Haematology

Question 0

Types of macrocytic anaemia

Answer 0

Megaloblastic and non-megaloblastic

Question 1

Definition of macrocytic anaemia

Answer 1

Anaemia associated with a high MCV of erythrocytes (>100fl in adults)

Question 2

Causes of megaloblastic macrocytic anaemia

Answer 2

Vitamin b12 deficiency
Folate deficiency
Drugs: methotrexate, hydroxyurea, azathioprine, zidovudine

Question 3

Causes of non-megaloblastic macrocytic anaemia

Answer 3

Alcohol excess
Liver disease
Myelodysplasia
Multiple myeloma
Hypothyroidism
Haemolysis (reticulocytosis)
Drugs: tyrosine kinase inhibitors: imatinib, sunitinib

Question 4

Causes of vitamin b12 deficiency

Answer 4

Decreased absorption:

• post gastrectomy
• pernicious anaemia
• terminal ilealresection or disease (crohns, bacterial overgrowth, pancreatic insufficiency, fish tapeworm, metformin, omeprazole)

Decreased intake (vegans)
Abnormal metabolism
- congenital tanscobalamin II deficiency
- inactivation of b12 by nitrous oxide

Question 5

Causes of folate deficiency

Answer 5

Decreased intake

• alcoholics
• elderly
• anorexia

Increased demand

• pregnancy
• lactation
• malignancy
• chronic inflammation.
• chronic haemolysis
• exfoliative dermatitis

Decreased absorption

• jejunal disease (coeliac disease)
• tropical sprue

Drugs

• phenytoin
• trimethoprim
• methotrexate

Question 6

Examination signs of anaemia

Answer 6

Pallor
Tachycardia
May be signs of cause: e.g. Malnutrition, jaundice, hypothyroid appearance

Question 7

Signs of pernicious anaemia

Answer 7

Lemon-tinted skin (mild jaundice)
Glossitis (red sore tongue)
Angular stomatitis (cheilitis)
Weight loss

Question 8

Signs of vitamin b12 deficiency

Answer 8

Peripheral neuropathy
Ataxia
Subacute combined degeneration of the spinal cord
Optic atrophy
Dementia

Question 9

What is subacute combined degeneration of the spinal cord?

Answer 9

= degeneration of dorsal and lateral columns of the spinal cord causing loss of joint and position sense, ataxia and UMN weakness.
Partially or completely relieved by restoring vitamin b12 levels.

Question 10

What is pernicious anaemia?

Answer 10

Autoimmune damage to gastric parietal cells causing atrophic gastritis and consequent decreased production of intrinsic factor needed for b12 absorption in the terminal ileum.
Pernicious anaemia can be associated with other autoimmune diseases (e.g. Vitiligo, hypothyroidism)

Question 11

Management of pernicious anaemia

Answer 11

IM hydroxycobalamin (3x wkly for 2 weeks, then every 3 months for life)

Question 12

Complications of pernicious anaemia

Answer 12

Increased risk of gastric cancer

Question 13

Definition of aplastic anaemia

Answer 13

Characterised by diminished haematopoietic precursors in the bone marrow and deficiency of all blood cell elements (pancytopaenia)

Question 14

Causes of aplastic anaemia

Answer 14

1. Idiopathic (>40%) - may be due to destruction or suppression of the stem cell by autoimmune mechanisms
2. Acquired
   - Drugs (chloramphenicol, gold, alkylating agents, antiepileptics, sulphonamides, methotrexate, nifedipine)
   - Chemicals (DDT, benzene)
   - Radiation
   - Viral infection (B19 parvovirus, HIV, EBV)
   - paroxysmal nocturnal haemoglobinuria
3. Inherited
   - Fanconi’s anaemia
   - Dyskeratosis congenita (associated with reticulated hyperpigmented rash, nail dystrophy and mucosa leukoplakia)

Question 15

What is Fanconi’s anaemia

Answer 15

Rare autosomal recessive or X-linked disorder, caused by an error in DNA repair.
Characterised by familial aplastic anaemia, short stature, abnormality of thumbs, café au lait spots, microcephaly, hypogonadism and renal tract defects.

Question 16

History findings of aplastic anaemia

Answer 16

Slow (months) or rapid (days) onset
Anaemia: Tiredness, lethargy, dyspnoea
Thrombocytopaenia: Easy bruising, bleeding gums, epistaxis
Leukopaenia: Increased frequency and severity of infections

Question 17

Examination findings of aplastic anaemia

Answer 17

Anaemia: Pale
Thrombocytopaenia: Petechiae, bruises
Leukopaenia: Multiple bacterial or fungal infections. No hepatomegaly, splenomegaly or lymphadenopathy

Question 18

Management of aplastic anaemia

Answer 18

1. Treat the underlying cause (e.g. drugs withdrawal)
2. Supportive: blood & platelet transfusions, antibiotics for infections, consider antibiotic prophylaxis
3. Patients with severe AA: allogeneic haematopoietic stem cell transplant (curative); immunosuppressive therapy (combined use of: anti-thymocyte globulin, cyclosporine, and corticosteroids, with or without GCSF) –> for patients who don’t have a sibling matched donor or who are >45 (increased chance of graft vs host)

