Ultrasonography in Hemophilic Joint Disease and Serum Markers

Study Summary

Hemophilia is a bleeding disorder (deficiency of a blood clotting factor/ protein) resulting in bleeding in joints and muscles. As patients continue to bleed into their joints they develop progressive joint damage leading to joint contractures, disability and days missed from work and school resulting in chronic debilitating pain and compromised quality of life. Current therapy is the administration of the missing protein or factor concentrate on a scheduled basis to prevent bleeding into the joints referred to as prophylaxis. This factor concentrate is expensive \~ $ 3,000 - 6,000 per infusion/ week in a child weighing 20 kg translating into $ 77,000 /yr for life. This regimen has been shown to be effective to prevent joint bleeds but the timing is unclear and not based on adequate evidence. Currently joint damage is diagnosed using MRI which is expensive and requires sedation in children \< 6 yrs of age. Therefore there is a need for a user friendly tool such as a ultrasound to monitor for the development of joint disease and tailor treatment based on an individual child's needs. This would also enable differentiating a joint bleed from a soft tissue bleed which present similarly and duration of treatment tends to be longer for a joint bleed. Acharya et al have previously shown that ultrasound is comparable to MRI for the diagnosis of hemophilic joint disease in hemophilia patients over the age of 6 years. However, the diagnostic findings in children \< 18 years with hemophilia on ultrasound is not well defined(1). The hemophilic synovium after repeated joint bleeds reveals the development of new vessels which are fragile and contribute to recurrent joint bleeds. Acharya et al have previously shown that angiogenesis, a process of new vessel formation is active in hemophilic synovium and angiogenic markers were significantly elevated in hemophilic patients with joint disease when compared to those without (2). Since ultrasound can detect these new vessel changes i

Primary Outcome

Synovial changes on USG- PDS: Scoring system for synovitis which has 2 components - joint effusion and synovial thickening: Joint effusion will be defined as a compressible anechoic intracapsular area and the amount of fluid will be semiquantitatively scored usinga previosuly described scoring system by Martinoli et al. Quantitative assessment of the power Doppler signal: Power Doppler signal will be assessed subjectively for degree of vascularity -Table 2, Table 2 Degree of Vascularity PDS Si

Interventions

• OTHER ultrasound