Anaemias of chronic disease and sickle cell anaemia
In part 2 of Beverley Bostock's review of anaemia, she discusses types of anaemia that are not caused by straightforward deficiency states
The word anaemia comes from the Greek meaning 'without blood'. In clinical terms it refers to a low haemoglobin level, which leads to a reduced capacity for oxygen transportation. As discussed in a previous article (Practice Nurse 18 November 2011), the main underlying cause of anaemia is a problem with the erythrocytes (red blood cells), which carry oxygen around the body on carriers known as haemoglobin (Hb). Anaemia may result from the body's inability to make enough erythrocytes or haemoglobin or both; alternatively the body may be losing erythrocytes from the circulation at an accelerated rate due to blood loss or excessive breakdown of these cells.
Blood cells (erythrocytes, leucocytes and platelets) are produced in the bone marrow, through a process known as haemopoiesis. Erythropoiesis, as the name suggests, refers to the production of red blood cells. The kidneys produce erythropoietin, an essential component of healthy red blood cell production.1 Chronic kidney disease, then, can lead to anaemia. The liver is also an important organ in terms of producing, transporting and storing iron. Liver disease may also lead to anaemia, therefore. Many inflammatory disorders have also been linked to anaemia, such as inflammatory bowel disease, rheumatoid arthritis and systemic lupus erythrematosus.
The aim of this article is to discuss some of the types of anaemia which are not directly linked to straightforward deficiency states such as low iron levels or low vitamin B12 levels. These include anaemia of chronic disease, including chronic kidney disease (CKD) and sickle cell anaemia.
ANAEMIA OF CHRONIC DISEASE
Many long term conditions, such as chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), carry the risk of a particular type of anaemia known as anaemia of chronic disease. In this condition, which is poorly understood, the Hb is reduced but other parameters are often normal although serum iron, transferrin and total iron-binding capacity (TIBC) levels may also sometimes be reduced. The presence of healthy levels of ferritin, B12 and folate leave little scope for treatment, however, in contrast to treating the deficiency anaemias, where iron or vitamin B12 can be used to replace the missing elements.
It is thought that infection and inflammation pay a role in the development of anaemia of chronic disease along with impaired production of erythropoietin. Many patients with chronic disease will have impaired liver function and this may also be linked to anaemia of chronic disease as the liver both stores and helps to produce iron.
According to Clinical Knowledge Summaries,2 over three quarters of patients with rheumatoid arthritis have anaemia of chronic disease whereas 23% have iron deficiency anaemia, possibly related to the use of non-steroidal anti-inflammatory drugs and oral steroids. Identifying the aetiology behind the anaemia is of great importance, then; otherwise the patient may be treated inappropriately. Optimising the management of the underlying condition is usually the best approach to treating anaemia of chronic disease and it rarely improves with iron supplements. In severe cases, blood transfusions may be given.3
ANAEMIA OF CHRONIC KIDNEY DISEASE (CKD)
The kidneys have an important role in the development of healthy red blood cells. In CKD, this role may be impaired, leading to a reduction in Hb levels. The current approach with regard to anaemia in CKD is to avoid the development of anaemia in the first place, where possible. People who develop severe anaemia due to CKD have higher levels of mortality and morbidity.4 Many patients with CKD stage 3 or more will take a daily iron tablet to help with this problem, although some may need transfusions to maintain Hb levels.
The aspirational Hb level for a person with CKD should be between 10-12g/dl but clinicians should not wait until the Hb has dropped below 10g/dl to start treatment. Once the Hb drops below 11g/dl, or following the development of typical anaemia symptoms such as tiredness and breathlessness, iron status should be assessed by measuring the ferritin level.
Treatment may consist of the use of erythropoietin stimulating agents (ESAs) and/or iron supplements orally or intravenously; all decisions regarding which treatment is indicated for each patient will be based on each individual's needs and preferences. A referral should be made to a nephrologist for further assessment if deemed necessary.5 The latest NICE guidance on managing anaemia in CKD has a useful algorithm which can help to guide clinicians in the management of this problem.4 (Box 1. Anaemia management in CKD)
SICKLE CELL ANAEMIA
Sickle cell anaemia comes under the heading of haemoglobinopathies. As its name suggests, the blood cells in sickle cell anaemia are shaped like sickles and their abnormal shape leaves them unable to function normally.