Question 19

Definition of haemolytic anaemia

Answer 19

Premature erythrocyte breakdown causing shortened erythrocyte life span (<120 days) and anaemia

Question 20

Classification of causes of haemolytic anaemia

Answer 20

Hereditary
- Membrane defects
- Metabolic defects
- Haemoglobinopathies 
Acquired
- Autoimmune
- Isoimmune
- Drugs
- Trauma
- Infection
- Paroxysmal noctural haemoglobinuria

Question 21

Hereditary causes of haemolytic anaemia

Answer 21

Membrane defects
- Hereditary spherocytosis
- Elliptocytosis
Metabolic defects
- G6PD deficiency 
- Pyruvate kinase deficiencies
Haemoglobinopathies
- Sickle cell disease
- Thalassaemia

Question 22

Acquired causes of haemolytic anaemia

Answer 22

Autoimmune
- Warm or cold antibodies attach to erythrocytes causing intravascular haemolysis and extravascular haemolysis
Isoimmune
- Transfusion reaction
- Haemolytic disease of the newborn
Drugs
- Penicillin
- Quinine (through formation of drug-antibody-erythrocyte complexes)
Trauma
- Microangiopathic haemolytic anaemia caused by red cell fragmentation in abnormal microcirculation (e.g. haemolytic uraemic syndrome, DIC, malignant hypertension, pre-eclampsia)
- Artificial heart valves
Infection
- Malaria, sepsis
Paroxysmal nocturnal haemoglobinuria
- Increased complement-mediated lysis caused by decreased synthesis of protein cellular anchor of complement-degrading proteins

Question 23

Examination findings of haemolytic anaemia

Answer 23

Pallor (anaemia), jaundice, hepatosplenomegaly

Question 24

'warm antibodies'

Answer 24

IgG agglutinate erythrocytes at 37°C | Associated with SLE, lymphomas or methyldopa

Question 25

'cold antibodies'

Answer 25

IgM agglutinate erythrocytes in at room temperature or colder. Associated with infections (e.g. mcyoplasma, EBV) or lymphomas.

Question 26

What is G-6PD deficiency?

Answer 26

(X-linked) G-6PD is important in maintaining glutathione in reduced state. Deficiency results in susceptibility to oxidative stress (e.g. precipitated by sulphonamides, nitrofurantoin, dapsone, fava beans).

Question 27

What is hereditary spherocytosis?

Answer 27

= autosomal dominant condition where decreased spectrin (structural membrane protein) causes decreased deformability of erythrocytes.

Question 28

Investigations for haemolytic anaemia

Answer 28

1. Blood: FBC (decreased Hb, increased reticulocytes, increased MCV, also increased unconjugated bilirubin, decreased haptoglobin), U&E, folate 2. Blood film: - Leucoerythroblastic picture - Macrocytosis - Nucleated erythrocytes - Reticulocytes - Polychromasia Identifies specific abnormal cells, such as spherocytes, elliptocytes, sickle cells, fragmented erythrocytes, malarial parasites, erythrocyte Heinz bodies (denatured Hb, stained with methyl violet seen in G-6PD deficiency) 3. Urine: Increased urobilirubinogen. If there is haemoglobinuria and haemosiderinuria. 4. Direct Coombs' test: Identifies erythrocytes coated with antibodies (agglutinins) using antihuman globulin. 5. Osmotic fragility test or Spectrin mutation analysis: to identify membrane abnormalities 6. Ham's test: Lysis of erythrocyte in acidified serum in paroxysmal nocturnal haemoglobinuria. More recently, red cells are analysed using monoclonal antibodies to the GPI-anchored proteins (CD55 and CD59) and flow cytometry. 7. Hb electrophoresis or enzyme assays 8. Bone marrow biopsy (rarely required): erythroid hyperplasia

Question 29

Definition of microcytic anaemia

Answer 29

Anaemia associated with low MCV (<80 fl)

Question 30

Causes of microcytic anaemia

Answer 30

1. Iron-deficiency = commonest cause - Blood loss (e.g. GI tract, urogenital tract, hookworm infection) - Decreased absorption: small bowel disease, post-gastrectomy - Increased demands: growth, pregnancy - Decreased intake: vegans 2. Anaemia of chronic disease: often normocytic, but may be microcytic 3. Thalassaemia 4. Sideroblastic anaemia: Abnormality of haem synthesis. Can be inherited (X-linked), or secondary to alcohol, drugs (e.g. isoniazid, chloramphenicol), lead, myelodysplasia

Question 31

What is anaemia of chronic disease?

Answer 31

Occurs in chronic inflammatory/autoimmune disease, chronic infections (e.g. TB/infective endocarditis), malignancy, chronic renal failure. Serum ferritin is normal or increased. It may be caused by decreased RBC survival, decreased erythropoietin response to the anaemia, decreased iron release from bone marrow to erythroblasts.