2. Deciding what is normal and interpreting blood counts

Question 1

What can normal blood cell count be affected by?

Answer 1

• Age
  
  • Gender
  • Ethnic Origin
  • Physiological Status (pregnancy or not)
  • Altitude
  • Nutritional Status
  • Cigarette Smoking
  • Alcohol Intake

Question 2

How does altitude affect the normal levels of Hb?

Answer 2

Hypoxia leads to an increased erythropoietin production and stimulates erythropoiesis so if you live at high altitudes you’ll have an increased erythropoietic drive and an increased Hb concentration

Question 3

What is the difference between a normal and a reference range?

Answer 3

• A REFERENCE range is derived from a carefully defined reference population e.g. children 5-10 yrs
  
  • A NORMAL range is a much vaguer concept - it should represent people that live in the local area and come to the hospital

Question 4

How is a reference range determined?

Answer 4

• Samples are collected from healthy volunteers with defined characteristics. You may need to define the time of day that you have taken the samples as some hematological variables change through the day
  
  • They are analysed by the instruments and techniques that will be used to analyse patient samples

Question 5

How do you determine what is normal?

Answer 5

• If the data follows a normal (Gausian) distribution you can determine what is normal by taking the mean and doing 2 standard deviations on each side
  
  • 2 standard deviations on either side will include 95% of the data
  • White blood cell count does NOT show a Gausian distribution but is a logarithmic distribution so must be analysed in other ways. You can take logs of each bit of data and then caluclate means and SD of that and convert the logs back

Question 6

What is the problem with calculating a normal range? What should be used instead?

Answer 6

• Normal does NOT necessarily mean that it is healthy e.g. the UK average cholesterol is probably quite high
  
  • A health related range may be more appropriate where anything above or below a certain level should be treated as a warning sign

Question 7

How is a WBC, RBC and platelet count measured?

Answer 7

• WBC, RBC and platelet count are all done by automated machines
  
  • They count the number of electrical impulses generated when cells flow between a light source and a sensor or when cells flow through an electric field

Question 8

How is Hb measured?

Answer 8

• Hb was initially measured by a spectrometer, by converting haemoglobin to a stable form and measuring light absorption at a specific wave length. The same procedure is now carried out by an automated machine.

Question 9

How was Hct and MCV initially measured and how are they measured now?

Answer 9

• Hct was initially measured by centrifuging a blood sample
  
  • MCV was initially counted by dividing the total volume of red cells by the number of red cells (PCV/RBC)
  • It is now determined indirectly by light scattering or by interruption of an electrical field

Question 10

What is MCHC and how do cells with a low MCHC appear?

Answer 10

MCHC is the concentration of haemoglobin in the cell. Cells with a lowered MCHC appear less red
MCHC is related to the SHAPE of the red cell

Question 11

What is MCH?

Answer 11

MCH is the absolute amount of haemoglobin in an individual red cell

Question 12

What is the difference between MCH and MCHC?

Answer 12

• Cells can have normal MCH but low/high MCHC depending on the size of the RBC
  
  • MCHC is the concentration of haemoglobin in the cell
  • MCHC is related to the SHAPE of the red cell
  • A reduced MHC but normal MCHC will mean that there is less Hb but also a smaller cell so there is no concentration change. A normal cell would be microcytic but won’t have an increased central pallour. This can be seen in people with thalassemia
  • A low MCHC would indicate that there isn’t enough Hb when compared to the size of the cell. Cells with a reduced MCHC will be small?? (microcytes ) but will also have an increased central pallor (hypochromia)

Question 13

Where can a high MCHC but a normal MCH be seen?

Answer 13

In spherocytes where there is a normal Hb concentration but it is just packaged more tightly. The high MCHC can be a clue to diagnose hereditary spherocytosis

Question 14

When would there be a low Hb and a low MCHC?

Answer 14

In iron deficiency or a severely thalassemic condition you will see cells with a reduced Hb concentration so MCHC will be low

Question 15

What would you look out for in white cells in a blood sample?

Answer 15

• White cell count – is there leukocytosis or leukaemia. If so why?
  
  • Identify which cell line is abnormal. If the count is low is it because of a lack of neutrophils or lymphocytes. If its high is it because of excess neutrophils, eosinophils, lymphocytes etc
  • Look at the clinical history – if they’ve just been admitted with pneumonia then WCC will be high and neutrophil count will be high

Question 16

Apart from the various white cell counts what would you do to analyse a blood sample?

