THE IMPACT OF BLEEDS AND FACTOR VIII INHIBITORS ON BONES IN CHILDREN WITH HAEMOPHILIA A

Osteoporosis, a disease characterised by low bone mineral density (BMD) and bone injury, is a matter issue of increasing concern in people with haemophilia. In recent years, many studies have been conducted on this topic, primarily in adults, but also in younger patients.¹

Pathological bone metabolism is considered to be a consequence of chronic inflammation related to recurrent bleeds, especially in joints, and the long periods of immobilisation that haemophilia patients are forced to endure.¹ Although people with haemophilia are, nowadays, on prophylactic treatment from an early age – in order to minimise the number of joint bleeds – as the years go by, they may develop one or more target joints or suffer subclinical joint bleeds. In addition, in children with severe haemophilia who develop inhibitors, the clinical phenotype is exacerbated in terms of the number and severity of bleeds and the subsequent occurrence of arthropathy.¹ Considering haemophilic arthropathy from a biochemical perspective, several studies have shown that patients with haemophilia have an altered balance in bone formation and resorption.¹

Recently, peripheral quantitative computed tomography (pQCT) has been introduced as a highly specific and sensitive diagnostic technique to detect deterioration of bone microstructure, geometry, and strength.¹

Peripheral quantitative CT gives detailed information not only on bone density, but bone geometry, size and strength, and may better predict skeletal fragility than bone density alone.² In addition, pQCT has minimal radiation, is quick and can be used at all ages.²

In a recent study, children with haemophilia A were examined for the impact of their disease on bone structure by measurements obtained with pQCT.¹ This is the first time that all four limbs have been examined with this technique in children with haemophilia, and side-to-side comparisons between limbs have been attempted. In addition, also for the first time, the effect of multiple bleeds on the bone structure and density of the target joints (radius or tibia) was studied and compared with other nontarget joints.¹

The study concluded that in children with haemophilia Α and a history of target joints and/or Factor VIII inhibitors, abnormalities may occur in the joints but also in the long bones, as revealed by pQCT, where low trabecular density and weak cortical bone quality were found in the upper and lower extremities, respectively.¹

Therefore, children with haemophilia may benefit not only from treatment with concentrates but also from targeted interventions such as exercise and daily lifestyle changes.¹

References:

1. Xafaki P, Balanika A, Pergantou H, Papakonstantinou O, Platokouki H. Impact of target joint and FVIII inhibitor οn bone properties in children with haemophilia A: A peripheral quantitative computed tomography study. Haemophilia. 2018;00:1–7. https://doi. org/10.1111/hae.13591
2. Vlok J, Simm PJ, Lycett K, et al. pQCT bone geometry and strength: population epidemiology and concordance in Australian children aged 11–12 years and their parents. BMJ Open 2019;9:63–74. doi:10.1136/ bmjopen-2018-022400