解析高胎儿血红蛋白型镰状细胞病表型：科威特患者研究

HbF concentration influences the clinical phenotype of sickle cell disease (SCD) and the prevailing management approach involves pharmacological or genetic stimulation of HbF expression. Understanding how HbF affects the disease's progression, in the context of other potential modifiers, is vital. Kuwaiti patients with SCD predominantly carry the Arab/Indian haplotype, and their average spontaneous HbF concentration varies from ∼15-30%. Our team has conducted a series of clinical studies on these patients between 1994 and 2024 to understand their clinical course; some of these studies are summarized here. Most patients show no symptoms before age 4 or 5, when their HbF level is about 30%. Splenic function remains intact in childhood and in 60-80% of adult patients, which may explain the rarity of severe bacterial infections. Other less common complications include stroke, leg ulcers, and priapism. Most patients do not develop cerebral vasculopathy, as shown by normal transcranial Doppler studies. However, osteonecrosis of the femoral head is relatively common, affecting about 25% of children and over 50% of adults. The factors that predispose to this complication remain unclear. While the overall phenotype in pediatric patients is generally mild, the disease becomes quite severe in adults, indicating that subclinical inflammatory events accumulate over time. The pattern observed in our patients provides insight into what to expect in those treated with HbF inducers or gene therapy. Indeed, increasing HbF alone is not a cure for SCD. The greatest benefit of elevated HbF is seen in younger patients, making early intervention crucial.