Anaemia

Question 1

What factors influence the normal range of haemoglobin?

Answer 1

○ Age
○ Sex
○ Ethnic origin
○ Time of day sample taken
○ Time to analysis

Question 2

What are the refernce ranges of haemaglobin?

Answer 2

• Male 12-70 (140-180)
• Male >70 (116-156)
• Female 12-70 (120-160)
• Female >70 (108-143)

Question 3

What are the clinical features of anaemia?

Answer 3

○ General features due to reduced oxygen delivery to tissues:
- Tiredness/pallor
- Breathlessness
- Swelling of ankles
- Dizziness
- Chest pain
○ Depend on age and Hb level
○ Related to underlying cause:
- Evidence of bleeding
□ Menorrhagia
□ Dyspepsia, PR bleeding				
- Symptoms of malabsorption
□ Diarrhoea
□ Weight loss
- Jaundice
- Splenomegaly/ Lymphadenopathy

Question 4

What is the pathophysiology of anaemia?

Answer 4

- Bone marrow
□ Cellularity
□ Stroma
□ Nutrient
- Red cell
□ Membrane 
□ Haemoglobin
□ Enzyme
- Destruction loss
□ Blood loss
□ haemolysis
□ Hypersplenism

Question 5

What are the red cell indices?

Answer 5

○ Automated measurement of red cell size and haemoglobin content
- MCV = Mean cell volume (cell size)
- MCH = Mean cell haemoglobin
○ Can give a morphological description of anaemia

Question 6

What are the different morphological desriptions for anaemia?

Answer 6

• Hypochromic microcytic (small and pale)
• Normochromic normocytic (normal)
• Macrocytic (big and dark)

Question 7

What investigations are done in anaemia?

Answer 7

○ Investigation involves use of a discriminating test to guide further investigations
○ If laboratory is given adequate clinical information it will advise on further appropriate investigations
○ Hypochromic microcytic
- serum ferritin (iron)
○ Normochromic normocytic
- reticulocyte count
□ Shows whether the bone marrow is working
○ Macrocytic
- B12/ folate
- bone marrow

Question 8

What reason could someone have hypochromatic microcytic anaemia?

Answer 8

○ Serum ferratin 
- Low
□ Iron deficiency
- Norma/ increased 
□ Thalassaemia
□ Secondary anaemia
□ Sideroblastic anaemia (rare)

Question 9

What is iron deficiency anaemia?

Answer 9

• Commonest cause of anaemia worldwide

- Description not a diagnosis – establish cause!

Question 10

what should be looked out for in a history from someone with iron deficiency anaemia?

Answer 10

□ Dyspepsia GI bleeding
□ Other bleeding, e.g. menorrhagia
□ Diet (NB children and elderly)
□ Increased requirement - pregnancy

Question 11

What should be done on examination of someone with iron deficient anaemia?

Answer 11

□ Signs of iron deficiency ® Atrophic tongue ® Angular cheilitis ® Koilonychia
□ Abdominal and rectal

Question 12

What are the causes of iron deficient anaemia?

Answer 12

□ GI blood loss
□ Menorrhagia
□ Malabsorption
® gastrectomy ® coeliac disease

Question 13

What is the management of iron deficient anaemia?

Answer 13

□ Correct the deficiency ® Oral iron usually sufficient ® IV iron if intolerant of oral ® Blood transfusion rarely indicated
□ Correct the cause ® Diet ® Ulcer therapy ® Gynae interventions ® Surgery

Question 14

What do the different results in reticulocyte count in normocytic anaemia mean?

Answer 14

• Increased □ Acute blood loss □ Haemolysis

- Normal/ low □ Secondary anaemia ® Hypoplasia ® Bone marrow infiltration

Question 15

What is haemolytic anaemia?

Answer 15

• Accelerated red cell destruction (decreased Hb)
• Compensation by bone marrow (Increased Retics)
• Level of Hb – balance between red cell production and destruction

Question 16

What are the causes of haemolytic anaemia?

Answer 16

□ Congenital e.g.
® Hereditary spherocytosis (HS)
® Enzyme deficiency (G6PD deficiency)
® Haemoglobinopathy (HbSS)
□ Acquired
® Auto-immune haemolytic anaemia (Extravascular)
® Mechanical e.g. artificial valve (Intravascular)
® Severe infection/DIC  (Intravascular)
® PET/HUS/TTP (Intravascular)

Question 17

What is the direct antiglobulin test (Coom’s test)?

Answer 17

□ Detects antibody or complement on red cell membrane
□ Reagent contains either ® anti-human IgG ® anti-complement
□ Reagent binds to Ab (or complement) on red cell surface and causes agglutination in vitro
□ Implies immune basis for haemolysis

Question 18

How can you tell if a patient is haemolysing?

Answer 18

□ FBC, reticulocyte count, blood film
□ Serum bilirubin (direct/indirect), LDH
□ Serum haptoglobin (mops up haemoglobin)

Question 19

What is the management of haemolytic anaemia?

Answer 19

□ Support marrow function
® Folic acid
□ Correct cause
® Immunosuppression if autoimmune ◊ Steroids ◊ Treat trigger e.g. CLL, Lymphoma ® Remove site of red cell destruction ◊ Splenectomy ® Treat sepsis, leaky prosthetic valve, malignancy etc. if intravascular

Question 20

What is secondary anaemia?

Answer 20

- “Anaemia of chronic disease”
□ 70% normochromic normocytic
□ 30% hypochromic microcytic
- Defective iron utilisation
□ Increased hepcidin in inflammation
□ Ferritin often elevated
- Identifiable underlying disease
□ infection, inflammation, malignancy

Question 21

What do the different results in the B12/ folate assay mean in macrocytic anaemia?

Answer 21

- Megaloblastic
□ B12 deficiency 
□ Folate deficiency 
- Non-megaloblastic
□ Myelodysplasia 
□ Marrow infiltration 
□ Drugs

Question 22

What happens in B12/ folate deficiency?

Answer 22

□ Anaemia

□ Neurological symptoms (subacute combined degeneration of the cord in B12 deficiency)

Question 23

What are the causes of B12 deficiency?

Answer 23

□ Pernicious anaemia □ Gastric/ileal disease

Question 24

What are the causes of folate deficiency?

Answer 24

□ Dietary
□ Increased requirements (haemolysis)
□ GI pathology (e.g. coeliac disease)

Question 25

What are the signs of megoblastic anaemia?

Answer 25

□ “Lemon yellow” tinge ® Bilirubin, LDH ® Red cells friable

Question 26

What is pernacious anaemia?

Answer 26

□ Commonest cause of B12 deficiency in western populations
□ Autoimmune disease
□ Antibodies against
® intrinsic factor (diagnostic) ® gastric parietal cells (less specific) □ Malabsorption of dietary B12 □ Symptoms/signs take 1-2 years to develop

Question 27

What is the treatment of megoblastic anaemia?

Answer 27

□ Replace vitamin ® B12 deficiency ◊ B12 intramuscular injection ◊ Loading dose then 3 monthly maintenance ® Folate deficiency ◊ Oral folate replacement ◊ Ensure B12 normal if neuropathic symptoms

Question 28

Other than B12/ folate deficiency what are the other causes of macrocytic anaemia?

Answer 28

• Alcohol
• Drugs
  □ Methotrexate, Antiretrovirals, hydroxycarbamide
• Disordered liver function
• Hypothyroidism
• Myelodysplasia