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

Ana Marco-Rico,1 José Manuel Calvo-Villas,2 Francisco-José López-Jaime,3 Mariana Canaro Hirnyk,4 Maria del Mar Nieto Hernández,5 Sonia Herrero Martín,6 Laura Entrena-Ureña,7 Shally Marcellini-Antonio,8 Bolívar L Díaz-Jordán,9 Sergio Jurado-Herrera,10 Noelia Florencia Pérez-González,10 Covadonga García-Díaz,11 Faustino García-Candel,12 Ihosvany Fernández-Bello,1 Pascual Marco-Vera1,13 1Hematology Department, Hospital General Universitario Dr. Balmis-ISABIAL, Alicante, Spain; 2Hematology Department, Hospital Universitario Miguel Servet, Zaragoza, Spain; 3Hematology Department, Hospital Regional Universitario de Málaga-IBIMA, Málaga, Spain; 4Hematology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain; 5Hematology Department, Complejo Hospitalario de Jaén, Jaén, Spain; 6Hematology Department, Hospital Universitario de Guadalajara, Guadalajara, Spain; 7Hematology Department, Hospital Universitario Virgen de las Nieves, Granada, Spain; 8Hematology Department, Complejo Asistencial de Segovia, Segovia, Spain; 9Hematology Department, Hospital General de Valdepeñas, Ciudad Real, Spain; 10Hematology Department, Hospital Universitario Torrecárdenas, Almería, Spain; 11Hematology Department, Hospital Universitario de Burgos, Burgos, Spain; 12Hematology Department, Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain; 13Clinical Medicine Department, Universidad Miguel Hernández, Alicante, SpainCorrespondence: Ihosvany Fernández-Bello, Hematology Department, Hospital General Universitario Dr. Balmis-ISABIAL. Pintor Baeza 11, Alicante, 03010, Spain, Tel +34 965913863, Fax +34 965913869, Email [email protected]: 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: mild hemophilia A, moderate hemophilia A, joint damage, HEAD-US, assay discrepancies, real-world data