A brief overview of anaemia and associated conditions.

1. Anaemia
HDT 2:1 – Semester 2

2. Composition of Blood
• 55% of the blood is comprised of plasma, of which 91% is water. The other 45% of the blood
consists of the buffy coat and the red blood cells.
• The plasma contains hormones, electrolytes, nutrients and water, whereas the buffy coat is made
up of white blood cells and platelets.
• Red blood cells deliver oxygen to tissues, white blood cells play a role in the immune system and
platelets have a role in coagulation and haemostasis.

3. Anaemia
• Anaemia is considered as a reduction in haemoglobin concentration, haematocrit or red cell count.
• WHO specify that for men, a haemoglobin concentration of less than 130g/L is anaemia, whilst for
women anaemia is defined as a haemoglobin concentration of less than 120g/L.
• Despite this, diagnoses of anaemia should not be looked at In isolation and should instead be
considered in terms of the patient. Pregnant women will have an apparent fall in haemoglobin
concentration, but this is due to an increase in plasma volume and not a lack of production. Also,
hypovolaemia can result in a normal reading for haemoglobin concentration, but this concentration
is relative to the lower blood volume and so the patient can still be anaemic.
• Taking blood films can be useful in assessing the size and shape of red cells, which can be used
to distinguish different types of anaemia. Changes in white cell size or shape can indicate
leukaemia or other disorders. Bone core biopsies can be taken in addition to blood tests and bone
aspirate smears to assess haematopoesis as a cause of anaemia.

4. Signs, Symptoms and Causes
• The symptoms of anaemia will depend on the degree of the condition and the rate of
development, but generally decreased oxygen reaching the tissues and hypovolaemia cause a
common subset of symptoms.
• These are exertion fatigue, palpitations, headaches, dizziness, angina and intermittent
claudication (pain in legs after exercise).
• Some of these symptoms are partly because of the compensatory mechanisms by which the body
tries to readjust. There are two mechanisms by which this occurs; biochemical compensation and
cardiovascular compensation.
• Cardiovascular compensation involved increased stroke volume and heart rate, in an attempt to
deliver more oxygen to the tissues. This can lead to palpitations.
• Biochemical compensation occurs via release of 2, 3-DPG (diphosphylglycerate) which increases
the extraction of oxygen by tissues. This occurs via binding to the beta chain of Hb to reduce
oxygen affinity and favour deposition in tissues.
• Anaemia will be caused broadly by one or more of three processes; reduced RBC production,
increased RBC destruction or blood loss.

5. Classifying Anaemia
• Red blood cells have the function of carrying oxygen from the lungs to respiring tissues, and
carbon dioxide from tissues to lungs. This is achieved by haemoglobin, which contains a haem
group (Fe²⁺ in a porphyrin ring) that becomes oxidized and reduced when bound and unbound to
oxygen. Haemoglobin is formed of two alpha subunits and two beta subunits.
• The production of RBCs can decline under any of the following circumstances; lack of haematinics
(nutrients like folic acid, iron and vitamin B12); bone marrow disorders like myelodysplasia; bone
marrow suppression as seen in irradiation and chemotherapy; reduced EPO production due to
renal failure; and anaemia of chronic diseases like infection, malignancy and inflammation.
• Anaemia can be classified by first looking at the haemoglobin concentration, to see if it’s below
normal, and then looking at the MCV (mean corpuscular volume; average volume held in a RBC)
to determine the cause.
• If the MCV is high, then the anaemia is macrocytic. Causes: B12/folate deficiency, alcohol excess.
• If the MCV is normal, then the anaemia is normocytic. Causes: anaemia of chronic disease.
• If the MCV is low, then the anaemia is microcytic. Causes: iron deficiency most common.
• The normal MCV range is 88 – 98fl (fl = femolitre).
• Haematinic deficiencies are when nutrients run out, haemolytic anaemia involves early destruction
and haemoglobinopathies include sickle cell anaemias.

6. Iron Deficiency
• Iron losses from humans aren’t large, because senescent RBCs have their iron recycled. This
leads to a loss of iron from a normal adult male of about 1mg per day, 2mg for women due to
averaging out the menstrual cycle losses.
• The body contains about 3000 – 4000mg of iron and the daily requirement for erythropoiesis is
about 20mg. The western diet contains about 15mg a day, so we usually consume enough.
However, iron deficiency is still the commonest cause of anaemia, estimated at 2 – 10% in the
UK. It also affects 1 in 4 of the global population.
• People at risk of developing iron deficiency are infants (premature, iron deficient mothers), young
women, men and women suffering GI blood losses, and children and adults with coeliac disease.
Coeliac disease impairs the ability to absorb iron.
• Iron is consumed in the diet principally via red meat, green veg, bread and eggs.
• Iron exists as haem iron (i.e. in red meat), ferrous complexes and ferric iron, which is unavailable
for absorption. The issue is that most dietary iron exists in the ferric form.
• Tannic acid in tea prevents iron absorption. Cereals impede absorption. Vitamin C enhances
absorption. Alcohol enhances absorption. Intolerance to oral iron means that simple dietary advice
can be of benefit in treating iron deficiency.
• Iron deficiency in the absence of anaemia is associated with fatigue and oral iron can be used to
improve functional capacity and quality of life. About 25% of menstruating women will have iron
deficiency so this can be important.
• Ferrous sulphate is not better than fumarate, 200mg is recommended but is excessive, side
effects are common and vitamin C/alcohol with a meal can increase absorption naturally.

