Approach to Anaemia Diagnosis

Question 1

What is anaemia?

Answer 1

Reduction in haemoglobin concentration below that which is optimum for that individual OR reduction in haemoglobin concentration below 95% range for the population

Question 2

What are the ways we can classify anemia?

Answer 2

1. Decreased production
   - Hypoproliferative (reduced amount of erythropoeisis)
   - Maturation abnormality (erythropoeisis present but ineffective):
   a) Cytoplasmic defects (impaired haemoglobinisation)
   b) Nuclear defects (impaired cell division)
2. Increased loss or destruction of red cells
   - Bleeding
   - Haemolysis

Question 3

Draw out the tree on how we can classify anaemias

Answer 3

Question 4

If there is a reticulocytosis, what should we do next?

Answer 4

Look for red cell breakdown products

1. If bleeding - red cells are gone, nothing to breakdown
2. If haemolysing, then increased products of red cell destruction are seen: increased unconjugated serum bilirubin; increased urinary urobilinogen

“Work hypertrophy” of macrophage rich tissues causes splenomegaly

Question 5

If you suspect haemolytic anaemia, what should we look for?

Answer 5

Evidence of red cell breakdown products + reticulocytosis

Then consider a potential cause

Question 6

Is red cell production relatively impaired?

Answer 6

Normal marrow can increase RBC production 3-4 fold

Reticulocyte count should be appropriately increased for the degree of anaemia

Anaemia with a lesser reticulocyte response is at least partly due to impaired red cell production

Question 7

What does MCV and MCH indicate?

Answer 7

MCV - cell size
MCH - cell Hb content

Question 8

What are causes of hypochromic microcytic anaemias? - problems with haemoglobin formation

Answer 8

Iron deficiency (commonest cause - find out why); some anaemias of chronic disease (iron availability to red cell reduced)

Haem defects (rare) - lead poisoning, congenital sideroblastic anaemia

Globin defects - thalassaemias

Question 9

What are causes of macrocytic anaemias?

Answer 9

Nuclear maturation defects (failure of cell division) - nutritional (B12/Folate - megaloblastic anaemias); myelodysplasia, drugs lik echemotherapy

Apparent - agglutination, (reticulocytosis)

Question 10

What are cause of macrocytosis without significant anaemia?

Answer 10

Hypothyroidism
Alcohol
Liver disease

Question 11

What are hypoproliferative causes for normochromic normocytic anaemias?

Answer 11

Marrow failure - drug induced, aplastic anaemia (can be macrocytic)
Hypometabolic (can be macrocytic)
Marrow infiltration (metastatic malignancy, fibrosis)
Renal impairment
Chronic disease (infective, inflammatory, malignant)

Question 12

What is renal anaemia?

Answer 12

An anaemia of chronic disease due to failure of erythropoietin production

Question 13

Describe how inflammation can cause anaemia of chronic disease

Answer 13

Question 14

Describe a summary of anaemia of chronic disease

Answer 14

Multiple mechanisms all driven by inflammatory cytokines induced by infection / malignancy / autoimmune disease dysregulation

Blunted epo response by kidney
Impaired iron availability to erythroid precursors
Inhibition of proliferation
Reduced red cell survival

Question 15

Why can anaemia of chronic disease sometimes be microcytic?

Answer 15

If predominant mechanism is through hepcidin stimulation

May be microcytic due to reduced release of iron from macrophages i.e. failure of haemoglobin synthesis

Explains low transferrin saturation despite normal / raised ferritin

Explains why it may respond to IV iron

Question 16

Describe differences in serum iron, transferrin, % transferrin saturation, ferritin and MCV in iron deficiency vs. anaemia of chronic disease

Answer 16

Question 17

Describe the diagnostic approach to anaemia

Answer 17