Novel Ultrasound Markers of Synovial Tissue Function to Differentiate the Severity of Synovial Proliferation in Patients with Hemophilia: A Cross-Sectional Analysis

Introduction Grey-scale ultrasonography is an established method for assessing joint damage and synovial proliferation (SP) in persons with hemophilia (PwH). However, the utility of Power Doppler sonography (PD) for examining hyperemia and shear wave elastography (SWE) for measuring synovial tissue stiffness remains underexplored. This research aimed to incorporate functional characteristics of synovial tissues into the sonographic assessment of PwH, potentially enabling a more nuanced evaluation of joint health. Method 50 PwH with mild, moderate, and severe hemophilia A and B (age: 49.5±15.5 years) were included. The Hemophilia Early Arthropathy Detection with Ultrasound protocol (HEAD-US) was conducted on elbow, knee, and ankle joints. Following the assignment of the HEAD-US score, PD was employed in all ultrasound planes used for evaluating SP. The area of pixels displaying a PD signal (PDarea) was measured within a defined measurement area. For analysis, the largest measured PDarea per joint was utilized. SWE was performed on the olecranon, suprapatellar, and anterior tibiotalar synovial recesses. Three 2 mm circular areas measured tissue stiffness in kilopascals and were averaged for analysis. All ultrasound markers were acquired utilizing a Canon Aplio a ultrasound system. Additionally, the Hemophilia Joint Health Score (HJHS) was conducted for each joint (HJHSjoint). The annual joint bleeding rate (AJBR) and average joint pain intensity over the prior two weeks, rated on a numerical scale (NRSjoint), were documented. For statistical analysis, all joints were pooled. Kruskal–Wallis tests assessed differences in PDarea and SWE across joint subgroups defined by SP severity (0=none, 1=moderate, 2=severe). Spearman correlations examined associations of parameters. Results A total of 257 joints were statistically evaluated, with 43 joints excluded due to endoprosthesis or missing data. Kruskal-Wallis tests revealed significant differences in PDarea between all SP subgroups. SWE showed no significant differences between SP subgroups ([ Fig. 1 ]). Correlation analyses revealed significant associations of PDarea with SP (r=0.54), HJHSjoint (r=0.37), AJBR (r=0.29) and NRSjoint (r=0.33). Similarly, SP correlated with clinically relevant parameters. SWE was weakly associated with SP (r=0.15) ([ Fig. 2 ]). Fig. 1 Boxplots showcasing data of joints without synovial proliferation (SP=0), with moderate synovial proliferation (SP=1) and severe synovial proliferation (SP=2). The boxplots display the first and third quartiles and a horizontal line representing the median, capped whiskers for 1.5 x Interquartile range, black dots for outliers, and red diamonds marking the means. P-values derived from Kruskal-Wallis tests were Bonferroni adjusted. N=number of joints, PD=Power Doppler, SWE=shear wave elastography. Fig. 2 Correlation matrix for Spearman correlation coefficients between synovial proliferation (SP), Power Doppler area (PDarea, in cm 2 ), shear wave elastography (SWE, in kPa), Hemophilia Joint Health Scores (HJHSjoint), subjective joint pain (NRSjoint), and annual joint bleeding rate (AJBR). Lower triangle shows scatter plots. The y-axis scale indicates the data distribution for each scatter plot. The diagonal line of figures represents the relative distribution of each parameter. All parameters refer to individual joints.*= p