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. 2022 Nov;28(6):1054-1061.
doi: 10.1111/hae.14636. Epub 2022 Aug 4.

Long-term joint outcomes in adolescents with moderate or severe haemophilia A

David E Schmidt  1   2   3 , Aikaterini Michalopoulou  4 , Kathelijn Fischer  5 , Jayashree Motwani  6 , Nadine G Andersson  7   8 , Helen Pergantou  4 , Susanna Ranta  1   2 ; PedNet Study Group
Affiliations

Long-term joint outcomes in adolescents with moderate or severe haemophilia A

David E Schmidt et al. Haemophilia. 2022 Nov.

Abstract

Introduction: Favourable joint outcomes are expected with modern haemophilia A (HA) management. Evaluation of long-term treatment outcomes is hampered by the delay between bleeding episodes during childhood and resulting joint outcomes in adulthood.

Aim: To measure the long-term joint health of adolescents with moderate and severe HA, according to severity and inhibitor status.

Methods: Pilot cross-sectional study of five European PedNet centres in moderate and severe HA patients aged 10-19 years. Structured assessment of joint status by physical examination (HJHS) and ultrasound (HEAD-US).

Results: In total, 141 HA patients were evaluable, 100 without inhibitors (81 severe, 19 moderate HA), and 41 severe HA with current/past inhibitors. On physical examination, 12/81 (15%) of severe HA without inhibitors, 3/19 (16%) of moderate HA, and 13/41 (32%) of severe HA patients with inhibitors exhibited joint abnormalities. Inhibitor persistence, longer inhibitor duration, and a high peak inhibitor level were associated with impaired joint health. Ultrasound showed joint damage (bone or cartilage) in 13/49 (27%) of severe HA without inhibitors, 1/12 (8%) of moderate HA, and 10/28 (36%) of severe HA patients with inhibitors. A discordant ankle evaluation by ultrasound versus physical examination was present in 53/169 joints (31%).

Conclusions: Most adolescents with severe or moderate HA show favourable joint health. Future research with combined ultrasound and/or MRI is needed to better understand joint outcomes in the remaining patients. Patents with inhibitors showed a two-fold increased proportion with joint deterioration. Ultrasound paired with physical examination increases sensitivity for detection of joint damage.

Keywords: adolescent; arthropathy; haemophilia A; paediatrics; ultrasonography.

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Conflict of interest statement

Susanna Ranta is an investigator in clinical trials sponsored by SOBI, Roche, Novo Nordisk, received grants for research from the Childhood Cancer Foundation and Stockholm County Council, and participated in Steering Committee for Roche. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Study flow chart. HA, haemophilia A; HJHS, Haemophilia Joint Health Score; US, ultrasound
FIGURE 2
FIGURE 2
Functional joint health and gait in adolescents with haemophilia A, using structured outcome assessment. (A) Physical examination of joint health between severe and moderate haemophilia A without inhibitors. Red diamonds indicate patients with no prophylaxis or unknown status. (B) Comparison of joint health of patients with severe haemophilia A by inhibitor status. HA, haemophilia A; HJHS, Haemophilia Joint Health Score; Inh, inhibitor; m, months
FIGURE 3
FIGURE 3
Determinants of joint health in adolescents with severe haemophilia A. (A) Age at the evaluation was not associated with the joint health and gait (severe haemophilia A without inhibitors). Older children showed no worse joint function than younger children. (B) Duration of a FVIII inhibitor presence and cumulative HJHS score (severe haemophilia A with inhibitors). C, Current; HA, haemophilia A; HJHS, Haemophilia Joint Health Score; BU, Bethesda units; rho, Spearman's rank correlation coefficient
FIGURE 4
FIGURE 4
Ultrasound to identify early signs of joint arthropathy, and synergistic use together with physical examination. (A) Comparison of ultrasound evaluation between moderate and severe haemophilia A without inhibitors. Red diamonds indicate patients with no prophylaxis or unknown status. (B) Comparison of ultrasound joint health between patients with severe haemophilia A and inhibitors, by inhibitor status. (C) Correlation between HEAD‐US and HJHS scores. Correlation is given for the Spearman rank coefficient rho. HA, haemophilia A; HEAD‐US, Haemophilia Early Arthropathy Detection by Ultrasound score
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