Anemia

Question 1

What can anaemia be classified into?

Answer 1

Anaemia can be classified according to the average size of the red blood cells (RBC), referred to as mean corpuscular volume (MCV):

• Microcytic anaemia: MCV < 80 fL
• Normocytic anaemia: MCV 80 – 100 fL
• Macrocytic anaemia: MCV >100 fL

Question 2

Symptoms of anemia

Answer 2

Pallor
Fatigue
Breathlessness
Dizziness
Palpitations
Cold hands and feet

Question 3

Areas to cover in a patient presenting with anaemia

Answer 3

• Dietary history (to rule out malnutrition)
• Check if the anaemia is new by comparing against historic blood test
• Causes of potential blood loss (e.g. menorrhagia)
• Issues with malabsorption (e.g. gastrectomy, coeliac disease)
• Family history of haematological disorders
• Any episodes of black tarry stools (suggestive of gastrointestinal bleeding)
• Cardiac diseases (due to transfusion reactions e.g. TACO) as furosemide may be required
• Symptoms of chronic disease (e.g. cardiac, renal, hepatic)

Question 4

Possible clinical findings in anemia

Answer 4

Possible clinical findings in anaemia include:9

• Pallor (e.g. general pallor or conjunctival pallor)
• Rapid or irregular heartbeat on cardiac auscultation
• Enlarged liver or spleen on palpation (consider lymphoma or leukaemia with splenomegaly)

Question 5

What happens in microcytic anemia?

Answer 5

As there is a lack of haemoglobin (Hb), an extra division of red blood cells (RBCs) occurs to maintain adequate Hb concentration. This results in smaller and paler (hypochromic) RBCs.

Question 6

Causes of microcytic anemia

Answer 6

• Iron deficiency anemia (most common cause)
• Sideroblastic anemia
• Anemia of chornic disease/inflammation (e.g heart failure, CKD, or rheumatoid arthritis
• Thalassemia
• Malignancy

Question 7

Concerning features of anemia to consider

Answer 7

• Haemodynamic instability
• An acute drop (particularly in surgery as this could suggest internal or external bleeding)
• Symptomatic anaemia (as this suggests the drop is acute)
• Those with a high risk of bleeding (on anticoagulants or bleeding disorders)
• Suspected or confirmed ACS (often aim for Hb target of 80 rather than 70)

Question 8

Iron tests in acute inflammation

Answer 8

For iron tests, remember that in acute inflammation, ferritin will increase and transferrin will decrease. Thus they can mask iron deficiency but a low ferritin is highly valuable in identifying true iron deficiency.

Question 9

What happens in normocytic anemia?

Answer 9

• Since the size of the RBCs isn’t altered, the decreased haemoglobin must be due to another cause, either haemolysis (intravascular or extravascular) or underproduction of normal-sized RBCs
• Unlike microcytic anaemias, normocytic anaemias are usually normochromic.

Question 10

What can help differentiate between causes of normocytic anemia?

Answer 10

The reticulocyte count enables differentiation between the two causes. A high reticulocyte count would indicate that the bone marrow was functioning normally and therefore the anaemia is not likely to be due to underproduction.

Question 11

Where can hemolysis occur?

Answer 11

• Haemolysis can occur in two locations. Extravascular haemolysis occurs primarily in the spleen. It is more common than intravascular haemolysis.
• Intravascular haemolysis is the breakdown of red blood cells within the circulation, leading to the release of free haemoglobin into the blood. It is less common than extravascular haemolysis.

= In clinical practice, the distinction between intravascular and extravascular haemolysis is not clear-cut, and there may be significant overlap between the two.

Question 12

What can cause normocytic anemia?

Answer 12

• Anemia of chronic disease (starts out as normocytic anaemia but it can progress to microcytic anaemia)
• Hereditary spherocytosis
• Sickle cell anemia
• G6PD deficiency
• Paroxysmal nocturnal haemoglobinuria
• Underproduction of RBCs
• Immune haemolytic anaemia

Question 13

What can macrocytic anemia be divided into?

Answer 13

They are further divided into megaloblastic and non-megaloblastic subsets.

