The hyperhemolysis paradigm that describes overlapping “hyperhemolytic-endothelial dysfunction” and “high hemoglobin-hyperviscous” subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2407 SCD patients (1751 SS or sickle β-zero-thalassemia [Sβ⁰], 495 SC, and 161 sickle β⁺-thalassemia [Sβ⁺]), aged 3 years old and over, were included at steady state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity [TRV], microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sβ⁰ adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sβ⁰ adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.

描述北美镰状细胞病（SCD）患者的“高溶血性内皮功能障碍”和“高血红蛋白-高黏液性”亚型重叠的高溶血性范例是基于北美的研究。我们在CADRE队列中进行了一项横向研究，分析了撒哈拉以南非洲患者稳态溶血与SCD血管并发症之间的关系。在马里，喀麦隆和象牙海岸，2407名SCD患者（1751 SS或镰刀β-零地中海贫血[Sβ ⁰ ]，495 SC，和161镰刀β ⁺地中海贫血[Sβ ⁺]），年龄稳定在3岁以上。根据主要成分分析得出的综合指数估算相对溶血强度，该综合指数包括胆红素水平或临床黄疸和乳酸脱氢酶水平。我们通过临床检查，实验室检查和超声心动图评估了血管并发症（三尖瓣反流射流速度[TRV]升高，微量白蛋白尿，小腿溃疡，阴茎异常勃起，中风和骨坏死）。在调整了年龄，性别，国家和SCD表型后，低血红蛋白水平显著用TRV和微量白蛋白尿在整个人口和与SS-Sβ腿部溃疡相关⁰成年人。高溶血指数在整个人群微量白蛋白尿，并与高架TRV，微量白蛋白尿，和SS-Sβ腿部溃疡相关⁰大人，但这些协会不再调整血红蛋白水平后显著。总之，居住在西非和中非的SCD患者在稳态下的严重贫血与TRV升高，微量白蛋白尿和小腿溃疡有关，但这些血管并发症并非与溶血增加的间接标志独立相关。其他导致贫血的机制，包括营养不良和传染病，也可能在SCD血管病的发展中起作用。