Amsterdam UMC, University of Amsterdam, Emma Children's Hospital, Pediatric Hematology, Amsterdam, the Netherlands.
Immunoscience, Nordic Bioscience, Biomarkers and Research, Herlev, Denmark.
J Thromb Haemost. 2023 Jul;21(7):1813-1823. doi: 10.1016/j.jtha.2023.03.030. Epub 2023 Apr 3.
Persons with nonsevere hemophilia A (NSHA) experience less frequent joint bleeding than persons with severe hemophilia A, but may still develop joint damage. Biomarkers of cartilage and synovial remodeling can reflect ongoing pathologic processes that may precede or coincide with damage on joint imaging. If so, biomarkers may be an important diagnostic tool for joint damage in NSHA.
To assess the correlation between biomarkers and MRI-detected joint damage in persons with NSHA.
In a cross-sectional study, men with NSHA (factor VIII [FVIII], 2-35 IU/dL) were included. Participants underwent magnetic resonance imaging of elbows, knees, and ankles and blood and urine sampling for biomarker analysis on a single visit. The following biomarker(s) were analyzed in urine: CTX-II or serum: cartilage oligomeric matrix protein, chondroitin sulfate 846, vascular cell adhesion molecule 1, osteopontin (OPN), neo-epitope of MMP -mediated degradation of type II collagen, N-terminal propeptide of type II collagen, collagen type IV M, and propetide of type IV collagen. Spearman's rank correlations were calculated between these biomarkers and the total International Prophylaxis Study group (IPSG) score, soft-tissue subscore, and osteochondral subscore.
In total, 48 persons with NSHA were included. Median age was 43 years (range, 24-55 years) and median FVIII was 10 IU/dL (IQR, 4-16 IU/dL). The median IPSG score was 4 (IQR, 2-9). Median IPSG soft-tissue subscores were 3 (IQR, 2-4) and osteochondral subscores were 0 (IQR, 0-4). No strong correlations were found between the studied biomarkers, total IPSG score, subsequent soft-tissue, and osteochondral subscores.
In this study, selected biomarkers indicative of different aspects of hemophilic arthropathy showed no consistent correlation with IPSG scores. This suggests that systemically measured biomarkers are currently not suitable for identifying milder joint damage in NSHA, as observed on magnetic resonance imaging.
非重度血友病 A（NSHA）患者的关节出血频率低于重度血友病 A 患者，但仍可能发生关节损伤。软骨和滑膜重塑的生物标志物可以反映可能先于或与关节影像学损伤同时发生的持续病理过程。如果是这样，生物标志物可能是 NSHA 关节损伤的重要诊断工具。
评估 NSHA 患者的生物标志物与 MRI 检测到的关节损伤之间的相关性。
在一项横断面研究中，纳入了 NSHA 男性（FVIII，2-35IU/dL）。参与者在单次就诊时接受肘部、膝盖和脚踝的磁共振成像和血液及尿液采样，用于生物标志物分析。尿液中分析了以下生物标志物之一：CTX-II 或血清：软骨寡聚基质蛋白、硫酸软骨素 846、血管细胞黏附分子 1、骨桥蛋白（OPN）、MMP 介导的 II 型胶原降解的新表位、II 型胶原 N 端前肽、IV 型胶原 M 和 IV 型胶原前肽。计算这些生物标志物与国际预防研究组（IPSG）总评分、软组织亚评分和骨软骨亚评分之间的 Spearman 秩相关。
共纳入 48 名 NSHA 患者。中位年龄为 43 岁（范围，24-55 岁），中位 FVIII 为 10IU/dL（IQR，4-16IU/dL）。中位 IPSG 评分为 4（IQR，2-9）。中位数 IPSG 软组织亚评分 3（IQR，2-4）和骨软骨亚评分 0（IQR，0-4）。研究生物标志物与 IPSG 总分、随后的软组织和骨软骨亚评分之间未发现强相关性。
在这项研究中，不同方面血友病性关节病的选定生物标志物与 IPSG 评分无一致相关性。这表明，系统测量的生物标志物目前不适合识别 MRI 观察到的 NSHA 较轻的关节损伤。
