Lecture 9 - Introduction to Haematological Disorders - Anaemia

Question 1

What is Aneamia?

Answer 1

Its a decrease in the RBC mass, as measured by the [RBC], [Hb] or haematocrit below the biological normal

Question 2

Clinical Signs of Anemia

Answer 2

Decreased [Hb]
- leads to decreased oxygen carrying capacity
- causes exercise intolerance and/or difficulty breathing with exercise, fatigue/tiredness, weakness and dizziness
Pallor
- a pale appearance may occur with decreased haemoglobin content or decreased perfusion of tissue
- including pale conjunctiva, pale mucous membranes, pale nail bed or pale palmar creases
A range of less specific clinical signs may also occur with some types of anaemia
- including irritability, headache, itchiness and abnormal appetite

Question 3

Mechanisms of Anaemia

Answer 3

Pathophysiological mechanisms underlying anemia may be divided into:

• decreased production (hypoproliferative)
• increased destruction (haemolysis)
• increased loss (haemorrhage)

Question 4

Decreased Production of RBC

Answer 4

Can occur due to:
Proliferation defects 
- bone marrow disorders
Maturation defects
- genetic
- nutritional

Question 5

Proliferation Defects

Answer 5

Includes a range of disorders of erythropoiesis 
- insufficient erythropoietin 
- bone marrow damage
- stem cell damage
Results in decreased production of RBC
Morphology: typically normocytic and normochromic 
Aetiology: many
- renal disease
- lymphoma
- radiation/chemotherapy

Question 6

Maturation Defects

Answer 6

Abnormal nuclear or cytoplasmic development of RBC during erythropoiesis
Nuclear defects
- affect all cell lines (RBC, WBC, PLT) not just RBC
- morphology: macrocytic, normochromic/hypochromic
- aetiology: e.g. B12, folate deficiency
Cytoplasmic defects
- abnormal haemoglobin production
- morphology: microcytic, hypochromic
- aetiology: e.g. iron deficiency

Question 7

Laboratory Investigation of Anaemia

Answer 7

Bone marrow assessment
Iron studies
Vitamin B12/folate
Haemoglobin electrophoresis
Biochemistry assays
- liver function
- renal function
- endocrine function

Question 8

Haemorrhagic Anaemia

Answer 8

Loss of RBC from the vasculature
May occur when:
- normal mechanisms of haemostasis are overwhelmed e.g. trauma or surgery
- defective mechanisms of haemostasis e.g. haemophilia, thrombocytopenia
Initially normocytic, normochromic
Complicated by:
- increased erythropoiesis; macrocytic
- blood transfusion
- production limitations e.g. Fe deficiency; microcytic

Question 9

Haemolytic Anaemia

Answer 9

Act to decrease lifespan of RBCs
Increased erythropoiesis may compensate
Two general endpoints to pathological processes
- intravascular haemolysis
- extravascular haemolysis

Question 10

Extravascular Haemolytic Anaemia

Answer 10

Occurs outside the vasculature
Mediated by macrophages resident in tissues
- particularly spleen
May be due to an immune process
- e.g. IgG opsinisation of RBC => Fc mediated phagocytosis of RBC
May be due to altered cell structure
- e.g. denatured haemoglobin => ↓ deformability => phagocytosis within splenic sinusoids
- e.g. Thalassemia, unstable Hb tetramer

Question 11

Intravascular Haemolytic Anaemia

Answer 11

Occurs within the vasculature
Intrinsic
- deficit within the RBC makes it susceptible to
haemolysis
- e.g. glucose 6 phosphate dehydrogenase (G6PD)
deficiency
Extrinsic
- process external to the RBC causes haemolysis
- e.g. complement mediated lysis
- e.g. mechanical damage to RBC while within vessels

Question 12

Laboratory Investigation - Haemorrhagic Anaemia

Answer 12

Look for coagulation

• prothrombin time
• activated partial thromboplastin time
• thrombin time
• PFA-100
• vWf concentration
• platelet aggregometry

Question 13

Laboratory Investigation - Haemolytic Anaemia

Answer 13

Plasma haemoglobin
Serum haptoglobin
Serum methemalbumin
Urine hemosiderin
Serum bilirubin
Urobilin/urobilinogen
Direct antiglobulin (Coomb’s) test 
Osmotic fragility
Membrane protein analysis
Detection of enzyme deficiencies