The many facets of sickle cell disease - emerging complications and issues in management

Abstract

Sickle cell disease (SCD) is an inherited disorder characterised by chronic haemolytic anaemia, interrupted by episodic acute pain, and acute clinical events resulting in organ damage and a shortened lifespan. It is caused by the presence of haemoglobin S (HbS, α 2 β S 2 ) which results from a single nucleotide mutation in the β-globin gene leading to the substitution of valine for glutamic acid in position 6 of the β-globin chain (β 6 Glu→Val or β S ). SCD is autosomal recessive, the homozygous state (HbSS or sickle cell anaemia) is the most common form of SCD but interaction of β S with other β-globin variants (including β-thalassaemia and β C ) also leads to SCD. With improved general healthcare in the last thirty years, childhood mortality has declined. Almost all children with SCD in Europe and the US can now expect to survive to adulthood. However, most would have manifestations of some sickle-related complications, such as silent cerebral infarcts, renal impairment or pulmonary disease. In adults, the combination of acute and chronic complications results in substantial morbidity, high healthcare utilisation and premature death. In prevalent areas, SCD also impacts and complicates management of many pathologies, including stroke, cancer and diabetes. Thus, optimal management of SCD carries specific challenges and necessitates good multidisciplinary interaction. Current treatment options are limited to hydroxyurea and blood transfusions on a chronic or intermittent basis. Bone marrow transplantation remains the only ‘cure’ but it is a high-risk procedure, appropriate and limited to a minority of patients, and often performed too late after major complications, such as stroke, have occurred. There is an urgent need in SCD for the ability to predict disease severity to facilitate early recognition and intervention to minimise or delay organ damage, hence the drive for genetic and biomarkers.