Haematology I *1

• Hematopoiesis gives rise to seven cell lines, each with a distinct function.
  • Red blood cells transport oxygen from the lungs to tissues.
  • Neutrophils are involved in chemotaxis, phagocytosis, and killing phagocytosed cells.
  • Eosinophils perform neutrophil functions, cause antibody-dependent damage to parasites, and mediate immediate hypersensitivity reactions.
  • Basophils mediate immediate hypersensitivity and modulate inflammatory responses via proteases and heparin.
  • Monocytes and macrophages are involved in chemotaxis, phagocytosis, microorganism killing, antigen presentation, and the release of IL-1 and TNF.
  • Platelets are responsible for primary hemostasis by adhering to subendothelial connective tissue.
  • Lymphocytes play a role in immune response and produce hematopoietic growth factors.

Normal Hemoglobin Levels

• Hemoglobin levels vary by age and sex.
  • Children (6 months - 6 years): 110-145 g/L
  • Children (6 years - 14 years): 120-155 g/L
  • Adult males: 130-170 g/L
  • Adult females: 120-155 g/L
  • Pregnant females: 110-140 g/L

Anemia Development

• Anemia arises when hemoglobin levels fall below the reference range for an individual's age and sex.
• The rate at which anemia develops determines the symptoms and signs.

Symptoms of Anemia

• Common symptoms include:
  • Lassitude
  • Fatigue
  • Dyspnea on exertion
  • Palpitations
  • Headache
  • Chest pain

Signs of Anemia

• Common signs include:
  • Pallor
  • Tachycardia
  • Wide pulse pressures
  • Systolic flow murmurs
  • Congestive cardiac failure

Mechanisms of Anemia Development

• Anemia can develop through several mechanisms:
  • Blood loss
  • Decreased red cell lifespan (hemolytic)
    • Congenital (e.g., sickle cell anemia)
    • Acquired (e.g., malaria, drugs)
  • Impairment of red cell formation
    • Insufficient erythropoiesis
    • Ineffective erythropoiesis
  • Pooling and destruction of RBCs in the spleen
  • Increased plasma volume (e.g., pregnancy)

Types and Causes of Anemia

• Anemia is classified by red blood cell size:
  • Microcytic (small)
    • Iron deficiency
    • Thalassemias
  • Normocytic (normal)
    • Acute blood loss
    • Anemia of chronic disease
    • Chronic renal failure
  • Macrocytic (large)
    • Alcoholism
    • Folate deficiency
    • Vitamin B12 deficiency
    • Drugs

Iron Deficiency Anemia

• Iron deficiency anemia is the most common cause of microcytic anemia worldwide.
• The body tightly controls iron absorption due to its potential toxicity in excess.
• Mechanisms of iron deficiency:
  • Poor dietary intake (vegetarians and vegans)
  • Malabsorption (duodenum in celiac disease, jejunum in Crohn's disease)
  • Increased iron loss (menorrhagia, GI issues like peptic ulcers, IBD, malignancy, or hookworm)

Manifestations of Iron Deficiencies

• Manifestations include:
  • Koilonychia (spoon-shaped nails)
  • Angular cheilitis (inflammation of mouth corners)
  • Atrophic glossitis (smooth, glossy tongue)
  • Recurrent oral ulceration
  • Burning mouth
  • Esophageal web (Plummer-Vinson/Patterson-Brown Kelly syndrome)

Iron Deficiency Management

• Management involves:
  • Investigation via blood film and iron studies
  • Addressing the underlying cause
  • Oral supplementation (ferrous sulfate 200mg x3 daily for 3 months)
  • Parenteral iron (in some cases, but with risks like fever, arthropathy, anaphylaxis)
  • Blood transfusion (only in severe cases)

Thalassemias

• Thalassemias are inherited blood disorders leading to less hemoglobin than normal, another cause of microcytic anemia.

