Introduction to anaemia and microcytic anaemia

Question 1

What is anaemia?

Answer 1

Anaemia is present when there is a decrease in haemoglobin in blood below the reference level for the age and sex of the individual.

Question 2

What is haematocrit?

Answer 2

Haematocrit measures the proportion of red blood cells in your blood.

Question 3

What are the haemoglobin and haematocrit values in anaemia for adult males and females?

Answer 3

Adult males Hb <130g/L Hct <0.38

Adult females Hb <120g/L Hct <0.37

Question 4

What is the normal response to anaemia?

Answer 4

To make more red cells (reticulocytosis)

Upregulation takes a few days

Reticulocytes: cells that have just left the bone marrow.
- Larger than average red cells
- Still have remnants of RNA - stain purple/deeper red, blood film appears “polychromatic”

Question 5

Does decreased red cell production result in a low or high reticulocyte count and what are some causes?

Answer 5

Low reticulocyte count

Potential causes:
- Hypoproliferative - reduced amount of erythropoiesis
- Maturation abnormality - erythropoiesis present but ineffective

Question 6

For maturation abnormality where erythropoiesis is present but ineffective, what are some of the potential causes?

Answer 6

Cytoplasmic defects - impaired haemoglobinisation

Nuclear defects - impaired cell division

Question 7

Does increased loss or destruction of red cells result in a low or high reticulocyte count, what are some of the potential causes?

Answer 7

High reticulocyte count

Potential causes:
- Bleeding
- Haemolysis (rupturing/lysis of red blood cells)

Question 8

What is the definition of a reticulocyte?

Answer 8

An immature red blood cell without a nucleus, having a granular or reticulated appearance when suitably stained.

Question 9

What are the symptoms of anaemia?

Answer 9

The symptoms of anaemia are non - specific and include breathlessness, fatigue, headaches, palpitations and faintness.

Question 10

What are the signs of anaemia?

Answer 10

• Pallor
• Tachycardia
• Systolic flow murmur
• Cardiac failure

Question 11

Investigations for anaemia?

Answer 11

Bloods: full blood count
- Hb concentration, MCV, haematocrit, mean cell haemoglobin and mean cell haemoglobin concentration.

Blood film: look at cellular morphology

Reticulocyte count: assess marrow response

Additional tests - depending on clinical details and lab findings.

Question 12

What is microcytic anaemia?

Answer 12

Anaemia caused by deficient haemoglobin synthesis (cytoplasmic defect)

Question 13

What are the causes of microcytic anaemia?

Answer 13

Haem deficiency

Globin deficiency

Question 14

What are the causes of haem deficiency in microcytic anaemia?

Answer 14

Lack of iron for erythropoiesis
- Iron deficiency - most common cause of microcytic anaemia
- Anaemia of chronic disease - IL-6 is released due to chronic diseases.

Problems with porphyrin synthesis
- Sideroblastic anaemia: excess iron build-up in mitochondria due to failure to incorporate iron into haem, can be hereditary (congenital sideroblastic anaemias) or acquired e.g. lead poisoning.

Question 15

What are the causes of globin deficiency in microcytic anaemia?

Answer 15

Thalassaemia (trait, intermedia, major)

Question 16

What are the causes of iron deficiency?

Answer 16

Insufficient intake to meet physiological need
- More likely in women and children due to greater requirements.
- Dietary factors

Losing too much - bleeding
- Causes of chronic blood loss: menorrhagia, GI (tumours, ulcers, NSAID’s, parasitic infection), haematuria.

Not absorbing enough - malabsorption e.g. coeliac disease (less common).

Question 17

Summary of iron metabolic pathway?

Answer 17

‘Closed’ system - only able to absorb a small amount of iron

Tiny amount in circulation moving to/from storage site to being utilized – principally by marrow

Turnover in plasma pool is fast (4mg in pool and move 20mg/day)
‏
Circulating iron is bound to transferrin.

It is transferred to the bone marrow macrophages that regulate iron uptake by transferrin receptor expression

They ‘feed’ iron to red cell precursors

Iron is stored in ferritin mainly in the liver

Question 18

What is circulating iron bound to?

Answer 18

Transferrin

Question 19

What available tests are used to assess iron status?

Answer 19

Functional iron
- Haemoglobin

Transported iron
- Serum iron
- Transferrin
- Transferrin saturation

Storage iron
- Serum ferritin

Question 20

What is transferrin?

Answer 20

A protein with two binding sites for iron

Transports iron from donor tissues (macrophages, intestinal cells and hepatocytes) to tissues expressing transferrin receptors (especially erythroid marrow)

Question 21

What can be used to measure iron supply?

Answer 21

% saturation of transferrin with iron is a measure of iron supply
- reduced in iron deficiency
- reduced in anaemia of chronic disease
- increased in genetic haemachromatosis

Question 22

What is ferritin?

Answer 22

Large intracellular protein

Spherical protein stores up to 4000 ferric ions

Tiny amount of ferritin is present in serum
- reflects intracellular ferritin synthesis in response to iron status of the host

Question 23

Can serum ferritin be easily measured?

Answer 23

Serum ferritin is easily measured but an indirect measure of storage iron.

Question 24

What does a low ferritin indicate?

Answer 24

Iron deficiency

Question 25

How can iron deficiency be confirmed?

Answer 25

Iron deficiency can be confirmed by a combination of anaemia (decreased functional iron) and reduced storage iron (low serum ferritin)

Question 26

Iron deficiency anaemia is a diagnosis. True/false?

Answer 26

False

It is a symptom and is important to figure out underlying diagnosis.

Is it:

Diet
Malabsorption
Blood loss
If blood loss where/what from – could be occult malignancy

Question 27

What are some ways to improve iron intake with iron deficiency anaemia?

Answer 27

Improve iron intake
- Review diet - haem and non haem iron
- Improve gastric acidity
- Vitamin C supplementation may benefit - facilitates absorption of iron

Question 28

What forms can iron preparations be available in?

Answer 28

Oral and IV forms

Question 29

What are the side effects of oral iron preparations?

Answer 29

Principally GI e.g. constipation, nausea + vomiting, abdominal pain, dark stools - can result in low compliance.

Question 30

What are the side effects of IV iron preparations?

Answer 30

Only considered when oral is unsuccessful due to poor tolerance, poor compliance, malabsorption issues.

Used in specific situations such as renal anaemia

Question 31

Why is it important to assess response for 4-6 weeks after period of iron treatment?

Answer 31

In order to identify for a potential cause if there is a poor treatment response

Question 32

How long is iron treatment required in order to replenish stores?

Answer 32

2-3 months

Question 33

Iron replacement therapy can treat the underlying problem. True/false?

Answer 33

False

Iron replacement therapy may relieve the symptom without treating the underlying problem - investigations essential to identify diagnosis e.g. early surgery for GI tumours may be curative.