Blood-induced joint damage: from mechanisms to clinical practice

Abstract

Blood-induced joint damage is an arthropathy which evolves as a consequence of joint bleeding (or: haemarthroses). These joint bleeds can occur as a consequence of joint trauma, such as intra-articular fracture or ligament rupture, but in patients suffering from the clotting disorder haemophilia, joint bleeds can occur spontaneously and repeatedly. Due to this is haemophilic arthropathy, so blood-induced joint damage in haemophiliacs, the major cause of morbidity in haemophiliacs. The research on blood-induced joint damage described in this thesis, contains studies on the mechanism of this arthropathy, possible treatments, translation of in vitro to animal in vivo situation and possible outcome measures in clinical practice in the treatment of haemophiliacs. Mechanism: Time and concentration dependency of blood-induced cartilage damage Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage. Susceptibility of degenerated cartilage Degenerated cartilage is as vulnerable to blood-induced damage as healthy cartilage is. Treatment: Poloxamer P188 The non-ionic surfactant poloxamer P188 does not prevent blood-induced cartilage damage. Interleukin-10 Interleukin-10 protects against blood-induced joint damage. Translation: Clearance rate of blood from the canine knee joint Very rapid clearance after a joint bleed in the canine knee can not prevent adverse effects on cartilage and synovial tissue. Exposure surface of cartilage Blood-induced cartilage damage in vitro: articular exposure versus total exposure. Clinical practice: Biomarkers as outcome measure of joint damage The combination of uCTX-II, sCOMP, and sCS846 reflects cartilage damage in haemophilic arthropathy. Digital scoring of radiographs to measure joint damage Digital scoring of haemophilic arthropathy using radiographs is feasible. Taken together, this thesis contains a variety of studies all aimed at the ultimate goal of research on blood-induced joint damage: the prevention of this arthropathy. More insight in the pathogenetic mechanism has been gained, possible treatment modalities have been explored, the in vitro and in vivo models of blood-induced joint damage have been further characterized and outcome measures as needed in clinical trials with possible treatment modalities have been investigated. All these results will be used in the continuation of this research.