Anaemia Overview
Disclaimer: This article aims to provide an overview of how the various causes of anaemia are classified. It does not go into detailed information of the individual causes of anaemia.
Background Information
Definition
Definition of anaemia (WHO): reduction in hemoglobin level, 2 standard deviations below the normal for age and sex.
In exams, the normal range for anaemia will almost always be provided, as in practice these ranges depend on individual laboratories. To provide some context, the WHO cut-offs for anaemia are:
- <13 g/L in men (>15 y/o)
- <12 g/L in non-pregnant women (>15 y/o)
- <12 g/L in children (12-14 y/o)
Note that anaemia cut-offs are slightly different in pregnant women and may be worth memorising:
- 1st trimester: <11 g/dL
- 2nd and 3rd trimester: <10.5 g/dL
- Postpartum: <10.0 g/dL
Clinical Features
Mild anemia may otherwise be asymptomatic.
Non-specific clinical features of anaemia: [Ref]
| Symptoms |
|
| Signs |
|
The clinical features listed above are non-specific features of anaemia and may be present regardless of the underlying cause.
Cause-specific features are not detailed here, as these are discussed in separate articles. Examples of cause-specific features include jaundice in haemolytic anaemia, neurological deficits in vitamin B12 deficiency, and koilonychia in iron deficiency anaemia.
Red Flags
In adults, anaemia may be a presenting feature of colorectal cancer. NICE outlined the following as red flags for colorectal cancer that warrant further investigations:
- Adults with iron deficiency anaemia
- >60 y/o AND anaemia (any type, even in the absence of iron deficiency)
These patients should be offered a FIT test to guide subsequent referral. See the Colorectal Cancer article for more details (NB that there are other non-anaemia related red flags for colorectal cancer).
Aetiology and Classification
The morphological classification (based on MCV) is the most widely used and is the best way to classify anaemia when learning causes and working through differentials. [Ref]
| Anaemia type | MCV (fl) |
|---|---|
| Microcytic anaemia | <80 |
| Normocytic anaemia | 80-100 |
| Macrocytic anaemia | >100 |
Note that the exact MCV cut-offs may vary depending on the source, and there is no single “correct” value to memorise. Exam questions will most likely provide a normal MCV range (e.g. 76–96 fL). Values below the lower limit of normal should be considered microcytic, values above the upper limit of normal should be considered macrocytic, and values within the normal range should be considered normocytic.
Microcytic Anaemia (MCV <80)
Main causes of anaemia can be memorised with the mnemonic “TAILS”:
- Thalassaemia
- Anaemia of chronic disease
- Usually normocytic at onset and may become microcytic if iron deficiency develops or co-exists [Ref]
- Iron deficiency anaemia (by far the most common cause of microcytic anaemia)
- Early stages of iron deficiency can be normocytic but subsequent progression to microcytic is typical
- Lead poisoning (uncommon)
- Sideroblastic anaemia (uncommon)
Normocytic Anaemia (MCV 80-100)
Normocytic anaemia can be sub-classified by proliferative status [Ref]
| Proliferative status | Reticulocyte count | Causes |
|---|---|---|
| Hypoproliferative (bone marrow under-production) | ↓ |
|
| Hyperproliferative (appropriate bone marrow production, but red cells are being lost of destroyed) | ↑ |
|
*It can be further sub-classified into immune-mediated and non-immune causes, with additional classification based on the site of haemolysis (intravascular vs extravascular). This is discussed in detail in a dedicated haemolytic anaemia article.
Macrocytic Anaemia (MCV >100)
Macrocytic anaemia is classifically sub-classified into the following 2 categories: [Ref]
| Type | Pathophysiology | Common causes |
|---|---|---|
| Megaloblastic | Impaired DNA synthesis → ineffective erythropoiesis |
There are various causes of B12 and B9 deficiency, which is discussed in detail in separate articles |
| Non-megaloblastic | Macrocytosis without a primary DNA synthesis defect |
|
The classification of macrocytic anaemia into megaloblastic and non-megaloblastic types is primarily based on the underlying pathophysiology. In practice, this distinction can be made using peripheral blood films, where the presence of hypersegmented neutrophils is characteristic of megaloblastic anaemia.
However, when macrocytic anaemia is identified, it is important to exclude vitamin B12 and folate deficiency first before considering other causes.