H A E M ATO LO G Y (/MEDICINE/HAEMATOLOGY/NOTES)
Anaemia overview
NOTES
Definition
The World Health Organisation (WHO) defines anaemia by the following haemoglobin
(Hb) concentrations:
Males < 130 g/L (130-175 g/L)
Females < 120 g/L (120-155 g/L)*
* In pregnancy, a Hb < 110 g/L is diagnostic.
Strictly speaking, anaemia is defined as a reduction in circulating red blood cell mass. However, in
clinical practice, anaemia is defined by more measurable variables such as:
Red blood cell (RBC) count
Haemoglobin (Hb) concentration
Haematocrit
Hb concentration is commonly used in the assessment of anaemia.It is important to understand
that anaemia is a manifestation of an underlying problem, not a diagnosis in itself. Its recognition
warrants further investigation to establish the underlying cause.
Classification
Causes of anaemia can be classified based upon aetiology or morphology.
Aetiological
The aetiological approach addresses the underlying mechanism leading to the reduction in Hb
concentration.
Aetiologically, causes can be arranged into three groups:
Decreased RBC production
Increased RBC destruction
Blood loss
Morphological
The morphological approach categorises anaemia based on the size of RBCs (e.g. the mean
corpuscular volume).
This approach arranges anaemia into three groups:
Microcytic (small RBCs)
Normocytic (normal sized RBCs)
Macrocytic (large RBCs)
Clinical features
Clinical features are dependent on the absolute degree of anaemia & rate of decline in
Hb concentration.
Patients with a sudden drop in Hb will generally be more symptomatic than patients with a
gradual decline in Hb concentration.
The clinical features associated with anaemia reflect a reduction in oxygen delivery. In cases of
acute blood loss, the signs and symptoms of hypovolaemic shock may be present.
Symptoms
Dyspnoea
Fatigue
Headache
Dizziness
Syncope
Confusion
Palpitations
Angina
Signs
Bounding pulse
Postural hypotension
Tachycardia
Conjunctival pallor
Shock
Aetiological classification
Classifies the causes of anaemia based upon the underlying mechanisms.
Impaired synthesis
Anaemia will develop if the rate of RBC production does not adequately meet the bodies
requirements.
A decrease in RBC production can occur due to two main mechanisms:
Insufficient production of RBCs
Ineffective production of RBCs
Insufficient production of RBCs occurs when the normal erythropoietic process is reduced or
inhibited. This may be due to a lack of required nutrients (e.g. iron), reduced hormonal influence
(e.g. low EPO, hypothyroid), bone marrow suppression or bone marrow infiltration.
Ineffective production of RBCs occurs due to abnormal erythropoiesis. There is a marked
increase in the erythroid cell line in the bone marrow, but erythroid precursors do not mature
properly and subsequently undergo apoptosis. Conditions that lead to ineffective erythropoiesis
include megaloblastic anaemias (e.g. folate and B12 deficiency), thalassaemias, myelodysplastic
syndromes and sideroblastic anaemia.
Increased destruction
Haemolysis refers to the destruction of red blood cells, which is broadly defined as a reduction in
the lifespan of RBCs below 100 days (normal 110-120 days).
If RBC production in the bone marrow cannot keep pace with the level of haemolysis, then
haemolytic anaemia with ensue. The haemolytic anaemias can be divided into inherited and
acquired.
Inherited haemolytic anaemias can be further classified based on the site of inherited defect:
Membrane abnormalities (e.g. hereditary spherocytosis)
Metabolic deficiencies (e.g. G6PD deficiency
(https://app.pulsenotes.com/medicine/haematology/notes/g6pd-deficiency))
Haemoglobin abnormalities (e.g. alpha-thalassaemia
(https://app.pulsenotes.com/medicine/haematology/notes/alpha-thalassaemia), beta-
thalassaemia (https://app.pulsenotes.com/medicine/haematology/notes/beta-
thalassaemia), sickle cell disease
(https://app.pulsenotes.com/medicine/haematology/notes/sickle-cell-disease))
Acquired haemolytic anaemias can be divided into immune and non-immune:
Immune (e.g. warm and cold autoimmune haemolytic anaemia)
Non-immune (e.g. mechanical trauma, hypersplenism, infections, drugs)
Blood loss
Blood loss is a common cause of anaemia, it may be obvious (e.g. trauma, haematemesis) or
occult (e.g. gastrointestinal malignancy).
Erythrocytes form a major store of iron within the body. This means a loss of erythrocytes could
lead to the development iron deficiency anaemia (IDA). Consequently, IDA commonly reflects
blood loss from an unidentified source that requires further investigation.
Two common sources of blood loss include menstruation in young females and gastrointestinal
bleeding in older populations.
Morphological classification
Classifies the causes of anaemia based upon the mean corpuscular volume (MCV).
The MCV is a measure of the average volume of a RBC. The MCV is measured in femtolitres (fL)
and usually resides between 82 and 99. RBCs that are > 99 fL are referred to as macrocytes,
RBCs that are < 82 fL are referred to as microcytes. A normal RBC is approximately 7 microns in
diameter.
Microcytic
Anaemia is described as microcytic when the MCV is < 82 fL.
Microcytic anaemia is commonly associated with a reduction in the mean corpuscular
haemoglobin concentration (MCHC), which leads to the appearance of pale (hypochromic) RBCs.
The most common cause of microcytic anaemia is iron-deficiency anaemia (IDA). This may be
evaluated with iron studies (transferrin and serum iron) and serum ferritin.
Other important causes of microcytic anaemia include:
Anaemia of chronic disease (predominantly causes normocytic anaemia)
Thalassaemia
Other haemoglobinopathies
Lead poisoning
Sideroblastic anaemia
Normocytic
Anaemia is described as normocytic when the MCV is within normal limits (82-99 fL).
The causes of normocytic anaemia are extremely broad and it may reflect the early stages of
either a microcytic or macrocytic anaemia.
Anaemia may be the first manifestation of a systemic disorder. One of the most common causes
of a normocytic anaemia is ‘anaemia of chronic disease’.
Other common causes of a normocytic anaemia include blood loss, renal disease, cancer-
associated anaemia and pregnancy.
Macrocytic
Anaemia is described as macrocytic when the MCV is > 99 fL.
There are numerous causes of a macrocytic anaemia, but it is commonly secondary to folate
and/or B12 deficiency. Folate and B12 deficiency cause a megaloblastic (immature) macrocytic
anaemia and abnormal nucleic acid metabolism.
Drugs that interfere with nucleic acid metabolism may also cause a macrocytic anaemia (e.g.
methotrexate).
Other important causes of a macrocytic anaemia include:
Alcohol abuse
Liver disease
Hypothyroidism
Haematological malignancies
Reticulocytosis
Last updated: October 2021
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