Question 14

Difference between megaloblastic and non megaloblastic anemia

Answer 14

• Megaloblastic causes of macrocytic anaemia result in an increased MCV due to impaired DNA synthesis.
• Non-megaloblastic causes do not affect DNA synthesis but result in an increased MCV nonetheless

Question 15

Causes of macrocytic anemia

Answer 15

This is usually due to alcohol, B12/folate deficiency or liver disease. More rarely, causes could include hypothyroidism, chemotherapy agents or myelodysplastic syndromes.
- Megaloblastic: B12 deficiency and folate deficiency
- Non-megaloblastic: alcoholism, hypothyroidism, reticulocytosis, and drugs such as fluorouracil

Question 16

Anemia testing

Answer 16

On detection of anaemia, regardless of the MCV, most people would do the minimum of a blood film and haematinics (B12, folate & iron tests – ferritin, TIBC, transferrin)

Question 17

Investigation findings in iron deficiency anemia

Answer 17

• Low MCV <80 fL. Although an MCV <95 fl is more sensitive for iron deficiency (97.6%)
• Reduced mean corpuscular haemoglobin (MCH): <27.5 picograms/red cell indicates hypochromia
• Reduced mean corpuscular hemoglobin concentration (MCHC)
• Serum iron: low
• Transferrin saturation: low
• Ferritin: low (low in iron deficiency but can be normal/high in inflammation)
• Total iron-binding capacity: high ( there is an increased capacity to bind iron due to reduced levels of iron)

Question 18

Findings in anemia of chronic disease

Answer 18

• Normal MCV (80-100 fL) or low MCV (<80 fL)
• Serum iron: low
• Transferrin saturation: low
• Ferritin: high
• TIBC: low

Question 19

Causes of iron deficiency anemia

Answer 19

Reduced iron absorption (dietary, malabsorption, drugs), increased iron utilisation (pregnancy, growth spurts), blood loss (menorrhagia, GI conditions, trauma, NSAIDs).

Question 20

Most common cause of anemia

Answer 20

IDA

Question 21

Amount of iron in blood and why blood is significant to that

Answer 21

Every 2.5 mL of whole blood or 1 mL of packed red blood cells contains 1 mg of iron.

In comparison, only 1 mg on average of iron is absorbed daily from the diet, so even modest blood loss over time can lead to iron deficiency.4

In women, menorrhagia is a major cause of blood loss.
Other potential causes include trauma, haematuria, recurrent nose bleeds, blood donation and haemolysis

Question 22

GI blood loss causes

Answer 22

Conditions causing blood loss from the gastrointestinal system can include gastro-oesophageal reflux disease (GORD), ulcers, inflammatory bowel disease (IBD), malignancy, hookworm/schistosomiasis in tropical countries, and drugs (NSAIDs).

Question 23

Clinical findings of iron deficiency anemia

Answer 23

Clinical findings of iron deficiency anaemia may include:

Conjunctival pallor
Angular cheilitis (ulcers at the corners of the mouth)
Atrophic glossitis (painful tongue with loss of papillae)
Koilonychia (spoon-shaped nails)
Dry skin and hair

Question 24

Acute phase reactants examples

Answer 24

Positive acute phase reactants
- CRP
- Fibrinogen
- Ferritin
Negative acute phase reactants
- Albumin
- Transferrin

Question 25

What are acute phase reactants?

Answer 25

• Acute phase reactants (APR) are inflammation markers that exhibit significant changes in serum concentration during inflammation.
• These are also important mediators produced in the liver during acute and chronic inflammatory states

Question 26

Relationship between ferritin and TIBC

Answer 26

there is an inverse relationship between ferritin and TIBC)

Question 27

Complications of iron deficiency anemia

Answer 27

• Cognitive and behavioural impairment in children
• Reduced exercise capacity and endurance
• High-output heart failure
• Immunodeficiency
• In the context of pregnancy, it can lead to increased morbidity for mother and infant, increased risk of preterm delivery and perinatal mortality

Question 28

What is ferritin?

Answer 28

An intracellular storage protein that collects excess intracellular iron and stores in an inactive form for future use in conditions of deficiency or high demand

Question 29

What is transferrin?

Answer 29

Protein in the blood that binds, deliver and transfer iron to all the various biological tissues between sites of absorption, utilization, and storage.