Answer 16

• Is there anaemia? Look at Hb and compare it to the normal range. Is MCV up or down? There may be clues of this in the patients history (if they have a poor diet or blood loss)
  
  • Look at the platelet count - high/low? Are there any clues in the blood count that tells you why this is? Clues in clinical history?

Question 17

What is polycythaemia and how is it diagnosed?

Answer 17

• Literally means ‘many cells’ - too many red blood cells in the circulation
The haemoglobin, red blood cell count and haematocrit are ALL increased compared with normal subjects of the same age and gender

Question 18

What are the two different types of polycythaemia and how do they arise?

Answer 18

• High Hb, RBC and Hct could result from a DECREASE in plasma volume - PSEUDOPOLYCYTHAEMIA or APPARENT POLYCYTHAEMIA. A decrease in plasma volume can be seen if someone is dehydrated or shocked (as plasma will leave the blood stream and go into tissues). There can also be a chronic reduction in plasma volume. In such cases the number of red cells will be normal but plasma volume will be low
  
  • When the abnormalities result from an increase in the number of circulating red blood cells is TRUE POLYCYTHAEMIA. Here the number of red cells and the concentration of Hb will be increased but the plasma volume will be normal

Question 19

What are the causes of polycythaemia?

Answer 19

• Blood doping – when athletes transfuse themselves with someone else’s blood to raise their Hb. Doctors may accidentally do this if they give too much blood during transfusion which can especially be a risk for babies or children as you can give them too much blood
• Too much erythropoietin - this can be appropriately elevated if you’re at high altitude. This can also happen if you are SOB all the time (e.g. you have COPD) and your body will try to produce more Hb.
○ Residents of the Tibetan plateau have a mutation that reduces the erythropoietin production in response to hypoxia so functionally they are anaemic. However, this is probably beneficial as if your Hb is too high you are at a risk of vascular events
• Erythropoietin can be inappropriately administered to normal subjects - another form of doping
• Tumour - a renal or other tumour can secrete inappropriate levels of EPO
○ Kidney tumours, liver tumours and even fibroids can produce EPO
• Abnormal function of the bone marrow - polycythaemia can result from:
○ Inappropriately increased erythropoiesis that is independent, or largely independent of EPO. SO Hb will be high even though EPO may be lower than normal

Question 20

What is polycythaemia Vera? What can this cause?

Answer 20

○ An intrinsic bone marrow disorder where there is inappropriately increased erythropoiesis that is independent, or largely independent of EPO. SO Hb will be high even though EPO may be lower than normal
○ It is classified as a chronic myeloproliferative neoplasm where the heamatopoietic stem cells are abnormal and they are producing too many erythroblasts/erythrocytes
○ Polycythaemia vera can lead to thick blood (known as hyperviscosity) which can cause vascular obstruction. IF this occurs in coronary vessels it can lead to a myocaridal infarction or if it occurs in cerebral vessels it can lead to a stroke

Question 21

How would you diagnose polycythaemia?

Answer 21

• Physical examination where there is an enlarged spleen (polycythaemia vera) or you might find an abdominal mass (tumour in the kidney).
  
  • Cyanosis (blueness of the lips and tongue ) which would show that the patient is hypoxic. There is also clubbing of the fingers associated with this suggesting an erythropioetin response to hypoxia. This is another form of true polycythaemia
  • You need to compare their blood values with a normal range which needs to be realted to their age
  • Hb, RBC and Hct are higher in neonates than at any other times in life. These factors are lower however in children than in adults
  • Think about whether it is likely to be genuine polycythaemia or pseudopolycythaemia. In acute situations it will be obvious that it is pseudopolycythaemia as the patient will be in shock but in chronic situations lab tests will need to be carried out that measure the amount of RBCs

Question 22

How would you treat polycythaemia?

Answer 22

• If there is no physiological need for a high Hb or if the hyperviscosity is extreme then you can remove blood to make it thinner until it reaches the normal range (venesection) . You wouldn’t do this in people that need a higher Hb (such with hypoxia)
  
  • If there is an intrinsic bone marrow disease, drugs can be used to reduce the production of red blood cells by the bone marrow. This would also help control the production of other cells that may be overproduced (often platelets)

Question 23

How does clinical context help when interpreting a full blood count with polycythaemia?

Answer 23

• A young healthy athlete – suspicion of blood doping
  
  • A breathless cyanosed patient – hypoxia
  • An abdominal mass – carcinoma of the kidney
  • Splenomegaly – polycythaemia vera