Anaemia is a condition which affects people around the world and occurs in many forms, some common and frequently encountered, others much rarer. Two of the most commonly diagnosed of these anaemia types will be reviewed here – iron deficiency anaemia and anaemia of chronic disease. Less common forms of anaemia are shown in Table 1.
Table 1. Less commonly encountered anaemia types
| Anaemia type | Additional information |
|---|---|
| Pernicious anaemia/B12 deficiency | Covered in an earlier article (Perry, 2020) |
| Aplastic anaemia | Aplastic anaemia is caused by a decrease in the number of all types of blood cells produced by the bone marrow. Inability to make enough blood cells to replace those that die causes symptoms to develop, including those of anaemia (tiredness, lethargy etc) |
| Haemolytic anaemia | Normally, red cells live for about 4 months. In haemolytic anaemia, this is shortened, sometimes to only a few days. The bone marrow is unable to produce new red blood cells (RBCs) quickly enough to replace those that have been destroyed. The decreased number of RBCs in the blood leads to a reduced ability to carry oxygen around the body, resulting in the symptoms of anaemia |
| Sickle cell anaemia | Occurs as a result of production of an abnormal form of haemoglobin known as HbS. Usually causes no difficulties in people who carry only one mutated gene from one of their parents, but severe clinical problems can arise when two mutated genes are inherited (one from each parent). RBCs are misshapen, unstable (leading to haemolysis) and can block blood vessels, causing pain and anaemia. Screening is usually done on new born babies. Treatment is usually based on the type, frequency and severity of symptoms |
| Thalassaemia | Thalassaemia is a hereditary abnormality of haemoglobin production and causes small RBCs that resemble those seen in iron deficiency. In its most severe form the red cells have a shortened life span. In milder forms (such as thalassaemia trait), anaemia is usually mild or absent, and the disease may be detected by finding small blood cells on a routine full blood count (FBC). Found most frequently in people of Mediterranean, African, and Asian heritage |
| Hereditary spherocytosis | Caused by a weakness in the red cell wall which causes abnormally shaped small dark rounded RBCs which may be seen on a blood film |
| Hereditary elliptocytosis | A rare red cell wall defect causing abnormally cigar-shaped RBCs seen on a blood film |
The Association for Clinical Biochemistry and Laboratory Medicine, 2016
Prevalence
Iron deficiency anaemia (IDA) is the most common cause of anaemia and is a problem worldwide, with an estimated 500 million people affected, occurring both in low-income countries such as sub-Saharan Africa and also in more affluent parts of the world (National Institute for Health and Care Excellence (NICE), 2021). Anaemia of chronic disease (ACD), also called anaemia of inflammation, is the second most common anaemia type.
Both can potentially affect any age, but the latter type is more common among older adults and is a frequent finding among those in this age group admitted to hospital (Madu and Ughasoro, 2017).
Risk factors and causes of IDA
Causes of IDA are due to (Royal College of Nursing, 2016; Tidy, 2020):
Inadequate dietary intake:
- Diets low in iron rich foods (limited meat or dark green vegetables)
- Vegetarian diet
- Older people and children with a poor diet.
Excess requirement for iron:
- Pregnancy
- Rapid growth spells in children.
Inadequate iron absorption:
- Certain drugs (eg ranitidine, cimetidine) can bind to iron and prevent absorption
- Antacids and proton-pump inhibitors (PPIs) (eg omeprazole) may impair absorption as they raise the gastric pH
- Other drugs (tetracyclines and quinolones) can bind to iron, interfering with its absorption
- Deficiency can also occur after a partial or total gastrectomy
- Colonisation by Helicobacter pylori is thought to reduce iron uptake and increase iron loss
- Conditions such as coeliac disease can also impair iron uptake and are usually associated with folic acid deficiency.
Excess blood loss:
There are many causes of excess blood loss and it is thought that bleeding from the gastrointestinal tract is the most common cause among adult men and post-menopausal women (British Society for Gastroenterology, 2011). Among younger women menorrhagia is the most common cause (Tidy, 2020).
Additional common causes of blood loss include (Camaschella, 2019):
- Gastric carcinoma
- Gastric and duodenal ulcers
- Non-steroidal anti-inflammatory drug (NSAID) use
- Anticoagulants (eg, warfarin)
- Colonic carcinoma.
Other less common causes of excess blood loss are shown in Table 2.
