Wambaka Bill, Mpungu Amiirah, Mboizi Vincent, Kalibbala Dennis, Nambatya Grace, Murungi Susan, Kabatabaazi Maxencia, Nakafeero Maria, Kasirye Phillip, Munube Deogratias, Namazzi Ruth, Idro Richard, Green Nancy S
Global Health Uganda, Kampala, Uganda.
Division of Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Pediatr Blood Cancer. 2025 Jul;72(7):e31722. doi: 10.1002/pbc.31722. Epub 2025 Apr 22.
Transcranial Doppler ultrasound (TCD) screening for primary stroke prevention in children with sickle cell anemia (SCA) was established in higher-resource regions, targeting interventions for highest velocity ("abnormal"). We sought to identify additional stroke risk factors in Uganda.
We conducted a 30-month open-label single-arm Ugandan hydroxyurea trial, dose-escalated to maximum-tolerated dose, aimed to test brain protection for children aged 3-9 years with SCA. Study procedures included history, clinical stroke examination, and prospective TCD and laboratory assessments.
Overall, 264 children received study HU, mean age 5.6 ± 1.7, hemoglobin 7.8 ± 1.2 g/dL, fetal hemoglobin (HbF) 11.9% ± 8.1%, enrolment TCD mean TAMV 148.4 ± 29.3 cm/sec; 15 (5.7%) had abnormal TCD. The mean TAMV at trial completion was 131.9 ± SD 25.7 cm/sec. Four participants without abnormal enrolment TCD developed acute stroke within the initial 16 months (incidence 0.62 per 100 person-years): two had enrolment HbF ≤3.1%, two had low oxygen saturation (90%), and one had recurring severe anemia necessitating multiple transfusions. Apparent stroke precipitants were severe malaria, acute chest syndrome, recent pain crisis, or uncertain cause. At trial completion, eight additional participants had a higher risk TCD category than at enrolment.
The effectiveness of TCD screening for stroke prevention may vary by region, as no participant with an incident stroke was at the highest risk. Antecedent and/or ongoing SCA-related risks of anemia, low HbF, hypoxemia, infections, and/or disease complications likely contributed to stroke despite trial HU. Results suggest that TCD alone may not fully identify the highest stroke risk in the region, and there is a need for primary stroke prevention from early childhood and continuous hydroxyurea therapy.
在资源较丰富的地区，已开展经颅多普勒超声（TCD）筛查，以预防镰状细胞贫血（SCA）患儿的原发性卒中，针对最高血流速度（“异常”）进行干预。我们试图在乌干达确定其他卒中危险因素。
我们开展了一项为期30个月的开放标签单臂乌干达羟基脲试验，剂量逐步递增至最大耐受剂量，旨在测试对3至9岁SCA患儿的脑保护作用。研究程序包括病史、临床卒中检查以及前瞻性TCD和实验室评估。
总体而言，264名儿童接受了研究性羟基脲治疗，平均年龄5.6±1.7岁，血红蛋白7.8±1.2 g/dL，胎儿血红蛋白（HbF）11.9%±8.1%，入组时TCD平均TAMV为148.4±29.3 cm/秒；15名（5.7%）TCD异常。试验结束时的平均TAMV为131.9±标准差25.7 cm/秒。4名入组时TCD无异常的参与者在最初16个月内发生急性卒中（发病率为每100人年0.62例）：2名入组时HbF≤3.1%，2名血氧饱和度低（90%），1名有反复严重贫血需要多次输血。明显的卒中诱发因素为重症疟疾、急性胸综合征、近期疼痛危象或病因不明。试验结束时，另外8名参与者的TCD风险类别高于入组时。
TCD筛查预防卒中的有效性可能因地区而异，因为没有发生卒中的参与者处于最高风险。尽管进行了羟基脲试验，但先前和/或持续存在的与SCA相关的贫血、低HbF、低氧血症、感染和/或疾病并发症风险可能导致了卒中。结果表明，仅TCD可能无法完全识别该地区最高的卒中风险，需要从幼儿期开始进行原发性卒中预防并持续进行羟基脲治疗。
