Patterns of joint damage in severe haemophilia A treated with prophylaxis

Goren, Rachel; Pullenayegum, Eleanor; Blanchette, Victor S.; Dover, Saunya; Carção, Manuel; Israels, Sara J.; Chan, Anthony; Rivard, Georges E.; Steele, MacGregor; Cloutier, Stéphanie; Klaassen, Robert J.; Sinha, Roona; Price, Victoria; Laferriere, Nicole; Paradis, Elizabeth; Wu, John; Feldman, Brian M.

doi:10.1111/hae.14345

Cited by 3 publications

(1 citation statement)

References 25 publications

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“…In another relevant study, Goren et al (2020), with a cohort of 55 boys with Hemophilia A, demonstrated that the age at first joint bleed was a strong predictor of subsequent joint damage [ 13 ]. These findings from various studies highlight the importance of early bleeding episodes as a prognostic factor in Hemophilia A.…”

Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Relationship among 785 Unrelated White Women with Inherited Congenital Factor VII Deficiency: A Three-Center Database Study

Halimeh,

Koch,

Kenet

et al. 2023

JCM

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Background: Congenital factor VII (FVII) deficiency, a rare bleeding disorder resulting from mutations in the F7 gene with autosomal recessive inheritance, exhibits clinical heterogeneity that lacks a strong correlation with FVII:C levels. The objective of this study was to discern genetic defects and assess their associations with the clinical phenotype in a substantial cohort comprising 785 white women exhibiting FVII:C levels below the age-dependent cut-off percentage. Patients and Methods: Individuals with verified inherited factor VII deficiency underwent i) genotyping using the Sanger method and multiplex ligation-dependent probe amplification (MLPA) to identify F7 mutations, including common polymorphic variants. Additionally, they were ii) categorized based on clinical bleeding scores (BS). Thrombophilic variants and blood groups were also determined in the study participants. Results: The probands in this study encompassed both asymptomatic individuals (referred for a laboratory investigation due to recurrent prolonged prothrombin time; n = 221) and patients who manifested mild, moderate, or severe bleeding episodes (n = 564). The spectrum of bleeding symptoms included epistaxis, gum bleeding, gastrointestinal bleeding, hematuria, postoperative bleeding, and gynecologic hemorrhage. The median ISTH bleeding score (BS) recorded within a two-year period prior to the work-up was 2 (0–17). Notably, this score was significantly higher in symptomatic women compared to their asymptomatic counterparts (3 versus 0; p < 0.001). The corresponding PBAC score before hormonal treatment stood at 225 (5–1200), exhibiting a positive correlation with the ISTH BS (rho = 0.38; p = 0.001). Blood group O was more prevalent in symptomatic women compared to asymptomatic individuals (58 versus 42%; p = 0.01). Among the 329 women (42%), known and novel mutations in the F7 gene, encompassing coding regions, exon/intron boundaries, and the promoter region, were identified, while common polymorphisms were detected in 647 subjects (95%). Logistic regression analysis, adjusted for clinical and laboratory data (including blood group, FVII activity, the presence of F7 gene mutations and/or polymorphisms, thrombophilia status, and additional factor deficiencies) revealed that older age at referral (increase per year) (odds/95% CI: 1.02/1.007–1.03), the presence of blood group O (odds/95% CI: 1.9/1.2–3.3), and the coexistence of further bleeding defects (odds/95% CI: 1.8/1.03–3.1) partially account for the differences in the clinical bleeding phenotype associated with FVII deficiency. Conclusion: The clinical phenotype in individuals with FVII deficiency is impacted by factors such as age, blood group, and the concurrent presence of other bleeding defects.

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Section: Discussionmentioning

confidence: 99%

Genotype–Phenotype Relationship among 785 Unrelated White Women with Inherited Congenital Factor VII Deficiency: A Three-Center Database Study

Halimeh,

Koch,

Kenet

et al. 2023

JCM

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Joint health and pain in the changing hemophilia treatment landscape

Mancuso,

McLaughlin,

Forsyth

et al. 2024

Expert Review of Hematology

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Assessment of joint health in patients receiving prophylaxis for haemophilia A: a cross-sectional survey in five European countries

De la Corte-Rodríguez,

Bystrická,

Ball

et al. 2024

BMJ Open

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ObjectivesTo evaluate joint health, pain and health-related quality of life (HRQoL) in patients with moderate/severe haemophilia A in Europe.DesignMultinational, cross-sectional survey, with retrospective data collection. Data were taken from the Adelphi Real World Haemophilia Disease Specific Programme Wave II, using surveys completed by physicians and patients between February 2020 and May 2021.SettingHaematologists/haemato-oncologists and their patients in France, Germany, Italy, Spain and the UK.ParticipantsMales aged ≥18 years with moderate or severe haemophilia A (baseline clotting factor level ≤5%), without existing inhibitors and currently receiving prophylaxis. Patients were grouped into those with or without haemophilia-affected joints (HAJs) based on bleeding, radiographic, surgical, mobility and joint pain data.Primary outcome measureCharacterisation of humanistic and clinical outcomes in patients with or without HAJs.ResultsA total of 120 physicians provided data for 351 eligible patients; 209 (59.5%) patients had HAJs and 142 (40.5%) had no HAJs. Pain/discomfort was significantly different (p=0.01) and reported more frequently in the HAJ (85.7%) vs non-HAJ group (53.3%). Pain medication use was significantly higher in the HAJ versus non-HAJ group (73.2% vs 60.6%; p=0.01). Up to half of the patients with HAJs had synovitis (49.8%) or arthropathy (48.4%), and one-third had undergone joint surgery (35.4%). Overall health status was significantly worse in the HAJ versus non-HAJ group (mean (SD) EuroQol Visual Analogue Scale score: 65.5 (19.3) vs 81.1 (14.6); p=0.01).ConclusionsIn this multinational real-world study, nearly two-thirds of adults with moderate/severe haemophilia A without inhibitors experienced HAJs despite prophylaxis. Individuals with HAJs had higher rates of pain and pain medication use, and lower HRQoL compared with those without HAJs. These data indicate that HAJs represent a clinically relevant burden and early identification/monitoring and management of affected joints should be an important consideration to help prevent long-term joint morbidity.

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Patterns of joint damage in severe haemophilia A treated with prophylaxis

Cited by 3 publications

References 25 publications

Genotype–Phenotype Relationship among 785 Unrelated White Women with Inherited Congenital Factor VII Deficiency: A Three-Center Database Study

Genotype–Phenotype Relationship among 785 Unrelated White Women with Inherited Congenital Factor VII Deficiency: A Three-Center Database Study

Joint health and pain in the changing hemophilia treatment landscape

Assessment of joint health in patients receiving prophylaxis for haemophilia A: a cross-sectional survey in five European countries

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