24th May 2023

Overview of sickle cell disease

Sickle cell disease is one of the most common monogenic, hereditary haemoglobinopathies. It is inherited in an autosomal recessive manner, where individuals with both alleles develop sickle cell anaemia (HbSS), and those who carry one allele acquire the sickle cell trait (HbSA).

Mutation in the beta globin gene results in substitution of glutamic acid with valine at the sixth amino acid of the beta globin chain. This alters the structure and properties of haemoglobin and causes red blood cells to sickle (see image below). This results in polymerisation of the abnormal haemoglobin within the red blood cell and the formation of haemoglobin tetramers.

Sickle cells on peripheral blood film.

Image Source: Wikimedia Commons (2012). Sickle cells, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Sickle_cells.jpg (Accessed on: 10 January 2023).

Acidosis, hypoxia, infection, dehydration, cold temperatures, pregnancy, and stress can all trigger polymerisation of abnormal haemoglobin and hence, sickling of red blood cells. These sickle cells adhere to the vascular endothelium, resulting in vaso-occlusion. The abnormal structure of the sickle cell makes them prone to haemolysis, which contributes to anaemia. Patients with sickle cell disease are subjected to acute and chronic complications of this disease.

There is a high prevalence of sickle cell in countries where malaria is endemic; sickle cell has protective properties against severe malaria. These include Sub-Saharan Africa, India, Eastern Mediterranean, and the Middle East.

The only cure for sickle cell disease is bone marrow transplantation. Management of sickle cell focuses on the following:

• Infection prevention – immunisation, lifelong prophylactic penicillin
• Symptom control – analgesia, hydroxycarbamide (reduces frequency of acute pain, blood transfusion and chest syndrome), crizanlizumab (reduces vaso-occlusive crises), blood transfusions
• Management of clinical complications