What is Sickle Cell Disease (SCD)?

From the Guidelines

Sickle cell disease is a genetic blood disorder characterized by abnormal hemoglobin that causes red blood cells to become rigid and sickle-shaped, leading to chronic hemolytic anemia, painful vaso-occlusive crises, and acute and chronic end-organ damage. According to the most recent guideline on the peri-operative management of patients with sickle cell disease 1, the disease is diagnosed in more than 1:2000 live births in England annually, with approximately 14,000 patients with sickle cell disease in the UK. The disease is characterized by a chronic haemolytic anaemia, painful vaso-occlusive crises, and acute and chronic end-organ damage. Management of patients with sickle cell disease has improved markedly in recent decades, with care focused on prevention and management of complications from birth, and death in childhood is uncommon in the UK (1–2%) 1.

Some key points about sickle cell disease include:

• It is one of the most common serious inherited conditions globally 1
• Patients may be homozygous for the sickle gene (sickle cell anaemia, HbSS), or have a compound heterozygous state with another abnormal haemoglobin (e.g. ß-thalassaemia, haemoglobin C, D, E or O Arab) 1
• The heterozygous carrier state HbAS is a mostly benign condition that only becomes important at extremes of physiology (e.g. in severe sepsis) 1
• Sickle cell disease is also seen in families originating in the Middle East, India, and the southern and eastern Mediterranean 1
• Approximately two-thirds of patients with sickle cell disease in the UK live in London, one third in cities in the North West, West Midlands, East Midlands, or Yorkshire and Humber 1

The primary goal of treatment is to manage symptoms and prevent complications, with hydroxyurea being a key medication in this regard, as noted in a study on hematopoietic stem cell transplantation in thalassemia major and sickle cell disease 1. Treatment should focus on increasing fetal hemoglobin production, reducing painful crises, and preventing end-organ damage, with a multidisciplinary approach to care. This may include medications such as hydroxyurea, as well as preventive measures like penicillin prophylaxis, pneumococcal and meningococcal vaccinations, and daily folic acid supplementation. Newer treatments, such as crizanlizumab and voxelotor, may also be considered in certain cases. Bone marrow transplantation offers a potential cure but carries significant risks, and is typically considered for patients with severe disease or significant morbidity 1.

From the Research

Definition and Overview of Sickle Cell Disease (SCD)

• Sickle cell disease (SCD) is a genetic hereditary blood disease that disrupts normal beta-globin production 2, 3, 4, 5.
• It is characterized by the polymerization of deoxygenated haemoglobin S and microvascular obstruction, leading to generalized pain, multi-organ damage, and premature death 4.
• SCD is the most prevalent inherited life-threatening disorder in the world, with over 85% of the world's 400,000 annual births occurring in low- and middle-income countries 4.

Symptoms and Compabilities of SCD

• Patients with SCD experience a broad range of symptoms, including anemia, pain crises, jaundice, acute coronary syndrome, and stroke 2.
• The disease can cause significant morbidity and mortality, affecting the economic and healthcare status of many countries 5.
• SCD complications begin with the polymerization of sickle hemoglobin (HbS), and therapies are focused on preventing HbS production or reducing the circulating amount of HbS 3.

Treatment Options for SCD

• Hydroxyurea has been the primary treatment for SCD since 1998, and it has been shown to increase the expression of fetal hemoglobin (HbF), which prevents sickling of red blood cells 2, 3, 5, 6.
• Other treatment options include L-Glutamine, Crizanlizumab, and Voxelotor, which have been approved by the FDA in recent years and have shown efficacy in reducing vaso-occlusive pain crises, hospitalization, and improving hemolytic anemia and quality of life 2, 4, 5.
• Hematopoietic stem cell transplant is a curative option for SCD, but it is only available to a limited number of patients with a suitable donor 3, 5.
• Gene therapy is also a promising treatment option, with recent approvals of Exa-cel and Lovo-cel in 2023 4.