For the past year, the world has been living under the shadow of disease. For most of us in the Western world, it has been a novel experience to have our boundaries shaped and misshapen by COVID-19, but for huge numbers of people in developing countries, disease and malnutrition are constant companions.
In 2015, the Global Burden of Disease Study determined that iron-deficient anaemia is the most common of these companions, affecting 2.36 billion people around the world [1]. To put that huge number into context, in 2015 almost one-third of the world’s population [2] was affected by anaemia associated with inadequate nutrition.
Anaemia and COVID-19
In a recent article published by the BMJ, Mark et al. described malnutrition as a silent pandemic, labelling the global prevalence of malnutrition as morally inexcusable. It is predicted that the COVID-19 pandemic will affect supply chains and increase food prices, resulting in even more of the world’s population becoming malnourished [3].
Similarly to patients with many other conditions, patients with anaemia are more vulnerable to COVID-19. A retrospective study in China found that patients with anaemia are more likely than the general population to have severe COVID‐19 and to suffer a severe inflammatory response. As such, the authors highlighted the need to recognise anaemia as a significant risk factor for COVID‐19 [4].
What is anaemia?
Anaemia is a condition of the blood in which there are too few red blood cells or the red blood cells have reduced capacity to carry oxygen. The most common symptoms of anaemia – fatigue, weakness, shortness of breath, dizziness and drowsiness – reflect the body’s diminished capacity to carry out work [5]. With the causes of anaemia ranging from treatable dietary deficiency to chronic autoimmune diseases and aggressive cancers of the bone marrow, patient experiences of anaemia vary greatly.
Anaemia is most commonly caused by dietary deficiency of iron, which is an essential component of haemoglobin (the protein that binds oxygen within red blood cells). Iron-deficient anaemia is particularly common in pregnant women, who have an increased need for red blood cells to meet the additional oxygen demands of the foetus [5].
Other causes of anaemia include deficiencies of other dietary nutrients, such as vitamin B12 (the resulting condition is known as pernicious anaemia) or folate, and diseases that impair the body’s ability to produce red blood cells or result in increased turnover of these cells [5].
Haemolytic anaemia
Haemolytic anaemia is caused by increased destruction of red blood cells. In sickle cell disease, which is the fastest growing genetic disorder in the UK [6], polymerisation of haemoglobin leads to sickling of red blood cells, which are more prone to destruction than normal red blood cells [7]. Other causes of haemolytic anaemia include other inherited blood disorders, autoimmune disorders and infections [8].
Hypoproliferative anaemia
Hypoproliferative anaemia (also called anaemia of central origin) is characterised by insufficient production of red blood cells that is not related to diet. Causes of hypoproliferative anaemia can be related to dysfunction of bone marrow, which is the site of red blood cell production [9]. This form of anaemia is also common in patients with chronic kidney disease; the causes are multifactorial but the condition primarily results from inadequate production of erythropoietin by the kidneys [10].
Treatments
Treatment of dietary anaemia is straightforward and the prevalence of the disease reflects the state of poverty that many people around the world live in. The NHS recommends that people with iron-deficient anaemia take iron supplements and eat iron-rich foods, including dark green leafy vegetables, cereals, bread, meat and pulses [11].
Patients with non-dietary anaemias may also be encouraged to take supplements or boost their dietary intake of nutrients relevant to red blood cell production, but this approach is likely to ameliorate rather than cure their anaemia. Unfortunately, many other causes of anaemia are very difficult to treat.
Sickle cell disease, for example, is extremely challenging to treat and the therapeutic armoury is limited. Stem cell therapy and bone marrow transplants offer potential cures but are rarely considered because they carry significant risks (particularly graft-versus-host disease) [12]. In 2019, the first drug to directly target the cause of the sickling (polymerisation of deoxygenated sickle haemoglobin) was approved by the Food and Drug Administration [12]. Prior to this, hydroxyurea (a myelosuppressive agent) was the only drug available to treat the disease [13].
The causes of anaemia in chronic kidney disease are also difficult to treat, and this remains an area in need of innovation. Hypoxia-inducible factor prolyl hydroxylase inhibitors are a novel therapy in development for the treatment of this type of anaemia; they work by stimulating endogenous erythropoietin [14].
Another therapeutic intervention (and potentially the only option for some patients with anaemia) is a blood transfusion. However, this is not a risk-free procedure, and the decision-making process around when patients should receive a transfusion is complex and evolving [15].
Further information
Anybody in the UK seeking further information about anaemia can visit the Anaemia Community at https://anaemia.org.uk, which aims to increase awareness of anaemia among patients and healthcare professionals. In addition, visit https://www.blood.co.uk to learn how to become a blood donor.
References
1. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388 (10053): 1545–1602.
2. Nations U. The World Population Prospects: 2015 Revision. Available at: https://www.un.org/en/development/desa/publications/world-population-prospects-2015-revision.html. Accessed January 2021.
3. Mark HE, Dias da Costa G, Pagliari C et al. Malnutrition: The silent pandemic. BMJ 2020; 371: m4593.
4. Tao Z, Xu J, Chen W et al. Anemia is associated with severe illness in COVID-19: A retrospective cohort study. J Med Virol 2020; Epub ahead of print (DOI: 10.1002/jmv.26444).
5. World Health Organization. Anaemia. Available at: https://www.who.int/health-topics/anaemia#tab=tab_1. Accessed January 2021.
6. NHS Blood and Transplant. Sickle cell awareness. Available at: https://www.nhsbt.nhs.uk/how-you-can-help/get-involved/download-digital-materials/sickle-cell-awareness-day-2020. Accessed January 2021.
7. Kato GJ, Piel FB, Reid CD et al. Sickle cell disease. Nat Rev Dis Primers 2018; 4: 18010.
8. National Heart, Lung, and Blood Institute. Hemolytic anemia. Available at: https://www.nhlbi.nih.gov/health-topics/hemolytic-anemia. Accessed January 2021.
9. Ishii K and Young NS. Anemia of central origin. Semin Hematol 2015; 52 (4): 321–338.
10. Babitt JL and Lin HY. Mechanisms of anemia in CKD. J Am Soc Nephrol 2012; 23 (10): 1631–1634.
11. National Health Service. Iron deficiency anaemia. Available at: https://www.nhs.uk/conditions/iron-deficiency-anaemia/. Accessed January 2021.
12. Steinberg MH. Primary polymerization prevention. Blood 2019; 133 (17): 1797–1798.
13. Agrawal RK, Patel RK, Shah V et al. Hydroxyurea in sickle cell disease: Drug review. Indian J Hematol Blood Transfus 2014; 30 (2): 91–96.
14. Gupta N and Wish JB. Hypoxia-inducible factor prolyl hydroxylase inhibitors: A potential new treatment for anemia in patients with CKD. Am J Kidney Dis 2017; 69 (6): 815–826.
15. British Heart Foundation. Focus on: Blood transfusions. Available at: https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/blood-transfusions. Accessed January 2021.
Author: Luke Smith, Associate Medical Writer, Porterhouse Medical Group
Group