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Hematology Study Notes

• Hematology is the study of blood and blood disorders.

Macrocytic Anemias

• Macrocytic anemias are characterized by red blood cells (RBCs) having a mean corpuscular volume (MCV) greater than 98 fl.
• Two types of macrocytic anemias exist:
  • Megaloblastic anemia
  • Non-megaloblastic macrocytic anemia

Non-Megaloblastic Macrocytic Anemias

• These anemias are not caused by vitamin B12 or folic acid deficiency.
• The macrocytes (red blood cells) in these conditions are round.
• Some conditions associated with non-megaloblastic macrocytic anemias include:
  • Reticulocytosis
  • Hypothyroidism/myxedema
  • Myelodysplastic syndrome
  • Scurvy (Vitamin C deficiency)
  • Liver disorders
  • Alcohol excess consumption (MCV not >110)
  • Congenital dyserythropoietic anemia (CDA I & III)
  • Erythroleukemia
  • Neonates

Megaloblastic Anemia

• Megaloblastic anemia is a group of anemias where erythroblasts in the bone marrow exhibit delayed maturation of the nucleus relative to the cytoplasm. This is due to deficiencies in vitamin B12 and folic acid.
• The underlying cause for this asynchronous maturation is DNA synthesis defects.
• Macrocytes in megaloblastic anemia are typically oval-shaped, hence also called macro-ovalocytes.

Causes of Megaloblastic Anemia

• Vitamin B12 deficiency
• Folate deficiency
• Abnormalities of Vitamin B12 or folate metabolism (such as transcobalamin deficiency).
• Other defects of DNA synthesis (like orotic aciduria)
• Acquired enzyme deficiencies due to alcohol or drugs such as hydroxyurea, cytosine arabinoside.

Vitamin B12

• The primary food sources for vitamin B12 include meat, fish, eggs, and dairy products.
• Daily requirement is approximately 1- 2 µg in adults.
• Body stores of vitamin B12 in the liver are sufficient for 2-4 years.
• Vitamin B12 absorption involves initial binding in the duodenum/jejunum to intrinsic factor (IF), a protein produced by gastric parietal cells. It's then absorbed in the terminal ileum.
• Pernicious anemia is the most frequent cause of vitamin B12 deficiency, resulting from autoimmune gastric atrophy and decreased intrinsic factor production.

Vitamin B12 Absorption

• Food protein binds B12; acid and pepsin release Vitamin B12 in the stomach.
• Intrinsic factor (IF) binds Vitamin B12 in the upper small intestine.
• Vitamin B12-intrinsic factor complex binds receptors to allow absorption in the lower small intestine.

Folate

• Folic acid is naturally found in foods like leafy greens, fruits, meat, and liver.
• Normal daily adult requirement of folate is 100-150 mcg per day.
• The body stores 10-12 mg of folate in the liver, enough for 3-4 months.

Causes of Folate Deficiency

• Dietary insufficiency
• Increased demand (pregnancy, hemolysis, renal dialysis)
• Malabsorption (sprue, celiac disease, jejunal resection)
• Medications (anticonvulsants, anti-cancer drugs)

Clinical Features of Megaloblastic Anemia

• Insidious onset with gradually progressive symptoms
• Common feature is a defect in DNA synthesis affecting rapidly dividing cells in the bone marrow.
• Symptoms can include shortness of breath, muscle weakness, pale skin, jaundice, loss of appetite, diarrhea, nausea, and fast heartbeat.
• Clinical signs include glossitis and splenomegaly, neurological signs (peripheral neuropathy, paresthesia, dementia), jaundic and splenomegaly.

Pernicious Anemia

• This is a type of megaloblastic anemia caused by autoimmune destruction of gastric epithelium-leading to decreased intrinsic factor.
• Pernicious anemia is more common among Northern Europeans.
• It often manifests with 60 -70 yrs old
• Patients with PA often develop chronic gastric inflammation, achlorhydria, and IF absence.
• Common associated features include vitiligo, myxoedema, thyroid diseases

Laboratory Diagnosis of Anemia

• Blood count to measure decreased hemoglobin and elevated MCV
• Increased serum bilirubin in some cases
• Bone marrow analysis showing large erythroblasts, megaloblasts, abnormal shape and maturations
• Serum B12 and folate levels, and other biochemical tests for deficiencies
• Antibody detection tests (e.g. anti-parietal cell antibodies, anti-intrinsic factor antibodies)

Treatment

• Treatment for megaloblastic anemia involves addressing the underlying cause and replacement therapies for deficiencies, like vitamin B12 and/or folate.
• Splenectomy may be necessary in some cases

Haemolytic Anaemia.

• Haemolytic Anaemia results from the increased rate of RBC destruction.
• The main mechanisms of red-cell destruction are intravascular and extravascular hemolysis.
• Common clinical signs include anaemia, jaundice, and pigment stone formation.

Hereditary Haemolytic Anaemia.

• Common types of hereditary haemolytic anaemias include membrane defects (congenital spherocytosis, hereditary elliptocytosis), metabolic defects (G6PD deficiency, pyruvate kinase deficiency), and haemoglobin defects (qualitative defects – sickle cell anaemia, quantitative defects – Thalassaemia).

G6PD Deficiency

• Inherited X-linked condition causing reduced NADPH production.
• The primary role of NADPH is reducing oxidative stress.
• Leads to haemolysis (destruction of red blood cells) as a result of oxidative damage when exposed to certain stressors (e.g. drugs).
• Characterised by acute and hemolytic episodes following exposure to certain stressors.

Pyruvate Kinase Deficiency

• Autosomal recessive disorder.
• Deficiency in enzyme pyruvate kinase results in ATP deficiency in erythrocytes, leading to reduced red cell survival.
• Leads to chronic or intermittent haemolytic anaemia.
• Primarily characterised by erythrocyte membrane fragility and premature destruction

Diagnosis of Haemolytic Anaemia

• Laboratory findings (increased serum bilirubin, decreased haptoglobin) ,(decreased amount of reticulocytes)
• Blood film analysis (abnormal cells' morphology)
• Screening tests (EMA, osmotic fragility tests, haptoglobin)

Other Investigations

• Rapid flow analysis
• Autohaemolysis test
• Direct antiglobulin test (Coombs test)

Treatment

• Splenectomy is commonly implemented.
• Folic acid supplementation may be administered in cases where folate deficiency is present.

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