Anemia Classification and Clinical Manifestations

Clinical Manifestation of Anemia

• Symptoms and severity of anemia depend on the absolute value of Hb, speed of onset, age, and overall performance of the patient
• Acute anemia is often due to acute blood loss
  • 10-15% blood loss leads to hypotension and decreased organ perfusion
  • >30% blood loss leads to postural hypotension and bradycardia
  • >40% blood loss leads to hypovolemic shock (confusion, dyspnea, diaphoresis, hypotension, tachycardia)
• Chronic anemia has different symptoms based on Hb levels
  • Hb > 70-80 g/L: no signs or symptoms due to intrinsic compensatory mechanisms
  • Hb < 70-80 g/L: anemic syndrome (fatigue, loss of stamina, dyspnea, tachycardia, weakness, pallor, palpitations, tinnitus)

Morphological Classification of Anemia

Based on MCV

• Microcytic anemia (MCV < 80fl)
  • Iron deficiency
  • Anemia of chronic disease
  • Globin deficiency (Thalassemia)
  • Sideroblastic anemia
• Macrocytic anemia (MCV > 100 fl)
  • Megaloblastic: B12 / B9 deficiency
  • Non-megaloblastic: chronic liver disease, alcoholism, aplastic anemia
• Normocytic anemia (MCV 80-100 fl)
  • Hemolytic
    • Corpuscular (intrinsic)
      • Membrane defects: hereditary spherocytosis
      • Enzymopathy: pyruvate kinase, Glc-6-P DH
      • Hemoglobinopathy: thalassemia, sickle cell disease, methemglobinemia, HbC, HbD, HbE
    • Extracorpuscular (extrinsic)
      • Mechanical/physical cause: heart valve, hemoglobinuria, microangiopathic hemolytic anemia
      • Metabolic cause: liver disease, alcoholism, hypophosphatemia, malnutrition, Cu overload, Wilson’s disease
      • Chemical substances: oxidative agents, snake venom
      • Infections: malaria, septicemia (clostridium perfringens), leptospira, borelia
  • Non-hemolytic
    • Primary impairment of blood marrow: aplastic, MDS (some), PNH, myelofibrosis
    • Secondary impairment of blood marrow: infiltration, infection, endocrinological and systemic diseases, acute kidney disease
    • Acute hemorrhage

Based on MCHC

• Hyperchrome
• Normochrome
• Hypochrome (RBCs are paler than normal): iron deficiency, anemia of chronic disease, sideroblastic anemia, lead poisoning

Based on Reticulocyte Count

• Lowered number
• Normal number
• Increased number

Iron Deficiency Anemia (IDA)

• Form of hypochromic microcytic anemia

Iron Metabolism

• Functional iron: 75% of total iron, mainly in hemoglobin (70%) and myoglobin (4%)
• Storage iron: 25% of total iron, mainly in liver as ferritin and hemosiderin
• Dietary intake: 10-20mg, with 1-2mg absorption in gut, and loss of iron via epithelial desquamation
• Pregnancy: 500-1000mg loss of iron

Iron Cycle

• Hepcidin: regulates iron absorption in duodenum and upper jejunum
• Hepcidin is regulated by HFE protein, which is low in iron deficiency
• Acidic conditions in stomach release iron from food protein
• Ferrireductase converts Fe3+ to Fe2+, which then enters enterocyte through DMT1
• Vitamin C increases iron absorption, while calcium decreases it
• Iron-containing heme enters via HCP1 and reaches plasma via ferroportin
• Transferrin transports iron in plasma, converting Fe2+ to Fe3+ with ferroxidase (ceruloplasmin)
• Ferritin stores iron in liver, mainly as Fe3+, with an outer protein shell and apoferritin
• Hemosiderin is an insoluble protein-iron complex formed from ferritin in macrophages

Etiology of Iron Deficiency Anemia

• Increased demand: growth, pregnancy, breastfeeding, EPO therapy
• Increased loss: chronic bleeding, GIT ulcers, hookworm infestation, malignancy, diverticulitis, respiratory tract, UGT, NSAIDs, hemodialysis
• Decreased intake/absorption: malnutrition, post-gastrectomy, Crohn's disease, celiac disease, SBD, achlorhydria/hypochlorhydria, H.pylori associated gastritis

Stages of Iron Deficiency Anemia

• Pre-latent: negative iron balance, mobilization from reticuloendothelial storage sites
• Latent: depletion of iron stores, gradual increase in TIBC
• Manifestation: impaired erythropoiesis, decrease in Hb and hematocrit, hypochromia and microcytosis

Laboratory Findings

• CBC: Hb < 120 g/L, low hematocrit, thrombocytosis (50% of patients)
• Red blood cell indices: RDW > 15%, MCV < 80fl, MCH < 25pg, reticulocyte count normal or decreased
• Peripheral blood smear: anisocytosis, hypochromasia
• Iron studies: ferritin < 20ug/l, transferrin increased with saturation < 15%, TIBC increased, serum iron decreased (< 50 μg/dL)