The Sub-Phenotypes of Sickle Cell Disease in Kuwait

Kuwaiti patients with sickle cell disease generally have a mild phenotype, but exhibit considerable heterogeneity, in spite of high Hb F levels. We have carried out a cross-sectional study of patients with sickle cell disease in the five major hospitals in Kuwait. Details of their hemoglobin (Hb) genotypes, clinical presentations and complications are presented. The study was over a span of 3 years and involved 396 patients, made up of 351 (88.6%) Kuwaitis and 45 (11.4%) expatriates. They were aged <1 to 73 years. Hb SS (β^S/β^S) was the most common (in 246 patients, i.e. 62.1%) followed by Hb S (HBB: c.20A>T)-β-thalassemia (Hb S-β-thal) in 138 (34.8%) and 11 (2.8%) Hb S/Hb D-Punjab (HBB: c.364G>C). Hb F ranged from 1.0 to 55.0%, with a mean of 21.2 ± 9.8%. The most common presentation was vaso-occlusive crises (VOCs), with 230 (54.8%) having had at least one prior to the study with 54 (13.2%) and 74 (18.9%) having between 2-3 and >3 VOCs, respectively. Hydroxyurea (HU) was prescribed to 157 (39.6%) patients. The most common complication was gallstones in 131 (33.1%), followed by acute splenic sequestration in 26.8% and avascular necrosis of the femoral head in 21.2% patients, respectively. Stroke, priapism and leg ulcers were rare. Gallstones, splenic sequestration and osteonecrosis were significantly more common in patients aged >16 years. Patients with Hb S-β-thal were similar to those with Hb SS in their clinical profiles. The phenotypic expression of sickle cell disease in Kuwaitis is unique in many respects. The role(s) of Hb F and other genetic modifiers require further elucidation.