Real-World Evidence on Joint Condition in Non-Severe Hemophilia A Patients: A Multicenter Study

Abstract

Purpose: Patients with non-severe hemophilia A (PwnSHA) may be at risk for joint damage (JD), yet data remain scarce. Our aim was to evaluate the joint condition in PwnSHA in a real-world setting.

Patients and methods: A nationwide, multicenter, cross-sectional study was conducted. To mitigate the impact of discrepancies between factor VIII (FVIII) assays, baseline FVIII levels were determined using chromogenic and one-step clotting assays. Mutation in F8 gene, baseline FVIII levels, thrombin generation and age were assessed. The joint condition was described using the HEAD-US score by trained specialists at each participating hospital.

Results: One hundred and twenty-four patients were recruited, 84 of them with an available HEAD-US evaluation, who were finally included in our analysis. The median age was 38.4 years (18.3-48.5). Twenty percent (16/84) had moderate hemophilia (MoH) with FVIII levels of 4.0 IU/dL (2.6-4.6), and 80% (68/84) had mild hemophilia (MiH) with FVIII levels of 14.8 IU/dL (10.4-19.9), (p< 0.001). JD (HEAD-US>0) was observed in 50% (8/16) of MoH patients (HEAD-US= 6.5 [5.5-8.5]) and in 40% (27/68) of those with MiH (HEAD-US= 3.0 [2.0-6.5]), p=0.198. In the moderate group, JD was primarily observed in ankles (44%), while in the MiH group, knees were the most affected (31%). MoH patients reported a hypocoagulable thrombin generation profile compared to MiH patients (p<0.05).

Conclusion: Near half of PwnSHA had JD. A worse joint health and a lower thrombin generation was observed in MoH population. These patients can benefit from an early prophylaxis and prevent further joint deterioration. Future research should explore additional variables that might influence joint condition.

Keywords: HEAD-US; assay discrepancies; joint damage; mild hemophilia A; moderate hemophilia A; real-world data.