Anaemia

Question 1

What is the definition of anaemia?

Answer 1

Decreased haemoglobin in the blood such that there is inadequate oxygen delivery to tissues
Hb <135g/L in men
Hb <115g/L in women

Question 2

What are the symptoms of anaemia?

Answer 2

Asymptomatic: a slowly falling haemoglobin allows for haemodynamic compensation
Non specific: fatigue, weakness, headaches
Cardiovascular: dyspnoea on exertion, angina, intermittent claudication, palpitations

Question 3

What are the signs if anaemia?

Answer 3

Pallor
Tachycardia
Systolic flow murmur
Cardiac failure

Question 4

What are the specific signs for certain types of anaemia?

Answer 4

Koilonychia: spoon shaped nails in IDA
Jaundice: haemolytic anaemia
Leg ulcers: often seen in sickle cell disease
Bone marrow expansion: leading to abnormal facial structure or pathological fractures, in thalassemia (rare)

Question 5

When is transfusion indicated?

Answer 5

Generally not indicated unless there’s an acute bleed and the patient is not symptomatic
Beware of associated heart failure
Should be given slowly alongside furosemide

Question 6

What does MCV and MCH stand for?

Answer 6

MCV: size of each red blood cell
MCH: amount of haemoglobin in each red blood cell

Question 7

What causes a low MCV (<80fL, microcytic anaemia)?

Answer 7

Iron deficiency anaemia (IDA): blood loss until proven otherwise
Thalassemia
Lead poisoning
Sideroblastic anaemia (rare)

Question 8

What causes a normal MCV (normocytic anaemia)?

Answer 8

Acute blood loss
Anaemia of chronic disease 
Renal anaemia 
Haemolytic anaemias (can be macrocytic due to reticulocytes)
Marrow failure 
Pregnancy
Connective tissue diseases 
Diamorphic blood film (combined microcytic/macrocytic processes)

Question 9

What causes a high MCV (>96fL microcytic anaemia)?

Answer 9

B12 deficiency (pernicious anaemia/Crohn's)
Folate deficiency (coeliac disease)
Alcohol excess (or severe liver disease)
Myelodysplastic syndromes 
Severe hypothyroidism (myoxedema can be normocytic)

Question 10

What should you find on examination in microcytic anaemia?

Answer 10

Koilonychia
Angular stomatitis
Brittle nails/hair

Question 11

What are further tests that should be done for microcytic anaemia?

Answer 11

Iron studies: serum iron, serum ferritin, total iron binding capacity, serum soluble transferrin receptors
Blood film: microcytic anaemia, generally also hypochromic (pale on the blood film, representing low MCH)
Film may show sideroblasts/signs of thalassemia

Question 12

What is iron deficiency anaemia (IDA)?

Answer 12

Most common cause of anaemia
Iron is much more readily taken up in the gut as ferrous iron (Fe2+) which is far less abundant than th insoluble ferric (Fe3+)
IDA develops when there is an inadequate iron for haemoglobin synthesis
There is a ‘latent iron deficiency’ period, where normal Hb is maintained despite the iron deficiency

Question 13

What are the causes of IDA?

Answer 13

Blood loss: hookworm the most common cause worldwide, UK due to heavy menstruation or GI bleeds
Decreased absorption: Coeliacs, patients on antacids (less ferric to ferrous iron conversion) or post gastrectomy
Increased demand: in growth/pregnancy
Inadequate intake: premature infants/prolonged breast fed infants most at risk

Question 14

How is IDA diagnosed?

Answer 14

Blood film: microcytic, hypochromic cells with poikilocytosis (shape variation) and anisocytosis (size variation)
Serum iron: decreased
Total iron binding capacity: increased
Serum ferritin: decreased
Represent amount of stored iron
Soluble transferrin receptor: increased (most specific test)

Question 15

What are the test results of anaemia of chronic disease?

Answer 15

Serum iron will be decreased
TIBC will also be decreased and STR will be normal
Ferritin will be raised

Question 16

What is ferritin?

Answer 16

This represents increased stored iron, but it is an acute phase reactant and is raised in infection or malignancy
If ferritin is low-normal in the presence of raised inflammatory markers then this can be a false negative and may suggest IDA

Question 17

What are further investigations which should be carried out in anaemia?

Answer 17

If there is a good history of menorrhagia start oral iron, and do coeliac serology
Ask about number of sanitary items used, clots
In all other patients without an obvious cause of bleeding, check coeliac serology then refer all patients for GI investigation
OGD and colonoscopy
Stool microscopy is also advised of recent foreign travel

Question 18

What other tests should be carried out in macrocytic anaemia?