The sickle haemoglobin gene (HbS) is carried by one in five West Africans and one in ten Afro-Caribbeans. Initially a full blood count may reveal a low Hb with a low mean cell volume (MCV). However, these measurements may also be within the normal range.
The full blood count may also show a raised red cell count (erythrocytosis) as the body tries to produce more red cells to compensate for the faulty sickle cells. The condition is definitively diagnosed by haemoglobin electrophoresis, which separates up the proteins within the haemoglobin molecule and thus identifies the typical abnormal shaped blood cell which is characteristic of sickle cell disease.
Carriers of the gene for sickle cell are said to have sickle cell trait; if both parents have this, their child will develop sickle cell disease. Antenatal education and screening is vital, therefore.
The cause of this haemoglobinopathy is an alteration in the globin molecule, due to a mutation in the beta globin gene.1 This genetic condition leads to distorted, sticky blood cells which cannot carry oxygen normally, and which die prematurely. This may lead to symptoms such as tiredness and breathless, similar to those seen in iron deficiency anaemia.
The changes to the blood cell shape happen in particular when the body is stressed, such as in situations of hypoxia, fever or dehydration, provoking the so-called sickle cell crisis. Reversing theses states can return the cells to their normal shape.
However, further risks associated with severe sickle cell disease can be significant. The abnormal blood cells can block vessels causing small infarctions in surrounding tissues leading to joint pain and cardiovascular complications, such as stroke. Oral anticoagulation may be needed to avoid this.
Damage to the spleen, which occurs as a result of sickle cell disease, leads to an inability to fight infection increasing the risk of pneumonia and other serious infections. Splenectomy may be advised to reduce the premature destruction of the blood cells.
Long term antibiotic treatment may be offered to reduce the risk of infections. Patients are also to have vaccinations against flu, hepatitis B, meningococcal and pneumococcal disease. The severity of sickle cell disease varies widely and some people have only mild symptoms while others have more severe disease with recurrent admissions to hospital for pain and infection. The condition cannot be cured but the use of hydroxyurea has reduced mortality rates by 40%.6 Management of sickle cell disease may involve transfusions of healthy red cells; however, there is a risk of iron overload after repeated infusions and iron removal (chelation) may be required. Bone marrow transfusions have been found to be successful but suitable donors are not always found.
CONCLUSION
In summary then, this article has explained that there are other types of anaemia apart from the deficiency anaemias. These types of anaemia, including anaemia of chronic disease and sickle cell anaemia, require a different approach in terms of treatment and ongoing management.
The management of anaemia of most chronic diseases depends largely on optimising the management of the underlying condition, whereas anaemia of chronic kidney disease requires early recognition and treatment in order to improve morbidity and mortality in these patients.
Sickle cell disease is a genetic condition with a wide spectrum of presentations. Management includes the provision of good antenatal care as well as education regarding the disease and the prevention and minimisation of the impact of sickle cell crisis.
Whichever type of anaemia the patient has, careful diagnosis and the use of evidence based care will help to ensure improved holistic wellbeing wherever possible. o
REFERENCES
1. Moore G, Knight G, Blann A (2010) Haematology Oxford University Press
2. CKS (2011) Rheumatoid arthritis management www.cks.nhs.uk/rheumatoid_arthritis/management/scenario_confirmed_ra/view_full_scenario
3.Weiss G, Goodnough LT. Anemia of chronic disease N Engl J Med 2005; 352(10):1011-23.
4.NICE. Anaemia management in people with chronic kidney disease. 2011. Available from http://guidance.nice.org.uk/CG114
5. NICE (2008) Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care. National Institute for Health and Clinical Excellence. www.nice.org.uk
6. Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA 2003;289:1645-1651.
