Caribbean Institute for Health Research - Sickle Cell Unit, The University of the West Indies, Mona Campus, Kingston, Jamaica.
Avicanna, Inc., Toronto, Ontario, Canada.
Br J Haematol. 2024 Oct;205(4):1570-1580. doi: 10.1111/bjh.19667. Epub 2024 Jul 31.
Viscosity-vaso-occlusion (VVO) and haemolysis-endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso-occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the Adult Sickle Cell Quality of Life Measurement Information System. The 'elbow method' determined the optimal number of clusters as three. Clustering was performed using K-prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot-PPT, 6.8% higher hand-PPT and 2.5% higher hand-HPT and foot-HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist.
黏附-血管阻塞（VVO）和溶血-内皮功能障碍（HED）是镰状细胞病（SCD）的病理生理机制和临床亚表型。反复发作的血管阻塞危象（VOC）可能导致神经可塑性改变和疼痛敏化。在 257 名 SCD 参与者中，我们使用定量感觉测试评估了亚表型与疼痛敏感性的关系，以确定热痛阈值（HPT）和压痛阈值（PPT）。使用成人镰状细胞生活质量测量信息系统评估 VOC 病史和睡眠、社会和情感功能。“肘部方法”确定了三个最佳聚类数。聚类使用 K-原型完成。在聚类 2 和 3 中，VOC 发生的频率和严重程度更高。聚类 1 和 3 的血红蛋白较低，网织红细胞和乳酸脱氢酶较高，腿部溃疡较多。在多变量回归中，与聚类 1 相比，聚类 3 的 PPT 约低 13.6%，女性的 PPT 和 HPT 在手部和足部均降低（p<0.001）。羟基脲的使用和睡眠功能的单位增加以及年龄的增加与足部 PPT 增加约 20.1%、手部 PPT 增加 6.8%、手部 HPT 和足部 HPT 分别增加 2.5%有关。研究结果表明，可能存在第三种具有混合 VVO 和 HED 特征且疼痛敏感性更差的亚表型。