7. Iron Deficiency
• The commonest cause of blood loss, leading to iron deficiency is menstruation, followed by
NSAID/aspirin use, colonic carcinoma, blood donation, gastric carcinoma and benign gastric
ulceration.
• Iron deficiency is not always associated with anaemia, but will eventually lead to it.
• Haematinic deficiencies can lead to microcytic anaemias, seen clinically by a low haemoglobin
concentration and low MCV (indicating smaller RBCs). The blood film may also show pencil cells
(elongation of cells).
• Most hospitals use serum ferritin as a measure of iron deficiency, however it can be misleading
because a patient ill with inflammation or malignancy will have raised serum ferritin (which brings
it up into the normal range for anaemic patients). This must therefore be considered.
• Assessing the patient history can be useful; is the patient on NSAIDs; GI loss (haemorrhoids);
Afro-Caribbean (thallassaemia trait); chronic diseases like rheumatoid arthritis?
• Angular stomatitis/cheilosis can indicate iron deficiency (cracked lips, fissures at corners of
mouth), as can koilonychias (thin, depressed/flat nails), underweight individuals can have
absorption problems and coeliac disease can all be quick identifiers.
• Just as pencil cells can indicate haematinic deficiencies, target cells (red, white, red appearance)
indicate that iron deficiency is not the cause of anaemia. This is more commonly caused by a
inherited condition called thalassaemia trait.

8. Anaemia of Chronic Disease
• Chronic diseases cause mild microcytic or normocytic anaemia. Inflammatory cytokines reduce
iron utilization and impair RBC production. The severity of the anaemia depends on the disease
progression and only improves if the underlying condition is addressed. .
• Haemolytic anaemias result from rapid destruction of RBCs that the bone marrow cannot
compensate for. Examples of conditions that cause this include thalassaemia and sickle cell
anaemia.
• Thalassaemia is a condition in which the production of alpha and beta subunits becomes
abnormal. Normal haemoglobin consists of α2-β2 units (97%), but thalassaemia is common in the
West Midlands due to the high population of Asians and Afro-Caribbeans, who originate from
areas of high incidence.
• The common form in the West Midlands is thalassaemia trait (minor), which does not result in
clinical symptoms but does produce blood results similar to patients with iron deficiency.
• Consequences of thalassaemia are ineffective erythropoiesis, haemolysis and iron overload.
Thalassaemia major leads to severe anaemia, hepatosplenomegaly and bone expansion. Survival
to adulthood depends on chelation of iron and bone marrow transplantation.
• β thalassaemia is caused by a deficiency in β chains, which causes the body compensate by
incorporating more δ chains, leading to elevated levels of the HbA2 variant of Hb.

9. Anaemia of Chronic Disease
• Sickle cell anaemia is a chronic disease characterised by HbS, a mutated Hb chain arising from a
point mutation leading to substitution of one amino acid. It is hereditary and patients with the
heterozygous inheritance pattern do not necessarily have symptoms (carriers) whilst homozygous
patients have the disease, resulting in sickle cells forming under conditions of low oxygen. This
results in intensely painful crises, infarcts in the blood vessels and chronic haemolysis.
• Autoimmune haemolysis (AIHA) is a condition of unknown cause or origin that causes the body to
recognise one’s own blood as foreign and produce antibodies against them. It can be detected by
low Hb concentration and raised reticulocyte (RBC precursor) concentration, which has a normal
range of 25 – 75. The Coomb’s test tests the presence of anti-RBC antibodies, where a positive
result indicates AIHA.
• Treatment of AIHA is via folic acid supplements and prednisolone, to dampen the immune
response. Second line treatments include mycophenolate, ciclosporin and Rituximab (anti-CD20).
Splenectomy can be used in difficult cases, as this is where opsonised RBCs are filtered out.

10. Macrocytic Anaemia
• Causes of macrocytic anaemia include; B12/folic acid deficiency, myelodysplasia, liver disease,
haemolytic anaemia and to an extent hypothyroidism (macrocytosis more than anaemia).
• Vitamin B12 deficiency can be the result of diet, in the case of strict vegans, or Addisonian
pernicious anaemia (can’t absorb B12 from diet), or GI/terminal ileal problems like Crohn’s or TB.
• The daily requirement for B12 is far smaller than the requirement for folic acid and so it takes a
longer time to develop a deficiency of B12 as the body is able to use stores for quite a while.
• Deficiency of B12 or folic acid can be seen clinically as low Hb concentration, large MCV and on
blood films as hypersegmented neutrophils.
• Folate deficiency can be bought on quickly through anorexia. Deficiency of this nutrient is
dangerous for pregnant mothers, as it can lead to the foetus developing neural tube defects
(NTD).
• When investigating macrocytic anaemia, the first thing to do is check folic acid and B12 levels.
Deficiencies of these vitamins can be rectified easily, though thyroid function is also often checked
(though is a rare cause). Response to B12 therapy is massively positive.
• Blood films may show signs of myelodysplasias.
• Addisonian pernicious anaemia can be detected by premature graying of hair, vitiligo of the skin
and thyroid problems (seen as bulging eyes, goitre and so on).