Sickle Cell Disease; more than sickled red blood cells

June 2021 General Jolien Blokken

June 19th is officially designated as World Sickle Cell Disease Awareness Day. The goal of this awareness day is to increase public knowledge and understanding of sickle cell disease (SCD), and the challenges experienced by patients and their families. For long SCD has been considered to be an African disease. However, the burden of SCD is also increasing in the Western World. Dr. Ann Van de Velde (Head of the haematology clinic at the University Hospital of Antwerp) explains: “Although the prevalence of SCD is still greatest in the regions affected by endemic malaria, SCD also affects one in 10,000 people in Europe. However, these numbers might be highly underestimated due to the lack of national registries and relatively poor access to care and diagnostic services. It is notable that SCD particularly affects vulnerable groups in Western society, who tend to have difficulties in assessing health care. In Belgium, the number of SCD patients is estimated at 1,000, although also this number is likely an underestimation. In the past, patients with SCD in Belgium were mainly from African origin, with the majority of patients coming from the Democratic Republic of the Congo (DRC). In recent years, however, new migration streams have changed this picture with more and more patients coming from other parts of the world, including the Caribbean, Brazil, and Central and South-East Asia.” To date, there is a huge effort to collect data from all these patients in a national registry, coordinated by the BHS Red Blood Cell Disorder Committee.

Pathophysiology and clinical presentation of SCD

Sickle cell disease is caused by a genetic mutation in the beta-globin chain of the oxygen-carrying protein haemoglobin, found in red blood cells (RBCs). When deoxygenated, this abnormal haemoglobin (HbS) can undergo polymerization, resulting in the sickling of RBCs.1,2 This sickling causes the premature breakdown of RBCs and results in haemolytic anaemia. However, SCD is more than just the sickling of RBCs. The rigidity of these RBCs causes endothelial tearing and, along with the by-products of haemolysis, promotes chronic vascular damage and inflammation. This leads to the overexpression of adhesion mediators, including selectins, which can cause sticky clusters of blood cells to form in a process called multicellular adhesion. A reduction in the blood flow caused by these sticky clusters promotes hypoxic conditions, which further induces HbS polymerization with consequent occlusion of the vessel.This ongoing, silent vaso-occlusion continually causes inflammation leading to vascular and organ damage ultimately resulting in vaso-occlusive crises (VOCs), ischaemia and organ damage.3-5

VOCs, also referred to as pain crises, are the hallmark of SCD and are the most important reason for hospitalisation.6 As SCD can affect almost every organ in the body (e.g. central nervous system, musculoskeletal, cardiopulmonary, lymphatic, gastro-intestinal and urogenital tract), multi-disciplinary care is of utmost importance for these patients.7 However, as these underlying complications are often not recognised in SCD, there is a need for close follow-up of SCD patients. Unfortunately, life expectancy for patients with SCD remains low and a higher number of reported VOCs may be associated with early death.8

Impact on quality of life

In addition to their physical impact, pain crises also have a severe impact on the patient’s daily life. Results of the Sickle Cell World Assessment Survey (SWAY), conducted in more than 2,100 patients in 16 countries across the world, indicated that 90% of patients had at least one pain crisis in the past year.9 Moreover, 39% reported to have five or more pain crises. However, only about one in three crises were treated with a hospital stay. Furthermore, nearly one in four crisis were managed at home. According to this study, the main reasons for not seeking medical help were poor hospital experience in the past (39%), the perception that doctors do not understand SCD (26%) and the fact that their crises was too painful to leave home and seek medical attention (19%).9 Dr Van de Velde adds “in my clinical practice many patients are single mothers. The fact that they have to take care of their children alone, often without a strong social network, imposes another important barrier to go to the hospital in response to a pain crisis.” Another striking SWAY finding is that 38% of patients indicate that SCD impacts their daily home activities, with the avoidance of intense activity, pain, exhaustion or dehydration during exercise and a large impact on their familial and social life. SCD also has a powerful effect on emotional life, with 59% of patients who feel frustrated with their symptoms.10 To address this, Dr Van de Velde underscored that “psychological therapies should be offered as standard of care in the management of SCD.” Finally, SCD has a high impact on work and school. SWAY data show that 53% (N= 509/968) of patients had reduced their working hours and 32% had been dismissed from their jobs because of their SCD.11

As SCD is a lifelong illness, timely recognition and an appropriate treatment plan to reduce symptoms and manage the disease conditions are of utmost importance to all SCD patients.

Do you want to learn more about SCD? Please listen to the complete podcast with dr Van de Velde!

This article is brought to you by the publisher of the Belgian Journal of Hematology (BJH) in partnership with Novartis.

References

  1. Steinberg MH. Cecil Medicine, 23rd ed. 2008;1217-1226.
  2. Kalpathhi R, et al. Hematology Am Soc Hematol Educ Program. 2018;2018(1):482-92.
  3. Conran N, et al. Hemoglobin. 2009;33(1):1-16.
  4. Puri L, et al. Paediatr Drugs. 2018;20(1):29-43.
  5. Zhang D, et al. Blood. 2016;127(7):801-809.
  6. Shah N, et al. PlosONE. 2019;14(70):1-12.
  7. Piel FB, et al. N Eng J Med. 2017;376(16):1561-73.
  8. Elmariah H, et al. Am J Hematol. 2014;89(5):530-5.
  9. James J, et al. Blood. 2019;134(Suppl_1):1017.
  10. Osunkwo I, et al. Blood. 2019;134(Suppl_1):2297.
  11. Osunkwo I, et al. Am J Hematol. 2021;96:404-17

BE2106025128 – 02/06/2021

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