PUBLICATIONS.

Susan Halimeh, MD, CRC – Coagulation Research Centre GmbHDisclosure: Please see Session Details (link below).

Background:
Prophylactic substitution of clotting factor concentrates in haemophilia patients starting in early childhood, defined as primary or secondary prophylaxis, is nowadays the gold standard in developed countries. Prophylaxis compared to on-demand treatment is known to reduce bleeding frequency and joint damage.The occurrence of bleeds, especially joint bleeds leads to joint arthropathy in haemophilia patients, even in young children. Prophylaxis compared to on-demand treatment is known to reduce bleeding frequency and joint damage. The occurrence of bleeds, especially joint bleeds leads to joint arthropathy in haemophilia patients, even in young children.

Aims: To determine the impact of bleeding events on the joint health of children with haemophilia.

Methods: Children with haemophilia aged 0-17 years of any type of severity and treatment regimen from a single HTC centre in Duisburg, Germany were compared to healthy children recruited from the environment of the Duisburg HTC. Joint health was measured using ultrasound (US), Clinician-Reported Outcomes (ClinRO) and Patient-Reported Outcomes (PRO). Joint physical structure and joint function were measured with the ClinRO Haemophilia Joint Health Score (HJHSv2.1); subjective physical functioning was assessed with the PRO HEP-Test-Q. US assessment used the Joint Tissue Examination and Damage Exam (JADE) Protocol. Ultrasound images were obtained with a Fujifilm Sonosite Edge II scanner using 13 – 6 MHz transducers. Evaluations were performed in all children by the same person who is experienced in musculoskeletal US scanning.

Clinical data of haemophilia patients in terms of treatment regime, total and joint bleeding rates in the past 12 months and target joints were collected from patient records.

Differences in the median or in the mean, respectively, were calculated between children with haemophilia and healthy controls and between haemophilia patients across different clinical subgroups.

Results: Forty-six children with haemophilia (mean age 9.1±5 years) and 59 healthy children (mean age 8.5±4.7 years) participated in the Energy Study.The majority of the haemophilic children had haemophilia A (91.3%), were severely affected (60.9%) and received prophylactic treatment (69.6%), most of them were on secondary prophylaxis (53.1%). Haemophilia patients had in average 1.57±1.9 total bleeds (range 0-9) and 0.65±1.2 joint bleeds (range 0-6) in the past 12 months, a HJHS of 2.39±3.8 (range 0-13). 43.5% had a target joint, mainly in the ankles. Most of the children with haemophilia participated in physical education in school (58.7%), mainly 1x/week (72.4%). Almost one quarter received physiotherapy (23.9%); only 2 patients had limitations in their mobility.

Only children = 6 years of age completed the self-rated HEP-Test-Q, resulting in 33 haemophilia patients and 45 controls. Patients treated on prophylaxis (p<.015), severely affected (p<.001), with joint impairments in the HJHS = 1 (p<.022), number of joint bleeds = 1 (p<.029), number of total bleeds = 2 (p<.0001), showed a worse total score in the HEP-Test-Q compared to children on-demand, with moderate/mild haemophilia, no impairment in HJHS, no joint bleeds, less < 2 total bleeds, respectively. No difference was found for type of prophylaxis and target joints.

Compared to controls, patients reported significantly worse subjective physical functioning (MP=77.16±9.5 vs. MC=86.0±7.1; p<0.0001), had a worse HJHS (p<.0001) and showed in the US a significant difference (p<.02) of the longitudinal gap been tibia and talus.

Conclusion: Children with haemophilia showed higher deterioration in their joint health of the ankle measured with US and reported higher impairments in their subjective physical functioning than healthy controls.

Although 96.4% of severe patients were on regular prophylaxis, early signs of synovitis were detected, especially in the ankle. Patients with haemophilia should be monitored early for arthropathy using US and standardized ClinROs and PROs.

Conflict of interest: The Energy Study was sponsored by an unrestricted educational grant from Biotest, Germany.