Anaemia

Question 1

What is anaemia defined as and what causes it?

Answer 1

Low Hb concentration
<135g/L in men and <115g/L in women

Due to ether a low red cell mass or increased plasma volume
-> reduced production or increased loss of RBCs

Question 2

What are the symptoms of anaemia?

Answer 2

Fatigue, dyspnoea, faintness, palpitations, headache, tinnitus, anorexia, angina if there is pre-existing coronary artery disease

Question 3

What are signs of anaemia?

Answer 3

Pallor (E.g. of the conjunctivae)
In severe anaemia (<80g/L) signs of hyperdynamic circulation (e.g. tachycardia, flow murmurs, cardiac enlargement, retinal haemorrhages

Question 4

What are the types of anaemia?

Answer 4

Low mean cell volume - microcytic anaemia:

Iron deficiency anaemia
Thalassaemia
Sideroblastic anaemia

Normal MCV (normocytic anaemia)

Acute blood loss
Anaemia of chronic disease
Bone marrow failure (also low WCC or low platelets)
Renal failure
Hypothyroidism
Haemolysis
Pregnancy

High MCV (macrocytic anaemia)

B12 or folate deficiency
Alcohol excess or liver disease
Reticulocytosis
Cytotoxics
Myelodysplastic syndormes
Marro infiltration
Hypothyroidism
Antifolate drugs (phenytoin)

Question 5

What are causes of microcytic anaemia?

Answer 5

Iron deficiency anaemia

Thalassaemia - genetic diseases of unbalanced Hb synthesis with underproduction of one global chain.

Sideroblastic anaemia - think sideroblastic anaemia when microcytic anaemia is not responding to iron. - Ineffective erythropoiesis leading to increased iron absorption, iron loading in marrow and haemosiderosis (endocrine, liver and heart damage due to iron deposition)
.
MCV<76

Question 6

What are causes of normocytic anaemia?

Answer 6

MCV 76-96

Acute blood loss
Anaemia of chronic disease
Bone marrow failure
Renal failure
Hypothyroidism
Haemolysis
Pregnancy

Question 7

What causes macrocytic anaemia?

Answer 7

MCV > 96

B12 or folate deficiency
Alcohol excess/liver disease
Reticulocytosis - young larger RBCs signifying active erythropoiesis - increased in haemolytic, haemorrhage
Cytotoxics
Myelodysplastic syndromes
Marrow infiltration
Hypothyroidism
Antifolate drugs (phenytoin)

Question 8

When is blood transfusion indicated?

Answer 8

Hb > 70g/L acute anaemia
In severe anaemia with heart failure, t transfusion is vital but must be given slowly with furosemide - check for signs of worsening overload - rising JVP and basal crackles

Question 9

What are causes of iron deficiency anaemia?

Answer 9

Blood loss e.g. menorrhagia or GI bleeding
Poor diet or poverty may cause IDA in babies or children
Malabsoprtion (coeliac’s disease) is a cause of refractory IDA
Hookworm (GI blood loss) in tropics

Question 10

What are signs of chronic IDA?

Answer 10

Koilonichia (spooning of nails)
Atrophic glossitis
Angular cheilosis (stomatitis - ulceration at the side of mouth)

Question 11

What tests for IDA?

Answer 11

Blood film: microcytic anaemia
Low ferritin
Check coeliac serology - if negative refer all males and females who are not mentruating for urgent gastroscopy and colonoscopy

Question 12

How is IDA treated? SE?

Answer 12

Oral iron  (ferrous sulphate)
SE: nausea, abdo discomfort, diarrhoea or constipation, black stools.

Hb should rise by 10g/L a week with a modest reticulocytosis
Continue for 3 months after Hn normalises

IV iron only indicated if oral rout is impossible or ineffective (chronic renal failure where there is inadequate mobilisation of iron stores in response to Epo therapy)

Question 13

What is anaemia of chronic disease?

Answer 13

Secondary anaemia
Arises from:
Poor use of iron in erythropoiesis
Cytokine induced shortening of RBC survival
Reduced production of and response to erythropoietin

Moild normocytic or microcytic anaemia
Check blood film, B12, folate, RSH and haemolytic

Treat underlying disease
IV iron if there is functional deficiency
Erythropoietin

Question 14

What are side effects of erythroietin

Answer 14

Flu-like symtppoms
Hypertension
Mild raise in platelets
Thromboembolism

Question 15

What is sideroblastic anaemia? When should you suspect it? Treatment?

