Ultrasonography in Hemophilic Joint Disease and Serum Markers

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 in the hemophilic synovium in hemophilia patients with joint disease and hemophilia patients with joint disease demonstrate elevated markers of new vessel formation these investigators would now like to determine whether radiological findings of hemophilic joint disease correlate with serological angiogenic markers. This may enable the development of biomarkers for hemophilic joint disease.

Findings from this study will enable the development of ultrasound as a user friendly tool in the hemophilia clinic in order to understand whether every pain and swelling in a joint is actually a joint bleed or soft tissue bleed and to monitor for joint changes to institute or augment scheduled factor infusions ( prophylaxis). This will also result in significant improvement in quality of life with tailored prophylaxis .

Conditions

• Hemophilia A
• Hemophilia B
• Hemarthroses

Interventions

OTHER

ultrasound

ultrasound will be performed in hemophilia boys with a history of 20 joint bleeds- Group I, less than 2 joint bleeds into a joint -Group II and no joint bleeds- Group III

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• University of California, San Diego

  collaborator OTHER

• Northwell Health

  lead OTHER

Eligibility

Min Age

6 Months

Max Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-01-31

Primary Completion

2019-08-31

Completion

2019-12-31

Countries

• United States

Study Locations