This is a prospective single blind randomized control study conducted between 2019/08/01 and 2020/07/31 (IRB number: 201800486B0C601 and 201900209B0A3). Hemophilia patients elder than 20-year-old were enrolled. Patients who had acute joint bleeding episodes were excluded.
All the patients were randomized for extracorporeal shock wave therapy to the left or right knee joint and energy-free sham therapy to the other knee. The treatments were performed by a senior specialist at the 1st and 2nd month. The ESWT treatment site was at the musculo-tendonous junction of the quadriceps tendon. As to the energy of ESWT, the chosen knee received 3000 shocks with the energy of 0.2mJ / mm2 by Storz Medical Duolith SD1® and the treatment duration was 15 minutes each time.
Since uncorrected coagulation abnormalities is regarded as a contraindication for ESWT, prophylactic coagulation factors were administrated before each treatment. The concentration of blood clotting factor was expected to be increased up to at least 60%.
As safety evaluation, hemophilia joint health score (HJHS) [12], knee society score (KSS) [13] , visual analog scale (VAS) [14] and ultrasound (HEAD-US) [11] were checked at the beginning and then at 1st, 2nd, 3rd and 6th month for every patient. In other words, the 2nd month HJHS, KSS, VAS and ultrasound were calculated one month after 1st ESWT while the 3rd month HJHS, KSS, VAS and ultrasound were calculated one month after the second ESWT. The 6th month HJHS, KSS, VAS and ultrasound were calculated 3 months after completing two sessions of ESWT. Knee MRI was performed at the beginning and at the 6th month.
Hemophilia joint health score (HJHS) [12] is an evaluation tool of bilateral joints related to swelling (0 to 3 points), duration (0 or 1 point), muscle atrophy (0 to 2 points), crepitus on motion (0 to 2 points), flexion loss (0 to 3 points), extension loss (0 to 3 points), joint pain (0 to 2 points) and strength (0 to 4 points). Higher score indicates worse clinical conditions. Originally the score summary included bilateral elbows, knees, ankles and the global gait score (walking, stairs, running, hopping on one leg). Bilateral joints are evaluated separately. In this study, only the scores of right and left knees were calculated. Knee score scale (KSS) [13] includes evaluating objective knee indicators and functional activities. The objective knee indicators are composed of evaluating alignment, instability, joint motion by doctors and evaluating symptoms, satisfaction, and expectations by hemophilia patients. The functional activities evaluation was performed by the patients and included walking and standing, standard activities, advances activities and discretionary knee activities. In both parts of KSS evaluation, higher score indicates better clinical conditions.
The ultrasound (HEAD-US) evaluation was composed of two parts including disease activity (synovitis; 0 to 2 points) and osteochondral damage (cartilage: 0 to 4 points, bone: 0 to 2 points) [11]. High score indicates severe synovitis, destructions of cartilage or deranged subchondral bone. The scoring scale included evaluation of bilateral elbows, knees and joints. Only scores of disease activity of knee were taken into evaluation in this study.
Adverse event included local redness, swelling and pain evaluated by physical examination as well as breakthrough knee joint bleeding evaluated by ultrasound. The whole study for each enrolled patient took 6 months.
The statistical analysis was performed with unpaired T-test and Mean±SEM by GraphPad PRISM® version 6.01.