Microcytic Anaemia

Question 1

.. anaemia describes the presence of a reduced haemoglobin concentration and a reduction in the mean corpuscular volume (MCV).

Answer 1

Microcytic anaemia describes the presence of a reduced haemoglobin concentration and a reduction in the mean corpuscular volume (MCV).

Question 2

There are numerous causes of a microcytic anaemia:

Answer 2

Iron-deficiency anaemia (IDA)
Anaemia of chronic disease
Thalassaemias (e.g. alpha / beta)

Question 3

Iron-deficiency anaemia

Answer 3

IDA is commonly seen in women of child-bearing age and children across the world. Premenopausal females are particularly at risk because of the loss of iron during menstruation and pregnancy.

In the developed world, it is estimated that 2-5% of adult men and postmenopausal women suffer from IDA.

Question 4

Dietary deficiency of iron is uncommon in the developed world because of adequate access to dietary components such as meat. Where meat is not a core component of the diet, the prevalence of IDA is … greater.

Answer 4

Dietary deficiency of iron is uncommon in the developed world because of adequate access to dietary components such as meat. Where meat is not a core component of the diet, the prevalence of IDA is 6-8 times greater.

Question 5

The total iron content within our body is approximately 3-4 grams, which is distributed among different structures:

Answer 5

Hb: 2-3 grams
Plasma iron (e.g. bound to transferrin): 3-7 mg
Iron-containing proteins (e.g. myoglobin): 300-400 mg
Stored iron (e.g. ferritin, haemosiderin): 1 gram

Question 6

The major causes of IDA can be grouped into three categories:

Answer 6

Increased requirements (e.g. pregnancy, lactation)
Increased loss (e.g. gastrointestinal bleeding)
Decreased uptake (e.g. dietary deficiency, malabsorption)

Question 7

Classical signs of IDA include …

Answer 7

Classical signs of IDA include glossitis, koilonychia (spoon-shaped nails), angular stomatitis, and conjunctival pallor.

Question 8

Interestingly, some children with IDA may be found to have peculiar dietary cravings (..) for materials such as soil, clay, or chalk. Whether this is a cause or consequence of IDA is not fully understood.

Answer 8

Interestingly, some children with IDA may be found to have peculiar dietary cravings (pica) for materials such as soil, clay, or chalk. Whether this is a cause or consequence of IDA is not fully understood.

Question 9

Iron studies include: ..

Answer 9

Iron studies include: serum iron, ferritin, and iron-binding globulin (transferrin).

Question 10

Serum iron, ferritin, and transferrin levels are essential in the diagnosis of..

Answer 10

Serum iron, ferritin, and transferrin levels are essential in the diagnosis of IDA.

Question 11

Management of IDA should involve investigation into the underlying cause & replacement of iron.

Answer 11

Male and postmenopausal female patients with unexplained IDA should be investigated for suspected gastrointestinal malignancy (or indeed benign GI pathology). The upper gastrointestinal tract is more commonly the site of pathology than the lower gastrointestinal tract.

Oral replacement of iron in the form of ferrous fumarate or ferrous sulfate are common pharmacotherapies. Follow-up blood tests should always be completed to assess for response to treatment and patients should be warned about side-effects. These may include constipation, black stools, diarrhoea, nausea, and dyspepsia/epigastric discomfort.

Question 12

Oral replacement of iron in the form of…

Answer 12

Oral replacement of iron in the form of ferrous fumarate or ferrous sulfate are common pharmacotherapies.

Question 13

Anaemia of chronic disease

Answer 13

Anaemia of chronic disease (ACD) is a complex and multi-factorial condition due to a chronic inflammatory process from underlying infection, malignancy or systemic disease.
ACD is the second most common cause of anaemia worldwide, and commonly seen among hospitalised patients.

Question 14

Aetiology & pathophysiology

Anaemia of chronic disease

Answer 14

ACD is classically described as a normocytic, normochromic anaemia secondary to systemic diseases, infection or malignancy.