Answer 15

When microcytic anaemia is not responding to iron, suspect sideroblastic anaemia.

Ineffective erythropoiesis leading to increased iron absorption, iron loading in marrow and haemosiderosis (endocrine, liver and heart damage due to iron deposition)

Raised ferritin

Treat cause
Pyridoxine ± repeated transfusions for severe anaemia

Question 16

What are causes of macrocytosis?

Answer 16

MCV > 96

Megaloblastic - megaloblast is a cell in which nuclear maturation is delayed compared with the cytoplasm. Occurs in B12 and folate deficiency as these are required for DNA synthesis.

Non-megaloblastic: alcohol excess, reticulocytosis e.g. in haemolytic, liver disease, hypothyroidism, pregnancy

Other haematological disease

Question 17

What tests for macrocytic anaemia?

Answer 17

B12 and folate levels
Blood films
LFT (GGT) , TFT, seum B12, serum folate
Bone marrow biopsy if the cause is not revealed by above

Question 18

Where ifs folate found, where is is absorbed? What causes its deficiency?

Answer 18

Found in green vegetables, nuts, yeast, liver
Synthesised by gut bacteria

Absorbed by duodenum/proximal jejunum

Causes of deficiency:
Poor diet - poverty, alcoholic, elderly
Increased demand - pregnancy or increased cell turnover in haemolysis, malignancy
Malabsorption - coeliac disease
Alcohol
Drugs - anti-epileptics (valproate, phenytoin), methotrexate, trimethoprim

Question 19

What does maternal folate deficiency cause?

Answer 19

Neural tube defects

Question 20

How is folate deficiency treated?

Answer 20

Assess for underlying cause
Folic acid 5mg/day PO for 4 months
With vitamin B12

In pregnancy, prophylactic doses of folate are given from conception.

Question 21

What is vitamin B12 for?

Answer 21

Water soluble vitamin - helps synthesise DNA so in deficiency, RBC production is slow.

Question 22

What are causes of B12 deficiency?

Answer 22

Dietary e.g. vegans, B12 is found in meat fish and dairy

Malabsorption: during digestion, intrinsic factor in the stomach binds B12 enabling it to be absorbed in the terminal ileum - malabsorption can therefore arise in the stomach due to lack of intrinsic factors (pernicious anaemia, post- gastrectomy) or the terminal ileum (ideal resection, Crohn’s, bacterial overgrowth)

Question 23

What are features of B12 deficiency?

Answer 23

Symptoms of anaemia
Lemon tinge to skin due to pallor and mild jaundice due to haemolysis
Glossitis
Angular stomatitis

Neuropsych: irritable, depression, psychosis, dementia

Neurological: Parasethesia, peripheral neuropathy

Subacute combined degeneration of the spinal cord - periphaer sensory neuropathy with UMN and LMN signs due to low B12.
Classi triad of:
Extensor plantar reflex UMN
Absent knee jerks LMN
Absent ankle jerks LMN

Insidious onset and signs are symmetrical

DCML loss causing sensory (joint position and vibration) and LMN signs and corticospinal tract loss causing motor and UMN signs. Spinothalamic tracts are preserved so pain and temperature remain in tact.

Question 24

What is pernicious anaemia?

Answer 24

Autoimmune condition in which atrophic gastritis leads to a lack of intrinsic factors secretion from the parietal cells of the stomach.

Dietary B12 therefore remains unbound and cannot be absorbed by the terminal ileum.

Question 25

What tests for pernicious anaemia?

Answer 25

Low Hb
Raised MCV
WCC and platelets low if severe
Reduced serum B12
Reiculocuytes may be reduced as production is impaired

Specific:
Parietal cell antibodies
Intrinsic factos antibodies specific for PA

Question 26

What is the treatment for pernicious anaemia?

Answer 26

Give B12 IM if due to malabsorption
If dietary, oral B12 after initial IM course
Improvement is indicated by a transient marked reticulocytosis (raised MCV)