Table 2. Less common causes of blood loss
|
Causes of ACD
ACD is thought to arise as a result of an inflammatory, infectious or malignant disease of a long-standing nature and includes conditions such as rheumatoid arthritis, severe trauma, heart disease, diabetes mellitus, and inflammatory bowel disease (Colbert, 2020). In some patients, the anaemia may have more than one cause. Patients with chronic kidney disease (CKD) may have inflammation as well as insufficient nutrients to make enough red blood cells, causing concurrent IDA, while those with irritable bowel disease may experience blood loss and inflammation, again resulting in both anaemia types (National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, 2018). Patients with cancer can also be affected by both types of anaemia, and cancer treatments such as radiotherapy and chemotherapy can potentially worsen co-existing IDA (National Cancer Institute, 2018).
Pathophysiology of IDA
Iron metabolism involves a number of complex processes including the regulation of intestinal iron absorption, iron transport to cells, storage of iron, incorporation of iron into proteins and the recycling of iron after breakdown of red cells (Royal College of Nursing, 2016). In healthy individuals, iron equilibrium in the body is carefully regulated by cells in the small intestine, to ensure body losses of iron are compensated for by a sufficient level of iron absorption. In those with IDA, these processes are not working correctly and supply fails to meet demand.
Pathophysiology of ACD
In ACD the low serum levels of iron are now known to be mediated by the regulatory hormone hepcidin, which is produced in the liver and is important in regulating iron balance and transport. Production of hepcidin is increased in ACD and by its action of binding to ferroportin (a protein that transports iron from the inside of a cell to the outside of the cell) iron export from macrophages and hepatocytes is blocked, while at the same time, iron absorption by duodenal enterocytes is reduced, leading to a state of iron deficiency (Cullis, 2013).
Signs and symptoms
Signs and symptoms of the two conditions are largely similar. IDA may be found when blood tests are requested for another reason. Symptoms of ACD often develop more slowly and may cause few or no symptoms in some patients (NIDDK, 2018).
When symptoms do appear they usually include (Tidy, 2016; NIDDK, 2018):
- Pallor
- Breathlessness
- Tachycardia
- Shortness of breath
- Fatigue
- Headaches
- Palpitations.
Assessment
A thorough history should be taken and include symptoms and their onset, any past medical history, including a previous IDA diagnosis, and current medical problems. Clinicians should also enquire about menstrual history in females, family history of IDA or any other blood disorder and any recent blood donation. A drug history should also be included to exclude NSAIDs or aspirin use as a cause, as use of these drugs can potentially cause gastrointestinal bleeding or ulceration, and also anticoagulant use, which can potentially provoke lesions such as ulcers to bleed.
Investigations
Investigations should include a full blood count (FBC) and serum ferritin level, and in addition a B12 and folate level to exclude either a mixed anaemia or another anaemia type. An erythrocyte sedimentation rate (ESR) is also advised to help in differentiating types (see below). Normal values for the above are shown in Table 3. Check your local guidance, as some areas suggest adding additional blood tests.
Table 3. Normal blood values for full blood count (FBC), B12 and folate, ferritin and erythrocyte sedimentation rate (ESR)
| Haematology normal adult reference ranges | Male | Female | Units |
|---|---|---|---|
| Haemoglobin (HB) | 130–180 | 115–165 | g/L |
| White cell count (WBC) | 4–11 | 4–11 | 109/L |
| Platelet count (PLT) | 150–450 | 150–450 | 109/L |
| Red blood count (RBC) | 4.5–6.5 | 3.8–5.8 | 1012/L |
| Mean cell volume (MCV) | 80–100 | 80–100 | fl |
| Packed cell volume (PCV)/Haematocrit (HCT) | 0.40–0.52 | 0.37–0.47 | L/L |
| Mean cell haemoglobin (MCH) | 27–32 | 27–32 | pg |
| Mean cell haemoglobin concentration (MCHC) | 320–360 | 320–360 | g/L |
| Neutrophil count | 2.0–7.5 | 2.0–7.5 | 109/L |
| Lymphocyte count | 1.5–4.5 | 1.5–4.5 | 109/L |
| Monocyte count | 0.2–0.8 | 0.2–0.8 | 109/L |
| Eosinophil count | 0–0.4 | 0–0.4 | 109/L |
| Basophil count | 0–0.1 | 0–0.1 | 109/L |
| Erythrocyte sedimentation rate (ESR) | 1–10 | 1–12 | mm/hr |
| Serum B12 | 197–771 | 197–771 | ng/L |
| Folate | 3–9 | 3–9 | ng/L |
| Ferritin | 30–400 | 30–150 below 6030–250 above 60 | ng/L |
Royal Wolverhampton Trust, 2019; York Teaching Hospital, 2019
Diagnosis and differentiating between the two types
Because of the similarities between the two anaemia types, it can be difficult for clinicians to be confident in making the diagnosis. When reviewing blood results, the following may be useful.
