PhD Defense: Improving blood-induced joint damage in haemophilia: from early detection to early treatment

PhD Defense of Eline Dorothea Petronellavan Bergen


The hereditary coagulation disorder haemophilia is characterised by spontaneous and traumatic bleeding. Recurrent joint bleeding leads to synovial inflammation and bone/cartilage damage and causes pain and impaired function. Although prophylactic administration of clotting factors has led to a substantial reduction in joint bleeding, complete prevention of bleeding is impossible. Early detection of joint damage and early start and adjustment of treatment is important to prevent (irreversible) progression of so-called 'haemophilia arthropathy'. Part I of this thesis (early detection) focuses on the prevention and detection of undetected ('subclinical') joint changes by imaging and biochemical markers. In 22% of patients who came to the outpatient clinic for routine check-ups with the haematologist, there was evidence of an 'active joint' on ultrasound. These patients reported no symptoms or recent bleeding. This indicates that regular imaging of joints by ultrasound is important to detect changes in joints and adapt treatment on time. In patients aged 16-32 years, an MRI of a bleed-free joint was performed. Nevertheless, signs of previous bleeding seen in 16% of joints. Biochemical markers in blood and urine are currently not useful to detect patients with an 'active joint'.

Part II of this thesis (early treatment) focuses on treatments that can prevent progression of joint damage and major orthopaedic surgery (such as ankle fixation or total ankle replacement). A systematic review showed that NSAIDs, effective analgesics recommended for the treatment of joint pain, pose no obvious risk for side effects such as bleeding or cardiovascular disease. Sometimes conservative treatments such as NSAIDs, physiotherapy and adapted shoes are not enough. At that point, surgical treatment may be needed to reduce pain and improve function. The final part of this thesis investigated a new treatment called ankle distraction. In this treatment, an external frame is applied around the ankle by an orthopaedic surgeon and this frame is then left in place for 8-10 weeks and causes tensile forces on the ankle joint. These tensile forces lead to a kind of reset of the cartilage. Three-year follow-up showed significant clinical progress in pain and function and this improvement was accompanied by changes on MRI. No bleeding occurred and the ankle joint remained good mobility. This new treatment could be an attractive alternative to postpone major disabling procedures such as ankle fixation (arthrodesis) and total ankle replacement, especially in the relatively young haemophilia population.

Start date and time
End date and time
Academiegebouw, Domplein 29 & online (livestream link)
PhD candidate
E.D.P van Bergen
Improving blood-induced joint damage in haemophilia: from early detection to early treatment
PhD supervisor(s)
prof. dr. R.E.G. Schutgens
prof. dr. F.P.J.G. Lafeber
dr. L.F.D. van Vulpen
dr. S.C. Mastbergen
More information
Full text via Utrecht University Repository