Question 15

Hepcidin

Answer 15

Hepcidin is the normal regulator of iron absorption from enterocytes and the tissue distribution of iron. It is an acute phase protein that usually works to reduce the availability of iron from infecting microorganisms.

Question 16

Chronic inflammation mediated by IL-6 can lead to a …-induced block of iron absorption and iron release from macrophages. This reduction in the availability of iron for the production of erythrocytes as part of erythropoiesis can lead to a microcytic anaemia. However, this is only seen in 25% of cases.

Answer 16

Chronic inflammation mediated by IL-6 can lead to a hepcidin-induced block of iron absorption and iron release from macrophages. This reduction in the availability of iron for the production of erythrocytes as part of erythropoiesis can lead to a microcytic anaemia. However, this is only seen in 25% of cases.

Question 17

The clinical presentation of ACD is generally that of the underlying disorder, and unless the haemoglobin concentration is severely reduced, patients may be asymptomatic.

Answer 17

If present, clinical features are typical of all anaemias including fatigue, headache and dizziness. If severely symptomatic, patients may develop palpitations, angina or dyspnoea.

Question 18

Key investigations in ACD include the FBC, CRP, haematinics, iron studies and blood film.

Answer 18

The FBC may show a normocytic normochromic anaemia (approx. 75%) or the development of a microcytic anaemia (approx. 25%). In ACD, the MCV is rarely below 70 fL.

Similar to IDA, serum iron, ferritin and transferrin are vital for the diagnosis of ACD.

Question 19

The beta-thalassaemias are a heterogenous group of conditions that result from a reduced or absent production of beta-globin chains.

Answer 19

The prevalence of the beta-thalassaemias varies widely depending on the ethnic population. Beta-thalassaemia is seen more commonly in African, Mediterranean and South-east Asian populations.

Question 20

Clinical features tend to reflect the severity of beta-thalassaemia. Patients with beta-thalassaemia major tend to have marked extramedullary haematopoiesis and complications secondary to iron overload from repeated transfusions.

Answer 20

Extramedullary haematopoiesis
Hepatomegaly
Splenomegaly
Skeletal abnormalities
Iron overload
Hypogonadism
Growth failure
Diabetes mellitus
Hypothyroidism

Question 21

The diagnosis of beta-thalassaemia is confirmed with haemoglobin …

Answer 21

The diagnosis of beta-thalassaemia is confirmed with haemoglobin electrophoresis.

Question 22

Patients with beta-thalassaemia major will require ..

Answer 22

Patients with beta-thalassaemia major will require early, frequent blood transfusions. Other management options include splenectomy and hematopoietic stem cell transplantation. Patients receiving recurrent transfusions may suffer with iron overload and require iron chelation therapy.

Question 23

Other causes of microcytic anaemia include sideroblastic anaemia, lead poisoning and other haemoglobinopathies.

Answer 23

Sideroblastic anaemia can be congenital (X-linked recessive) or acquired. It results in the inclusion of a perinuclear ring of coarse iron-containing granules (‘ring-sideroblasts’) within erythrocyte progenitors.

Acquired causes may be seen in myelodysplastic syndromes or following the use of pharmaceuticals such as isoniazid or chloramphenicol.

Lead poisoning is an uncommon cause of microcytic anaemia that can cause a reduction in the synthesis of haem and a reduced lifespan of erythrocytes.

Question 24

… poisoning is an uncommon cause of microcytic anaemia that can cause a reduction in the synthesis of haem and a reduced lifespan of erythrocytes.

Answer 24

Lead poisoning is an uncommon cause of microcytic anaemia that can cause a reduction in the synthesis of haem and a reduced lifespan of erythrocytes.

Question 25

… anaemia can be congenital (X-linked recessive) or acquired. It results in the inclusion of a perinuclear ring of coarse iron-containing granules (‘ring-sideroblasts’) within erythrocyte progenitors.

Answer 25

Sideroblastic anaemia can be congenital (X-linked recessive) or acquired. It results in the inclusion of a perinuclear ring of coarse iron-containing granules (‘ring-sideroblasts’) within erythrocyte progenitors.