Serum ferritin level
When iron is not immediately needed it is stored intracellularly as ferritin. A low serum ferritin is regarded as the best indicator of iron deficiency and therefore diagnostic of IDA (Bouri and Martin, 2018).
Iron studies
Iron studies look at several parameters and include serum iron level, transferrin, total iron binding capacity, or transferrin concentration, as well as ferritin levels. In IDA, the ferritin, serum iron and transferrin levels are low but total iron-binding capacity (TIBC) increases and alongside this, serum transferrin levels also increase as the body tries to compensate for low iron levels, but in contrast, in anaemia of chronic disease, ferritin is normal or raised and ESR is high (Tidy, 2020).
Mean cell volume (MCV) and mean cell haemoglobin (MCH)
In IDA, the MCH is reduced due to a lack of haemoglobin in the cells, which also makes cells smaller leading to the additional finding of a reduced MCV (Royal College of Nursing, 2016), but in ACD these parameters may be normal or low (Bouri and Martin, 2018).
‘Because of the similarities between the two anaemia types, it can be difficult for clinicians to be confident in making the diagnosis’
Red cell distribution width
The red cell distribution width (RDW) is a measure of the variation in the diameter of the red cells and is raised in IDA, B12 deficiency and folate deficiency, but is normal in ACD (Bouri and Martin, 2018).
A summary table of the above is shown in Table 4 with additional explanation.
Table 4. Laboratory investigations to aid diagnosis
| Laboratory marker | IDA | ACD | IDA/ACD |
|---|---|---|---|
| Hb | Low | Low | Low |
| MCV/MCH | Low | Normal/low | Low |
| Inflammatory markers | Normal | Raised | Raised |
| Ferritin | Low | Raised | Normal |
Cullis, 2013. MCV, mean cell volume; MCH, mean cell haemoglobin; IDA, Iron deficiency anaemia; ACD, anaemia of chronic disease
Treatment and management of IDA
Treatment aims to restore abnormal haemoglobin levels to within the normal range and restore iron stores to an acceptable level. NICE guidelines recommend ferrous sulfate 200 mg three times daily with follow up FBC in 2–4 weeks to assess response (NICE, 2021). Adverse effects are common with oral iron but may be minimised if tablets are taken with food. If this does not help, either a lower dose can be tried, or a switch to an alternative. In this case ferrous gluconate 300 mg is recommended as this preparation contains less elemental iron content than ferrous sulfate (NICE, 2021).
Treatment and management of ACD
Treatment of ACD usually centres around improving the management of the underlying cause and correction of the anaemia with iron therapy is rarely thought to be beneficial.
However, in patients with conditions such as advanced cancer or cardiac failure, the degree of anaemia reflects the severity of the underlying cause, so correction may improve both prognosis and quality of life (Cullis, 2013).
Prognosis
IDA, once treated, in most cases has a good outcome. However, in rare cases, where the anaemia may have been caused by an underlying condition with a poor prognosis, such as neoplasia, or the patient has a comorbid condition, such as coronary artery disease, prognosis will be less favourable (Harper, 2020). In ACD prognosis is difficult to predict and is governed by several factors. The underlying cause of the anaemia and its severity, together with the speed of its development, the patient's age and the existence of comorbid conditions will all impact on outcomes (Tidy, 2016).
Conclusion
The two types of anaemia discussed, although sharing similar presenting signs and symptoms, clearly have different causes, treatments and prognosis. It is hoped that this article will have given general practice nurses and non-medical prescribers a brief insight into the recognition and differences between these two anaemia types and give them greater confidence in assessing their patients and managing these two diseases.
KEY POINTS:
- Iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD) have similar signs and symptoms
- IDA can affect people at any age, whereas ACD is more common in older adults
- There are variable degrees of severity for both types of anaemia
- IDA, once treated, in most cases has a good outcome. In ACD prognosis is difficult to predict
CPD reflective practice:
- Can you explain the differences between iron deficiency anaemia (IDA) and anaemia of chronic disease (ACD)? Which patient groups are more likely to be affected by each type?
- Why does treatment differ for IDA and ACD?
- How does the prognosis vary for both types of anaemia?