Answer 18

Blood film: Hypersegmented neutrophils in B12/folate deficiency, may reveal other clues (target cells in liver)
LFTs/TFTs: thyroid/hepatic cause, raised bilirubin in B12/folate deficiency
Serum B12/folate levels: serum folate reflects recent intake, so many labs do red cell folate

Question 19

What should you do if B12 is low?

Answer 19

Anti-parietal cell Ab, anti-IF Ab
Schilling test: distinguishes between pernicious anaemia and small bowel disease (radiolabelled B12 given with, and then without IF, amount of labelled B12 excreted in urine then detected)

Question 20

What does a bone marrow biopsy show?

Answer 20

Megaloblasts suggest B12/folate deficiency, also seen in myelodysplasia
Deoxyuridine suppression test: can be used to differentiate B12/folate deficiency in vitro after bone marrow biopsy

Question 21

How do B12 and folate deficiency lead to megaloblastic anaemia?

Answer 21

B12 acts as a co-enzyme for the conversion of folate (B9) to activated folate
Activated folate is required for DNA synthesis and thus there is a deficiency in either B12 or folate, DNA synthesis malfunctions
In this case the DNA fails to stop erythrocyte development, leading to very large cells, which are eventually trapped and destroyed in the reticule-endothelial system

Question 22

How is B12 excreted?

Answer 22

Liver contains a very large store of B12 and it’s excreted in the bile but around 70% of this is normally absorbed

Question 23

Where does B12 bind?

Answer 23

Free vitamin B12 binds to R proteins in the upper GI tract, but these complexes are degraded by pancreatic proteases
Intrinsic factor is secreted by the gastric parietal cells and binds free B12 with far less affinity than R proteins, but the IF-B12 complex is highly resistant to protease degradation
Receptors for the IF-B12 complex are present on the brush border of the terminal ileum, where B12 is absorbed

Question 24

How is B12 ingested?

Answer 24

IF is general necessary for B12 ingestion, even in its absence around 2% can still be ingested
High dose PO supplementation can be enough to treat pernicious anaemia
Even in total malabsorption, body stores will last for 3 years

Question 25

What are the causes of B12 deficiency?

Answer 25

Chronic low dietary intake: vegans
Impaired binding in the stomach: pernicious anaemia, congenital absence of IF, gastrectomy
Small bowel disease: resection, Crohn’s/backwash ileitis in UC, bacterial overgrowth
Pancreatitis, coeliac disease and metformin can all cause mild impairment of B12 absorption, but not enough to cause significant B12 deficiency

Question 26

What is pernicious anaemia?

Answer 26

Autoimmune disease resulting in severe B12 deficiency
3 autoanitbodies that may contribute to disease:
Autoantibodies against parietal cells
Blocking antibodies- prevent IF-B12 binding, most common abnormality
Binding antibodies- prevent IF binding to ileal receptors

Question 27

What isa subacute combined degeneration of the cord?

Answer 27

Simultaneous posterior column (LMN) and CST (UMN) loss due to B12 deficiency and gives a combination of UMN and LMN signs
Initial presentation is with peripheral neuropathy and on examination there is a classical triad of extensor plantars, brisk knee jerk but absent ankle jerks
Tone and power are usually normal, gait may be ataxic

Question 28

What is folate deficiency

Answer 28

Folate (folic acid mono glutamate) is not itself present in nature, but occurs as polyglutamates dihydrofolate (DHF) or tetrahydrofolate (THF)
Found in green vegetables, and offal, however cooking causes a loss of up to 90% of the folate
DHF and THF are converted to folate in the upper GI tract and folate is then absorbed in the jejunum
The body’s reserves of folate are low and on a deficient diet then folate deficiency will develop in around 3 months

Question 29

What are the causes of folate deficiency?

Answer 29

Poor nutritional intake: poor diet, alcohol excess (impairs utilisation), anorexia
Malabsoprtion: coeliac disease
Anti-folate drugs: trimethoprim, methotrexate, anti convulsants
Excess physiological use: pregnancy, lactation, prematurity
Excess pathological use: excess erythrocyte production (e.g in haemolysis), malignancy, inflammatory diseases

Question 30

What is the approach for normocytic anaemia?

Answer 30

Is there acute blood loss? (Hb is a concentration, so does not fall immediately, usually after fluid replacement)
Is there underlying chronic disease
Is it haemolytic
Are other cells affected i.e bone marrow failure

Question 31

What is the approach to anaemia of chronic disease?

Answer 31

Normochromic or hypochromic, rarely severe
Seen in chronic infection, malignancy, CKD and rheumatoid disorders
Pathology involves predominant WBC production in the bone marrow
Low serum iron, raised ferritin, low TIBC, normal STR