Diagnostic Approach to Anaemia

Question 1

What is anaemia?

Answer 1

Low haemoglobin which is:

Men <13.5g/dl

Women <11.5g/dl

Question 2

Symptoms of anaemia

Answer 2

Fatigue
Dyspnoea
Faint
Palpitations
Headache
Tinnitus

Normally symptoms are due to cause more than anaemia

Question 3

Outline the diagnostic approach to anaemia

Answer 3

FBC to confirm anaemia

MCV to categorise anaemia

Microcytic: iron panel

Normocytic: reticulocyte count to assess bone marrow

Macrocytic:
Peripheral blood smear to decide if megaloblastic or non-megaloblastic

Question 4

Classifications of anaemia based on MCV

Answer 4

MCV <80fL: microcytic

MCV 80-100fL: normocytic

MCV >96: macrocytic

Question 5

Causes of microcytic anaemia

Answer 5

IRON LAST

Iron deficiency
Lead poisoning
Anaemia of chronic disease
Sideroblastic anaemia
Thalassaemia

Question 6

What is the most common cause of microcytic anaemia?

Answer 6

Iron deficiency

Question 7

Investigation results seen in iron deficiency anaemia

Answer 7

Low serum iron

Low ferritin

High transferrin

High TIBC

Low TIBC SATURATION

Blood films can show poikilocytosis, target and pencil cells

Question 8

Clinical features of iron deficiency anaemia

Answer 8

Fatigue
SOB
Palpitations
Pallor
Hair loss
Atrophic glossitis
Angular stomatis

Question 9

What tests might you consider doing in someone with iron deficiency anaemia?

Answer 9

Occult blood tests, haemoglobin electrophoresis, anti-TTG
endoscopy/colonoscopy

Men of any age with a Hb under 110g/L should be referred under 2WW

Patients >60 should be referred for colonoscopy

Question 10

Management of iron deficiency anaemia

Answer 10

Ferrous sulfate oral TDG 200mg.

Reticulocyte count will improve in 7 days and treatment should carry on for 5-6 months

Question 11

What is sideroblastic anaemia?

Answer 11

Iron granules form a ring around the nucleus in developing erythroblasts due to a defect in haem synthesis

Question 12

What type of anaemia does sideroblastic anaemia cause?

Answer 12

Hypochromic microcytic picture

Question 13

Investigation findings in sideroblastic anaemia

Answer 13

Low TIBC

Raised serum iron

Hypochromic RBC’s

Ringed sideroblasts

Question 14

Management of sideroblastic anaemia

Answer 14

Regular transfusions and iron chelation

Question 15

What is the effect of haemolysis on reticulocyte count?

Answer 15

Increased as more RBC’s are produced by the bone marrow to try and compensate

Question 16

Causes of normocytic anaemia

Answer 16

Anaemia of chronic disease

CKD/RA

Pregnancy (due to increased plasma volume)

Acute blood loss

Aplastic anaemia

Haemolytic anaemias

Question 17

What is aplastic anaemia?

Answer 17

Bone marrow failure causes a normocytic anaemia, leukopenia and thrombocytopenia

Question 18

Causes of aplastic anaemia

Answer 18

Phenytoin

Sulphonamides

Chloramphenicol

ALL

AML

Parvovirus

Hepatitis

Congenital is X linked recessive

Question 19

Investigation findings in aplastic anaemia

Answer 19

Low reticulocyte count (as bone marrow can’t produce new RBC’s)

Neutropenia

Question 20

Investigation for aplastic anaemia

Answer 20

Bone marrow biopsy

Question 21

What are types of haemolytic anaemia?

Answer 21

Intrinsic defects:
Haemoglobinopathies (sickle cell, HbC)
Enzyme deficiencies (pyruvate kinase deficiency, G6PD deficiency)
Membrane defects (paroxysmal nocturnal haemoglobinuria, hereditary spherocytosis)

Extrinsic defects:
Autoimmune haemolytic anaemia
Microangiopathic haemolytic anaemia
Infections
Mechanical destruction

Question 22

What are the two categories of macrocytic anaemia?

Answer 22

Megaloblastic vs non megaloblastic

Megaloblastic:
Have large and immature nuclei due to delayed nuclear maturation with defective DNA synthesis

Non-megaloblastic:
Normal DNA synthesis and no hypersegmented neutrophils

Question 23

Causes of megaloblastic macrocytic anaemia

Answer 23

Vitamin B12 deficiency

Folate deficiency

Myelodysplasia

Question 24

What is the neurological consequence of vitamin B12 deficiency?

Answer 24

Subacute combined degeneration of the spinal cord

Affects the pyramidal and dorsal columns

Symmetrical polyneuropathy

Question 25

Causes of vitamin B12 deficiency

Answer 25

Inadequate intake: Poor diet Vit B12 comes from animal sources mainly milk, eggs etc Malapsorption: Perncious anaemia Gastrectomy Congenital intrinsic factor deficiency Intestinal causes: Bacterial colonisation Ileal resection Crohn's disease

Question 26

What is pernicious anaemia?

Answer 26

Autoimmune gastritis and reduced secretion of intrinsic factor and acid Often have antibodies to intrinsic factor and parietal cells

Question 27

What investigations can you consider for someone with vitamin B12 deficiency?

Answer 27

Intrinsic factor antibody Parietal cell antibodies Serum gastrin levels Upper GI endoscopy

Question 28

Management of vitamin B12 deficiency

Answer 28

1mg IM hydroxocobalamin *if folate AND B12 deficient, treat the B12 first to prevent neuropathy

Question 29

What is the most common cause of vitamin B12 deficiency?

Answer 29

Pernicious anaemia

Question 30

How much folate acid does the body store?

Answer 30

4 months worth

Question 31

Why does pernicious anaemia lead to vitamin B12 defiency?

Answer 31

You have intrinsic factor antibodies which bind to intrinsic factor preventing vitamin B12 binding You have gastric parietal cell antibodies which mean reduced acid production and atrophic gastritis This leads to less intrinsic factor being produced and therefore less vitamin B12 absorption

Question 32

What is vitamin B12 important for?

Answer 32

Production of blood cells Myelination of nerves

Question 33

What antibody test is most specific for pernicious anaemia?

Answer 33

Anti-intrinsic factor antibodies is highly specific Anti-gastric parietal cell antibodies are sensitive but have low specificity

Question 34

Causes of folate deficiency

Answer 34

Nutritional: old age, poverty and famine Malabsorption: gluten induced enteropathy, dermatitis herpetiformis Increased use: pregnancy, lactation, haemolytic anaemia, carcinoma, lymphoma, myeloma, Crohn's, RA, malaria. Excess urinary loss: congestive heart failure and chronic dialysis Drugs: anticonvulsants and sulfasalazine Mixed: liver disease and alcoholism

Question 35

Causes of non-megaloblastic macrocytic anaemia

Answer 35

Pregnancy Alcohol excess Liver disease Hypothyroid Myeloma Reticulocytosis

Question 36

What are the associations of Plummer Vinson syndrome?

Answer 36

Iron deficient anaemia Dysphagia (post cricoid) Oesophageal webs

Question 37

Causes of macroytosis

Answer 37

Alcohol Aplastic anaemia Cytotoxic drugs Myeloma Liver disease Myxoedema Pregnancy Newborn