Biomarkers of cartilage and bone damage after joint bleeds in haemophiliacs

Haemophilia is an X-chromosome linked, recessive bleeding disorder due to a
deficiency or functional defect of coagulation factor VIII or IX. Due to
recurrent joint bleeds (haemarthroses) specific changes occur in synovium and
cartilage in joints of patients suffering from haemophilia. In vitro and animal
in vivo experiments suggest that a single joint bleed results in rather acute
adverse changes in cartilage. These acute adverse changes of a single bleed on
cartilage, relatively easily detectable in vitro and animal models, are
difficult to detect in humans. Therefore, there is a need for more sensitive
measures that describe degenerative joint changes in the process of
blood-induced joint damage. This would improve early diagnosis, evaluation of
damage during the course of disease, and could have its impact on treatment of
haemophilia.
Biomarkers for cartilage and bone damage could be such a tool. Biomarkers are
molecules of connective tissue matrices, which are released into biological
fluid during the process of tissue turnover. Several (immuno)-assays have been
developed to detect such components, reflecting degradation and/or repair
activity of the tissue, in easily accessible body fluids such as serum and
urine. Recently several biomarkers of cartilage and bone related to the joint
diseases osteoarthritis and rheumatoid arthritis have been studied. These
biomarkers may also be used for detection of joint damage after a joint bleed
in haemophiliacs.

Evaluation of acute joint damage immediately after a joint bleed in patients
with haemophilia, by use of a panel of state-of-the-art biomarkers of cartilage
and bone turnover measured in blood and urine. The question that will be
addressed is whether joint damage as a result of an acute joint bleed in
haemophiliacs can be detected by use of a panel of state-of-the-art biomarkers
of cartilage and bone turnover.

Patients with haemophilia, being eighteen years or older, that visit the Van
Creveld Clinic for treatment of a joint bleed will be asked to participate in
this study. Initially a total of 10 patients will be included. Blood and urine
samples will be collected at four time-points after a joint bleed: within <48
hours, between 3 and 5 days, between 12 and 14 days and 3 months after the
joint bleed. Most haemophilia patients are used to vena puncture themselves to
administer clotting factor routinely. They will be demonstrated once how to
draw blood instead of administer clotting factor. Patients will take 10 ml
blood samples by venous puncture and will keep it at room temperature. Urine
(about 30 ml in a 50 ml vessel) will be collected, preferably the second
morning urine, and kept at 4*C (refrigerator). Blood and urine samples taken
will be collected by the researcher. Patients who can not or are not willing to
draw blood themselves, can come to the Van Creveld Clinic and an experienced
nurse will perform the venous puncture.
Serum and urine samples will be analysed for state-of-the-art biomarkers.
This study will last 3 months for each patient. Blood and urine will be
collected at four specific time-points (within <48 hours, between 3 and 5 days,
between 12 and 14 days and 3 months after the joint bleed), either in the Van
Creveld Clinic or at home.

There are no considerable risks nor benefits for the patients.