:
    • Low serum iron, low ferritin, increased TIBC, low transferrin saturation, increased free erythrocyte porphyrin, increased RDW
  • Peripheral smear: Hypochromic, microcytic RBCs, anisocytosis, thrombocytosis, normal reticulocyte count, decreased RBC count
  • Bone marrow: Erythroid hyperplasia, increased RBC precursors, elevated serum transferrin receptor
  • Clinical features: Fatigue, pallor, pica, hair loss, dyspnea, koilonychia, smooth tongue, mucosal/scleral pallor
  • Plummer-Vinson syndrome: Triad of dysphagia, iron-deficiency anemia, esophageal webs; increased risk of pharyngeal/esophageal SCC

Key RBC Morphologies

  • Microcyte: Small RBC (microcytic anemia)
  • Oval macrocyte: Large, oval RBC (macrocytic anemia)
  • Tear drop cell: Myelofibrosis, marrow infiltration
  • Target cell: Thalassemia, liver disease
  • Stomatocyte: Hereditary stomatocytosis, liver disease
  • Rouleaux formation: Multiple myeloma, chronic inflammation
  • Howell-Jolly bodies: Asplenia, hemolytic anemia
  • Burr cells (echinocytes): Uremia, pyruvate kinase deficiency
  • Neutrophil hypersegmentation: Megaloblastic anemia
  • Smudge cells: Chronic lymphocytic leukemia (CLL)