Normocytic Anemias

• Normocytic anemias are associated with chronic conditions:
  • Chronic inflammatory/connective tissue diseases (rheumatoid arthritis)
  • Chronic infections (tuberculosis)
  • Chronic renal disease (reduced erythropoietin)
  • Malignancies (bone marrow infiltration)

Macrocytic Anemia Divisions

• Macrocytic anemias are divided into:
  • Megaloblastic erythropoiesis (abnormal red cell development due to disordered DNA synthesis)
  • Normoblastic erythropoiesis (normal red cell maturation)

Megaloblastic Anemia

• Megaloblastic anemia is a type of macrocytic anemia.
• Deficiencies in folate (vitamin B9) and vitamin B12 are associated with megaloblastic anemia.
  • Folate is essential for DNA synthesis and found in green leafy vegetables.
  • Vitamin B12 is required for enzymatic reactions and found only in animal-derived foods.

Causes of Folate and Vitamin B12 Deficiencies

• Folate deficiency:
  • Inadequate intake (elderly, alcoholism)
  • Malabsorption (celiac disease, Crohn’s disease, resection)
  • Increased requirement (pregnancy, hemolytic anemias, myelofibrosis)
  • Increased loss (dialysis, liver disease, congestive heart failure)
  • Drugs (methotrexate, phenytoin, trimethoprim)
• Vitamin B12 deficiency:
  • Inadequate intake (strict vegans)
  • Inadequate secretion of intrinsic factor (pernicious anemia, gastrectomy)
  • Inadequate release from food (gastritis, PPIs, EtOH abuse)
  • Diversion of dietary B12 (bacterial overgrowth, small intestinal strictures)
  • Malabsorption (Crohn’s disease, ileal resection)

Clinical Features of Folate and Vitamin B12 Deficiencies

• Folate and Vitamin B12:
  • General anemia symptoms and signs
  • Occasional mild jaundice
  • Glossitis
  • Oral ulceration
• Vitamin B12 specific:
  • Peripheral neuropathy (loss of proprioception and vibration sense)
  • Demyelination with subacute combined degeneration of spinal cord
  • Dementia

Management of Megaloblastic Anemia

• Management involves:
  • Blood film
  • Serum folate and B12 measurement (always test together)
  • Addressing the underlying cause
  • Oral supplementation (never folate only if B12 level not known)
  • Parenteral vitamin B12 (IM) for pernicious anemia

Causes of Normoblastic Macrocytosis

• Causes include:
  • Alcohol excess
  • Liver dysfunction
  • Hypothyroidism
  • Drugs (methotrexate, azathioprine)

Types of Hemolytic Anemias

• Hemolytic anemias are categorized as:
  • Congenital
  • Acquired

Defects in Congenital Hemolytic Anemias

• Congenital hemolytic anemias can arise from:
  • Membrane defects: Mutations lead to increased fragility and hemolysis (e.g., hereditary spherocytosis)
  • Enzyme defects: G6PD deficiency results in increased sensitivity to oxidative stress
  • Globin defects

Defects in Acquired Hemolytic Anemia

• Acquired hemolytic anemias can be:
  • Immune: IgG-coated red cells interact with macrophages, leading to phagocytosis
    • Autoimmune (idiopathic or secondary to infections, drugs, SLE, hematological malignancies)
    • Alloimmune (transfusion reactions)
  • Non-immune: Mechanical trauma (metallic valves), burns, infections (malaria), or drugs (dapsone)

Clinical Features of Hemolytic Anemias

• Clinical features include:
  • Pallor
  • Jaundice (elevated bilirubin)
  • Splenomegaly
  • Expansion of erythropoiesis leading to bone deformities (frontal bossing) and pathological features

Hemoglobin Composition

• Hemoglobin: transports oxygen.
• Normal hemoglobin comprises two alpha and two beta chains.
• Adult hemoglobin composition:
  • Hb A (α2β2): 97%
  • Hb A2 (α2δ2): 1.8-3.6%
  • Hb F (α2γ2)