What is Sickle Cell Disease (SCD)?

From the Guidelines

Sickle Cell Disease (SCD) is a genetic blood disorder characterized by abnormal hemoglobin that causes red blood cells to become sickle-shaped, leading to chronic haemolytic anaemia, painful vaso-occlusive crises, and acute and chronic end-organ damage. This inherited condition primarily affects people with ancestry from Africa, Mediterranean countries, the Middle East, and India [ 1 ]. The abnormal cells can block blood vessels, causing pain crises, organ damage, and increased susceptibility to infections.

Key Characteristics of SCD

• Chronic haemolytic anaemia
• Painful vaso-occlusive crises
• Acute and chronic end-organ damage
• Increased risk of peri-operative complications, both sickle-related and non-sickle-related [ 1 ]

Management and Treatment

Management includes preventive care with daily penicillin and folic acid supplementation, and hydroxyurea therapy to increase fetal hemoglobin production and reduce sickling episodes [ 1 ]. Pain crises require prompt treatment with hydration and analgesics, ranging from acetaminophen to opioids depending on severity. Regular vaccinations, including pneumococcal and annual influenza vaccines, are essential. Blood transfusions may be necessary for severe anemia or to prevent stroke in high-risk patients. Bone marrow transplantation offers a potential cure but carries significant risks [ 1 ].

Important Considerations

• SCD is associated with substantial morbidity, leading to both reduced quality of life and shortened life expectancy [ 1 ]
• Survival has improved significantly in the last two decades, with 94% of children with SCD now surviving until the age of 18 years [ 1 ]
• The only curative approach for SCD is hematopoietic stem cell transplantation (HSCT) [ 1 ]

From the Research

Definition and Overview of Sickle Cell Disease (SCD)

• Sickle Cell Disease (SCD) is a group of inherited blood disorders that affect the hemoglobin, leading to a shortened lifespan of erythrocytes and causing them to take on a distinctive sickled shape, resulting in vaso-occlusion 2.
• SCD is characterized by polymerization of deoxygenated haemoglobin S and microvascular obstruction, leading to generalized pain, multi-organ damage, and premature death 3.
• It is one of the most common inherited diseases worldwide, associated with lifelong morbidity and a reduced life expectancy 4, 5.

Pathophysiology and Clinical Features

• The disease is caused by an inherited mutation in the HBB gene, leading to the production of abnormal hemoglobin S 2.
• The abnormal hemoglobin S polymerizes under certain conditions, causing red blood cells to become sickled and leading to vaso-occlusion and tissue damage 3.
• Clinical features of SCD include recurrent episodes of pain, anemia, infections, and increased risk of stroke and other complications 4, 5.

Treatment and Management

• Current treatment options for SCD include hydroxyurea, erythrocyte transfusion, and hematopoietic stem cell transplantation 2.
• Hydroxyurea is an oral chemotherapeutic drug that ameliorates some of the clinical problems of SCD, particularly pain, by raising fetal haemoglobin 4, 5, 6.
• Other treatment options, such as L-glutamine, Crizanlizumab, and Voxelotor, have also been approved for use in SCD 3.
• Gene therapies, such as Exa-cel and Lovo-cel, have also been recently approved for use in SCD 3.